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Biomedical subjects

J Harkness

Publications and source records attributed to J Harkness.

10 recordsLinked to original sources

Gastrointestinal viral infections in homosexual men who were symptomatic and seropositive for human immunodeficiency virus.

Gastrointestinal viruses, predominantly rotaviruses and adenoviruses, were detected by enzyme-linked immunosorbent assay, electron microscopy, or cell culture in greater than 50% of two groups of homosexual men with symptomatic human immunodeficiency virus (HIV) infection, who did (54%) or did not (50%) have diarrhea. Lower detection rates were observed in HIV-seronegative (15%) and asymptomatic HIV-seropositive (16%) men. In the patients with diarrhea, 95% of the isolates of virus were found in the most immunosuppressed patients, those patients with AIDS-related complex or opportunistic infections associated with AIDS. High excretion rates of these viruses are probably associated with both anal-oral transmission and immunosuppression. These viruses apparently cause acute episodes or relapses of diarrhea in some patients but may be co-pathogens or noncontributory to chronic diarrhea in others.

AIDS-Related Complex

Antibodies to a synthetic peptide can be used to distinguish between muscarinic acetylcholine receptor binding sites in brain and heart.

Since the reports elucidating the sequence of four subtypes of muscarinic cholinergic receptors appeared, it has been clear that pharmacological approaches to the study of subtypes of these receptors are inadequate to selectively detect one subtype in the presence of the others. One methodology that can provide more selective reagents with which to study these subtypes is immunology. Thus, using the information on the primary sequence of these receptors available in the literature, rabbits were injected with an oligopeptide, CRKIPKRPGSVHRTPSRQ, conjugated to keyhole limpet hemocyanin. This oligopeptide (m1 C-terminal peptide) corresponds to the 17-amino acid sequence of the carboxyl terminus of a rat m1 muscarinic receptor. This portion of the amino acid sequence of the muscarinic receptor protein has been shown to be unique to the m1 receptor and has not been found in the other subtypes of the receptor thus far sequenced. The antisera (anti-m1 antisera) had high titer against the m1 C-terminal peptide in a solid phase radioimmunoassay. The anti-m1 antisera were shown to immunoprecipitate [3H] quinuclidinyl benzilate ([ 3H]QNB) binding activity solubilized from rat forebrain. [3H]Pirenzepine ([ 3H]PZ) has been shown to interact with a subset of [3H]QNB binding sites in forebrain and heart. The anti-m1 antisera were shown to immunoprecipitate [3H]PZ binding sites in cerebral cortex, hippocampus, and corpus striatum, areas believed to be rich in the m1 subtype of the muscarinic receptor. Although [3H]PZ binding activity was present in receptor preparations solubilized from heart, neither [3H]PZ- nor [3H]QNB-binding activities could be immunoprecipitated from this tissue using the anti-m1 antisera. A monoclonal antibody raised against the porcine atrial muscarinic receptor was shown to immunoprecipitate both [3H]PZ- and [3H]QNB-binding activities solubilized from rat heart, but only [3H]QNB-binding activity could be immunoprecipitated from forebrain using this antibody. Immunoprecipitation of [3H]PZ- and [3H]QNB-binding activity by anti-m1 antisera could be inhibited by the m1 C-terminal peptide. Peptides corresponding to the C-terminal portions of the rat m3 and m4 muscarinic receptor were not inhibitory in the immunoprecipitation assay. This study provides further evidence for subtypes of muscarinic receptors in rat tissues and supports the hypothesis that receptor subtypes defined using PZ can be further subclassified on the basis of differences in primary structure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Pulmonary manifestations of the acquired immunodeficiency syndrome.

Between 1983 and 1985, 71 patients with the acquired immunodeficiency syndrome (AIDS) were evaluated. Pulmonary manifestations were present in 42 patients (59%). Pneumocystis carinii pneumonia (PCP) was the most common pulmonary manifestation, present in 32 patients (45%). Other pulmonary findings were cytomegalovirus pneumonia (one patient), Candida pneumonia (one patient), cryptococcal pneumonia (one patient), bacterial pneumonia (three patients), nonspecific pneumonitis (three patients), Kaposi's sarcoma (one patient), and non-Hodgkin's lymphoma (one patient). The presenting features of PCP were reviewed and in seven patients the chest X-ray and blood gases were normal at the time of diagnosis of PCP. Bronchoscopy was a safe and useful technique for obtaining specimens for diagnosis promptly, and a combination of samples obtained by bronchial washings/brushings and transbronchial biopsy was found to give a higher diagnostic yield than any single sample. Drug side-effects were common during therapy, requiring change of therapy in 16 patients. At one month after diagnosis 16% of patients with PCP had died. PCP is a common pulmonary manifestation in patients with AIDS which is treatable and has an initially favourable outcome.

Acquired Immunodeficiency Syndrome

Kinetic studies suggest that light-activated cyclic GMP phosphodiesterase is a complex with G-protein subunits.

Cyclic GMP phosphodiesterase (PDE) in rod disk membranes has three subunits of molecular weight 88 000 (alpha), 84 000 (beta), and 13 000 (gamma). Physiological activation of the enzyme by light is mediated by a GTP binding protein (G protein). The enzyme can also be activated by controlled digestion with trypsin, which destroys the gamma subunit, leaving the activated enzyme as PDE alpha beta [Hurley, J. B., & Stryer, L. (1982) J. Biol. Chem. 257, 11094-11099]. Addition of purified gamma subunit to PDE alpha beta inhibited the enzyme fully. This suggested the possibility that G protein could also activate PDE by removing the gamma subunit and leaving the active enzyme in the form of PDE alpha beta. Should this be true, the properties of light- and trypsin-activated enzymes should be comparable. We found this not to be the case. The Km of light-activated enzyme for cyclic GMP was about 0.9-1.4 mM while that of trypsin-activated enzyme was about 140 microM. The cyclic AMP Km was also different for the two enzymes: 6.7 mM for light-activated enzyme and 2.0 mM for trypsin-activated enzyme. The inhibition of both enzymes by the addition of purified gamma subunit also differed significantly. Trypsin-activated enzyme was fully inhibited by the addition of about 200 nM gamma, but light-activated enzyme could not be fully inhibited even with 2600 nM inhibitor subunit. The Ki of the trypsin-activated enzyme for gamma was 15 nM and of the light-activated enzyme 440 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases

Controlled comparison of short-wave diathermy treatment with osteopathic treatment in non-specific low back pain.

The effectiveness of spinal manipulation carried out by a non-medical qualified osteopath was compared with that of short-wave diathermy (SWD) and a placebo (detuned SWD) in 109 patients with low back pain. More than half the subjects in each of the 3 treatment groups benefited immediately from therapy. Significant improvements were observed in the 3 groups at the end of 2 weeks' treatment, and these were still apparent at 12 weeks. The outcome of treatment was unrelated to the initial severity or duration of pain or to the trend of pain towards deterioration or improvement. It is, therefore, unlikely that the results simply reflect the natural history of low back pain. Benefits obtained with osteopathy and SWD in this study may have been achieved through a placebo effect.

Adult

Plasma viscosity in the elderly.

Plasma viscosity has been measured by a standardised technique in an unselected series of elderly subjects. Results have been grouped according to the severity of clinical disease and are found to give a good statistical differentiation between most groups, although with a wide overlap. Repeated tests show only a fair correlation with the course of an individual patient's illness. These results are compared with those previously reported. In general, values are lower in elderly than in younger subjects with diesease of comparable clinical severity. "Normal' values are, however, slightly higher in the elderly. Further studies are planned to analyse apparently anomalous results in an attempt to determine more exactly the clinical value of plasma viscosity estimation in the elderly.

Aged

Why urinalysis?

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Cardiovascular Diseases