African tick-bite fever: a new spotted fever group rickettsiosis under an old name.
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Adult↗
Biomedical subjects
P Mason
Publications and source records attributed to P Mason.
Brainstem auditory evoked responses (BAERs) during the menstrual cycle in women with and without premenstrual syndrome.
Brainstem auditory evoked responses (BAERs) were recorded at three menstrual cycle phases (menstrual, late follicular, and late luteal) in a sample of healthy control women (n = 21) and in a sample of women (n = 30) diagnosed as suffering from Late Luteal Phase Dysphoric Disorder (LLPDD). The latter were divided on the basis of retrospective and prospective self-ratings into moderate (PMS+) and severe (PMS++) symptom groups. Results showed (1) no change in BAER latencies at different phases of the menstrual cycle; (2) increased BAER latencies for wave III in women with moderate PMS symptoms compared with healthy controls; (3) increased BAER latencies for waves III and V in women with severe PMS symptoms compared with healthy controls. These results raise the possibility of brainstem dysfunction in PMS women, and support the idea of a neurobiological predisposition to this order.
Adult↗
Rat procathepsin B. Proteolytic processing to the mature form in vitro.
Expression of rat procathepsin B in yeast led to the secretion of both the latent and mature forms of the enzyme. Culture in the presence of a cysteine proteinase inhibitor prevented this processing. We have expressed and purified a mutant form of rat procathepsin B whose active-site cysteine residue has been changed to a serine, and which also lacks the glycosylation site in the mature region of the protein. This non-active mutant protein was secreted essentially in an unprocessed form. The purified protein has been incubated with a variety of proteinases, and results indicate that cathepsins D and L, as well as mature cathepsin B itself, can produce a processed (single-chain) form of cathepsin B from this precursor. Amino-terminal sequencing of these processed forms has revealed that they are all elongated by a few residues with respect to the mature form found in vivo. The action of a combination of cathepsin B with dipeptidylpeptidase I produced a single-chain form of cathepsin B with the correct amino terminus. This work has also shown that the processing of procathepsin B to a single-chain form can be an autocatalytic process, in at least an intermolecular manner.
Amino Acid Sequence↗
Increases in soluble CD8 antigen in plasma, and CD8+ and CD8+CD38+ cells in human immunodeficiency virus type-1 infection.
Increases in plasma levels of soluble CD8 (SCD8) antigen and expansion of the CD8+ CD38+ lymphocyte compartment were early immunologic alterations frequently observed prior to detection of antibodies against human immunodeficiency virus type 1 (HIV-1) and diminution of CD4+ cells in subjects at risk to develop AIDS. These increases identified in the 49 seronegative homosexual men were manifest in all 164 homosexual subjects and 45 intravenous drug users (IVDU) positive for HIV-1 antibodies (HIV-1+), 19 patients with ARC, and 29 AIDS patients. Augmentation of plasma sCD8 antigen correlated with increases in both CD8+ and CD8+ CD38+ cells in HIV-1(-) homosexual men (r = 0.35, P less than 0.013; r = 0.48, P less than 0.0005; respectively) and the 258 HIV-1+ subjects (r = 0.25, P less than 0.0003; r = 0.33, P less than 0.0001, respectively). In vitro examination of unstimulated peripheral blood lymphocytes from HIV-1+ homosexuals and IVDU confirmed the fivefold higher constitutive levels of cellular release of sCD8 antigen in these subjects compared to heterosexual controls. Inclusion of radiolabeled amino acids during the 3-day culture period in the presence or absence of phytohemagglutinin resulted in negligible levels of radioactivity associated with the sCD8 antigen indicative of a lack of de novo synthesis. Throughout clinical progression to AIDS, sCD8 antigen levels continued to escalate relative to the numbers of CD8+ cells bearing CD38+ antigen. The data confirm the interrelationship between sCD8+ antigen and CD8+ and CD8+ CD38+ cells.
ADP-ribosyl Cyclase↗
Contingent negative variation as an indicator of sexual object preference: revisited.
This study attempted to replicate the finding of Costell et al. (1972) that contingent negative variation (CNV) in anticipation of opposite sex nudes is of greater amplitude than CNV in anticipation of same sex nudes. In order to control for variation in level of attention, which may have accounted for the result of Costell et al., a 'match/mismatch' CNV paradigm was used in which S2 was either identical to S1 or differed from it. Subjects (n = 6 males) were required to indicate a same/different judgement by button pressing at S2 offset. CNV in anticipation of opposite sex nudes was of significantly greater amplitude than CNV in anticipation of same sex nudes, confirming the finding of Costell et al. This offers encouragement for the application of CNV to the assessment of sexual object preference in sex offenders.
Adult↗
The molecular basis of glucose-6-phosphate dehydrogenase deficiency.
With more than 300 different variants reported, the human enzyme glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is one of the most polymorphic proteins known. An estimated 400 million people throughout the world are deficient in G6PD; numerous lines of evidence indicate that this is because female heterozygotes have a selective advantage in malaria infections. The cloning of the G6PD gene has made it possible to clarify the molecular basis underlying this enzyme deficiency and polymorphism.
Amino Acid Sequence↗
Molecular basis of chronic non-spherocytic haemolytic anaemia: a new G6PD variant (393 Arg----His) with abnormal KmG6P and marked in vivo instability.
More than 80 genetic variants of glucose-6-phosphate dehydrogenase (G6PD) are associated with chronic non-spherocytic haemolytic anaemia (CNSHA). In order to help clarify the molecular basis of this association, we have carried out a detailed biochemical and genetic characterization of two G6PD deficient brothers affected by CNSHA. The G6PD from the two patients has altered electrophoretic mobility, abnormally elevated Michaelis constant (Km) for G6P, and extreme instability in vivo and in vitro. By comparison with published information we found that this is a new G6PD variant which we have designated G6PD Portici. The entire coding region of the gene has been sequenced, and a single point mutation, a G----A transition, was found at position 1178 in exon X, causing a substitution of histidine for arginine at residue 393 in the polypeptide chain. By polymerase chain reaction (PCR) amplification followed by diagnostic restriction enzyme analysis and allele-specific oligonucleotide hybridization we have demonstrated the inheritance of this mutation in the patient's family. Our results support the notion of a causative link between this mutation in the G6PD gene and CNSHA. Our data, in combination with previous data in the literature, suggest that the three-dimensional structure of G6PD is such as to cause interaction in the binding of its two substrates, G6P and NADP.
Adolescent↗
Prospective endoscopic study of duodenal ulcer in Zimbabwean Blacks.
One thousand seven hundred and fourteen Black Zimbabwean patients underwent upper gastrointestinal endoscopy. Demographic details of the patients were analysed. A randomly chosen cohort of 50 patients with duodenal ulceration was compared to age and sex matched controls regarding lifestyle and H. pylori infection. Five hundred and sixteen patients had active duodenal ulcers, giving a crude prevalence rate of ulceration of 456 per 100,000 new hospital cases. There is a difference from the disease in Western countries in several respects. The incidence appears to be increasing in Zimbabwe. There was no significant difference between ulcer patients and controls in their association with alcohol consumption, cigarette smoking, urban residence and salicylate ingestion (p > 0.1), Ulceration was most strongly associated with H pylori gastritis compared to control (p < 0.001). Duodenal ulceration was most prevalent in the 21 to 30 year age group. The overall male to female ratio was 4.7:1. A significant proportion of patients had persistence of ulceration after a standard course of Cimetidine. Pain did not always correlate with presence or absence of ulcers.
Adolescent↗
Regulation of insulin-like growth factor 1 gene expression in skeletal muscle.
Insulin-like growth factor 1 (IGF-1) is implicated in the growth processes of many tissues in the adult animal. This hormone can act in an endocrine manner or can be produced in the specific tissues in response to growth promoting stimuli to act in an autocrine/paracrine manner. We have examined, in the rat, changes in serum concentrations of IGF-1 and muscle IGF-1 mRNA levels in several studies in which muscle growth has been significantly altered. In the first study we examined the interactions of growth hormone (GH) and under-nutrition upon muscle growth. We observed that when GH was administered to hypophysectomised rats the anabolic effect of this hormone was independent of dietary intake. In a similar manner muscle IGF-1 mRNA levels were also elevated by GH but unaffected by food intake. In contrast serum IGF-1 levels were markedly reduced by under-nutrition. These data suggested that the anabolic action of GH on muscle could be mediated through the autocrine/paracrine action of the IGF-1 hormone. Similarly we observed in other studies that muscle hypertrophic stimuli of work-overload and passive stretch are associated with significantly increased muscle IGF-1 mRNA levels. In contrast insulin dramatically affected muscle protein synthesis rates but had no measurable effect upon muscle IGF-1 mRNA levels, which suggests that the anabolic action of this hormone is not mediated through the autocrine/paracrine action of IGF-1. These studies suggest that IGF-1 may mediate growth in muscle in response to variety of stimuli by autocrine/paracrine action or in response to certain stimuli possibly by endocrine action.
Animals↗
Neurocysticercosis: experience with diagnosis by ELISA serology and computerised tomography in Zimbabwe.
Over a three-year period, 646 sera from 630 patients with signs and symptoms compatible with neurocysticercosis were investigated for antibodies to cysticercal antigens using an ELISA test. Overall, 12 pc specimens were positive. The sensitivity of the ELISA, when compared with a limited number of computerised tomography investigations, was over 70 pc. False negative serology was associated with HIV infection in some patients. The positive predictive value was 87 pc and the negative predictive value was 85 pc when patients with active infection, potentially amenable to chemotherapy, were considered. The specificity, determined from serological tests of patients with a variety of trematode, cestode and other infections, was over 90 pc. Three of 11 patients with intestinal taeniasis, and each of two patients with hydatid disease were seropositive. The results suggest the value of ELISA serology as a more cost-effective diagnostic method for all patients with suspected cysticercosis.
Adult↗
A confocal laser microscopic study of enkephalin-immunoreactive appositions onto physiologically identified neurons in the rostral ventromedial medulla.
Neurons in the rostral ventromedial medulla (RVM) are important in the opioid modulation of dorsal horn nociceptive transmission. Systemically administered morphine inhibits one class of RVM cells, the on-cells; excites a second class of RVM cells, the off-cells; and has no effect on a third class, neutral cells. In contrast, iontophoretic application of morphine inhibits on-cells but does not alter the activity of either off- or neutral cells. The present study addresses whether the differential sensitivity to exogenous opioids is correlated with a differential termination pattern onto the three classes of RVM neurons by afferents containing endogenous opioids. Intracellular recordings were made from RVM neurons in rats under light halothane anesthesia. Physiologically characterized neurons were injected with Neurobiotin and then subsequently visualized with a Texas red fluorophore. Thick (50 microns) sections containing labeled RVM cells were processed for enkephalin immunoreactivity (ENK-IR) using an FITC fluorophore and then optically sectioned at 1.5 micron intervals using a dual-channel confocal laser scanning microscope. ENK-IR appositions were found on the somata and dendrites of all on-cells. Although ENK-IR varicosities were also apparently apposed to off- and neutral cells, the density of such appositions was significantly less than the density of ENK-IR appositions onto on-cells. The greater overall density of ENK-IR appositions onto on-cells was apparently due to a concentration of appositions on the soma and proximal dendrites of these neurons. These results support a model of RVM function in which endogenous opioid peptides produce an antinociceptive action by a direct inhibitory action on on-cells that facilitate nociceptive transmission. This on-cell inhibition may produce an additional antinociceptive effect by removing a possible on-cell inhibition of off-cells, which are thought to inhibit nociceptive transmission.
Animals↗
Implantable cardioverter defibrillator: a review.
Sudden cardiac death claims 400,000 to 450,000 lives annually. It is believed that sudden cardiac death results predominantly from ventricular fibrillation or sustained ventricular tachycardia that deteriorates into ventricular fibrillation. Conventional treatments for patients who suffer from ventricular arrhythmias have been limited to antiarrhythmic drugs or surgery. These treatments have proved ineffective to a portion of arrhythmia sufferers. The implantable cardioverter defibrillator offers hope to a segment of ventricular arrhythmia sufferers whose disease is resistant to conventional therapies.
Electric Countershock↗
Deficiency in red blood cells.
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Amino Acid Sequence↗
Quantitative neurologic and neurobehavioral testing of persons infected with human immunodeficiency virus type 1.
Assessment of neurobehavioral and peripheral neurologic performance among homosexual men was made on two occasions, using a computer-administered neurobehavioral instrument and quantitative vibration threshold testing, respectively. Persons studied included high-risk human immunodeficiency virus (HIV)-negative men (n = 13), asymptomatic HIV-positive men (n = 30), and patients with acquired immunodeficiency syndrome (AIDS)-related complex of AIDS (n = 17). In addition, subjects were characterized immunologically at the time of neurologic and neuropsychologic assessment via determination of circulating lymphocyte counts (total lymphocytes, helper T cells, suppressor T cells, total T cells, activated T cells) and markers of HIV type 1 (HIV-1) infection. At the first cycle of testing, the results of asymptomatic HIV-positive men were indistinguishable from those of HIV-negative men, while persons with AIDS-related complex or AIDS tended to have lower mean performance. These differences did not achieve statistical significance on any single test, but the group with AIDS-related complex or AIDS had the worst mean performance on 12 of 13 individual performance tests. Thirty-seven men underwent repeated testing after a mean interval of approximately 4.5 months. There was little change in mean neurobehavioral performance and vibratory thresholds among all three groups. Measures of neurobehavioral performance and vibrotactile thresholds were not correlated with measures of immunological status. These results are consistent with the concept that asymptomatic infection with HIV-1 does not imply the presence of measurable or significant neurologic or neurobehavioral impairment.
AIDS-Related Complex↗
Effect of a single oral dose of metrifonate on human plasma cholinesterase levels.
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Administration, Oral↗
Neurotransmitters in nociceptive modulatory circuits.
Significant advances have been made in our understanding of nociceptive modulation from RVM. Among the most useful conceptually has been the discovery that there are two classes of modulatory neurons in the RVM that are likely to have opposing actions on nociception: on-cells, which may facilitate nociceptive transmission, and off-cells, which probably have a net inhibitory effect on nociception. The similarity in response properties among the members of each class, their large, somatic "receptive fields," and the wide distribution of the terminal fields of axons of individual neurons to the trigeminal sensory complex and to multiple spinal segments indicate that these neurons exert a global influence over nociceptive responsiveness. Drug microinjections into the RVM presumably shift the balance between states of on- or off-cell firing and also produce measurable changes in the threshold for nocifensor reflexes. The meaningful unit of function in the RVM nociceptive modulatory system therefore probably consists of large ensembles of physiologically and pharmacologically similar neurons. The strong coordination of activity of the two classes of RVM neuron may depend largely upon intranuclear projections from RVM off-cells that excite other off-cells and inhibit on-cells. The off-cell pause is GABA-mediated, and it is likely that there is a subset of GABA-containing RVM on-cells that directly inhibit off-cells. Furthermore, the available evidence indicates that exogenous opiates activate off-cells by inhibiting GABAergic release. Presumably, enkephalinergic cells in the RVM disinhibit off-cells in a similar way. Although non-serotonin-containing off-cells certainly exist, we propose that some off-cells contain serotonin. Other possible connections are based on more limited data; however, ACh, neurotensin, NE, and EAAs are present in neurons that project to the RVM, and each of these compounds, when microinjected into the RVM, has a modulating effect on nociceptive transmission. The local circuits in the RVM that underlie these actions remain to be elucidated. At the level of the dorsal horn, there is good evidence for each of three inhibitory mechanisms: direct inhibition of nociceptive projection neurons, inhibition of excitatory relay interneurons, and excitation of an inhibitory interneuron. The relative contribution made by each of these circuits is unknown.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Influence of HIV on lower genital tract neoplasia.
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Acquired Immunodeficiency Syndrome↗
In vitro use of Schwann cells to elucidate neurotoxic injury.
Schwann cells are responsible for the maintenance of the peripheral myelin sheath and neurotoxic insult directed against these cells can result in demyelination with a concomitant loss of neural function. We have utilized several in vitro techniques to investigate the effects of neurotoxins on the complex interactions between SC and axons. SC may be isolated from fresh neonatal sciatic nerves and used to examine the effect of neurotoxins on the axonal membrane induction of SC proliferation and specific myelin protein mRNA expression. We have recently devised a method to obtain SC from frozen sciatic nerves. This method allows pooling of neonatal nerves to generate enough cells for subsequent study. We have also transfected primary Schwann cells with a plasmid containing the large T antigen to obtain a SC line suitable for neurotoxicology studies. The functional status of cultured SC may also be studied via expression of SC specific antigens such as glial fibrillary acidic protein, CNPase, S100, laminin, P0 and myelin basic protein. We also propose culturing SC with dorsal root ganglion neurons to investigate the effect of neurotoxins on all stages of SC maturation, from proliferation to the in vitro synthesis of a compact myelin sheath. These strategies will allow us to investigate the cellular mechanisms of neurotoxicity in the PNS.
Animals↗