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Biomedical subjects

S Rothman

Publications and source records attributed to S Rothman.

At least 19 recordsLinked to original sources
PubMed1991

Nonparallel transport and mechanisms of secretion.

After many years of controversy, it is now clear that at least some cells and tissues that secrete more than one product can vary the composition of the secreted mixture as the result of the differential transport of various substances out of the cells that secrete them. In this article we discuss this phenomenon, non-parallel transport or secretion, and how it has and continues to inform us about how cells release the products they manufacture. We focus on expression of the phenomenon in the secretion of digestive enzymes by the exocrine pancreas, where it has been studied most extensively.

Animals↗
PubMed1991

The relationship between the light scattering properties of zymogen granules and the release of their contained proteins.

The optical density of suspensions of the digestive enzyme-containing zymogen granule, a roughly spherical 1 micron diameter membrane-enclosed subcellular structure isolated from the exocrine pancreas of mammals, is reduced greatly when they are suspended in physiological media. This reduction in optical density is accompanied by the release of the granule's protein contents. It has traditionally been assumed that this property is due to granule lysis; that is, dissolution of the particle and its consequent disappearance as a strongly scattering object. Thus, lysis would decrease optical density by decreasing the number density of suspended spheres (N) according to Beer's law. However, as a general matter, changes in the optical density of suspensions of spheres may be a function of changes in the refractive index (m) or radius (r) of the objects as well. In this study, we apply Mie theory of scattering by small particles, which, in conjunction with Beer's law, allows us to evaluate whether changes in the scattering properties of granule suspensions are due to changes in N, m or r. Scattering by granule suspensions was reduced in three ways-pH, calcium ion concentration, and detergent concentration. A simple reduction in particle number did not account for decreased scattering and protein release in any of these circumstances. Instead, the changes appear attributable to decreases in particle size and refractive index.

Animals↗
PubMed1991

Cytochrome c oxidase-associated Leigh syndrome: phenotypic features and pathogenetic speculations.

Fourteen new cases of cytochrome oxidase (COX)-associated Leigh syndrome (LS) are combined with 20 reported cases to describe the clinical, laboratory, and radiological features of this devastating metabolic condition. Three clinical stages are identified. Most patients have normal neurological development during the first 8-12 months (stage I). Somatic complaints are common, including chronic diarrhea, recurrent vomiting, anorexia, and decelerating body and head growth. The second stage evolves during late infancy and early childhood when motor regression becomes evident. Eye signs, altered breathing patterns, pyramidal, extrapyramidal, and cerebellar signs emerge and sudden clinical deterioration occurs during intercurrent infectious or metabolic stress. The last stage may extend from 2 to 10 years and is manifested by extreme hypotonia, swallowing difficulties and undernutrition. Feeding assistance is necessary and seizures may occur. The CSF lactate concentration is consistently elevated and MRI abnormalities are seen in the subcortical structures. COX deficiency affects most tissues, but is not always generalized. For example, 3 patients with a cardiomyopathy had normal COX activity in cultured skin fibroblasts. Nearly normal amounts of cross-reacting material are present by ELISA and immunoblot analyses. Parental consanguinity has been found in several families, the hereditary pattern is recessive and males are affected more commonly (2:1). The biomolecular abnormality causing COX deficiency in LS is unknown, but the available evidence implicates a nuclear-encoded protein that affects the structure or the stability of the holoenzyme complex.

Adolescent↗
PubMed1991

Lumbar facet fracture as a possible source of pain after lumbar laminectomy.

This study compared 50 patients with lumbar facet fractures and continued pain after lumbar laminectomy with a postlaminectomy control group without facet fractures. Computed tomographic analysis compared variables including direct measurements of bone resection. Average follow-up between surgery and postsurgical computed tomographic examination was 3.2 years. In the fracture group, more than one half of the bone immediately above the flare of the inferior articular process at the level of the laminectomy, measured in a medial to lateral direction, had been resected. No one in the control group had more than one quarter of this bone removed (P = .0001). Lumbar facet fractures may be one cause of late postlaminectomy pain. Caution in resection of a particular area of bone may avoid this problem.

Follow-Up Studies↗
PubMed1989

Comparison of computerized tomography parameters of the cervical spine in normal control subjects and spinal cord-injured patients.

The cross-sectional area and the sagittal and transverse diameters of the cervical spinal canal were measured, using high-resolution, thin-section computerized-tomography images, in 100 control subjects and forty-two patients who had a traumatic injury to the spinal cord. No significant differences were found between the control and the spinal cord-injured group with regard to the cross-sectional area of the spinal canal; however, the differences between the two groups were significant with regard to mean sagittal and transverse diameters of the spinal canal. The sagittal diameters of the spinal canal of the control group were significantly larger than those of the spinal cord-injured group. Conversely, the transverse diameters of the spinal canal of the spinal cord-injured group were significantly larger than those of the control group. These findings suggest that certain patients may be predisposed to spinal cord injury, given sufficient trauma. It is not the total volume of space in the spinal canal that is the critical factor; rather, it is the shape. An index of shape is the ratio of the sagittal to the transverse diameter. The difference between the two groups, based on the ratio of sagittal to transverse diameter, was highly significant. Because this measure is a ratio, there is no need to evaluate an individual on the basis of measurements of absolute values.

Adolescent↗
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

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↗