Biomedical subjects
Publications and source records attributed to P Ghosh.
Two sets of testicular tumors involving nontwin siblings are reported. The possibility dysgenesis and dysgonesis and the totipotentiality of the cells in the pathogenesis of these tumors are described and discussed
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The anti-inflammatory drugs, sodium salicylate, indomethacin, hydrocortisone, ibuprofen, and flurbiprofen, were examined for their effects on sulphated glycosaminoglycan synthesis in aged human cartilage in vitro. Cartilage was obtained from femoral heads removed during surgery and drug effects were found to vary significantly from one head to another. Statistical analysis of the results showed that sodium salicylate exhibits concentration-dependent inhibition of glycosaminoglycan synthesis over the concentration range used. Indomethacin, hydrocortisone, and ibuprofen, at concentrations comparable to those attained in man, caused a statistically significant depression of sulphated glycosaminoglycan synthesis in cartilage from some femoral heads but not others, reflecting the variable response of human articular cartilage to anti-inflammatory drugs. Sodium salicylate and indomethacin at higher doses produced significant (Pless than 0-005) inhibition of sulphated glycosaminoglycan synthesis in all femoral heads studied. The results for flurbiprofen were less conclusive; this compound appears not to inhibit glycosaminoglycan synthesis over the concentration range used.
The total nitrogen, collagen and non-collagenous protein (NCP) content of the nucleus pulposus (NP), transitional zone (TZ) and annulus fibrosus (AF) of the beagle (a chondrodystrophoid breed) and greyhound (a non-chondrodystrophoid breed) intervertebral discs have been determined over the age range birth to 124 months. Discs were sampled at three spinal levels - lumbosacral, lumbar and thoracic regions. The beagle NP attains an average NP collagen content of 25% dry weight before 11 months of age, whereas the greyhound NP content is less than 5% collagen for most of its life. The NCP of the young greyhound disc is greater than that of the beagle of corresponding age. Plots of the ratio of collagen/NCP for discal regions at various ages highlight the large differences between the two breeds of dog. It is suggested that these differences in protein distribution are related to the elevated incidence of intervertebral disc prolapse in the beagle.
The chemical composition of the intervertebral disc of 9-month-old chondrodystrophoid and nonchondrodystrophoid dogs was studied for collagen, noncollagenous protein and glycosaminoglycan. Content of these substances differed significantly between breeds. The differences were most marked in the nucleus pulposus; the noncollagenous protein content of the nonchondrodystrophoid breed was higher than in that of the chondrodystrophoid dogs. The total nitrogen value of the nonchondrodystrophoid nuclei pulposi was less than that of the corresponding chondrodystrophoid discs mainly because of the high collagen content of the latter discs. Histochemically, it was found that the nuclei pulposi of the nonchondrodystrophoid breed contains larger amounts of glycosaminoglycan than in the discs of the chondrodystrophoid breeds.
Through the use of a critical electrolyte concentration staining technique, the glycosaminoglycans (GAGs) in the nucleus pulposus region of the canine intervertebral disc were arbitrarily identified as "hyaluronic acid", chondroitin sulphate and keratan sulphate. Approximate estimates of GAG concentration could be qualitatively deduced by determining the appropriate GAG "ALCIANOPHILIC INDEX". This index was considered to be an effective qualitative adjunct to chemical quantitation of GAGs in the intervertebral disc.
Gemfibrozil was found to be an effective hypotriglyceridaemic agent in types IV, IIb and V hyperlipoproteinaemia. When given at a dose level of 800 mg/day its activity was nearly of the same order of magnitude as 1.5 g/day of clofibrate.
Time intervals between the onset of the presenting symptom (chest pain) and arrival in a coronary care unit were studied for 221 admissions arranged by conventional means. The median figure for "patient delay" was 60 minutes, for "general-practitioner delay" 20 minutes, for "ambulance delay" 30 minutes, and for "transit delay" 30 minutes. The median "total delay" was three hours 30 minutes.Only 4.5 per cent of the patients were under intensive coronary care within one hour, the time of the highest mortality risk. A mobile coronary service should be capable of increasing the proportion of patients brought under special care within the first hour, but the time taken by the patient to realise the nature of the emergency and summon aid is likely to remain the most critical factor.
The nucleus pulposus (NP) and annulus fibrosus (AF) of immature rabbit intervertebral discs (IVD) have been subjected to the dissociative extraction procedure of Sajdera and Hascall (1969). The soluble, insoluble and unextracted fractions so obtained were analysed for total nitrogen, collagen, tyrosine, uronic acid, hexosamine and sialic acid content. A high proportion of non-collagenous protein, hexose and sialic acid in the NP insoluble fraction suggests the presence of glycopeptides associated with collagen and/or proteoglycans. The levels of proteoglycan in the soluble NP and AF fraction are similar. Immature (soluble) collagen, however, resides largely in the AF region. The metabolism of rabbit IVD protein components was also investigated both chemically and by autoradiography. L-Tyrosine-3,5-H3 was administered intraperitoneally (3 mc/kg) to 4 week-old rabbits. Animals were sacrificed at various time intervals and the harvested tissues extracted as before and lumbar discs collected. The levels of L-Tyrosine-3,5-H3 in the NP and AF insoluble and soluble fractions were determined using a tritium scintillation counting procedure and localisation by autoradiography. Pronounced extracellular activity of proteoglycan and glycoprotein is not evident before 24 hours. Soluble collagen, however, is synthesized and dispersed within 4 hours of isotope administration.
The plasma urate concentration of 70 patients with acute myocardial infarction increased progressively up to the seventh day and was significantly higher than in a group of 23 patients with ischaemic changes only. Diuretic treatment might have accounted for an early rise in urate levels but the persistent increase seen at seven days could not be so explained.
A potential enzymic mechanism for the degradation of glycosaminogly cans was characterised using enzymes found in rheumatoid synovial fluid from the knee joint. This mechanism involves a true hyluronidase together with the concerted action of beta-glucuronidase and beta-N-acetylhexosaminidase. The contribution of the exopolysaccharidases to hyaluronate degradation was demonstrated by the use of specific inhibitors, while the distinct identity of a true hyaluronidase was shown by ammonium sulphate and agarose gel column fractionations. Only the hyluronidase fraction was capable of degrading high molecular weight hyaluronate. The exopolysaccharidase activities were shown to be markedly elevated in rheumatoid as compared to osteoarthritic synovial fluid and also normal serum. On the other hand, hyluronidase was similarly active in rheumatoid and osteoarthritic synovial fluids; both these levels were lower than that of normal human serum. Hyaluronidase in synovial fluid may thus be derived by diffusion from serum, since it is of relatively low molecular weight (60 000). The pH requirements of this enzyme system and the strong inhibition of hyaluronidase by synovial fluid make it unlikely that the mechanism operates extracellularly. It is proposed that as a lysosomal mechanism, however, it is an important contributing factor in the chronic erosion process characteristic of rheumatoid arthritis.
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In a double-blind controlled trial lasting 12 months, long-term practolol therapy had no significant effect on plasma-lipid concentrations in twenty patients who had had acute myocardial infarction.
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