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Biomedical subjects

E White

Publications and source records attributed to E White.

At least 199 records · Page 11Linked to original sources
PubMed1994

Streptomycin reverses a large stretch induced increases in [Ca2+]i in isolated guinea pig ventricular myocytes.

OBJECTIVE: The aim was to test the hypothesis that in single guinea pig ventricular myocytes a large stretch induced increase in resting calcium was sensitive to the mechanosensitive channel blocker streptomycin. METHODS: Carbon fibres were used to stretch cells loaded with the fluorescent calcium indicator indo-1. Force, sarcomere length, and internal calcium activity ([Ca2+]i) were measured. RESULTS: In approximately 60% of the cells studied, a stretch which increased sarcomere length by approximately 6% caused a large increase in [Ca2+]i (up to 60% of the size of a [Ca2+]i transient at 0.25 Hz). When a mixture of antibiotics (streptomycin-penicillin) was used in solutions to isolate and store cells, this phenomenon was never observed (n = 19 cells). Direct application of physiological saline solution (PSS) could not reverse the increase in [Ca2+]i within 60 s of application (n = 7 cells). Direct application of penicillin [1000 IU per 50 ml (40 microM)] reversed the increase in [Ca2+]i within 60 s of application in only 3/7 cells. In contrast direct application of the aminoglycoside antibiotic streptomycin (40 microM) rapidly reversed the large increase in [Ca2+]i induced by stretch in each of 13 cells [within 18(SD 10) s of application]. Acute application of 40 microM streptomycin did not modify L-type Ca2+ currents measured under whole cell patch clamp conditions. Measurement of the resting tension--sarcomere length curves in cells stored in solution containing streptomycin and penicillin revealed two populations of cells on the basis of their stiffness. CONCLUSIONS: This stretch induced increase in [Ca2+]i may be associated with stretch activated arrhythmias in the heart. The effects of streptomycin are consistent with its reported inhibitory action on stretch activated channels.

Animals↗
PubMed1994

Reduction in the contraction and intracellular calcium transient of single rat ventricular myocytes by gadolinium and the attenuation of these effects by extracellular NaH2PO4.

Gadolinium (Gd3+) is the most commonly used blocker of stretch-activated channels (SACs). The actions of Gd3+ in unstretched adult heart were investigated by observing its effects on the contraction and intracellular calcium transient of single rat ventricular myocytes. We found that Gd3+ caused a profound reduction in both these parameters at doses typically used to block SACs. However, the actions of Gd3+ were severely attenuated by the presence of 0.33 mM NaH2PO4, which possibly chelates the Gd3+ ion.

Animals↗
PubMed1994

The role of the sarcoplasmic reticulum in the response of isolated ferret cardiac muscle to beta-adrenergic stimulation.

beta-Adrenergic stimulation of cardiac muscle leads to an increase in the strength of contraction and an abbreviation of its time course. We have investigated the role of the sarcoplasmic reticulum in these changes by monitoring force and cytoplasmic [Ca2+] in ferret papillary muscles, and the Ca2+ current in isolated ferret myocytes, during the application of isoprenaline in the absence and presence of the sarcoplasmic reticulum inhibitor ryanodine (10(-6) mol/l). Isoprenaline (10(-6) mol/l) led to a marked increase in the size of both the twitch and Ca2+ transient, and a decrease in their duration. In the presence of ryanodine, application of isoprenaline had no significant effect on either the size or the time course of the twitch. However, the increase in the Ca2+ current in response to isoprenaline was the same in the absence and presence of ryanodine. Increasing bathing [Ca2+] led to a prolongation of both the twitch and the Ca2+ transient. In the presence of ryanodine, increasing bathing [Ca2+] still increased the size, but decreased the duration, of the twitch. These data provide direct evidence that both the inotropic and lusitropic effects of isoprenaline are mediated via the sarcoplasmic reticulum.

Animals↗
PubMed1994

Functional complementation of the adenovirus E1B 19-kilodalton protein with Bcl-2 in the inhibition of apoptosis in infected cells.

Expression of the adenovirus E1A oncogene induces apoptosis which impedes both the transformation of primary rodent cells and productive adenovirus infection of human cells. Coexpression of E1A with the E1B 19,000-molecular-weight protein (19K protein) or the Bcl-2 protein, both of which have antiapoptotic activity, is necessary for efficient transformation. Induction of apoptosis by E1A in rodent cells is mediated by the p53 tumor suppressor gene, and both the E1B 19K protein and the Bcl-2 protein can overcome this p53-dependent apoptosis. The functional similarity between Bcl-2 and the E1B 19K protein suggested that they may act by similar mechanisms and that Bcl-2 may complement the requirement for E1B 19K expression during productive infection. Infection of human HeLa cells with E1B 19K loss-of-function mutant adenovirus produces apoptosis characterized by enhanced cytopathic effects (cyt phenotype) and degradation of host cell chromosomal DNA and viral DNA (deg phenotype). Failure to inhibit apoptosis results in premature host cell death, which impairs virus yield. HeLa cells express extremely low levels of p53 because of expression of human papillomavirus E6 protein. Levels of p53 were substantially increased by E1A expression during adenovirus infection. Therefore, E1A may induce apoptosis by overriding the E6-induced degradation of p53 and promoting p53 accumulation. Stable Bcl-2 overexpression in HeLa cells infected with the E1B 19K- mutant adenovirus blocked the induction of the cyt and deg phenotypes. Expression of Bcl-2 in HeLa cells also conferred resistance to apoptosis mediated by tumor necrosis factor alpha and Fas antigen, which is also an established function of the E1B 19K protein. A comparison of the amino acid sequences of Bcl-2 family members and that of the E1B 19K protein indicated that there was limited amino acid sequence homology between the central conserved domains of E1B 19K and Bcl-2. This domain of the E1B 19K protein is important in transformation and regulation of apoptosis, as determined by mutational analysis. The limited sequence homology and functional equivalency provided further evidence that the Bcl-2 and E1B 19K proteins may possess related mechanisms of action and that the E1B 19K protein may be the adenovirus equivalent of the cellular Bcl-2 protein.

Adenovirus E1A Proteins↗
PubMed1994

Bcl-2 blocks p53-dependent apoptosis.

Adenovirus E1A expression recruits primary rodent cells into proliferation but fails to transform them because of the induction of programmed cell death (apoptosis). The adenovirus E1B 19,000-molecular-weight protein (19K protein), the E1B 55K protein, and the human Bcl-2 protein each cause high-frequency transformation when coexpressed with E1A by inhibiting apoptosis. Thus, transformation of primary rodent cells by E1A requires deregulation of cell growth to be coupled to suppression of apoptosis. The product of the p53 tumor suppressor gene induces apoptosis in transformed cells and is required for induction of apoptosis by E1A. The ability of Bcl-2 to suppress apoptosis induced by E1A suggested that Bcl-2 may function by inhibition of p53. Rodent cells transformed with E1A plus the p53(Val-135) temperature-sensitive mutant are transformed at the restrictive temperature and undergo rapid and complete apoptosis at the permissive temperature when p53 adopts the wild-type conformation. Human Bcl-2 expression completely prevented p53-mediated apoptosis at the permissive temperature and caused cells to remain in a predominantly growth-arrested state. Growth arrest was leaky, occurred at multiple points in the cell cycle, and was reversible. Bcl-2 did not affect the ability of p53 to localize to the nucleus, nor were the levels of the p53 protein altered. Thus, Bcl-2 diverts the activity of p53 from induction of apoptosis to induction of growth arrest, and it is thereby identified as a modifier of p53 function. The ability of Bcl-2 to bypass induction of apoptosis by p53 may contribute to its oncogenic and antiapoptotic activity.

Animals↗
PubMed1993

History of lactation and breast cancer risk.

A self-administered questionnaire was completed by 1,018 women diagnosed with breast cancer during 1988-1989 identified through the British Columbia Cancer Registry and by 1,025 controls selected at random from the Provincial Voters List. Parous premenopausal women who had never nursed (odds ratio (OR) = 1.3, 95% confidence interval (CI) 0.9-2.0) or who had lactated for 1 month or less (OR = 1.8, 95% CI 1.3-2.5) had an increased risk of breast cancer adjusted for age and parity, compared with women who had breast-fed 2 months or longer. The risk was particularly elevated (OR = 3.0, 95% CI 1.6-5.4) among women who reported having tried to nurse, but who were unsuccessful. Among women who nursed for at least 2 months, there was an indication of decreasing risk with increasing duration of nursing. Among postmenopausal parous women, no relation between lactation history and breast cancer risk was evident.

Adult↗
PubMed1993

Alcohol and nutrients in relation to colon cancer in middle-aged adults.

A population-based case-control study was conducted from 1985 to 1989 in western Washington State to assess the relation between nutrients and the incidence of colon cancer in men and women aged 30-62. A food frequency questionnaire was used to document the usual diet 7 years before diagnosis for 424 cases and at a similar time for 414 controls. Alcohol consumption was strongly related to the risk of colon cancer in both men and women, with age-adjusted odds ratios (ORs) of colon cancer = 1.0, 1.9, 1.7, and 2.6 for 0, < 10, 10-29, and > or = 30 g/day intake for men and adjusted odds ratios = 1.0, 1.3, 1.8, and 2.5 for the same categories for women. The trend odds ratio associated with a one-category increment in the four-level alcohol consumption variable was 1.3 (95% confidence interval (CI) 1.0-1.5) in men and 1.4 (95% CI 1.0-1.7) in women. For both sexes, higher dietary fiber intakes were associated with lower relative risks for colon cancer, with age-, energy-, and alcohol-adjusted odds ratios = 1.0, 0.9, 0.8, and 0.6 across quartiles of consumption for men (trend OR for a one-quartile increment = 0.8, 95% CI 0.7-1.1) and adjusted odds ratios = 1.0, 0.9, 0.5, and 0.5 for women (trend OR = 0.8, 95% CI 0.6-1.0). In men, this was mostly attributable to intake of cereal fiber (trend OR = 0.8, 95% CI 0.6-1.0) while, in women, this association mostly reflected the effect of fruit fiber (trend OR = 0.8, 95% CI 0.6-0.9) and vegetable fiber (trend OR = 0.8, 95% CI 0.7-1.0). Calcium was associated with a decreased risk of colon cancer among women only (adjusted OR across quartiles = 1.0, 0.5, 0.6, 0.3; trend OR = 0.7, 95% CI 0.6-1.0). There was no indication of an association between colon cancer and fat or protein consumption or dietary vitamins.

Adenocarcinoma↗
PubMed1993

The effect of a range of alcohols on the contraction of guinea-pig ventricular myocytes.

Previous results have shown that ethanol and some anaesthetics have a negative inotropic effect on the heart. This study was undertaken to investigate the influence of a range on n-alcohols (with chain lengths from 2 to 8) on contractility in guinea-pig ventricular myocytes. The results demonstrate that the negative inotropic action of alcohols increases dramatically as the chain length increases. The concentration required to reduce the magnitude of contraction to 50% of control (IC50) was 274 mM, 26 mM, 1.4 mM and 235 microM for ethanol, butanol, hexanol and octanol, respectively. The relationship between the logarithm of IC50 and chain length was linear for all the alcohols tested (up to a chain length of 8).

Alcohols↗
PubMed1993

Breast cancer among black and white women in the 1980s. Changing patterns in the United States by race, age, and extent of disease.

BACKGROUND: This national study of breast cancer incidence and mortality was conducted to determine whether patterns of change differ for black and white women, to evaluate patterns by extent of disease, and to determine whether recent patterns of breast cancer are consistent with results that one would expect due to increases in use of screening examinations by women. METHODS: The study included 104,351 cases of in situ or invasive breast cancer diagnosed between 1983 and 1989 among women from the nine geographic areas participating in the National Cancer Institute Surveillance, Epidemiology, and End Results program. Breast cancer incidence patterns were examined by extent of disease for black and white women and by age at diagnosis. RESULTS: Significant increases occurred in the incidence of all early-stage breast cancers. Concomitantly, significant decreases occurred in the incidence of the most advanced-stage breast cancers. Although both white and black women experienced significant increases in early-stage breast cancer, black women have substantially lower rates of the least extensive breast cancers. CONCLUSIONS: These results strongly suggest that a major explanation for the increase in breast cancer incidence in the 1980s may well be the increased prevalence of breast cancer screening among women in the United States. They also suggest a consistent benefit of screening across all age groups from 40 to 49 years through 70 years and older.

Adult↗
PubMed1993

Isotope dilution mass spectrometry and the National Reference System.

The clinical laboratory community of the United States, which is well represented by the NRSCL/NCCLS, has endorsed the IDMS/DMs developed at NIST. These DMs provide the accuracy (true value) base for the U.S. National Reference System for a number of specific analytes in human serum. Fortunately, the U.S. government through (a) actions of NIST administrators and scientists, (b) financial support from NIH (NIGMS) and FDA, and (c) interagency agreements with CDC has accepted the responsibility for developing and maintaining IDMS/DMs for clinically important analytes as an essential part of this national measurement system infrastructure. Furthermore, it is important to note that several professional organizations, particularly, The American Association for Clinical Chemistry (AACC) and The College of American Pathologists (CAP), have interacted heavily with NIST in full support of these national standardization activities. CAP supports three full-time Research Associates at NIST so that target values on serum samples used in its Interlaboratory Comparison Survey Programs may be traced to DMs. This remarkable cooperation and teamwork between government agencies and private sector organizations, as well as numerous individual scientists and physicians, which promotes greater accuracy of patient results, depends heavily upon the continued timely availability of IDMS/DM measurements. In short, NIST's value assignments on human serum samples (e.g., SRMs and materials for CLIA '88 proficiency testing programs) by this critical IDMS/DM metrology provide the pragmatic base for assuring accurate test results in medicine. The resources required to support IDMS/DM technology at NIST over many decades are not trivial and from time to time require renewed R&D efforts to upgrade methodology and recapitalization in mass spectrometry instrumentation.

Blood Chemical Analysis↗
PubMed1993

The glutathione S-transferase mu polymorphism as a marker for susceptibility to lung carcinoma.

Glutathione S-transferase (GST) enzymes detoxify carcinogens in tobacco smoke. Interindividual variation in GST function may be related to differences in risk for smoking-related cancer. Leukocytes from 50% of Caucasians lack GST activity toward trans-stilbene oxide (TSO), due to a deletion of the gene for the GST-mu enzyme. Presence of GST-TSO activity in leukocytes has been associated with low risk for lung cancer among cigarette smokers. We sought to determine whether GST activity in lung tissue is determined by the same gene polymorphism and whether it is associated with risk for lung cancer. Subjects were cigarette smokers, identified at the time of lung resection or autopsy in Seattle hospitals. Uninvolved lung tissue was obtained from 35 patients with lung carcinoma and 43 control patients and assayed for GST-mu activity with TSO, for the presence of the GST-mu gene product with an immunological assay, and for the GST-mu gene with Southern blotting. Mailed questionnaires were used to collect information on subjects' smoking histories and exposures which might alter enzyme activity. Interindividual results from the three assays correlated well. Smokers with high GST-TSO enzyme activity present in their lung tissue had a lower risk for lung carcinoma than did smokers with no or low activity (relative risk = 0.30; 95% confidence interval, 0.11-0.79), as did smokers with GST-mu antigen identified in lung tissue versus those with no antigen (relative risk = 0.30; 95% confidence interval, 0.11-0.79). Smokers with both maternal and paternal copies of GST-mu DNA (n = 7) had a lower cancer risk than smokers lacking GST-mu DNA (n = 30; relative risk = 0.35; 95% confidence interval, 0.06-2.10). High GST-mu activity appeared to be associated with a greater decrease in lung cancer risk among 38 heavy cigarette smokers (relative risk = 0.15; 95% confidence interval, 0.03-0.64) than among 38 light smokers (relative risk = 0.61; 95% confidence interval, 0.14-2.60). Presence or absence and number of copies of the GST-mu gene appear to determine activity of the GST-mu enzyme in lung. Smokers with the GST-mu enzyme have approximately one-third of the risk for lung carcinoma of smokers without the enzyme.

Adult↗
PubMed1993

Recent cohort trends in malignant melanoma by anatomic site in the United States.

The incidence of malignant melanoma has been increasing steadily in the United States. The increase may be due to lifestyle changes in subsequent generations or birth cohorts. The nine population-based tumor registries in the Surveillance, Epidemiology, and End Results program (SEER) have been in existence for a sufficient time to begin to investigate cohort trends for the US population. Cases were the 18,787 Caucasians aged 20 to 84 years, who reported to SEER registries with a diagnosis of melanoma in 1974-86. Among men born between 1890 and 1919, each subsequent five-year birth cohort experienced 45 to 57 percent increases in age-adjusted melanoma incidence of the arm and trunk, and 14 to 20 percent increases were experienced across each site (arm, leg, head, and trunk) for the 1920-44 cohorts of men. Among women born between 1890 and 1919, 24 to 29 percent increases were seen for melanoma of the trunk, arms, and legs for each subsequent five-year birth-cohort, followed by six to 29 percent increases in the 1920-44 cohorts. Recent birth cohorts, 1945-64, have shown stabilizing rates, even after an attempt to adjust for the increasing tendency for diagnoses to be made in doctors' offices. Thus, the dramatic birth-cohort effects appear to have ended beginning with those born in 1945. However, melanoma rates will continue to rise until those born after 1945 represent the majority of the population. Furthermore, for the most recent cohorts, the trunk has become the most common site (per square meter of body surface) for men and the second most common site for women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Immunogold labelling of Listeria monocytogenes virulence-related factors within Caco-2 cells.

We demonstrated by immunoelectron microscopy that listeriolysin O (LLO), phospholipases and other putative virulence-related proteins produced by Listeria monocytogenes were primarily cell-wall-associated when the bacterium infected Caco-2 tissue culture cell monolayers. Antibodies made to LLO, serogroup 1/2a reacted poorly with serogroup 4b cells and vice-versa, indicating fundamental structural differences in the two proteins. Finally, comet-tail pseudopod structures shown to be involved in cell-to-cell passage of Listeria in Caco-2 cells did not possess detectable Listeria antigens on their anterior surface or within their structure, suggesting that the phagocytic process is primarily host-cell-dependent once it is initiated by the bacterial cell.

Antibodies, Bacterial↗
PubMed1993

Phosphorus studies in pigs. 1. Available phosphorus requirements of grower/finisher pigs.

Two experiments were conducted to determine the available P requirements of grower and grower/finisher pigs and to define the conditions for conducting a growth assay for P availability. In the first experiment, diets with four levels of calculated available P (1-4 g/kg) and four Ca:available P ratios (1.7-2.9) were used to determine the available P requirements of grower pigs. The diets were formulated by substituting the required amounts of limestone and sodium tripolyphosphate for sugar in a soya-bean meal and sugar-based diet. In addition to measuring growth responses, a range of bones were examined to determine the most suitable criteria for assessing the response to available P. There was a small quadratic response of feed intake and growth rate of the pigs to level of available P, with maximum responses occurring to approximately 3 g available P/kg (P < 0.05). There were linear depressing effects of increasing Ca:available P ratios on carcass gain and feed conversion ratio (P < 0.01) but most of these effects occurred when the ratio exceeded 2.5:1. All bone variables examined increased linearly (P < 0.05) or curvilinearly (P < 0.01) with increasing available P concentration. In general, these variables were not affected by the Ca:available P ratio. The results of the growth responses and bone development indicate that the grower pig requires approximately 3 g available P/kg. However, for availability assays, where linearity of response is needed, the dietary concentration of available P should be a maximum of approximately 2 g/kg. In the second experiment four levels of calculated available P (1-4 g/kg) with a Ca:available P ratio of 2.5:1 were used to determine the available P requirements of grower/finisher pigs from 20 to 90 kg live weight. At 50 kg live weight the dietary available P concentration for half the pigs fed at 2, 3 and 4 g available P/kg was reduced to 1, 2 and 3 g/kg respectively. The pigs were fed ad lib, and growth performance, bone characteristics, P retention and ash concentration in the empty body were taken as response criteria to assess P adequacy. Among the variables tested, the ash concentration in the radius/ulna bone and P and ash concentrations in the empty body appeared to be more responsive than other variables to the changes in dietary P levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Nutritional Physiological Phenomena↗