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Biomedical subjects

A Sherman

Publications and source records attributed to A Sherman.

At least 73 records · Page 4Linked to original sources
PubMed1990

Domain model for Ca2(+)-inactivation of Ca2+ channels at low channel density.

The "shell" model for Ca2(+)-inactivation of Ca2+ channels is based on the accumulation of Ca2+ in a macroscopic shell beneath the plasma membrane. The shell is filled by Ca2+ entering through open channels, with the elevated Ca2+ concentration inactivating both open and closed channels at a rate determined by how fast the shell is filled. In cells with low channel density, the high concentration Ca2+ "shell" degenerates into a collection of nonoverlapping "domains" localized near open channels. These domains form rapidly when channels open and disappear rapidly when channels close. We use this idea to develop a "domain" model for Ca2(+)-inactivation of Ca2+ channels. In this model the kinetics of formation of an inactivated state resulting from Ca2+ binding to open channels determines the inactivation rate, a mechanism identical with that which explains single-channel recordings on rabbit-mesenteric artery Ca2+ channels (Huang Y., J. M. Quayle, J. F. Worley, N. B. Standen, and M. T. Nelson. 1989. Biophys. J. 56:1023-1028). We show that the model correctly predicts five important features of the whole-cell Ca2(+)-inactivation for mouse pancreatic beta-cells (Plants, T. D. 1988. J. Physiol. 404:731-747) and that Ca2(+)-inactivation has only minor effects on the bursting electrical activity of these cells.

Animals↗
PubMed1990

Managing myopia.

Explore the source record for details and available documents.

Humans↗
PubMed1989

Perirectal abscess in the Hermansky-Pudlak syndrome.

The Hermansky-Pudlak syndrome (HPS) is a triad of tyrosine-positive albinism, platelet dysfunction, and the deposition of an abnormal ceroid-like pigment in the tissues. Complications of the syndrome, such as pulmonary fibrosis, renal failure, and cardiomyopathy, have been described. Granulomatous colitis has been documented in several families with the HPS. The bowel disease of the HPS is a unique type of inflammatory bowel disease with clinical features suggestive of idiopathic ulcerative colitis and pathologic features suggestive of Crohn's disease. Analogous to the presentation of Crohn's disease with perianal and perirectal involvement, we describe the occurrence of perianal disease and a perirectal abscess in a 29-yr-old woman with HPS and mild granulomatous colitis.

Abscess↗
PubMed1989

Studies on contact activation: effects of surface and inhibitors.

Contact activation is initiated when the plasma proteins, Hageman factor (factor XII), prekallikrein and high molecular weight kininogen interact with negatively charged materials. The activation of the intrinsic pathway of blood coagulation and the production of bradykinin are among the sequelae of contact activation. The kinetics of the activation of the contact system are modified by plasma inhibitors, C1 inhibitor being quantitatively the most important. We propose that the activation of the system requires that the stimulus provided by the surface must be greater than a threshold value to overcome the effects of the inhibitors. We show in this paper that the amount of surface required for activation is much reduced in the absence of C1 inhibitor (Hereditary Angioedema) or in the cold where the inhibitor loses much of its effectiveness. Antithrombin III inhibition of activated Hageman factor is augmented by heparin which is also an activator of Hageman factor. The rate constants for inhibition remain much lower than for C1 inhibitor, however.

Antithrombin III↗
PubMed1989

Spontaneous intramural hematoma of the esophagus.

Spontaneous intramural hematoma of the esophagus (SIHE) is a rare condition usually affecting middle-aged or elderly women. It presents as acute substernal or epigastric pain, typically accompanied by dysphagia or hematemesis. SIHE is not usually associated with vomiting, and is therefore clearly distinguished from emetogenic esophageal disorders, such as the Mallory-Weiss lesion and the Boerhaave syndrome. The diagnosis has traditionally been made by barium esophagram. Therapy is conservative; a favorable prognosis is the rule. The pathogenesis is in dispute. We present a case of SIHE without a discernible mucosal breach, suggesting a primary intramural bleed as the initiating event. We document the utility of computed tomographic scan and magnetic resonance imaging in the diagnosis of SIHE.

Aged↗
PubMed1988

Emergence of organized bursting in clusters of pancreatic beta-cells by channel sharing.

Pancreatic beta-cells in an intact Islet of Langerhans exhibit bursting electrical behavior. The Chay-Keizer model describes this using a calcium-activated potassium (K-Ca) channel, but cannot account for the irregular spiking of isolated beta-cells. Atwater I., L. Rosario, and E. Rojas, Cell Calcium. 4:451-461, proposed that the K-Ca channels, which are rarely open, are shared by several cells. This suggests that the chaotic behavior of isolated cells is stochastic. We have revised the Chay-Keizer model to incorporate voltage clamp data of Rorsman and Trube and extended it to include stochastic K-Ca channels. This model can describe the behavior of single cells, as well as that of clusters of cells tightly coupled by gap junctions. As the size of the clusters is increased, the electrical activity shows a transition from chaotic spiking to regular bursting. Although the model of coupling is over-simplified, the simulations lend support to the hypothesis that bursting is the result of channel sharing.

Action Potentials↗
PubMed1987

Flow cytometry and Feulgen cytophotometry in evaluation of effusions.

Fifty-eight effusions (42 pleural and 16 ascitic fluids) from patients with and without cancer were analyzed by conventional cytology and the results compared with DNA patterns generated by flow cytometry of 10(4) nuclei and several modes of Feulgen cytophotometry. In 31 patients (24 without evidence of cancer and seven with history of cancer and cytologically negative fluids), the fluids were diploid by flow cytometry. One fluid with atypical cells from a lymphoma suspect was also diploid. Flow cytometry of 26 cytologically cancerous fluids disclosed aneuploid DNA patterns in 16 and diploid patterns in ten. Feulgen cytophotometry of 11 of these fluids (three aneuploid, eight diploid) was performed on nuclear preparations identical to those used in flow cytometry and on restrained smears used for visual analysis. The analysis was performed in two modes: as a study of 500 sequential nuclei in an automated system, mimicking flow cytometry, and visually selected large, presumably malignant nuclei. In nine of the 11 cases, the DNA content of visually selected cancer cells was aneuploid, even though this DNA pattern was not evident in the analysis of 500 sequential cells. In two cases, both diploid by flow cytometry, the Feulgen analysis confirmed the presence of cancer cells in the diploid range. In samples of 10(4) nuclei representing a mixed population of cells occurring in effusions, the presence of aneuploid cancer cells may not be disclosed by conventional flow cytometry. A larger sample of cells, a detailed analysis of DNA histograms, and perhaps sorting of select cells in the hypertetraploid range, may prove essential before flow cytometry can be accepted as a diagnostic tool in the laboratory in the assessment of effusions.

Aneuploidy↗
PubMed1987

Desipramine plasma levels and clinical response: evidence for a curvilinear relationship.

Twenty-six outpatients with major depression completed a 6-week, fixed dose trial of desipramine and provided plasma samples. Recovery after 6 weeks, defined in either of two ways, corresponded to lower desipramine levels, while clinical status at 4 weeks bore no apparent relationship to plasma levels. Upper limits of 140 or 155 ng/ml emerged depending on the outcome measure used. Patients with endogenous depression, those with primary depression, and those with abnormal dexamethasone suppression test results yielded similar therapeutic thresholds, while the sharpest blood level/response relationship emerged in the subgroup with an abnormal escape from dexamethasone.

Adolescent↗
PubMed1987

Primary gastrointestinal Kaposi's sarcoma in a patient with acquired immune deficiency syndrome.

Gastrointestinal involvement by Kaposi's sarcoma in patients with cutaneous or lymph node involvement is common. Since the advent of the acquired immune deficiency syndrome in 1981, primary gastrointestinal involvement, i.e., without skin or lymph node involvement, has not been adequately documented. We describe a patient with acquired immune deficiency syndrome and primary gastrointestinal involvement by Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Metabolism of an ingested serine load in psychotic and nonpsychotic subjects.

Our previous studies have shown that in psychotics, the plasma serine level is abnormally high and that plasma serine hydroxymethyltransferase (which cleaves serine to glycine) activity is abnormally low as compared with that in nonpsychotic subjects. In this study, psychotic and nonpsychotic subjects ingested a large bolus of L-serine (4 mM/kg) at breakfast and blood was drawn before breakfast, 2 hr, 4 hr, and 6 hr after serine ingestion. Baseline serine and SHMT activity differentiated between psychotics and nonpsychotics with high degrees of significance (p less than 0.0001) and p less than 0.01, respectively). Plasma serine levels 2 hr after serine ingestion were significantly higher (p less than 0.01) in nonpsychotics as compared with psychotics. Elimination of serine in psychotics was bimodal and was significantly different from that of nonpsychotics (p less than 0.0079, Moses test). These findings provide additional evidence for abnormal serine metabolism in psychotic patients.

Age Factors↗
PubMed1984

The treatment of tricyclic antidepressant overdose with repeated charcoal.

Activated charcoal given repeatedly through a nasogastric tube to three patients in coma from amitriptyline overdose greatly accelerated tricyclic elimination: the apparent half-life fell below 10 hours for each patient to as low as 4 hours. This contrasts with extended half-lives for amitriptyline elimination averaging 36.8 hours and regularly over 60 hours previously reported for overdoses treated without repeated charcoal. The enterohepatic recirculation of amitriptyline and nortriptyline appears to be a major influence on keeping their blood levels up. In one case, intravenous diazepam inhibited tricyclic elimination.

Adolescent↗
PubMed1984

Nuclear pores and DNA ploidy in human bladder carcinomas.

The number of nuclear pores per sq micron was determined on the freeze-fractured nuclei of 20 human bladder tumors and five control samples of normal bladder epithelium. Measurements of the nuclear surface and volume were also performed, and the mean number of pores per nucleus and the ratio of pore to volume were calculated. The DNA distribution pattern on the same samples was determined by flow cytometry. All control samples and 12 tumors were diploid, and eight tumors were aneuploid. The mean number of pores per sq micron and mean total number of pores per nucleus in the control samples and in diploid tumors were similar. In the aneuploid tumors, both values were significantly higher. However, the ratio of pore to volume was shown to be constant regardless of the DNA content. It was further observed that, in aneuploid tumors, there are two populations of nuclei, one with density of pores similar to the diploid tumor and one with a higher pore density. Because aneuploid bladder tumors have been shown to have more aggressive behavior than diploid tumors, increased density of nuclear pores or their total number per nucleus may be related to tumor behavior. This view is supported by the observation that five of eight tumors with increased density and total pore number were invasive, while all tumors with low pore number were noninvasive.

DNA, Neoplasm↗
PubMed1982

DNA distribution in human colon carcinomas and its relationship to clinical behavior.

Striking differences in outcome of surgically treated colon adenocarcinomas were observed in 33 patients according to the DNA distribution patterns in tumor nuclei, measured by flow cytometry. As discussed and defined in the text and confirmed by appropriate control studies, the tumors were classified into 2 groups: predominantly diploid (20 tumors) and predominantly nondiploid (13 tumors). During the follow-up period of 3-5 years, 12 of the 13 patients with "nondiploid" tumors died of disease within 4-34 months, and the 1 patient still alive after 59 months has extensive metastases. Only 6 of the 20 patients with "diploid" tumors died of disease, sometimes after a slow, protracted clinical course. There were 14 patients with no evidence of disease for periods ranging from 30 to 60 months; 1 of these patients died of other causes. Histologic grading and Dukes' staging appeared to play a relatively limited role in the outcome, although lymph node metastases and vascular invasion were more often observed in the nondiploid tumors. These observations suggest that the determination of DNA distribution in colon carcinomas may prove to be of prognostic value.

Adenocarcinoma↗