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Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 253 records · Page 14Linked to original sources

Blood coagulation abnormalities associated with envenoming by Trimeresurus albolabris in Hong Kong.

Snake bites in Hong Kong are most commonly due to Tr. albolabris (White-lipped pit viper, bamboo snake). We studied 21 cases of envenoming by Tr. albolabris prospectively in order to document the incidence and severity of associated coagulation abnormalities. Eighteen patients (86%) had increased blood concentrations of fibrin degradation products (FDP) ranging from 10-40 micrograms/l to greater than 200 micrograms/l (normal: less than 10 micrograms/l), the majority of whom also had detectable soluble fibrin monomers. Among these 21 patients, 10 had decreased blood concentrations of fibrinogen ranging from 0.3 kg/l to 1.9 g/l (normal: 2-4 gl/l). In 11 cases (52%), the euglobulin clot lysis time was shortened (less than 150 minutes) in association with elevated blood concentrations of FDP (n = 10) and decreased circulating fibrinogen levels (n = 8). Thrombocytopenia and/or prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and/or thrombin time (TT) were present in 10 patients (28%). Increased blood concentrations of FDP and decreased circulating fibrinogen levels were present in most of these cases. Envenoming by Tr. albolabris is therefore frequently associated with a coagulopathy compatible with increased fibrin/fibrinogenolysis. Measurement of blood concentrations of FDP is the most sensitive test for detecting the coagulopathy. There is, however, little correlation between the patterns of clinical manifestations and coagulation abnormalities although more severe clinical features were usually associated with high circulating FDP levels. Only one patient developed systemic bleeding but no fatality was observed. The coagulation abnormalities are usually correctable by replacement therapy. Further studies are required to study the mechanisms of this coagulopathy and its relationship with venom antigenaemia.

Adult↗

Perturbations in potassium balance.

Hyperkalemia and hypokalemia are commonly encountered in medical practice. Differential diagnosis and therapeutic approaches have been presented to provide an informed choice for the practicing physician.

Humans↗

Substrate preference of metalloproteinases secreted by ts-110 Moloney murine sarcoma virus-transformed normal rat kidney cells.

In this study, the two forms of affinity-purified transformation-associated proteins (TAPs) (68 and 64 kD) were shown to have different substrate preferences. For the 68-kD TAP, the order of substrate preference was collagen types I, III, and V; fibronectin; gelatin; and collagen IV. For the 64-kD TAP, the order of substrate preference was collagen I, III, and V and gelatin. The 64-kD TAP did not cleave collagen IV and fibronectin. We also found a 71-kD metalloproteinase in the concentrated purified TAPs that reacted only weakly with a TAP monoclonal antibody and showed this substrate preference: collagen I, III, and V; gelatin; and collagen IV. Whether this 71-kD TAP is a new member of the rat metalloproteinase family will be investigated.

Animals↗

Comparison of enalapril and nifedipine in treating non-insulin dependent diabetes associated with hypertension: one year analysis.

OBJECTIVES: To compare the efficacy, safety, and tolerance of enalapril and nifedipine in hypertensive patients with non-insulin dependent diabetes. DESIGN: One year double blind follow up of patients randomly allocated to either enalapril or nifedipine with matching placebos for the alternative drug. SETTING: Metabolic Investigation Unit, Hong Kong. SUBJECTS: 102 patients were randomised: 52 to nifedipine and 50 to enalapril. At baseline 44 patients had normoalbuminuria, 36 microalbuminuria, and 22 macroalbuminuria. MAIN OUTCOME MEASURES: Blood pressure, albuminuria, and parameters of renal function and glycaemic control. RESULTS: In patients who completed one year's treatment the median dose required by the nifedipine group (n = 49) was 60 mg/day; seven (14%) required additional diuretics. Of 41 patients given enalapril, 37 required the maximum dose (40 mg/day) and 27 (76%) required diuretics. At one year mean arterial blood pressures were similar in both groups. Albuminuria fell by 54% in the enalapril group and 11% in the nifedipine group (p = 0.006). Fractional albumin clearance ratio fell by 47% in the enalapril group and increased by 3% in the nifedipine group (p = 0.009). Creatinine clearance fell similarly in both groups but plasma creatinine concentration was increased by 20% in the enalapril group versus 8% in the nifedipine group (p = 0.001). CONCLUSION: Patients taking enalapril often required diuretics to control blood pressure. Enalapril reduced proteinuria significantly more than nifedipine in the microalbuminuric and macroalbuminuric patients but increased plasma creatinine concentrations. Longer follow up is required to clarify the importance of enalapril's antiproteinuric effect.

Albuminuria↗

The inter-relationships between albuminuria, plasma albumin concentration and indices of glycaemic control in non-insulin-dependent diabetes mellitus.

We studied the relationship between albuminuria (measured as albumin/creatinine ratio (alb/Cr) in a random urine sample) and measures of glycaemic control (fructosamine, HbA1 and glucose) in 470 patients with non-insulin-dependent diabetes mellitus (NIDDM). Albumin excretion was in the microalbuminuric range (alb/Cr ratio > 5.4-40.3) in 112 (23.8%) and in the macroalbuminuric range (alb/Cr ratio > 40.3 mg/mmol) in 89 patients (18.9%). Fourteen percent (n = 67) of patients had a normal plasma HbA1 (< or = 8.5%) while 27% (n = 127) had a normal plasma fructosamine concentration (< or = 2.2 mmol/l). Using stepwise multiple regression analysis, plasma fructosamine concentration was found to be independently and negatively associated with urine albumin/creatinine ratio (B = 0.24, P < 0.006) in the macroalbuminuric group. Further analysis of the relationship between plasma albumin concentration and indices of glycaemic control showed that plasma albumin concentration correlated negatively with random plasma glucose concentration in the normoalbuminuric patients (r = -0.16, P = 0.008) but not in microalbuminuric or macroalbuminuric groups. HbA1 was not correlated with plasma albumin concentration. Our results indicate that albuminuria has an effect on the plasma fructosamine concentration which is independent of plasma albumin concentration.

Adult↗

Molecular cloning and characterization of v-mos-activated transformation-associated proteins.

Using monoclonal antibodies we previously detected two forms of transformation-associated proteins, a 64-kDa protein and a 68-kDa protein, in temperature-sensitive 110-Moloney murine sarcoma virus-mutant-transformed rat kidney 6m2 cells. The identity and functions of the transformation-associated proteins were previously unknown. By molecular cloning techniques and immunoscreening, we have isolated two cDNA clones (34A and 79B3) that were found by Western blot analysis to code for a monoclonal anti-transformation-associated protein antibody-reactive polypeptide of approximately 58 kDa. Limited restriction enzyme mapping indicated 34A and 79B3 are two different cDNA clones. The nucleotide sequence of 34A cDNA was determined, and a search of GenBank revealed that it is identical to that of rat transin-2. The deduced amino acid sequence of 34A shares 71% sequence identity with rat transin and 41-76% identity with six human metalloproteinases. The limited restriction enzyme mapping and partial nucleotide sequencing data indicated that 79B3 may be the rat transin gene. When either 34A cDNA or 79B3 cDNA was used as a probe in Northern blot analysis, one mRNA band of approximately 1.9 kilobases was detected in 6m2 cells grown at the permissive temperature of 33 degrees C, at which the cells exhibited transformation properties, and a much lower level in 6m2 cells grown at the nonpermissive temperature of 39 degrees C, at which the cells reverted to normal phenotypes. These results suggest that at 39 degrees C, these two genes were not transcribed at the same level as at 33 degrees C. Zymogram and Western blot analysis of 6m2 cells further confirmed that the 64- and 68-kDa proteins have metalloproteinase activities and that the synthesis of metalloproteinases was also temperature-sensitive. Apparently, the two proteins we formerly designated transformation-associated proteins are members of the rat transin gene family. Therefore, within v-mos transformed 6m2 cells, the absence of transformation-associated protein (metalloproteinase) synthesis at the nonpermissive temperature was due to the absence of transcription of two rat transin genes.

Amino Acid Sequence↗

The effect of growth hormone on the growth failure of chronic renal failure.

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX, n = 40), GH-treated nephrectomized rats (NX+GH, n = 18), sham-operated rats fed ad libitum (SHAMAL, n = 27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF, n = 10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean +/- SEM) 49 +/- 3 and 54 +/- 4 mg/dl, respectively, compared with 16 +/- 4 and 19 +/- 0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0 +/- 3.3 g) and length (3.5 +/- 0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2 +/- 4.0 g, P less than or equal to 0.0001 and 4.1 +/- 0.2 cm, P less than or equal to 0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2 +/- 5.0 g) and length (3.4 +/- 0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81 +/- 2 mg/dl versus 55 +/- 3 mg/dl in SHAMAL (P less than or equal to 0.0001), was not increased in the NX+GH group, 87 +/- 3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.

Animals↗

Growth hormone secretion from pituitary cells in chronic renal insufficiency.

To examine whether growth hormone (GH) secretion is adversely affected by chronic renal insufficiency (CRI), the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (CRI, N = 18) and sham-operated (N = 18) rats. Two weeks after nephrectomy, during a period of stable uremia, CRI rats had significantly higher serum concentrations (mean +/- SEM) of urea nitrogen and creatinine than sham rats, 16.8 +/- 1.4 mmol/liter (47 +/- 4 mg/dl) and 79.6 +/- 0.0 mumol/liter (0.9 +/- 0.0 mg/dl) versus 6.1 +/- 0.4 mmol/liter (17 +/- 1 mg/dl) and 35.4 +/- 0.0 mumol/liter (0.4 +/- 0.0 mg/dl), respectively (P less than 0.0001). Incremental gains in body weight and nose to tail-tip length of CRI rats over two weeks were also significantly depressed, 53.3 +/- 5.38 g (CRI) versus 87.0 +/- 3.78 g (sham; P less than 0.0001) and 3.2 +/- 0.2 cm (CRI) versus 3.6 +/- 0.1 cm (sham; P less than 0.05). The cumulative food intake as well as food efficiency (g food consumed/g weight gain) were also adversely influenced by the uremic state: food intake 304 +/- 1 g (CRI) versus 397 +/- 6 g (sham; P less than 0.0001) and food efficiency 0.173 +/- 0.013 g/g of weight gain (CRI) versus 0.219 +/- 0.008 g/g of weight gain (sham). No significant difference in GH secretory rate (ng/min/10(7) cells) was found between the uremic and sham animals under basal conditions, 65.2 +/- 2.1 (CRI) and 67.9 +/- 2.2 (sham) or in response to GH-releasing hormone, 282.8 +/- 42.4 (CRI) versus 306.2 +/- 42.6 (sham).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Atrial natriuretic peptide and urinary dopamine output in non-insulin-dependent diabetes mellitus.

1. Disturbances of sodium and water homoeostasis may contribute to the close association between diabetes, hypertension and proteinuria. We therefore studied the patterns of two natriuretic hormones, plasma atrial natriuretic peptide and urinary dopamine, in 165 Chinese patients with non-insulin-dependent diabetes mellitus controlled by diet or oral hypoglycaemic agents on two occasions over a 6-week period. Patients were divided into three groups based on the mean value of two 24h urinary albumin excretion measurements. In group 1, 88 patients had normoalbuminuria (urinary albumin excretion < or = 30 mg/day), in group 2, 48 patients had microalbuminuria (urinary albumin excretion between 30 and 300 mg/day), and in group 3, 29 patients had macroalbuminuria (urinary albumin excretion > or = 300 mg/day). 2. The supine systolic blood pressure (mean +/- SD) was higher in patients with abnormal albuminuria (group 1: 140.9 +/- 27.4 mmHg; group 2: 158.1 +/- 26.4 mmHg; group 3: 166.7 +/- 23.9 mmHg; F = 13.1, P < 0.001, analysis of variance). Urinary sodium output was similar in these three groups of patients. The geometric means (anti-logarithm of 95% confidence interval logarithm) of plasma atrial natriuretic peptide concentrations increased with increasing proteinuria [group 1: 33.3 (29.9-37.1) pg/ml; group 2: 39.1 (34.2-44.6) pg/ml; group 3: 50 (38.6-54.7) pg/ml; F = 4.24, P < 0.01; analysis of variance], whereas those of urinary dopamine output were related inversely to proteinuria [group 1: 1291.7 (1167.2-1437.0) nmol/day; group 2: 1142.3 (975.9-1337.2) nmol/day; group 3: 982.7 (775.7-1245) nmol/day; F = 3.10, P < 0.05, analysis of variance].(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗

Fatal adult Henoch-Schönlein purpura due to small intestinal infarction.

A 57-year-old woman presented with classical symptoms of Henoch-Schönlein purpura including arthralgia, abdominal pain, palpable purpuric rash and abnormalities of the urinary sediments. The clinical course was subsequently complicated by severe paralytic ileus leading to respiratory embarrassment. Laparotomy confirmed patchy areas of small bowel infarction due to necrotizing vasculitis. Skin biopsy revealed extensive leukocytoclastic vasculitis with granular deposits of IgA in the blood vessels. Anti-neutrophil cytoplasmic autoantibodies (ANCA) were not detectable. The patient continued to deteriorate despite bowel resection, intensive immunosuppressive therapy and plasma exchange, and eventually died. Gastrointestinal involvement in adult Henoch-Schönlein purpura has previously been reported to have a favourable clinical course. However, our case illustrates the rate but lethal complication of intestinal infarction in patients who fail to respond to conservative treatment.

Female↗

Growth hormone secretory capacity of individual somatotropes in rats with chronic renal insufficiency.

Growth failure is a common consequence of chronic renal insufficiency (CRI) in children and may be due to a number of factors. With regard to growth hormone (GH), regulation is often abnormal in CRI patients. The present study investigated the effect of CRI on the GH secretory responsiveness to GH-releasing hormone in individual rat pituitary somatotropes. Male Sprague-Dawley rats underwent a 5/6 nephrectomy to produce CRI. Control rats (SHAM) received sham operations, which included kidney decapsulation but not removal. Two wk later, during a period of stable uremia, serum creatinine [CRI: 1.1 +/- 0.08 mg/dL (97 +/- 7 mumol/L); SHAM: 0.4 +/- 0.04 mg/dL (35 +/- 4 mumol/L)] and serum urea nitrogen [CRI: 60.7 +/- 8.3 mg/dL (21.7 +/- 3.0 mmol/L); SHAM: 15.8 +/- 1.2 mg/dL (5.6 +/- 0.4 mmol/L)] were significantly elevated in the CRI rats (p less than 0.0005). Weight gain (p less than 0.0005), length gain (p less than 0.0005), food intake (p less than 0.0005), and food efficiency (p less than 0.005) were all significantly lower in the CRI rats. The GH secretory capacity of individual somatotropes was determined using the reverse hemolytic plaque assay technique. Plaque areas were measured to assess relative amounts of GH secreted. The total number of pituitary cells per rat, the percentage of somatotropes, and the mean plaque areas were similar for the two groups. These findings compare favorably with our in vitro study of GH responsiveness in perifused rat pituitary cells under conditions of mild uremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hypercholesterolemia in rats with chronic renal insufficiency not aggravated by recombinant human growth hormone.

The lipid metabolic disorders in chronic renal insufficiency (CRI) are related to increased hepatic lipid synthesis, reduced triglyceride removal coupled with insulin insensitivity and impaired lipoprotein lipase activity. Growth hormone is lipolytic, and the effects of recombinant human growth hormone (rhGH) on the hypercholesterolemia of CRI are unsettled. To test this question, we gave rhGH for 14 days at a dosage of 3 units/day intraperitoneally to two-stage, 5/6 nephrectomized, male Sprague-Dawley rats (n = 18) compared to sex- and age-matched control (n = 27) and CRI (n = 40) rats. At the end of the study, CRI rats and those treated with rhGH had a similar degree of renal impairment, as assessed by serum concentrations (mean +/- SEM) of urea nitrogen (49 +/- 3 vs. 54 +/- 4 mg/dl), creatinine (0.9 +/- 0.0 vs. 1.0 +/- 0.1 mg/dl) and cumulative food intake (311 +/- 8 vs. 290 +/- 12 g). Serum urea nitrogen (16 +/- 4 mg/dl) and creatinine (0.4 +/- 0.1 mg/dl) concentrations as well as food intake (412 +/- 9 g) of control rats were significantly (p < 0.0001) different. Serum cholesterol concentration of CRI rats treated with rhGH (87 +/- 3 mg/dl) was not higher than those of CRI rats (81 +/- 2 mg/dl, p < 0.1338) but was significantly higher than in control rats (55 +/- 3 mg/dl, p < 0.0001). CRI rats treated with rhGH showed a similar serum albumin concentration and lower serum glucose than CRI rats (0.9 +/- 0.1 vs. 0.9 +/- 0.0 g/dl and 144 +/- 4 vs. 163 +/- 3 mg/dl, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mexican-American migrant students' academic success: sociological and psychological acculturation.

This study attempted to describe and compare academically successful and academically unsuccessful high-risk Mexican-American migrant high school students. The two groups were compared on sociological and psychological indicators of acculturation, urbanization, and socioeconomic status (SES). It was hypothesized that the successful group would have higher SES, be more acculturated, urbanized, and psychologically adjusted to modern value systems, and have higher occupational aspirations and expectations than the unsuccessful group. In addition, their world views were compared by exploring early recollection data. The results showed that the unsuccessful group came from families that were larger, poorer, more rural, and more "foreign" (i.e., more parents and children born in Mexico) than the successful students' families. Regarding the psychological indicators of acculturation, the successful group was found to score higher on modernism, to be more stably acculturated, to have a clearer sense of themselves, to have higher occupational aspirations and expectations, and tended to desire jobs with greater responsibility and stability than did the unsuccessful group.

Acculturation↗

Overproduction of metalloproteinases by v-mos-transformed rat kidney (6m2) cells.

Using monoclonal antibodies, we previously detected two forms of transformation-associated proteins (TAPs), P64 and P68, in the rat kidney (6m2) cells transformed by the temperature-sensitive 110-murine sarcoma virus-Moloney-mutant. TAPs were secreted as glycoproteins by 6m2 cells grown at 33 degrees C, but not by 6m2 cells grown at 39 degrees C. The identity and functions of TAPs were previously unknown. By molecular cloning techniques and immunoscreening, we have isolated two different cDNA clones (34A and 79B3) that were found by Western blot analysis to code for an anti-TAP monoclonal antibody-reactive polypeptide of approximately 58,000 daltons. The nucleotide sequence of 34A cDNA was determined and found to be identical to that of rat transin-2. The deduced amino acid sequence of 34A shares 71% sequence identity with rat transin and 41% to 76% identity with three human metalloproteinases. Partial nucleotide sequencing data indicated that 79B3 may be the rat transin gene. When either 34A cDNA or 79B3-cDNA was used as a probe in Northern blot analysis, one mRNA band of approximately 1.9 kb was detected in 6m2 cells at the permissive temperature of 33 degrees C. Similar RNA was either not detected or detected at very low level in 6m2 cells grown at the non-permissive 39 degrees C. These results suggest that at the non-permissive 39 degrees C, these two genes were not transcribed at the same level as that at 33 degrees C. Zymogram further confirmed that P64 and P68 have metalloproteinase activities. Apparently, the two proteins which we formerly designated TAPs are members of the rat transin gene family. Therefore, within v-mos transformed 6m2 cells, the absence of TAPs (metalloproteinases) at the non-permissive temperature was due to the very poor transcription of the two rat transin genes. This article presents a review of the biochemical properties of TAPs and their eventual identification as rat transin-2 and transin.

Animals↗

Temperature-sensitive synthesis of a metalloproteinase in ts110-MSV-M-transformed NRK cells.

Previously, we reported that transformation associated protein (TAP) was over-expressed in the 6m2 line, but not in their normal counterparts (1,2). 6m2 is a culture of NRK cells transformed by the ts-110 mutant of MSV-M. The synthesis of TAP and the expression of transformation properties in the 6m2 cells are all temperature-sensitive (2; 3; 4). TAP is secreted as two polypeptides of 64 kD and 68 kD (P64 and P68) (2). Experiments were carried out to determine whether any metalloproteinase (MP) activity was associated with TAP. Results of zymograms indicated that the two forms of purified TAP (P64 and P68) had MP activity, using gelatin or collagen type IV as substrates. Serum-free medium (SFM) of 6m2 cells incubated at 33 degrees C also showed two bands of MP activity, while the corresponding SFM from 6m2 cells at 39 degrees C lacked such MP activity, indicating that the synthesis of MP was temperature-sensitive. The association of MP activity with the P64 and P68 bands of TAP (purified or in SFM) was confirmed by simultaneous Western blot analysis, which showed the reactivity of the two MP bands with monoclonal or polyclonal antibodies to TAP. Accordingly, what we previously designated as TAP is apparently one form of MP, which are known to be involved in tumor cell metastasis.

Animals↗

X-linked hypophosphatemia. Genetic and clinical correlates.

X-linked hypophosphatemia is a hereditary form of rickets that results from an isolated renal tubular wasting of phosphate. The clinical features unique to this disorder, and the recent advances in our understanding of vitamin D metabolism and molecular genetics in X-linked hypophosphatemia are reviewed. Finally, a succinct critique of the controversial treatment modalities round up this review.

Animals↗