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Biomedical subjects

K Jones

Publications and source records attributed to K Jones.

At least 415 records · Page 23Linked to original sources

Rescue of the Drosophila phototransduction mutation trp by germline transformation.

Phototransduction is the process by which light-stimulated photoreceptor cells of the visual system send electrical signals to the nervous system. Many of the steps that follow the initial event in phototransduction, absorption of light by rhodopsin, are ill-defined. The fruitfly, Drosophila melanogaster, provides a means to dissect phototransduction genetically. Mutations such as transient receptor potential (trp) affect intermediate steps in phototransduction. In order to facilitate molecular studies of phototransduction, the trp gene was isolated and its identity was confirmed by complementing the mutant trpCM allele of the trp gene by P-element mediated germline transformation of a 7.1-kilobase DNA fragment. Expression of the trp gene begins late in pupal development and appears to be limited to the eyes and ocelli.

Animals↗

Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse.

C57 black mice given a single injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 40 mg/kg, developed marked reduction of striatal dopamine content and loss of dopaminergic neurons in the zona compacta of the substantia nigra. However, pretreatment with any one of four different antioxidants, alpha-tocopherol, beta-carotene, ascorbic acid or N-acetylcysteine, significantly decreased MPTP-induced striatal dopamine loss, and alpha-tocopherol prevented neuronal loss in the substantia nigra. Four chemical analogues of MPTP (cinnamaldehyde, N,N-dimethylcinnamylamine, arecoline and 2-methyl-1,2,3,4-tetrahydro-6,7-isoquinolinediol) were all found to lack dopaminergic nigrostriatal neurotoxicity in the mouse.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its metabolite, N-methyl-4-phenylpyridinium ion, on dopaminergic nigrostriatal neurons in the mouse.

A single subcutaneous injection in the C57 black mouse of 40 mg/kg of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a 90% depletion of striatal dopamine, as well as loss of 33% of neuronal cell bodies in the substantia nigra, zona compacta. By 4.5 months, there appears to be partial recovery of striatal dopaminergic function. After injection into mice, the MPTP metabolite, N-methyl-4-phenylpyridinium ion (MPP+) enters the striatum, and through some unknown mechanism is even more toxic than MPTP. However, repeated injections of maximally tolerated amounts of MPP+ do not damage dopaminergic nigrostriatal neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) does not destroy nigrostriatal neurons in the scorbutic guinea pig.

Guinea pigs were injected subcutaneously with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in maximal tolerated doses (8 mg/kg, once daily) for 10 or 15 days. No neurological effects were noted, other than sedation and hypotonia lasting a few hours after each injection, either in animals maintained on normal diet or in animals fed an ascorbate-deficient diet and rendered severely scorbutic. Subsequent chemical analyses of the striatum showed no evidence of lasting damage to nigrostriatal dopaminergic neurons in MPTP treated guinea pigs on normal diet, and minimal evidence of permanent damage to these neurons in scorbutic animals. MPTP was undetectable in the urine of MPTP-treated animals, although a metabolite, presumably 1-methyl-4-phenylpyridinium ion (MPP+) was regularly present in urine. The relative lack of neurotoxicity of MPTP in the guinea pig remains unexplained. This species clearly is not a suitable small animal for MPTP-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

On the extraction of the signal-excitation function from a non-Poisson cochlear neural spike train.

In two recent papers in this Journal, Johnson and Swami [J. Acoust. Soc. Am. 74, 493-501 (1983)] and Gaumond et al. [J. Acoust. Soc. Am. 74, 1392-1398 (1983)] have given procedures for estimating the signal-excitation function s(t) conveyed by a non-Poisson cochlear neural spike train with a known neural recovery function r(t - t'). For a delayed step form of r(t - t'), we show how s(t) may be directly (noniteratively) determined from the post-stimulus-time (PST) histogram response. We also show that for more general recovery functions, s(t) may be determined from the PST histogram response by using a simple iterative method.

Animals↗

Understanding the Italian Experience.

The "Italian Experience" in closing down mental hospitals has been highly praised by some British observers, who have seen lessons for Britain in the development of community care. However, it has been the subject of heated debate in Italy--and the policy is now to be reversed by law. Two questions arise: why have the claims been exaggerated? And why have they found such ready and uncritical acceptance in Britain?

Community Mental Health Services↗

Elevation of gamma-aminobutyric acid in human brain may increase dopaminergic neuronal function.

Studies in experimental animals have yielded conflicting findings as to the influence of gamma-aminobutyric acid (GABA) on the activity of nigrostriatal and mesolimbic dopaminergic neurons. We measured cerebrospinal fluid (CSF) concentrations of GABA and homovanillic acid (HVA) in 19 patients before and during treatment with isoniazid. CSF GABA concentrations increased markedly during isoniazid administration, presumably reflecting increases in brain GABA content. At the same time, HVA concentrations in CSF rose significantly. The net effect of elevating brain GABA content in humans appears to be to increase dopamine release from dopaminergic neurons.

Brain↗

Immunochemical studies on the binding properties of Brucella abortus lipopolysaccharides to bovine precipitating antibodies.

The binding properties of Brucella abortus smooth lipopolysaccharides (LPS) to the precipitating antibodies in the serum of a B. abortus S2308 infected cow were studied by quantitative precipitin and precipitin-inhibition assays. Crude B. abortus lipopolysaccharides (cLPS) and chemical modification products of strains 1119.3, 19 and 2308 (virulent) were used for this study. In the quantitative precipitin assay, 13 micrograms of cLPS precipitated about 4.0-5.2 micrograms nitrogen of precipitating antibodies in 10 microliter of serum. After alkaline treatment (0.125 N NaOH at 56 degrees C for 1 hr), the alkali-treated lipopolysaccharides (aLPS) from S19 and S1119.3 maintained the maximum precipitability, but the precipitation profile was changed from a sigmoidal to a bell-shaped curve, and aLPS from S2308 was reduced to about 40% of its reactivity. These results indicate that some of the antigenic determinants blocked by other molecules were reshielded by alkaline treatment, and possibly that structural differences exist between virulent (S2308) and nonvirulent (S19 and S1119.3) strains. Among the monosaccharides and glycosides tested for inhibition of precipitation, methyl alpha-D-mannose was most active and about 3.3 times as active as D-mannopyranose (DMan) and only 1/200 as active as acid hapten or the carbohydrate moiety of cLPS prepared from S1119.3 (expressed as a monosaccharide of mol. wt 200) implying that the carbohydrate determinants of this antigen are probably related to a DMan alpha 1----linked compound. The precipitability of the antibodies in this serum was greatly reduced after absorption with cLPS and the precipitin reaction was completely inhibited by the carbohydrate moiety of LPS (O-antigen) S1119.3 demonstrating that the common antigenic determinants (hapten) of B. abortus LPS reacting with these precipitating antibodies are in the region of the carbohydrate moiety of the LPS.

Animals↗

Interactions among spontaneous otoacoustic emissions. I. Distortion products and linked emissions.

Spontaneous otoacoustic emissions (SOAEs) can be recorded from human ears with a sensitive microphone in the ear canal. The evidence to date strongly indicates that the origin of these emissions in an active electro-mechanical process at the basilar membrane level. In this report we present data on interactions among SOAEs in ears with multiple SOAEs, including: intermodulation distortion products, mutual suppression, and noncontiguous-linked SOAEs which apparently share energy between two quasi-stable states. These results demonstrate the highly nonlinear and extremely complex nature of the active process, and present a challenge for mathematical modeling of the mechanisms involved.

Acoustics↗

Robert Gardiner Hill and the non-restraint movement.

An account is given of the professional life of Robert Gardiner Hill before and after the publication in 1839 of his lecture on the Total Abolition of Restraint in the Treatment of the Insane. The lecture is summarized and an attempt is made to evaluate his work which has been overshadowed by that of John Connolly . This paper was researched before the author came to North America. A library request to check that no recent work had appeared on the history of the restraint controversy produced two papers published in 1978. One roundly advocates restraint (1) the other acknowledges its widespread practice in Canada (2).

History, 19th Century↗

Comparison of the spatial response properties of the human retina and cortex as measured by simultaneously recorded pattern ERGs and VEPs.

Electroretinograms and visual evoked potentials were simultaneously recorded from adult subjects using a checkerboard pattern stimulus reversing at 0.94, 3.75 and 7.5 Hz. Two contrast levels were used: 30 and 85%. The data obtained from the cortex (VEPs) show spatial tuning properties for all temporal frequencies at both contrast levels, with the peak of the amplitude-check size function occurring between 15 and 30 min. Tuning properties were found at the retina but only at the high contrast level and for the faster (3.75 and 7.5 Hz) temporal frequencies. The results demonstrate that spatial tuning is present in the human retina but not under as wide a range of conditions as found at the cortex.

Adult↗

Correlations between skin sensitization potential and chemical reactivity for p-nitrobenzyl compounds.

Quantitative relationships between skin sensitization potential and certain physico-chemical properties of alkylating agents have been reported. This study demonstrates the correlation of the relative alkylation index (RAI), derived from the alkylation rate and lipophilicity of an alkylating agent, with a set of experimental sensitization data obtained for a series of p-nitrobenzyl compounds.

Alkylation↗

A double-blind comparison of quinine sulphate and placebo in muscle cramps.

Muscle cramps are painful and common in elderly patients but have largely escaped medical investigation. Quinine sulphate is usually the sole drug prescribed, even though firm evidence for its efficacy is not available. The results of the present double-blind cross-over study show that quinine was significantly superior to placebo in decreasing the number, severity and duration of nocturnal cramps. Since quinine is not a primary drug in any other condition, further studies of drugs with similar pharmacological actions may thus improve our management of this painful complaint.

Clinical Trials as Topic↗