Double primary carcinoma of gall bladder and bile duct.
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Biomedical subjects
Publications and source records attributed to A Khare.
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Transforming growth factor beta (TGF beta) and 1,25-dihydroxyvitamin D3 (1,25D3), when added simultaneously to a human osteosarcoma cell line, MG-63, induce alkaline phosphatase activity 40-70-fold over basal levels, 6-7-fold over 1,25D3 treatment alone, and 15-20-fold over TGF beta treatment alone. TGF beta and 1,25D3 synergistically increased alkaline phosphatase specific activity in both matrix vesicles and plasma membrane isolated from the cultures, but the specific activity was greater in and targeted to the matrix vesicle fraction. Inhibitor and cleavage studies proved that the enzymatic activity was liver/bone/kidney alkaline phosphatase. Preincubation of MG-63 cells with TGF beta for 30 min before addition of 1,25D3 was sufficient for maximal induction of enzyme activity. Messenger RNA for liver/bone/kidney alkaline phosphatase was increased 2.1-fold with TGF beta, 1.7-fold with 1,25D3, and 4.8-fold with the combination at 72 h. Human alkaline phosphatase protein as detected by radioimmunoassay was stimulated only 6.3-fold over control levels with the combination. This combination of factors was tested for their effect on production of three other osteoblast cell proteins: collagen type I, osteocalcin, and fibronectin. TGF beta inhibited 1,25D3-induced osteocalcin production, whereas both factors were additive for fibronectin and collagen type I production. TGF beta appears to modulate the differentiation effects of 1,25D3 on this human osteoblast-like cell and thereby retain the cell in a non-fully differentiated state.
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A new cardenolide tetraglycoside, oxyline, was isolated from the dried roots of Oxystelma esculentum. On the basis of chemical and spectroscopic evidence the structure of oxyline was established as 3-epi-uzarigenin-3-O-beta-D-cymaropyranosyl-(1----4)-O-beta- D-thevetopyranosyl-(1----4)-O-beta-D-cymaropyranosyl- (1----4)-O-beta-D-digitoxopyranoside.
Several recent observations carried out by many investigators have offered some clues in understanding the mechanism of how food restriction (FR) acts in the prolongation of life-span, but the precise mechanisms involved in modulating the immune system have not been clearly understood. Our own ongoing studies indicate that FR may act at the molecular level and may extend the life-span by modulating functional activities of several genes in various target tissues. For instance, while cytochrome P-450 IIB1 and IIB2 expression is known to decline with age in ad libitum-fed rats, FR prevented the loss of (drug-inducible) P-450 enzymes in liver tissues. In addition, both alpha 2u-globulin and senescence marker protein 2 expressions, which are regulated by hormones, were also modulated during aging by FR in Fischer 344 male rats. In short-lived autoimmune-prone mice, both FR and omega-3 (n-3) fatty acids diet lowered the severity of autoimmune disease both in lupus-prone (NZB x NZW)F1 mice and in mice prone to develop lymphoproliferative and renal diseases, whereas saturated (n-9) and polyunsaturated (n-6) dietary lipids not only exacerbated autoimmune disease, but also significantly enhanced expression of several oncogenes in lymphoid tissues. FR and omega-3 fatty acids decreased the expression of certain oncogenes. Both FR and omega-3 fatty acids may modulate the aging and autoimmune disease processes by not only altering the fatty acid composition, membrane fluidity, and signal transduction, but also by modulating the lymphokine hormone receptors and their functions and thereby modulating expression of several genes in various tissues during the aging process.
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This review addresses the role of lipids and membranes in biologic calcification and examines their regulation during endochondral ossification. The close association of lipids with mineral deposition has been well established. Early observations indicated that lipids, particularly phospholipids, can not be totally extracted from calcified tissues until the tissues are decalcified. Phospholipids associated with mineral are also enriched in extracellular membrane vesicles, called matrix vesicles. Numerous studies indicate that mineral deposits in calcifying cartilage are first seen in these phosphatidylserine and alkaline phosphatase enriched vesicles and that the process of endochondral calcification of epiphyseal growth plate is possibly mediated by them. Matrix vesicles, and the phospholipids present in them, appear to be involved in initial formation of calcium hydroxyapatite crystals via the interaction of calcium and phosphate ions with phosphatidylserine to form phospholipid:Ca:Pi complexes (CPLX). CPLX is present in tissues which are undergoing initial mineral deposition but are absent from nonmineralizing tissues. Evidence suggests that CPLX resides in the interior of matrix vesicles where the earliest mineral crystals are formed in association with the vesicle membrane. More recently, it has been determined that specific membrane proteins, called proteolipids, participate in CPLX formation and hydroxyapatite deposition, in part by structuring phosphatidylserine in an appropriate conformation. Phosphatidylserine involvement in the initiation of mineralization has been extensively investigated because of its extremely high binding affinity for Ca2+. In addition to structuring a specific phospholipid environment, proteolipids may also act as ionophores, promoting export of protons and import of calcium and phosphate, both requirements of biologic calcification.(ABSTRACT TRUNCATED AT 250 WORDS)
Matrix vesicles are membrane organelles found in the extracellular matrix of calcifying cells. Vitamin D-responsive alkaline phosphatase specific activity has been localized to matrix vesicles in chondrocyte and osteoblast cultures. The effect of hormone is both metabolite and cell specific. Alkaline phosphatase in matrix vesicles produced by resting zone chondrocytes is stimulated by 24,25(OH)2D3 whereas alkaline phosphatase in matrix vesicles produced by growth zone chondrocytes is responsive to 1,25(OH)2D3. However, mesenchymal cell cultures, which exhibit a chondrogenic phenotype when exposed to bone inductive proteins in vitro, produce vesicles with alkaline phosphatase activity that is unaffected by either 1,25(OH)2D3 or 24,25(OH)2D3. Incorporation and release of arachidonic acid into phosphatidylethanolamine is also differentially regulated by 1,25(OH)2D3 and 24,25(OH)2D3 in chondrocytes. These data suggest that vitamin D metabolites may regulate endochondral ossification by altering matrix vesicle enzyme activities, perhaps through changes in membrane phospholipid metabolism.
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This study was conducted on 50 patients in the Central Institute of Orthopaedics, Safdarjung Hospital, New Delhi, from June to October 1985. With the help of a child's stethoscope and a tuning fork of 128 Hz, the sound conducted by an injured limb was compared with that by the uninjured limb. The presence of a fracture reduced or abolished the conduction of sound by a bone. This method allows a quick examination without causing any pain, which is an advantage in an uncooperative patient. It is also reliable in the unconscious. The test is so simple that paramedical staff can use it. The results were correct in 94 per cent of patients and were confirmed by radiological examination whereas clinical diagnosis was correct in only 88 per cent of cases.
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Serum copper estimations were carried out in 44 cases of acute myocardial infarction, 23 cases of angina and 40 age and sex matched healthy controls. A highly significant degree of rise in serum copper levels was observed in patients with acute myocardial infarction as compared to cases of angina and controls. The levels showed a gradual rise with peak on 7th day followed by a gradual decline returning to normal on 28th day. The pattern was the same both in complicated and uncomplicated cases except that values were still higher on the 28th day in complicated cases of acute myocardial infarction. Mean peak serum copper levels were significantly higher (p less than .001) in complicated cases of acute myocardial infarction as compared to uncomplicated cases. Significant correlation was found between serial serum copper changes and creatinine phosphokinase and lactic dehydrogenase levels. The prognostic and diagnostic significance of serum copper has been discussed.
A histomorphologic study was done at intervals up to 10 days after causing a fracture in both hindleg tibiae in dogs and giving direct electrical stimulation in one tibia, the other being used as control (20 microns ampere of direct current were passed in 28 limbs and the current was maintained with the help of a simple regulator developed by the authors). The radiologic and histomorphologic study showed definite evidence of early start and completion of healing processes in the electrically stimulated hindlegs. Negative potentials induced at the fracture sites appeared to be the cause of improved healing. The incidence of infection and focal necrosis at the anode was minimal in this experiment.