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Biomedical subjects

P Foley

Publications and source records attributed to P Foley.

18 recordsLinked to original sources

Neuropeptide content of purified rat brain cholinergic synaptosome subpopulations.

Cholinergic synaptosomes from rat cerebral cortex were isolated by a magnetic immunoaffinity technique, i.e. immunomagnetophoresis. This subpopulation was extracted and subjected to radioimmunoassay for 4 neuropeptides:neuropeptide Y (NPY); vasoactive intestinal peptide (VIP); substance P (SP); and somatostatin (SRIF). Three of the 4 neuropeptides were enriched in the sorted fraction compared with the mother fraction with respect to the cytosolic marker lactate dehydrogenase (LDH). The most enriched neuropeptide was NPY followed by SP and VIP. Somatostatin was not enriched in the cholinergic synaptosome subpopulation. The presence of NPY has not previously been reported in cortical cholinergic neurones.

Animals

The presence of neuropeptides in GABAergic and cholinergic rat cerebrocortical synaptosome sub-populations.

GABAergic and cholinergic synaptosomes from rat cerebral cortex were isolated by a magnetic immunoaffinity technique, i.e. immunomagnetophoresis. These subpopulations were extracted and subjected to radioimmunoassay for four neuropeptides: Neuropeptide Y (NPY); vasoactive intestinal peptide (VIP); substance P (SP); and somatostatin (SRIF). In each of the sub-populations three of the four peptides were enriched in the sorted fraction compared with the mother fraction with respect to the cytosolic marker lactate dehydrogenase (LDH). In the GABAergic sub-population the order was SP > SRIF > NPY > or = VIP whilst in the cholinergic sub-population they were enriched in the order VIP > or = NPY > SP > SRIF. The presence of NPY has not previously been reported in cortical cholinergic neurons.

Animals

HIV infection of monocytes inhibits the T-lymphocyte proliferative response to recall antigens, via production of eicosanoids.

Human monocytes infected in vitro with human immunodeficiency virus (HIV) soon after adherence to plastic substrate demonstrated a significantly decreased ability to restimulate autologous immune T-lymphocyte proliferation after exposure to soluble (tetanus toxoid) and particulate [herpes simplex virus (HSV)] antigen. Incubation with the cyclo-oxygenase inhibitor, indomethacin (2-5 microM), prevented inhibition of antigen-stimulated lymphocyte proliferation. The inhibitory activity was identified in ultrafiltrates containing the low molecular weight fraction (less than 3000 MW) of supernatants from HIV-infected monocyte cultures. This activity was significantly and markedly reduced in similar ultrafiltrates prepared from indomethacin-treated cultures. Increased concentrations of prostaglandin E2 (PGE2) were detected in ultrafiltrates from HIV-infected monocyte cultures compared with uninfected cultures and cultures preincubated with indomethacin. Ultrafiltrates were inhibitory when added during the presentation of antigen to T lymphocytes but not when removed from monocyte cultures prior to the addition of lymphocytes. In addition, ultrafiltrates inhibited antigen-stimulated lymphocyte proliferation and PHA-induced lymphocyte proliferation to the same extent. These data indicate that cyclo-oxygenase products of arachidonic acid, including PGE2, are produced in excess by HIV-infected monocytes and that PGE2 and perhaps other cyclo-oxygenase products are implicated in the inhibition of antigen-stimulated lymphocyte proliferation via a direct effect on T lymphocytes.

Cell Division

The role of childhood exposure to sunlight in the development of solar keratoses and non-melanocytic skin cancer.

The age-standardized proportion of persons with solar keratoses in 1232 Australian-born persons who were aged 40 years and older was 44.5% compared with a proportion of 15.7% in 1332 British persons who had migrated to Australia at various ages. Stratification of the British migrants into those who had arrived in Australia between one and 20 years of age and those who had arrived in Australia after the age of 20 years revealed that the proportion of persons with solar keratoses in the latter group never reached the proportion in Australian-born persons of the same age, in spite of many years in Australia after migration. Those persons who arrived in Australia between one and 20 years of age showed a lower proportion with solar keratoses in the younger age-groups, but with increasing age the proportion with solar keratoses equalled or exceeded that which was seen in Australians. These results suggest that a reduction in exposure to sunlight in childhood will reduce substantially the incidence of solar keratoses, and by implication, squamous-cell carcinomas, in adulthood.

Adult

The neurological sequelae of mononucleosis.

A 37-year-old white woman presented with bilateral symmetrical ascending motor weakness. Subsequent evaluation revealed she was suffering from infectious mononucleosis. This case demonstrates that one should consider mononucleosis when presented with an idiopathic disease of the nervous system. The classic features of mononucleosis, such as pharyngitis, lymphadenopathy or splenomegaly, need not be present.

Adult

Glutaminase inhibition and the release of neurotransmitter glutamate from synaptosomes.

Cerebrocortical synaptosomes were incubated with glutamine together with 6-diazo-5-oxo-L-norleucine (DON) and NH4Cl (which are known to inhibit phosphate-stimulated glutaminase) in order to assess the effect of such inhibition on the pool sizes and extent of evoked release of endogenous amino acids, particularly glutamate. DON (5 mM) inhibited glutaminase by 73-89% and NH4Cl (1-4 mM) inhibited the enzyme by 45-53% under the conditions employed. NH4Cl (4 mM) incubated with synaptosomes for 30 min reduced pool sizes of aspartate and glutamate by 28% and inhibited release of glutamate by 55% compared to control release. DON caused a decrease in both the pool size of glutamate (22%) and the extent of veratrine-evoked release of amino acids (21%).

Ammonium Chloride

Antibodies in serum of patients with Alzheimer's disease cause immunolysis of cholinergic nerve terminals from the rat cerebral cortex.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged

Variations in CD4 expression by human monocytes and macrophages and their relationships to infection with the human immunodeficiency virus.

The expression of CD4 antigen on the surface of LeuM3-positive human blood monocytes was found to be variable with 65 to 90% of cells from 46 normal human volunteers being positive by dual staining flow cytometry. When monocytes adhered to plastic (but not when cultured on Teflon), a marked decrease in CD4 expression was observed between 1 and 24 h post-adherence. CD4 expression could not be detected in macrophages adhered to plastic for 5 days by using four anti-CD4 monoclonal antibodies in flow cytometry or direct immunofluorescence. Conversely an increasing proportion of adherent cells expressed LeuM3 and OKM5 surface antigens over the 5 days. CD4 mRNA levels were measured by slot-blot and Northern hybridization, and total cellular CD4 protein levels by immunoprecipitation. Both cellular mRNA and CD4 levels remained constant throughout the 5 day period but membrane CD4 protein levels were greatly reduced indicating that the down-regulation of CD4 was post-translational. Infection with two of six fresh human immunodeficiency virus (HIV) isolates showed different kinetic patterns when tested on purified monocytes recently adhered to plastic and macrophages adherent for 5 days. HIV antigen and reverse transcriptase levels in infected monocyte cultures remained high for 3 to 4 weeks before detachment and necrosis of the cells occurred. Infection of macrophages generated much lower levels of antigen and reverse transcriptase which declined to very low or undetectable levels over 2 weeks, leaving persisting viable macrophages. One week after infection HIV nucleic acid was detected in 69 +/- 7% of monocytes and 6 +/- 3% of macrophages by in situ hybridization. Blocking experiments with anti-Leu3a monoclonal antibody suggested that HIV infection of 5 day adherent macrophages occurred mainly by a mechanism other than binding to CD4.

CD4 Antigens

Mode of inheritance of Perthes' disease in Manchester terriers.

A test mating between two Manchester Terriers affected by Perthes' disease (PD) resulted in the birth of three affected males and two unaffected females. In the three puppies with PD, roentgenographically detectable changes in the affected femurs were observed two to three weeks before the onset of lameness and muscle atrophy in the corresponding limb. Analysis of the related pedigrees and of the results of the test mating indicated that PD is an inherited condition with high heritability.

Animals

Incidence of non-melanocytic skin cancer treated in Australia.

In 1985, as part of a national random household omnibus survey by a market research company, 30,976 Australians (mostly of European origin) were asked whether they had ever been treated by a doctor for skin cancer. The treating doctor or hospital was then approached for confirmation of the diagnosis of all those people who claimed to have been so treated within the past 12 months. Demographic data were also collected, permitting analysis by age, sex, country of birth, current residence, and skin reaction to strong sunlight. Melanomas accounted for less than 5% of the tumours treated. The world standardised incidence of melanoma was 19/100,000 population. The standardised incidence of treated non-melanocytic skin cancer in Australia was estimated to be 823/100,000. The standardised rates for basal cell carcinoma and squamous cell carcinoma were 657 and 166/100,000 respectively, yielding a standardised rate ratio of about 4:1. Standardised rates based on medically confirmed cases only were 555, 443, and 112/100,000 for all non-melanocytic skin cancers, basal cell carcinomas, and squamous cell carcinomas respectively. Significant differences and trends in incidence were noted with respect to age and sex. Rates in men were higher than those in women but significantly so only after the age of 60. People born in Australia had a rate of 936/100,000 compared with 402/100,000 in British migrants. Rates for non-melanocytic skin cancer showed a gradient with respect to latitude within Australia. The rate in people residing north of 29 degrees S was 1242/100,000 compared with a rate of 489/100,000 in those living south of 37 degrees S. A person's skin reaction to strong sunlight was a good indicator of the risk of skin cancer, tanning ability being inversely related to its incidence. The rate in those who always burnt and never tanned when exposed to strong sunlight was 1764/100,000 compared with a rate of 616/100,000 in those who always tanned and never burnt. These findings have important implications for public education programmes in relation to exposure to sunlight in Australia.

Adolescent

Evidence for the presence of antibodies to cholinergic neurons in the serum of patients with Alzheimer's disease.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data presented support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged

Molecular clock rates at loci under stabilizing selection.

Under stabilizing selection in a finite population, lambda, the rate of allelic substitutions at a locus is approximately lambda approximately mu(1 + S)-1/2, where mu is the mutation rate. S, the stringency of selection upon new mutants, is defined by S = NVm/Vs, where N is the population size and Vm/Vs is a measure of the average fitness decrease experienced by new mutants. The approximation holds both for a "lonely" locus, which is the sole provider of genetic variation for the character under selection, and for an "embedded" locus, which is not. In both cases I use the Crow and Kimura model of a continuum of alleles with Gaussian selection and mutation. Monte Carlo simulations corroborate the substitution rate formula. Some molecular evolution data suggest the potential utility and limitations of the formula for estimating population size, mutation, and selection parameters. This work agrees with the rest of nearly neutral theory in emphasizing the important role of population size for substitution rates.

Alleles

Spontaneous remission of solar keratoses: the case for conservative management.

One thousand and forty people aged 40 years and over, 616 (59.2%) of whom had solar keratoses, were followed for 12 months. Two hundred and twenty-four people (36.4%) had a spontaneous remission of at least one of their solar keratoses. A total of 485 lesions (25.9%) underwent spontaneous remission out of the 1873 lesions that were present at the first examination of these 224 people. There was no significant difference between the number of lesions present at the initial examination in those who had a spontaneous remission compared with those who did not. There was a 21.8% increase in the total number of solar keratoses in the 1040 people studied in the 12-month period, due to new lesions forming at the same time as remissions were occurring. The incidence rate of squamous cell carcinoma occurring in the people with solar keratoses was 0.24% for each solar keratosis present at the original examination. With a substantial proportion of solar keratoses remitting spontaneously, plus the low rate of malignant transformation and the low potential for metastasis to occur from squamous cell carcinoma arising in a solar keratosis, the rationale of treating all solar keratoses appears questionable.

Adult

Fluphenazine decanoate and fluphenazine enanthate in the out-patient management of chronic schizophrenia.

39 chronic schizophrenic out-patients were given either fluphenazine decanoate or enanthate for a 1-year double-blind trial. Doses of 25 mg were given for the first 6 months and 37.5 mg for the last 6 months. For both agents the intervals between treatments lengthened significantly over the course of the trial. Fluphenazine decanoate showed a non-significant trend for a longer duration of action coupled with a significantly lower incidence of extrapyramidal side effects.

Adult

Computerized controlled drug inventory system.

The development and use of a computerized system for controlled drug inventory is described. The system configuration, processing and report programs are discussed. The system is capable of producing reports on controlled drug prescriptions and receipts, current balances, and close-out inventory levels, as well as patient use and physician screens. This flexible system, developed with limited hardware, has the ability to provide up-to-the-minute accounting of controlled drugs.

Computers