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K Williams

Publications and source records attributed to K Williams.

At least 73 records · Page 4Linked to original sources
PubMed2001

The relation of body fat mass and distribution to markers of chronic inflammation.

OBJECTIVE: To study the relation of fibrinogen and C-reactive protein (CRP) to various measures of body fat and body fat distribution and to investigate whether these relations were explained by differences in insulin sensitivity. DESIGN AND SUBJECTS: Cross-sectional analysis of the IRAS (Insulin Resistance Atherosclerosis Study), a large (n=1559) tri-ethnic population (non-Hispanic whites, African-Americans and Mexican-Americans) across different states of glucose tolerance. MEASUREMENTS: Glucose tolerance (oral glucose tolerance test), insulin sensitivity (frequently sampled intravenous glucose tolerance test and minimal model analysis), assessment of body fat mass and distribution (weight, girths, bioelectrical impedance), subclinical atherosclerosis (B-mode ultrasonography of carotid artery intima-media thickness, IMT), CRP (highly sensitive immunoassay), fibrinogen (standard assay). RESULTS: Both CRP and fibrinogen were related to all measures of body fat. Strong correlations (correlation coefficient r > or = 0.35) were found between CRP and body mass index (BMI), waist circumference and adipose body mass, respectively. The associations were consistent in non-diabetic and type-2 diabetic subjects, were generally stronger in women, and were only moderately attenuated by the prevailing insulin sensitivity (S(I)). In a multivariate linear regression model waist circumference explained 14.5% of the variability of circulating CRP levels (P=0.0001), BMI 0.4% (P=0.0067), and S(I) 1.7% (P=0.0001). Common carotid artery IMT was related to CRP and fibrinogen in men, but not in women, and was attenuated after adjusting for BMI or waist. CONCLUSION: Our findings show that measures of body fat are strongly associated with circulating levels of CRP and fibrinogen. These associations were not explained by lower S(I) in obese subjects. Chronic, subclinical inflammation may be one pathophysiological mechanism explaining the increased risk of atherosclerotic disease associated with adiposity.

Adipose Tissue↗
PubMed2001

Lung cancer in pregnancy: case reports and review of the literature.

Lung cancer diagnosed in pregnancy is rare. The number of reported cases has been escalating in recent years, probably reflecting the increasing number of women of reproductive age who smoke. This review presents three cases of lung cancer in pregnancy with different manifestations and outcomes, with a review of the literature. Physicians should have a low threshold using different diagnostic tools for investigating unusual symptoms during pregnancy without fear for fetal safety. Once diagnosed, lung cancer represents a major ethical and medical dilemma. The optimal management of lung cancer in pregnancy is not known, because of the rarity of the cases reported during pregnancy and insufficient follow-up data.

Adenocarcinoma↗
PubMed2001

Differential expression of oestrogen receptor alpha and beta proteins in the testes and male reproductive system of human and non-human primates.

The role(s) oestrogens play in male adult reproductive function remains uncertain. We have used antibodies specific for oestrogen receptor- alpha (ERalpha) and - beta (ERbeta) to investigate their distribution within the male. In testes from adult human, macaque and marmoset, ERbeta protein was detected in Sertoli cells, Leydig cells and peritubular myoid cells. In germ cells, the intensity of immunostaining for ERbeta was variable between species. Immunoexpression in preleptotene, leptotene and zygotene spermatocytes was low/absent in all species. Elongated spermatids were consistently immunonegative. No ERalpha immunoexpression was detected in testes. ERbeta was detected in epithelial and stromal cell nuclei throughout the male reproductive system [efferent ductules (ED), epididymis, vas deferens, seminal vesicles] and in the bladder. ERalpha was detected in non-ciliated epithelial cells in the ED, but rarely in epithelial and basal cells within the epididymis. Epithelial cells from seminal vesicles and bladder were immunonegative for ERalpha. Expression of ERalpha in stromal cells was rare in the ED, epididymis and bladder but more frequent in seminal vesicles. Expression of ERalpha, and long and short forms of ERbeta, was confirmed by Western blotting. The widespread expression of ERbeta suggests that it is the primary target for modulation of tissue function via oestrogenic ligands in the male reproductive system.

Adult↗
PubMed2001

Medical Samaritans: is there a duty to treat?

This article argues that doctors and other health care professionals should be obliged to provide emergency treatment to those in immediate and nearby need regardless of the absence of any prior professional relationship between the parties. It concludes that the common law should accordingly recognize a specific duty of 'medical rescue'. It examines some of the conventional objections to affirmative duties, finding them unconvincing in this particular context. It draws on two recent appellate decisions, one Australian and the other English, for support, as well as on more general arguments concerning moral sentiment, professional ethics, public expectation, and respect for human rights.

Emergency Medical Services↗
PubMed2001

A comparison of 3 alloy surface treatments for resin-bonded prostheses.

PURPOSE: The most frequent cause of clinical failure of resin-bonded fixed partial dentures is a debonding at the metal-cement interface. The purpose of this in vitro study was to compare the tensile bond strengths of 3 different alloy-surface treatments when cemented to human enamel with a resin cement. MATERIALS AND METHODS: Cylinders of a nickel-chromium-beryllium (Ni-Cr-Be) and a gold-palladium (Au-Pd) alloy were fabricated and assigned to different surface treatment groups as follows: Group 1: Ni-Cr-Be, chemically etched; Group 2: Au-Pd, airborne particle-abraded and tin-plated; and Group 3: Au-Pd, airborne particle-abraded and treated with the Alloy Primer (Kuraray Co, LTD, Osaka, Japan). The cylinders were bonded to the enamel surfaces of extracted, human third molars and stored in normal saline at 37 degrees C for 48 hours. The tensile bond strength of 21 specimens from each group was measured on a Universal Testing Machine (Instron, Canton, MA). Three failed specimens of each group were evaluated using scanning electron microscopy and energy dispersive spectroscopy. RESULTS: Statistically significant differences (p <.05) were found between all 3 treatment groups. The mean tensile bond strengths (+/- the standard error of mean) recorded as follows: Group 1: 10.6 MPa (+/-1.3), Group 2: 0.9 MPa (+/-0.2), and Group 3: 13.4 MPa (+/-1.0). Specimens from groups 1 and 3 revealed a trend towards mixture of cohesive, within the resin cement, and adhesive failures at the metal-cement interface. Group 2 specimens exhibited primarily adhesive failures at the metal-cement interface. CONCLUSIONS: The tensile bond strength of Au-Pd alloy specimens was significantly increased with the Alloy Primer.

Acid Etching, Dental↗
PubMed2001

Application of high-density array-based signature-tagged mutagenesis to discover novel Yersinia virulence-associated genes.

Yersinia pestis, the causative agent of plague, and the enteropathogen Yersinia pseudotuberculosis have nearly identical nucleotide similarity yet cause markedly different diseases. To investigate this conundrum and to study Yersinia pathogenicity, we developed a high-density oligonucleotide array-based modification of signature-tagged mutagenesis (STM). Y. pseudotuberculosis YPIII mutants constructed with the tagged transposons were evaluated in the murine yersiniosis infection model. The DNA tags were amplified using biotinylated primers and hybridized to high-density oligonucleotide arrays containing DNA complementary to the tags. Comparison of the hybridization signals from input pools and output pools identified a mutant whose relative abundance was significantly reduced in the output pool. Sequence data from 31 transposon insertion regions was compared to the complete Y. pestis CO92 genome sequence. The 26 genes present in both species were found to be almost identical, but five Y. pseudotuberculosis genes identified through STM did not have counterparts in the Y. pestis genome and may contribute to the different tropisms in these closely related pathogens. Potential virulence genes identified include those involved in lipopolysaccharide biosynthesis, adhesion, phospholipase activity, iron assimilation, and gene regulation. The phospholipase A (PldA) mutant exhibited reduced phospholipase activity compared to the wild-type strain and in vivo attenuation of the mutant was confirmed. The combination of optimized double tag sequences and high-density array hybridization technology offers improved performance, efficiency, and reliability over classical STM and permits quantitative analysis of data.

Animals↗
PubMed2001

Mice devoid of fer protein-tyrosine kinase activity are viable and fertile but display reduced cortactin phosphorylation.

The ubiquitous Fer protein-tyrosine kinase has been proposed to regulate diverse processes such as cell growth, cell adhesion, and neurite outgrowth. To gain insight into the biological function of Fer, we have targeted the fer locus with a kinase-inactivating missense mutation (fer(D743R)). Mice homozygous for this mutation develop normally, have no overt phenotypic differences from wild-type mice, and are fertile. Since these mice lack both Fer and the testis-specific FerT kinase activities, these proteins are clearly not essential for development and survival. No differences were observed in overall cellularity of bone marrow, spleen, or thymus in the absence of Fer activity. While most platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation was unchanged in fer(D743R) homozygous embryonic fibroblasts, cortactin phosphorylation was reduced. However, Fer kinase activity was not required for PDGF-induced Stat3, p120(ctn), or epidermal growth factor (EGF)-induced beta-catenin phosphorylation. Also, no defects were observed in changes to the actin cytoskeleton, adherens junctions, or focal adhesions in PDGF- or EGF-stimulated fer(D743R) homozygous embryonic fibroblasts. Therefore, Fer likely serves a redundant role in regulating cell growth, cell adhesion, retinal development, and spermatogenesis but is required for efficient phosphorylation of cortactin.

Actins↗
PubMed2001

Use of Washington State newspapers for submersion injury surveillance.

OBJECTIVES: To evaluate the usefulness of newspapers as a surveillance tool for submersion injury, the proportion of submersion events and important details reported in Washington State newspapers was determined. It was also determined whether a letter sent to newspaper editors to encourage reporting changed the proportion and content of reported submersion events. METHODS: Newspaper articles regarding submersion were collected from 225 Washington newspapers from June 1993 through September 1998. Newspaper articles were linked to computerized state death and hospital records. Reporting during periods before and after a letter was sent encouraging more newspaper articles on submersion injury and preventative factors was compared. RESULTS: A total of 1,874 submersion victims were identified in the three data sources. Of the 983 victims who had a death certificate, 52% were reported in at least one news article. Of the 471 persons in hospital discharge data, 25% were reported in a newspaper. Reporting of pediatric victims who died increased from 63% to 79% (p=0.008); reporting of hospitalized persons increased from 23% to 27% (p=0.3). There were increases in reporting of swimming ability (7% to 15%, p<0.001), supervision (82% to 91%, p<0.001), and alcohol use (7% to 24%, p<0.001). Reporting of life vest use decreased (35% to 23%, p<0.001). CONCLUSIONS: Newspapers failed to report about one half of fatal submersions and three quarters of submersions that resulted in a hospitalization. An effort to improve reporting was associated with an increase in the proportion of pediatric drownings that were reported, but a consistent improvement in content was found. The usefulness of newspaper articles as a surveillance tool may be limited.

Adolescent↗
PubMed2001

Age-, cell- and region-specific immunoexpression of estrogen receptor alpha (but not estrogen receptor beta) during postnatal development of the epididymis and vas deferens of the rat and disruption of this pattern by neonatal treatment with diethylstilbestrol.

This study in rats sought to 1) characterize immunoexpression of estrogen receptor alpha (ERalpha) and ERss in the efferent ducts, epididymis, and vas deferens during postnatal development; 2) establish whether ER expression changed after neonatal treatment with diethylstilbestrol (DES); and 3) determine whether ER changes coincided with abnormal epididymal/vas development. Rats were administered 10 microg DES or vehicle on days 2, 4, 6, 8, 10, and 12 and were sampled on days 10, 18, 25, 35, and 90+. At all ages, ERalpha was immunoexpressed intensely in the efferent ducts. On day 10, immunoexpression of ERalpha was absent from the epididymis and vas, but was detectable on day 18 in epithelial cells in the caput, corpus, and proximal cauda. Epithelial expression of ERalpha was absent from the distal cauda and in the proximal and distal vas was confined to a band of periductal stromal cells. Thus, on day 18, the site of ERalpha expression delineated the epididymis-vas boundary. On days 25-35, epithelial expression of ERalpha was absent, but stromal expression persisted in the vas and distal cauda. In adults, immunoexpression of ERalpha in the epididymis and vas was absent. In contrast, ERbeta was immunoexpressed in epithelial cells and some stromal cells in the efferent ducts, epididymis, and vas at all ages. In the vas, stromal expression of ERalpha and ERbeta was in different layers. DES treatment caused 1) underdevelopment of the epididymal duct and reduced epithelial height in epididymis and vas; 2) coiling of the extraepididymal vas; 3) thickening of the periductal actin-free stromal layer in the distal cauda and vas; and 4) reduced cell proliferation on day 18 in the epididymis and vas, based on incorporation of bromodeoxyuridine, especially in the epithelium. These changes coincided with abnormalities in cell- and region-specific immunoexpression of ERalpha, but not ERbeta. Thus, in DES-treated rats on day 18, epithelial expression of ERalpha occurred in all regions of the epididymis and vas instead of being confined to the caput, corpus, and proximal cauda as in controls. Similarly, stromal ERalpha expression in the vas of DES-treated rats was not confined to a periductal layer as in controls, but occurred diffusely in the muscle layer. It is suggested that 1) estrogens play a role in peripubertal development of the epididymis and vas; 2) the cellular site of expression of ERalpha either plays a role in or reflects demarcation of the epididymal/vas boundary; and 3) blurring of this boundary in DES-treated rats coincides with altered ERalpha immunoexpression.

Aging↗
PubMed2001

Estrogen receptor beta, but not estrogen receptor alpha, is present in the vascular endothelium of the human and nonhuman primate endometrium.

Estrogen action is dependent upon the presence of specific ligand-activated receptors in target tissues. The aim of the present experiments was to compare the spatial and temporal pattern of expression of estrogen receptor beta (ERbeta) with that of ERalpha in full thickness endometrial samples (from the superficial to the basal zone) obtained from both women and rhesus macaques. Immunohistochemical localization with specific antibodies revealed that ERalpha and ERbeta were both expressed in nuclei of the glands and stroma. Consistent with previous studies, expression of ERalpha declined in the glands and stroma of the functionalis during the secretory phase. The luminal epithelium also displayed positive immunoreactivity for ERbeta. Expression of ERbeta declined in glandular cell nuclei, but not stroma, within the functionalis during the late secretory phase. Levels of expression of ERalpha and ERbeta in all cellular compartments remained unchanged in the basalis. Both receptor subtypes were detected on Western blots using proteins extracted from uterine samples obtained throughout the menstrual cycle. There was a striking contrast between the pattern of expression of ERalpha and ERbeta in the vascular endothelium and the perivascular cells surrounding endometrial blood vessels; only ERbeta was present in the endothelial cell population, although both forms of ER were expressed in perivascular cells. We conclude that estrogen action(s) within the vascular endothelium in the endometrium may be mediated via direct binding to the ERbeta isoform and that these cells could therefore be a target for agonists or antagonists that selectively target the beta form of the ER.

Adult↗
PubMed2001

Relationship between expression of sex steroid receptors and structure of the seminal vesicles after neonatal treatment of rats with potent or weak estrogens.

In this study we evaluated the effect of manipulating the estrogen and androgen environment of the neonatal male rat on subsequent immunoexpression of sex steroid receptors in the seminal vesicles (SVs) at age 18 days. The aim was to establish to what extent such changes were associated with and predictive of changes in SV structure/composition. Treatments were either diethylstilbestrol (DES; 10, 1, or 0.1 microg/injection), ethinyl estradiol (EE; 10 microg/injection), tamoxifen (2 mg/kg/day), flutamide (50 mg/kg), a gonadotropin-releasing hormone antagonist (GnRHa; 10 mg/kg), genistein (4 mg/kg/day), octylphenol (2 mg/injection), or bisphenol A (0.5 mg/injection). Compared with controls, treatment with DES (10 microg) induced loss of epithelial and stromal androgen receptor (AR) immunoexpression coincident with induction of stromal progesterone receptor (PR) immunoexpression and upregulation of stromal immunoexpression of estrogen receptor-alpha (ERalpha). These changes were associated with gross distortion (increase) of the normal stromal:epithelial tissue proportions in the SVs. DES (1 microg) and EE induced similar but less pronounced changes, and DES (0.1 microg) had no noticeable effect. Tamoxifen and flutamide induced PR and slightly upregulated ERalpha immunoexpression but had only a minor or no effect on AR expression and the stromal:epithelial ratio, though flutamide retarded normal development of the SVs. The latter was also evident in GnRHa-treated males, but otherwise this treatment had no effect on AR and PR immunoexpression. None of the foregoing treatments had any detectable effect on the immunoexpression of ERss in stromal or epithelial cells. The major treatment-induced changes in immunoexpression of AR, PR, and ERalpha and lack of change in ERss were confirmed by Western blots of SV protein extracts. None of the three weak (environmental) estrogens tested caused any detectable change in sex steroid receptor immunoexpression or SV tissue composition. We conclude that treatment-induced loss of AR is a prerequisite for altered stromal:epithelial proportions in the SVs and that such loss is always associated with induction of PR and upregulation of ERalpha; the latter two changes are insufficient on their own to bring about such a change. Nevertheless, induction of PR expression was always associated with altered SV development and is a potentially useful marker because it is not normally expressed in male reproductive tissues.

Animals↗
PubMed2001

A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory.

OBJECTIVES: Hoping to increase hepatitis B (HB) vaccination of adolescents, we did the following: 1) studied if modified regimens of the recombinant HB vaccine, Recombivax HB (2 or 3 doses of 5 or 10 microg given over 4 or 6 months), induce protective anti-hepatitis B surface antibody [anti-HBsAb] levels (>/=10 mIU/mL) comparable to the recommended regimen (5 microg at 0 and 1, and 6 months); 2) measured early antibody response after a single dose; and 3) assessed immunologic memory after 2- and 3-dose regimens. DESIGN: One thousand twenty-six adolescents were randomized to 1 of 5 treatment groups (10 microg at 0 and 4 or 0 and 6 months; 5 microg at 0 and 6 or 0, 2, and 4 or 0, 1, and 6 months) in an open trial. Anti-HBsAb was measured in all participants just before and 1 month after the last dose, and at several other times in a subset of vaccinees. Anti-HBsAb response to a booster dose 2 years later was examined to assess immunologic memory in participants vaccinated with 5 microg at 0 and 6 or 0, 1, and 6 months. RESULTS: All regimens induced >/=10 mIU/mL of anti-HBs in >/=95% of vaccinees. Geometric mean titers ranged from 674.8 to 3049.4 mIU/mL. Geometric mean titers were higher with regimens using the following: 1) 10 versus 5 microg; 2) 3 versus 2 doses; and 3) vaccination intervals of 6 versus 4 months. After 6 months, 63.8% of vaccinees given one 10-microg dose had >/=10 mIU/mL of anti-HBsAb versus 41.6% after one 5-microg dose. Participants vaccinated with either two or three 5-microg doses retained robust immunologic memory. CONCLUSIONS: . The results of this study show that a 2-dose regimen of Recombivax HB is as immunogenic and induces immunologic memory as effectively as the recommended 3-dose regimen. A regimen of two 10-microg doses may be of significant benefit for vaccinees who are poorly compliant or deviate from the intended vaccination schedule.

Adolescent↗
PubMed2001

Ifenprodil, a novel NMDA receptor antagonist: site and mechanism of action.

Ifenprodil is a novel N-methyl-D-aspartate (NMDA) receptor antagonist that selectively inhibits receptors containing the NR2B subunit. As such, it has become widely used as a tool to study subtypes of NMDA receptors both in vitro and in vivo, and as a tool for molecular studies of the properties and regulation of NMDA receptors. Ifenprodil has an unusual form of activity-dependence and its mechanism of action may involve an increase in proton inhibition of NMDA receptors. These properties are shared by analogs or derivatives of ifenprodil, some of which may be lead compounds for therapeutically useful NMDA antagonists. Such antagonists have potential as neuroprotectants, anticonvulsants, analgesics, and for the treatment of Parkinson's disease and other disorders of the nervous system. The location of the ifenprodil binding site on NMDA receptors and the structural and mechanistic basis of its effects are still unknown. Recent work suggests that at least part of the ifenprodil binding site is located in the R1/R2 domain of the NR1 subunit. This region, like the S1/S2 agonist binding domain, shares homology with bacterial periplasmic binding proteins.

Animals↗
PubMed2001

Was the historic contribution of Spain to the Mexican gene pool partially responsible for the higher prevalence of type 2 diabetes in mexican-origin populations? The Spanish Insulin Resistance Study Group, the San Antonio Heart Study, and the Mexico City Diabetes Study.

OBJECTIVE: Mexican-American populations in San Antonio, Texas (SA-MA) and Mexico have a higher prevalence of type 2 diabetes than non-Hispanic whites in San Antonio (SA-NHW). However, the higher prevalence of type 2 diabetes in Mexican-origin populations might be related, in part, not to Native American genetic admixture but to Spanish genetic admixture. RESEARCH DESIGN AND METHODS: Four population-based epidemiological surveys conducted with Mexican-origin and European-origin samples provided data relevant to this question. In all four surveys, type 2 diabetes was defined as fasting plasma glucose > or =7.0 mmol/l or 2-h glucose > or =11.1 mmol/l or use of antidiabetic agents. RESULTS: A comparison of the two Mexican-origin populations showed that the age- and sex-adjusted prevalence of type 2 diabetes was lower in Mexico than in SA-MA (15.1 vs. 17.9%, P = 0.032). Between the two European-origin populations, the prevalence of type 2 diabetes was lower in SA-NHW than in Spain (6.2 vs. 9.1%, P < 0.0001), but differences were attenuated by adjustment for BMI or after stratification by education. In logistic regression analyses, type 2 diabetes was associated with Mexican ethnic origin after adjusting for age, education, BMI, and waist-to-hip ratio. CONCLUSIONS: The prevalence of type 2 diabetes in Spain was intermediate between that in Mexican-origin populations and SA-NHW. Although the higher degree of Native American admixture is a major contributor to the higher rates of type 2 diabetes, we cannot completely rule out a partial contribution of Spanish admixture to diabetes susceptibility among Mexican- origin populations.

Age Factors↗
PubMed2001

Elevated incidence of type 2 diabetes in San Antonio, Texas, compared with that of Mexico City, Mexico.

OBJECTIVE: To compare the incidence of type 2 diabetes between low-income Mexican-Americans residing in San Antonio, Texas, and low-income residents in Mexico City, Mexico. RESEARCH DESIGN AND METHODS: Using data from the San Antonio Heart Study and the Mexico City Diabetes Study, we compared the incidence of type 2 diabetes in 35- to 64-year-old low-income Mexican-American residents of San Antonio with similarly aged low-income residents of Mexico City. Because of the different follow-up times in the two studies, Poisson regression was used to compare the rates of diabetes. Potential risk factors for diabetes were also analyzed to determine whether they explained or contributed to a difference in incidence. RESULTS: The age- and sex-adjusted incidence of type 2 diabetes was significantly higher in San Antonio (RR 2.01) compared with Mexico City. This difference was seen primarily in the oldest age group (55-64 years of age) and remained statistically significant after adjusting for a number of diabetes risk factors, including demographic, anthropometric, and metabolic variables. Follow-up rates were similar in both cities. CONCLUSIONS: We conclude that there was a higher incidence of type 2 diabetes in San Antonio than in Mexico City, and that difference occurred primarily in individuals in the oldest age group. The potential mediating factors we examined did not account for this difference. Other factors, such as exercise and diet, which were not available for analysis in this study, in addition to a cohort effect, may have contributed to the difference in incidence of type 2 diabetes in the two cities. In addition, there was no evidence of a higher case fatality among diabetic individuals from Mexico City compared with San Antonio.

Adult↗
PubMed2001

Home healthcare nurses--why they leave and why they stay.

This is a second article in a series of two reports on the National Association for Home Care's (NAHC) study of nursing recruitment and retention. The first article presented the results of the quantitative analysis. This article presents results of the qualitative analysis.

Community Health Nursing↗