Tuesday, 25 August 2015

Marriage of younger brother.




Some pics were modified.


















Mere ghar ayi ek nanhi pari

Dekho kudrat ki jadugari,
ayi hai ghar me nanhi pari,
aanken hain kuch to bhari bhari,
dekho na jhad jaye motiyon ki ladi.

Ghadi ayi hai zindagi me mubarak,
dulhan ke aane se aaye ghar me raunak,
zindagi me ho tumhare barkat,
khushiyon ki sada rahe shirkat.

Kab se tha is din ka intezar,
aayi hai aaj mere ghar bahar,
sar ko chumoon kar loon tumhe pyar,
kayam rahe sada ye dulaar.

Sada rahe tum dono ka saath,
hathon me rahe ek doosre ka haath,
khushhal si ho ek nayi shuruaat,
duaaon bhare uthe sar par haath.

Zindagi tumhari phoole phale,
pyar dilon me hardam pale,
kabhi ek ruke to doosra chale,
chand aur sooraj nikle dhale.
May God protect:).

Sunday, 23 August 2015

Haldi ceremony n a Message of love.



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The winds have brought a msg of love,
will be flying together the little doves,
fly out from their nest together,
under the blue sky where the clouds gather.

Fly together with their little wings,
a farewell song dear ones sing,
arm in arm as they move along,
may the blessings shower on them long.

As they pass thru sunshine n rain,
learn to laugh in laughter n pain,
together survive the spring n storm,
in the coldest weather may love keep warm.

Maintain goodness no substitute for this gold,
live n share life and together grow old,
as the years pass by fom january to december,
may everyday the bond grow stronger.

May the tomorrows be sunnier n brighter,
with passing time the loads grow lighter,
together life long will write their story,
every chapter be full of promises n glory. 

From Ranchi to Hyderabad.

At Ranchi station.

Took Jr Blackie along, early morning view from the window.My around one dozen bunnies sent to Kafeel uncle a vet dr n father's friend thankful to him just hope to meet them again or else my little world will be gone. As I packed they pulled the suitcases as if saying will not let u go, most reluctantly had to go, sacrifice for family, female thy name is sacrifice:).
A view of South India from the train.
View of a river from the train, donno the name, sat like a statue bcoz of neg indn:(.


The Balika badhu grasses, bade ache lagte hain ..

Around half an hour from this station is Hyderbad, reached safe with family,  parents condn not very normal, had seen this pic earlier during one of bros trip to south with friends as we reached started raining went out to take a snap in the light drizzle.Remembered my last  visit to south India in 2004, Dec 26th when there  was a tsunami, ppl all hudled up at the station, Love the south Indian culture, esp here appreciated the  language n way of speaking :) .
The water droplets appeared beautiful.


Found Hyderabad too beautiful at the first glimpse, simplicity n freshness n tahzeeb,



















Sunday, 16 August 2015

Happy Independence day friends!.

























Pyara desh hamara.2:44 AM 8/15/2015 

Har taraf goonj rahi hai desh raag,
swatantrta ki lapak rahi hai aag,
badhta desh age jab jagta samarpan tyag,
ugte suraj ke sath sab rahe hain jag.

Bharat ma ki aa rahi hai pukar,
asani se har na karo sweekar,
prayatn karne se jeet me badalti har,
bahte chalo jaise nadiya ki dhar.

Bharat  ki god me hua janm hamara,
isme samaya hai sara jahan hamara,
desh hamara hum sab ko hai pyara,
bane ye duniya ki ankhon ka tara.

Bapu ne kaha bacche yahake vividh prakar,
agar sab hon safal to kaisa bhar,
ekta ki shakti ko kaise karen nakar,
sabhi desh vasi hon safal hon udar.

Har jatil samasya ka nidan,
milta agar ham lagayen dhyan,
har manushya ke pas hai mastishk mahan,
nahi kar sakte uski mahima ka vitan.

Bhai bandhu sakha sabmilkar rahen hai sar,
aapas me hi na  kar baithe hum prahar,
kuch kar dikhane ka dhun ho sir par sawar,
kuch to vyakt ho hamara prem hamara abhar.

Sab ke sapne hon pure sab hon safal,
jeevan kaal sankhipt nahi koi rahta aviral,
jab chod jayen hum apna  karmsthal,
bahe prem purna sathiyon ke nayan jal.



 4:24 PM 8/15/2015
Heart Failure--Give growth factors like TGF-alpha, epidermal growth factor, IL-6, TNF-alpha.These factors will cause hyperplasia,

TGF beta,IGF-1, Fibroblast Growth Factor,alpha adrenergic agonist, endothelin-1, angiotensin-2--These cause cardiac hypertrophy, this leads to release of ANF. This causes lowering of BP, vasodialatation, natriuresis n suppression of renin angiotensin axis.ANF will be a substitute for diuretic n a hypotensive agent/vasodialator. So the point is give these factors as well in heart Failure if the cardiac size not very high.The above will take care of pump failure.

If there is a stenotic lesion go for baloon valvulotomy or gamma ray or lazer induced valvulotomy.

 Use the factors studied earlier while studying cancer.. that causes vasculogenesis after MI, give growth factors.

Vaccine against organ transplant heart as well --Make abs against Activated T cells n B cells against MHC class 1 ag of the foreign tissue. MHC class 2 presents exogenous ags  extracellular microbes, soluble proteins.
Preperation for bro's marriage no study since almost two days:(. Sorry cud not post yesterday, I also missed u all:).



Friday, 14 August 2015

Science

Was going thru the chart of Classification of anaemia
For enz defn--Red cell enz defn for eg---give enzymes
For str proteins defn,--Red cell memb disorders for eg-- Give rt proteins
For polypeptide defn--Globin synthesis eg in thalassemia,abnormal globin eg Sickle cell anaemia--Give rt globins or rt mRNA or DNA.
Antibody mediated--Transfusion rkn--Give sensitized B n T cell vaccine against antibody A n antibody B.
Erythroblastosis fetalis--Give B n T cell vaccine against Rh + antigen
DIC --Give vac against an early factor in the coagulation cascade prophylatically to pts in the post partum period n after cancer, after burn wonder will work bcoz may lead to massive bleeding from the burnt surface.
TTP-Thrombotic trombocytopenic purpura--Vac against n early factor in the coagulation cascade will act as an anti clotting or throbus vac.
when ever trying a lymphocyte vaccine try giving both B n T cell vaccine, will take care of things in a better manner, however B cells will not be sufficient when cells n viruses involved.

Chronic inflammatory dermatosis--
Psoriasis--Lymphocytes from the pts with psoriasis are capable of inducing abnormal growth of keratinocytes n dermal blood vessels,if these results hold true the this ia a disorder of the immune system capable of provoking an activation n disordered growth of skin cells.Find out if there is a defect in the lymphocytes n then give abs or T n B vacccines against those lymphocytes also give rt T n B stem cells.
Lupus Ertthematosus--Defect in the lymphocytes affecting pigment containing basal cells  give or T n B vacccines against those lymphocytes also give rt T n B stem cells.
Blistering bullous disease
Pemphigous--Autoimmune blistering disorder. Abs +nt against intercellular cement subst of skin n mucous membrane , make vac using activated T n B cells against pemphigus ab which reacts with desmoglein 3 molecules, a compt of desmososmes that appear to bind keratinocytes together.
Bullous Pemphigoid--There is generation of abs against the bullous pemphigoid antigen 1 n 2.Make vaccines against these abs activated T n B cells against pemphigus ab .
Dermatitis herpetiformis--Develop abs IgA n Ig G classes against gliadin n reticulin...Give vac against the Igs.
Non inflammatory blistewring dosease : Epidermolysis bullosa, porphyria--The pathogenesis is not well understood although serum proteins including igs typically form glassy deposits in the walls of superficial dermal microvessels make vac against identified ab.
Disorders of epidermal appendages--
Acne vulgaris--Make a vac against bacterial lipases of propionibacterium acnes that break down the sebacious oils liberating highly irritating fatty acids resulting in the earliest inflammatory phase of acne.Isotretinoin found to bring marked improvement.
Panniculitis
Erythema Nodosum n Erythema induratum--

Warts--Remove by laser or gamma rays.
Molluscum contagiousum--Self limited viral disease. Remove the virus by laser or gamma rays.
Arthropod bites, stings n infestations--Their secretions n poisons cud be used as vaccines.
Freckle--Ephelis--Remove by laser or gamma rays.
Melasma--Remove by laser or gamma rays.
Lentigo--Remove by laser or gamma rays
Nevocellular nevus--Remove by laser or gamma rays
Dysplastic nevi--Remove by laser or gamma rays
Benign epithelial tumors--
Seborrheic keratosis--Remove by laser or gamma rays
Acanthosis nigricans--hyperplasia of stratum spinosum of epidermis--Remove by laser or gamma rays
Fibroepithelial polyp--Excision can by laser or gamma rays.
Epithelial cysts (Wen)--Incision n expulsion
Keratoacanthoma--Treat like a tumor, remove by laser or gamma rays
Adnexal (appendicular)tumor--Benign tumor--remove by laser or gamma rays
Premalignant n malignant epidermal tumors--
Actinic keratosis--Remove by laser or gamma rays
Squamous cell carcinoma--Remove by laser or gamma rays
Basal cell carcinoma--Remove by laser or gamma rays
Basal cell nevus syndrome--Remove by laser or gamma rays
Merkel cell carcinoma--Remove by laser or gamma rays
Tumors of the dermis--
Benign fibrous histiocytoma--Remove by laser or gamma rays
Dermatofibrosarcoma protuberans--Remove by laser or gamma rays
Xanthoma--tumor like collection of foamy histiocytes--Remove by laser or gamma rays
Dermal vascular tumors--Remove by laser or gamma rays, use sclerosant or else a thrombus to cut off the nutrient supply.
Tumors of cellular immigrants to the the skin--Remove by laser or gamma rays
Histiocytosis X--Make vaccine against surface ags on langerhans cells n histiocytosis X cells.
Mycosis Fungoides(Cutaneous T cell lymphoma)--Remove by laser or gamma rays, Use a high magnification n resolution MRI/gamma imager to visualize the tumor n once they are visualised n identified bcoz of the numerous tumor markers present in a tumor cell one can destroy them thru radns beta ,gamma.
Mastocytosis--Here the pic is different the condn is not localised so tt will be a vaccine that is we will try n make a vaccine against mast cells but the titre will have to be low which means that we will give low amount of lymphocyte stem cells, T cells are able to produce a lot of activated T cells n some form memory cells n B lymphocyte clone that is activated forms lymphoblasts n some of the lymphoblasts form lymphocytes similar to those of the original clone which forms the memory cells .If the lymphocytes did not multiply after activation then this vac will be a failure.
So to give a vaccine give both T n B fused lymphocyte's clone/activated T n B lymphocyte's clone but where u have to take care of the titre there give low amounts of the lymphocytes,as happens in a primary response see that the titre rises n comes to a stable state wanted slowly if memory cells formed the titre will not decline instead will reach a very high titre bcoz of the constant presence of ag in the body this will happen in cancers BUT in other conditions the macrophages will not present self as antigens so no further activation of T n B cells so no more augmentation of response, so what we can do is where we have to give the vaccine against self ag  as a drug whose dose needs to be increased with time we will give it like passive immunity that is give the sensitized lymphocytes in a low titre/amt n see that sufficient titre is produced to supress the ags in the proportion wanted once the level of the ab declines we will have to give another dose.
Point to be remembered is that here memory cells may be formed when the titre goes high HARDLY MATTERS MEMORY CELLS FORMED OR NOT:) but there will be no second exposure bcoz the body's T n B lymphocyte will not recognise the self as foreign or antigen If this vaccine is used against infective organisms then take care of memory cells bcoz there the titre may go down n will rise in a secondary response n further but here in the case of self ags no need of memory cells other than in cancer. So in no way can a vaccine be made against self normal ags only against cancer ags or infections viral, bacterial etc will augment immunity there.So against self this will be a passive immunity n active as well will tell u how. Sequence of evolution of thoughts:).

Higher the titre faster will be the immunity like in measles the immunity is achieved in 12 days, in rubella when we give a vac RA27/3 that induces very high titre like an infection the immunity lasts for 14 t0 16 yrs n pbly for life. So more the ab titre higher n longer is the immunity.This means that the T n B cells that are activated  are too many in no n they will stay active for years that is why the titre of ab remains high even after a single exposure whether it is a vaccine or infection this depends on two factors the antigenicity of the antigen n the immune state of the person so two things to be taken care of during a vaccination or infection give a lot of CD28 cells n  CD95 cell antagonists n next give too many activated lymphocytes this will augment immunity act as an additional vaccine.
So these activated cells they go on multiplying for life bcoz very few people are exposed to an antigen a second time n they still remain protected which means that the protective role is bcoz of the high no of activated lymphocytes n not the formation of memory cells bcoz only those ppl are protected who have a high titre of ab that is why we give multiple doses of vaccines to inc the titer,  so for a proper vaccine when u give a high titre of activated lymphocytes it itself will be sufficient n act as  a vaccine n that high titre  will form memory cells that will come to use next time there is an exposure n the titre will continue to rise after every exposure this will work wonderfully when used for infections, but when u use it against self antigens the high titre itself will act as vaccine. Howz it?:).
We cud also try slightly altered self ags n make them cross react howz this?:)
B cells on activation will form a clone of activated  B cells  which will form a clone of plasma cells, these plasma cells form abs  for several days or weeks. When there is primary ag exposure the abs formed for a very short time in low titres in the next exposure the ab titre formed is higher n stays for months n as the ag exposure continues the ab response becomes more potent same happens in T cells, the T lymphocyte of the specific lymphoid tissue clone proliferate n release large nos of activated T cells in ways that parallel ab release by activated T cells, the principal difference is that instead of releasing abs, activated T cells are formed n released into lumph. These activated T cells pass into circulation n are distributed thruout the body, sometimes lasting for months or even years--This is responsible for life long immunity.
Covered this day b4 yesterday's evening n a bit by yesterday afternoon, but cud not put up.

Summary --
Vac will consist of activated T n B cells taken n grown in culture in the presence of growth factors n then given into the body.
Fuse foreign activated T n B cells with T n B cells from the clone in human beings that will form  a clone of activated T cells n B cells against self ags, use growth factors n then after a huge no of such cells created use it as a vaccine.

Disorders of epidermal maturation--Icthyosis--Give steroid sulphatase this is deficient....
Acute inflammatory dermatosis--
Urticaria--
IgE dependant--Involvement of IgE n mast cells--gIVE abs or antagonists.
IgE independant--Involvement of certain  chemicals such as aspirin that supress pg synthesis--stop those chemicals
Defn of C1 activator--Give C1 activator.
Acute eczematous dermatitis--
Contact dermatitis--We will use that sensitized T cell as ag n make T cells against them or make antibodies against them.This will prevent transplant rejection, skin allograft rejection n all sorts of rejection baccha log:) we can also use this type of vaccine in TB bcoz in Cell mediated delayed hypersensitivity what happens is Sensitized T lymphocytes---->release of lymphokines n T cell mediated cytotoxicity.This is responsible for the above three neg condns, so make a vac against sensitized T cells.
Gr8:)
Atopic dermatitis--
Drug related eczematous dermatitis--Make a vac against T n B cells sensitized against penicillin (My bhai bandhu this VAC will help pts allergic to penicillin) or other chemicals responsible 4 eczematous dermatitis.
Photoeczematous eruptions--Prevent exposure to light if due to damage to DNA can do nothing if another isomer of a chemical formed then use it as a ag n eliminate from body.
Primary irritant dermatitis--Prevent trauma n friction.
Erythma multiforme--make a vac against the sensitized T n B lymphocytes, here the ag is CD8 T lymphocyte.
Amniotic band --Remove with the help of radns.
Came across a child with hydramnios in the book.
T/t of oligohydramnios--Bcoz of renal agenesis so what u can do is give amniotic fluid transfusion in the form of isotonic fluids n the kidneys function will be taken care of by the mother n after the child is born give him/her a new kidney n give the Vac against the sensitized T n B lymphocytes as mentioned above.
Cord around the neck--We can make the fetus move n try n get the problem solved, bujhti padi have already covered this topic two yrs back:).
If pt in hospital n there is chance of throttling then cogulate or produce a thrombus in the 3 bld vessels of the cord n then cut the cord so that life is saved then give incision on the skin n all the layers below n the uterus after taking care that there is no bleeding n then the baby will be out the nearby doc can complete the rest of the work this is to save the life of the child, thru gamma ray activation of the spinal nerve roots supplying the area, pain can also be taken care of, sterilization also by gamma rays.

Amyloidosis--1)AL--is bcoz of deposition of AL amyloid light chains2)AA is a unique non immunoglobulin  protein synthesiszed in the liver.3)A beta amyloid is found in cerebral lesions of alzheimers, use these chemicals as ags n use the sensitized T n B cells n prepare vaccine, back after a very long time 36 hrs or so body n mind was busy making preperations for my brother's marriage hope n pray it is a success.

Again came across the same page so started this lesson dis of infancy n childhood--*/8
APGAR score--Give oxygen to the mother around delivery, don't clamp n cut the cord soon keep the placenta raised above the level of the body of the baby n keep the placenta in sterile distilled water well oxygenated by bubbling oxygen into it till the baby has cried properly n has achieved a good apgar score, howz it :), head to be placed at a lower level than the body for proper blood supply to the brain, give slight amt of cardiac stimulant around birth to improve circulation, give some surfactant if need arises i.v, give oxygen mixed with air to prevent retrolental fibroplasia, howz this:).
Oligohydramnios--Mentioned above
Agenesis--Transplant organs n give the vaccine.
Atresia-- Absence of an opening , such as trachea n intestine. Make an opening thru radiations, For TOF use sclerosant.
Syndromes caused due to viral infections or genetic defects--Have dealt with some.
Hypoplasia--Give growth factors n see or transplant for eg can transplant lung using a heart lung machine, if neonatal organs retreived there will be no dearth for organs for transplantation in neonates:).
Causes of malformations--Trisomy can be corrected in the zygote by radns if the zygote survives it else the beginning of pregnancy is aborted.
Viral cause--Give vaccines to the mother enzyme, acti B n T cell vaccines.
In cancer cells there is rapid growth just like a fetus n blood n germ cells but the apoptosis gene in all cancers gets inactivated that is why no cell death takes place here n the cells grow in the presence of growth factors n accumulate, pbly they supress the apoptosis gene which was thought to occur in some cancers.
HOX--Homeobox gene-For mutated genes give mRna antagonist n give the rt gene.
Pax-paired box---For mutated genes give mRna antagonist n give the rt gene.
Perinatal infections--Give vaccines to the mother.
Neonatal respiratory distress syndrome--Already covered. Give surfactant i.v.
Erythroblastosis fetalis--Already covered. Give vaccine T n B cell against Anti D, ab against Rh +ve blood.
Inborn errors of metabolism--
PKU--Give phenylalanine hydroxylaser.
Galactosemia--for the common variant give galactose -1-PO4uridyl transferase.For the rare variety give Galactokinase in the circulation.
Cystic fibrosis--Most common abnormality is a deletion of three nucleotide coding phenylalanine at amino acid position 508. Give the correct gene.CFTR has two transmembrane domains the two nucleotide domains n a regulatory domain that contains protein kinase A n C phosphyration sites--The nucleotide domain n the R domain is mutated so the t/t For mutated genes give mRna antagonist n give the correct genes thru circulation or viral vectors.In some pts there is congenital absence of vas deferens what u do is u transplant the testes n join 4 structures 1) arteries  2) veins 3)vas deferens use a stent to maintain patency as the site of joining then irradiate the vas deferens n place the primordial germ cell n leave it. Give the vaccine against graft rejection.
SIDS--Although cause remains unknown, it is now tht that SIDS is a heterogeneous disorder sometimes caused by specific disorders. For eg-- a deficiency in medium chain acyl coenzyme A dehydrogenase.
Tumor n tumor like lesions of infancy n childhood
Benign tumors n tumor like lesions--
Haemangioma--Give radns, give cancer vaccine
Lymphatic tumors--Give radns, give cancer vaccine
Fibrous tumors--Give radns, give cancer vaccine
Teratoma--Go for surgery, Give radns, give cancer vaccine.
Malignant tumors--Give radns, give cancer vaccine






 

Tuesday, 11 August 2015

Science

'
Waking from sleep once again--T cells containing CD 28 binds to antigen presenting cells that contain B7-1 n B7-2, IF no B7 receptor then no immune activation n  there is anergy.
To produce cross rection a rat model was created with both viral protein n B7-1 under the insulin promoter, this breaks down peripheral tolerance n T cell mediated injury to the islet cells occur. This is for autoimmunity against self antigens i.e if the normal str is slightly disturbed n there is inflammation as well then the ligands formed n Tcells with CD28 starts working.
Find out whether CD28 is sufficient 4 autoimmunity.
Then what happens in orchitis that is not autoimmunity.
Inflmmation n mutaion causes autoimmunity.. inflammation generates the B7 receptors.
Autoimmune thrombocytopenia, here abs formed against platelets-- we can control thrombosis--Vac against thrombosis.
When there is inflammation in the body n there is formation of B7-1,2 n  that binds with CD28 T cells n is responsible for induction of CMI, so in the vac where autoimmunity is augmented with CD28 T cells will not react against body's cells without the ligand, how will it  react against body's chemicals like insulin, abs like in RA where there are no cells involved, had been thinking all this yesterday afternoon today got the answer, given below..
We will make abs against FAS +ve i.e CD95 T cells to produce hyperimmune state.
We will give CD28 T cells.

Vac against self ags--
So for creation of a vaccine against self we will have to give CD28 T cells n then give an antagoinst against CD95 T cells then we will make ab against the CD95 T cells n once that takes place we will create other vaccines (can stop an ab formation against a chemical by making abs against them) CMI again will not work without the augmentation of B7 ligand which can be induced to form during an infection n inflammation (may have to control that sensitized T cell if hyperimmune state arises by making abs against it) a tough job but possible, work out n see.
Draw back of the earlier vaccine--
There will be an autoimmune picture, if we r be able to counteract the immune process against other parts of the body, well n good, else we will make abs against all the abs formed n T cells or abs against the Tcells.
Try this vaccine--Fuse sensitized T cell with a stem cell, fuse a sensitized B cell with B cell n then make a vaccine n give growth factors as well . CUD be from self or another animal. If u use a lot of sensitized stem cells from body's own lymphocytes will also be like a vaccine has to be in large amts will be difficult to gather a huge pool of such sensitized lymphocytes so culture in a medium with gfs n use as a vaccine.
Else try this:)--ANOTHER vac if it works an alt of gene therapy in simple words-- U take a B stem cell n replace the ab gene with the gene of ab wanted n give the stem cells in adequate amt prepare the ab gene by recombinant DNA tech. Similarly Tcells can also be given. Got this idea when studying Ig A defn later, have added it here bcoz the topic is relevant.
Else try one more:)--Had tht it n noted it down but had  forgotten to mention it--BY studying the antigen n antibody structure artificial creation of antibody n vaccine, artificial creation of antagonist n artficial creation of agonist abs can be done, that is one can design abs with different properties  which is already known for passive immunity we can also use it for active immunity.
TO PRODUCE ABS AGAINST DM THAT ARE AGONIST.
What we will do is make an antibody every component will be the same as an ab but the variable region will contain agonist like structure n this will act as an agonist rather than antagonist.
Here what u do is u will have to produce an ab gene that will code for three regions V, J n C. Now we will make a designer antibody i.e we will find out the amino acid sequence of insulin that binds with its receptors n this will act as the variable region we will accordingly use the three bases that code for the amino acid the rest joining n constant region segment be modified n we will make Ig E the  Igs  differ in their life span, better to give IgE shorter life span will act somewhat like insulin find out the half life of various abs, found out-- Ig G has 23days,Ig A has 6-8 days, Ig M has 5 days,Ig D has 3 days,Ig E has--2 days.Insulin has half life 5-9 mins. See whether will work bcoz evrything depends on the titre of ab being produced n whether the dose matches that of insulin. Try Ig with a new constant region IgS :) with a shorter half life, howz this, came out accidentally:).
Other vaccine will also work with T cells that have been given CD 28 genes.yesterday spent a lot of time thinking how ag presenting cells got the B7 ligand n then how were the insulin abs formed, now things are clearer today abs n CMI can develop against cells as well as chemical compounds but they need to be presented by the antigen presenting cells n another point to prevent anergy have to carry B7 ligands which will be a sequelae of inflammation n infection so what u do is give IL-12 n produce the pic of inflammation that leads to ligand formation on the APC. Keep forgetting things, there is so much of torture, shock friends  is a cause of memory loss or iS god giving too much?:) so again revised things:).Go thru this given below, came across this today will clear concepts.

Tlymphocytes are found in the paracortical areas of lymph nodes n periarteriolar sheaths of spleen. Each T cell is genetically programmed to recognize a specific cell bound antigen by means of antigen specific Tcell receptor.
In approximately 95% of T cells , the TCR consists of a disulphide linked heterodimer made of alpha n a beta polypeptide chain each having a variable n a constant region. In a minority of peripheral blood T cells another type of TCR composed of gamma n delta polypeptide chains is found.
The TCR gamma/delta cells tend to aggregate at epithelial interfaces,such as mucosa of respi n GIT. Both the alpha/beta n gamma/delta TCRs are non covalently linked to a cluster of 5 polypeptide chains, referred to CD3 mol complex.They do not bind antigen but are involved in the transduction of signals into the T cell after it is bound to the antigen.TCR diversity is generated by somatic rearrangement of the genes that encode the 4 chains.The mechanism is just like B cell ab syntheisis here T cell receptors are formed instead.
The principal physiologic function of the cell surface histocompatibility molecule is to bind peptide fragments of foreign proteins for presentation to appropriate antigen specific T cells. Remember that T cells (unlike B cells) can recognise only membrane bound antigens and hence histocompatibility ags are critical to the induction of Tcell immunity.
several genes encode for histocompatibility antigens but that  code for most important transplantation ag are clustered on a small segment of chromosome 6.This cluster constitutes the human MHC n is also ka Human leukocyte antigen complex.
In a transplant pt use this ag n give its antagonist so that this ag will not be presented to the ab n no graft rejection takes place.

Class 1 ag are expressed on all nucleated cells n platelets.They are encoded by 3 closely linked loci, designated HLA-A, HLA-B, HLA-C.each of these molecules is a heterodimer consisting of a polymorphic alpha1,2,3 heavy chain linked to beta 2 microglobulin, the latter is not coded in MHC.The extracellular region of the heavy chain is divided into alpha 1,2 n 3. Crystal structure of class 1 molecule has revealed that the alpha1 n 2 domains contain a cleft or groove where peptides bind to The MHC molecule.Biochemical analysis of several different class 1 alleles have revealed that almost all the peptides line the side or base of the peptide binding groove. As a result diff class1 alleles bind to diff peptide fragments.See the representation of HLA complex n its subregions for clarity.
Dear friends has manipulated my pendrive so that my patho-robbins not opening n I need to type lots, study-- Str n Function of Histocompatibilty ags on ur own. Torture as usual going on dhamki after dhamki. Says will kill u n steal ur work n protect myself as well, no one will know all the neg have done.
In general class 1 MHC molecules bind to those peptides that r derived from proteins such as viral ags synthesized within the cell. The generation of peptide fragments within the cell n their association with MHC molecules n transport to the cell surface is a complex process.Involved are PROTEOSOMES, which digest antigenic proteins  into short peptides n transport proteins which ferry peptide fragments from the cytoplasm in2 endo reticulum.Here peptides bind to ag binding cleft of newly synthesized class 1 heavy chains which then associate with beta 2 microglobulin to form a stable trimer tht is transported to the cell surface for presentation to CD8+ cytotoxic T lymphocyte.In this interaction the TCR recognizes the MHC peptide complex     n the CD8 molecule, acting as co receptor binds to non  polymorphic alpha3 domain of the class 1 heavy chain. CD8+Cytotoxic Tcells can recognize viral or other peptides only if presented as a complex with self class 1 antigens.

What happens will now summarize antigen enters body this is phagocytosed by the macrophages they process n present the antigen to the immunocompetent T cells  The T cells cannot be activated by soluble antigens there4 presentation of processed membrane bound ag by macrophages or other ag presenting cells dendritic n B cells surprisingly this is obligatory for induction of CMI. The above digestion n presentation on the groove on the MHC also ka HLA, followed by presentation to T cells.If u dont go thru str of  HLA  class1 molecule will understand nothing.


How to prevent ca metastasis?

A cancer spreads is invasive it metastasizes while a benign tumor does not. Cancer penetrates the bld vsls ,lymphatics n body cavities.Now again God helped me I opened my book of cell biology all eaten by my bunnies somehow opened cancer half eaten n then that page that said that proteolytic enzymes were released that n I automatically understood this was the answer n then went to the topic of invasiveness n it said that invasiveness cud be bcoz of changes in the plasma membrane and or proteases.So to prevent metastasis will have to antagonise these enzymes either make an antagonist or make a vaccine.Wow!
Use beta catenins as antigens n create a cancer vaccine this protein in the cytoplasm enters the nucleus n causes the transcription of growth promoting genes....APC a tumor supressor gene degrades it.

Another point that opened up is that Beta catenins they adhere to E cadherin n this cell surface protein  maintains intracellular adhesiveness,cancer cells have reduced adhesivenes resulting possibly from defect in cadherin catenin axis.
Cadherins are a family of glycoproteins that act as glues between epithelial cells. Loss of cadherins can favor the malignant phenotype by allowing easy disaggregation of cells which can invade locally or metastasize.
LOSS OF CADHERIN or antagonism if we use it as an antigen will cause a benign tumor like adenoma to form a carcinoma in a mouse model of pancreatic beta cell tumor.
So first use vac to prevent cancer then give vac that prevent its further growth n then stop the benign getting malignant or malignant from metastasizing.
Cancer vaccine--Ca prevention n cancer growth prevention--
USE cancer receptors that are activated without the presence of gfs as ag BCOZ this is unique to cancer cells only n fuse that sensitized Bcell with a B stem cell n Tcell with a T stem cell n augment immunity, will act like a vaccine for both benign n malignant tumors.
Use the MAP kinase (this activates nuclear transcription factors n thus promote mitogenesis)as antigen can work as anticancer...use the other antigens discussed earlier.
Use Cyclins....as ag.

Use anti catenin vac
Vac that prevents benign getting malignant--stop invasion n metastasis. 
Give cadherin. Stop defective cadherin catenin axis. Give antiprotease. Use the factors mentioned below.
Steps involved in metastasis--
1.Detachment of tumor cells from each other-Cadherin antagonism or loss--t/t-Give Cadherin.
2.Attachment to matrix component--Laminin specific receptors n integrins that serve as receptors for many components like fibronectin,laminin,collagen n vibronectin. Make antibodies against laminin specific receptors n integrins.

3.Degradation of extracellular matrix--Action of proteases by tumor cells or stromal fibroblasts or infiltrating fibroblasts--Give antiproteases, sorry had mentioned about digesting the cancer with proteases but it instead digests the surrounding tightly regulated by antiproteases.Three classes of proteases identified  serine, cysteine n metalloproteinases.Type 4 collagenase is one of the metalloproteinases, later read even book says inhibition of metalloproteinases cud be a t/t  for cancer. Cathepsin D a cysteine proteases n urokinase type plasminogen activator a serine type protease/proteinase are imp in degradation of EC matrix, Use these enzymes as antigens n create vaccines the new variety fused activated B cell n B stem cell N fused activated T cell n T stem cellor hope it works.
4.Migration of tumor mass--Migration mediated by --
1.Tumor cell derived motility factor,several autocrine motility factors n thymosin beta 15. Hepatocyte growth factor is another factor.
use them as ag n create vaccines n remove them from circulation n prevent metastasis.
2.Cleavage product of matrix component--derived from collagen n proteoglycan have growth promoting, angiogenic, chemotatic activities.
--Antagonize them use them as ag in vaccines.
--Use the the cleavage product after a heart stroke or brain stroke will help in vasculogenesis:) anoxia also predisposes to vasculogenesis hope am rt:).



Telomerase extends life span of body cells prevents aging n cessation of cell division, in germ cells the telomere shortening is prevented by sustained action of telomerase, but this happens only in the males.So in a pt with oligospermia give a lot of primordial germ cells to the seminiferous tubules of testes n growth factors or telomerase will be a cure for infertility.
So if we try perpetual ovulation n egg release in a female what we will do is give some primary oocytes formed from own stem cells to the ovaries around menopause, bcoz telomerase wont work here, only one or two eggs a month in multiovulation some more. Can be given to aging pts.
Three blood vsl Testicular artery n two veins on rt n left can be ligated in those where the mullerian i.e the female reproductive organs n the wolffian that is male reproductive organs both are formed, then the person can live like a female or else remove the ovaries.Depending on the reproductive tract formed remove the testes or ovaries.


The superior vena caval syndrome is caused by tumors,aortic aneurysm compressing on it or invading it--Use gamma n laser to burn the tumor.
Inferior vena caval syndrome--is caused by tumors, aortic aneurysm  compressing on it or invading it--Use gamma n laser to burn the tumor.
Lymphangitis--Give antibiotics.
Lymphedema--Occlusion of lymphatic drainage is followed by the abnormal accumulation of interstitial fluid in affected part, referred to as obstructive lymphedema .Lymphatic blockage is most commonly secondary to
1.Spread of malignant tumors obstructing either the lymphatic channels or regional grp of lymph nodes.
2.radical surgical procedures with removal of regional group of lymph nodes eg--axillary dissection of radical mastectomy.
3.Post irradiation fibrosis.
4.Fibrosis.
5.Post inflammatory thrombosis n scarring.
Primary Lymphedema may occur as--
Simple congenital lymphedema
Milroy disease
Lymphedema precox
Sclerose the lymphatic vessels n treat lymphedema
Thrombophlebitis or phlebothrombosis--Are two manifestations of venous thrombosis--t/t--Use gamma rays n laser beams.
--Clinical predisposition--Cardiac failure, neoplasia, pregnancy, obesity, post operative state, prolonged bed rest or immobilisation.
Deep leg veins a/c for more than 90% of cases of thrombophlebitis.The first menifestation of thrombophlebitis is an embolic episode.
Migratory thrombophlebitis--Trousseu sign.

Varicose veins--Use a sclerosant.
Aortic Dissection (Dissecting haematoma)--This arises when the blood enters the wall of artery, dissecting between its layers n creating a cavity within the vessel wall. Aortic dissection is a catastrophic illness characterised by dissection of blood in between n along the laminar planes of the media, with the formation of blood filled channels within aortic wall. Arterial --a dissecting intramural haematoma that often ruptures causing massive haemorrhage. Usg guided suction of collected blood n injection of sclerosant.
Aneurysm --is a localized abnormal dialation of a bld vsl tht occurs most commonly in the aorta or heart.Aneurysms can be true or false.A true aneurysm is bounded by generally complete but often attenuated arterial wall components.
A false aneurysm  is an extravascular haematoma that communicates with the intravascular space.
Have already discussed, for aotic aneurysm try the same that is apass a stent n use a sclerosant outside or else go for conventional surgery.

Came across a khesari seed in chana:), BOOA TOXIN present in Lathyrus sativus can be removed by gene therapy n that pulse used as a source of protein with a different flavor, flavor rules things..
Use anti RNA VAC use the activated B cell n fuse with B cell n create vaccine against cancers n genetic condns where wrong protein released.
Inhibition of endogenous anticoagulants such as protein C, Give antagonist of Protein C will inhibit bleeding. Anti bleeding vaccine.

T/t of some Primary Immunodeficiencies.
Wiskott aldrich syndrome--Characterized by eczema, thrombocytopenia n repeated infections. Caused by mutation in WASP gene, WASP protein is expressed in cells of all haematopoetic lineage .It may serve a cytoskeletal organizing role for signalling elements that are particularly imp in platelets n T cells.
T/t--Give rt WASP gene to PHSC in the bone marrow or go for gene therapy in the pts cells from his or her cloned zygote cud be used as a source of stem cells when his or her stem cells not stored at birth, or use one of the cells formed after divsn of the zygote b4 passes the 8 celled stage this stage is better the stem cell is not commited yet n can form a fetus,  cut out the mutated gene segment n give the rt WASP gene use growth factors n create PHSC n infuse into bone marrow.
SCID--Defect in humoral n cell mediated immunity.The most common cause is defn of adenosine deaminase which leads to accumuln of deoxyadenosine n its derivatives eg--deoxy-ATP which are particularly toxic to immature lymphocytes.So give the enzyme from outside or else give stem cells with the rt gene.
Genetic deficiencies in the complement system--Hereditary deficiencies have been described for virtually all components of the complement system n two of the inhibitors.Defn of c2 is the most common of all, give this C2 n other compts of the classic pathway there is inc susceptibilty to infns but dominant pic is tht of SLE.Presumably the alt complement pathway is adequate 4 control of most infns. In the absence of complements there is defn of clearance of ag-ab complexes by monocyte-macrophage system.The defn of alt pathways components is rare this is responsible for recurent pyogenic infection.C3 is reqrd for both pathways defn gives rise to serious n recurent pyogenic infections....So give the missing complement.
Defn of C1 INHIBITOR--- Give C1 inhibitor.They are protease inhibitor  whose target enzymes are C1r n C1s of the complement cascade, factor 12 n kallikrein pathway.Give from outside n see whether will work, or else give stem cells after gene therapy.
Hyper Ig M syndrome--Mutation in the gene for CD40L tht maps for Xq26. Go for gene therapy n give the rt gene.
Isolated Ig A defn--Defect in the  differentiation of Ig A lymphocyte. Give lymphoid stem cells with gene from a normal person.
This is also like a vaccine that is u take a B stem cell n n replace the ab gene, being more specific the CL N cH with the rt gene wanted.
This is also like a vaccine that is u take a B stem cell n replace with the gene of ab wanted FOR vaccine again self ags.
Common variable immunodeficiency--Affect all Ig class sometimes only Ig G. Give normal T n B lymphocyte stem cells bcoz here there is a  defect in B cell differentiation into plasma cells n there is an abnormality of T cell mediated regulation of B cells.
Xlinked agammaglobulinaemia of Bruton--There is a block in differentiation due to mutation in cytoplasmic tyrosine kinase called bruton's tyrosine kinase.The btk gene maps to long arm of the X chromosome at Xq21.2-22. Go for gene therapy in the B stem cells replace with the rt gene.





Babesia microti malaria like protozoan transmitted by the deer ticks:). T/t--Economically imp disease in cattle known as Texas cattle fever.
We will make a vac using the ribosomes from babesia, check no cross rkn with human ribososmes n then give, use heme polymerase as ag n create a vaccine n give to man, cattle n deer:)--Reason we use Clindamycin/Azithromycin n quinine for t/t.

Lyme's disease also transmitted by deer tick caused by Borrelia burgdorferi a spirochaete give B cell enz vac,(enz synthesising peptidoglycan) against it like any bacteria n see whether works.

Go thru Father Robbins differentiation of haematopoetic cells--U can prepare diff types of cells from the stem cells by using the factors that are used in the body that way u can culture cells in vitro n use it to transfuse pts later on suspending the cells in a suitable medium.

Using the principle of Haemophilia n Von Willebrand disease as two condn where there is defn of factor 8 n vWF complex--We can create B cell vac against the two components.Yesterday the B cell vaccine was modified to T cell vaccine for cancer metastasizing enz vac by the Hitler n so many things being dirtied all very obvious to friends.The Von Willebrand factor serves as a carrier of factor8 n shortens the half life of factor 8 from 12 to 2.4 hrs.

HLA Alleles--See the association of HLA with disease,the chart in Robbins, to treat this disease n all genetic diseases n cancers where abnormal gene prdts being released make a B cell vac against mRNA,or abnormal protein this will be formed not in all cells, like the HLA allele +nt in all the cells so HLA cannot be used as ag. Give the right stem cells after correcting the defect where required.

Tumor markers as antigen on cancer cell when attacked by the T cells will destroy cancer go thru Robbins also give lots of interferon gamma n IL-2 will activate Tcells, NK cells, macrophages respectively:).

Tu antigens--2 grps--Tumor specific--present only on tumor cell.
Tumor associated --present on tumor cell as well as some normal cell.

Use the former n create as many vaccies u want:)Thank u God.

Bk says....In experimental model system, tumor antigenicity is assesed by....
1.The ability of an animal to resist a live tumor implant after previous immunization with live or killed tumor cells
2.The ability of tumor free host animals to resist challenge when infused with sensitized T cells with tumor immunized syngeneic donor.
3.The demonstaration in vitro of tumor cell destruction by cytotoxic CD8+Tcell derived from a tumor immunized animal.

In short use the killed tumor cells as ag n create vaccine no time to go into details, use the sensitized T cells as vaccine.

Tumor specific shared antigen--Expressed in a no of tumors of various histologic types--Prototype ag of this group are encoded by the MAGE family of genes.Testes is the only organ where MAGE ag cannot be expressed on the cell surface bcoz male germ cells do not express HLA molecules, thus  4 all practical purpose these ags are tumor specific. They are but not unique to a tumor cell, found in many tumor cells, OK:).Go thru the details even book says that MAGE ags in an immunogenic form cud be given to cancer pts with the idea of boosting their MAGE specific T cells.

Tissue specific antigens--present on tumor cell as well as their normal counterparts--So will cause damage to body....

Antigens resulting from mutations--Prdt of mutated protooncogene or tumor supressor gene--bcoz such mutaion only present in tumor cells this ag will be tumor specific.Bk says --It has been possible to generate CD8+T cells against several ags including peptides derived from mutated p53, K-ras, CDk4 n the bcr-c-abl gene product.

Overexpressed antigens--WILL not be specific c-erbB2 or neu protein this ag is overexpressed in 30% breast n ovarian cancers is also present in normal ovarian n breast cells but its expression is below the threshold level required for recognition by cytotoxic cells n I feel that is why enz vaccines dont work in nature if we increase the level of ag will work.

Most cool child of Mother India I feel wud be a bihari or a jharkhandi, a relaxed mind set:)things were editted there as well even one word matters.

Viral ags-- Ags derived from oncogenic viruses cud also be recognised by T cells, the BEST eg in humans is peptides derived from the E7 protein of HPV-16.Bcoz this virus is present in many cervical ca, the cytotoxic T cells can lyse the ca cells.

Other tumor ags-- Tumor associated --present on tumor cell as well as some normal cell. No use making abs against them.

In the heart n haematopoetic system the same pic arises as in a fetus during anoxia, that is release of ANF in the heart in valvular lesions n HbF syntheis in sickle cell anaemia, Thalassemia.. is protective find out the factors involved that cause the synthesis of Hb F n give more such factors.

 Oncofetal ags n Carcinoembryonic ag are released during fetal life their release later in life means a derepression of genetic program n is an indicator of cancer, bcoz the body recognises this ag during fetal life I don't think that abs cud be formed against them in later life so these ags cannot be used as an ag vaccine, can be if u use activated B cells taken from another species n fused with a norml B cell:).

Differentiation ag--are particular to the differentiation state at which cancer cells are arrested , eg CALLA ag expressed in early B lymphocytes is expressed in early B cell  leukemia n lymphoma n similarly PSA is expressed in cancerous prostatic epithelium, the titre will tell u the stage. Where the ag is specific cud be used as an antigen.


Friends my book says tha

( God remember two yrs back had mentioned about giving pool of abs to AIDS pt had also mentioned about giving B n T lymphocytes but not very sure whether had mentioned about sensitized B n T cells, so close to creation of vaccine n how beautifully things evolve .Activated B cells cud act as vaccine as well but will have to be given in  large amounts, but to create a vac Fuse the activated B or T cell with stem cells many in no n give growth factors as well n u have a vaccine, one more step n its a giant leap for mankind:), so cute.)

Squatting is a good position for delivery decreases load on the heart, use of comode very unhygenic, see that the drainage is better so that water doesn't accumulate at the base dont let the drain make a u turn up that makes water collects n if it splashes up is unhygenic practical problems if discussed will give better products.

Onchocerciasis--Caused by Onchocerca volvulus is responsible for blindness Give IL-12 antagonist. Vac-- Make the glutamate gated channel as the antigen will potentiate gabaergic transmission of worms  n cause tonic palsy, See whether will affect the GABA receptors in humans.

A ureteric stent when placed may cause haematuria, encrustation, biofilm formation, kinking, ureteric rupture, stent migration:), tissue hyperplasia, obstruction, inflammation--So can happens with a stent placed in a in a blood vessel, so use a laser beam or gamma ray n remove the plaque n also remove the stent:)if been in the blood vessel is there any way to remove it?

Radns will work even in the heart bcoz they travel too fast n prophylactically slow or stop the heart for a second or use it during diastole when the heart is in isovolumic/isometric  contraction phase the vessels will not be moving then n nor will the heart.This lasts for 0.02 to 0.03 seconds During this phase in the heart muscles tention on the rise but no bshortening of muscle fibres occurs. Not strictly true bcoz there is apex to base shortening n circumferential elongation but relatively motionless, AV valves open against the pressure being mounted.

Radn causes periaortitis--retrograde stent is placed for t/t
Causes--Inflammtory aneurysm of abdominal aorta n idiopathic retroperitoneal fibrosis an autoimmune disorder where there is T n B cell associated vasculitis.
t/t of aortic aneurysm--even a sclerosant will do use it outside the vessel n place a stent inside, sclerosant but will be difficult to reach the thoracic aorta the abdominal however can be reached USG guided,  while placing the stent inject sclerosant periarterially, can use radns to produce fibrosis around an aneurysm.








Kahan hai kinara.

Kahan hai Kinara.
Taare batane aaye the andheron me disha,
chandrma aakash ke phere laga raha tha us nisha,
jana tha mujhe akele us jeevan roopi nadiya par,
patwar ko sambhale dagmag naiyya par thi sawar.

Aakash me badalon ne laya tha barsane boondon me jal,
bula rahe the lataon se jhoolte pawas hindol,
samne the andhkarmay raaste kuch sankeern,
rupa si kiranen ho rahi thi un raston par vikeern.

Lahron ki awaazen antarman ko thi sweekrit,
door kahin se ek geet kar rahi thi man ko jhankrit,
chandni chitak rahi thi us rat me shyamal,
hawayen chehre par bikherta ja raha tha mere kuntal.

Chandrama me dhulkar sabkuch dikh raha tha pawan,
kahin chamakta roopa kahin chamakta kanchan,
akele thi par door se dekh rahe the do chitwan,
hawaon me phaila sangeet lag raha tha manbhavan.

Chandrma door andhkar me ek deval ko thi rajti,
uske mand prakash me prajjwalit thi ek rajni,
khilta kuvlay muska raha tha jal me dekh apna swaroop,
chandi me chamak raha tha bahte kinare ka sundar roop.
O! majhi re apna kinara, nadiya ki dhara hai..