Biomedical subjects

B M Johnson

Publications and source records attributed to B M Johnson.

13 recordsLinked to original sources

PubMed1988

Ultrastructural and paraphenylene studies of degeneration in the primate visual system: degenerative remnants persist for much longer than expected.

It is a widely held belief that the products of axonal degeneration in the CNS are transitory and are caused by metabolic and phagocytic processes. However, recent light microscopic examinations of human and primate brains using the paraphenylene diamine staining method (PPD), which stains degenerating axons, have confirmed that the products of degeneration persist for years in visual pathways. The routine utilization of the PPD method for delineating human visual pathways requires further confirmation of axonal degeneration. Optic nerves, optic tracts, and lateral geniculate nuclei were collected from human brains that had clinical documentation of optic nerve damage prior to death. Optic nerves, optic tracts, and lateral geniculate nuclei taken from the brains of cynomolgus monkeys that had undergone enucleation 3 months to 1 year prior to sacrifice were also examined. All tissue was processed for electron microscopy; ultrathin sections were cut for electron microscopy, and consecutive sections were cut for light microscopy. In all cases, the homology of the degenerated processes was confirmed between the light microscopic (PPD) and the electron microscopic sections. Such ultrastructural examination demonstrates that the products of axonal degeneration remain in the primate visual system longer than previously supposed.

Animals↗

PubMed1978

o,p'-DDD (mitotane) therapy of adrenal cortical carcinoma: observations on drug dosage, toxicity, and steroid replacement.

Four patients with adrenal cortical carcinoma were treated with standard doses of o,p'-DDD. Plasma levels of o,p'-DDD and its metabolites o,p'-DDA and o,p'-DDE were measured. o,p'-DDD was measurable for up to 8 months after stopping therapy, and trace levels of metabolites were detectable at 18 months. Although 2 of 3 patients with measurable disease had objective tumor response and one patient achieved a complete response, severe drug toxicity occurred in all patients and signs of adrenal insufficiency occurred in three. Low dose therapy with o,p'-DDD is suggested, together with full gluco and mineralocorticoid replacement. Measurement of o,p'-DDD and its metabolites in plasma may prove clinically useful in developing effective but less toxic dosage schedules.

Adrenal Cortex Neoplasms↗

PubMed1977

Aryl and heterocyclic diazo compounds as potential environmental electrophiles.

4-Aminoimidazole-5-carboxamide, a component of human urine derived from the de novo purine biosynthetic pathway, was evidenced to undergo in vivo diazotization in rats following its sequential administration with NaNO2. The diazotization product, 4-diazoimidazole-5-carboxamide, undergoes intramolecular cyclization to yield 2-azahypoxanthine, the urinary presence of which was confirmed mass spectrometrically. 4-Diazoimidazole-5-carboxamide demonstrated dose-related mutagenicity in Salmonella typhimurium TA 100 and represents a potent electrophilic reactant similar to the proposed ultimate carcinogenic forms of arylalkylnitrosamines and arylnitrosamides. It is suggested that aryl and heterocyclic diazo compounds, as a class, warrant further study as environmental electrophiles representing potential biological hazard.

Animals↗

PubMed1975

Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes.

The relative functional maturity of neonatal mouse spleen T- and B-cell populations was assessed by comparing the ability to respond to the thymic-independent antigen, DNP-Ficoll, or thymic-dependent SRBC by producing antibody in vitro. Although mouse spleen cells responded to DNP-Ficoll at an earlier age than they responded to SRBC or TNP-SRBC, the reason for the lag in the T-dependent response was confounded by the finding of high numbers of suppressor T lymphocytes in the neonatal spleen. Thus, small numbers of neonatal spleen T cells or thymocytes significantly decreased the in vitro antibody response of adult spleen cells. Although B lymphocytes appear to be functionally mature soon after birth, their acitivity may be modulated by an excess of suppressor T cells; e.g., the reconstitution of helper cell function in the neonatal spleen required anti-theta treatment before addition of adult helper cells. Suppressive activity attributable to T cells seems to play a dominant role in determining the ability of the neonatal animal to react positively or negatively to antigenic stimulation.

Age Factors↗

PubMed1975

Effect of deoxyuridine coadministration on toxicity and antitumor activity of fluorouracil and floxuridine.

The addition of deoxyuridine (UDR) to fluorouracil (FU) or floxuridine (5-fluoro-2' deoxyuridine) (FUDR) produced a substantial increase in their toxicity in BDF1 mice. Antitumor assays using sarcoma 180 tumor-bearing mice showed a concomitant increase in tumor growth inhibition for the nucleoside-drug combination over identical doses of the single drug. However, no significant increase in antitumor activity with the combination treatment was demonstrated when equitoxic doses were given. Additional support for the therapeutic equality of the single and combination drug regimens was the similarity of the therapeutic indexes for each treatment regimen involving either fluorouracil or floxuridine. The results suggested that any therapeutic benefit achieved with the combination therapy could be duplicated with either fluorouracil or floxuridine at a higher dose.

Animals↗

PubMed1975

The use of radioactive microspheres to compare the effects of hydralazine, guanethidine and SK & F 24260 on the redistribution of cardiac output in anaesthetized rabbits.

1 The use of radioactive microspheres is described for the measurement of cardiac output in anaesthetized rabbits and its redistribution after the administration of drugs which lower blood pressure. 2 Hydralazine increased peripheral vascular conductance by 123%. The vascular beds in which it had most effect were those of the carcass (mainly muscle) and the kidneys. 3 SK&F 24260, (1,4 dihydro-2, 6-dimethyl-4(2-trifluoremethylpheny)-3,5,-pyridinedicarboxylic acid diethyl ester), had similar vasocilator actions. Its effect in the carcass contributed relatively more to the increase of total peripheral conductance. It also caused a remarkable degree of cerebral vasodilatation. 4 Guanethidine had a relatively small effect on total peripheral conductance and lowered blood pressure mainly by reducing stroke volume and cardiac output.

Anesthesia↗

PubMed1975

Toxicity and antitumor activity of hexamethylmelamine and its N-demethylated metabolites in mice with transplantable tumors.

N-Demethylated metabolites of the antineoplastic agent hexamethylmelamine were synthesized, and their toxicities and antitumor activities were determined in vivo. Determinations of the lethal dose for 10% of the male C57BL X DBA/2 F1 (hereafter called BD2F1) mice showed hexamethylmelamine toxicity to be decreased by N-demethylation; the metabolites showed a direct relationship between potency (mmoles/kg/day) and number of methyl groups present. In BD2F1 mice bearing Sarcoma 180 or Lewis lung carcinoma, the antitumor activities of the methylmelamines decreased with a reduction in number of methyl groups, but were similar at equitoxic levels. Results were similar in L1210 leukemic mice treated with lethal dose levels of the metabolites for 10% of the mice when mean survival times were measured. The therapeutic equality produced with equitoxic levels, together with the ineffectiveness of melamine, suggested that the presence of a methyl group, rather than the number, was the determining factor in the antitumor activity of the methylmelamines.

Altretamine↗

PubMed1974

Cellular requirements for the primary in vitro antibody response to DNP-ficoll.

The cellular requirements for the primary in vitro IgM and IgG response to dinitrophenyl-substituted Ficoll were examined. Neither thymus-derived lymphocytes nor macrophage-rich splenic adherent cells were required for anti-DNP antibody synthesis. DNP-Ficoll is therefore tentatively classified as a "thymic-independent" antigen.

Animals↗

PubMed1974