Biomedical subjects

M H Tan

Publications and source records attributed to M H Tan.

At least 91 records · Page 5Linked to original sources

PubMed1989

Association of oral candidiasis with diabetic control.

Factors associated with oral candidiasis in 51 diabetics were examined. The prevalence of oral yeast infection was 49 (n = 25)%. The association with diabetic control, as measured by fasting blood glucose concentration, urinary glucose concentration, and glycosylated haemoglobin, with the presence of yeast was analysed in the 51 diabetic patients. Glycosylated haemoglobin above 12% was strongly associated with oral yeast infection (odds ratio = 13.00) (p less than 0.001), while fasting blood and urinary glucose concentrations were not. The risk of oral candidiasis among diabetics wearing dentures was significantly higher than among dentate diabetics (odds ratio = 4.78). After controlling for the effect of denture wearing, glycosylated haemoglobin greater than 12% remained highly predictive of oral yeast infection, particularly among diabetics without dentures.

Adult↗

PubMed1989

The use of a cell-free perfusate in the perfused rat hindquarter: methodological concerns.

The viability of using a cell-free perfusate in a rat hindlimb preparation to assess skeletal muscle glycogenesis was investigated. A perfusate containing 10 mM glucose and 10 microCi (1 Ci = 37 GBq) of D-[5-3H]glucose was recycled for a 60-min period. In agreement with other studies using more complex media, oxygen uptake of the preparation indicated adequate tissue oxygenation (8 mumol.min-1.g-1). Skeletal muscle fiber type heterogeneity in basal glycogen synthesis from glucose was shown (slow oxidative greater than fast oxidative glycolytic greater than fast glycolytic fibres). Insulin (4.2 mU/mL) markedly stimulated glycogenesis from D-[5-3H]glucose in the soleus (slow oxidative fiber), red gastrocnemius (fast oxidative glycolytic fiber), and white gastrocnemius muscles (p less than 0.05). A recent report indicates that tissue edema in this preparation did not affect insulin responsiveness of the tissue. In contrast, our observations indicate that glucos uptake was enhanced by insulin when edema was absent (p less than 0.05), but not when edema was present (p less than 0.05). In addition, the presence of tissue edema negated insulin-mediated glycogenesis in slow oxidative and fast oxidative glycolytic muscle (p less than 0.05 compared with control) but not in fast glycolytic muscle (p less than 0.05). These data warrant caution when using a cell-free media in the perfused rat hindquarter; however, in the absence of edema, normal responses of glucose metabolism are observed.

Animals↗

PubMed1988

Hindlimb suspension increases insulin binding and glucose metabolism.

After 28 days of hindlimb-suspension, insulin binding, 2-deoxy-D-glucose (2-DG) uptake, and glucose metabolism (glycolysis and glycogenesis) were determined at various insulin concentrations (0.2-30 nM) in soleus muscle of young (18-day-old) and adult (150-day-old) rats. Compared with age-matched controls the young (YS) and adult suspended (AS) rats had lower soleus and body weights and insulin levels (P less than 0.05). Per milligram of protein, insulin binding, 2-DG uptake, and the rate of glycolysis were increased by approximately 200%, and the rate of glycogenesis was increased approximately 100% in the YS group (P less than 0.05). Except for a reduction in glycogenesis (P less than 0.05) all other parameters also increased in the AS rats (P less than 0.05). On the basis of the whole muscle the rate of glucose metabolism (glycogenesis + glycolysis) was reduced in the YS rats (P less than 0.05), but in the AS rats glucose metabolism was similar to the controls. Thus the increased glucose metabolism (i.e., per milligram of protein) in the YS and AS groups may represent a compensatory response by atrophied muscle to attempt to sustain glucose removal from the circulation. Because greater insulin binding occurred in YS muscle [35% slow-twitch (ST)] than in the control group (70% ST), and greater insulin binding occurred in the AS (81% ST) than in the control group (90% ST), higher insulin binding capacities are not always related to a high proportion of ST muscle fibers. In conclusion, after hindlimb suspension, marked increments in insulin binding and glucose metabolism occur in the soleus muscle.

Aging↗

PubMed1987

Effect of exercise training on insulin binding and glucose metabolism in mouse soleus muscle.

Training stimulates glucose uptake and metabolism by muscles independent of a rise in serum glucose. Whether this increased insulin action is associated with enhanced insulin binding in muscles is unknown. We studied the effect of 6 weeks of treadmill running on insulin binding, uptake of 2-deoxy-D-glucose, glycolysis, and glycogenesis by the soleus muscle of Swiss Webster mice. Training was progressively increased. The in vitro studies using intact soleus preparations were done 48 h after the last exercise bout. Training increased insulin binding, insulin-stimulated uptake of 2-deoxy-D-glucose, and glycogenesis but not glycolysis in the soleus. Our data suggest that the enhanced glucose uptake and metabolism in muscles induced by exercise training are associated with an increase in insulin binding.

Animals↗

PubMed1986

Effect of diabetes mellitus and end-stage renal disease on HDL metabolism.

Different types of diabetes mellitus have different effects on high density lipoprotein (HDL) metabolism. Impaired glucose tolerance may be associated with no change or a slight decrease in HDL cholesterol. Type I diabetes may have normal or elevated HDL cholesterol levels. This HDL elevation may be due to an increase in HDL2 or HDL3. Apo A-I/Apo A-II ratio is also higher in these diabetics. Type II diabetics may have normal or low HDL cholesterol levels as well as normal or decreased Apo A-I levels. In gestational diabetics, the mean HDL cholesterol is lower than controls. Dietary therapy resulting in greater than 10% weight loss in obese diabetics leads to an increase in their HDL-cholesterol levels, although the effect on the latter is controversial. Intensive insulin therapy (for 2-3 weeks) increases serum apo A-I and HDL-cholesterol levels. End-stage renal disease also affects HDL metabolism. In general, patients with this disorder have a decrease of cholesterol and an increase in triglyceride in their HDL. There is an increase in apo E and a decrease in apo CII in their HDL. Apo A-I levels are unaffected whereas apo A-II levels are decreased. Renal transplant patients may have low, normal or high HDL cholesterol and normal or high apo-I levels. In non-diabetic, normotriglyceridemic patients peritoneal dialysis increases their HDL-cholesterol. In non-diabetic hypertriglyceridemic and diabetic patients, peritoneal dialysis causes no change in their HDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Pretreatment effects on the uptake/retention kinetics of L-dopa in Harding-Passey melanoma.

Malignant melanoma cells possess a unique biochemical pathway that converts L-3,4-dihydroxyphenylalanine (L-dopa) to the biopigment melanin. Selective cytotoxic incorporation of exogenous L-dopa into melanoma cells in vivo may provide a means of designing specific chemotherapeutic agents useful in the treatment of this disease. Using the Harding-Passey murine melanotic tumor model, a preferential uptake of [3H]L-dopa by the tumor was characterized. Following pretreatment of the tumor-bearing mice with nonradioactive L-dopa, a significant enhancement (p less than 0.01) of [3H]L-dopa incorporation and retention into melanoma for a period of 24 h was observed, when compared with the concomitant tissue distribution and clearance of radioactivity in the control animals. This finding suggests that by initial pretreatment of melanoma with nonradioactive L-dopa, the subsequent selective accumulation of [3H]L-dopa in tumor may provide a useful tool in testing new modalities of therapy in malignant melanoma.

Adrenal Glands↗

PubMed1986

Chronic exercise increases insulin binding in muscles but not liver.

It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, we investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed (P less than 0.05) or fasted (P less than 0.05) state and after an oral glucose tolerance test (n = 8) (P less than 0.05). Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. From control animals, killed at the same time of day, muscles and liver were also obtained. Insulin binding to plasma membranes increased in S, P, and EDL (P less than 0.05) but not in WG (P = 0.07), RG (P greater than 0.1), or in liver (P greater than 0.1). There were insulin binding differences among muscles (P less than 0.05). Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver.

Animals↗

PubMed1986

Characterization of a new primary human pancreatic tumor line.

A primary human pancreatic tumor line (BxPC-3) has been established from a biopsy specimen of a histologically confirmed adenocarcinoma of the body of the pancreas. Tumorigenicity was proven by xenograft in athymic nude mice. Upon re-establishment of tumor xenografts in tissue culture, the epithelial tumor cells retained their original morphology. Histopathologically, the tumors grown in nude mice exhibited the original characteristics of the primary adenocarcinoma in the patient, producing traceable mucin and displaying moderately well to poorly differentiated adenocarcinomas with occasional lymphocytic infiltrations at the tumor peripheries. Furthermore, the tumor xenografts differentially expressed carcinoembryonic antigen, human pancreas cancer-associated antigen, and human pancreas-specific antigen. Karyotyping and glucose-6-phosphate dehydrogenase isoenzyme characterization revealed that this tumor line was of human origin and devoid of HeLa cell contamination. The BxPC-3 tumor line has been maintained for more than four years in our laboratory and represents a valuable model for primary human pancreatic cancer.

Adenocarcinoma↗

PubMed1985

Continuous-flow enzymic determination of serum total and high density lipoprotein cholesterol using microlitre sample volumes.

We determine serum total cholesterol and high-density lipoprotein cholesterol (HDL-C) using a modified Technicon Auto Analyzer II-BMC enzymic system. The method uses 25 microL of sample (serum or supernate) for cholesterol determinations. Pooled serum which was calibrated indirectly against CDC's Abell-Kendall method was used for standardization. Accuracy and precision for total cholesterol determinations are comparable to those obtained using a modified Technicon AAII method. Coefficients of variation for the determination of HDL-C prepared by heparin/Mn++ precipitation are 6.4% and 4.6% at concentration levels of 0.70 mmol/L and 0.94 mmol/L respectively. The interchangeable use of deionized-distilled water and 0.15 mol/L NaCl solution for dilution of samples analyzed by the micro method is shown to produce significantly different cholesterol estimates. The reduced reagent volumes significantly lower the cost of cholesterol determinations. The system is simple, inexpensive and yields reliable cholesterol and HDL-C results.

Autoanalysis↗

PubMed1985

Is the glucocorticoid-induced hypertriglyceridemia in uremic rats caused by decreased tissue lipoprotein lipase activity?

The glucocorticoid-induced hypertriglyceridemia in uremic rats is partly due to defective removal of triglyceride (Tg)-rich lipoproteins. To determine whether this was due to decreased lipoprotein lipase (LPL), the key enzyme involved in the hydrolysis of Tg-rich lipoproteins, the LPL activity in soleus, heart and adipose tissue and the triglyceride secretion rates (TgSR) of uremic rats treated with Triamcinolone or placebo were studied. Sprague-Dawley rats were made uremic by a 2-stage 5/6 nephrectomy and studied three weeks later. During the 3rd week, one group was treated with a five day course of Triamcinolone (0.5 mg/kg body weight i.m.) and the other given an equal volume of saline. Triamcinolone aggravated the hypertriglyceridemia in uremic rats. This was associated with an increase in soleus and heart LPL with no change in adipose tissue LPL. The TgSR was also increased in the Triamcinolone-treated rats. These data suggest that decreased LPL activity is not the cause of hypertriglyceridemia in these rats.

Adipose Tissue↗

PubMed1985

The in vitro effect of corticosterone on insulin binding and glucose metabolism in mouse skeletal muscles.

We studied the in vitro effect of corticosterone on insulin binding, uptake of 2-deoxy-D-glucose, glycolysis, and glycogenesis in the soleus and extensor digitorum longus (EDL) of Swiss-Webster mice. In each experiment, one muscle (soleus/EDL) was incubated with corticosterone (0.1, 1, 50, and 100 micrograms/mL) and the respective contralateral muscle was incubated without corticosterone, but at the same insulin and pH levels. Corticosterone did not affect insulin binding in both muscles. However, corticosterone decreased the uptake of 2-deoxy-D-glucose and the rate of glycolysis and glycogenesis in both muscles when the dose was pharmacologic (50 and 100 micrograms/mL), but not when it was physiologic (0.1 and 1 microgram/mL). For glycolysis and glycogenesis, the suppression was greater in the EDL when compared with the soleus. This suppression was seen in both basal and insulin-stimulated conditions. In this in vitro system, where the experimental muscle is not exposed to prior hyperinsulinemia as in the in vivo model, corticosterone, at pharmacologic doses, affects postreceptor events without altering the insulin binding in the skeletal muscle.

Animals↗

PubMed1985

Effects of exercise on insulin binding to human muscle.

A procedure was developed to measure insulin binding to human skeletal muscle obtained via the percutaneous muscle biopsy technique. With this method the effects of exercise on insulin binding were investigated. Subjects (n = 9) exercised for 60 min on a bicycle ergometer at intensities ranging from 20-86% maximum O2 consumption (VO2max). Blood samples were obtained before, during, and after exercise and analyzed for glucose and insulin. Muscle samples (250 mg) for the vastus lateralis were obtained 30 min before exercise, at the end of exercise, and 60 min after exercise. Two subjects rested during the experimental period. There was no linear relationship between exercise intensities and the changes in insulin binding to human muscle. At rest (n = 2) and at exercise intensities below 60% VO2max (n = 5) no change in insulin binding occurred (P greater than 0.05). However, when exercise occurred at greater than or equal to 69% VO2max (n = 4), a pronounced decrement in insulin binding (30-50%) was observed (P less than 0.05). This persisted for 60 min after exercise. These results indicate that insulin binding in human muscle is not altered by 60 min of exercise at less than or equal to 60% VO2max but that a marked decrement occurs when exercise is greater than or equal to 69% VO2max.

Adult↗

PubMed1985

Insulin receptors: their roles in the pathogenesis and management of type II diabetes mellitus.

In Type II Diabetes Mellitus associated with insulin resistance, the defect is in insulin action. This may take the form of decreased insulin sensitivity, responsiveness, or both. The decrease in insulin binding is due to a decrease in the number of insulin receptors per cell. When the obese Type II diabetic loses weight after being on a weight reducing diet, the insulin sensitivity abnormality is restored towards normal. In so doing the number of insulin receptors per adipocyte or monocyte is restored towards normal. The effect of exercise on insulin binding in skeletal muscles of Type II diabetics has not been studied. Recent experiments in rodents and humans indicate that insulin binding is not affected by acute exercise but the post-receptor events are increased. Finally oral hypoglycemic medications can increase the insulin sensitivity and/or the insulin responsiveness of various tissues.

Administration, Oral↗

PubMed1985

Characterization of the tumorigenic and metastatic properties of a human pancreatic tumor cell line (AsPC-1) implanted orthotopically into nude mice.

An orthotopic xenograft of the human pancreatic tumor was established by inoculating human pancreatic tumor AsPC-1 cells into the duodenal lobe of the pancreas of the athymic nude mouse. Microscopically, the xenograft was formed by a heterogeneous population of tumor cells, displaying moderately to poorly differentiated adenocarcinomas with the latter capable of invading the adjacent pancreatic islets or non-endocrine elements. At 4 weeks post-transplantation, the tumor was detectable as a focal implant at the site of inoculation and thereafter grew progressively leading to extensive visceral invasion and metastasis. In contrast to the subcutaneous xenograft, all the mice (9/9) bearing orthotopically transplanted tumor developed secondary foci in the gut and at the peritoneum, with 7, 6, and 4 animals showing additional kidney, mesenteric lymphnodal, and diaphragm metastases, respectively. Distant metastases in the lungs were found in 3 mice and malignant ascites developed in two. Human pancreas cancer associated antigen was detected in the tumor, serum, and ascitic fluid of the mice at 63 +/- 24 micrograms/gm, 15 +/- 6 micrograms/ml, and 5 micrograms/ml, respectively. The finding of these regional and distant metastases was quite different from that in the animal bearing subcutaneously xenografted tumor where no metastases to internal organs was observed. The results suggest the potential use of this experimental system in tumor biology and antigen expression of human pancreatic cancer in vivo.

Animals↗

PubMed1984

Insulin binding in human skeletal muscle.

Insulin binding to crude plasma membranes derived from human skeletal muscle was characterized. Incubations were performed for 22 h at 4 degrees C. Typical insulin binding characteristics were found, i.e., (a) specificity for insulin, (b) pH sensitivity, (c) dissociation of insulin by the addition of excess insulin and (d) concave Scatchard curves. Half-maximal inhibition of 125I-labeled-insulin binding occurred at 1 X 10(-8) M. Affinity constants were 0.76 X 10(9) and 0.02 X 10(9) M-1 for the high- and low-affinity receptor (2-site model), respectively, and the corresponding receptor numbers were 89 and 1450 fmol/mg protein, respectively. The procedures employed permit the determination of insulin binding to small quantities of human muscle (approx. 250 mg).

Adult↗

PubMed1984

Distribution of the molecular species of phospholipids in human umbilical cord blood.

The composition of phosphatidylcholine (PC) and sphingomyelin (SM) was studied in cord blood lipoproteins to determine whether equilibration of the molecular species of phospholipids among lipoproteins was comparable with that reported for adults. The molecular species distributions of PC in low density lipoprotein (LDL) differed from that of high density lipoprotein (HDL). Whereas LDL PC was richer in combinations of fatty acids with 16 and 18 carbon atoms than HDL, the HDL was markedly enriched in combinations of fatty acids with 18 and 20 carbon atoms. Sphingomyelins in LDL were richer in palmitic acid than HDL while HDL had a greater proportion of long chain sphingomyelin than LDL. The molecular species of PC and SM do not equilibrate in cord blood. The results for the SM distributions were similar to other reports for adult human lipoprotein. However, the marked differential distribution of PC among lipoproteins appears unique to cord blood. The mechanisms responsible for equilibrating PC among lipoproteins are less well developed in the neonate when compared with the adult.

Ceramides↗

PubMed1984

The lipoproteins of human umbilical cord blood apolipoprotein and lipid levels.

The levels of apolipoproteins B, E and A-1 and the molecular species of triacylglycerols, phospholipids and cholesteryl esters were individually quantitated by electroimmunoassay and gas chromatographic total lipid profiling in 50 fresh samples of umbilical cord sera obtained from full term, normal delivery, healthy human neonates. All samples were screened for IgA to eliminate those samples with maternal blood contamination. The whole serum apolipoprotein levels in mg/dl +/- SEM for all neonates were; Apo B = 25.4 +/- 1.2; Apo E = 5.0 +/- 0.3; Apo A-1 = 86.6 +/- 2.3. These values represented 25% and 60% of adult serum values for Apo B and A-1, respectively, with normal adult values for Apo E. Apo A-1 was higher (P less than 0.020) in sera from female when compared to male neonates. The whole serum lipid values in mg/dl +/- SEM for all neonates were: 20.8 +/- 2.0 for triacylglycerols; 74.2 +/- 2.6 for lecithin and sphingomyelin; 79.8 +/- 2.7 for cholesteryl esters and 20.4 +/- 0.8 for unesterified cholesterol. Phospholipids, cholesteryl esters and total cholesterol levels were higher (P less than 0.025) in sera from female neonates when compared to males. The proportion of unesterified cholesterol relative to cholesteryl esters was high in comparison to adult sera, however the total cholesterol to phospholipid ratios were similar. The molecular species of cord sera triacylglycerols indicated a decreased proportion of C16 fatty acids with increased C18 and C20 when compared to adult sera. The molecular species of cord sera phospholipids similarly contained a decreased proportion of C16/18 fatty acids with increased C18/20 or C16/22 fatty acid combinations when compared to adults. The cord sera cholesteryl esters contained a significantly higher proportion of cholesterol esterified to C16 fatty acids with decreased amounts of cholesterol esterified to C18 and C20 fatty acids when compared to adults. Good correlations were obtained between Apo B and total serum cholesterol (R = 0.77) and also between Apo B and total serum triacylglycerols (R = 0.78).

Animals↗

PubMed1984

Insulin binding and 2-deoxy-D-glucose uptake in fast- and slow-twitch mouse skeletal muscle at 18 and 37 degrees C.

Insulin binding, insulin degradation, and 2-deoxyglucose uptake were examined at 18 and 37 degrees C in soleus and extensor digitorum longus muscles of mice. Insulin binding and degradation were greater in the soleus than in the extensor digitorum longus at both temperatures (p less than 0.05). At 37 degrees C, binding was decreased in both muscles while percentage degradation was increased in comparison with 18 degrees C (p less than 0.05). Dose--response curves (percentage of binding at 4 nM of insulin) remained the same for both muscles at the two temperatures. Basal (no insulin) 2-deoxyglucose uptake was increased at 37 degrees C in the extensor digitorum longus but not the soleus. Insulin responsiveness in terms of the amount of 2-deoxyglucose taken up per femtomole of insulin bound was almost identical for the two muscles at 18 degrees C, whereas at 37 degrees C it was increased more in the soleus than in the extensor digitorum longus. The results indicate that in the presence of physiological concentrations of insulin (0.2-4 nM), insulin binding trends are minimally affected by increased temperature. In contrast, the ability of insulin to stimulate 2-deoxyglucose uptake varies between the two temperatures, and at the higher temperature between fast- and slow-twitch muscle.

Animals↗