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Biomedical subjects

M Neal

Publications and source records attributed to M Neal.

At least 37 records · Page 2Linked to original sources

Nitric oxide enhancement of cholinergic amacrine activity by inhibition of glycine release.

PURPOSE: To investigate a possible interaction between cholinergic and nitrergic amacrine cells in the rabbit retina. METHODS: The activity of cholinergic amacrine cells was estimated by measuring the light-evoked release of [3H]-acetylcholine (ACh) from the retina of rabbits anesthetized with urethane. An eyecup was prepared and filled with Krebs-Ringer bicarbonate solution, containing [3H]-choline. After washing with fresh medium containing physostigmine, 0.5 ml of medium was placed in the eyecup. The medium was replaced every 5 minutes, and the radioactivity in the resultant samples was measured. In some experiments the release of [3H]-ACh and glycine was measured using isolated retinas. RESULTS: Local application of the nitric oxide (NO) donors, S-nitroso-N-acetyl-DL-penicillamine and sodium nitroprusside strikingly enhanced the light-evoked release of [3H]-ACh. In contrast, inhibition of nitric oxide synthase with L-nitromonomethylarginine (LNMMA) or N-nitro-L-arginine (LNA) greatly reduced the light-evoked release of [3H]-ACh. In that the response of cholinergic amacrine cells is damped by an inhibitory feedback circuit involving glycinergic amacrine cells, the effect of strychnine on the inhibitory action of LNMMA was examined, Strychnine abolished the inhibitory effect of LNMMA on the light-evoked release of [3H]-ACh, suggesting that endogenous NO normally has an inhibitory effect on glycinergic amacrine cells. This idea was supported by experiments using isolated retinas, in which sodium nitroprusside and S-nitroso-N-acetyl-DL-penicillamine inhibited the potassium-evoked release of glycine but enhanced the release of [3H]-ACh. CONCLUSIONS: Endogenous NO is released in the retina and acts indirectly to facilitate the light-evoked response of cholinergic amacrine cells.

Acetylcholine↗

A presenilin 1 mutation in an early onset Alzheimer's family: no association with presenilin 2.

Genes on four chromosomes have been associated with Alzheimer's disease. Mutations in the chromosome 14 gene (S182 or presenilin 1) have been linked with an aggressive very early form of the disease while mutations in a chromosome 1 gene (STM2 or presenilin 2) have been linked with Volga German kindreds. When we screened our Alzheimer's patients for the first mutations reported, we only found one in the presenilin 1 gene in an extended family with three affected siblings, all of whom had onset of symptoms in their 4Cs. ApoE and ApoCI genotyping indicated that these risk factors were not associated with the disease in this family. None of our patients with early or late onset disease had the mutation described for presenilin 2.

Age of Onset↗

A closely linked gene to apolipoprotein E may serve as an additional risk factor for Alzheimer's disease.

The E4 allele of the apolipoprotein E (APOE) gene has been identified as a risk factor for Alzheimer's disease. Immediately downstream from the APOE gene on chromosome 19 is the gene for apolipoprotein CI (APOCI). We have found that the frequency of an APOCI restriction site is 0.45 for Alzheimer's patients and 0.14 for control spouses, which is similar to the frequencies for the APOE4 allele. The APOE4 allele is in linkage disequilibrium with the APOCI restriction site. Thus both the APOE4 allele and the APOCI restriction site may be considered as risk factors for Alzheimer's disease.

Aged↗

Mapping of two phenol sulphotransferase genes, STP and STM, to 16p: candidate genes for Batten disease.

The cytosolic phenol sulphotransferase gene (STP) was mapped to a region of chromosome 16, within the interval defined by human-rodent somatic cell hybrid breakpoints CY160(D) and CY12, which contains FRA16E. YAC and cosmid clones from this 16p interval were screened for the presence of STP. Two non-overlapping cosmid contigs were identified which contain STP-like sequences. Sequencing of these STP-like sequences confirmed that STP is contained within contig 343.1 and maps proximal to FRA16E, and that a related sulphotransferase STM, encoding the catecholamine-sulphating enzyme, is contained within contig 55.4 and maps to the adjacent hybrid interval CY12-CY180A. Thus two phenol sulphotransferase genes (STP and STM) have been finely localised to chromosome 16p12.1-p11.2, to the same region as CLN3, the gene for Batten disease. Both genes are therefore candidate genes for Batten disease.

Animals↗

Modulation by endogenous ATP of the light-evoked release of ACh from retinal cholinergic neurones.

The retina is an area of the central nervous system that possesses intrinsic cholinergic neurones which release acetylcholine (ACh) in response to stimulation with flickering light. Using an eye-cup preparation in anaesthetized rabbits we found that when the retina was exposed to the P2-purinoceptor antagonist, PPADS, the light-evoked release of ACh was strikingly increased (by over 40%). In contrast, ATP reduced the light-evoked release of ACh by 20%. The inhibitory effect of ATP was not due to its catabolism to adenosine because it was not affected by the A1-adenosine receptor antagonist, DPCPX, in combination with adenosine deaminase. The actions of both ATP and PPADS were completely blocked by strychnine. We conclude that during physiological stimulation of the retina with light, ATP is co-released with ACh and partially inhibits ACh release by activating (with ACh) an inhibitory glycinergic feedback loop.

Acetylcholine↗

Blood spot screening and confirmatory tests for syphilis antibody.

We developed a blood spot test for syphilis antibody using enzyme-linked immunosorbent assay (ELISA) technology. Dried blood was eluted by buffered saline or, for a supplementary confirmatory test, by treponemal-antibody test diluent. Eluates were diluted in an absorption buffer (Calypte Biomedical, Berkeley, Calif.) and added to plate wells coated with cardiolipin antigen (ADI Diagnostics, Toronto, Ontario, Canada). The wells were washed and treated sequentially with an immunoglobulin G conjugate, buffer washes, and enzyme substrate. Substrate conversion was measured photometrically, and specimen reactivity was determined by reference to nonreactive controls. The optimum test protocol was established by tests of serum and plasma. The serum ELISA specificity with normal specimens was 98.9%. The sensitivity with sera from patients with undefined syphilis was 97.4%, that with sera from patients with documented primary and secondary disease was 100%, and that with sera from patients with early and late latent disease was 95.7%. The specificity of the spot test with donor blood was 94.2%, and its specificity with newborn blood was 94.9%. The sensitivity with 25 spots spiked with reactive sera was 96%. The seroprevalence rates for parturient women in one hospital were 6.01% according to spot tests of sera from 599 newborns and 6.81% according to Rapid Plasma Reagin tests of 499 maternal serum specimens. Seventy percent of infants born to 50 seropositive women were reactive by either the newborn spot or the Rapid Plasma Reagin serum test. The results show that blood spots may be used in seroprevalence or serodiagnostic studies, especially to identify women who are infected or to identify possible cases of congenital infection. The test provides for studies of children and adults when routine venipuncture and serum handling and storage are problematic.

Antibodies, Bacterial↗

A program for caregivers in the workplace.

In four demonstration sites, an educational seminar series was offered to employed caregivers, followed by a choice of service options (i.e., care planning, a support group, a buddy system). An increase in absenteeism and knowledge of aging services was associated with attendance at the seminar series. Among the service options, only care planning and support groups were utilized by employees. A decrease in negative affect was associated with each of the options.

Aged↗

Microtitre plate measurement of platelet response to hypotonic stress.

The conventional method of assessing the platelet response to hypotonic stress (HSR) was adapted to allow microtitre plate technology to be used. After water is added to a platelet suspension two sequential readings are taken at 414 nM on a vertical microplate reader. The difference between the second (three minutes) and the first (one minute) was defined as the HSR. This method allowed the relation between platelet concentrate pH and viability to be confirmed, and an HSR value for use in quality control was established. The method correlated well with the conventional technique and permitted measurement of undiluted samples as well as of products with a high free haemoglobin concentration.

Blood Platelets↗

Effect of automatic blood pressure devices on vigilance of anesthesia residents.

The response time of anesthesia residents to interruption in auditory blood pressure monitoring was compared between two anesthesia training programs that have different blood pressure monitoring traditions. Program A relies exclusively on manual blood pressure cuffs, whereas program B uses automated blood pressure devices for approximately 90% of patients. In this limited, short-term study, the time that lapsed between interruption of auditory monitoring and recognition of the interruption was less in the program that used manual blood pressure cuffs. The impact of the automated blood pressure device on resident vigilance in anesthesia training programs may be negative.

Anesthesia↗

Stimulated release of endogenous GABA and glycine from the goldfish retina.

The release of endogenous gamma-aminobutyric acid (GABA) and glycine from the isolated goldfish retina, measured by high-pressure liquid chromatography (HPLC), was Ca2+-independent when evoked by L-glutamate or L-aspartate and partially Ca2+-dependent when evoked by 50 mM K+. D-Aspartate potentiated GABA and glycine release evoked by L-glutamate and inhibited that evoked by L-aspartate. These data are similar to those reported for radiolabeled GABA and glycine. However, the relative amount released compared to the total amino acid content in the retina was much less (10%) for the endogenous compounds. We suggest that results obtained with [3H]GABA and [3H]glycine can be generalized in a qualitative manner to their endogenous counterparts in goldfish retina.

Animals↗

Epidemiologic features of Reye syndrome seen in southwestern Pennsylvania 1970-80.

In 11 years of surveillance in southwestern Pennsylvania there were 97 cases of Reye syndrome. Peak incidence was in February and March, corresponding to periods of influenza A and B activity. Mean age of cases was 7.9 years; 57 per cent were female. Case fatality declined from 55 per cent in 1970-75 to 16 per cent in 1976-80 (p less than .001). Influenza was associated with 45 per cent of cases, varicella 19 per cent; the remaining 36 per cent of cases did not occur during periods of influenza activity. Reye syndrome occurred significantly more frequently in suburban and rural areas than in central city (p less than .01), more frequently among White persons than Blacks (p less than .01), and more frequently in counties where the total population under 17 years was less than 25,000 (p less than .01).

Adolescent↗