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H Stephens

Publications and source records attributed to H Stephens.

At least 19 recordsLinked to original sources
PubMed2001

Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism.

BACKGROUND & AIMS: Recent studies suggest that major histocompatibility complex-encoded susceptibility to primary sclerosing cholangitis (PSC) maps to the HLA B-TNFA region on chromosome 6p21.3. METHODS: The present study uses a standard polymerase chain reaction protocol to investigate the 16 common alleles of the MICA locus as candidates in 2 patient populations (King's College Hospital, London, and John Radcliffe Hospital, Oxford). RESULTS: The MICA*002 allele was found in 4 of 62 (6.4%) patients and none of 50 patients vs. 41 of 118 (35%) controls (pc = 0.00018, odds ratio [OR] = 0.12, and P = 0.0000016, OR = 0.0, respectively). Overall, the MICA*008 allele was more common in PSC (gene frequency 66% vs. 48% of controls, P = 0.0023, OR = 2.11). However, unlike MICA*002 in which the difference was a result of the absence of MICA*002 heterozygotes, the MICA*008 association may be caused by an increased frequency of MICA*008 homozygosity in patients (58% vs. 22%, pc = 0.000015, OR = 5.01 and 58% vs. 22%, P = 0.0000056, OR = 4.51, respectively). Though MICA*008 is found on the ancestral 8.1 haplotype, stratification analysis indicates that this association is independent of B8 and other HLA haplotypes associated with PSC. CONCLUSIONS: The MICA*002 allele has a strong dominant effect in reducing the risk of PSC, whereas the increased risk of disease associated with MICA*008 may be a recessive effect requiring 2 copies of the MICA*008 allele.

Adolescent↗
PubMed1999

Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type 1 highly exposed, persistently seronegative female sex workers in northern Thailand. Chiang Mai HEPS Working Group.

Characterization of persons highly exposed to human immunodeficiency virus (HIV)-1 who remain uninfected may help define protective immunity. Seventeen HIV-1-seronegative Thai female sex workers (CSWs) with epidemiologic evidence of exposure to HIV-1 were studied for humoral immune responses and phenotypic and genotypic analyses of HLA class I and CCR5 allelic profiles. Infected CSWs and low-risk HIV-1-seronegative Thai women were controls. Highly exposed, persistently seronegative (HEPS) CSWs did not differ from HIV-infected CSWs in HIV risks, condom use, or sexually transmitted diseases. Significant differences were seen in humoral immune responses: gp160-specific IgA responses were detected in cervicovaginal lavage fluids in 6 of 13 HEPS CSWs but 0 of 21 seronegative subjects. All women had wild-type CCR5. HEPS CSWs were more likely to have the HLA-B18 phenotype and genotype than were matched controls (corrected P=.018). Epidemiologic exposure to HIV-1 without apparent infection, an unusual distribution of HLA class I alleles, and HIV-1 gp160-specific IgA responses suggest a biologic basis for this phenomenon.

Adolescent↗
PubMed1997

Mental health. Making the right links.

Intensive care management has not been widely adopted, partly because of the initial costs involved. Control of inpatient beds is crucial to successful initiatives. Implementing this approach in part of Newport, including appointing a link nurse who liaises with acute and community teams, has led to reduced bed use.

Case Management↗
PubMed1992

Morphometric analysis of coated vesicles in developing rat muscle spindles.

The incidence of coated vesicles under sarcolemmal surfaces of equatorial, juxta-equatorial and polar regions in developing and adult spindles of the rat soleus muscle was examined by quantitative morphometry of transverse ultrathin sections. Coated vesicles were more numerous: 1) under primary sensory endings than under other types of neuromuscular contacts; 2) under the appositional sarcolemma between neighbouring intrafusal fibres than under free surfaces of the sarcolemma; and 3) in developing than in mature spindles. Factors such as location and age of the animal often interacted to produce an additive effect on the incidence of coated vesicles. Although there was a high incidence of coated vesicles at the postsynaptic surface under sensory terminals of bag2 fibres in 18 and 19 day gestational embryonic rats, it peaked in 4 day postnatal animals. The high incidence of coated vesicles at sensory endings supports the view that coated vesicles mediate neurotrophic interactions between afferents and intrafusal fibres during the critical late gestation and early postnatal time period, as sensory axons first contact their target fibres and exert a maximal directing influence on the differentiation of intrafusal fibre types. In addition, the preferential localization of coated vesicles under appositional rather than free surfaces of developing intrafusal fibres in 0-4 day rats suggests that they play a role in the transport of active substances among intrafusal fibres exhibiting different stages of maturity.

Aging↗
PubMed1990

Physiologic and pathologic alterations associated with ultrasonically generated shock waves.

Kidneys of 25 dogs were treated with ultrasonic shock waves and examined for both physiologic and pathologic changes. The number of pulses ranged from 2,000 to 8,000. The rate of the shock waves varied from one to 20 pulses per second. The difference in pulse rate did not affect the changes seen either acutely or in the delayed examination of the kidneys during the repair process. The physiologic and pathologic changes which occurred involved the renal tubule to a greater degree than the glomerulus. These alterations were resolving by one week following exposure to the shock waves.

Animals↗
PubMed1990

Chronic doxorubicin induced cardiomyopathy in rabbits: mechanical, intracellular action potential, and beta adrenergic characteristics of the failing myocardium.

STUDY OBJECTIVE: The aim was to assess myocardial, electrophysiological, and adrenergic changes caused by chronic administration of doxorubicin. DESIGN: Doxorubicin induced cardiotoxicity was produced in three groups of rabbits by injecting doxorubicin 0.75 mg.kg-1 three times a week for 7, 9 and 11 weeks. There were 36 controls. All studies were conducted within 16 to 36 h after the last injection. Histological, mechanical, and action potential changes produced by doxorubicin were examined in vitro. The effects of doxorubicin on beta adrenergic receptors and cyclic adenosine monophosphate (AMP) generation in myocardial membrane preparations were also evaluated. EXPERIMENTAL MATERIAL: 145 New Zealand white rabbits, 2.4-2.7 kg, were used. After excision of the heart, a papillary muscle was used for mechanical studies, a portion of the septum for intracellular action potential studies, and the rest of the heart for histological or biochemical studies. MEASUREMENTS AND RESULTS: Histological studies showed widespread myocardial damage that became more severe as the cumulative doses increased. Right ventricular papillary muscles of doxorubicin treated rabbits had lower total tension (1.5 v 3.3 g.mm-2 for controls, p less than 0.05) and dT/dt, shorter contraction duration, and lower velocity of shortening than the control muscles under all loading conditions. The changes progressed as the cumulative doxorubicin dose increased. Action potential duration was shorter in the doxorubicin treated groups (APD50 = 76 v 62 ms for controls, p less than 0.01), although resting action potential amplitude was normal. Tension-frequency response (6-36 stimuli.min-1) and response to increasing calcium concentrations (2.54-6.32 mM) were attenuated in the doxorubicin group. Percent change in tension and dT/dt in response to noradrenaline (50 microM), isoprenaline (20 microM), or dibutyryl cyclic AMP (40 mM), was increased in the doxorubicin group v controls (300-600% v 100-200% respectively), despite chronic increase in circulating catecholamines, depletion of myocardial catecholamines, and no change in beta adrenergic receptor number or affinity. The apparent increase in beta adrenergic responsiveness in the doxorubicin group may have been partly due to decreased basal cyclic AMP production (13 v 31 pMol.mg-1 protein.min-1, p less than 0.01), although maximum catecholamine stimulated cyclic AMP production was only mildly decreased (251 v 315 pMol.mg-1 protein.min-1, p less than 0.05). CONCLUSIONS - The subacute effects of chronic doxorubicin become progressively more marked as the cumulative dose increases, and there are significant differences in the myocardial characteristics between this chronic model and other models of heart failure. These differences may be related to the cytotoxic effects of doxorubicin on membranes and membrane bound enzymes.

Action Potentials↗
PubMed1989

Mechanical properties of papillary muscle in cardiac failure: importance of pathogenesis and of ventricle of origin.

In an attempt to better understand what causes impairment of failing myocardium, the mechanical characteristics of papillary muscles from three different models of congestive heart failure were compared at varying stages of hypertrophy and failure: adriamycin cardiotoxic rabbit, cardiomyopathic hamster and infra-renal aorto-caval shunted dog. Except for right ventricular muscles from the shunted dogs, in all groups there was a significant decrease in total twitch tension, +dT/dt, -dT/dt, Vmax, +dL/dt, and -dL/dt. However, there were major differences in twitch duration between the three models with time to attain peak tension and peak shortening and time to attain half tension decline decreasing in right ventricular papillary muscles from adriamycin rabbits but increasing in right ventricular papillary muscles from shunted dogs and no change occurring in left ventricular papillary muscles from cardiomyopathic hamsters or shunted dogs. Load dependence as assessed by time to relaxation index for 30% afterload contractions was decreased in all but right ventricular muscles from shunted dogs. These results indicate that despite some common characteristics, major differences exist between papillary muscles from different models of congestive heart failure depending on the pathophysiological process involved and the ventricle of origin.

Animals↗
PubMed1988

Effects of flurazepam on sleep, arousal threshold, and the perception of being asleep.

This study examined the effects of flurazepam on arousal threshold and on quality of sleep during nights in which arousal threshold studies were performed. Ten patients with subjective insomnia received 30 mg flurazepam or placebo on nights in which arousal thresholds in response to electronic tones or a recording of the subjects' names were determined. Arousal thresholds differed across waking and sleep stages, but there was less difference in response to the subjects' names than to electronic tones. Flurazepam raised arousal thresholds to both stimuli, but did not selectively influence response in any individual sleep stage. Flurazepam did not alter subjects' estimates of elapsed time or duration of sleep between tests.

Adult↗
PubMed1985

Acquired immunodeficiency syndrome in New York City. Evaluation of an active surveillance system.

In January 1983, the New York City Department of Health initiated an active surveillance program for acquired immunodeficiency syndrome (AIDS) in 19 hospitals and a modified-active surveillance program in the remaining 69 hospitals. We reviewed hospital laboratory and autopsy records in 12 active surveillance hospitals and three modified-active surveillance hospitals six months later. Patients who had opportunistic diseases characteristic of AIDS diagnosed in 1982 (before active surveillance) and 1983 (after implementation of active surveillance) were matched against health department AIDS surveillance reports. For the 16 months we evaluated, 96% of patients identified with AIDS in the 12 active surveillance hospitals and 100% of those in the three modified-active surveillance hospitals had been reported to the health department. The delay between diagnosing a case and reporting it to the health department significantly decreased between 1981 and the first six months of 1983 in all hospitals. The proportion of cases reported within one month of diagnosis increased from 45% to 69% during this period. We conclude that the current surveillance program for AIDS in New York City is effective and that case reporting is sufficiently complete for accurate analysis of disease trends.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Simultaneous labelling of basal lamina components and acetylcholinesterase at the neuromuscular junction.

A double labelling technique has been developed which permits the concomitant localization of basal lamina constituents together with acetylcholinesterase in mouse skeletal muscles. First, using the protein A-gold technique, type IV collagen and laminin were revealed on basal laminae ensheathing skeletal muscle fibres. The immunolabelling for both proteins was higher in synaptic than extrasynaptic regions. At synaptic sites the anti-type IV collagen immunolabelling exhibited an asymmetry; it was more intense on the portion of basal lamina closest to the postsynaptic membrane, whereas the anti-laminin immunolabelling was more uniformly distributed. It was also observed that the laminin immunoreactivity associated with Schwann and perineural cells was higher than that of skeletal muscle fibres. Secondly, the two basal lamina antigens were revealed simultaneously with another synaptic protein, acetylcholinesterase, using a refined cytochemical technique prior to the immunolabelling. The cytochemical reaction, which facilitates the location of endplates, did not alter the immunolabelling pattern. This double labelling procedure permits ready comparison of the distributions of type IV collagen and laminin with that of acetylcholinesterase, and may prove to be a useful approach in studies on synaptic components in developing and diseased muscle.

Acetylcholinesterase↗
PubMed1984

Abuse of a fire-extinguishing agent and sudden death in adolescents.

Two cases of abuse of bromochlorodifluoromethane (BCF - a fire-extinguishing agent) by inhalation are reported. In the first case, a 15-year-old youth presented in ventricular fibrillation; the second youth was dead on arrival at hospital. Port-mortem toxicological investigations confirmed BCF inhalation in the latter patient. Management of the surviving patient included cardioversion, controlled mandatory hyperventilation, intravenous infusions of mannitol, and barbiturate protection against cerebral ischaemia. He had completely recovered after eight days. Community agencies report that BCF inhalation occurs frequently on the Gold Coast, Queensland. This behaviour can be associated with sudden death from ventricular arrhythmias after cardiac sensitization to endogenous adrenaline. The "lone sniffer" is at greatest risk, and identification of such individuals may prevent a fatal outcome.

Adolescent↗
PubMed1984

The ontogeny of seizures induced by leucine-enkephalin and beta-endorphin.

Rats ranging in postnatal age from 6 hours to 28 days were implanted with cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. We then administered varying amounts of the opiate peptides leucine-enkephalin and beta-endorphin intracerebroventricularly with continuous electroencephalographic monitoring. Leucine-enkephalin produced electrical seizure activity in rats as young as 2 days. beta-Endorphin administration was associated with seizures at the fifth postnatal day, with a high incidence of apnea resulting in death in animals as young as 6 hours. An adult seizure response to beta-endorphin and leucine-enkephalin was seen at 15 and 28 days of age, respectively. Naloxone blocked the seizure produced by these opiate peptides in all age groups. The data indicate that the opiate peptides are potent epileptogenic compounds in developing brain, that seizures induced by leucine-enkephalin differ from those caused by beta-endorphin, and that petit mal-like seizure activity can be an adult response in the rodent.

Aging↗
PubMed1983

Dedifferentiation of a transplantable papillary thyroid carcinoma over a 15-year period.

Fischer 344 rats on a prolonged low-iodine diet developed thyroid nodules which were transplanted subcutaneously into 33 thyroidectomized rats. One graft took and gave a papillary carcinoma. Serially transplanted syngeneically at 3- to 4-month intervals, it became autonomous in third generation hosts. With electron microscopy examination it was microfollicular in year 8 and anaplastic, with totally unpolarized epithelial cells, in year 15. Basement membrane present in year 1 was no longer visible in specimens of years 8 and 15. Tight and gap junctions still present in year 8 were absent in year 15, although a few desmosomes persisted. From years 8 to 15, free ribosomes and microfilaments became more frequent, whereas the number of mitochondria and the development of the Golgi complex declined.

Animals↗
PubMed1983

Recognition and regulation of progenitor marrow elements by NK cells in the mouse.

The cytotoxicity of radiolabelled YAC-1 target cells by natural killer (NK) cells from the spleens of immunocompetent CBA mice is inhibited by unlabelled YAC-1 competitor cells, but not by resting bone marrow from syngeneic or allogeneic adult mice. Rapidly proliferating haemopoietic cells recovered from the spleens of lethally irradiated, bone marrow-reconstituted CBA mice, however, compete strongly in the NK assay. The competitive ability of early regenerating marrow correlates with the presence of an increased percentage of morphologically immature cells of mixed lineages. Competition declines in reconstituted spleens recovered more than 10 days after engraftment, as the proportion of immature elements falls towards that of resting marrow. Although the numbers of unlabelled YAC-1 cells required to produce equivalent competition of unstimulated and interferon-activated NK killing are similar, 10 times fewer regenerating marrow competitors compete cytotoxicity by unstimulated NK effectors to the same degree as interferon activated cells. The numbers of granulocyte-macrophage colonies formed in soft agar by regenerating marrow is also influenced by prior incubation of the marrow cells with NK effector populations. Spleen cells from homozygous athymic mice produce the same effect as cells from their heterozygous littermates. These data suggest that NK cells recognize and regulate the differentiation of progenitor elements within the marrow.

Animals↗
PubMed1982

Acetylcholinesterase content in both motor nerve and muscle is correlated with twitch properties.

The activity and molecular forms of acetylcholinesterase (AChE) were studied in the rat soleus muscle and its nerve, as compared to their fast-twitch counterparts. The soleus muscle and its nerve exhibited both significantly lower AChE activity and less of the G4 (10S) molecular form. In addition, the soleus muscle displayed a specific increase in the A8 (13S) and A4 (8.8S) asymmetric forms, not seen in any of the fast-twitch muscles examined. These results indicate that the AChE content of a muscle and its nerve are linked and depend on the twitch properties, and that the slow-twitch muscle is characterized by a specific set of AChE molecular forms.

Acetylcholinesterase↗
PubMed1981

Enhanced noradrenaline response in cardiomyopathic hamsters: possible relation to changes in adrenoceptors studied by radioligand binding.

To assess the possible relation between catecholamine responses and adrenoceptor affinity and density, we compared the effect of noradrenaline, isoprenaline and ouabain on the right ventricular muscle strips from normal and cardiomyopathic hamsters with alpha 1- and beta-adrenoceptor characteristics assessed by radioligand binding methods. At concentrations of 1.28, 2.56, 5.0 and 10 x 10 (-6) mol . litre (-1) noradrenaline raised isometric tension by 27 +/- 4, 39 +/- 5, 52 +/- 5 and 61 +/-6% in normal animals (n = 6). Corresponding increase of 65 +/- 8, 92 +/- 8, 109 +/- 9 and 115 +/- 10% occurred in cardiomyopathic hamsters (n=11, all P less than 0.02). The responses to isoprenaline (Emax =82%) and ouabain did not differ between the two groups of hamsters. [3H]-prazosin, a new radioligand, and [-3H]-dihydroalprenolol were used to assess alpha 1- and beta-adrenoceptors in cardiac membranes. By Scatchard analysis, the KD values for both ligands did not differ between normal and cardiomyopathic hamsters, but the maximum number of binding sites was higher in the myopathic group: 5.5 vs 3.9 fmol . mg [-1] protein for [3H]-prazosin and 27 vs 20 fmol . mg [-1] protein for [-3H]-dihydroalprenolol (both P less than 0.05). Histochemically, oxidative and glycolytic activity were normal but lysosomal acid phosphatase was high. Possible explanations for the raise response to noradrenaline in cardiomyopathic hamster include and increased concentration of noradrenaline in the synaptic cleft due to defective neuronal uptake and / or stimulation of an augmented population of alpha 1-(postsynaptic) adrenoceptors.

Animals↗