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Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 217 records · Page 12Linked to original sources

Urinary dopamine and noradrenaline outputs during large acute changes in oral salt intake in healthy Chinese subjects.

1. In order to investigate the role of renal dopamine and sympathetic activity in the natriuretic response to oral sodium loading in Chinese subjects, we studied the effects of two different sodium intakes (20 followed by 220 mmol day-1 each given for 5 days) on mean arterial pressure (MAP) and the urinary excretion of sodium, dopamine (DA) and noradrenaline (NA) in eight healthy subjects. 2. MAP did not change. There was an eight- to ninefold increase in sodium excretion (P < 0.01). An 8-17% increase in urinary DA (P < 0.05) over the first 3 days, and a 22% decrease in urine NA (P < 0.05) on the last day of the high sodium intake were seen. 3. The relatively small increase in urinary DA, despite an eleven-fold increase in sodium intake from a state of marked sodium deprivation, may suggest that, in healthy Chinese subjects, the renal DA mechanism only contributes partly to the acute natriuretic response. Furthermore, the renal DA response appeared to be attenuated during the period of high sodium intake. 4. There is no evidence from the present study that a reduction in sympathetic activity plays an important role in the acute natriuretic response to sodium loading in this group of subjects.

Administration, Oral↗

Insulin-like growth factor and growth hormone receptor in nephrotic rats.

In an attempt to elucidate the mechanism of growth retardation in the nephrotic syndrome, specific serum and hepatic growth factors were measured in Sprague-Dawley rats in which nephrotic syndrome was produced by administration of puromycin (1.5 mg.100 g body wt-1.day-1) for 12 days. On the 13th day, the results of these nephrotic animals were compared with those of an equal number of pair-fed and control animals: the mean dietary intake of the nephrotic group was 71% that of the control group (P < 0.001). Serum insulin-like growth factor (IGF) binding protein-3 was significantly reduced (P < 0.005) in the nephrotic rats, compared with the pair-fed and the control groups. Hepatic IGF-I mRNA in the nephrotic rats averaged 36% that of control (P < 0.001) and 46% that of the pair-fed animals (P < 0.001). Hepatic growth hormone receptor (GHr) mRNA in the nephrotic rats averaged 19% of that of the control (P < 0.001) and 27% of that of the pair-fed rats (P < 0.001). These results indicate that the growth retardation of the nephrotic rats may be associated with the significant decrease in IGF-I mRNA and reduction in GHr mRNA.

Animals↗

History of medicine and nephrology in Asia.

The beginning of Chinese medicine has been attributed to 3 mythical emperors who gathered herbs for medicines. During the 2nd century BC, Han dynasty physicians developed cranial trephining and sedation with wine and herbs for anesthesia. Chiang Chung-Ching (142-212 AD) used the appearance of rashes in diagnosis, treated infections with anthelmintics and asthma with ephedra, described the symptoms of diabetes mellitus and expanded medical ethics. The specialties of obstetrics, pediatrics, ophthalmology and dentistry were described in the records of the Han and Tang dynasties, and methods of setting fractures and treating trauma were comparable with those of Roman military doctors. Shen Tua (1031-1095 AD) compiled a pharmacopeia and studied acupuncture and the pulses. Forensic medicine was developed during the 10th century by Sung Tse, who also advocated hand washing with sulfur and vinegar to avoid infection during autopsies. The Daoist physicians used androgens and estrogens to treat hypogonadism with therapeutic preparations of placentas. They also had an advanced knowledge of alchemy, claiming to achieve 'immortality' by their preservation techniques. Qualifying examinations for physicians were conducted by the Chinese state as early as the 1st century AD, and later incorporated philosophy and art to conform with the Confucian ideal. Throughout these eras, Chinese medicine profited from contact with western Asia. In ancient Chinese medicine, the excretory function of the kidney was attributed to the bladder. 'Kidney weakness', which refers to somatized depression, was treated by acupuncture along the 'kidney channel'. Pulse examination was also used to give a measure of the imbalance of renal Yin and Yang.(ABSTRACT TRUNCATED AT 250 WORDS)

Alchemy↗

Tumor epidermal growth factor receptor studies in patients with non-small-cell lung cancer or head and neck cancer treated with monoclonal antibody RG 83852.

PURPOSE: Tumor tyrosine kinase activity associated with the epidermal growth factor receptor (EGFR) and localization of anti-EGFR monoclonal antibody RG 83852 were studied in patients with non-small-cell lung cancer (NSCLC) and head and neck cancer. PATIENTS AND METHODS: Fifteen patients were treated with escalating doses of RG 83852 by continuous intravenous infusion for 5 days. Fresh tumor specimens were obtained 24 hours after therapy in 10 patients (of whom five had a pretherapy sample taken). Tumor EGFR tyrosine kinase activity was determined in fresh tumor samples by autophosphorylation of EGFR isolated in immunocomplexes with RG 83852. Tumor EGFR saturation with RG 83852 was assessed semiquantitatively by comparing the EGFR tyrosine kinase activity in immunocomplexes of tumor specimens obtained after therapy with total EGFR tyrosine kinase activity assessed by exogenous addition of RG 83852 to tumor lysates. Modulation of EGFR tyrosine kinase activity after the administration of RG 83852 was assessed by comparing EGFR tyrosine kinase activity from the same malignant lesion obtained before and after therapy. Tumor localization of RG 83852 and EGFR saturation were also assessed by immunohistochemistry. RESULTS: No significant side effects were observed up to a total dose of 600 mg/m2. Based on tyrosine kinase activity, a high degree of EGFR saturation (> or = 50%) was observed at doses > or = 200 mg/m2, and EGFR saturation was estimated to be 100% at a dose level of 600 mg/m2 both in tumor tissue and skin used as surrogate EGFR-positive tissue. Immunohistochemistry studies showed that RG 83852 localized in tumor tissue and skin, but not in stroma, at doses > or = 400 mg/m2, and high EGFR saturation was observed at 600 mg/m2. Tumor EGFR tyrosine kinase activity was studied in five patients (four with EGFR-positive tumors) before and 24 hours post-therapy; a threefold to fourfold upregulation of EGFR tyrosine kinase activity in posttherapy specimens was observed in two patients. Moderate upregulation of EGFR itself was suggested in both of these patients and in two additional patients by immunohistochemistry. CONCLUSION: RG 83852 causes no toxic effects at doses that result in high tumor EGFR saturation. Treatment with RG 83852 may enhance EGFR tyrosine kinase activity and/or EGFR expression. Because high EGFR expression by tumors has been associated with increased sensitivity to cytotoxic therapy, the suggestion of antibody-mediated upregulation of EGFR by agents such as RG 83852 may prove useful in enhancing chemotherapeutic efficacy.

Antibodies, Monoclonal↗

Effects of deflazacort and cortisone on body growth, thymus weight and gene expression of growth-related proteins in the rat.

Deflazacort is an oxazoline derivative of cortisone with presumably less serious side effects, but its effects on growth factors are unknown. The present experiments in Long Evans rats were carried out to investigate how deflazacort administration affected the growing rat, especially in relation to hepatic insulin-like growth factor I (IGF-I) and growth hormone receptor (GHR) messenger ribonucleic acid (mRNA). Four groups of animals were used: those treated with cortisone, with two different doses of deflazacort and with vehicle. Subcutaneous injections were given daily for 8 days. Thymus weight was reduced in all treated groups, with a comparable magnitude of reduction in the groups treated with cortisone and the higher dose of deflazacort (DF1). Daily weight gain was reduced significantly after cortisone treatment, but less so in the DF1 rats. Liver IFG-I and GHR mRNA were lower in the cortisone and deflazacort than in controls. However, GHR mRNA was reduced significantly only by cortisone and not by DF1. We conclude that growth failure is less severe in the DF1 rats compared to cortisone rats, which corresponds to the reduction in hepatic GHR mRNA.

Animals↗

The effects of enalapril and nifedipine on carbohydrate and lipid metabolism in NIDDM.

OBJECTIVE: To compare the effects of nifedipine and enalapril on carbohydrate and lipoprotein metabolism in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. RESEARCH DESIGN AND METHODS: A 12-week, double-blind, randomized study of plasma lipid levels and glycemic control in patients treated with nifedipine (n = 52) or enalapril (n = 50) was conducted. None of the patients were treated with insulin. Diet and dosages of oral hypoglycemic agents remained unchanged during the 12-week treatment period. RESULTS: Mean arterial pressure was reduced more by nifedipine than by enalapril (23.1 vs. 11.1 mmHg, P < 0.001). Similar reductions in body mass index and plasma triglycerides and increases in apolipoprotein A-I were seen with both treatments, but HbA1 was reduced more during treatment with enalapril than with nifedipine (0.49 vs. 0.20%, P = 0.035) and serum apolipoprotein B (apoB) also declined more with enalapril than with nifedipine (8.2 vs. 2.3 mg/dl, P = 0.009). CONCLUSIONS: Twelve weeks of treatment with enalapril in hypertensive NIDDM patients was associated with greater improvement in glycemic control and greater reduction in serum apoB concentration, although the reduction in blood pressure was less than with nifedipine. These changes in cardiovascular risk profile warrant investigation for a longer term.

Apolipoprotein A-I↗

Aconitine poisoning due to Chinese herbal medicines: a review.

Both "chuanwu", the main root of Aconitum carmichaeli, and "caowu", the root of A kusnezoffii, are believed to possess anti-inflammatory, analgesic and cardiotonic effects and have been used in Chinese materia medica mainly for the treatment of musculoskeletal disorders. They contain the highly toxic C19 diterpenoid alkaloids of aconitine, mesaconitine and hypaconitine. After ingestion, patients may present with signs and symptoms that are typical of aconitine poisoning. Death may occur from ventricular arrhythmias, which are most likely to occur within the first 24 h. Management of aconitine poisoning is essentially supportive. There are no adequate studies in humans to indicate the most effective treatment of the ventricular arrhythmias. All clinicians should be alerted to the potential toxicity of "chuanwu" and "caowu".

Aconitine↗

Poisoning by Chinese herbal medicines in Hong Kong: a hospital-based study.

The harmful effects of some Chinese herbal medicines (CHM) have become a cause for concern among the medical profession and the general public in Hong Kong. From 1989 to 1993, at least 33 patients were treated in the Prince of Wales Hospital because of severe poisoning by CHM. Of these, 20 presented with clinical features typical of aconitine poisoning following the ingestion of "chuanwu", the main root of Aconitum carmichaeli, or "caowu", the root of Aconitum kusnezoffii. Strict legislation controlling the use of chuanwu and caowu alone would have prevented many of the severe poisonings by CHM in Hong Kong.

Adolescent↗

Atrial natriuretic peptide and renin-angiotensin-aldosterone system in non-insulin-dependent diabetes mellitus.

A total of 78 Chinese patients with clinically uncomplicated non-insulin-dependent diabetes (NIDDM) who had plasma creatinine concentrations of < 150 mumol/l were studied. Antihypertensive treatment was discontinued for at least six weeks prior to measurements of routine biochemistry, proteinuria, plasma atrial natriuretic peptide (ANP) concentrations and components of the renin-angiotensin-aldosterone system (RAAS). BP was measured on three occasions during the six weeks period prior to these measurements. At the end of the six week period, a total of 33 patients had definite hypertension (supine BP > or = 160/95 mmHg). The hypertensive patients had significantly higher plasma sodium (mean +/- SD): 140.3 +/- 1.9 vs. 138.5 +/- 2.0 mmol/l, P < 0.001) and lower plasma potassium (3.8 +/- 0.5 vs. 4.2 +/- 0.5 mmol/l, P < 0.01) concentrations. These were associated with reduced plasma aldosterone (median (range): 297 (98-1145) vs. 448.5 (93-1330) pmol/l, P < 0.01) and renin concentrations (16.8 (7.4-71.8) vs. 23.5 (7.4-83.7) ng/l, P = 0.06). The hypertensive patients also had significantly higher plasma ANP concentrations (36.5 (20.5-125.1) vs. 23.2 (11.7-63.0) pg/ml, P < 0.001), serum angiotensin converting enzyme (ACE) activity (65 (26-140.9) vs. 47 (22-106) units/l, P < 0.001) and urinary albumin excretion (UAE) (35.4 (1.6-4800) vs. 7.8 (1.8-310.4) mg/day, P < 0.001). Glycaemic control and renal function were similar between the two groups. Mean arterial pressure (MAP) correlated positively with plasma ANP concentration (r = 0.53, P < 0.001) and serum ACE activity (r = 0.37, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Activated production of metalloproteinases in Ki-ras-transformed human osteosarcoma cells.

The human osteosarcoma cell culture HOS does not produce matrix metalloproteinases (MPs). However, after transformation with the Ki-ras oncogene, the resulting culture (KHOS) produced readily detectable MPs. The molecular weight of the major MP was 66 kDa, while the molecular weights of two other minor bands were 71 kDa and 60 kDa. The activity of all three enzymes was inactivated by treatment with ethylene diaminetetra acetic acid, indicating that they are probably MPs. The substrate preference of the 66-kDa MP (in decreasing order) was gelatin and collagens V, I, III, and IV. Treatment of the MPs with p-aminophenylmercuric acetate led to the appearance of 62-kDa activated enzyme. The MP produced by KHOS cells did not react with the monoclonal anti-rat stromelysin antibody MC. Treatment of KHOS cells with retinoic acid and dexamethasone, which are known to suppress c-fos/c-jun and AP-1, suppressed the production of the MPs. Therefore, the activation of MPs by Ki-ras in KHOS cells may involve c-fos/c-jun and the AP-1-responsive pathway.

Genes, ras↗

Changes in hepatocyte NADH fluorescence during prolonged hypoxia.

Deprivation of oxygen reduces oxidative phosphorylation and rapidly causes an increase in cellular NADH which can be monitored by fluorimetry. Previous studies have established that increases in NADH fluorescence accurately reflect the impairment in oxidative phosphorylation which occurs during brief periods of acute hypoxia. However, the potential usefulness of fluorimetry for following longer, clinically relevant periods of ischemia has not been explored. We studied changes in NADH fluorescence in rat hepatocyte suspensions and in isolated-buffer-perfused rat livers during hypoxia (pO2 < 50 mm Hg) for periods as long as 180 min. NADH fluorescence of hepatocyte suspensions consistently increased by about 15% after 13 to 15 min of hypoxia and coincided with a marked decrease in tissue ATP levels. Reoxygenation after 15 or 30 min of hypoxia resulted in recovery of ATP and NADH with minimal loss of viability, as measured by trypan blue exclusion. After 60 to 180 min hypoxia, the initial increase in NADH fluorescence was followed by a progressive, irreversible decline which correlated with decreased cell viability. Similar changes in NADH fluorescence were observed in isolated-perfused rat livers in which NADH fluorescence was monitored at the liver surface with a fiberoptic probe. Hypoxia for 30 min had no effect on NADH fluorescence, but hypoxia for longer periods caused a steady increase in fluorescence after 45-60 min. When hypoxia was prolonged (120 or 180 min), fluorescence peaked after 60-75 min and then declined progressively to levels below baseline. The greatest decrease in fluorescence was seen after 180 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hyperlipidemia in childhood nephrotic syndrome.

Hyperlipidemia is an important characteristic of nephrotic syndrome (NS). Elevation of plasma total cholesterol, or more specifically low-density lipoprotein cholesterol, is the major lipid abnormality in NS, although hypertriglyceridemia may develop as the disorder progresses. The pathophysiology of nephrotic hyperlipidemia is complex. The prevailing view is that both hepatic synthesis of lipids and of apolipoproteins is increased, and that the clearance of chylomicrons and very low-density lipoproteins is reduced. The precise contribution of increased lipogenesis and decreased lipid catabolism to hyperlipidemia, and their relationship to urinary protein loss, hypoalbuminemia and reduced serum oncotic pressure remain controversial. There are two potential risks of elevated plasma lipids: atherosclerosis and progression of glomerular injury. Although neither of these complications has been proved with certainty, there is growing evidence that both may be long-term consequences of NS. Therefore, the diagnosis and treatment of lipid abnormalities, important aspects of the management of nephrotic children, is summarized here to provide pediatric nephrologists with an informed choice.

Child↗

The peritoneal equilibration test in children.

Eight children, aged 15 months to 17 years 9 months, maintained by continuous ambulatory peritoneal dialysis (CAPD)/continuous cycling peritoneal dialysis and nine adults, aged 20-59 years, managed by CAPD were compared using a standardized peritoneal dialysis protocol, the peritoneal equilibration test (PET). The peritoneal glucose concentration tended to equilibrate with the serum glucose more rapidly in children, but the percentage of the glucose load absorbed was not different between the two age groups. There was an inverse trend between the percentage of glucose absorbed and age in children. Peritoneal creatinine clearance scaled to surface area in children was significantly less than that of the adults; however, the clearances became similar when adjusted for body weight. Peritoneal creatinine clearance scaled to surface area bore a positive and significant relationship to age which, when expressed per kilogram body weight, disappeared. Children had a significantly higher dialysate/plasma (D/P) creatinine ratio after the first 2 h of the PET, but this ratio approached unity by 4 h and was not different from adults. The fractional change in the creatinine D/P ratio during the PET was not different between the two age groups. Drain volume adjusted to surface area was significantly less in children than adults. This difference was reversed when drain volume was factored by weight. Similarly drain volume scaled to surface area demonstrated a significant and positive relationship to age, which disappeared when drain volume was expressed per kilogram body weight. Ultrafiltration, whether factored by weight or scaled to surface area, did not differ between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗