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Biomedical subjects

R Clayton

Publications and source records attributed to R Clayton.

At least 37 records · Page 2Linked to original sources
PubMed1998

Complete genome sequence of Treponema pallidum, the syphilis spirochete.

The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi, the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes.

Bacterial Proteins↗
PubMed1998

Tyrosine phosphorylation of a 95 kDa protein and induction of the acrosome reaction in human spermatozoa by recombinant human zona pellucida glycoprotein 3.

Protein tyrosine phosphorylation and induction of the acrosome reaction (AR) in non-capacitated and capacitated human spermatozoa was investigated in response to recombinant human zona pellucida glycoprotein (rhZP3) produced by Chinese hamster ovary cells transfected with a plasmid containing human ZP3 cDNA. rhZP3-containing medium promoted the AR in a high proportion of capacitated spermatozoa (48.6 +/- 3.2%; P < 0.01) compared with control (no rhZP3) samples (14.8 +/- 2.1%). However, rhZP3-containing medium did not cause increased acrosomal exocytosis in non-capacitated spermatozoa (16.8 +/- 3.0%). Induction of the AR was associated with increased tyrosine phosphorylation of a 95 +/- 5 kDa epitope only in capacitated spermatozoa. A dose-dependent increase in the protein phosphorylation of a 95 kDa epitope in response to rhZP3 was detected by [gamma-32P]-ATP labelling of detergent-solubilized sperm proteins. When spermatozoa were co-incubated with monoclonal antibody 97.25 (mAb 97.25) recognizing a 95 kDa tyrosine kinase epitope, there was no rhZP3 induction of tyrosine phosphorylation of the 95 kDa protein. Such co-incubation also markedly inhibited the AR (23.9 +/- 3.1%). These results support the model that initial interaction of the fertilizing spermatozoon with ZP3 involves the tyrosine phosphorylation of a 95 kDa tyrosine kinase protein and that this requires capacitation.

Acrosome Reaction↗
PubMed1998

A combinatorial phage display library for the generation of specific Fab fragments recognizing human spermatozoa and inhibiting fertilizing capacity in vitro.

To select a source of lymphocytes for the generation of an anti-sperm-biased combinatorial phage display library, venous blood was obtained from 34 vasovasostomy (vasectomy reversal) patients approximately 3 mo after surgery. Using a variety of immunoassays, serum was analyzed for antibodies against human spermatozoa, and a patient was selected on the basis of high titer of antibodies that recognized the equatorial region of the sperm head and inhibited sperm fertilizing capacity in vitro. Total RNA isolated from the stored lymphocytes of this individual was reversed transcribed, and gamma1 (Fd) region and kappa chains were amplified by polymerase chain reaction for the successful construction of an antibody phage display library. The library was panned against human spermatozoa to isolate sperm-specific phage that recognized the equatorial region of the sperm head. Three preparations of Fab were tested via the hamster egg penetration test. Each preparation significantly (p < 0. 005) inhibited sperm-egg binding and fusion, with one preparation (designated Fab-G) causing complete inhibition. Sequence analysis of the kappa light gene encoding Fab-G revealed a 93% homology with the light chain of human anti-human immunodeficiency virus gp120 p35 variable region. This technology may have a practical application in characterization of the immune response to spermatozoa and for the design of sperm-based contraceptive vaccines.

Amino Acid Sequence↗
PubMed1997

Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi.

The genome of the bacterium Borrelia burgdorferi B31, the aetiologic agent of Lyme disease, contains a linear chromosome of 910,725 base pairs and at least 17 linear and circular plasmids with a combined size of more than 533,000 base pairs. The chromosome contains 853 genes encoding a basic set of proteins for DNA replication, transcription, translation, solute transport and energy metabolism, but, like Mycoplasma genitalium, it contains no genes for cellular biosynthetic reactions. Because B. burgdorferi and M. genitalium are distantly related eubacteria, we suggest that their limited metabolic capacities reflect convergent evolution by gene loss from more metabolically competent progenitors. Of 430 genes on 11 plasmids, most have no known biological function; 39% of plasmid genes are paralogues that form 47 gene families. The biological significance of the multiple plasmid-encoded genes is not clear, although they may be involved in antigenic variation or immune evasion.

Biological Transport↗
PubMed1996

Influence of depression on cognitive functioning in Fragile X females.

We sought to determine the frequency of a history of major depression in women with Fragile X syndrome. In addition, we attempted to disentangle the cognitive effects of major depression from those of Fragile X syndrome. Thirty-seven mothers of developmentally delayed children (Fragile X syndrome: n = 18; comparison group n = 19), matched for age, educational level, and socioeconomic status, were administered psychiatric and neuropsychological measures. Women with Fragile X syndrome had a higher frequency of lifetime diagnosis of major depressive disorder (78%) than the comparison group (37%). Mild impairment was seen on visuospatial construction and memory tasks in women with Fragile X syndrome, while women with depression showed subtle deficits in several aspects of visuospatial perception and learning. There was no interaction of Fragile X syndrome and depression in their influence on cognition. The results underscore the importance of considering the influence of depression on cognitive performance in studies of genetic disorders.

Adult↗
PubMed1996

Recombinant human zona pellucida glycoprotein 3 induces calcium influx and acrosome reaction in human spermatozoa.

Recombinant human ZP3 (rhuZP3) generated by Chinese hamster ovary cells transfected with a plasmid containing human ZP3 cDNA was used to study the acrosome reaction (AR) and intracellular calcium fluxes in capacitated human spermatozoa. Conditioned medium containing rhuZP3 significantly induced the AR (P < or = 0.005) in 59.4 +/- 4.7% of spermatozoa (control = 8.5 +/- 3.1%) and caused complete acrosomal loss in a further 17.2 +/- 3.8% of cells (control = 3.7 +/- 0.7%; mean +/- SEM, n = 5). Sperm motility was not affected and acrosomal exocytosis in response to rhuZP3 was also shown to be time-dependent. Basal concentrations of sperm intracellular calcium were measured (82 +/- 7 nM; mean +/- SEM, n = 9). A transient increase in intracellular calcium (typically up to 400-450 nM) occurred within 1 min of rhuZP3 addition and was followed by sustained lower values of calcium (200-400 nM). These responses were dependent on the amount of rhuZP3. This is the first report of zona protein-induced changes in intracellular calcium levels in human spermatozoa. The results support the premise that ZP3 is an agonist of the human sperm AR and that rhuZP3 generated in a eukaryotic cell is effective in this respect.

Acrosome↗
PubMed1995

Effect of hypoxia and beta 2-agonists on the activity of the renin-angiotensin system in normal subjects.

1. We have reported that the renin-angiotensin system is activated in acute asthma, and also by high-dose nebulized beta 2-agonists. The contribution of other possible stimuli such as hypoxia is unknown. The present study examined the effect of hypoxia alone and also combined with beta 2-agonists on the activity of the renin-angiotensin system. 2. In a double-blind crossover study, eight healthy subjects were randomized to inhale a hypoxic (FiO2 = 12%) or normoxic mixture for a period of 30 min, with either nebulized salbutamol (5 mg) or placebo administered into the circuit after 10 min. Plasma renin, angiotensin II and serum angiotensin-converting enzyme were measured at baseline and at intervals up to 2 h. Pulse rate and oxygen saturation were monitored continuously throughout the study. 3. After hypoxia alone, there was no change in the levels of plasma renin or angiotensin II. When salbutamol was added to the hypoxic mixture, there was a significant rise in plasma renin and angiotensin II [mean (SEM) maximal increase in angiotensin II of 5.6 (2.9) pg/ml and renin of 15.5 (6.3) mu-units/ml at 60 min, P < 0.05 compared with normoxia]. When salbutamol was administered in the normoxic mixture, plasma renin and angiotensin II also increased but this effect was similar to the effect of salbutamol in the hypoxic mixture. Serum angiotensin-converting enzyme levels were unaffected by hypoxia or salbutamol. 4. We conclude from these results that there is activation of the renin-angiotensin system in healthy subjects by salbutamol, but not hypoxia. (ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1994

Hyperandrogenism in polycystic ovary syndrome. Evidence of dysregulation of 11 beta-hydroxysteroid dehydrogenase.

BACKGROUND: Hyperandrogenemia is the hallmark of the polycystic ovary syndrome, yet the relative contributions of the adrenal cortex and ovary to the overproduction of androgen remain unclear. To identify possible causes of adrenocortical overactivity, we studied the metabolism of adrenal and ovarian steroid hormones in women with this disorder. METHODS: We measured 24-hour urinary excretion of steroid hormone metabolites by high-resolution capillary gas chromatography in 65 women with the polycystic ovary syndrome and 45 normal women matched for body-mass index. RESULTS: After adjustment for body-mass index, the urinary excretion of testosterone and androstenedione metabolites was 1.9 times higher in the women with the syndrome than in the normal women, and the excretion of dehydroepiandosterone metabolites (C19 steroid sulfates) and cortisol metabolites was 1.5 and 1.3 times higher, respectively (P < 0.01 for all comparisons). The affected women also had significantly higher ratios of 11-oxo (oxygenated) metabolites to 11-hydroxy metabolites of cortisol (1.4 times higher, P < 0.001) and of 11-oxo to 11-hydroxy metabolites of corticosterone (1.8 times higher, P < 0.001). In the group with the polycystic ovary syndrome, 55 percent of the nonobese women and 24 percent of the obese women had ratios above the upper limit of normal; the ratios in the obese women did not differ significantly from those in the nonobese women. CONCLUSIONS: Adrenal secretion of cortisol and androgens is increased in women with the polycystic ovary syndrome. The increases may be explained by dysregulation of 11 beta-hydroxysteroid dehydrogenase causing increased oxidation of cortisol to cortisone, which cannot be accounted for by obesity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

A mouse model of early social interactions after prenatal drug exposure: a genetic investigation.

The aim of the present study was to (i) characterise the mouse behavioural profile (particularly social interactions) during the preweaning period, (ii) assess the effects of prenatal exposure to an anticonvulsant drug widely used in clinical practice, (iii) examine possible genetic differences both in baseline behavioural profiles and in sensitivity to drug-induced effects. Following a balanced intra-strain fostering procedure, the offspring of C57BL/6J and CBA inbred mouse strains from mothers exposed during pregnancy to either phenobarbitone (PHB, 60 mg/kg) or vehicle (VEH) given intraperitoneally (IP) during days 10-16 of gestation, were observed for early social interactions in the home cage during the last part of the preweaning period (days 20 and 21). The behavioural repertoires of the two strains differed markedly, in that C57 pups were more involved in Play soliciting, Locomotor-rotational play, and in Maintenance activities, while CBA mice spent much more time being inactive or exploring the environment. C57 and CBA mice also differed in the sensitivity to PHB exposure. On the whole, time spent in Investigative/Affiliative behaviours was increased, while the frequency of Play soliciting patterns was reduced in PHB-treated mice. The treatment of the fostering mother had only negligible effects, suggesting that PHB-induced changes in behaviour were largely due to direct effects of the substance on the foetus. These results indicate that specific items of the preweaning behavioural profile, and particularly social interactions, are influenced by early PHB exposure, and that the responses are heavily affected by the genotype.

Animals↗
PubMed1994

Effects of age and genetic growth rate on the crystallin composition of the chick lens.

This two part study continues and extends our examination of the effects of age and of genetically determined intrinsic growth rate on the overall protein composition of chick lens epithelia, lens fiber masses and whole lenses. Water-soluble proteins were analyzed by SDS-polyacrylamide and 2-dimensional gel electrophoresis. First, detailed age-related changes in protein expression between day 4 of embryonic development and the 8-week adult stage are described for one normal chick strain. Secondly, comparisons are made between day-old post-hatch chicks of four different genotypes: two genetically unrelated chick strains with a high growth rate and propensity for hyperplasia of the lens epithelium and two unrelated slow-growing strains, both with normal lens morphology. We find that the beta/delta-crystallin ratio in lens epithelia and fiber masses is higher in both the slow- than in both the fast-growing strains. The data emphasizes the importance of quantitative and non-coordinate changes in crystallin polypeptide expression during lens growth and development, and implicates growth rate as a modifier of the pattern of crystallin expression.

Aging↗
PubMed1993

Behavioural effects of gestational exposure to aluminium.

The involvement of aluminium in the aetiology of a number of human pathological diseases has altered its status from being a nontoxic, nonabsorbable, harmless element. This maybe of particular concern to the developing foetus which is more susceptible to agents and at lower levels than the adult. Little attention has been given to aluminium's potential reproductive toxicity until recently and further research is required for a full evaluation of its toxicity. Our preliminary results demonstrate behavioural and neurochemical alterations in the offspring of mice exposed to aluminium during gestation. Further, the effects of such exposure are also present in the adult animal suggesting persistent changes in behaviour following prenatal exposure.

Abnormalities, Drug-Induced↗
PubMed1992

Treating the drug-abusing offender.

The association between drug abuse treatment and criminal justice control is examined in this article. A framework is presented for mental health administrators and policy-makers to examine and appreciate the use of authority derived from the criminal justice system for drug abusers involved in community treatment. In addition, an overview of relevant literature is provided to encapsulate the literature related to the drug-abusing criminal offender which is most useful for mental health administrators and policy-makers.

Community Mental Health Centers↗
PubMed1992

Human immunodeficiency virus type I. Infection among dentists.

The largest collection yet assembled of year-to-year data on the seroprevalence of antibody to HIV in practicing dentists confirms that dentists--along with other health care workers--remain at low risk for occupationally acquired HIV infection.

AIDS Serodiagnosis↗
PubMed1990

Genetic differences in maternal behaviour patterns in mice administered phenobarbital during pregnancy.

In a study designed to examine the role of the genotype on sensitivity to drug-induced behavioural changes, pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital (PHB) intraperitoneally during days 10-16 of gestation. Following a balanced intrastrain fostering procedure, the behaviour of lactating dams was observed in their home cage at 2, 3, 5, 7 and 14 days postpartum. As the pups became older, maternal behaviour declined in control groups, whereas PHB dams of the CBA strain persisted in nursing their pups. C57 dams were generally affected in an opposite way by PHB exposure. For example, treated dams spent significantly less time in licking behaviour. Nest quality score was especially elevated in PHB dams of the CBA strain, while in C57 dams, nest-building was inhibited and nest quality unaffected by the previous PHB exposure. These results indicate that specific items of maternal behaviour can be differently affected by PHB exposure, and that the responses are affected by the genotype. To summarise, pups raised by treated dams may receive either exaggerated or insufficient maternal attention, as a result of changes in neurotransmitter systems and behavioural regulation following phenobarbital exposure. These results point to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on postnatal development.

Animals↗
PubMed1990

Involvement of tobacco in alcoholism and illicit drug use.

Survey data from the United States indicate that tobacco use is associated with the initiation of use of other addicting substances, and that increasing levels of tobacco use are associated with increasing levels of use of other psychoactive substances. Furthermore, factors affecting initiation, abstinence, and relapse to the use of tobacco, alcohol, and opioids are similar in nature. In addition, there are similarities in the addictive process underlying the use of these substances. Taken together, these data suggest that tobacco use is involved, possibly more than by simple association, in the use of other substances containing psychoactive chemicals. In the present paper we discuss the involvement of tobacco in the use of alcohol, opioids, cocaine, and other substances, as well as some of the implications of these observations for researchers and clinicians. One such implication is that it may be possible to use tobacco and nicotine as models for phenomena of interest to other substance use researchers. For example, drug abuse treatment and prevention strategies could be explored using tobacco use as a target behavior, and biological phenomena such as the development of tolerance and physical dependence may be more readily studied with nicotine than with many other drugs. Certain pharmacologic differences across substances are also discussed in light of their implications for development of treatment and drug control policies.

Adolescent↗
PubMed1989

Increased sensitivity of various genes to endogenous DNase activity in terminal differentiating chick lens fibers.

In the lens, epithelial cells from the equatorial zone differentiate into postmitotic elongated fibers. One aspect of this differentiation is nuclear shape transformation and DNA degradation. This process is controlled by DNase activity which in fiber nuclei increases with development. DNase activity is also present in the epithelial cell nuclei which appears to be non-functional but could be activated in vitro by exogenous addition of Ca2+. We have analyzed the possible selective action of endogenous DNase on 3 genes involved in lens terminal differentiation, namely delta-crystallin, beta-tubulin and vimentin, and on 1 gene not thought to participate in this process, ovalbumin. We have compared restriction DNA patterns of these genes in nuclei isolated from 11-day-old chick embryos and incubated in Ca2+-free medium or in fresh epithelial and fiber lens tissue at 11 and 18 days of development. During incubation in vitro of 11-day fiber nuclei, there is a net increase in the sensitivity of the delta-crystallin, beta-tubulin, ovalbumin and vimentin chromatin to the endogenous DNase. The vimentin gene appears to be more stable than the beta-tubulin and delta-crystallin genes indicating a degree of specificity of the endogenous DNase activity. In the epithelial nuclei, the lens-specific genes appear to be more stable but paradoxically there is a net degradation of the ovalbumin gene. In freshly isolated tissues the 4 genes were detected in epithelial and fiber cells at 11 and 18 days. Furthermore, in the mature fibers in which the nuclei were degenerating, the latter genes were still not completely digested.

Animals↗
PubMed1988

Dust emission during cutting of polyurethane-impregnated bandages.

The airborne dust generated when cutting splinting bandages represents a potential respiratory hazard, particularly to those who regularly remove casts with a power saw. Plaster of Paris (POP) dust is already classified by the Health and Safety Executive as a nuisance dust. This paper reports on a study to determine the nature, size and concentration of dust produced when cutting polyurethane (PU) impregnated bandages using a power saw. It has been shown that, under severe conditions PU bandages produce lower airborne dust concentrations than POP bandage but that all of the bandages tested produced particles small enough to reach the final divisions of the lung. It is therefore recommended that a dust extraction unit be used when cutting all types of bandage.

Air Pollutants, Occupational↗