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Biomedical subjects

L Wong

Publications and source records attributed to L Wong.

At least 235 records · Page 13Linked to original sources

Change in degree of type 1 piliation of Escherichia coli during experimental peritonitis in the mouse.

To determine whether expression of type 1 pili varies during the course of Escherichia coli infection in vivo, mice were injected intraperitoneally with 5 X 10(7) CFU of piliated or nonpiliated phase variants per ml, and the degree of piliation was measured in peritoneal exudate by an enzyme-linked immunosorbent assay inhibition method. In the animals challenged with the piliated bacteria, the numbers of organisms increased a log over 9 h and the amount of pilus antigen decreased from 3 to 0.075 micrograms/10 bacteria. After a 4-h delay, nonpiliated bacteria also increased by one log over 9 h; however, the amount of piliation remained virtually undetectable. Piliated E. coli were more virulent than nonpiliated variants in this model (50% lethal dose of 7.5 X 10(6) versus 3 X 10(7), respectively). The difference was significantly reduced by prior passive immunization with rabbit serum containing high titers of antipili antibody. Piliated bacteria adhered in significantly greater numbers to isolated mouse peritoneal membranes than did nonpiliated variants (15,400 +/- 2,700 versus 1,300 +/- 700 bacteria/mm2, respectively; P = 0.05). Adherence was inhibited by the presence of 0.1 M alpha methyl mannose (1,500 +/- 1,800 bacteria/mm2, P = 0.01). These results confirm the results of previous qualitative studies showing that phase variation of type 1 pili occurs in vivo and suggest that these pili may confer an initial advantage for growth of E. coli in the peritoneal cavity, presumably by fostering colonization of the peritoneal serosal surface.

Animals↗

Celiprolol: a new beta adrenoceptor antagonist with novel ancillary properties.

Celiprolol HC1 is a new cardioselective beta-blocker with properties which may make it the next advance in the evolution of this class of compounds. Its cardioselectivity has been demonstrated both in vitro and in vivo, with an intravenous potency equivalent to atenolol. The compound is devoid of a membrane stabilizing effect which is reflected in anesthetized dogs by a lack of myocardial electrophysiological effects. The compound induces a vasodilator effect in anesthetized dogs which is partially attenuated by propranolol, suggesting a weak beta 2-agonist activity. This beta 2-agonist property is also manifested in other peripheral tissues and undergoes down-regulation with repeat exposure. In contrast to other beta-blockers, celiprolol produces a bronchodilation in anesthetized cats which is propranolol-resistant. Isolated tissue studies suggest that a weak alpha 2-blocking effect contributes to this bronchodilation, although another unknown mechanism participates as well. Celiprolol induces a cardiac stimulation in anesthetized dogs which is inhibited by propranolol. The mechanism for this effect appears to be due to adrenergic interaction. These unique properties of celiprolol convey salutary effects in the clinical use of celiprolol.

Adrenergic beta-Antagonists↗

The effects of aerobic conditioning and/or caloric restriction in overweight men and women.

The purpose of this study was to compare the effects of exercise and/or caloric restriction for 12 wk on body composition, maximal aerobic power (VO2max), and serum lipids and lipoproteins in overweight individuals. Forty-eight males and 48 females (means age = 36.6 yr), 120-140% of ideal body weight, were randomly assigned to groups (N = 12 each) of diet-exercise (DE), diet (D), exercise (E), and sedentary control (C). The dietary regimen consisted of 1,200 kcal X d-1, while exercise consisted of 5 d X wk-1 of 30 min of walk/running. For the males, body weight (BW) and fat weight loss in the DE group (-11.8 and 23%, respectively) were significantly greater than in the D group (-9.1 and -18%), with both groups significantly greater than for E and C. In the females, BW and fat weight loss for DE (-10.4 and -24%) were significantly greater than for D (-7.8 and -20%), with both groups significantly greater than E and C. Both DE and D males and females had a decrease in fat-free weight of -4.5 and -2.4%, respectively. In both sexes, the increase in VO2max-BW (ml X kg -1 X min-1) in DE (25%) was significantly greater than for E (15%), D (11%), and C (0%), with differences between E and D nonsignificant. However, increases in absolute VO2max (1 X min-1) and VO2max-fat-free weight (ml X kg-1 X min-1) were similar (P greater than 0.05) for DE and E (14%) but significantly greater compared to D and C (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗

Excretion of cyclosporine and its metabolites in human bile.

Quantitative and qualitative studies of cyclosporine and its metabolites were performed on human bile from liver transplant and liver disease patients. The concentration of CsA in bile is higher in patients with normal liver function than in those with poor liver function but in neither case could account for more than 2% of an absorbed dose of CsA. Although concentrations of CsA plus metabolites in bile measured by RIA were 18 to 36 times higher than HPLC concentrations, they accounted for less than 50% of an absorbed CsA dose. By means of mass spectrometry and HPLC retention times of known metabolites, peaks equivalent to the previously isolated CsA M8, M13, M17, M1, M18, and M21 of Maurer et al were found in the ether extracts of bile. Future studies should not only concentrate on the pharmacologic and toxicologic effects of the metabolites but should also accurately quantitate these compounds in blood, plasma, urine, and bile.

Bile↗

Production and characterization of a monoclonal antibody to dog hepatic lipase.

Partially purified dog hepatic lipase was used as antigen to produce monoclonal antibodies in mice. In addition to enzyme-linked immunosorbent assay (ELISA), a reliable and efficient procedure for screening antibodies reacting to hepatic lipase has been developed. A method to distinguish antibodies directing to active site or non-active site epitopes has also been described. We obtained three positive clones that survived after subcloning and expansion. All three monoclonal antibodies possess gamma one (gamma 1) heavy chains and kappa (kappa) light chains. Specificity of monoclonal antibody LDHL No. 537 to dog hepatic lipase was demonstrated by passing post-heparin plasma through its immunoaffinity column. Only dog hepatic lipase was removed by LDHL No. 537 from post-heparin plasma. The immunoaffinity chromatography also demonstrated the co-existence of three enzyme activities (mono- and triacylglycerol lipase and phospholipase A1) on the dog hepatic lipase molecule. The subunit weight of dog hepatic lipase has been estimated at 57500 +/- 600 (n=3) by using immunoaffinity chromatography and the combination of immunoprecipitation and autoradiography methods.

Animals↗

Calcium metabolism in aluminum encephalopathy.

Electrophysiologic deficits occurred in the in vitro hippocampal slice preparation removed from rabbits at various stages of an aluminum-induced encephalopathy. These deficits were associated with a progressive increase in total tissue calcium content. The deficits were reversed, in part, by increasing extracellular calcium concentration. Whereas calmodulin and calcium-binding protein, as measured by radioimmune assay, did not change in amount, the activity of calmodulin, as a calcium-calmodulin activator of the enzyme 3',5'-cyclic nucleotide phosphodiesterase, declined progressively as the aluminum encephalopathy developed. Cholinergic neurochemical transmission, measured by choline acetyltransferase activity and muscarinic binding, did not change in the encephalopathy. We postulate that aluminum alters brain calcium homeostasis, perhaps through an effect on calmodulin.

Aluminum↗

Monoclonal antibodies to rat C apolipoproteins: production and characterization of a unique antibody whose binding to apoC-I is inhibited by nonionic detergents.

Four monoclonal antibodies to rat apo (apolipoproteins) C were produced. Three of the monoclonals reacted to apoC-I and one to apoC-III. The IgG monoclonals LRB 21 and LRB 45 recognized a spatially close together or identical apoC-I epitope. The monoclonal LRB 80, however, recognized an epitope that is close to, but distinct from, that recognized by LRB 45 and LRB 21. The antibody LRB 45 recognized an apoC-I epitope that is specific for rat apoC-I, and the antibody did not cross-react with dog or human lipoproteins. Rat apoC-I could be detected in all lipoprotein density fractions, but not in the d greater than 1.21 g/ml fraction. Freezing and thawing of serum did not alter the antibody antigen binding. However, lipolysis of whole serum resulted in a 30% increase in antigenic epitope expression. Antibody antigen reaction could be inhibited by subcritical micellar concentration of nonionic detergents. The inhibition was specific but could be partially reversed if lipid-containing serum was used as a dilution buffer. On feeding animals a diet of olive oil and cholesterol for 2 weeks, apoC-I levels decreased.

Amino Acids↗

Monoclonal antibody to rat apoC: multiple binding to apoC-I on lipoproteins increases its affinity constant.

Using solid phase systems, the kinetics of binding of monoclonal antibody (LRB 45, IgG2b,kappa) to apoC-I and apoC-I on lipoproteins were investigated. At 25 degrees C, the association constant of LRB 45 antibody to apoC-I (3.56 X 10(6) M-1 X sec-1) was almost three times slower than the association constant LRB 45 antibody to lipoproteins (10.4 X 10(6) M-1 X sec-1). However, the dissociation constant of apoC-I from LRB 45 antibody (0.865 X 10(-4) sec-1) was also slower than the dissociation constant of lipoprotein from antibody (1.5 X 10(-4) sec-1). Thus, the calculated affinity constant (association constant/dissociation constant) of LRB 45 antibody for apoC-I was approximately half of that for lipoproteins (4.12 X 10(10) M-1 vs. 6.92 X 10(10) M-1). The intrinsic affinity constants for antibody binding to apoC-I and apoC-I on lipoproteins were determined by Scatchard analysis. The intrinsic affinity constant of antibody bound to apoC-I was estimated to be 5.49 X 10(10) M-1 whereas that of antibody binding to lipoproteins was 30 to 200 times less. Furthermore, ascites fluid from LRB 45 cell lines could immunoprecipitate serum lipoproteins. Thus, it is concluded that there is multiple binding of antibody to apoC-I on lipoproteins. This binding appears to increase the calculated affinity constant (avidity) for antibody-antigen interaction.

Animals↗

A single high-cholesterol, high-fat meal preferentially increases low molecular weight apolipoprotein B concentration in rat plasma.

Rats were fed either rat chow (control), chow + 20% olive oil (olive oil), or chow + 20% olive oil + 2% cholesterol (olive oil/cholesterol) as a single meal to study the short-term effects of fat and the above combination of fat/cholesterol-containing diets on plasma apoB concentration and its influence on the distribution of apoB subspecies. Rats were given their meals and allowed to consume them ad libitum until they were killed, 3 hr or 9 hr afterwards. Three hours after feeding, serum triglyceride concentrations were increased to the same extent in both the olive oil and olive oil/cholesterol-fed rats as compared with concentrations in control rats, but serum apoB concentrations did not differ among the groups. Nine hours after feeding, serum triglyceride concentrations were still equally elevated in both experimental groups; however, in the olive oil/cholesterol-fed rats, total serum apoB as well as total serum cholesterol were increased above both the control and olive oil groups. In addition, the d less than 1.21 g/ml lipoprotein apoBl/apoBh ratio of the olive oil/cholesterol-fed rats was greatly increased at 9 hr, whereas apoBl/apoBh ratio in the d less than 1.21 g/ml fraction of the olive oil group was unchanged, despite the increase in plasma triglyceride concentration. In the olive oil/cholesterol-fed rats at 9 hr, cholesterol, total apoB, apoBl, and apoBh of both VLDL and IDL were greater than in the control or olive oil rats. In d less than 1.21 g/ml lipoproteins, VLDL, and IDL, the increases in apoBl concentrations were of a greater magnitude than the increases in apoBh.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Isometric detrusor pressure during bladder filling and its dependency on bladder volume and interruption to flow in control subjects.

We characterized the isometric pressures generated by the bladder during voluntary detrusor contraction and interruption of flow. Urodynamic studies were done in 34 healthy female volunteers, with a mean age of 29.6 plus or minus 9.3 years. Control urodynamics were done first to characterize bladder and urethral parameters to filling and voiding. Subsequently, isometric detrusor pressures were elicited during bladder filling at increments of 100 ml. by asking subjects to attempt to void against a urethral obstruction produced by an inflated Foley balloon. Isometric pressures also were obtained by interruption of flow through the lumen of the 22F Foley catheter. The results showed that the maximum isometric pressure increase generated remained relatively constant during bladder filling at 39.6 plus or minus 13.1 cm. water. This pressure is not significantly different from voiding pressures developed with a 10F urethral catheter. On the other hand, isometric pressure increases during voiding showed that the increase in bladder pressure following interruption of flow was volume sensitive. The possibility that this volume dependency may result in errors in the interpretation of bladder contractility is discussed.

Adult↗

Serum amylase, isoamylase and lipase in acute alcoholism.

Hyperamylasemia is found in asymptomatic alcoholics. The aim of this study was to document the incidence of elevations of serum amylase and lipase in asymptomatic alcoholics and to evaluate the contribution of salivary isoamylase to the total serum amylase. One hundred and three patients with acute alcohol withdrawal were studied. Total serum amylase was elevated in 7 patients (6.8%) of whom 4 (57%) showed elevation of salivary isoamylase. Elevated lipase levels were found in 11 patients (10.7%) but correlation of lipase levels with either amylase or isoamylase levels was poor. Thus there was a low but significant incidence of hyperamylasemia which resulted from an elevated salivary isoamylase in the majority of cases. Lipase determination did not assist in defining the origin of the hyperamylasemia and correlated poorly with the other enzymes. It is probably more sensitive than amylase in reflecting the toxic effects of alcohol on the pancreas.

Adult↗

Ecologic regression analysis and the study of the influence of air quality on mortality.

This presentation focuses entirely on the use and evaluation of regression analysis applied to ecologic data as a method to study the effects of ambient air pollution on mortality rates. Using extensive national data on mortality, air quality and socio-economic status regression analyses are used to study the influence of air quality on mortality. The analytic methods and data are selected in such a way that direct comparisons can be made with other ecologic regression studies of mortality and air quality. Analyses are performed by use of two types of geographic areas, age-specific mortality of both males and females and three pollutants (total suspended particulates, sulfur dioxide and nitrogen dioxide). The overall results indicate no persuasive evidence exists of a link between air quality and general mortality levels. Additionally, a lack of consistency between the present results and previous published work is noted. Overall, it is concluded that linear regression analysis applied to nationally collected ecologic data cannot be used to usefully infer a causal relationship between air quality and mortality which is in direct contradiction to other major published studies.

Air Pollutants↗

The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency.

Eight cases of isolated human pyruvate carboxylase deficiency were examined from seven families. Although all patients presented with a chronic lacticacidemia, two particular patients presented with the added features of hyperammonemia, citrullinemia, and hyperlysinemia. When cultured skin fibroblasts from these patients were examined for their ability to synthesize [3H]biotin-containing proteins, it was found that the two patients who presented with hyperammonemia, citrullinemia, and hyperlysinemia did not synthesise a protein of the correct subunit molecular weight (Mr = 125 K daltons) corresponding to pyruvate carboxylase. In addition, when skin fibroblast proteins were labeled with [35S]methionine, cross-reacting material (CRM) corresponding to pyruvate carboxylase was immunoprecipitated by antipyruvate carboxylase antiserum in most patients, but again the two patients with the atypical presentation showed no CRM. We propose that the different clinical presentation of human pyruvate carboxylase deficiency is a manifestation of two different mutations in the pyruvate carboxylase gene, one that results in the synthesis of a relatively inactive pyruvate carboxylase protein CRM(+ve) and one that results in the lack of expression of the gene in the form of a recognizable protein CRM(-ve).

Biotin↗

Rice flour, breath hydrogen, and malabsorption.

In contrast to the incomplete intestinal absorption of many dietary carbohydrates in healthy humans, it has been suggested that rice flour is completely absorbed. The aims of this study were (a) to confirm efficient absorption of rice flour in healthy individuals, (b) to evaluate a "rice breath hydrogen (H2) test" in the investigation of patients with suspected malabsorption, and (c) to compare H2 results with quantitative fecal fat excretion. The test meal consisted of 100 g of carbohydrate in the form of rice pancakes. End expiratory breath samples were collected at 30-min intervals over 8 h and the H2 concentration was analyzed by gas chromatography. Three-day stool fat collections were performed on a 70-g fat intake. The results of the experiment indicated that healthy controls (n = 23) produced minimal H2 [mean increase (delta) +/- SE] = 6.9 +/- 1.4 parts per million (ppm). Patients with pancreatic disease produced 43.2 +/- 8.0 ppm. Complete or partial correction was achieved in each of 6 subjects with oral pancreatic supplements. Twenty-two patients with a variety of small bowel diseases produced a mean increase of 73.2 +/- 21.4 ppm. Breath H2 excretion was maximal in patients with bacterial overgrowth. Disease controls (n = 10) with diarrhea of colonic origin did not produce significant H2. The sensitivity of the rice-breath H2 test compared favorably with quantitative fecal fat excretion. Within individuals, there was a lack of correlation between breath H2 data (an index of CHO malabsorption) and daily stool weight that reflects the presence or absence of diarrhea. This lack of correlation supports the concept that the endogenous microflora salvage considerable quantities of unabsorbed carbohydrate.

Adult↗

Argininosuccinic aciduria. A developmental and biochemical case study.

An infant with argininosuccinic aciduria was detected through the routine newborn screening program for inborn metabolic diseases and has been followed for over 7 years. Treatment consisting of restricted protein intake and arginine base supplementation was initiated at the age of 8 months and was continued intermittently. She maintained normal psychomotor development to the age of 3 years and currently at the age of 7.3 years, she has measured intelligence in the borderline range. She has had mild symptoms of cerebellar ataxia. Her physical growth has been below normal. Biochemical abnormalities are described. Special metabolic investigations and the effects of treatment are discussed.

Amino Acid Metabolism, Inborn Errors↗

The role of Tennessee antigen in the diagnosis of gastrointestinal malignancy.

Tennessee antigen (TAG) is a glycoprotein which has been extracted from adenocarcinoma of the colon. It is one of the numerous tumour associated antigens which has been developed and there is evidence that it differs considerably from carcino-embryonic antigen (CEA) preparations. A commercial kit using a haemagglutination inhibition assay is available and its ability to discriminate between benign and malignant conditions of the gastrointestinal tract has been studied, using 7.7 units/ml as the upper limit of normal. With upper gastrointestinal disease, discrimination is comparable to that achieved with TAG by other workers and also to that achieved with CEA. For gastric carcinoma TAG has a sensitivity of 71% and a specificity of 77%. With lower gastrointestinal tract disease discrimination was poor, TAG having a sensitivity of 76% but a specificity of 44% for colorectal carcinoma. Discrimination between pancreatic carcinoma and chronic pancreatitis was poor, TAG having a sensitivity of 100% for carcinoma and a specificity of 22%.

Adenocarcinoma↗