A new muscle transplantation operation for orbitoplasty after total maxillectomy: report of case.
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Biomedical subjects
Publications and source records attributed to P Ghosh.
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The concentration of hyaluronic acid (HA) and proteins in synovial fluids of hip and shoulder joints of a variety of canine breeds has been investigated. In the Australian Kelpie, a working dog with a low incidence of hip dysplasia, shoulder synovial fluid viscosity and HA concentration were higher than in similar joints of Alsatians in which hip dysplasia is relatively common. Moreover, the HA levels and viscosity in shoulder fluids of animals with clinically defined hip dysplasia were substantially lower than in all other breeds studied. On the basis of these findings, we propose that hip dysplasia and other joint abnormalities may arise as a consequence of a deficiency in the levels of HA in synovial fluids.
Nineteen 4-hydroxy- and 4-methoxy-2-pyrones related to elasnin (I) have been assayed for in vitro inhibition of human sputum elastase (HSE), porcine pancreatic elastase, alpha-chymotrypsin, and trypsin. Inhibition is reported as Ki and Ki'; percentage inhibition was dependent on [S] in a number of cases, making it unsuitable as a measure of relative inhibition. The 3-(1-oxoalkyl)-4-hydroxy-6-alkyl-2-pyrones were found to be most effective, the octyl homologue 11 being the most potent inhibitor (Ki = 4.6 microM, 30 times better than the lead compound). A further reduction in inhibition was observed when the hitherto hydrophobic 6-substituent was substituted by a branched functionality of hydrophilic nature. Conversely, methylation of the 4-hydroxy group of the 6-alkyl-2-pyrones increased inhibitory activity. The mechanism of inhibition varied from pure noncompetitive to mixed type to uncompetitive and was found to be dependent on the pattern of substitution. We believe that the 4-hydroxy-2-pyrone binds to the S4 subsite, with the 6-substituent extending across the S4-S1 subsites and the 3-substituent occupying the S5 subsite. The length of the inhibitor binding region was calculated to be approximately 24 A. None of the hydrophobic compounds were found to have any appreciable inhibition (less than 10%) with porcine pancreatic elastase, bovine alpha-chymotrypsin, and bovine trypsin when tested at the limit of their solubility. The hydrophilic compounds were nonspecific, inhibiting all four enzymes. Dialysis was used to show that the interaction is fully reversible.
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Generally, protein energy malnutrition is accompanied with vitamin A deficiency. The present study was undertaken to evaluate the importance of the quality and the quantity of dietary proteins on the in vitro secretion and uptake of vitamin A in growing rats. The results show that the in vitro release of radioactive vitamin A was greater in rats fed Bengal gram diets as compared to those fed casein diets. However, this relationship between the two groups of rats was reversed for the in vitro uptake of radioactive vitamin A from plasma by various extrahepatic tissues. Thus the vitamin A status of the animal is profoundly influenced by the quality and the quantity of dietary proteins.
It is now well established that the meniscus performs a number of roles that are important to the efficient performance of the knee joint. Of particular importance is the recognition of its load-bearing function and its stabilization of the joint during flexion-extension. The compression of the wedge-shaped meniscus during loading is translated into circumferential stresses, and the collagen fiber distribution and orientation is well adapted for this mechanical role. Proteoglycans of the meniscus have structural characteristics in common with those of articular cartilage but do not appear to influence the tensile properties of menisci. With aging and degeneration, compositional changes take place within the meniscus that reduce its ability to transmit tensional stresses, and this contributes to failure. Total meniscectomy is not a benign procedure. Partial excision has less deleterious effects on the joint. Surgical repair of meniscus lesions has now emerged as a procedure of some significance and laboratory research suggests that a solution to this problem may be within reach. Experimental studies in dogs also indicate that chondroprotective agents such as semisynthetic sulfated polysaccharides may protect articular cartilage after meniscectomy.
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A series of non-steroidal anti-inflammatory drugs (NSAIDs) and some of their metabolites were evaluated for their ability to inhibit the proteolytic activity of human granulocyte elastase (HGE) and cathepsin G (HGC-G). The enzyme activity was monitored using specific synthetic chromogenic substrates. The results obtained indicated that phenylbutazone, sulindac, piroxicam and gold sodium thiomalate significantly inhibited HGE (Ki less than 0.5 mM), while only sulindac, diflunisal and gold sodium thiomalate were effective inhibitors of HGC-G (Ki less than 0.4 mM). Studies on metabolites of some of the NSAID tested were found to be superior inhibitors of both HGE and HGC-G than the parent molecules. Moreover, of the 18 compounds examined, the major metabolite of sulindac, sulindac sulphide was the most potent inhibitor of HGE (Ki = 0.01 mM) and HGC-G (Ki = 0.15 mM).
Human lumbar disc tissue when extracted with 4M GuHCl and subjected to dissociative CsCl density gradient ultracentrifugation yielded trypsin inhibitor activity in the low bouyant density fractions (rho less than or equal to 1.38 g/ml). Disc proteoglycans sedimented in the high bouyant density fractions (rho greater than or equal to 1.5 g/ml). Sephadex G75F gel filtration of the low bouyant density protein fractions afforded a major low molecular weight (Kav = 0.5) trypsin inhibitor pool which was further purified by trypsin affinity chromatography. This latter step facilitated separation of the trypsin inhibitors from neutral proteinase activity also present. The trypsin inhibitor fraction so isolated was shown to possess potent inhibitory activity against a range of human serine proteinases including leukocyte elastase and cathepsin G, urokinase, kallikrein, plasmin and thrombin. Significantly this serine proteinase inhibitor preparation effectively prevented degradation of proteoglycans by a neutral proteinase also isolated from the human intervertebral disc.
Using a peritoneal macrophage/articular cartilage co-culture system, it was shown that the serine proteinase inhibitor derived from human articular cartilage modulated the release of 35S-labelled proteoglycan into media in a concentration dependent manner. Since the cartilage inhibitor fractions used were free of metallo-proteinase and cysteine proteinase inhibitory activity, but strongly inhibited serine proteinases, it was suggested that such enzymes may be implicated in the activation of latent metallo-proteoglycanases produced by chondrocytes on exposure to IL-1.
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It is proposed that primary atrophic rhinitis belongs to a group of conditions under the heading 'Reflex Sympathetic Distrophy Syndrome'. This leads to decalcification of the turbinals, as in Sudeck's atrophy. Collapse of the decalcified turbinals is brought about by the impact of the inspiratory stream, and this is followed by atrophic changes. Based on this hypothesis, a new operation ('Vestibuloplasty') has been devised in order to direct the stream away from the turbinals and to dissipate the force of the stream so that its impact on the turbinals is minimized. Following this operation, 92 per cent of the cases have benefitted; this is comparable to the result following Young's or a modified Young's operation. After vestibuloplasty the patient can breathe through the nose and clean the nose as normal persons do; a second-stage procedure for reopening the nostril is not necessary and the chances of recurrence are negligible as compared to those following Young's operation.
The imino proton nuclear magnetic resonance spectrum of Escherichia coli 5S ribonucleic acid (RNA) changes when the Mg2+ ion concentration drops below physiological levels. The transition between the physiological and low magnesium spectral forms of 5S RNA has a midpoint at approximately 0.3 mM Mg2+. Many of the most conspicuous changes observed in the downfield spectrum of 5S RNA as the magnesium concentration is reduced are due to adjustments in the structures of helices I and IV and the disappearance of resonances originating in helix V. The binding of ribosomal protein L25 to 5S RNA in the absence of magnesium stabilizes helix V structures.
A group of young (2.0 +/- 0.6 years) (group 1) and old (9.7 +/- 1.5 years) (group 2) beagle dogs were given Na2 35SO4 (1.0 mCi/kg) intravenously 60 days prior to being killed to radiolabel their proteoglycans. Lumbar discs were removed and dissected into nucleus pulposus and annulus fibrosus. Proteoglycans were extracted at 4 degrees C from these tissues with buffered 4.0 M Gdn-HCl containing proteinase inhibitors, and purified by CsCl density gradient ultracentrifugation. The average hydrodynamic size and ability of the purified proteoglycans to aggregate in the presence of excess hyaluronic acid was determined by Sepharose CL-2B chromatography. The galactosamine/glucosamine ratios of these proteoglycans as well as their non-aggregating fractions were also ascertained. The proteoglycan content of discs of old animals was significantly less than in the young. The proportion of 35S-labelled, or non-labelled proteoglycans which could aggregate in the presence of hyaluronic acid was also much lower in the preparations isolated from the older discs. In contrast, the average hydrodynamic size of the non-aggregating proteoglycans isolated from the annuli fibrosi of group 2 animals were larger than the corresponding population of group 1 animals. Aminosugar analysis of these same proteoglycan fractions from older animals afforded galactosamine/glucosamine ratios (mean 1.81 +/- 0.14) which were less than the younger age group (mean 2.63 +/- 0.40). These data suggest that with ageing and degeneration the proteoglycans of the beagle disc undergo increased degradation with the accumulation in the annulus fibrosus of a population which is of larger average hydrodynamic size and richer in keratan sulphate than proteoglycans present in younger tissues.
The proteoglycans, and proteinase inhibitors of normal and degenerate human articular cartilage have been isolated by 4.0M GuHCl extraction, CsCl density gradient ultracentrifugation and Sephadex G-75 gel filtration chromatography. While a small amount of trypsin inhibitory activity eluted in the Sephadex G-75 void volume, the major proteinase inhibitors were included in the column with MWs within the range 1 - 3 X 10(4) daltons. The large molecular weight trypsin inhibitor was identified as alpha 1-trypsin inhibitor, which was present in greater amounts in degenerate tissue. The Sephadex G75 included fractions (LMWCI) showed inhibition against cysteine and serine proteinases and were reduced in degenerate tissue, but slightly elevated in aged "normal" cartilage. We suggest that the resistance of ageing cartilage to enzymatic degradation may be related to the levels of LMWCI within these tissues.
The in vitro synthesis of HA in synovial fibroblasts derived from normal and rheumatoid joints was investigated. Incubation of these cells with ArteparonR and a variety of sulphated dextrans showed that macromolecular HA synthesis could be modified by these drugs. ArteparonR and a dextran sulphate (DS1) of molecular weight 20,600 and 0.8 sulphate substitution stimulated HA synthesis in rheumatoid cells by approximately 150%. In contrast the dextrans with higher sulphate substitution but similar molecular weight were less effective. Gel filtration chromatography of media from drug-treated cells showed an increase in HA hydrodynamic size.
As part of a project to study the effect of copper deficiency (CD) on bone development in young dogs, the composition and metabolism of proteoglycans (PGs) and extractability of collagens in the epiphyseal growth plate cartilage (EGPC) and articular cartilages (AC) were investigated. Copper deficiency was induced by feeding ammonium tetrathiomolybdate (TTM) a copper antagonist. The collagen of cartilages from TTM-treated animals was significantly more soluble in 0.5 saline than control tissues. While no distinction between TTM-treated and control cartilages was evident in terms of PG content or extractability under associative (0.5 M-GuHCl) or dissociative (4.0 M-GuHCl) conditions, the sedimentation behaviour of the PG aggregates following CsCl density gradient ultracentrifugation suggested less polydispersity of PGs in preparations from the TTM-treated animals. Moreover, analysis of the PG monomers from EGPC of TTM animals showed galactosamine/glucosamine ratios higher than control preparations, suggesting a reduced keratan sulphate content in these preparations. Organ culture of EGPC showed a significant reduction in the incorporation of 35S into PGs and of 3H-thymidine into DNA in the tissues of TTM-treated animals relative to controls. From these findings we deduce that the catabolism of PGs and the extent of collagen cross-linking in EGPC of TTM-treated animals may be reduced relative to age-matched control tissues.