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Biomedical subjects

H Ling

Publications and source records attributed to H Ling.

At least 55 records · Page 3Linked to original sources
PubMed1997

Emerging therapies for acute renal failure.

Ischemia is the most common cause of acute renal failure (ARF). In the last decade, several new and important pathophysiological mechanisms that underlie the renal dysfunction have been discovered. These pathophysiological mechanisms include the role of both calcium and calcium-dependent enzymes, oxidant stress, loss of polarity of the tubular cell, tubular obstruction and arginine-glycine-aspartic acid (RGD) peptides, neutrophils, intracellular adhesion molecules (ICAM), and growth factors. A better understanding of tubular and vascular mechanisms has led to therapeutic studies in animals and clinical trials in humans. In this review, the pathophysiology of ischemic ARF will be correlated with the rationale for both current and future therapies.

Acute Kidney Injury↗
PubMed1997

The nature of renal cell injury.

The main functional change in patients with acute renal failure (ARF) is a decrease in glomerular filtration rate (GFR). The virtual complete recovery of renal function in those patients who survive ARF, as well as the minimal renal histological abnormalities during ARF when the GFR is less than 10 ml/min, suggest that a major component of the renal tubular cell injury is sublethal or reversible. Experimental models of acute tubular necrosis frequently have placed the emphasis on irreversible proximal tubular cell death. The nature of the renal tubular cell injury in ischemic acute renal failure, however, includes not only cell death (necrosis or apoptosis) but also sublethal injury causing cell dysfunction. The role of intracellular calcium, the calcium-dependent enzymes calpain, phospholipase A2 and nitric oxide synthase (NOS), in the pathophophysiology of this renal tubular cell injury during hypoxia/ischemia is described. The effects of calpain and nitric oxide (NO) on the cytoskeleton and cell adhesion are discussed. Potential mechanisms whereby tubular injury leads to a profound fall in GFR, including increased tubuloglomerular feedback and increased distal tubular obstruction, in ischemic acute renal failure are proposed.

Acute Kidney Injury↗
PubMed1997

Effect of glycine on prelethal and postlethal increases in calpain activity in rat renal proximal tubules.

The effect of glycine on hypoxia- and ionomycin-induced increases in calpain activity in rat proximal tubules was determined. Calpain activity was determined both in vitro and in the intact cell using the fluorescent substrate N-succinyl-Leu-Leu-Val-Tyr-7-amido-4-methyl coumarin (N-succinyl-Leu-Leu-Val-Tyr-AMC) and Western blotting for calpain-specific spectrin breakdown products (BDP), respectively. At 7.5 minutes of hypoxia (prelethal injury model) there was a significant (10-fold) increase in in vitro calpain activity that was not inhibited by glycine. At 15 minutes of hypoxia (postlethal injury model) there was a further increase in calpain activity that was inhibited by glycine. Normoxic tubules incubated with the calcium ionophore ionomycin (5 microM) for two minutes and 10 minutes had a significant increase in calpain activity that was not inhibited by glycine. After 15 minutes of hypoxia in the presence of glycine, there was an increase in calpain-specific spectrin breakdown products (BDP) in both Triton X-100 soluble and cytosolic extracts from proximal tubules. Glycine in concentrations up to 10 mM had no direct effect on the in vitro calpain activity of purified calpains. The present study demonstrates that: (1) prelethal increases in calpain activity stimulated by hypoxia and ionomycin treatment are not affected by glycine; (2) calpain-mediated spectrin breakdown during hypoxia occurs in the presence of glycine; (3) glycine does prevent the additional postlethal increase in calpain activity probably by maintaining membrane integrity to calcium influx.

Animals↗
PubMed1997

[Mechanical structure design of over tubetable remote control diagnostic X-ray unit model X08].

Over tube-table remote control diagnostic X-ray unit model X08 is a product with good performances and high attached technical value, which is designed and manufactured in consideration of production technology and cost, which meets clinical requirements for general use of X-ray radiography. Its main mechanical structures are that its outward appearance is in a shape of island; its table frame makes use of sheet-metal structure; the fulcrum of table body tilting structure is changeable; and its spot film carrier moves much widely. A new high level is attained by correct use of key parts with high manufacturing accuracy, of linear rolling guide system, and of new components and technology, such as converter and microprocessor.

Equipment Design↗
PubMed1997

Effect of cellular hydration on protein metabolism.

In the past few years, the paramount importance of cell volume for the regulation of cell function, including protein metabolism, has been recognized. Among many other effects, cell swelling inhibits proteolysis and stimulates protein synthesis, whereas cell shrinkage stimulates proteolysis and inhibits protein synthesis. Moreover, cell swelling and cell shrinkage influence the expression of a number of genes, including carriers, enzymes, and signaling molecules. Hormones exploit the influence of cell volume on metabolism to exert their effects. Insulin swells hepatocytes by activation of Na-/H+ exchange and Na+,K+,2Cl- cotransport, while glucagon shrinks hepatocytes by activation of ion channels. The effects of these hormones on hepatic proteolysis completely depend on their influence on cell volume. The effects of cell volume are mediated in part by alterations of lysosomal pH, which modifies the activity of acidic lysosomal proteases. Transforming growth factor-beta 1, as other growth factors, activates the Na+/H+ exchanger, swells cells, leads to lysosomal alkalinization, inhibits proteolysis and may thus contribute to renal hypertrophy in chronic renal disease. Moreover, a decrease in cell volume correlates with catabolic states in a variety of diseases.

Animals↗
PubMed1997

Effects of protease therapy in the remnant kidney model of progressive renal failure.

This study investigated whether protease treatment ameliorates the progressive course of chronic failure in the rat model of subtotal nephrectomy. Fourteen male Wistar rats underwent 5/6 nephrectomy, and were randomized into a control group (C, n = 7) given 2 ml of 0.9% NaCl intraperitoneally (i.p.) daily, and a study group (P, n = 7) treated with 12 mg Phlogenzym (combination of trypsin, bromelain, and rutosid) in 2 ml saline i.p. daily. After 6 weeks treatment, the Phlogenzym group showed lower proteinuria (C: 19.6 +/- 9.1 vs. 10.2 +/- 6.2 mg/24 h, p < 0.05). Endogenous creatinine clearance was higher (C: 192.3 +/- 99.4, P: 300.5 +/- 47.9 microliters/min per 100 g, p < 0.05), while plasma creatinine was decreased (C: 106.7 +/- 33.9, P: 76.0 +/- 6.3 mumol/l, p < 0.01). Blood urea nitrogen levels did not change, although urea clearance tended to a higher level in the protease-treated rats. Decreased renal formation of cytokines was reflected by a lower urinary excretion ratio of transforming growth factor (TGF)-beta/ creatinine (C: 0.363 +/- 0.183, P: 0.232 +/- 0.085 ng TGF-beta/mg creatinine, p < 0.05). Renal morphology revealed less infiltration of mononuclear cells and an amelioration of interstitial fibrosis as expressed by the volume index of the cortical region (C: 17.17 +/- 1.43; P: 12.3 +/- 0.5%, p < 0.001). In addition, the activities of lysosomal proteinases (cathepsin B, L + B, and H), which are decreased in the remnant kidney model of chronic renal failure, were significantly higher in the enzyme-treated group both in isolated glomeruli and proximal tubules. The body and kidney weight tended to be lower, probably due to a catabolic action of the enzymes. In summary, we provide evidence that protease treatment may be beneficial in a nonimmune mediated renal disease. Phlogenzym ameliorated the course of chronic renal failure in the rat model of subtotal nephrectomy and retarded the development of tubulointerstitial fibrosis. Decreased cytokine formation in the remnant kidney is supposed to play a key role.

Animals↗
PubMed1996

Fine genetic map of mouse chromosome 10 around the polycystic kidney disease gene, jcpk, and ankyrin 3.

A chlorambucil (CHL)-induced mutation of the jcpk (juvenile congenital polycystic kidney disease) gene causes a severe early onset polycystic kidney disease. In an intercross involving Mus musculus castaneus, jcpk was precisely mapped 0.2 cM distal to D10Mit115 and 0.8 cM proximal to D10Mit173. In addition, five genes, Cdc2a, Col6a1, Col6a2, Bcr, and Ank3 were mapped in both this jcpk intercross and a (BALB/c x CAST/Ei)F1 x BALB/c backcross. All five genes were eliminated as possible candidates for jcpk based on the mapping data. The jcpk intercross allowed the orientation of the Ank3 gene relative to the centromere to be determined. D10Mit115, D10Mit173, D10Mit199, and D10Mit200 were separated genetically in this cross. The order and genetic distances of all markers and gene loci mapped in the jcpk intercross were consistent with those derived from the BALB/c backcross, indicating that the CHL-induced lesion has not generated any gross chromosomal abnormalities detectable in these studies.

Animals↗
PubMed1996

Spontaneous coronary artery dissection in young women.

Spontaneous dissection of the coronary arteries is quite rare. It is usually a catastrophic event with fatal outcome. We report two interesting cases of spontaneous dissection whose presentations exemplify the variable course the disorder may take. The first is the only report to our knowledge associated with aerobic exercise; the second is the only reported attempt at treatment with intracoronary thrombolysis.

Adolescent↗
PubMed1996

A potential clinical method for calculating transmural left ventricular filling pressure during positive end-expiratory pressure ventilation: an intraoperative study in humans.

OBJECTIVES: This study sought to investigate whether right atrial pressure could be used to estimate pericardial pressure during positive end-expiratory pressure (PEEP). BACKGROUND: Because of elevated intrathoracic pressure during PEEP, pulmonary capillary wedge pressure may not accurately reflect left ventricular preload. An estimate of pericardial pressure during PEEP would allow assessment of transmural filling pressure. METHODS: In eight patients, at the start of cardiac surgery, pericardial and pleural pressures were recorded by balloon transducers placed over the anterolateral left ventricular wall. We also recorded intravascular pressures and left ventricular short-axis area by transesophageal echocardiography. RESULTS: A stepwise increase in PEEP from 0 to 15 cm H2O caused a linear increase in pleural pressure from 0.3 +/- 0.6 (mean +/- SEM) to 6.1 +/- 0.8 mm Hg (p < 0.01). Pericardial pressure increased from 2.3 +/- 0.5 to 5.9 +/- 0.6 mm Hg (p < 0.01). The correlation between right atrial (Pra) and pericardial pressure (Pperic) was good: Pra = 0.85 x Pperic + 1.8, r = 0.77. The correlation between changes in right atrial pressure and in pericardial pressure was better: delta Pra = 0.96 x delta Pperic -0.2, r = 0.97. Pulmonary capillary wedge pressure increased with PEEP (p < 0.05), whereas left ventricular area decreased (p < 0.05). However, there was a progressive reduction in transmural pressure, calculated as wedge pressure minus pericardial pressure (p < 0.05), and in transmural pressure, estimated as wedge pressure minus right atrial pressure (p < 0.05). The estimated transmural filling pressure correlated (r = 0.86) with end-diastolic area. CONCLUSIONS: The present observations suggest that right atrial pressure may be used to estimate changes in pericardial pressure with PEEP and that pulmonary capillary wedge pressure minus right atrial pressure is a potentially clinically useful approximation of transmural filling pressure.

Adult↗
PubMed1996

Role of lysosomal cathepsin activities in cell hypertrophy induced by NH4Cl in cultured renal proximal tubule cells.

An increase of renal ammoniagenesis has been implicated in renal hypertrophy associated with various clinical disorders such as metabolic acidosis, diabetic nephropathy, and renal insufficiency. In vivo and in vitro studies have shown that ammonia promotes hypertrophy in tubular epithelial cells. To elucidate its role on protein turnover, the effects of NH4Cl on the activities of cathepsins B, H, and L+B, as well as on protein synthesis and degradation in LLC-PK1 cells, were investigated. The results show that NH4Cl (20 mM) induced cell hypertrophy, as defined by an increase in both cell protein content and cell volume (+25.5 +/- 1.3 and +10.4 +/- 0.1% after 48 h). This hypertrophy was associated with the suppression of the activities of cathepsins B and L+B (-57.0 +/- 0.9 and -54.5 +/- 1.5% after 48 h) and a reduction of protein degradation rate (-59.7 +/- 4.1% after 48 h), but without enhanced protein synthesis. The findings were further supported with an additional experiment, showing that the protein synthesis inhibitor cycloheximide (10 microM) did not blunt NH4Cl-induced cell hypertrophy. Moreover, NH4Cl (20 mM) resulted in a persistent elevation of the lysosomal pH, whereas the rise in the cytosolic pH was only transient. This alkalinization in lysosomes may be causatively involved in the impairment of the activities of cathepsins B and L+B. In conclusion, the suppression of the activities of cathepsins B and L+B and the subsequent reduction of protein breakdown due to intralysosomal alkalinization contribute to NH4Cl-induced hypertrophy in LLC-PK1 cells.

Ammonium Chloride↗
PubMed1996

Spinal cord protection with distal perfusion for thoracic and thoracoabdominal aortic surgery.

Spinal cord protection is of extreme importance to avoid the catastrophic complication of paraplegia related to surgery for thoracic and thoracoabdominal aortic disease.P-' Spinal cord injury from surgi- cally induced ischemia for aortic surgery has a variable risk of paraplegia. The incidence of spinal cord injury varies extensively-aneurysms of the proximal descending thoracic aorta and thoracoabdominal aorta 3% to 35%;to repair of traumatic rupture of the thoracic aorta performed with simple cross-clamping with- out distal perfusion, 25%;to repair of acute type B dissections of the thoracoabdominal aorta, as high as 35%.

Journal Article↗
PubMed1996

Impaired proteolytic activity as a potential cause of progressive renal disease.

Renal hypertrophy (an increase in cellular protein content and cellularity as well as an accumulation of extracellular matrix) is due to the imbalance between protein synthesis and degradation. Proteolytic activity in the kidney plays an important role in maintaining this balance. Impaired renal proteolytic activity caused by such factors as high protein intake, metabolic acidosis, angiotensin II and transforming growth factor-beta 1 in vivo and in vitro may result in decreased protein degradation and subsequent induction of cellular hypertrophy, even in the absence of increased protein synthesis.

Acidosis↗
PubMed1996

Influence of nitric oxide on renal function in toxic acute renal failure in the rat.

Besides other mechanisms, nitric oxide (NO) plays a major role in maintaining the high renal blood flow (RBF) and is also involved in the regulation of glomerular hemodynamics and contractility of mesangial cells. We examined the hypothesis that L-arginine-derived NO exerts beneficial effects in toxic acute renal failure (ARF) in the rat. To induce ARF uranyl nitrate (UN) was given intravenously as a bolus injection (25 mg/kg over 5 min) following a basal period. After the initiation phase of ARF (3 h) saline in the control group (C) and drugs in the experimental groups (I-III, each n = 8) were administered for 60 min. Group I: Arg (= L-arginine, 300 mg/kg), group II: MeArg (= N-methyl-L-arginine, 30 mg/kg), group III: Arg + MeArg (300 mg/kg, 30 mg/kg respectively). The experiments were continued for additional 60 min following the infusion period. Glomerular filtration rate (GFR, inulin clearance) was reduced 3 h after UN to about 50% of normal values in group I-III and control group. After infusion of Arg GFR had significantly improved, but remained unchanged after MeArg in relation to control. One hour after the infusion period these effects were even more pronounced. We conclude that NO exerts beneficial effects on renal function in this animal model of ARF. These results underline the regulatory role of the L-arginine/NO pathway for renal function not only under basal conditions but also in ARF.

Acute Kidney Injury↗
PubMed1996

Effects of parathyroid hormone on renal tubular proteinases.

Parathyroid hormone (PTH) has been implicated to exert detrimental effects on remnant nephrons in chronic renal failure. The present investigation addressed the influence of PTH on the proteolytic capacity of isolated proximal tubules both from normal (SHAM) and partially nephrectomized rats (5/6-NX). Proteolytic activities were measured either against azocasein (pH 5.4) or with specific fluorogenic peptidyl substrates for individual cysteine proteinases. Azocaseinolytic activity was enhanced 6 weeks after 5/6-NX in tubules (SHAM 19.0 +/- 1.0 vs. 5/6-NX 24.4 +/- 1.5 U/mg protein), while thereafter activities declined progressively with time (5/6-NX 16 weeks: 12.9 +/- 1.2 U/mg protein). This loss in proteolytic activity could almost completely be prevented by parathyroidectomy (PTX) (5/6-NX + PTX 16 weeks: 18.6 +/- 1.1 U/mg protein). By contrast, severe hyperparathyroidism (induced by a low calcium/high phosphorus diet fed for 6 weeks) in 5/6-NX animals resulted in a significant decline in proteolytic activities in remnant tubules (5/6-NX 24.4 +/- 1.5 vs. 5/6-NX+diet 16.4 +/- 1.9 U/mg protein). When specific activities of tubular cathepsins were measured in healthy rats who had received exogenous PTH, each individual cysteine proteinase (cathepsin L: -42%; cathepsin B: -27%; cathepsin H: -51%) was suppressed. This effect of PTH could readily be abolished by the simultaneous administration of verapamil. These results suggest that chronic PTH excess exerts a suppressive effect on tubular proteinase activities both in normal and partially nephrectomized rats. This PTH effect seems to be mediated by an increase of cytosolic calcium.

Animals↗
PubMed1995

Influence of coronary artery bypass and age on clinical performance after aortic and mitral valve replacement with biological and mechanical prostheses.

The influence of prosthetic type, age, and coronary artery bypass grafting (CABG) on valve-related complications by valve position was evaluated in a population of 2353 bioprosthesis patients (mean age, 66.5 years; range, 13 to 89 years) and in a population of 1112 mechanical prosthesis patients (mean age, 59.1 years; range, 13 to 91 years). The follow-up was complete to 96% and 98%, respectively, for the bioprosthesis and mechanical prosthesis groups. The patient groups were evaluated by actuarial assessment of survival and valve complications and composites. Preoperative factors were evaluated for determination of significant independent predictors by multivariate proportional-hazard regression analysis. CABG was an influential factor in the actuarial analysis. Survival was superior for aortic mechanical replacements without CABG and for mitral replacements, both biological and mechanical, without CABG (P < .05). The freedom from thromboembolism (TE) and antithromboembolic hemorrhage (ATH) was greater for biological prostheses with and without CABG for aortic replacements (P < .05) but not for mitral replacements (P = NS). The freedom from valve-related mortality was not influenced by CABG for either position (P = NS). The freedom from valve-related reoperation was greater for biological prostheses with CABG than without CABG for both aortic and mitral replacements (P < .05). The evaluation of covariates as independent predictors revealed CABG to be a nonpredictor for aortic valve replacement (AVR) (P = NS) but a predictor of survival and valve-related reoperation for mitral valve replacement (MVR) (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Dose-dependent stimulation/inhibition effects of cyclosporin A on lysosomal cathepsin activities in cultured proximal tubule cells.

The effects of cyclosporin A on the activities of lysosomal cysteine proteinases (cathepsin B, H, L+B) in LLC-Pk1 cells were investigated to elucidate their potential role in cyclosporin A-induced nephrotoxicity. Cyclosporin A at lower doses (0.1--1,000 ng/ml) stimulated cathepsin B, H, L+B. In contrast, at a higher dose (10,000 ng/ml), it inhibited these proteinase activities associated with a reduction in protein degradation. In line with the altered proteinase activities, cellular protein content was decreased at the lower dose (10 ng/ml) and increased at the higher dose. The higher dose of cyclosporin A also enhanced cellular lipid peroxide content after an exposure of 4 and 10 h. Co-incubation with superoxide dismutase (40 U/ml) did not ameliorate the inhibition of cathepsin B activity induced by the high dose of cyclosporin A. On the contrary, the calcium channel blocker verapamil (10(-6) M) prevented this inhibition. In conclusion, cyclosporin A exerts a dose-dependent biphasic effect on lysosomal cysteine proteinase activities. A rise in cytosolic Ca2+ concentration, but not an enhanced lipid peroxidation, may be involved in the suppression of cathepsin B activity induced by the higher dose of cyclosporin A. These studies raise the possibility that alterations of tubular proteinase activity may play a role in the cyclosporin A-induced nephrotoxicity.

Calcimycin↗
PubMed1995

Carpentier-Edwards supraannular porcine bioprosthesis: clinical performance to twelve years.

The Carpentier-Edwards supraannular porcine bioprosthesis, a second-generation biologic prosthesis, has had clinical performance assessment to 12 years. This bioprosthesis was used in 2,489 operations in 2,444 patients between 1982 and 1992, inclusive (mean age 64.1 years, age range 6 to 89 years). There were 1,335 aortic valve replacements (AVR), 938 mitral valve replacements (MVR), and 200 multiple valve replacements (MR). Concomitant procedures were performed in 1,017 cases (40.9%). The age group distribution was: 35 years or younger, 83 patients; 36 to 50 years, 245; 51 to 64 years, 728; 65 to 69 years, 458; and 70 years and older, 975. The total follow-up was 12,785 patient-years (mean, 5.1 years) and was 96% complete. The early mortality rate was 7.4% (185 patients), and the late mortality was 4.9%/patient year (623). Concomitant procedures influenced both early and late mortality (p < 0.05). The overall patient survival at 12 years was 44% +/- 3% (p < 0.05, AVR > MVR, MR). The freedom from thromboembolism was not different by valve position. The freedom from major thromboembolism at 12 years was 82% +/- 4% (p = not significant by valve position). The overall freedom from antithromboembolic hemorrhage was 96% +/- 1% at 12 years (p < 0.05, AVR > MVR > MR). The overall freedom from valve-related reoperation at 12 years was 58% +/- 5% (p < 0.05, AVR > MVR, MR), and from valve-related mortality 89% +/- 2% (p < 0.05, AVR > MVR > MR). The freedom from residual morbidity (permanent impairment) at 12 years was 87% +/- 4% (p = not significant by valve position).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗