Biomedical subjects

H S Cheung

Publications and source records attributed to H S Cheung.

At least 55 records · Page 3Linked to original sources

PubMed1994

Induction of stromelysin-1 and collagenase synthesis in fibrochondrocytes by tumor necrosis factor-alpha.

Stromelysin-1 and collagenase mRNA levels were assayed in fibrochondrocytes by Northern blot analysis at 0, 2, 4, 8 and 24 h after stimulation with tissue necrosis factor-alpha (TNF-alpha). Peak collagenase mRNA levels occurred 24 h after stimulation and were increased nine-fold over the level at time 0. Stromelysin-1 mRNA levels peaked 8 h after stimulation, with a five-fold increase over the level at time 0. A TNF-alpha dose-related response to both collagenase and stromelysin-1 mRNA accumulation was also demonstrated. Confirmation of the presence of secreted metallo-proteinases in the conditioned media was established by immunoprecipitation of stromelysin-1 and Western blotting of collagenase. Both enzymes were secreted in latent forms. Consistent with stromelysin-1 activity, substrate gels demonstrated a doublet of caseinase activity with molecular masses at 57 kDa and 59 kDa in TNF-alpha stimulated samples. Collagenase assays of conditioned media also demonstrated a significant increase in collagenase activity after stimulation by TNF-alpha. While epidermal growth factor had a minimal effect on stromelysin-1 and collagenase expression, transforming growth factor-beta, and insulin-like growth factor-1 did not induce either enzyme activity.

Animals↗

PubMed1993

Protein kinase regulation of tumor necrosis factor alpha stimulated collagenase and stromelysin message levels in chondrocytes.

TNF stimulated transcription and secretion of the metalloproteinases collagenase and stromelysin in porcine articular chondrocytes. TNF induced metalloproteinase transcription could be inhibited with either protein kinase inhibitors (H7 or staurosporine) or by raising intracellular cAMP levels. HA1004, a protein kinase inhibitor structurally related to H7 but with a higher Ki for protein kinase C had no effect on TNF induced message levels. TNF treatment of chondrocytes did not induce membrane associated PKC or increase intracellular cAMP levels. Our results are consistent with the involvement of a staurosporine and H7 sensitive protein kinase distinct from PKC in TNF signal transduction in chondrocytes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

A comparison of the effect of transforming growth factor beta 1 on pyrophosphate elaboration from various articular tissues.

OBJECTIVE: The purpose of this study was to determine the effect of transforming growth factor beta 1 (TGF beta 1) on inorganic pyrophosphate (PPi) elaboration from articular tissues to better understand the pathophysiology of calcium pyrophosphate dihydrate (CPPD) crystal deposition in the joint. METHODS: PPi was measured in the media of adult porcine articular tissue in organ culture and monolayer cultures. RESULTS: TGF beta 1 strongly stimulated PPi elaboration by porcine fibrocartilage and hyaline cartilage. It modestly increased PPi elaboration by ligament, and had no effect on PPi elaborated by synovium. Of all cell types tested in cell culture, only chondrocytes responded to TGF beta 1 by significantly increasing PPi elaboration. CONCLUSION: TGF beta 1 stimulates PPi elaboration from hyaline cartilage, fibrocartilage, and ligament, indicating that there is in situ CPPD crystal formation in these tissues. The ability of tissues to respond to TGF beta 1 by increasing PPi elaboration correlates with the prevalence of CPPD crystal deposition found clinically. The unique response of chondrocyte monolayers to TGF beta 1 reinforces the key role of the chondrocyte in PPi elaboration in the joint. These findings support an etiologic role for responsiveness to TGF beta 1 in CPPD disease.

Animals↗

PubMed1993

Phosphocitrate prevents disease progression in murine progressive ankylosis.

OBJECTIVE: Mice with progressive ankylosis, a spontaneous arthropathy, were treated with phosphocitrate (PC) in vivo to determine the effect of PC on disease progression. METHODS: Two groups of mice with progressive ankylosis (matched for age, weight, and sex) were treated parenterally for 6 weeks with either PC or saline vehicle. RESULTS: Clinically, histologically, and microradiographically, there were significant differences in disease progression and severity in the PC-treated and the saline-treated mice. CONCLUSION: PC appears to inhibit disease progression in murine progressive ankylosis.

Animals↗

PubMed1993

Misoprostol, a prostaglandin E1 analogue, inhibits basic calcium phosphate crystal-induced mitogenesis and collagenase accumulation in human fibroblasts.

Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathy. BCP crystals induce the secretion of matrix-degrading enzymes such as collagenase. No prophylactic or therapeutic agents are recognized to ameliorate the cartilage damage associated with BCP deposits in joints. As a chondroprotective effect of prostaglandins (PG) has been suggested, we studied the effect of misoprostol, a PGE1 analogue, on BCP crystal-induced mitogenesis and collagenase messenger RNA (mRNA) accumulation in human fibroblasts (HF). Mitogenesis was determined by 3H-thymidine incorporation assays and collagenase mRNA accumulation by Northern blot analysis, in HF stimulated with BCP crystals in the presence or absence of misoprostol. Misoprostol caused concentration-dependent inhibition of BCP crystal-induced mitogenesis. The inhibition of BCP-stimulated mitogenesis was not specific as misoprostol also inhibited the mitogenic response to 10% serum. There was only 50 (+/-5)% inhibition of serum-induced mitogenesis by misoprostol at 500 ng/ml, the concentration that completely inhibited BCP crystal-induced mitogenesis. Misoprostol also inhibited the accumulation of collagenase mRNA in BCP-stimulated HF by 63%. These data suggest that misoprostol may inhibit the synovial proliferation and cartilage degradation that accompany BCP crystal deposition.

Blotting, Northern↗

PubMed1993

Inhibition of neutral endopeptidase 3.4.24.11 in conscious dogs with pacing induced heart failure.

OBJECTIVE: The effects of a selective neutral endopeptidase inhibitor, SQ 28,603 (N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta-alanine), were determined in an experimental model of heart failure. METHODS: The symptoms of heart failure were induced by rapid ventricular pacing for one or three weeks in dogs with surgically implanted catheters for measurement of atrial pressures and mean arterial pressure and with ultrasonic flow probes for determination of cardiac output and renal blood flow. RESULTS: Inhibition of neutral endopeptidase by 10, 30, or 100 mumol.kg-1 SQ 28,603 given intravenously increased sodium excretion, cyclic GMP excretion, and plasma concentrations of atrial natriuretic peptide in a dose related manner in conscious dogs paced for one week. SQ 28,603 (100 mumol.kg-1) stimulated similar natriuretic and cyclic GMP responses in dogs paced for three weeks although baseline glomerular filtration rate was reduced. Because the natriuresis was maintained despite the smaller filtered sodium load, the increase in fractional sodium excretion was significantly greater after three weeks of pacing (from 0.5(0.2) to 3.7(0.7)%) than after one week of tachycardia (from 0.1(0.0) to 2.0(0.3)%). By contrast, SQ 28,603 (100 mumol.kg-1) did not affect renal, haemodynamic, or hormonal variables in normal conscious dogs where baseline atrial natriuretic peptide (18(3) fmol.ml-1) was lower than in the paced animals (104(10) fmol.ml-1). CONCLUSIONS: Inhibition of neutral endopeptidase in dogs with pacing induced heart failure protected endogenous atrial natriuretic peptide from degradation and stimulated sustained natriuresis, presumably via a tubular mechanism.

Alanine↗

PubMed1993

Vascularized iliac crest grafts: evaluation of viability status with marrow scintigraphy.

Forty-three vascularized iliac crest grafts in the femoral neck region in 38 patients were assessed with marrow scintigraphy. Twenty grafting procedures had been performed for treatment of fractures, 16 for nontraumatic osteonecrosis, and seven for focal bone lesions. Scintiscans were obtained preoperatively and in the early and late postoperative period. Anterior images of the hips were obtained 30 minutes after intravenous injection of 4 mCi (148 MBq) of technetium-99m tin colloid by using a gamma camera with a low-energy, general-purpose collimator. The viable graft was detected as an area of tracer uptake corresponding to the configuration of the graft on radiographs. Marrow scintigraphy at 12 weeks showed that 24 grafts were viable, 11 were nonviable, and eight were indeterminate. Early and late results concurred in 36 of 43 (84%) grafts. Nonviable grafts occurred most frequently in fractures in the elderly. In seven patients who subsequently required total hip replacement, six grafts were nonviable while one was indeterminate at 12 weeks. Results indicate that marrow scintigraphy is useful in the treatment of patients with vascularized iliac crest bone grafts.

Adolescent↗

PubMed1992

Basic calcium phosphate crystals stimulate cell proliferation and collagenase message accumulation in cultured adult articular chondrocytes.

OBJECTIVE: To investigate BCP (basic calcium phosphate) crystal-stimulated mitogenesis and collagenase gene transcription in primary cultures of porcine chondrocytes. METHODS: The role of protein kinases in BCP crystal-stimulated DNA synthesis was investigated using thymidine incorporation, kinase inhibitors, and protein kinase C (PKC) assays. Northern blot analysis was used to determine the levels of collagenase c-fos and c-jun message. RESULTS: BCP crystals stimulated chondrocyte proliferation in a PKC-dependent manner. Increased levels of collagenase message were preceded by an increased accumulation of c-fos, but not c-jun. CONCLUSION: BCP crystals could contribute to the abnormal chondrocyte proliferation and collagenase secretion observed in some rheumatic diseases.

Calcium Phosphates↗

PubMed1992

Basic calcium phosphate crystals cause coordinate induction and secretion of collagenase and stromelysin.

Synovial fluid basic calcium phosphate crystals (BCP) are often found in severely degenerated joints. Crystalline BCP is a growth factor stimulating fibroblast mitogenesis and acting as a competence factor similar to platelet-derived growth factor. In human fibroblasts (HF), the synthesis of collagenase and stromelysin is coordinately induced after stimulation with a variety of cytokines and growth factors. We sought to determine whether BCP, like other growth factors, might induce proteases that would damage articular tissue. Northern blot analysis of mRNA for collagenase and stromelysin in HF stimulated with BCP was performed. Secreted enzymes were analyzed by immunoblot using a monoclonal antibody to collagenase and by immunoprecipitation using a polyclonal antibody to stromelysin. Stromelysin activity was confirmed using casein substrate gels. A significant, dose-dependent accumulation of collagenase and stromelysin message was evident after 4 h and continued for at least 24 h in BCP-stimulated cultures. Forty-nine and 54 kD proteins immunoreacting with collagenase antibody were identified in the conditioned media (CM) from BCP-stimulated cultures while 50 and 55 kD proteins were identified by immunoprecipitation with stromelysin antibody. Collagenase activity was increased significantly in the CM from BCP treated cells; casein substrate gels showed casein degrading bands at molecular weights consistent with stromelysin. BCP stimulates coordinate induction of collagenase and stromelysin which may mediate the joint destruction associated with these crystals.

Blotting, Northern↗

PubMed1992

Radiological imaging of urinary tract infection in Malaysian children--a private hospital experience.

The results of radiological investigations performed on 81 children with urinary tract infection (UTI) were reviewed. Investigations included 91 voiding cystourethrograms (VCU), 59 intravenous urograms (IVU) and 36 ultrasonograms (US). The aim was to study the local spectrum of renal tract abnormalities in childhood UTI and to compare the diagnostic yield of combining US and VCU against IVU and VCU. Renal tract abnormalities were detected in 37%. Vesico-ureteric reflux (VUR) was the commonest, detected in 26%, with renal scarring found in 9% of refluxing units. Ultrasound should replace IVU in the initial diagnostic work-up of these children.

Child↗

PubMed1991

Transforming growth factor beta 1 stimulates inorganic pyrophosphate elaboration by porcine cartilage.

The overproduction of inorganic pyrophosphate (PPi) by cartilage is thought to be a key element in the formation of calcium pyrophosphate dihydrate (CPPD) crystals in joints, and the subsequent development of pseudogout or chondrocalcinosis. We report herein that transforming growth factor beta 1 (TGF beta 1), alone and in synergy with epidermal growth factor (EGF) or TGF alpha, markedly stimulates PPi elaboration by porcine articular cartilage in organ culture and monolayer culture. This effect is not seen with platelet-derived growth factor, basic fibroblast growth factor, or insulin-like growth factor types 1 and 2, substances which also affect chondrocyte metabolism or are mitogenic. TGF beta 1 produces only a modest increase in nucleoside triphosphate pyrophosphohydrolase (NTPPPH), a chondrocyte ectoenzyme that produces PPi; this implies the existence of other pathways for PPi elaboration. TGF beta 1 is present in joint fluid and cartilage. TGF beta 1, TGF alpha, and EGF are the first known physiologic modifiers of cartilage PPi production. They provide a novel model for the study of CPPD crystal formation in cartilage, as well as new insights into the pathogenesis of this common affliction of aging.

Animals↗

PubMed1991

The mitogenic response to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase in human fibroblasts.

Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathies that are characterized by synovial proliferation and digestion of articular collagenous structures. BCP crystals are potent mitogens, which may account for this proliferation. The role of collagenase in articular degradation is controversial because, despite the massive loss of collagen, no studies have confirmed collagenolytic activity in synovial fluid, as originally reported. We investigated collagenase messenger RNA induction and enzyme activity in human foreskin fibroblasts proliferating in response to stimulation with BCP crystals, and analyzed the associated secreted proteins. Northern blots revealed a dose-dependent accumulation of collagenase message, evident by 4 hours and continuing to at least 36 hours, in BCP-stimulated cultures. One- and 2-dimensional polyacrylamide gel electrophoresis of conditioned media from BCP crystal-stimulated cultures revealed the selective induction of 2 proteins with molecular weight and pI values consistent with those of collagenase. Increased enzyme activity was also found. Thus, the mitogenic response of fibroblasts to BCP crystals is accompanied by collagenase induction and secretion, supporting the hypothesis that they act as a mediator of joint destruction in BCP crystal-associated arthropathies.

Calcium Phosphates↗

PubMed1991

Tumor necrosis factor alpha and epidermal growth factor regulation of collagenase and stromelysin in adult porcine articular chondrocytes.

Chondrocyte-derived metalloproteases have been postulated to play a role in the degradation of articular cartilage during the development of chronic arthritic disorders. TNF alpha (tumor necrosis factor alpha), an inflammatory mediator released by activated macrophages, has been detected in the synovial fluid of patients with rheumatoid diseases. We have found that TNF alpha is a potent stimulator of collagenase and stromelysin mRNA accumulation, collagenase activity, and immunoprecipitable stromelysin in monolayer cultures of adult porcine articular chondrocytes. In contrast EGF (epidermal growth factor), which stimulates collagenase and/or stromelysin synthesis in fibroblast systems, stimulated minimal amounts of these enzymes at both the message and protein levels. Nuclear run-on transcription analysis demonstrated that the TNF alpha-stimulated increase in stromelysin and collagenase message levels was, at least partially, due to increased transcription. Elevated transcription of these genes, in response to TNF alpha, was apparent by at least 2 hours post-stimulation. The degree of c-fos and c-jun stimulation by TNF alpha or EGF did not correlate with the levels of collagenase and stromelysin message stimulated by these factors. EGF stimulated significant accumulation of both c-fos and c-jun mRNAs while only very low amounts of these messages were stimulated by TNF alpha. Our data suggests that TNF alpha may contribute to articular cartilage degradation by stimulating chondrocyte-derived matrix metalloproteases. In addition the regulation of metalloprotease genes in chondrocytes may be different from their regulation in fibroblasts.

Animals↗

PubMed1991

Stimulation of cartilage inorganic pyrophosphate elaboration by ascorbate.

Ascorbate (0-500 microM) stimulates synthesis and secretion of collagen by cartilage explants in a dose-dependent fashion as estimated by [3H]proline incorporation. Concurrent elaboration of inorganic pyrophosphate (PPi) parallels [3H]proline incorporation (less than 0.001, Wilcoxon rank sum). The effect on proline and PPi is abolished by ascorbate oxidase. Another reducing agent, Vitamin E, did not promote PPi accumulation about cartilage. Inhibitors of collagen synthesis, including monensin, tumor necrosis factor alpha, and 2',2'dipyridyl also inhibited PPi elaboration. Cycloheximide (1 micrograms/ml) inhibited the ascorbate stimulated PPi elaboration 54% but did not attenuate the secretion of PPi by unstimulated cartilage. Cosecretion of collagen and PPi by chondrocytes may explain these results. Moreover, at least two pathways exist for PPi elaboration, a cycloheximide sensitive path and another independent of new protein synthesis.

2,2'-Dipyridyl↗

PubMed1990

Inhibition of basic calcium phosphate crystal-induced mitogenesis by phosphocitrate.

Basic calcium phosphate crystals control the traverse of cells from the Go/G1 to S-phase of the cell cycle and initiate proliferation by rendering fibroblasts competent to respond to insulin-like growth factors in plasma. Simultaneous addition of phosphocitrate [a powerful inhibitor of hydroxyapatite crystallization] to cells exposed to basic calcium phosphate crystals caused a dose-dependent inhibition of crystal-induced DNA synthesis and c-fos transcription. This inhibition was specific for crystal-induced mitogenesis, since similar concentrations of phosphocitrate had no effects on either PDGF or 10% calf serum-induced thymidine incorporation and c-fos transcription.

Animals↗

PubMed1990

Cartilage inorganic pyrophosphate elaboration is independent of sulfated glycosaminoglycan synthesis.

Inorganic pyrophosphate (PPi), a product of glycosaminoglycan synthesis, may be cosecreted with matrix proteoglycan to reach the extracellular site where calcium pyrophosphate dihydrate crystals form. To test this hypothesis, sulfated glycosaminoglycan synthesis by articular cartilage in culture was stimulated or inhibited while the effect on extracellular PPi was measured. When stimulated by 0.8 mM xyloside to increase 35SO4 incorporation (mean +/- SEM % of control 183 +/- 16, n = 5), PPi accumulation changed little (from 54 +/- 6 pmoles/mg to 63 +/- 8 pmoles/mg of cartilage wet weight). Inhibition of sulfation with monensin or diethylcarbamazine disproportionately lowered 35SO4 incorporation compared with PPi elaboration. Using 60 mM diethylcarbamazine, PPi production was preserved (105 +/- 8% mean +/- SEM) compared with control cultures, while sulfation was markedly inhibited (7 +/- 1%). This dissociation of sulfate incorporation and PPi secretion indicates that it is not likely that glycosaminoglycan sulfation is the source of the PPi that escapes from chondrocytes to participate in the formation of extracellular crystals.

Animals↗

PubMed1990

Experience with 395 extracorporeal shockwave lithotripsy in the treatment of renal and ureteric calculi.

Three hundred and ninety five cases in 358 consecutive patients (male-232, female-126) with renal and ureteric stones were treated with extracorporeal shockwave lithotripsy (ESWL) from March to November 1988. They either had ESWL alone, or in combination with stone manipulation or debulking percutaneous nephrolithotripsy (PCNL). Seventy five percent of the stones were found in the pelvicalyceal system and 25% in the ureter. Seventy-six percent of the stones were less than 25mm size. Two hundred and ninety (79%) cases were followed up to three months. Two hundred and forty nine (85.9%) cases were stone free and 36 (12.4%) had residual sand less than 3mm size. Five (1.7%) cases failed to fragment with ESWL monotherapy and were salvaged by either percutaneous or ureteroscopic intervention. None of the cases required any open surgery intervention.

Adult↗

PubMed1990

Percutaneous renal surgery for urolithiasis.

Sixty eight consecutive cases of percutaneous renal surgery, percutaneous nephrolithotripsy (PCNL), were performed on 64 patients (male-41, female-23) at the Subang Jaya Medical Centre from April 1988 to July 1989. All the cases were done as a one stage procedure. Fifty eight stones were large renal or staghorn and ten were ureteric. Thirty cases (41%) were stone free after PCNL alone. Thirty eight cases had residual fragments needing extracorporeal shockwave lithotripsy (ESWL). Mean operating time was 109.6 +/- 36.0 minutes. Mean hospital stay was 4.5 +/- 1.8 days. At three months follow-up, 86% of the cases were stone free. The remaining had residual sand (less than 3mm). Minor complications occurred in six patients. None required major surgical intervention post PCNL.

Female↗