Biomedical subjects

P Ghosh

Publications and source records attributed to P Ghosh.

At least 145 records · Page 8Linked to original sources

PubMed1997

Topographical variation in the catabolism of aggrecan in an ovine annular lesion model of experimental disc degeneration.

An established model of experimental disc degeneration (Osti et al., Spine 15:762, 1990; Melrose et al., J Orthop Res 10:655, 1992) was used in this study. Four 2-year-old sheep received anterolateral incisions (4 x 10 mm) in the outer one-third of the annulus fibrosus of their L2-L3 and L4-L5 discs (lesion group). The annulus was not incised in another four sham-operated animals. After 6 months the sheep were killed, lumbar discs were dissected into lateral halves of the annulus fibrosus and the nucleus pulposus. Cells were isolated from disc tissues enzymatically and were grown in alginate bead culture to examine the proteoglycan metabolism of cells from lesion and control zones. The media of lesion zone cultures contained relatively high levels (compared with sham cultures) of catabolic fragments of the large, high-buoyant-density proteoglycans as demonstrated by Western blotting using monoclonal antibodies (5-D-4, 3-B-3, 1-C-6) and biotinylated hyaluronan and also by gel chromatography. Furthermore, cells from the vicinity of the lesion site also synthesized significantly lower levels (compared with sham cultures) of aggrecan that was retained within the alginate beads. Collectively, these data indicated that focal depletion of large, high-buoyant-density proteoglycans was evident within lesion sites in this model of experimental disc degeneration. The introduction of an annular lesion therefore significantly affected the proteoglycan metabolism of endogenous disc cell populations. The unique hydrodynamic and viscoelastic properties of the intervertebral disc are dependent to a large degree on the tissue levels of aggrecan. The focal depletion of aggrecan by annular lesions therefore may represent an important predisposing factor to the subsequent degeneration of these intervertebral discs.

Aggrecans↗

PubMed1997

Chronic ethanol induced impairment of hepatic glycosylation machinery in rat is independent of dietary carbohydrate.

In recent years, a number of studies have been reported that have clearly established that hepatic glycosylation machinery is affected by chronic ethanol treatment in rats. We have previously reported that chronic ethanol treatment in rats resulted in decreased glycosylation of transferrin and apolipoprotein E with concomitant decreases in enzymatic activities of Golgi galactosyltransferases and sialyltransferases. In all these studies investigators have invariably used the well-accepted dietary formulation of alcohol diet as proposed by Lieber and DeCarli. However, questions were raised whether the lower carbohydrate content in Lieber's alcohol diet may be responsible for observed effects of ethanol on hepatic glycosylation machinery. Therefore, to verify whether or not the crucial effects of chronic ethanol treatment on hepatic glycosylation machinery as observed in our studies, were truly caused by ethanol, we have extended our studies on protein glycosylation with the inclusion of a third dietary group that was compensated for carbohydrate content. In this investigation, rats were fed with three dietary regimen corresponding to control, ethanol, and carbohydrate compensated ethanol group and studies were done on (i) labeled leucine, galactose and N-acetylmannosamine incorporation into transferrin and apolipoprotein E, and (ii) hepatic galactosyltransferase and sialyltransferase activities in Golgi rich fraction in rat. Our results clearly showed that regardless of the carbohydrate content, marked decreases in the incorporation of labeled sugars into transferrin and the enzymatic activities of galactosyltransferase and sialyltransferase occurred in rats administered chronic ethanol. Thus, it is reasonable to conclude that it is not the carbohydrate content of the diet but ethanol per se, when administered chronically, greatly impairs the glycosylation machinery of rat liver and that the magnitudes of these effects are selectively specific with regard to the type of sugar or the glycosylation enzyme.

Animals↗

PubMed1997

[Animal models used for the evaluation of anti-osteoarthritis drugs].

Naturally occurring osteoarthritis occurs in a variety of animal species including mice, guinea pigs, dogs and cynomolgus macaques and some of these animals have been used to evaluate the ability of anti-osteoarthritis drugs to reduce synovial inflammation and preserve cartilage integrity. However, the genetically determined animal models of osteoarthritis require the establishment of colonies which may take several years to develop and may be influenced by the strain of animal used and ill-defined environmental factors. On the other hand, the injection of irritants or enzymes into joints, or destabilization by surgical means, can rapidly and reproducibly lead to joint arthropathy and has therefore been more widely used. Although small animals, particularly rats and rabbits, have been the favoured target species, large animals such as dogs and sheep offer many advantages including the opportunity to undertake topographical analysis of joint cartilage and serial aspiration of synovial fluid. Meniscectomy is a common orthopaedic procedure which, in man and animals, is known to lead to osteoarthritis. In the past we have used this technique to induce osteoarthritis in pure bred dogs but more recently we have employed pure bred Merino sheep, which were matched for age, sex and weight. Using this ovine model we have been able to monitor the early and intermediate stages of cartilage metabolism, as well as identify key proteinases responsible for the loss of proteoglycans from these tissues in osteoarthritis. The effects of anti-osteoarthritis drugs on inflammatory mediators and cartilage metabolism has been successfully studied using the ovine model of osteoarthritis.

Animals↗

PubMed1997

Histomorphological and immunohistochemical evaluation of joint changes in a model of osteoarthritis induced by lateral meniscectomy in sheep.

OBJECTIVE: To evaluate the histomorphological and immunohistochemical changes induced in cartilages of ovine stifle (knee) joints 6 months after unilateral lateral meniscectomy. METHODS: Osteochondral sections were obtained from 8 distinct regions of knee joints of 6 adult Merino wethers that 6 months earlier had undergone lateral meniscectomy. Joint regions of 6 age matched sheep housed under identical conditions were used for controls. Serial sections were stained with toluidine blue or immunolocalized with monoclonal antibodies (Mab) 3B3(-), 7D4, and 5B10, which recognize epitopes on proteoglycans. RESULTS: In control joints the cartilage from the region of the tibial plateau not protected by the meniscus had significantly (p < 0.005) more structural abnormalities than other joint regions. After meniscectomy, only cartilages in the lateral femorotibial compartment showed histomorphological changes consistent with osteoarthritis (OA). The nature and severity of the lesions differed between the topographical regions within the joint. The most severe were found on the lateral femoral condyles and tibial plateaus. Reactivity with Mab 3B3(-), 7D4, and 5B10 was increased only in the lateral compartment cartilages, and was stronger in mild rather than moderate OA. CONCLUSION: Six month lateral meniscectomy in sheep produces histomorphological and immunohistochemical cartilage changes analogous to those described for early human OA and in other animal models. The severity and type of lesions obtained were dependent on the topographical joint location, but were most evident in cartilages from the lateral compartment.

Animals↗

PubMed1996

Assembly, specific binding, and crystallization of a human TCR-alphabeta with an antigenic Tax peptide from human T lymphotropic virus type 1 and the class I MHC molecule HLA-A2.

T lymphocytes use TCR-alphabeta to bind and to recognize complexes of antigenic peptides bound to MHC proteins located at the surface of APCs. We have assembled and crystallized this intercellular complex of TCR/peptide/MHC from soluble human TCR-alphabeta and soluble peptide/HLA-A2 complexes. The soluble TCR-alphabeta binds specifically to its in vivo ligand, the complex of HLA-A2, and a peptide from the Tax protein of human T lymphotropic virus type 1. The soluble TCR also binds in vitro to an altered peptide ligand, which appears to be a partial agonist in T cell assays as determined by its ability to elicit different cytolytic and lymphokine secretion responses. Heterodimerization and the antigenic specificity of the TCR do not require its interchain disulfide bond, transmembrane segments, or glycosylations. Crystals of the TCR/peptide/HLA-A2 complex diffract x-rays, providing the means to study in atomic detail the mechanism of Ag-specific cell-cell recognition between T cells and target cells.

Amino Acid Sequence↗

PubMed1996

Association of human fas (CD95) with a ubiquitin-conjugating enzyme (UBC-FAP).

A novel human ubiquitin conjugating enzyme (UBC) was found to associate with Fas (CD95). The mRNA for this UBC Fas-associated protein (FAP) was widely expressed in human tissues, and the protein was identified in several mammalian cell lines. UBC-FAP shows strong homology to two recently identified UBCs, Hus5 and Ubc9, which control yeast cell cycle progression. UBC-FAP, but not an active site mutant, complemented ubc9-1(ts) mutants. This suggests that UBC-FAP is a human homologue of Ubc9, possesses ubiquitin conjugating activity, and may play an important role in mammalian cell cycle regulation. A single amino acid substitution in the death domain of Fas that abolishes Fas-mediated apoptosis also abolished Fas association with UBC-FAP, suggesting that UBC-FAP may play a role in Fas signal transduction. The sequence of UBC-FAP is identical to that of HsUbc9, a UBC recently shown to interact with Rad51.

Animals↗

PubMed1996

Structure of the complex between human T-cell receptor, viral peptide and HLA-A2.

Recognition by a T-cell antigen receptor (TCR) of peptide complexed with a major histocompatibility complex (MHC) molecule occurs through variable loops in the TCR structure which bury almost all the available peptide and a much larger area of the MHC molecule. The TCR fits diagonally across the MHC peptide-binding site in a surface feature common to all class I and class II MHC molecules, providing evidence that the nature of binding is general. A broadly applicable binding mode has implications for the mechanism of repertoire selection and the magnitude of alloreactions.

Crystallography, X-Ray↗

PubMed1996

Retinoic acid-induced transcriptional modulation of the human interferon-gamma promoter.

Disregulation of vitamin A metabolism is able to generate different immunological effects, including altered response to infection, reduced IgG production, and differential regulation of cytokine gene expression (including interleukin-2 and -4 and interferon-gamma (IFN-gamma)). In particular, IFN-gamma gene expression is significantly affected by vitamin A and/or its derivatives (e.g. retinoic acid (RA)). Here, we analyze the effect of retinoic acid on IFN-gamma transcription. Transient transfection assays in the human T lymphoblastoid cell line Jurkat demonstrated that the activation of the IFN-gamma promoter was significantly down-regulated in the presence of RA. Surprisingly, two different AP-1/CREB-ATF-binding elements situated in the initial 108 base pairs of the IFN-gamma promoter and previously shown to be critical for transcriptional activity were unaffected by RA. Utilizing promoter deletions and electrophoretic mobility shift analysis, we identified a USF/EGR-1-binding element cooperating in the modulation of IFN-gamma promoter activity by RA. This element was found to be situated in a position of the IFN-gamma promoter close to a silencer element previously identified in our laboratory. These results suggest that direct modulation of IFN-gamma promoter activity is one of the possible mechanisms involved in the inhibitory effect of retinoids on IFN-gamma gene expression.

Humans↗

PubMed1996

Using antibodies to perturb the coordination sphere of a transition metal complex.

Metal ions in the active sites of many metalloenzymes exhibit distinctive spectral and chemical features which are different from those of small inorganic complexes. These features are the result of the unusual geometric and electronic constraints that are imposed on the metal ion within the protein environment. Much effort has been invested to try to mimic this feature of metalloenzymes in synthetic systems, but this remains a formidable task. Here we show that one of the key lessons learned from the science of catalytic antibodies--that binding energy can be converted into chemical energy--can be exploited to 'fine-tune' the physicochemical properties of a metal complex. We show that an antibody's binding site can reversibly perturb the coordination geometry of a metal ion, and can stabilize a high-energy coordinated species. Specifically, antibodies designed to bind the organosilicon compound 1 also bind the geometrically similar Cu(I) complex 2. However, the antibody binds a slightly compressed form of 2, which is closer in size to 1. This distortion is manifested by a spectral shift--an 'immunochromic' effect.

Animals↗

PubMed1996

Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.

The mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex. Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced. We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28. Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner.

Base Sequence↗

PubMed1996

Intervertebral disc reconstitution after chemonucleolysis with chymopapain is dependent on dosage.

STUDY DESIGN: The current report describes a study in beagles in which the effects of intradiscal injection of three doses of chymopapain were evaluated with respect to the reduction of disc width and reconstitution of the nucleus pulposus. OBJECTIVES: To establish an intradiscal dose of chymopapain that would achieve optimal reduction in disc height followed by maximum reconstitution of the nucleus pulposus. SUMMARY OF BACKGROUND DATA: Earlier reports of the efficacy of high and low doses of chymopapain for chemonucleolysis have provided conflicting data, and a scientific basis for an appropriate dose is lacking. METHODS: Four mature, female beagles were subjected to chemonucleolysis using three doses of chymopapain as Chymodiactin (31, 63 and 125 picokatals/disc) injected into the L2-L3, L1-L2, and L3-L4 discs. Disc widths were monitored radiographically over 32 weeks. Proteoglycans were radiolabeled by intravenous injection with Na2 35SO4 (1 mCi/kg) 24 hours before sacrifice, and their specific activities (disintegrations per minute/mg proteoglycan), hydrodynamic size, and ability to aggregate determined. RESULTS: Sixty-three picokatals of Chymodiactin produced optimal disc reconstitution after chemonucleolysis. A reduction in disc height of approximately 35% was evident within 1 month and this slowly returned to approximately 90% of the preinjection value after 32 weeks. The nucleus pulposus contained approximately 75% of the proteoglycan content of control tissues, and most of these formed aggregates with hyaluronan. Disc collagen levels remained relatively unaffected by treatment. CONCLUSIONS: This study demonstrates that an effective reduction in disc width compatible with later reconstitution of the nucleus pulposus can be achieved experimentally with an appropriate dose of chymopapain. These data clearly indicate that an optimal dose of chymopapain for chemonucleolysis in humans needs to be established.

Animals↗

PubMed1996

Biotinylated hyaluronan: a versatile and highly sensitive probe capable of detecting nanogram levels of hyaluronan binding proteins (hyaladherins) on electroblots by a novel affinity detection procedure.

Hyaluronan influences cellular proliferation and migration in developing, regenerating and remodelling tissues and in tissues undergoing malignant tumour-cell invasion. The widespread occurrence of hyaluronan-binding proteins indicates that the recognition of hyaluronan is important to tissue organisation and the control of cellular behaviour. A number of extracellular matrix and cellular proteins, which have been termed the hyaladherins, have specific affinities for hyaluronan. These include cartilage link-protein, hyaluronectin, neurocan, versican and aggrecan, which all bind to HA within the extracellular matrix. Cellular receptors for hyaluronan such as CD44 and RHAMM (receptor for hyaluronate-mediated motility) have also been identified. In the present study biotinylated hyaluronan (bHA) was prepared by reacting adipic dihydrazide with a 170 kDa hyaluronan sample using the bifunctional reagent 1-ethyl-3-[3-(dimethylamino) propyl] carbodiimide. The resultant free amine moeity of the hydrazido-hyaluronan was then reacted with biotin succinimidyl ester (sulfo-NHS-biotin) to prepare the bHA. After 4-20% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotting to nitrocellulose membranes, bHA and avidin alkaline phosphatase conjugate could be used in conjunction with nitroblue tetrazolium/5-bromo-4-chloro-3-indolyl phosphate substrates to specifically visualise with high sensitivity (> or = 2 ng), bovine nasal cartilage link-protein, aggrecan hyaluronan binding region, and human fibroblast hyaluronan receptors such as CD-44. Conventional Western blotting using specific monoclonal antibodies to these proteins was also used to confirm the identities of these proteins.

Aggrecans↗

PubMed1996

Biotinylated trypsin and its application as a sensitive, versatile probe for the detection and characterisation of an ovine chondrocyte serine proteinase inhibitor using Western blotting.

Biotinylated trypsin (bT) was used as a probe on Western blots of 10-20% polyacrylamide gradient Tris-Tricine gels for the detection of serine proteinase inhibitors (SPIs) isolated from extracts of ovine articular cartilage and from chondrocyte conditioned culture medium. The major cartilage SPI, a 58 kDa glycoprotein, was purified by sequential Sephacryl S--300 gel permeation, concanavalin A affinity, anion exchange and Superose 12 fast protein liquid chromatography (FPLC). A low molecular weight SPI of approximately 6 kDa was also detectable in cartilage extracts after prolonged storage at 4 degrees C and following affinity chromatography on immobilised chymotrypsin, suggesting that the 6 kDa inhibitor may have arisen from proteolytic modification of the 58 kDa SPI. Analysis of chondrocyte conditioned culture medium using the bT detection system revealed that the major SPI present was the 6 kDa species although a small amount of the 58 kDa SPI was also detectable. The large molecular weight 'native' cartilage SPI was distinct from ovine alpha1-proteinase inhibitor (alpha1-PI) when examined by native polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF). The 6 kDa cartilage SPI was indistinguishable from basic pancreatic trypsin inhibitor (BPTI, aprotinin) following sodium dodecyl sulfate (SDS)-PAGE under reduced and nonreduced conditions. Amino terminal sequencing of the 6 kDa cartilage SPI revealed a strong (90%) homology with BPTL.

Amino Acid Sequence↗

PubMed1996

Topographic variation in biglycan and decorin synthesis by articular cartilage in the early stages of osteoarthritis: an experimental study in sheep.

Articular cartilage contains large molecular weight proteoglycans that aggregate with hyaluronic acid (aggrecan) and small species, particularly biglycan (dermatan sulphate proteoglycan-1) and decorin (dermatan sulphate proteoglycan-2), that do not. Mechanical stresses have been shown to profoundly influence the metabolism of aggrecan by articular chondrocytes; however, there are limited corresponding data on the metabolism of dermatan sulphate proteoglycans 1 and 2. The objective of this study was to examine the metabolism of aggrecan, biglycan, and decorin in articular cartilage from different weight-bearing areas of normal ovine stifle joints and in joints 6 months after menisectomy, a procedure that has been shown to induce early osteorthritic changes. [35S]proteoglycans synthesised by cartilage explants from eight different weight-bearing regions of unoperated and meniscectomised ovine stifle joints during 48 hours of culture were separated by size-exclusion chromatography, hydrophobic chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were quantitated by phosphor-screen autoradiography. The synthesis and degradation of the proteoglycans were expressed relative to the DNA content of the explants. In control joints, the cartilage exposed to high contact stress synthesised significantly less proteoglycan overall and more decorin than joint regions bearing less stress. Explants from high stress regions also released significantly greater amounts of resident proteoglycans (dimethylmethylene blue positive) into media during culture. After lateral meniscectomy, the lateral tibial and femoral cartilages showed elevated biosynthesis of both 35S-dermatan sulphate proteoglycans 1 and 2. This chondrocyte biosynthetic response was accompanied by increased catabolism of aggrecan and the release of its degradation products into culture media. These experiments revealed, in normal joints, a topographic variation in proteoglycan synthesis by articular cartilage that was related to the mechanical stress to which the tissues were subjected in vivo. This biosynthetic pattern changed when the load distribution of the joint was altered by unilateral meniscectomy. These data suggest that an altered chondrocyte phenotypic expression of proteoglycans in response to abnormal mechanical loading is an early event in osteoarthritis.

Aggrecans↗

PubMed1996

Increased synthesis of matrix metalloproteinases by aortic smooth muscle cells is implicated in the etiopathogenesis of abdominal aortic aneurysms.

PURPOSE: The objective of this study was to identify the metalloproteinases elaborated by medial smooth muscle cells (SMCs) isolated from abdominal aortic aneurysm (AAA) and control arterial tissues and to ascertain if the levels produced by AAA SMCs were elevated. METHODS: SMC monolayers cultured from the outgrowth cells of tunica media explants were established, and their identity was determined by fluorescent microscopy by using a fluorescein isothiocyanate conjugated anti-SMC alpha-actin antibody. Matrix metalloproteinases (MMPs) produced by SMC monolayers in serum-free culture were examined by gelatin zymography and Western blotting with monoclonal antibodies to MMP-2, 3, and 9. RESULTS: Serum-free media from AAA SMCs contained metal-dependent elastolytic activity that cleaved the synthetic substrate succinyl trialanyl 4-nitroanilide (pH optima 7.2) and also 14C-insoluble elastin. The level of proteolytic activity found in these cultures was significantly greater than from control SMC media. Zymography established that AAA SMC media samples contained metal-dependent gelatinases of 50 to 64 and 92 kDa, which were identified respectively as MMP-2 and 9 by Western blotting by using monoclonal antibodies to these proteases. CONCLUSION: Medial SMCs isolated from AAA tissue produce significantly higher levels of MMP-9 and 2 than SMCs from control arterial tissues. These proteinases have the capacity to degrade elastin and a range of extracellular matrix proteins. From these data, we suggest SMCs may be involved in the abnormal degradation of the aortic wall in AAA through the excessive metalloproteinase activity produced by SMCs.

Adult↗

PubMed1996

Interactions of pentosan polysulfate with cartilage matrix proteins and synovial fibroblasts derived from patients with osteoarthritis.

Pentosan polysulfate (PPS) has been shown to improve symptoms of patients with osteoarthritis (OA) when studied under double-blinded conditions. Laboratory studies indicated that this drug exhibits multiple actions, including the preservation of articular cartilage (AC) proteoglycans in animal models of OA and the stimulation of hyaluronan synthesis by synovial fibroblasts in vitro and in vivo. As PPS is strongly anionic and has a molecular weight of approximately 5700 Da its ability to enter connective tissues rich in proteoglycans and interact with the resident cells has been questioned. In the present studies, experiments were undertaken to isolate and characterize proteins in human AC which have the potential to bind PPS. Thrombospondin was identified in 4.0 M GuHCl extracts of human AC as a PPS-binding protein. Furthermore, synovial fibroblasts derived from OA joints were shown to secrete thrombospondin and also bind PPS. Using bovine erythrocytes conjugated with PPS a rosetting of the synovial fibroblast could be demonstrated. The level of rosetting was not affected by pre-incubating cultures with thrombospondin antibody suggesting that PPS was interacting directly with the cells. Kinetic studies of 3H-PPS uptake by synovial fibroblasts showed saturation of binding sites within 30 min when cells were maintained at 4 degrees C but preservation of drug uptake for up to 120 min when cells were cultured at 37 degrees C. These data, together with the finding that cells labeled with drug at 37 degrees C showed higher incorporation, than at 4 degrees C after trypsin digestion suggests that PPS first binds to the cell membrane when at 37 degrees C is internalized, possibly by pinocytosis.

Aged↗

PubMed1996

Smooth muscle cell migration and proliferation is enhanced in abdominal aortic aneurysms.

BACKGROUND: The aetiology of abdominal aortic aneurysms (AAA) is as yet undetermined. Smooth muscle cells (SMC) have been implicated in the pathogenesis of AAA as a result of their ability to produce elastin degrading proteases. The present study was undertaken to examine AAA SMC and aortic occlusive disease (AOD) SMC in terms of their respective migration and proliferation in vitro, in order to identify intrinsic differences between these cells. METHODS: Five AAA specimens, four AOD and five inferior mesenteric artery (IMA) specimens were established in culture. The cultures were examined for the extent and the rate of SMC outgrowth and proliferation. Cells were counted following trypsinization using a haemocytometer. RESULTS: For the AAA explants, the cellular outgrowths were first seen at 6.7 days, after culture initiation, while the corresponding outgrowth in the AOD group required 8.8 days (P < 0.05) and the IMA group 11.4 days (P < 0.05). AAA cells reached confluency at a mean of 22.4 days while AOD SMC required 28.6 days (P < 0.05) and IMA 31 days (P < 0.05). In the first passage, the time for AAA SMC doubling was 5.3 days compared to 6.2 days for AOD (P < 0.05) and 8.1 days for the IMA group (P < 0.05). Greater than 98% of the cells, in both groups, stained positive to SMC alpha-actin. CONCLUSION: From these data it is clear that there are intrinsic differences in cellular kinetics between SMC from the two disease states, supporting the hypothesis that AAA are not the result of atherosclerosis.

Aged↗

PubMed1996

Variation in intervertebral disc serine proteinase inhibitory proteins with ageing in a chondrodystrophoid (beagle) and a non-chondrodystrophoid (greyhound) canine breed.

Intervertebral disc (IVD) proteoglycans (PGs) and trypsin inhibitory protein levels were assessed for groups of beagles and greyhounds aged between 4 and 80 months. A significant age-dependent decline in PGs and in trypsin inhibitory protein levels was evident in extracts of the beagle nucleus pulposus (NP). This was confirmed for the semi-purified trypsin inhibitor, using Western blotting. These age changes, however, were not evident in the greyhound NP. Furthermore, no significant ageing trends in PG or trypsin inhibitory protein levels were evident in extracts of the annulus fibrosus of either animal. The early onset of IVD degeneration in the beagle, a canine breed of the chondrodystrophoid (achondroplastic) classification, may be related to this decline in the anti-catabolic effects of the endogenous serine proteinase inhibitory proteins.

Aging↗