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Biomedical subjects

J H Williams

Publications and source records attributed to J H Williams.

At least 37 records · Page 2Linked to original sources
PubMed2001

Glycogen and glycogen phosphorylase associated with sarcoplasmic reticulum: effects of fatiguing activity.

The purpose of the present study was to investigate the effects of fatiguing muscular activity on glycogen, glycogen phosphorylase (GP), and Ca(2+) uptake associated with the sarcoplasmic reticulum (SR). Tetanic contractions (100 ms, 75 Hz) of the gastrocnemius and plantaris muscles, elicited once per second for 15 min, significantly reduced force to 26.5 +/- 4.0% and whole muscle glycogen to 23% of rested levels. SR glycogen levels were 415.4 +/- 76.6 and 20.4 +/- 2.1 microg/mg SR protein in rested and fatigued samples, respectively. The optical density of GP from SDS-PAGE was reduced to 21% of control, whereas pyridoxal 5'-phosphate concentration, a quantitative indicator of GP content, was significantly reduced to 3% of control. GP activity after exercise, in the direction of glycogen breakdown, was reduced to 4% of control. Maximum SR Ca(2+) uptake rate was also significantly reduced to 81% of control. These data demonstrate that glycogen and GP associated with skeletal muscle SR are reduced after fatiguing activity.

Animals↗
PubMed2001

The first reported case of equine nocardioform placentitis in South Africa.

Since the late 1980s a distinct form of focally-extensive mucoid to mucopurulent uterine body chronic placentitis,caused by nocardioform organisms, hasbeen recognised in horses in the USA state of Kentucky and possibly in other areas. This disease has led to increasing numbers of foal losses from late abortions, still-births, prematurity, or early neonatal deaths. The foals are usually not infected, but may be small or emaciated. Modes of infection and transmission are as yet unknown. Nocardia spp. and related nocardioform bacteria as causes of equine infertility, endometritis and foal death are briefly reviewed. A case of near full-term abortion involving a Friesian mare in the Pretoria district of Gauteng Province in South Africa during February 2000, with the same placental lesion as described in the Kentucky cases, is presented. Nocardioform organisms were visualised on impression smears and histological sections of affected foetal membranes, and were also cultured. The organism has been identified at the Livestock Disease Diagnostic Center of the University of Kentucky as an Amycolatopsis sp. of the less-commonly diagnosed group of nocardioforms causing placentitis in the USA. The organism was cultured from the uterus of the mare 18 days post-foaling, but after a 2-week course of oral trimethoprim and sulphamethoxazole, based on antibiogram sensitivity testing, a uterine flush yielded no growth. A semen sample from the sire of the aborted foal did not yield any Gram-positive filamentous branching bacteria. The mare subsequently conceived to a single insemination.

Abortion, Veterinary↗
PubMed2001

Incivility in the workplace: incidence and impact.

This study extends the literature on interpersonal mistreatment in the workplace by examining the incidence, targets, instigators, and impact of incivility (e.g., disrespect, condescension, degradation). Data were collected from 1,180 public-sector employees, 71% of whom reported some experience of workplace incivility in the previous 5 years. As many as one third of the most powerful individuals within the organization instigated these uncivil acts. Although women endured greater frequencies of incivility than did men, both genders experienced similarly negative effects on job satisfaction, job withdrawal, and career salience. Uncivil workplace experiences were also associated with greater psychological distress; however, indices of psychological and physical health were relatively unaffected. The authors discuss these findings in the context of organizational and cognitive stress theories.

Adult↗
PubMed2001

Correlates contributing to involvement in violent behaviors among young adults.

The study examines the extent to which gender, personality attributes, household, community, and environmental factors are associated with violent behaviors in young adulthood. The authors present findings from a sample of 765 21-year-old individuals participating in a drug and delinquency prevention study. Personality attributes, opportunities, and social acceptability of antisocial behaviors were identified as accounting for gender differences and having more influence on violent behavior than environmental correlates. Implications for preventive intervention are discussed.

Adolescent↗
PubMed2000

"Kiss and run" exocytosis at hippocampal synapses.

We have combined electrophysiology and imaging to measure the release of neurotransmitter and fluorescent dye at synapses of cultured hippocampal neurons. These experiments have revealed a "kiss and run" mode of exocytosis in which synaptic vesicles release glutamate normally but do not permit dye to enter or escape from the vesicle. During "kiss and run," the vesicle interior may be exposed very transiently (<6 ms), or a special configuration of the fusion pore may prevent dye exchange. We estimate that about 20% of the vesicles normally use this "kiss and run" pathway, and that the fraction of "kiss and run" events can be increased to over 80% by superfusing the synapses with hypertonic solution.

Action Potentials↗
PubMed2000

Ectopic expression of transcription factor NF-E2 alters the phenotype of erythroid and monoblastoid cells.

In this study, regulation of transcription factor NF-E2 was examined in differentiating erythroid and myeloid cells, and the impact of raising NF-E2 concentrations within these cell types was assessed. NF-E2 was expressed in the J2E erythroid cell line, but the levels increased only marginally during erythropoietin-induced differentiation. In contrast, rare myeloid variants of J2E cells did not express NF-E2. Although NF-E2 was present in M1 monoblastoid cells, it was undetectable as these cells matured into macrophages. Compared with erythroid cells, transcription of the NF-E2 gene was reduced, and the half-life of the mRNA was significantly shorter in monocytoid cells. Ectopic expression of NF-E2 had a profound impact upon the J2E cells; morphologically mature erythroid cells spontaneously emerged in culture, but the cells failed to synthesize hemoglobin, even in the presence of erythropoietin. Although proliferation and viability increased in the NF-E2-transfected J2E cells, their responsiveness to erythropoietin was severely diminished. Strikingly, increasing the expression of NF-E2 in M1 cells produced sublines that contained erythroid or immature megakaryocytic cells. Finally, overexpression of NF-E2 in primary hemopoietic progenitors from fetal liver increased erythroid colony formation in the absence of erythropoietin. These data demonstrate that elevated NF-E2 (i) had a dominant effect on the phenotype and maturation of J2E erythroid cells, (ii) was able to reprogram the M1 monocytoid line, and (iii) promoted the development of erythroid colonies by normal progenitors.

Blotting, Northern↗
PubMed2000

Osteoprotegerin ligand regulates osteoclast adherence to the bone surface in mouse calvaria.

The stimulators of bone resorption, prostaglandin E(2) (PGE(2)) and 1,25-dihydroxyvitamin D(3) (1,25D(3)), act through osteoblast-like cells to activate osteoclasts. One candidate for the intermediary produced by osteoblasts that subsequently stimulates the osteoclast is osteoprotegerin ligand (OPGL). OPGL has been shown to stimulate osteoclast differentiation and activation. The aim of the work reported here was to determine if soluble recombinant extracellular domain of human OPGL would bring about the change in osteoclast adhesion from the periosteum of mouse calvaria to the adjacent bone surface that occurs with the above-mentioned stimulators of resorption. This change in adherence or translocation of osteoclasts onto the bone surface required the expression and functioning of the integrin subunit, beta 3. We show that this soluble OPGL, like PGE(2) and 1,25D(3), stimulated the release of osteoclasts from the periosteum and their adherence to the bone surface accompanied by an increase in staining for immunolocalized integrin subunit beta 3. Recombinant human osteoprotegerin (OPG), which binds strongly to OPGL, inhibited this translocation of osteoclasts that occurred with PGE(2) and 1,25D(3), leaving integrin beta-3-negative osteoclasts on the periosteum. PGE(2) and 1,25D(3) increased the expression of messenger RNA for OPGL compared with indomethacin-treated controls after 6 h exposure. Evidence is presented that the change in the adhesion of osteoclasts from the periosteum to the bone surface, resulting in osteoclast activation, is mediated by OPGL.

Acid Phosphatase↗
PubMed2000

HS1 interacts with Lyn and is critical for erythropoietin-induced differentiation of erythroid cells.

Erythroid cells terminally differentiate in response to erythropoietin binding its cognate receptor. Previously we have shown that the tyrosine kinase Lyn associates with the erythropoietin receptor and is essential for hemoglobin synthesis in three erythroleukemic cell lines. To understand Lyn signaling events in erythroid cells, the yeast two-hybrid system was used to analyze interactions with other proteins. Here we show that the hemopoietic-specific protein HS1 interacted directly with the SH3 domain of Lyn, via its proline-rich region. A truncated HS1, bearing the Lyn-binding domain, was introduced into J2E erythroleukemic cells to determine the impact upon responsiveness to erythropoietin. Truncated HS1 had a striking effect on the phenotype of the J2E line-the cells were smaller, more basophilic than the parental proerythoblastoid cells and had fewer surface erythropoietin receptors. Moreover, basal and erythropoietin-induced proliferation and differentiation were markedly suppressed. The inability of cells containing the truncated HS1 to differentiate may be a consequence of markedly reduced levels of Lyn and GATA-1. In addition, erythropoietin stimulation of these cells resulted in rapid, endosome-mediated degradation of endogenous HS1. The truncated HS1 also suppressed the development of erythroid colonies from fetal liver cells. These data show that disrupting HS1 has profoundly influenced the ability of erythroid cells to terminally differentiate.

Adaptor Proteins, Signal Transducing↗
PubMed1999

HLS7, a hemopoietic lineage switch gene homologous to the leukemia-inducing gene MLF1.

Hemopoietic lineage switching occurs when leukemic cells, apparently committed to one lineage, change and display the phenotype of another pathway. cDNA representational difference analysis was used to identify myeloid-specific genes that may be associated with an erythroid to myeloid lineage switch involving the murine J2E erythroleukemic cell line. One of the genes isolated (HLS7) is homologous to the novel human oncogene myeloid leukemia factor 1 (MLF1) involved in the t(3;5)(q25.1;q34) translocation associated with acute myeloid leukemia. Enforced expression of HLS7 in J2E cells induced a monoblastoid phenotype, thereby recapitulating the spontaneous erythroid to myeloid lineage switch. HLS7 also inhibited erythropoietin- or chemically-induced differentiation of erythroleukemic cell lines and suppressed development of erythropoietin-responsive colonies in semi-solid culture. However, intracellular signaling activated by erythropoietin was not impeded by ectopic expression of HLS7. In contrast, HLS7 promoted maturation of M1 monoblastoid cells and increased myeloid colony formation in vitro. These data show that HLS7 can influence erythroid/myeloid lineage switching and the development of normal hemopoietic cells.

Amino Acid Sequence↗
PubMed1999

A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-conducting channel SEC61beta subunit.

We report here the isolation of a new member of the ADP-ribosylation factor (ARF)-like family (ARL-6) present in the J2E erythroleukemic cell line, but not its myeloid variants. Consistent with this lineage-restricted expression, ARL-6 mRNA increased with erythropoietin-induced maturation of J2E cells, and decreased with interleukin 6-induced differentiation of M1 monoblastoid cells. In tissues, ARL-6 mRNA was most abundant in brain and kidney. While ARL-6 protein was predominantly cytosolic, its membrane association increased following exposure to GTP-gammaS, like many members of the ARF/ARL family. Using the yeast two-hybrid system, six molecules which interact with ARL-6 were identified including SEC61beta, a subunit of the heterotrimeric protein conducting channel SEC61p. Co-immunoprecipitation of ARL-6 confirmed a stable association between ARL-6 and SEC61beta in COS cells. These results demonstrate that ARL-6, a novel member of the ADP-ribosylation factor-like family, interacts with the SEC61beta subunit.

ADP-Ribosylation Factors↗
PubMed1999

Developmental selection within the angiosperm style: using gamete DNA to visualize interspecific pollen competition.

Among flowering plants, females often have little control over the genetic relatedness of pollen deposited on stigmas. Thus, postpollination processes are of primary importance for mate discrimination. The ability to screen and select among male gametes during pollen tube growth within the female tissues of the stigma, style, and ovary is critical to the process of mate choice and reproductive isolation. However, direct evidence of the mechanistic/developmental processes associated with mate choice in flowering plants is sparse. We studied the contribution of postpollination, prefertilization processes to reproductive isolation in two wind-pollinated species of birch (Betula) that commonly hybridize in nature. We exploited the 3-fold difference in ploidy level between these two species to determine the paternity of individual pollen tubes growing within female reproductive tissues. We then tracked their developmental fate in conspecific, heterospecific, and mixed-species crosses. This design allowed a direct comparison of developmental processes responsible for reproductive isolation in both single-species and mixed-species pollinations. Our results have important implications for the population genetic outcome of hybridization dynamics in natural populations. Paternity analysis of progeny from mixed-species pollinations revealed that conspecific pollen tubes sired more than 98% of seedlings. Biased siring success was not the result of differential embryo abortion. We detected strong, early postpollination barriers such as pollen tube incompatibility, slower pollen tube growth, and delayed generative cell mitosis. Conspecific fertilization precedence was mediated by favorable or unfavorable male-female interactions, but there was no evidence for antagonistic male-male interactions.

Crosses, Genetic↗
PubMed1999

Maintenance of sinus rhythm with oral d,l-sotalol therapy in patients with symptomatic atrial fibrillation and/or atrial flutter. d,l-Sotalol Atrial Fibrillation/Flutter Study Group.

Currently d,l-sotalol is widely used to prevent recurrence of atrial fibrillation and/or atrial flutter, although a randomized dose-response study has not previously been conducted to guide therapy for this indication. This study summarizes findings of a double-blind, placebo-controlled, multicenter, randomized trial evaluating the efficacy, safety, and dose-response relation of 3 fixed doses of d,l-sotalol (80, 120, and 160 mg twice daily) for the maintenance of sinus rhythm in 253 patients with atrial fibrillation and/or atrial flutter. All patients were in sinus rhythm at randomization. Treatment (69 patients on placebo, 59 on 80 mg, 63 on 120 mg, and 62 on 160 mg given twice daily) was continued for 12 months or until documented recurrence of symptomatic atrial fibrillation and/or flutter. Transtelephonic electrocardiographic monitoring was used to detect symptomatic recurrences. Demographic characteristics were not different in the 4 groups. Structural heart disease was present in 57% of patients. Patients with a history of heart failure were excluded. The time from randomization to symptomatic arrhythmia recurrence was significantly longer in the 2 higher d,l-sotalol dose groups than in the placebo group. The median times to recurrence were 27, 106, 229, and 175 days for the placebo, 80, 120, and 160 mg groups, respectively. There were no deaths or cases of torsade de pointes, sustained ventricular tachycardia, or ventricular fibrillation reported. Thus, d,l-sotalol appeared to be both safe and effective in maintaining sinus rhythm in patients with symptomatic atrial fibrillation and/or flutter. Further, the 120-mg twice daily dose appeared to provide the most favorable benefit and/or risk.

Anti-Arrhythmia Agents↗
PubMed1999

Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group.

BACKGROUND: Patients with implantable cardioverter-defibrillators often receive adjunctive antiarrhythmic therapy to prevent frequent shocks. We tested the efficacy and safety of sotalol, a beta-blocker with class III antiarrhythmic effects, for this purpose. METHODS: In a multicenter trial, patients were stratified according to left ventricular ejection fraction (< or =0.30 or >0.30), randomly assigned to double-blind treatment with 160 to 320 mg of sotalol per day (151 patients) or matching placebo (151 patients), and followed for 12 months. Kaplan-Meier analyses of the time to an event were performed. Three end points were used: the delivery of a first shock for any reason or death from any cause, the first appropriate shock for a ventricular arrhythmia or death from any cause, and the first inappropriate shock for a supraventricular arrhythmia or death from any cause. RESULTS: Compliance with double-blind treatment was similar in the two groups. There were seven deaths in the placebo group and four in the sotalol group. As compared with placebo, treatment with sotalol was associated with a lower risk of death from any cause or the delivery of a first shock for any reason (reduction in risk, 48 percent; P<0.001 by the log-rank test), death from any cause or the delivery of a first appropriate shock (reduction in risk, 44 percent; P=0.007), or death from any cause or the delivery of a first inappropriate shock (reduction in risk, 64 percent; P=0.004). Sotalol also reduced the mean (+/-SD) frequency of shocks due to any cause (1.43+/-3.53 shocks per year, as compared with 3.89+/-10.65 in the placebo group; P=0.008). In the sotalol group, the reduction in the risk of death from any cause or the delivery of a first shock for any reason did not differ significantly between patients with ejection fractions of more than 0.30 and those with ejection fractions of 0.30 or less. CONCLUSIONS: Oral sotalol was safe and efficacious in reducing the risk of death or the delivery of a first defibrillator shock whether or not ventricular function was depressed.

Adrenergic beta-Antagonists↗
PubMed1999

Continuous axenic cultivation of Pneumocystis carinii.

Continuous axenic culture of Pneumocystis carinii has been achieved. A culture vessel is used that allows for frequent medium exchange without disturbance of organisms that grow attached to a collagen-coated porous membrane. The growth medium is based on Minimal Essential Medium with Earle's salt supplemented with S-adenosyl-L-methionine, putrescine, ferric pyrophosphate, N-acetyl glucosamine, putrescine, p-aminobenzoic acid, L-cysteine and L-glutamine, and horse serum. Incubation is in room air at 31 degrees C. The pH of the medium begins at 8.8 and rises to approximately 9 as the cells grow. Doubling times calculated from growth curves obtained from cultures inoculated at moderate densities ranged from 35 to 65 hours. With a low-density inoculum, the doubling time is reduced to 19 hours. The morphology of cultured organisms in stained smears and in transmission electron micrographs is that of P. carinii, and P. carinii-specific mAbs label the cultured material. Cultured organisms are infective for immunosuppressed rats and can be stored frozen and used to reinitiate culture.

Adenosine Triphosphate↗