PubMed Health⌕ Search

Biomedical subjects

J H Pincus

Publications and source records attributed to J H Pincus.

At least 55 records · Page 3Linked to original sources

Barbiturates and transmitter release at the frog neuromuscular junction.

The effects of the convulsant and anticonvulsant barbiturates, 5(2-cyclohexylidine ethyl)-5-ethyl barbituric acid (CHEB) an phenobarbital (PHB) were studied at the frog neuromuscular junction. Spontaneous transmitter liberation was augmented by both drugs irrespective of the external Ca2+ concentration, but CHEB was considerably more active than PHB. Miniature end plate potential amplitude was equally reduced by both drugs. The net effect of these agents on end plate potential (e.p.p.) amplitude varied depending on the external Ca2+ concentration. In Ca2+-deficient Ringer's solution both drugs increased the quantal content and the e.p.p. amplitude (CHEB more than PHB). In Ringer's solution containing a normal concentration of Ca2+ ions, both drugs depressed the evoked response and failed to alter the quantal content significantly.

Animals↗

On the mutagenicity and immunogenicity of a beta-propiolactone-treated therapeutic IgG-preparation.

During the production of Intraglobin, an i.v. tolerable IgG-immunoglobulin preparation, fraction Cohn II is treated with beta-propiolactone. Thereby the IgG-molecules are chemically modified thus preventing an increase in secondary aggregates which could give rise to adverse reactions in the patients treated with the IgG-preparation. The safety tests described here neither showed any evidence for the presence of unhydrolysed mutagenic-beta-propiolactone in the final product nor that neoantigenic determinants had been created by the reaction of beta-propiolactone with the protein molecules.

Animals↗

Characterization and use of neuraminidase-modified L1210 plasma membranes for protection against tumor growth.

Purified plasma membranes were prepared from L1210 ascites tumor cells and analyzed for their protein and carbohydrate composition. Conditions were developed for treating the isolated plasma membranes with Vibrio cholerae neuraminidase (VCN) so that 88% of the N-acetylneuraminic acid was removed without changing membrane proteins or other membrane carbohydrate constituents. The VCN-induced modifications were characterized by labeling VCN-treated and untreated L1210 cells by the galactose oxidase:sodium [3H]borohydride procedure. This showed that N-acetylneuraminic acid is the predominant saccharide at the nonreducing terminus of plasma membrane glycoproteins and that galactose and/or N-acetylgalactosamine residues are penultimate to these. VCN modification exposed the penultimate residues and was not limited to any single plasma membrane glycoprotein. DBA/2J mice were given i.p. injections of VCN-treated or untreated membranes and were challenged 3 weeks later with 10(4) viable L1210 cells. Mice pretreated with VCN-treated membranes resisted the tumor challenge; those receiving untreated membranes or no treatment succumbed to the tumor. Our results demonstrate that appropriately modified plasma membranes can be used to induce resistance to tumor growth. They also suggest that tumor cell membrane carbohydrate structures have an important role in this phenomenon.

Animals↗

Immunotherapy of L1210 leukemia using neuraminidase-modified plasma membranes combined with chemotherapy.

Purified L1210 plasma membranes treated with Vibrio cholerae neuraminidase (VCN) were used for active immunotherapy of L1210 tumors in DBA/2J mice. Immunotherapy with VCN-treated membranes was effective only when combined with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU). Successful therapy was a function of the dose of MeCCNU, the dose of VCN-treated membranes, and the time after MeCCNU treatment when VCN-treated membranes were administered. Optimum conditions for treating animals with tumors initiated with 10(4) cells were MeCCNU (20/kg) given 3 days after tumor inoculation and 0.25 mg VCN-treated membranes given 1 day after chemotherapy. Control membranes, not treated with VCN, that were administered 1 day after MeCCNU were ineffective; when given 4 days after chemotherapy, the caused accelerated mortality, suggesting immunological enhancement of tumor growth. Our results indicate that VCN-treated plasma membranes can be used for active immunotherapy of established tumors and underscore the importance of carefully designing immunotherapy protocols to achieve optimum desirable effects.

Animals↗

Phenytoin and transmitter release at the neuromuscular junction of the frog.

The effects of phenytoin (diphenylhydantoin, DPH) on transmitter release were studied at the frog neuromuscular junction. It was found that in Ringer's solutions containing a normal concentration of Ca2+ ions, DPH (1-2 X 10(-4) M) depresses neurally evoked transmitter release, whereas in Ca2+-deficient Ringer's solutions it produces an increase in evoked release. Spontaneous transmitter liberation is augmented by DPH under all the above conditions. An abrupt disappearance of the evoked response occasionally occured with stimulation at 0.5 Hz, but a normal response could be elicited by a second stimulus delivered shortly after the first. At 100-200 Hz, DPH regularly induced a partial block in synaptic transmission. In 8 mM MgCl2, this phenomenon appeared at 50 Hz and developed into a total neuromuscular blockade.

Animals↗

The role of thiamine in nervous tissue.

The possibility that thiamine (vitamin B1) has a role in nervous tissue that is independent of its well-documented coenzyme function is discussed. After reviewing the localization and metabolism of the vitamin and its phosphate esters, the effects of either thiamine deprivation or antimetabolites of thiamine on conduction and transmission, and the relationship between thiamine triphosphate and the genetic, neurological disease, subacute necrotizing encephalomyelopathy (Leigh's disease), it is suggested that despite the lack of hard evidence, it is likely that the vitamin possesses this alternate function.

Animals↗

Juvenile male sexual assaulters.

This study compares the psychiatric, neurological, and psychoeducational status of sexually assaultive male juveniles and other violent juveniles. The authors found that juvenile sexual assaulters suffered from neuropsychiatric problems similar to those of other violent juveniles, had committed violent acts other than sexual assault, and had had seriously aberrant behavior since early childhood. The findings contradict prevailing assumptions that sexual assaults by juveniles are rare occurrences and that juvenile sex offenders have low rates of recidivism. Theoretical and treatment implications are discussed.

Adolescent↗

Urine test in SNE.

Explore the source record for details and available documents.

Encephalomyelitis↗

Depression of synaptic transmission by diphenylhydantoin.

Diphenylhydantoin (phenytoin, DPH) depresses synaptic transmission at the frog neuromuscular synapse by presynaptic and postsynaptic mechanisms. In normal Ringer's solution the amplitude of the neurally evoked end-plate potentials and their quantal content are reduced. Somewhat paradoxically, miniature end-plate potential (mepp) frequency is increased by the drug. These effects could result if DPH blocked both calcium transport at the axonal membrane and intracellular calcium sequestration. Mepp amplitude is reduced, and DPH also induces nerve conduction block at high rates of stimulation. The relevance of these effects to the anticonvulsive activity of DPH is discussed.

Animals↗

Thiamine triphosphate levels and histopathology. Correlation in Leigh disease.

Thiamine and thiamine triphosphate (TTP) values were assayed in various brain regions in 11 controls and 13 patients with subacute necrotizing encephalomyelopathy (SNE, Leigh disease). The TTP values of normal brain were 5% of the total thiamine value. The relative TTP (or % TTP) level was consistently low in the pons, midbrain, and cerebellum of all the SNE brains. Twenty-five percent of the SNE brains had normal TTP levels in the frontal region. The TTP values correlated with the degrees of pathologic involvement in all sampled regions of the brain except the cerebellum. The concentration of thiamine in the mammillary bodies exceeded its concentration elsewhere in both control and SNE brains. The finding of low TTP levels in morphologically abnormal regions supports the hypothesis that TTP deficiency is etiologically related to SNE.

Adult↗