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Biomedical subjects

M M Wu

Publications and source records attributed to M M Wu.

At least 37 records · Page 2Linked to original sources

Activity-related features of synapse morphology: a study of endbulbs of held.

The myelinated fibers of the auditory nerve can be divided into two separate populations on the basis of sensitivity to sound, average levels of spike activity, and central branching patterns. The synaptic endings of these populations were investigated for the presence of structural specializations that might correlate with levels of neural activity. We applied intracellular recording and staining methods in cats to analyze directly the relationship between spike activity and the structure of synapses using endbulbs of Held, the large synaptic endings in the anteroventral cochlear nucleus. Endbulbs from fibers having low or high levels of activity were examined and compared using light and electron microscopic methods. All endbulbs exhibited relatively large but incomplete coverage by one-to-several lamellae of glial processes. Endbulbs of high activity fibers were large and contained larger mitochondria than endbulbs of low activity fibers. Furthermore, the synapses of high activity endbulbs were on average smaller but more numerous, possessed greater numbers of associated synaptic vesicles, and exhibited greater curvature of their postsynaptic densities. These structural features are hypothesized to reflect specializations that optimize synaptic transmission.

Animals↗

Effect of exercise and dietary restraint on energy intake of reduced-obese women.

Self-selected food intake of 15 reduced-obese women living in a metabolic ward was studied for 14 consecutive days to determine the effect of exercise and other metabolic and behavioral variables on energy intake. A choice of prepared food items were offered at breakfast, lunch and dinner, and a variety of additional food items were available continuously 24 h/day. Subjects performed either moderate intensity aerobic exercise (A-EX) (n = 8) expending 354 +/- 76 kcal/session or low intensity resistance weight training (R-EX)(n =7) expending 96 +/- kcal/session, 5 days/week. Mean energy intakes (kcal/day, +/- SEM) of the exercise groups were similar: 1867 +/- 275 for A-EX, 1889 +/- 294 for R-EX. Mean energy intakes of individuals ranged from 49 to 157% of the predetermined level required for weight maintenance. Resting metabolic rate per kg 0.75 and the Eating Inventory hunger score contributed significantly to the between subject variance in energy intake, whereas exercise energy expenditure did not. Regardless of exercise, eight women consistently restricted their energy intake (undereaters), and seven other consumed excess energy (overeaters). Overeaters were distinguished by higher Eating Inventory disinhibition (P = 0.023) and hunger (p = 0.004) scores. The overeaters' diet had a higher fat content 34 +/- 1% (p = 0.007). Also, overeaters took a larger percentage of their daily energy, than that of undereaters, 27 +/- 1 energy intake in the evening, 13 +/- 2%, compared to undereaters, 7 +/- 1% (p = 0.005). We conclude that the Eating Inventory is useful for identifying reduced-obese women at risk of overeating, and these individuals may benefit from dietary counseling aimed at reducing fat intake and evening snacking.

Adult↗

Multiple risk factors associated with arsenic-induced skin cancer: effects of chronic liver disease and malnutritional status.

In order to evaluate the prevalence and multiple risk factors of arsenic-induced skin cancer among residents in Taiwanese villages in which chronic arseniasis is hyperendemic, a total of 1571 subjects aged 30 or more years were recruited between September 1988 and March 1989. All of them were interviewed personally by a public health nurse using a structured questionnaire, and 1081 interviewed study subjects, including 468 men and 613 women, participated in physical examination, giving a participation rate of 68.8%. The overall prevalence of skin cancer was as high as 6.1%, showing an increase with age in both men and women. There was a significant dose-response relation between skin cancer prevalence and chronic arsenic exposure as indexed by duration of residence in the endemic area, duration of consumption of high-arsenic artesian well water, average arsenic exposure in parts per million (p.p.m.) and cumulative arsenic exposure in p.p.m.-years. Chronic carriers of hepatitis B surface antigen with liver dysfunction had an increased prevalence of skin cancer. Undernourishment, indexed by a high consumption of dried sweet potato as a staple food, was also significantly associated with an increased prevalence of arsenic-induced skin cancer. All these risk factors remained statistically significant in the multiple logistic regression analysis. Consistent with animal experiments, the findings imply that liver function and nutritional status may affect the metabolism of inorganic arsenic and the development of subsequent skin cancers.

Adult↗

Increased prevalence of hypertension and long-term arsenic exposure.

To examine the association between long-term exposure to inorganic arsenic and the prevalence of hypertension, we studied a total of 382 men and 516 women residing in villages where arseniasis was hyperendemic. Hypertension was defined as a systolic blood pressure of 160 mm Hg or greater, a diastolic blood pressure of 95 mm Hg or greater, or a history of hypertension treated regularly with antihypertensive drugs. The long-term arsenic exposure was calculated from the history of artesian well water consumption obtained through standardized interviews based on a structured questionnaire and the measured arsenic concentration in well water. Residents in villages where long-term arseniasis was hyperendemic had a 1.5-fold increase in age- and sex-adjusted prevalence of hypertension compared with residents in nonendemic areas. Duration of artesian well water consumption, average arsenic concentration in drinking water, and cumulative arsenic exposure were all significantly associated with hypertension prevalence. The higher the cumulative arsenic exposure, the higher the prevalence of hypertension. This dose-response relation remained significant after adjustment for age, sex, diabetes mellitus, proteinuria, body mass index, and serum triglyceride level. The results suggest that long-term arsenic exposure may induce hypertension in humans.

Adult↗

Ingested inorganic arsenic and prevalence of diabetes mellitus.

To examine the association between ingested inorganic arsenic and prevalence of diabetes mellitus, in 1988, the authors studied 891 adults residing in villages in southern Taiwan where arseniasis is hyperendemic. The status of diabetes mellitus was determined by an oral glucose tolerance test and a history of diabetes regularly treated with sulfonylurea or insulin. The cumulative arsenic exposure in parts per million-years was calculated from the detailed history of residential addresses and duration of drinking artesian well water obtained through standardized interviews based on a structured questionnaire and the arsenic concentration in well water. The body mass index was derived from body height and weight measured according to a standard protocol, while the physical activity at work was also obtained by questionnaire interviews. Residents in villages where the chronic arseniasis was hyperendemic had a twofold increase in age- and sex-adjusted prevalence of diabetes mellitus compared with residents in Taipei City and the Taiwan area. There was a dose-response relation between cumulative arsenic exposure and prevalence of diabetes mellitus. The relation remained significant after adjustment for age, sex, body mass index, and activity level at work by a multiple logistic regression analysis giving a multivariate-adjusted odds ratio of 6.61 and 10.05, respectively, for those who had a cumulative arsenic exposure of 0.1-15.0 and greater than 15.0 ppm-year compared with those who were unexposed. These results suggest the chronic arsenic exposure may induce diabetes mellitus in humans.

Adult↗

Effects of a carotene-deficient diet on measures of oxidative susceptibility and superoxide dismutase activity in adult women.

The effect of consuming a low carotene diet (approximately 60 micrograms carotene/day) on oxidative susceptibility and superoxide dismutase (SOD) activity in women living in a metabolic research unit was evaluated. The diet had sufficient vitamins A, E, and C. The women ate the diet supplemented with 1500 micrograms/day beta-carotene for 4 days (baseline), then the unsupplemented diet for 68 days (depletion), followed by the diet supplemented with > 15,000 micrograms/day carotene for 28 days (repletion). Production of hexanal, pentanal, and pentane by copper-oxidized plasma low density lipoproteins from carotene-depleted women was greater than their production of these compounds when repleted with carotene. Erythrocyte SOD activity was depressed in carotene-depleted women; it recovered with repletion. Thiobarbituric acid reactive substances in plasma of carotene-depleted women were elevated and diminished with repletion. Dietary carotene seems to be needed, not only as a precursor of vitamin A, but also to inhibit oxidative damage and decrease oxidation susceptibility.

Adult↗

Decreased systemic thromboxane A2 biosynthesis in normal human subjects fed a salmon-rich diet.

Nine normal male subjects were fed a reference diet typical of that consumed in the United States and a diet containing approximately 450 g salmon (salmon-rich diet). The salmon diet contained approximately 6 g omega 3 fatty acids that comprised 2.0% energy intake/d for each individual. The percent energy contribution of protein, carbohydrate, and fat (19%, 56%, and 25%, respectively) was identical for the two diets. Urinary excretion of 2,3-dinor-thromboxane B2 was significantly lower (0.74 +/- 0.26 ng/24 h) with the salmon diet compared with the reference diet (0.95 +/- 0.31 ng/24 h). In addition, in vitro generation of thromboxane B2 in response to collagen-stimulated aggregation of platelet-rich plasma from subjects consuming the salmon diet was reduced (1.87 +/- 0.79 ng/mL) compared with subjects consuming the reference diet (3.10 +/- 1.81 ng/mL). Urinary 2,3-dinor-6-oxo-prostaglandin F1 alpha excretion in subjects was not significantly different between the salmon diet (0.69 +/- 0.33 ng/24 h) and the reference diet (0.81 +/- 0.44 ng/24 h).

Adult↗

Effect of a low beta-carotene diet on the immune functions of adult women.

We examined the effect of beta-carotene depletion and repletion on the immune status of nine healthy women who lived in the metabolic suite for 100 d. For the first 4 d all women were fed a basal diet supplemented with 1.5 mg beta-carotene/d (baseline). During the next 68 d, the basal diet without beta-carotene supplementation was fed to all subjects (depletion), and during the last 28 d the diet of each women was supplemented with 15.0 mg beta-carotene/d (repletion). Neither beta-carotene depletion nor repletion significantly (P < or = 0.05) altered proliferation of peripheral blood mononuclear cells cultured with phytohemagglutinin or concanavalin A, in vitro production of soluble interleukin 2 receptor, or the concentration of circulating lymphocytes and their subsets. Thus, in healthy adults consuming adequate vitamin A, beta-carotene depletion had no adverse effect on the indexes tested, nor was there any beneficial effect of modest beta-carotene supplementation.

Adolescent↗

Homocysteine increases as folate decreases in plasma of healthy men during short-term dietary folate and methyl group restriction.

Ten healthy adult men were fed a diet low in folate and exogenous methyl groups to study the effects on folate requirement and status. The men were housed in a metabolic unit for the entire 108-d study. After a 9-d base-line period (P1), the men were fed an amino acid-defined soybean product diet for 45 d, which provided 25 micrograms/d of folate for 30 d (P2) and (with a folate supplement) 99 micrograms/d for 15 d (P3). During P2 and P3, the low methionine and choline diet was supplemented with methionine for half the subjects to vary the dietary methyl group intake. The periods were then repeated over the next 54 d (P4-P6), with a cross-over of methionine intakes in P5 and P6. Restricting dietary methyl group intake did not increase the dietary folate requirement. Plasma total homocysteine rose during folate depletion and correlated inversely with plasma folate; however, the response of homocysteine to changes in folate intake varied among individuals from very strong to absent. The results support previous suggestions that increased plasma homocysteine concentrations provide a marker of functional folate deficiency, and further indicate that individuals may differ greatly in their susceptibility to hyperhomocysteinemia due to low folate intakes. Judged by the lack of normalization of high homocysteine concentrations during folate repletion, the current folate RDA for adult men may not provide the expected margin of protection.

Adult↗

Moderate diet restriction alters the substrate and hormone response to exercise.

Substrate and hormone responses to submaximal exercise were studied in 10 overweight women (119-141% ideal body weight) to learn if a moderately restricted diet would influence the responses. Subjects consumed diets with adequate energy (ADEX), N = 5, or low energy (LDEX)--50% reduction in energy, N = 5. Three times during the 12-wk study, blood was drawn before and immediately following exercise; results were combined since there were no differences between replicates. Postexercise free fatty acids and glycerol increased to 465 +/- 27 mg.l-1 in LDEX but only to 245 +/- 19 mg.l-1 in ADEX. Postexercise insulin increased to 129 +/- 13 pmol.l-1 in LDEX, but did not increase in ADEX. Postexercise growth hormone increased to 10.5 +/- 1.0 microgram.l-1 in ADEX but only to 6.6 +/- 1.0 microgram.l-1 in LDEX. All postexercise increases within diet groups were highly significant (P < 0.0001), and the postexercise responses between diet groups were also different (P < 0.01). Respiratory gas exchange indicated that both groups increased fat utilization during exercise, but diet restriction altered postexercise hormones so that fat mobilization and utilization might be inhibited. The postexercise recovery period should be studied further to determine whether diet restriction results in a sustained altered hormone pattern that would curtail lipolysis and possibly limit body fat loss.

3-Hydroxybutyric Acid↗

Prevalence of human papillomaviruses 16 and 18 in transitional cell carcinoma of bladder.

It has been speculated that human papillomaviruses (HPV) might be a causative agent of transitional cell carcinoma of the bladder. With the polymerase chain reaction technic, fresh specimens of 53 transitional cell carcinomas of the bladder were examined, and bladder epithelium from 12 patients with hyperplasia of prostate and peripheral blood lymphocytes of 8 normal individuals served as controls. The primers set for HPV-16 and 18 were selected from E6/E7 regions of open reading frames. HPV-16 was positive in 52.8% of the specimens examined, whereas HPV-18 positive in only 3.7%. No controls showed either HPV-16 or 18. Reports on the role of HPVs in carcinogenesis of bladder are scanty and yet there exist conspicuous discrepancies among them. There is a diversity of opinions on the contamination and variation of technical procedures. More work should be done before the relationship between HPV-16 and development of bladder carcinoma can be clarified.

Base Sequence↗

Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water.

In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.

Adult↗

A novel score for predicting the mortality of septic shock patients.

OBJECTIVE: To establish a prognostic scoring system for septic shock patients. DESIGN: The clinical, biological, and hemodynamic data of these patients were retrospectively explored to select variables independently associated with outcome. According to the risk of death, ratings from 0 to 2 points were attributed to each value. SETTING: Medical intensive care service of a 1,000-bed tertiary care university medical center. PATIENTS: Eighty-eight patients in septic shock in whom hemodynamic measurements were performed using pulmonary artery flotation catheters. RESULTS: Fourteen clinical, biological, and hemodynamic variables were selected and rated for each patient. A Simplified Septic Shock Score, available immediately after admission and catheterization, was established by adding the rates of these variables. The mean Simplified Septic Shock Score was 2.5 +/- 1.7 (SD) in 43 survivors and 6.5 +/- 2.3 in 45 nonsurvivors (p less than .0001). Some underlying diseases and characteristics of infections also correlated with the outcome. Further ratings from 0 to 2 points were attributed to these conditions. A Complete Septic Shock Score was calculated by adding these rates to the Simplified Septic Shock Score. The Complete Septic Shock Score had a slightly better prognostic value than the Simplified Septic Shock Score, but it could be determined only after the availability of the microbiological data. The mean Complete Septic Shock Score was 3.1 +/- 1.9 in survivors and 8.4 +/- 2.6 in nonsurvivors (p less than .0001). Both Simplified and Complete Septic Shock Scores showed better association with patient outcome than the Simplified Acute Physiology Score or the Acute Physiology and Chronic Health Evaluation (APACHE II) score. CONCLUSIONS: The Simplified and the Complete Septic Shock Scores are simple scoring systems that appear to predict the outcome of septic shock patients more accurately than general scoring systems, such as the Simplified Acute Physiology Score and APACHE II score. These septic shock scores might be useful in assessing the severity of septic shock patients.

Adult↗

Voltage dependence of current through the Na,K-exchange pump of Rana oocytes.

We have studied current (IStr) through the Na,K pump in amphibian oocytes under conditions designed to minimize parallel undesired currents. Specifically, IStr was measured as the strophanthidin-sensitive current in the presence of Ba2+, Cd2+ and gluconate (in place of external Cl-). In addition, IStr was studied only after the difference currents from successive applications and washouts of strophanthidin (Str) were reproducible. The dose-response relationship to Str in four oocytes displayed a mean K0.5 of 0.4 microM, with 2-5 microM producing 84-93% pump block. From baseline data with 12 Na(+)-preloaded oocytes, voltage clamped in the range [-170, +50 mV] with and without 2-5 microM Str, the average IStr depended directly on Vm up to a plateau at 0 mV with interpolated zero current at -165 mV. In three oocytes, lowering the external [Na+] markedly decreased the voltage sensitivity of Ip, while producing only a small change in the maximal outward IStr. In contrast, decreasing the external [K+] from 25 to 2.5 mM reduced IStr at 0 mV without substantially affecting its voltage dependence. At K+ concentrations of less than 1 mM, both the absolute value of IStr at 0 mV and the slope conductance were reduced. In eight oocytes, the activation of the averaged IStr by [K+]0 over the voltage interval [-30, +30 mV] was well fit by the Hill equation, with K' = 1.7 +/- 0.4 mM and nH (the minimum number of K+ binding sites) = 1.7 +/- 0.4. The results unequivocally establish that the cardiotonic-sensitive current of Rana oocytes displays only a positive slope conductance for [K+]0 greater than 1 mM. There is therefore no need to postulate more than one voltage-sensitive step in the cycling of the Na, K pump under physiologic conditions. The effects of varying external Na+ and K+ are consistent with results obtained in other tissues and may reflect an ion-well effect.

Animals↗

Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group.

Serum concentrations of immunoreactive tumor necrosis factor/cachectin (TNF), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), and interferon-alpha (IFN alpha) were prospectively measured in 70 patients with septic shock to determine their evolution and prognostic values. In a univariate analysis, levels of TNF (P = .002) and IL-1 beta (P = .05) were associated with the patient's outcome, but not IFN alpha (P = .15) and IFN gamma (P = .26). In contrast, in a stepwise logistic regression analysis, the severity of the underlying disease (P = .01), the age of the patient (P = .02), the documentation of infection (nonbacteremic infections vs. bacteremias, P = .03), the urine output (P = .04), and the arterial pH (P = .05) contributed more significantly to prediction of patient outcome than the serum levels of TNF (P = .07). After 10 days, the median concentration of TNF was undetectable (less than 100 pg/ml) in the survivors, whereas it remained elevated (305 pg/ml, P = .002) in the nonsurvivors. Thus, in patients with septic shock due to various gram-negative bacteria, other parameters than the absolute serum concentration of immunoreactive TNF contributed significantly to the prediction of outcome.

Adolescent↗

Risk factors for gallstones among Chinese in Taiwan. A community sonographic survey.

A health survey of adults aged 30 years or more was carried out in southwest Taiwan to determine the prevalence of gallstones and to study risk factors associated with gallstones. Blood samples were collected and abdominal sonographic examination and anthropometric measurements were performed on a total of 923 people. The 40 gallstone cases detected resulted in a prevalence of 4.3%. The risk factors explored included age, sex, hepatitis, obesity, hyperlipidemia, and diabetes mellitus (DM). Age and DM were the only significant factors associated with gallstones in our study. With a reference group of 30-39-year-olds as a comparison, multiple logistic regression analysis showed a trend effect with odds ratios of 1.73, 3.74, and 6.32 for age groups of 40-49, 50-59, and 60 or above, respectively. The odds ratio for DM was as high as 2.59. However, sex, body weight index, chronic hepatitis B, and hyperlipidemia were not significantly associated with gallstones.

Adult↗

Demethylation pathways in caffeine metabolism as indicators of variability in 1,1,1-trichloroethane oxidation in man.

Twenty volunteers were exposed to 191 +/- 7 p.p.m. 1,1,1-trichloroethane or 50 +/- 2 p.p.m. perchloroethylene vapour for 6 hr. They were then evaluated for their rate of caffeine metabolism, mephenytoin hydroxylation and debrisoquine hydroxylation. Seven subjects were identified as 'fast acetylators' of caffeine and one person as a slow metabolizer of debrisoquine. The "slow acetylators" exposed to perchloroethylene excreted an average of 3.83 +/- 0.35 mg trichloroacetic acid within 24 hr (N = 13, +/- S.E.) and the 'fast acetylators' 3.58 +/- 0.48 mg (N = 7, +/- S.E.). The excretion of trichloroethanol by the same persons after 1,1,1-trichloroethane exposure was 14.1 +/- 1.12 mg and 16.7 +/- 1.48 mg, respectively. The excretion of trichloroacetic acid in the latter exposure varied significantly between the seven 'fast' and 13 'slow acetylators' (0.43 +/- 0.08 mg versus 1.03 +/- 0.19 mg; +/- S.E.; P = 0.037). A multiple linear regression analysis confirmed this association when other factors, such as body weight, creatinine clearance, smoking habit and alcohol consumption, were taken into account. One volunteer proved to be a poor hydroxylator of debrisoquine and excreted half the amount of trichloroacetic acid in the perchloroethylene exposure and half the amount of trichloroethanol in the 1,1,1-trichloroethane exposure compared to the others. A reduction in the solvent metabolism could thus be predicted by the debrisoquine test. On the other hand, the caffeine test predicted faster oxidation of trichloroethanol which could be of toxicological and pharmacological importance e.g. in the clinical use of chloral.

Adult↗