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Biomedical subjects

A M Stevens

Publications and source records attributed to A M Stevens.

At least 55 records · Page 3Linked to original sources

The transcription factor interferon regulatory factor-1 is expressed during both early G1 and the G1/S transition in the prolactin-induced lymphocyte cell cycle.

PRL induces quiescent Nb2 rat T-lymphoma cells to undergo mitogenesis. Upon PRL stimulation, the transcription factor interferon regulatory factor-1 (IRF-1) is induced as a novel T-cell activation gene in Nb2 cells. Surprisingly, IRF-1 is expressed twice during a single PRL-induced growth cycle: first during the early G1 phase, in an immediate transient peak from 15 min to 2 h, and second during the G1/S phase transition, in a broader peak beginning at 8 h. The unusual biphasic expression of IRF-1 mRNA is accompanied both times by de novo IRF-1 protein synthesis. However, the rate of IRF-1 protein turnover appears to be different in G1 and S phases. IRF-1 protein expressed in G1 exhibits a half-life of about 25 min, whereas in the S phase, the half-life is about 60 min. By washing out PRL at various times during G1, we found a direct correlation among the length of PRL exposure, the second peak of IRF-1 mRNA expression, and DNA synthesis. Our data suggest that PRL and one putative nuclear mediator, IRF-1, may be important in two distinct phases of the cell cycle: first in cell cycle activation, and then in S phase progression.

Animals↗

[Dental hygiene in 10-to-18-year-old youths in Flanders. Results of a school survey].

This study is part of the cross-national Survey on Health and Lifestyles in School-aged children--a WHO collaborative study (HELENA). The aim of this report was to describe the oral health habits (oral hygiene, use of dental floss and fluoride, consumption of sugar snacks) in schoolchildren aged 10 to 18 in the Flemish-speaking community of Belgium. Toothbrushing was consistently less frequent among boys than among girls. There is a negative correlation between the frequency of toothbrushing and the consumption of soft drinks in both sexes, and between toothbrushing and sweets consumption in girls. The use of dental floss is still very rare. Efforts must be continued to reduce the consumption of sweets and soft drinks. No differences in oral health habits were noted among children from different school types. Parental profession did not influence oral health habits in this study.

Adolescent↗

Postnatal transmission of human immunodeficiency virus type 1 from mother to infant. A prospective cohort study in Kigali, Rwanda.

BACKGROUND: Although transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant has been well documented during pregnancy and delivery, little is known about the possible transmission of HIV-1 during the postnatal period. METHODS: We conducted a prospective cohort study in Kigali, Rwanda, of 212 mother-infant pairs who were seronegative for HIV-1 at delivery. All the infants were breast-fed. The subjects were followed at three-month intervals, with Western blot assays for antibodies to HIV-1 and testing of mononuclear cells by a double polymerase chain reaction (PCR) using three sets of primers. To evaluate potential risk factors, each mother who seroconverted was matched with three seronegative control women. RESULTS: After a mean follow-up of 16.6 months, 16 of the 212 mothers became seropositive for HIV-1. Of their 16 infants, 9 became seropositive. One infant was excluded from the analysis because of a positive test by PCR on the blood sample obtained at birth. Postnatal seroconversion to HIV-1 occurred in four of the five infants born to the mothers who seroconverted during the first 3 months post partum, and in four infants of the 10 mothers who seroconverted between month 4 and month 21. In all cases, the infant seroconverted during the same three-month period as the mother. The main risk factor for maternal seroconversion was being single. CONCLUSIONS: HIV-1 infection can be transmitted from mothers to infants during the postnatal period. Colostrum and breast milk may be efficient routes for the transmission of HIV-1 from recently infected mothers to their infants.

Base Sequence↗

Perinatal transmission of HIV-1: lack of impact of maternal HIV infection on characteristics of livebirths and on neonatal mortality in Kigali, Rwanda.

We present the baseline results of a prospective cohort study on the perinatal transmission of HIV-1 in Kigali, Rwanda. HIV-1-antibody testing was offered to all women of urban origin delivering a live newborn at the maternity ward of the Centre Hospitalier de Kigali from November 1988 to June 1989; 218 newborns of 215 HIV-positive mothers were matched to 218 newborns of 216 HIV-negative mothers. The matching criteria were maternal age and parity. No differences in socioeconomic characteristics were observed between HIV-positive and HIV-negative women. HIV-positive mothers more frequently reported a history of at least one death of a previously born child (P less than 0.01) and a history of abortion (P less than 0.001). Most of the HIV-positive women were asymptomatic, but 72.4% of them had a CD4; CD8 ratio less than 1 versus 10.1% in the HIV-negative group (P less than 0.001). The frequency of signs and symptoms was not statistically different in the two groups, except for a history of herpes zoster or chronic cough, which was more frequent among HIV-positive women. The rates of prematurity, low birth weight, congenital malformations and neonatal mortality were comparable in the two groups. However, infants of HIV-positive mothers had a mean birth weight 130 g lower than the infants of HIV-negative mothers (P less than 0.01). The impact of maternal HIV-1 infection on the infant seems limited during the neonatal period.

Abortion, Spontaneous↗

The region of a Bacteroides conjugal chromosomal tetracycline resistance element which is responsible for production of plasmidlike forms from unlinked chromosomal DNA might also be involved in transfer of the element.

Large (greater than 50 kilobases) conjugal chromosomal tetracycline resistance (Tcr) elements have been found in many human colonic Bacteroides strains. Recently, N. B. Shoemaker and A. A. Salyers (J. Bacteriol, 170:1651-1657, 1988) reported that some of these Tcr elements appeared to mediate production of plasmidlike forms, NBU1 and NBU2, from an unlinked region of the chromosome of Bacteroides uniformis 0061. Production of the plasmidlike forms and the transfer frequency of the Tcr elements were both enhanced by preexposure to tetracycline. Thus it appeared that genes involved in production of plasmidlike forms (Plf activity) might be coregulated with transfer genes and that Plf activity might have a role in transfer of the Tcr elements. By screening subclones of a Tcr element, Tcr Emr DOT, we have shown that the genes necessary for Plf activity on the Tcr element are within a 10-kilobase region adjacent to the Tcr gene. Subclones of this region were then used to construct insertional gene disruptions in a Tcr element, Tcr ERL, which is closely related to the Tcr Emr DOT element. Two of the disruption mutants were Plf-. Both had reduced transfer frequencies, one (omega RDB2) 10(2)-fold lower than that of the wild-type element and the other (omega RDBT) 10(4)-fold lower. omega RDB2 was also deficient in the ability to mobilize coresident plasmids, whereas omega RDBT exhibited nearly wild-type mobilization activity. The phenotypes of the mutants indicate that there are at least two genes necessary for Plf activity and that both may be involved in transfer of the element. The third disruption mutant (omegaRDB1), which expressed Plf constitutively, also had a transfer frequency 10(2) -fold lower than that of the wild-type element and was deficient in mobilization of coresident plasmids. The relationship between Plf genes and transfer, therefore, appears to be a complex one.

Bacteroides↗

Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells.

The pituitary peptide hormone prolactin (Prl) is a potent inducer of Nb2 T lymphoma cell proliferation. To analyze the early genetic response to the mitogenic signals of Prl, a cDNA library was constructed from Nb2 T cells stimulated for 4 h with Prl and the protein synthesis inhibitor cycloheximide. Of 26 distinct clones isolated by differential screening, one clone, designated c25, exhibited extremely rapid but transient kinetics of induction by Prl and superinduction by Prl plus cycloheximide. Run-on transcription analysis indicated that c25 gene transcription was induced greater than 20-fold within 30 to 60 min of Prl stimulation. Surprisingly, DNA sequence analysis of c25 cDNA revealed that this Prl-inducible early-response gene is the rat homolog of the mouse transcription factor interferon-regulatory factor 1 (IRF-1), sharing 91% coding sequence similarity with mouse IRF-1. At the protein level, rat IRF-1 shares 97% and 92% homology with mouse IRF-1 and human IRF-1, respectively, suggesting that this molecule has been functionally conserved throughout evolution. Our studies show that the gene for IRF-1 is an immediate-early gene in Prl-stimulated T cells, which suggests that IRF-1 is a multifunctional molecule. In addition to its role in regulating growth-inhibitory interferon genes, IRF-1 may, therefore, also play a stimulatory role in cell proliferation. The gene for IRF-1 is one of the earliest genes known to be transcriptionally regulated by Prl.

Amino Acid Sequence↗

Treatment of adult gonococcal keratoconjunctivitis with oral norfloxacin.

We evaluated the efficacy of oral norfloxacin in 15 patients with culture-proven gonococcal eye disease caused by Neisseria gonorrhoeae. The first seven patients received 1,200 mg of oral norfloxacin for three consecutive days. The other eight patients were each treated with a single oral dose of 1,200 mg of norfloxacin. All control cultures were negative, and there was no progression of the corneal lesions after treatment was initiated. No adverse effects were observed. The results of this study suggested that a single dose of oral norfloxacin may be a valuable alternative to the currently recommended treatment regimens for gonococcal eye disease because it combines high efficacy and low toxicity with low cost and excellent patient compliance.

Administration, Oral↗

Nicotinic and muscarinic agonists stimulate rapid protein kinase C translocation in PC12 cells.

Phosphoinositide hydrolysis, a major mechanism for signal transduction in neural cells, generates diacylglycerol, which can in turn activate protein kinase C (PKC). Although cholinergic agonists elicit phosphoinositide hydrolysis in neural tissues, little is known about activation of PKC by cholinergic agonists. PKC requires phosphatidylserine for activation, and in intact cells this lipid requirement is satisfied by binding of the enzyme to cell membranes. Therefore, in intact cells, activation of PKC is often associated with a decrease in cytosolic PKC activity accompanied by an increase in membrane-associated activity. We studied cholinergic-induced activation of PKC by examining changes in the subcellular distribution of the enzyme in PC12 cells treated with cholinergic drugs. Carbachol (1 mM) induced large and rapid increases in membrane-associated PKC activity; a maximal increase of 460% occurred after 5 sec of incubation. Carbachol-induced PKC translocation was concentration-dependent, with a biphasic dose-response curve yielding approximate EC50 values of 10(-6) M and 10(-4) M for the high- and low-affinity components, respectively. Experiments with selective cholinergic agents demonstrated that both muscarinic and nicotinic receptors are involved in carbachol-induced PKC translocation, but the response is predominantly mediated by nicotinic receptor stimulation. Muscarinic-induced association of PKC with cell membrane fractions was resistant to extraction by chelators, whereas nicotinic-mediated membrane binding was partially reduced by homogenization of cells in the presence of EGTA. Omission of calcium from the incubation medium or chelation of calcium with EGTA completely blocked muscarinic- and nicotinic-induced translocation. In addition, the calcium channel blocker nifedipine reduced the nicotinic response by 60%. (ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗

Involvement of the esterase active site of egasyn in compartmentalization of beta-glucuronidase within the endoplasmic reticulum.

Organophosphorous compounds, which are potent inhibitors of egasyn-esterase activity, caused a rapid dissociation of the high molecular weight egasyn-microsomal beta-glucuronidase complex when administered in vivo or when added in vitro to microsomal suspensions. The dissociation was relatively specific to phosphodiester inhibitors of the esterase active site. Also, the egasyn-esterase active site was inaccessible to substrates and to inhibitors when egasyn was complexed to beta-glucuronidase. Dissociation of the egasyn-microsomal beta-glucuronidase complex in vivo by organophosphorous compounds was followed by massive and rapid secretion of microsomal beta-glucuronidase, but not egasyn, into plasma. These experiments implicate the egasyn-esterase active site in attachment of microsomal beta-glucuronidase to egasyn by a novel mechanism that, in turn, compartmentalizes beta-glucuronidase within the endoplasmic reticulum.

Animals↗

Severe herpes zoster ophthalmicus in young African adults: a marker for HTLV-III seropositivity.

This report proves the relationship between herpes zoster ophthalmicus and seropositivity for HTLV-III in young and often apparently healthy African patients. The ophthalmologist should screen patients with herpes zoster ophthalmicus for antibodies against HTLV-III in areas where this virus is endemic or if the patient belongs to a known risk group. If the test is positive, the patient should be instructed about the infectious nature of his condition to prevent spread of this sexually transmitted disease. As the rate of corneal involvement and postherpetic neuralgia are very high in these patients, it would be worthwhile to ascertain whether routine use of acyclovir treatment in HTLV-III seropositive patients with herpes zoster has a beneficial effect on these complications.

Adult↗

Studies on the control of mucin production.

The process of synthesizing a mucin molecule is discussed, primarily from the standpoint of glycoconjugate biosynthesis. The control of the activation steps in the making of nucleotide sugars is detailed, stressing the molecular mechanisms operating. These include: supply of glycolytic intermediates; the pyridine nucleotide redox potential; the energy state as expressed in nucleotide potential; and feedback modifiers. Next, the glycosyl transferases are discussed, as are suggestions of control at the first committment step and the subjects of specificity of donor and acceptor molecules and the associational state of the glycosyl transferases. The secondpart of the paper describes a model system in vivo. The paired cat submandibular glands are exposed and, in one, blood supply and salivary duct are cannulated and the parasympathetic and sympathetic nerve exposed. This preparation uses the contralateral gland as control and enables certain questions to be asked: 1. Does the cell produce incomplete mucins when the biosynthetic rate is high? 2. Does the energy state of the cell 'keep up with' the high rates of synthesis? 3. What is the extent of post-synthetic modifications? 4. What cell types are involved in mucin elicited by different chemical or electrical stimuli? 5. What is the time involved in synthesis and storage?

Animals↗

Drug utilization review in an HMO. I. Introduction and examples of methodology.

An experimental drug utilization review program was developed for a health maintenance organization (HMO). The objectives of the program were to develop and implement an ongoing mechanism for reviewing drug use using criteria based on the scientific literature, and to evaluate the effect of the drug use review program on physician precribing patterns. Seven therapeutic categories of drugs, accounting for over 65 per cent of prescribing, were selected and criteria developed for their use. The drug use review prcedure is described briefly. The evaluation of the drug use review program is based on a comparison of rates of prescription use for specific therapeutic categories before and after the criteria were ceveloped and approved. As an example, data for the antihistamine therapeutic category are presented. Criteria for prescribing antihistamines suggested restricting use of combination cold preparations and refraiming from antihistamine use in viral upper respiratory tract infections. After the criteria were adopted, prescribing of antihistamines for viral URIs declined, particularly in pediatrics. In general, prescribing of combination antihistamine preparations did not change; where one combination preparation was deleted from the formulary, prescribers appeared to substitute another combination preparation.

Adolescent↗