Vision 2020: the right to vision.
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Biomedical subjects
Publications and source records attributed to K Sarkar.
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Cataract is the major cause of blindness worldwide. The transition of couching of cataract to most modem phaco-emulsification gained popularity with more scientific capsulorhexis. Ongoing research is taking place with laser technologies for removal of cataract. Surgery has an important role in advanced corneal diseases. Corneal transplantation is the most successful form. The refractive errors can be corrected by laser-assisted in-situ keratomileusis, intrastromal corneal rings and phacic intra-ocular lenses. Current research is going on to identify the gene responsible for glaucoma and once this is identified, medical therapy can be developed to control the disease. Thermocautery or photocoagulation and indenting the globe so as to bring the choroid nearer the break by scleral buckling forms the basis of modern surgery of retinal detachment. Vitreoretinal diseases, macular degeneration, diabetic retinopathy are no longer considered problematic. We are optimistic that more clinical breakthroughs are expected in the 21st century with new advances of ophthalmic researches.
Active targeting of muramyl dipeptide (MDP) to macrophages was studied by conjugation with the neoglycoprotein, mannosyl human serum albumin (mannose-HSA) using visceral leishmaniasis as the model macrophage disease. Conjugation did not decrease the affinity of the neoglycoprotein for macrophage mannose receptor. Mannose-HSA-MDP was 50 times more efficient than free MDP in inhibiting the growth of Leishmania donovani inside peritoneal macrophages. Moreover, in a 60-day murine model of visceral leishmaniasis, 95% of the spleen parasite burden was reduced by mannose-HSA-MDP at a dose of 0.5 mg/kg/day given for 4 days. Free MDP at a similar dose had very little effect. In vitro exposure of MDP caused enhanced generation of O2- by macrophages, whereas generation of nitric oxide (NO) was not induced. The elevated antileishmanial activity of MDP-treated macrophages in culture was abrogated by O2- scavengers. In contrast, considerably enhanced amounts of NO and O2- were generated from macrophages of mannose-HSA-MDP-treated animals, and their splenocytes secreted soluble factors providing all the signals required for the induction of NO biosynthesis. The increase in NO production was paralleled by a concomitant increase in antileishmanial activity, which was reversed by NO synthesis inhibitors. Splenocyte supernatants treated with anti-IFN-gamma or anti-TNF-alpha Abs suppressed inducible NO generation by macrophages. Moreover, i.v. administration of anti-IFN-gamma and anti-TNF-alpha along with mannose-HSA-MDP greatly reduced protection against L. donovani infection. Neoglycoprotein-conjugated MDP, therefore, activated mouse macrophages in vivo to kill L. donovani, and this may depend on the physiologic generation of NO induced by IFN-gamma and TNF-alpha.
The collagen composition of the supraspinatus, infraspinatus, and subscapularis tendons, which form part of the rotator cuff of the shoulder, was determined. Tendons were obtained from adult, male beagle dogs and total collagen was estimated by measurement of hydroxyproline. There was little variation in collagen content among the three major cuff tendons and the quantity approximated that cited in the literature for other tendons. However, the collagen content in the insertion zone of the supraspinatus tendon was significantly higher than in the tendon proper. NaCl fractionation of supraspinatus collagen indicated that type I was the predominant collagen but significant amounts of type III and possibly some type II and type V were also present. Interestingly, there appeared to be more type III collagen in the insertion zone than in the tendon proper, cyanogen bromide digestion and peptide mapping confirmed this finding. The differential collagen composition of the supraspinatus tendon may contribute to the high incidence of tear that is associated with this rotator cuff tendon.
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Both the promastigote and amastigote forms of the intracellular parasite, Leishmania donovani bind the basement membrane glycoprotein laminin with high affinity (Kd = 3.56 x 10(-9) M and 3.98 x 10(-9) M respectively) with approximately 9000 and approximately 800 sites per cell. Bound laminin was identified by direct autoradiography and the binding protein through analysis of the parasite extract by SDS-PAGE and immunoblotting. A major component of 67 kDa was detected. The same protein was obtained when parasite outer membrane proteins were adsorbed to laminin-sepharose affinity matrix and subsequently eluted with SDS. The binding affinity of the isolated receptor was similar to that of the whole cells. Such a receptor isolated in Leishmania for the first time, may function as one of the bridging molecules for extracellular matrix recognition.
The characteristics of the recognition system involved in the receptor mediated endocytosis of the neoglycoprotein, fucose-human serum albumin (HSA) were studied. It was found that (i) fucose-HSA showed strong affinity binding and uptake by various macrophages; (ii) binding was specific for L-fucose and D-mannose; (iii) binding was found to be inhibited by oxidant like H2O2 and swainsonine whereas it was elevated by dexamethasone; (iv) clearance of 125I-fucose-HSA was rapid and strongly inhibited by unlabelled fucose-HSA. Greater than 70% of fucose-HSA was found in liver and more than 60% of this was found in liver lysosomes; (v) uptake of fucose-HSA was thirty-fold more efficient in liver macrophages (Kupffer cells) than in hepatocytes; (vi) moreover, mannose-HSA and ovalbumin which are potent inhibitors of mannose/N-acetylglucosamine receptors inhibited clearance and uptake of fucose-HSA by liver as well as by isolated Kupffer cells suggesting the involvement of both fucose and mannose receptors or a single type of receptor having greater affinity for fucose-HSA than for mannose-HSA. These results emphasize the important role of fucose-terminated glycoproteins in site-specific drug targeting.
The functional and structural consequences of remobilization of the glenohumeral joint after 12 weeks of immobilization were studied in 10 beagle dogs. The dogs were grouped in pairs: 2 were used as controls, and in 8 others 1 forelimb was immobilized. At the end of 12 weeks, 2 dogs in the experimental group were euthanized, as were the 2 dogs used as controls. The cast was removed from the other 6 dogs, and the remobilized animals were euthanized in pairs at the end of 4, 8, and 12 weeks. It was found that after 12 weeks of immobilization, the passive range of motion was markedly impaired, intraarticular pressure was raised during movements, and the filling volume of the joint cavity was reduced. Histologically, the capsule showed synovial lining hyperplasia and vascular proliferation in the wall. Immunohistochemical labeling for collagen Types I and III failed to show an increase of fibrous collagens in the capsular wall. Both the functional and structural changes were unaltered after 4 weeks of remobilization, but after 8 weeks they began to reverse, and they returned to normal levels after 12 weeks. Both functional and structural changes after 12 weeks of immobilization of the uninjured glenohumeral joint are reversible by remobilization. The collagen composition of the capsule seems unrelated to the degree of capsular contraction that occurs during 12 weeks of immobilization and subsequent remobilization.
In this contribution we stress the fact that not all rotator cuff tendinopathies are degenerative in nature. Moreover, we insist on a clear distinction between intrinsic and extrinsic tendinopathies. In a final note we point out that the impingement syndrome is not always due to a developmental or acquired spur of the anterior part of the acromion.
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Since 1989, injecting drug use (IDU) related HIV infection has affected thousands of young adults in Manipur, a north eastern state of India bordering Myanmar following a similar kind of epidemic in adjoining countries like Thailand and Myanmar. During a clinical surveillance of a group of HIV positive IDUs for a natural history study at Manipur, herpes zoster (HZ) emerged as the most specific early HIV related illness (positive predictive value of 100%) in patients belonging to the age group of 12-45 years. Data collected from the dermatology departments of the two main hospitals of the state revealed that there had been an epidemic of HZ since 1990 (rate of 1990 being 11.3/1000 compared to 6.5/1000 in 1989, P value < 0.0001) among males of 12-45 years. The epidemic of HZ has been attributed to the preceding epidemic of IDU related HIV in the same age and gender group occurring 1 year earlier. HZ should be recognised as a marker condition similar to tuberculosis indicating the necessity of screening for HIV in regions where the dual problem of IDU and HIV exist in young adults.
OBJECTIVE: The attachment zone of the rotator cuff tendons in the elderly was studied immunohistochemically in order to determine how degenerative changes affected the pattern of collagen fiber distribution. METHODS: Twenty-seven cuffs with their bony insertion were obtained from 22 postmortem cases of both sexes ranging in age from 52 to 90 years and without a history of shoulder ailments. In addition, 3 cuff specimens from cadavers in the 3rd and 4th decades were examined for comparison. Sections of formalin fixed tissues were stained by peroxidase antiperoxidase (PAP) technique using monoclonal antibodies against types I, II and III collagen. RESULTS: Degenerative changes affecting the fibrocartilage primarily were characterized by calcification, fibrovascular proliferation and microtears. In addition, they were found in all the cuff tendons of elderly individuals but not in those from younger subjects. Immunohistochemically, the attachment zone in areas without degenerative lesions showed collagen type I labelling strongly in bone but only moderately in the fibrocartilage. The predominant labelling in the fibrocartilage was for collagen type II, and collagen type III labelled principally in perichondrocytic areas. The tide-mark showed inconsistent labelling for any of the collagen types. In the presence of degenerative lesions, the disposition of fiber types was interrupted by calcification and microtears. Collagen type II composition of the fibrocartilage was markedly altered by the presence of fibrovascular tissue which labelled only for collagen type III. CONCLUSION: We conclude that severe degenerative changes in the cuff tendons of elderly individuals, alter the collagen characteristic of the rotator cuff and that the changes could be associated with impairment of biomechanical properties of the attachment zone, and may give rise to the clinical syndrome of enthesopathy.
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A 25-year-old man developed a false aneurysm as a result of acute disruption of the aortic wall immediately after successful balloon dilatation of his coarctation. He underwent emergency resection of the false aneurysm and end-to-end anastomosis of the descending aorta with an excellent result. The diagnosis and management of this complication are discussed.
The collagen fibres in the area of attachment of the supraspinatus tendon to bone were studied immunohistochemically in 12 mature female New Zealand white rabbits. The labelling of type I collagen was uniformly prominent in the bone as well as in the fascicles of the tendon proper but inconspicuously scattered in the unmineralised and mineralised zones of the fibrocartilage. Type II collagen, not detected in the tendon proper, was widespread in both zones of the fibrocartilage. Type III collagen, on the other hand, appeared to be confined mainly to the zone of unmineralised fibrocartilage, in addition to its presence in the endotenon of the tendon proper. The region of the tidemark failed to show immunostaining for any of the collagen fibre types. In conclusion, this study demonstrates that, although all the principal fibrous collagen types are constituents of the supraspinatus tendon at its attachment site, the distribution pattern of immunolabelling varies from zone to zone.
The effects of immobilization on the function of the glenohumeral joint and its capsule were investigated in eight beagle dogs. One foreleg of each animal was immobilized in a spica cast, and the dogs were euthanized after 4, 8, 12, and 16 weeks of immobilization in groups of two. The contralateral limb and the forelegs of two normal beagles were used as controls. At the time of euthanasia, the range of motion, intraarticular filling volume during passive movements of the joint, and intraarticular filling volume to rupture the capsule were measured. The synovium, including the capsule and the subscapular bursa, were examined histologically. In the immobilized limb, there was progressive restriction in the range of motion with increases in intraarticular pressure, and the filling volume that was required to cause a rupture of the capsule diminished. Morphologically, the capsule and the subscapular bursa showed focal adhesions. Thus, it appeared that immobilization of these canine forelimbs produced changes in the glenohumeral joint that resembled those of frozen shoulder in humans.
The antileishmanial potency of doxorubicin conjugated to mannose-human serum albumin (man-HSA) was tested in experimental visceral leishmaniasis. Conjugation of doxorubicin did not decrease the affinity of the neoglycoprotein for the macrophage mannose receptor. Conjugated doxorubicin eliminated intracellular amastigotes of Leishmania donovani in peritoneal macrophages almost 12.5 times more efficiently than did the free drug and greatly reduced and possibly eliminated splenic intracellular parasites in four consecutive dosages at 5 micrograms/kg/day for 45 days. Free drug at a similar dose had little effect. The leishmanicidal effect of doxorubicin conjugate can be prevented by competitive inhibitors such as man-HSA or mannan and inhibitors of receptor-mediated endocytosis such as colchicine and monensin. These results not only indicate the potential of doxorubicin as an effective chemotherapeutic agent for leishmaniasis but also establish the use of mannosylated neoglycoprotein as a drug carrier in the therapy of macrophage-associated diseases.