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Biomedical subjects

M Sussman

Publications and source records attributed to M Sussman.

At least 55 records · Page 3Linked to original sources

Serologically distinguishable alterations in the molecular specificity of cell cohesion during morphogenesis in Dictyostelium discoideum.

Cells of the mutant strain JC-5 of the slime mold Dictyostelium discoideum exhibit at a specific, late developmental stage a temperature-sensitive morphogenetic defect associated with the loss of cell cohension. We show that at the restrictive temperature, the loss of cohesion and attendant dispersal of multicellular aggregates is associated with the disappearance or sequestration of a plasma membrane-bound moiety capable of reacting with and, hence, absorbing cohesion-blocking Fab. At the permissive temperature, the maintenance of cohesiveness past the critical stage or the recovery of lost cohesiveness is correlated with the presence or reappearance of the Fab-reactive moiety.This moiety is absent or sterically incapable of reaction with Fab preparations at an earlier developmental stage in either mutant or wild-type cells-i.e., at a time when they have just entered into multicellular aggregates. Conversely, a serologically distinguishable membrane-bound moiety present in the early mutant or wild-type cells, whose reaction with homologous Fab also precludes their cohesion, is absent or serologically unreactive in either mutant or wild-type cells that are at comparable late developmental stages. We conclude that the cohesive moiety responsible for initiation of cell aggregates is supplanted by or transformed into a serologically distinct, cohesive complex responsible for the maintenance of the aggregate's integrity through the later stages of development.

Journal Article↗

Pharmacokinetics of intravenous and intraperitoneal cefuroxime in patients undergoing peritoneal dialysis.

The pharmacokinetics of cefuroxime sodium, a parenteral beta-lactam antibiotic, were investigated in 9 patients during peritoneal dialysis. In 6 patients cefuroxime 500 mg was administered intravenously. Mean plasma levels of cefuroxime thereafter fell from 28.0 +/- 5.0 mg/l at 1 hr to 6.0 +/- 1.6 mg/l at 24 hr. Mean peak levels 4.6 +/- 1.9 mg/l in peritoneal effluent were found 7 hr after dosing and clearance of the drug by peritoneal dialysis averaged 4.7 ml/min. There was no evidence of net tubular secretion or of increased non-renal elimination. In 5 patients, the administration of cefuroxime, 100 mg/2 l dialyzate, in each cycle of dialysis maintained mean cefuroxime levels of 25.4 +/- 13 mg/l in the dialysis effluent. An average of 44% of the dose was not recovered in the effluent, and was presumably absorbed by the patient, and mean plasma levels of cefuroxime increased from 1.1 +/- 0.4 mg/l at 1 hr to 14.0 +/- 8.1 mg/l at 24 hr. If cefuroxime is used to treat peritoneal infections associated with peritoneal dialysis it should be given by both intraperitoneal and intravenous routes and followed up with parenteral therapy alone.

Adult↗

Enzyme-linked immunosorbent assay for circulating anti-glomerular basement membrane antibodies.

An enzyme-linked immunosorbent assay for the quantitative determination of anti-glomerular basement membrane antibodies in human sera, which is both sensitive and reproducible, is described. The test detected circulating antibodies in each of seven patients with active anti-glomerular basement membrane disease, whilst sera from 42 patients, with a variety of other glomerulonephropathies, were negative by the test. It has also been possible to demonstrate a good correlation between the levels of circulating anti-glomerular basement membrane antibodies and the clinical course of disease in one patient with Goodpasture's syndrome.

Antibodies↗

Delayed skin test reactivity to Propionibacterium acnes correlates with severity of inflammation in acne vulgaris.

Propionibacterium acnes is the bacterial species most consistently isolated from acne lesions. Intradermal injection of a heat-killed suspension of P. acnes induced a delayed erythematous and often popular inflammatory reaction which was maximal after 24-48 h. This response was dose related and was probably mediated at least partly by immune mechanisms. In eighty-one subjects with acne of varying severity of the acne. These findings indicate that the host response to P. acnes is an important variable in determining the severity of inflammatory acne.

Acne Vulgaris↗

Spore differentiation by isolated Dictyostelium discoideum cells, triggered by prior cell contact.

Cells of D. discoideum mutant Fr-17 were allowed to form multicellular aggregates and develop undisturbed through 12 h (out of 18-required for terminal morphogenesis and cytodifferentiation). Then the cells were disaggregated and redeposited at densities so low as to preclude further sustained cell contacts and were incubated in the presence of certain diffusible metabolites. In this condition they transformed into spores and stalk cells with normal timing and, in the case of the spores, in proportions approaching those observed in undisturbed fruiting bodies. In contrast, mutant cells dispersed from aggregates at earlier stages or wild type cells dispersed from aggregates at any stage, remained as amoebae under the same conditions. The completion of cytodifferentiation by the isolated cells was found to require threshold concentrations of diffusible, dialysable metabolites. A part of this requirement could be satisfied by addition of 10 mM NH4Cl particularly in conjunction with an amino acid mixture. At least one metabolite, however, had to be supplied by feeder cells separated from the test cells by a dialysis membrane or by increasing the population density of the test cells themselves.

Amino Acids↗

Haemodialysis-induced leucopenia and activation of complement: effects of different membranes.

The effects on neutrophil count and complement activity of five different haemodialysis membranes were studied. There was no correlation between the degree of neutropenia and intensity of complement activation. With cuprophan membrane both occurred simultaneously but to unrelated degrees; polyacronitrile induced mild, not significant neutropenia but marked activation of complement; polycarbonate membranes induced severe neutropenia without detectable complement activation. Where complement activation occurred it was via the alternative pathway. Haemodialysis induced neutropenia may have many causes and complement activation is probably not the major responsible factor.

Acrylic Resins↗

Mutant of Dictyostelium discoideum defective in cell contact regulation of enzyme expression.

Previous work has shown that aggregation and disaggregation of cells during development of D. discoldeum significantly affects the expression of certain developmentally regulated enzymes. We have examined this cell contact regulation in a previously isolated mutant, Fr-17, and found that during the course of its developmental sequence it becomes specifically defective in this function.

Adenosine↗

Guanosine metabolism and regulation of fruiting body construction in dictyostelium discoideum.

A cell aggregate of Dictyostelium discoideum either constructs a fruiting body directly or transforms into a migrating slug and fruits later on in some other locale. In the presence of formycin B, an inosine analog, and in an environment that otherwise favors fruiting, aggregates having reached a relatively late (17 hr) stage of fruit construction abandon that program and transform into migrating slugs. They then revert to the fruiting mode and construct normal fruiting bodies without further interference [Brackenbury et al. (1974) J. Mol. Biol. 90, 529-539]. The data presented here suggest that formycin B exerts its morphogenetic effect by interfering competitively with the metabolism of guanosine. Thus: see article. The recovery from formycin B is thought to result from the ensuing accumulation of guanosine and reversal of the inhibition. In support of this are the following: (1) Formycin B does cause, in vivo, an accumulation of guanosine. Exogenoug guanosine reverses the effect of formycin B, depending on their relative concentrations. (2) Guanosine is phosphorylitically cleaved to guanine and ribose-1-P by purine ribonucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyl transferase, EC 2.4.2.1), present in D. discoideum extracts, and formycin B is a competitive inhibitor or this reaction with a very high affinity for the enzyme. (3) Four other analogs, also competitive inhibitors of this enzyme, produce precisely the same morphogenetic deviation. The concentrations required are consistent with the relative K1 values.

Antibiotics, Antineoplastic↗

Mutants of Dictyostelium discoideum defective in spore germination.

After activation, wild-type Dictyostelium discoideum spores germinate rapidly and synchronously in phosphate buffer as well as in complex medium. Mutants defective in spore germination were isolated and characterized. These mutants (called grm) did not germinate normally in buffer but did germinate in complex medium in the presence of bacteria. One mutant (grm B) swelled normally, but amoebae were not formed. Another mutant (grm F) swelled and germinated poorly in buffer. The members of the third group of mutants (A, C, D, and E) did not swell or give rise to amoebae in buffer.

Buffers↗