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Biomedical subjects

S Rothman

Publications and source records attributed to S Rothman.

At least 37 records · Page 2Linked to original sources
PubMed1988

Noncompetitive N-methyl-D-aspartate antagonists affect multiple ionic currents.

Recent reports have indicated that the dissociative anesthetic ketamine and the related drugs phencyclidine and MK-801 noncompetitively antagonize excitation mediated by the N-methyl-D-aspartate receptor; they have little effect at kainate or quisqualate receptors. However, this action does not readily explain all the behavioral or metabolic effects of these drugs. In view of previous reports that phencyclidine interacts with potassium channels in a variety of excitable cells, the author investigated the ability of phencyclidine, ketamine and MK-801 to block voltage-gated potassium currents in cultured rat hippocampal neurons. Under voltage clamp all three drugs reduced both early, transient potassium currents and steady-state potassium currents when neurons were stepped between -80 and -10 mV. In current clamp, phencyclidine and MK-801 diminished the action potential peak, its maximum rate of rise and its maximum rate of fall, suggesting that they antagonize sodium as well as potassium currents. Both phencyclidine and MK-801 produced a slowly developing blockade of N-methyl-D-aspartate currents which was present at a holding potential of -50 mV. The selective potassium channel blocker 4-aminopyridine had no effect on N-methyl-D-aspartate responses. These findings indicate that this group of drugs can interact with voltage-gated channels, in addition to N-methyl-D-aspartate gated channels. However, the high concentrations required to block voltage-gated channels suggests that these effects are not behaviorally relevant.

Action Potentials↗
PubMed1987

X-ray holograms at improved resolution: a study of zymogen granules.

X-ray holography offers the possibility of three-dimensional microscopy with resolution higher than that of the light microscope and with contrast based on x-ray edges. In principle, the method is especially advantageous for biological samples if x-rays in the wavelength region between the carbon and oxygen K edges are used. However, until now the achieved resolution has not exceeded that of the light microscope because of the poor coherence properties of the x-ray sources and the low resolution of the detectors that were available. With a recently developed x-ray source based on an undulator on an electron storage ring, and high resolution x-ray resist, a hologram has been recorded at about 400-angstrom resolution. The experiment utilized x-rays with wavelengths of 24.7 angstroms and required a 1-hour exposure of the pancreatic zymogen granules under study.

Animals↗
PubMed1984

Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death.

The pathophysiology of hypoxic neuronal death, which is difficult to study in vivo, was further defined in vitro by placing dispersed cultures of rat hippocampal neurons into an anoxic atmosphere. Previous experiments had demonstrated that the addition of high concentrations of magnesium, which blocks transmitter release, protected anoxic neurons. These more recent experiments have shown that gamma-D-glutamylglycine (DGG), a postsynaptic blocker of excitatory amino acids, was highly effective in preventing anoxic neuronal death. DGG also completely protected the cultured neurons from the toxicity of exogenous glutamate (GLU) and aspartate (ASP). In parallel physiology experiments, DGG blocked the depolarization produced by GLU and ASP, and dramatically reduced EPSPs in synaptically coupled pairs of neurons. These results provide convincing evidence that the synaptic release of excitatory transmitter, most likely GLU or ASP, mediates the death of anoxic neurons. This result has far-reaching implications regarding the interpretation of the existing literature on cerebral hypoxia. Furthermore, it suggests new strategies that may be effective in preventing the devastating insults produced by cerebral hypoxia and ischemia in man.

Animals↗
PubMed1983

Attention deficit disorder: quantitative analysis of CT.

We compared the measurements of CTs in two groups of children: 35 satisfying DSM III criteria for attention deficit disorder (ADD) and 27 controls with other conditions. The groups were comparable in age, sex, and IQ. Measurements of the anterior horns of the lateral ventricles, bifrontal width, and right and left hemispheres did not differ. The ratio of ventricular size/bifrontal brain width (Evan's Index) averaged 0.237 in ADD and 0.263 in controls--results similar to those obtained in normal children by other investigators. Our findings suggest that when quantitative techniques, contrast populations, and "blind" analysis of CTs are employed, the results are indistinguishable in children with ADD and contrasts. If anatomic abnormalities are present in ADD, they are not discernible with current CT technology.

Adolescent↗
PubMed1981

A scanning electron microscope study of the in vitro development of dissociated hippocampal cells.

Cultures of dissociated hippocampal neurons from 18-day-old rat fetuses were examined by scanning electron microscopy after periods between one hour and 20 days following plating on a poly-L-lysine coated substrate. Cell attachment was virtually complete within one hour after plating, and at that stage many cells could be seen which had started to extend processes with broad growth cones. By four hours in culture, process formation was well advanced and some cells had already assumed a pyramidal configuration. After 16 hours in culture, numerous contacts were seen between neighboring growth cones, and this frequently led to fasciculation of the interacting fibers. During the next three weeks the cell bodies enlarged considerably and rounded-up, and two distinct types of processes became evident: large, rapidly tapering dendrite-like processes and finer, essentially uniform-diametered processes that resemble axons. In most of the older cultures a dense plexus of processes was formed, and many of the finer processes appeared to have "bouton-like" swellings as they traversed the upper surfaces of the neuronal perikarya. Non-neuronal elements, which comprised only about 5% of the cells initially plated, rapidly proliferated in our cultures and within three to six days formed a confluent monolayer beneath the neurons.

Animals↗
PubMed1981

Case report. Rapid development of cerebral atrophy due to perinatal herpes simplex encephalitis.

A case of neonatal herpes simplex virus (HSV) encephalitis is reported in which diffuse cerebral hemorrhagic lesions were seen in the neonatal period. Severe progressive cortical atrophy with parenchymal calcification developed over the subsequent 9 months, resulting in a striking computed tomography (CT) appearance. The range of CT findings in neonatal HSV encephalitis is reviewed, and differential diagnostic considerations in the present case are discussed.

Atrophy↗
PubMed1979

Unilateral cryptophthalmia.

Two patients had the variable clinical features of unilateral cryptophthalmia. A 5-month-old boy had isolated unilateral cryptophthalmia: a small boney orbit, deformed optic canal, and a small amorphous mass with no normal intraocular tissue representing the globe. No extraocular muscles or optic nerve were identified by B-scan ultrasound or by computed axial tomography x-ray techniques. The second patient, a 13-year-old girl, had unilateral cryptophthalmia, and numerous systemic abnormalities including a head circumference less than the third percentile, severe mental retardation, hypoplasia of the left side of the head, and a left facial cleft deformity. She also had contractures of hips, knees and ankles, and bilateral spasticity and jerky movements. The left boney orbit was contracted and deformed and contained a small amorphous tissue with no ocular detail, as revealed by B-scan and computed tomography scan.

Abnormalities, Multiple↗
PubMed1979

Two kinds of radicals: a discriminant analysis of a projective test.

Rorschach tests were administered to 36 subjects grouped according to ethnicity and political ideology. Pairwise discriminant analyses of scores significantly differentiated both Jewish and non-Jewish radicals from nonradicals in a manner consistent with previous survey findings.

Journal Article↗
PubMed1979

Role of clostridial toxin in the pathogenesis of clindamycin colitis in rabbits.

The pathophysiology of antibiotic-associated colitis was studied in rabbits with severe ileocolitis induced by oral administration of clindamycin. Cell-free, sterile filtrates of cecal contents of rabbits with clindamycin colitis contained a toxin that was lethal for mice and cytotoxic for HeLa-cell monolayers. The toxin was heat labile, was inactivated by pronase but not trypsin, and had a mol wt by gel filtration on Sephadex G-100 of 45,000. The toxin was neutralized by antiserum to Clostridium perfringens type E, but not by other clostridial antisera. The toxin also caused severe necrosis of rabbit rectal epithelium during 18-hr organ culture, which could be completely reversed by neutralization with C. perfringens type E antiserum. These studies indicate that clindamycin colitis in rabbits is caused by overgrowth of a clostridial species, which releases a heat-labile toxic protein of mol wt of 45,000 capable of necrosing colonic epithelial cells.

Administration, Oral↗
PubMed1978

Pathological involvement of primary sensory neurons in Werdnig-Hoffmann disease.

Seven patients with the typical clinical picture and muscle biopsy findings of classical Werdnig-Hoffmann disease showed Wallerian degeneration in their biopsied sural nerves. In dorsal root ganglia of one patient there were residual nodules and several chromatolytic neurons. By electron microscopy the changes of chromatolysis were confirmed and found to be consistent with an axonal reaction. Involvement of the primary sensory neuron is probably a regular pathologic feature of Werdnig-Hoffmann disease. The type of abnormality suggests in initial failure of the axon distal to the nerve roots.

Axons↗
PubMed1976

The childhood type of dermatomyositis.

The childhood type fo dermatomyositis, which occurs in children and young adults, shows a specific constellation of pathologic changes in muscle. Capillary necrosis leads to capillary loss, generally starting on the periphery of muscle fascicles. Electron microscopy discloses undulating tubules in endothelial cells, lymphocytes, pericytes, and pseudosatellite cells. The muscle fiber damage is coextensive with capillary damage and probably results from progressive ischemia. The muscle cells, before atrophying, show mitochondrial elongation, Z disk streaming, focal myofibrillary loss, and occassionally selective thick filament loss. Muscle cell necrosis is rare and limited to infarctlike lesions. Inflammatory infiltrates, if present, occur only in connective tissue septa. The cause of the capillary damage has not been determined.

Adult↗
PubMed1975

The syndrome of systemic carnitine deficiency. Clinical, morphologic, biochemical, and pathophysiologic features.

An 11-year old boy had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped musculature. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. Hypertrophied smooth endoplasmic reticulum and excessive microbodies were present in liver. Marked carnitine deficiency was shown in skeletal muscle, plasma, and liver. Ketogenesis was impaired on a high fat diet, but omega oxidation of fatty acids was enhanced. There was excessive glucose uptake and essentially no oxidation of labeled long-chain fatty acids by perfused forearm muscles in vivo. Oral replacement therapy restored plasma carnitine levels to normal, but not liver or muscle carnitine levels, and was accompanied by clinical improvement.

Adenosine Triphosphatases↗
PubMed1974

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History, Modern 1601-↗