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Biomedical subjects

K Jones

Publications and source records attributed to K Jones.

At least 397 records · Page 22Linked to original sources

Alpha-tocopherol and beta-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Idiopathic Parkinson's disease (PD) may possibly be caused by one or more unidentified neurotoxins present in the environment, or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in humans, lower primates and mice that closely resemble those found in PD. Because the mechanisms of neuronal damage in both idiopathic PD and in the MPTP model of PD may involve free radical formation in the substantia nigra, antioxidants might protect dopaminergic neurons. Previously, we found that both alpha-tocopherol and beta-carotene partially protected mice against MPTP. However, in the experiments described in this paper, neither alpha-tocopherol nor beta-carotene, each administered in massive doses, had any demonstrable protective effect for dopaminergic nigrostriatal neurons in marmosets injected with low doses of MPTP. Without more knowledge about the identity of the neurotoxin(s) causing idiopathic PD, and their mechanism of action, it is not possible at this time to predict whether these 2 antioxidants might be clinically useful in preventing or ameliorating PD.

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

Distant procurement of organs for clinical heart-lung transplantation using a single flush technique.

A more widespread application of combined heart-lung transplantation (HLT) for the treatment of pulmonary vascular disease has been limited by the lack of a simple and inexpensive method for preserving donor organs for transplantation from distant hospitals. Of the 12 HLT patients treated at Papworth Hospital, the last 7 involved distant procurement of donor organs. For this, a single flush hypothermic system was used, with a Ringer's solution containing albumin, mannitol, prostacyclin, and heparin. This was preceded by a prostacyclin infusion into the donor's pulmonary artery. A retrospective comparison has been made of the post-operative pulmonary function between the HLT patients with distant procurement, those with near procurement of organs, and a group of patients who underwent coronary artery bypass graft (CABG) over the same time span. The mean ischemic time for distant-procurement patients was 110 (+/- 10) min, compared with 50 (+/- 0.5) min for near procurement. During the initial 18 hr postoperatively, the alveolar-arterial oxygen gradients (A-aDO2) for both groups of HLT patients and the CABG patients were closely comparable. Two near-procurement patients died: 1 from tracheal dehiscence, and 1 from cytomegalovirus (CMV). One distant-procurement patient died of CMV. All the others recovered fully and are alive and well at home. No patient developed a classical reimplantation response, and pulmonary function in the distant-procurement group compared closely with the CABG patients. These observations suggest that a simple single flush preservation system can effectively extend the pulmonary ischemic time so facilitating distant organ procurement.

Coronary Artery Bypass↗

Enumeration of Klebsiella spp. in cold water by using MacConkey-inositol-potassium tellurite medium.

MacConkey-inositol-potassium tellurite agar was field tested for its ability to selectively enumerate Klebsiella species from the waters of the Saint John River Basin, which include fresh and marine waters. Water temperature varied from 1 to 6 degrees C during the survey period. Results of the study indicated that 77% of the typical colonies on MacConkey-inositol-potassium tellurite medium were Klebsiella species, but the total Klebsiella population enumerated was greatly underestimated.

Culture Media↗

Brain glutamate deficiency in amyotrophic lateral sclerosis.

Amino acid contents were measured in autopsied brains of eight patients with the sporadic form of amyotrophic lateral sclerosis (ALS) and in brains of control subjects dying without neurologic or psychiatric disease. Glutamic acid content was reduced in most brain regions and in the cervical cord in the ALS patients, while glutamine contents were normal. Taurine contents were increased, and gamma-aminobutyric acid contents were decreased in some brain regions in the ALS patients. The brain glutamate deficiency in ALS is unexplained, but insufficient production or release of this excitatory neurotransmitter might have important secondary effects on motor neurons.

Amino Acids↗

A rhodopsin gene expressed in photoreceptor cell R7 of the Drosophila eye: homologies with other signal-transducing molecules.

We have isolated an opsin gene from D. melanogaster that is expressed in the ultraviolet-sensitive photoreceptor cell R7 of the Drosophila compound eye. This opsin gene contains no introns and encodes a 383 amino acid polypeptide that is approximately 35% homologous to the blue absorbing ninaE and Rh2 opsins, which are expressed in photoreceptor cells R1-6 and R8, respectively. Amino acid homologies between these different opsins and other signal-transducing molecules suggest an important role for the conserved domains of rhodopsin in the transduction of extracellular signals.

Amino Acid Sequence↗

A second opsin gene expressed in the ultraviolet-sensitive R7 photoreceptor cells of Drosophila melanogaster.

We have identified a second Drosophila opsin gene, Rh4, which is expressed specifically in the ultraviolet-sensitive R7 photoreceptor cells. The two R7 opsins, Rh3 and Rh4, are expressed in nonoverlapping subsets of R7 cells. The Rh4 opsin shares 72% amino acid identity with Rh3, but is only about 35% homologous with the other 2 Drosophila opsins, ninaE and Rh2. Twenty-eight amino acids are conserved among all 4 invertebrate and 5 vertebrate opsin genes thus far sequenced, suggesting that these residues play an important role in rhodopsin function.

Amino Acid Sequence↗

Manipulation of glutathione contents fails to alter dopaminergic nigrostriatal neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse.

Administration of glutathione monoethyl ester to mice increased hepatic glutathione (GSH) levels modestly, while administration of butylated hydroxyanisole increased hepatic glutathione content markedly. Yet neither substance protected mice from the toxic effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopaminergic nigrostriatal neurons, as shown by marked depletion of striatal dopamine content when animals were sacrificed. Conversely, marked lowering of GSH levels in the livers of mice by administration of buthionine sulfoximine, or in both liver and brainstem following the injection of diethyl maleate, failed to accentuate the neurotoxicity of a low dose of MPTP. Thus, although MPTP produces a drop in brainstem GSH content, this GSH deficiency may not be casually related to the neurotoxic effects of MPTP.

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

Paraquat and two endogenous analogues of the neurotoxic substance N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine do not damage dopaminergic nigrostriatal neurons in the mouse.

C57 black mice were injected repeatedly with maximal tolerated doses of 4 different chemical analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or its metabolite N-methyl-4-phenylpyridinium ion (MPP+), in order to assess their possible neurotoxicity for dopaminergic nigrostriatal neurons and their potential for causing idiopathic Parkinson's disease. The 4 analogues were the herbicide paraquat, reduced paraquat (having two N-methyl-tetrahydropyridine moieties), N-methyl-1,2,3,4-tetrahydroisoquinoline, and 2-methyl-1,2,3,4-tetrahydro-beta-carboline, the latter two compounds being possible endogenous neurotoxins. Contents of striatal dopamine, measured by high-performance liquid chromatography with electrochemical detection one month after injections were completed, were not depleted by any of these 4 compounds in mice. They might conceivably prove more neurotoxic in primates.

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

The influence of chemical carcinogens on natural killer cell function in rats. A comparison of 2-acetylaminofluorene with 4-acetylaminofluorene.

The influence of the carcinogen 2-acetylaminofluorene (2AAF) administration on splenic natural killer (NK) cell function in two strains of rats has been examined and compared with that of the non-carcinogenic analogue 4-acetylaminofluorene (4AAF). In both strains it was observed that daily exposure to 25 mg kg-1 2AAF induced a significant depression of both native and interferon (IFN)-activated NK cell function which was first apparent between 7 and 13 days following initiation of treatment. In contrast 4AAF failed to influence NK cell activity. These data indicate that 2AAF in common with some other carcinogens has the capacity to influence natural cytotoxic function and lend support to the hypothesis that carcinogenic potential may in some cases be associated with immunosuppressive properties.

2-Acetylaminofluorene↗

The Italian experience in mental health care.

Italy's Law 180, passed in 1978, abolished mental hospitals and replaced them with community services. The Italian literature suggests that the law has been far less successful in improving services for mental patients than reports by foreign visitors have indicated. The authors visited Italy on two occasions in 1984 and 1985 to assess for themselves the impact of the law. In many parts of the country hospitals were still open but badly understaffed and physically deteriorated; in Trieste, where the reform movement started, there was a good system of services, but a hospital whose closing had been publicly celebrated still housed several hundred patients. The authors describe the social and political climate in which Law 180 was passed, discuss the central role of Franco Basaglia and his Psichiatria Democratica movement, summarize the findings of their two visits, and attempt to explain why members of Psichiatria Democratica consider hospitals that remain open to be closed.

Aged↗

The 'Italian Experience' reconsidered.

Our analysis of the problems of the Italian psychiatric services has drawn a lively correspondence challenging our findings. In September 1985, we undertook a second study tour in Italy. This is now reported, with notes on specific criticisms of the earlier paper.

Community Mental Health Centers↗

The influence of 7,12-dimethylbenzanthracene on natural killer (NK) cell function in rats.

The administration to 2 strains of rat (Alderley Park and Sprague Dawley) of 40 (2 X 20) mg of 7,12-dimethylbenzanthracene (DMBA) on a single day caused a transient depression of NK cell function. The splenic natural cytotoxic capacity of both DMBA treated and control animals was augmented by inclusion within the assay of interferon (IFN) but IFN failed to restore carcinogen-treated splenocyte cytotoxicity to normal values. Splenocyte populations from DMBA treated animals exhibiting reduced cytotoxic activity possessed normal frequencies of target-binding lymphocytes suggesting that the impairment of reactivity was attributable to a defect in the post-recognitive stage of NK mediated lysis. Administration of DMBA was not associated with a reduction in spleen weight or cellularity or with an impairment of splenic lymphocyte responsiveness to phytohaemagglutinin (PHA) indicating that depressed NK cell function was not a result of general lymphotoxicity. These data confirm previous reports that administration of chemical carcinogens may be associated with a depression of NK cell function.

9,10-Dimethyl-1,2-benzanthracene↗