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Biomedical subjects

M Sussman

Publications and source records attributed to M Sussman.

At least 37 records · Page 2Linked to original sources
PubMed1987

Postradiation slipped capital femoral epiphyses (SCFE).

This study details the case reports of two children who developed slipped capital femoral epiphyses (SCFE) after receiving external irradiation. The clinical and diagnostic features of postradiation SCFE are reviewed and discussed. Guidelines for the management of children who receive pelvic irradiation are presented.

Child↗
PubMed1986

Aggregation-related and post-aggregation-related cohesive systems in Dictyostelium discoideum involve stage-specific, Ca2+-dependent, di- or polymeric associations of membrane-bound moieties.

The cells of D. discoideum acquire developmentally regulated cohesive properties during aggregation and fruiting body construction. On the bases of genetic, serological, and physiological evidence, it has been suggested that two distinct cohesive systems operate: an aggregation-related (AR) system that facilitates the formation of multicellular aggregates and post-aggregation-related (PAR) system that maintains the integrity of the aggregate thereafter. We had previously demonstrated that ghosts and membrane fragments retain the cohesive properties of the cell from which they were derived. Here, we describe a two-phase assay involving the Ca2+-dependent binding of 125I-labeled cell ghosts in suspension to their unlabeled counterparts immobilized on plastic surfaces. Using this assay we show that the ghosts of newly aggregation-competent (8 h) cells and of cells from the 'Mexican hat (18 h) stage' of fruit construction can bind, each to its immobilized counterpart, but not heterologously. Furthermore, neither binds to the immobilized ghosts of vegetative cells. This provides direct, functional evidence demonstrating the existence of the two stage-specific cohesive systems. It also suggests that both cohesive acts involve at least dimeric associations of molecules or molecular complexes located within or on juxtaposed membranes. Using immobilized 8 and 18 h ghosts, the specific binding activities of ghosts prepared from cells harvested at stages throughout the morphogenetic sequence were assayed in order to describe the developmental kinetics of the two cohesive systems. The binding data suggest that the AR system appears soon after the start of the morphogenetic sequence, peaks during early aggregation and is progressively diminished thereafter. The PAR system makes its appearance after aggregation and accumulates thereafter. Both systems are present in migrating slugs.

Calcium↗
PubMed1986

Further evaluation of the Scolitron treatment of idiopathic adolescent scoliosis.

One hundred forty-two patients were treated by the Scolitron method of lateral electric surface stimulation (LESS) for scoliosis. Using 10 degrees progression as a failure point, clinicians reported the following: 56.3% of patients were classified as failures, 26.8% as successes; and 16.9% were still under treatment. When broken down into individual groups, true protocol patients, at risk for progression, had the lowest success rate; whereas those that were nonprotocol, and least at risk, had the highest success rate. This method should still be considered experimental and cannot be considered an alternative to bracing at this time.

Adolescent↗
PubMed1986

NH3 and propionate modulate the morphological response of aggregation-competent Dictyostelium discoideum to cAMP.

Two metabolites, NH3 and propionic acid, are known to act as morphogens during the development of Dictyostelium discoideum, specifically altering the course of morphogenesis and cytodifferentiation. They have also been shown to modulate the cAMP relay in this organism: NH3 by restricting intracellular accumulation, and propionate by inhibiting extracellular release. In the present study, we utilized the light-scattering properties of aggregation-competent cells in agitated suspension to demonstrate that the morphological responses of such cells to exogenous cAMP are also modulated by NH3 and propionate in a manner that has interesting implications for the overall control of morphogenetic movements in D. discoideum. Our experiments were conducted using a newly designed continuous-flow apparatus that represents a significant improvement in the technique. The apparatus is described in detail.

Ammonium Chloride↗
PubMed1986

Renal transplantation in diabetes mellitus. Influence of preexisting vascular disease on outcome.

We reviewed the recommendations and outcomes for all patients with diabetes mellitus and end-stage renal disease referred to the Medical Center Hospital of Vermont from 1971 through December 1983. During this period, we recommended transplantation in 53 of 73 patients evaluated. Thirty-two transplants were performed in 30 patients. Of the 30 patients, 10 had clinical vascular disease prior to transplantation, i.e., claudication, amputation, active angina, myocardial infarction, or stroke. Seven of the 10 had only claudication or amputation. These 10 patients showed a clear excess in graft failure and mortality. One- and 2-year graft survival was 37 and 13%; patient survival was 48 and 24%. By comparison, the 20 patients without evident vascular disease had 1- and 2-year graft survival rates of 83 and 75% and patient survival rates of 85% at both 1 and 2 years. The incidence of cardiovascular death in the group with vascular disease was 45% at 1 year and 63% at 2 years, as compared with none in the group without vascular disease. The high graft loss and mortality in this group after transplantation should be a major consideration when therapeutic alternatives are considered in diabetics with end-stage renal disease.

Adult↗
PubMed1985

Two alkaline phosphatase genes positioned in tandem in Bacillus licheniformis MC14 require different RNA polymerase holoenzymes for transcription.

Southern transfer analysis of Bacillus licheniformis MC14 DNA, using as probe a DNA fragment from within the coding region of a previously cloned alkaline phosphatase (APase) gene, revealed a second area of hybridization adjacent to the cloned APase gene. A second APase gene (APase II) was subcloned from the same plasmid clone, pMH8, from which the first APase gene (APase I) had been subcloned. The two genes are arranged in tandem with several hundred base pairs separating them. Immunoblot analysis showed that both code for Mr 60,000 proteins that crossreact with anti-APase. Both proteins enzymatically cleave 5-bromo-4-chloro-3-indolyl phosphate. In vitro transcription showed that APase I and APase II are transcribed in the same direction but that the two genes require different forms of Bacillus RNA polymerase: sigma 55- and sigma 37-containing RNA polymerase holoenzymes, respectively.

Alkaline Phosphatase↗
PubMed1985

Stage-specific cohesion of cell ghosts and plasma-membrane fragments from Dictyostelium discoideum.

During fruiting-body construction by Dictyostelium discoideum, the formation and subsequent maintenance of the multicellular assembly involve two stage-specific cohesive systems that are acquired sequentially and are distinguishable on serological and genetic grounds. We demonstrated that both systems, termed aggregation related (AR) and postaggregation related (PAR), can function in vitro. Ghosts prepared from cells of the wild-type and of a cohesion-defective mutant that were harvested during growth and at aggregation and postaggregative stages of fruiting-body construction exhibited the same cohesive properties as the cells from which they were derived. Membrane fragments prepared from the ghosts by mechanical disruption retained these cohesive properties.

Adhesiveness↗
PubMed1984

Modulation of the cAMP relay in Dictyostelium discoideum by ammonia and other metabolites: possible morphogenetic consequences.

Using a perfusion technique (P.N. Devreotes, P.L. Derstine, and T.L. Steck, 1979, J. Cell Biol. 80, 291-299), it has been shown that cAMP secretion by aggregation-competent cells in response to an exogenous cAMP signal is significantly reduced by exposure to NH4Cl or any of a set of carboxylic acids that includes propionate, succinate, pyruvate, and acetate. The effects of NH4Cl and any of the carboxylic acids are additive and the combinations restrict cAMP secretion to barely detectable or insignificant levels. The inhibitions are rapidly expressed, and are reversible. The activity of NH4Cl is marked at pH 7.2 and undetectable at pH 6.2. Hence, NH3 is presumably the active molecular species. Propionate activity is significantly greater at pH 6.2 than 7.2, indicating that the un-ionized acid is the active species. The data presented herein indicate that these effects are exerted via two separate and independent routes. During exposure of cAMP-stimulated cells to NH4Cl, the decrease in intracellular cAMP accumulation was even greater than the decrease in extracellular accumulation. Hence, NH3 appears to act as a cAMP accumulation inhibitor (CAI). In contrast, exposure to carboxylic acid concentrations that drastically reduce extracellular cAMP accumulation can actually enhance or, at worst, only slightly reduce intracellular accumulation. Hence, the carboxylic acids appear to act as cAMP release inhibitors (CRI). Stationary phase cells incubated on solid substratum in the presence of NH4Cl plus succinate (or propionate) for 18 hr failed to exhibit even the earliest signs of aggregation. If then harvested and redeposited in the absence of the metabolites, they proceeded through the morphogenetic sequence with approximately normal kinetics, suggesting that no significant morphogenetic competence had been achieved during their previous tenure. The morphogenetic implications of cAMP relay modulation are discussed.

Adenosine Triphosphate↗
PubMed1984

Reversible inhibition of aggregation-related cohesivity in Dictyostelium discoideum by diffusible metabolites.

Evidence presented elsewhere (G.B. Williams, E.M. Elder, and M. Sussman 1984, Dev. Biol. 105, 377-388) indicates that NH3 and certain carboxylic acids including propionate, succinate, and acetate modulate the cAMP relay in Dictyostelium discoideum. The former appears to act as a cAMP accumulation inhibitor, the latter as cAMP release inhibitors. The cohesive properties of aggregation competent cells have been assayed quantitatively in the presence of these modulators. The following results were obtained: (1) At pH 7.5, EDTA-resistant cohesivity was greatly inhibited by NH4C within the concentration range tested (30-3.8 mM). Even at the higher concentrations the effect was not immediate but required ca. 10 min for full expression. At the lower concentrations, the inhibitory level was only slightly reduced but the time for full expression progressively increased. At pH 6.5, the level of inhibition was marginal, indicating that NH3 is the active molecular species. By themselves, neither ambient pH nor ionic strength appeared to affect cohesive performance within the ranges employed. The inhibition was immediately and completely reversed upon removal of NH4Cl or a shift of ambient pH from 7.5 to 6.5. The presence of cycloheximide did not affect the recovery of cohesivity after NH4Cl removal. (2) The presence of 15 mM succinate, propionate, or acetate also reduced cell cohesivity. The timing and extent of the inhibition were identical at pH 7.5 and 6.5. The inhibition was expressed immediately and was reversible. Each of the acids acted synergistically with NH4Cl. The relative potencies of these metabolites acting singly or in combination as inhibitors of cohesivity corresponded roughly to their potencies as modulators of the cAMP relay (Williams et al., 1984). (3) The sensitivity to the metabolites was stage specific, being maximal during and shortly after aggregation and disappearing abruptly at 11-12 hr. This corresponds to the time at which this cohesive system, responsible for the end-to-end cell associations evident during aggregation (H. Beug, G. Gerisch, S. Kempff, V. Riedel, and G. Cremer, 1970, Exp. Cell. Res. 63, 147-158) is supplanted by a newly arisen, serologically and genetically distinct system which thereafter maintains the integrity of the aggregate (C. Steinemann and R.W. Parish, 1980, Nature (London) 286, 721-724; D.K. Wilcox and M. Sussman, 1981, Dev. Biol. 82, 102-112, and Proc. Natl. Acad. Sci. USA 78, 358-362; C.L. Saxe III and M. Sussman, 1982, Cell 29, 755-759). The activities of the metabolites, detailed above, are discussed in relation to their previously demonstrated activities as morphogens.

Ammonia↗
PubMed1982

Induction of stage-specific cell cohesion in D. discoideum by a plasma-membrane-associated moiety reactive with wheat germ agglutinin.

Dictyostelium discoideum strain JC-5 is a temperature-sensitive, cohesion-defective mutant. At the restrictive temperature, aggregates are formed and develop normally to a specific late stage, but then disperse to a lawn of noncohesive cells. The defect stems from the inability of the mutant at the restrictive temperature to accumulate or retain an adequate level of a newly arisen, plasma-membrane-associated cohesive moiety during the later stages of morphogenesis. We now report that the noncohesive mutant cells can be induced to cohere at a level of greater than 99% by addition of a fraction reactive with wheat germ agglutinin and isolated from the plasma membranes of late-stage, cohesive mutant or wild-type cells. Furthermore, the cohesivities of late-stage, cohesive mutant or wild-type cells can be significantly enhanced by the same preparations but early-stage cohesive cells remain unaffected. The cohesion-inducing activity can be recovered from two regions of a one-dimensional polyacrylamide gel electropherogram following elution and renaturation. The first is associated with a single silver-staining band (apparent molecular weight 95,000). It appears de novo at a postaggregative stage, and accumulates in a thermostable fashion in the wild-type and in a thermosensitive fashion in the mutants, concurrent with the loss of cohesivity. The second is associated with a complex of silver-staining bands (apparent molecular weights 40,000-50,000). The activity of the eluate reactive with wheat germ agglutinate is destroyed within 5 min at 100 degrees C.

Cell Adhesion↗