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Biomedical subjects

F Osman

Publications and source records attributed to F Osman.

At least 37 records · Page 2Linked to original sources

A central gamma-aminobutyric acid mechanism in cardiac vagal control in man revealed by studies with intravenous midazolam.

1. Animal studies show that cardiac vagal tone can be modified by gamma-aminobutyric acid neurons acting at several sites in the central nervous system. The present study has attempted to determine whether similar control exists in humans by using midazolam, a benzodiazepine. Benzodiazepines exert their main actions on the central nervous system by interacting co-operatively at the gamma-aminobutyric acid receptor. 2. Twenty patients took part in the study before undergoing cardiac catheterization. After resting for 20 min in a semi-supine position on a couch, ECG, blood pressure and respiration were recorded for 5-min periods with either controlled (fixed) or free respiration. During this time a baroreceptor sensitivity test was conducted. 3. Doses of 1 mg and 5 mg of midazolam were administered intravenously. 4. Five-minute segments of data, before and after midazolam, were subjected to power spectral and time-domain analysis. 5. Midazolam caused a decrease in the high-frequency and an increase in the low-frequency components of the power spectral density plot, and in addition reduced the mean R-R interval and R-R variability expressed as the interquartile difference, and pNN50. There were no significant changes in the sensitivity of the baroreflex or in the systolic, diastolic and average blood pressures. 6. This decrease in variability of heart period, particularly at a controlled respiratory frequency, strongly suggests that cardiac vagal tone in man can be regulated by gamma-aminobutyric acid neurons.

Blood Pressure↗

Molecular studies on bromovirus capsid protein. IV. Coat protein exchanges between brome mosaic and cowpea chlorotic mottle viruses exhibit neutral effects in heterologous hosts.

Two members of the bromovirus group, brome mosaic virus (BMV) and cowpea chlorotic mottle virus (CCMV), selectively infect barley and cowpea, respectively, and also differ in their ability to systemically infect a common permissive host, Chenopodium quinoa. CCMV is confined to inoculated leaves of C. quinoa, whereas BMV causes rapid systemic mottling. To examine whether host-specific determinants for systemic movement of BMV and CCMV in each of these hosts are localized in the coat protein (CP), sequences encoding this gene were exchanged between biologically active clones of BMV RNA3 (B3) and CCMV RNA3 (C3) to create chimera expressing heterologous CP genes (B3/CCP and C3/BCP). Inoculation of each chimera with its respective wild-type (wt) RNAs 1 and 2 to barley or cowpea or C. quinoa plants resulted in symptom phenotype and long distance movement characteristics similar to those of the parental virus donating RNAs 1 and 2. These observations suggest that neither BMV CP nor CCMV CP has host-specific determinants for long distance movement. Inoculation of additional recombinant viruses, constructed by reassorting wt genomic RNAs 1 and 2 of BMV and CCMV with either heterologous wt RNA3 (i.e., B1 + B2 + C3 and C1 + C2 + B3) or heterologous chimeric RNA3 (i.e., B1 + B2 + C3/BCP and C1 + C2 + B3/CCP), to susceptible hosts resulted only in localized infections. The significance of these observations in relation to bromovirus movement is discussed.

Bromovirus↗

Characterization of the alternative excision repair pathway of UV-damaged DNA in Schizosaccharomyces pombe.

Schizosaccharomyces pombe cells deficient in nucleotide excision repair (NER) are still able to remove photoproducts from cellular DNA, showing that there is a second pathway for repair of UV damage in this organism. We have characterized this repair pathway by cloning and disruption of the genomic gene encoding UV damage endonuclease (UVDE). Although uvde gene disruptant cells are only mildly UV sensitive, a double disruptant of uvde and rad13 (a S. pombe mutant defective in NER) was synergistically more sensitive than either single disruptant and was unable to remove any photoproducts from cellular DNA. Analysis of the kinetics of photoproduct removal in different mutants showed that the UVDE-mediated pathway operates much more rapidly than NER. In contrast to a previous report, our genetic analysis showed that rad12 and uvde are not the same gene. Disruption of the rad2 gene encoding a structure- specific flap endonuclease makes cells UV sensitive, but much of this sensitivity is not observed if the uvde gene is also disrupted. Further genetic and immunochemical analyses suggest that DNA incised by UVDE is processed by two separate mechanisms, one dependent and one independent of flap endonuclease.

Cloning, Molecular↗

Analysis of spontaneous and double-strand break-induced recombination in rad mutants of S. pombe.

Schizosaccharomyces pombe strains containing direct repeats of adeó heteroalleles separated by a functional uro4+ gene, and a DNA site for induction of a double-strand break (DSB), have been used to analyze pathways of spontaneous and DSB-induced intrachromosomal mitotic recombination. These substrates yield Ade+ Ura+ convertants or Ade+ Ura- deletions, by the DSB/gap repair and single-strand annealing (SSA) pathways of recombination, respectively. In S. cerevisiae, the DSB/gap repair pathway is RAD52 dependent, and the RAD1 and RAD10 genes are involved in the SSA pathway. We have sought to understand the genetic control of the pathways of mitotic recombination in S. pombe by determining the effects of mutations in six rad genes involved in DNA repair: rad1 and rad3 involved in checkpoint control in response to unreplicated or damaged DNA; rad5 (homologue of S. cerevisiae RAD3) and rad10 (homologue of S. cerevisiae RAD1) involved in nucleotide excision repair; rad21 and rad22 (homologue of S. cerevisiae RAD52) involved in the repair of ionizing radiation-induced DNA damage. The results suggest that the genetic control of the pathways of spontaneous and DSB-induced mitotic intrachromosomal recombination in S. pombe is different from that in S. cerevisiae.

Adenosine Triphosphatases↗

Down-regulation of human tumor necrosis factor-beta gene expression by cells with suppressive activity.

Human TNF-beta (lymphotoxin) gene expression is down-regulated by immunosuppression. Induction of TNF-beta mRNA in lymphoid cells is greatly enhanced by gamma-irradiation, cyclophosphamide and cimetidine, agents that each inhibit activation of suppressive cells. The level of TNF-beta mRNA expressed in response to stimulation, whether by mitogen or antigen, is reduced strongly by concomitant activation of suppressive cell subsets. Removal of CD8 or CD11b cells leads to a pronounced superinduction of TNF-beta mRNA in the depleted cell population. Induction of TNF-beta mRNA precedes appearance of suppressive cell activity, allowing for temporary expression. The TNF-beta gene is as sensitive as IFN-gamma and IL-2 genes to suppression. Hence, three genes characteristically expressed in Th1 cells, encoding IL-2, IFN-gamma, and TNF-beta, are similarly regulated by cell-mediated suppression. Actual levels of TNF-beta during an immune response are determined by the balance between activities of expressing and suppressing cell subsets, both transiently manifested.

CD8 Antigens↗

Double-strand break-induced mitotic intrachromosomal recombination in the fission yeast Schizosaccharomyces pombe.

The Saccharomyces cerevisiae HO gene and MATa cutting site were used to introduce site-specific double-strand breaks (DSBs) within intrachromosomal recombination substrates in Schizosaccharomyces pombe. The recombination substrates consisted of nontandem direct repeats of ade6 heteroalleles. DSB induction stimulated the frequency of recombinants 2000-fold. The spectrum of DSB-induced recombinants depended on whether the DSB was introduced within one of the ade6 repeats or in intervening unique DNA. When the DSB was introduced within unique DNA, over 99.8% of the recombinants lacked the intervening DNA but retained one copy of ade6 that was wild type or either one of the heteroalleles. When the DSB was located in duplicated DNA, 77% of the recombinants were similar to the deletion types described above, but the single ade6 copy was either wild type or exclusively that of the uncut repeat. The remaining 23% of the induced recombinants were gene convertants with two copies of ade6 and the intervening sequences; the ade6 heteroallele in which the DSB was induced was the recipient of genetic information. Half-sectored colonies were isolated, analyzed and interpreted as evidence of heteroduplex DNA formation. The results are discussed in terms of current models for recombination.

Chromosomes, Fungal↗

2-Aminopurine selectively inhibits splicing of tumor necrosis factor alpha mRNA.

2-Aminopurine (2-AP) inhibits specific kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor 2. One of these, PKR, is also involved in signal transduction. We show here that 2-AP selectively inhibits expression of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human lymphoid cells. 2-AP does not inhibit transcription of the human TNF-alpha gene, nor does it affect mRNA stability. Instead, the flow of short-lived precursor transcripts into mature TNF-alpha mRNA is blocked. When 2-AP is present during induction, unspliced TNF-alpha precursor transcripts accumulate at the expense of mRNA. Using RNase protection analysis with genomic probes for different exon-intron junctions, we show that 2-AP blocks splicing of TNF-alpha mRNA. Neither the TNF-beta nor the interleukin-1 beta gene shows such regulation. 2-AP also inhibits splicing of precursor RNA transcribed from an exogenous human TNF-alpha gene. Sequences within this gene thus confer sensitivity to 2-AP. Yet, control is not exerted at a specific splice site. Our results reveal the involvement of a 2-AP-sensitive component, expressed in functional form before induction, in the splicing of TNF-alpha mRNA.

2-Aminopurine↗

The isolation of mutagen-sensitive nuv mutants of Aspergillus nidulans and their effects on mitotic recombination.

More than 200 mutants of Aspergillus nidulans were isolated as hypersensitive to the monofunctional alkylating agent MNNG and/or UV-irradiation (designated nuv mutants). Of these, 23 were selected for further characterization. All were markedly hypersensitive to both MNNG and the quasi-UV-mimetic mutagen 4-NQO. The hypersensitive phenotype of each mutant was shown to result from mutation of a single gene. The nuv mutants exhibited a diverse range of growth responses on solid media containing various concentrations of MNNG or 4-NQO. This suggested that they represented many nonallelic mutations. Analysis to determine the dominance/recessiveness of the nuv mutations with respect to hypersensitivity revealed that most were fully recessive, although several appeared to be semidominant. A novel system to assay homologous mitotic recombination using simple plating tests was developed. The system was exploited to determine the effects of the nuv mutations on mitotic recombination. Of the 23 mutations tested, 10 caused a hypo-recombination phenotype and three a hyper-recombination phenotype, while 10 appeared to have no effect on recombination. The hypo-rec effect of one of the mutations, nuv-117, appeared to be semidominant. Transcomplementation analysis between seven of the nuv mutations defined at least six nonallelic loci.

4-Nitroquinoline-1-oxide↗

Contraceptive steroid concentrations in women with early active schistosomiasis: lack of effect of antischistosomal drugs.

Plasma concentrations of the oral contraceptive steroids (OCS) ethinyloestradiol (EE2) and levonorgestrel (LNG) have been determined in women with early active schistosomiasis and compared to those obtained in healthy volunteers. Steroid concentrations following a single dose of Ovral (500 micrograms LNG, 50 micrograms EE2) or during a multiple dose regimen were unaffected by the disease. There was no significant effect of the antischistosomal drugs praziquantel (40 mg X kg-1) or metrifonate (10 mg X kg-1 X 3 at 2-week intervals) on plasma steroid concentrations. In regular users of OCS, significantly higher concentrations of LNG were observed than in women who received only a single dose. We conclude that there is no pharmacokinetic reason for withholding OCS from patients with early active schistosomiasis who are also receiving either praziquantel or metrifonate.

Adolescent↗

Pharmacokinetics of oral contraceptive steroids in Egyptian women: studies with Ovral, Nordette and Norminest.

Plasma concentration profiles and pharmacokinetic parameters have been obtained following single dose administration of three commonly used oral contraceptive steroid preparations, Ovral, Nordette and Norminest to Egyptian women. The constituents of the preparations are as follows: Ovral (50 micrograms ethinyloestradiol, EE2 and 500 micrograms levonorgestrel, LNG); Nordette (30 micrograms EE2 and 150 micrograms LNG); and Norminest (35 micrograms EE2 and 500 micrograms norethisterone, NOR). Peak plasma concentrations of EE2 ranged between 116-160 pg ml-1 for Ovral, 55-78 pg ml-1 for Norminest and 30-70 pg ml-1 for Nordette. There was no significant difference in half-life (t1/2), oral clearance (CL) or apparent volume of distribution (Vd). The relative values of the area under the plasma concentration-time curve (AUC) reflected well the different amounts of oestrogen in each preparation. There was no significant difference in t1/2, CL or Vd for LNG in the 2 preparations containing this progestogen. The mean AUC following Nordette (150 micrograms LNG) was 40% of that following Ovral (500 micrograms LNG; p less than 0.001). Comparing pharmacokinetic parameters for the same dose of LNG (Ovral) and NOR (Norminest) showed the AUC to be decreased and CL and Vd increased in the latter group. The study indicates that the kinetic profile of the OCS in healthy Egyptian women are similar to other ethnic populations.

Adult↗

Scanning electron microscopic changes in vaginal epithelium of suckling neonatal mice in response to estradiol or insecticide chlordecone (Kepone) passage in milk.

Groups of lactating mice received daily 9 intraperitoneal injections consisting of the following chemicals: sesame oil only or 10.0, 20.0 or 40.0 micrograms estradiol-17 beta or 250.0, 500.0 or 1000.0 micrograms chlordecone. Reproductive tracts and vaginal surface changes were examined in the neonates that were nursed by the treated lactating dams for 12 days. Ingestion of milk from dams treated with estradiol or chlordecone did not produce any toxic symptoms or mortality in the offspring. However, the neonatal reproductive tract weights and vaginal epithelium exhibited significant changes indicating the passage of these compounds in milk. The vaginal epithelium in the neonates that nursed the estradiol-treated dams exhibited mucification, keratinization, and desquamation. Neonates that ingested milk from chlordecone-treated dams exhibited similar but dose-dependent changes in the vaginal canals. However, the keratinized vaginal cells in these mice were morphologically different and lacked the well-developed microridge patterns on the cell surfaces that characterized keratinized cells in the estradiol group. The significance of these changes on the reproductive functions in adult animals are discussed in the text.

Animal Population Groups↗

Use of panoramic radiographs in general dental practice in England.

The rapid growth in the use of panoramic radiographs provoked this survey of the reasons why general dental practitioners in Avon take such views. Of the 193 dentists who responded, 42 (22%) took one or more panoramic radiographs during a specified week. A total of 195 patients, 8% of those x-rayed, had a panoramic radiograph taken either alone or in combination with other views. Panoramic radiographs were stated to have been taken primarily for the diagnosis of caries (48%) and surgical (24%), periodontal (20%), orthodontic (20%) and endodontic/apical assessment. These findings are discussed with respect to published guidelines on the use of panoramic radiographs and the teaching of radiology in dental schools.

Adolescent↗

Reasons for taking radiographs in general dental practice.

This survey investigated the reasons why general dental practitioners take radiographs. 179 (54%) dentists responded and provided information for 2359 patients who were radiographed during a specified week. Of those patients aged less than 15 yr, 62% were radiographed primarily for orthodontic purposes and 22% for caries. In older age groups, caries was the predominant reason for taking radiographs but endodontic assessment assumed increasing importance with age and accounted for 37% of radiographs in patients aged more than 45 yr. Only 8% of patients were radiographed for periodontal reasons. These findings are discussed with respect to the changing pattern of disease and treatment provided in general dental practice.

Adolescent↗

The pharmacokinetics of antipyrine in patients with graded severity of schistosomiasis.

The pharmacokinetics of antipyrine have been studied in patients with schistosomiasis. In comparison to a control group of subjects (n = 6), patients with early (active) schistosomiasis (passing live ova in urine or stools without clinical and laboratory evidence of liver involvement; n = 6) exhibited similar pharmacokinetic parameters. Of seven patients with hepatosplenic schistosomiasis (exhibiting hepatic fibrosis, splenomegaly, at least one episode of haematemesis, ascites), five showed markedly enhanced antipyrine half-life and reduced clearance. Compared to controls, the mean half-life of this group was increased from 10.9 +/- 2.4 to 19.9 +/- 9.5 h (mean +/- s.d.; P less than or equal to 0.05) and clearance reduced from 3.81 +/- 0.74 to 2.18 +/- 0.80 l h-1 (P less than or equal to 0.01). There was no change in the apparent volume of distribution. Liver biopsy was performed on all patients diagnosed as having hepatosplenic schistosomiasis in the 2 weeks prior to the antipyrine study. The results of this study indicate that hepatic microsomal metabolism is impaired in patients with advanced hepatosplenic schistosomiasis.

Adult↗

Radiographs taken for orthodontic purposes in general practice.

This paper deals with the orthodontic aspects of a wider survey undertaken to determine the use of radiographs in general dental practice in the county of Avon. During the sample week 218 patients had radiography for orthodontic purposes of whom 184 were below the age of 15 years. There were marked differences in the radiographs used by general practitioners and specialist orthodontists and the possible reasons for these differences are discussed.

Adolescent↗

Fatty acid patterns of breast milk of Egyptian mothers from the city and the village.

The fatty acid pattern of 25 human milk collected from lactating Egyptian mothers living under rural and urban conditions are reported in the present work. The fatty acid pattern is quite similar among the two different groups, except for the absence of the essential linolenic fatty acid among those from the city. Tabulation and comparison with literature data were presented and the differences were discussed.

Diet Surveys↗