Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 325 records · Page 18Linked to original sources

PubMed1984

Psychomotor epileptic symptoms in six patients with bipolar mood disorders.

Of 12 consecutive patients with bipolar mood disorders satisfying DSM-III criteria, six were discovered to have five or more psychomotor epileptic symptoms. All of the six had olfactory hallucinations, metamorphopsias, and multiple déjà vu or mystical experiences. Each of them responded to lithium carbonate and had a first-degree relative with a bipolar disorder. The authors suggest that psychomotor symptoms may be more prevalent in bipolar patients than has hitherto been recognized.

Adult↗

PubMed1984

Abnormal parasympathetic vagal function in patients with spasmodic dysphonia.

Gastric vagal function was assessed in 15 patients with spasmodic dysphonia by measuring gastric acid output in response to sham feeding. Patients secreted significantly less acid than controls (p less than 0.001). Cardiac vagal function was assessed in 11 patients by measuring heart rate during deep respiration and also during and after Valsalva maneuver. Patients with spasmodic dysphonia had a significantly reduced fluctuation of heart rate during deep respiration (sinus arrhythmia). The expiratory to inspiratory R-R interval averaged 1.08 +/- 0.08 (mean +/- SD) in patients and 1.22 +/- 0.10 in controls (p less than 0.005). The ratio of tachycardia during Valsalva maneuver to bradycardia after Valsalva maneuver was also lower in patients than in controls (p less than 0.005). The auditory brainstem response was abnormal in 11 of 15 patients. Our results show either a central brainstem abnormality or several cranial nerve abnormalities in some patients with spasmodic dysphonia.

Adult↗

PubMed1984

Effect of indomethacin on gastric acid and bicarbonate secretion in humans.

The role of endogenous prostaglandins in the physiologic regulation of gastric secretion is unclear. We evaluated the effect of indomethacin, an inhibitor of endogenous prostaglandin synthesis, on basal gastric secretion in humans using a two-component model for calculating gastric acid and bicarbonate secretion. After a control, gastric secretory study, 11 healthy volunteers were given 50 mg of indomethacin orally every 8 h for a total of 10 doses, after which the gastric secretory experiment was repeated. Indomethacin significantly (p less than 0.05) increased basal gastric juice volume, hydrogen ion concentration, osmolality, and acid output. Indomethacin increased acid secretion significantly (from 4.9 +/- 1.2 to 7.4 +/- 1.7 mmol/75 min, p less than 0.02) without affecting gastric bicarbonate secretion (control 2.7 +/- 0.8, indomethacin 3.0 +/- 0.7 mmol/75 min; p greater than 0.05). The increase in basal acid secretion after indomethacin administration was quite variable from subject to subject and was unaccompanied by significant changes in basal serum gastrin concentrations. Unlike basal acid secretion, indomethacin had no significant effect on acid secretion stimulated by intragastric infusion of homogenized food. Moreover, indomethacin did not prevent intravenous somatostatin 14 from inhibiting food-stimulated acid secretion, in contrast to a previous study in rats in which indomethacin blocked the inhibitory effect of somatostatin on acid secretion. Assuming the effect of indomethacin is due to reduced endogenous prostaglandin synthesis, we conclude that (a) in some individuals endogenous prostaglandins suppress basal acid secretion by a mechanism independent of the hormone gastrin; (b) endogenous prostaglandins play little, if any, role in the regulation of basal bicarbonate secretion by the stomach; and (c) endogenous prostaglandins do not regulate food-stimulated acid secretion, nor do they mediate the inhibitory effect of somatostatin on gastric acid secretion in humans.

Adult↗

PubMed1984

Inhibition of gastric acid secretion by selective and nonselective anticholinergics.

Anticholinergics have been used for many years to reduce gastric acid secretion (e.g., in peptic ulcer patients). Because of their side effects and the advent of histamine-2 receptor antagonists, however, anticholinergics are now used much less frequently as antisecretory agents. Recently, a selective antimuscarinic type of anticholinergic, pirenzepine, has been developed. This agent reduces acid secretion and heals ulcers without producing serious side effects, probably by preferentially blocking a certain subtype of muscarinic receptor for acetylcholine (M1 receptor). This article will review the current types and subtypes of cholinergic receptors and the mechanisms by which antimuscarinic agents, including pirenzepine, reduce gastric acid secretion.

Benzodiazepinones↗

PubMed1984

Loss of the H-2.33 private specificity by 3LL tumor cells correlates with the tumor potential to metastasize across the H-2K region genetic barriers.

Grafts of the metastatic 3LL Lewis lung carcinoma result in pulmonary metastases in mouse strains which share with the tumor strain of origin (C57BL/6, H-2b) the non-H-2 background genes and the H-2D/H-2L region of the major histocompatibility complex. Lung metastases across H-2K region disparities correlated with low expression of H-2Kb-encoded molecule on the tumor cell surface. We tested whether the 3LL tumor cells lack H-2Kb private and/or public specificities by staining 3LL tumor cells and spleen cells of different recombinant mouse strains with H-2d anti-H-2b and anti-3LL antisera, respectively, following absorption of the antisera on spleen cells from various recombinant mouse strains. The data demonstrated weak expression of H-2Kb public specificities (which could represent H-2Db/H-2Kb biregional encoded molecules) and a complete lack of expression of the H-2.33 H-2Kb private specificity by 3LL tumor cells. The findings provide a possible explanation for the 3LL metastatic potential across H-2Kb region disparities.

Animals↗

PubMed1984

Gastric emptying of solid radiopaque markers: studies in healthy subjects and diabetic patients.

The purpose of these studies was to develop a radiologic method for assessing gastric emptying of an indigestible solid in humans and to apply this technique to the evaluation of patients with diabetes mellitus. Thirty healthy subjects ingested 10 solid radiopaque markers (small pieces of nasogastric tubing) together with a standard meal (donuts and 7-Up). Radiographs of the upper abdomen were obtained hourly for up to 6 h until all markers had emptied from the stomach. Although most of the liquid component of the meal, labeled with 111In, emptied during the first hour (as assessed simultaneously by radionuclide scintigraphy), few radiopaque markers emptied from the stomach during the first 2 h after the meal. Most markers emptied during the fourth postprandial hour, and all 10 markers had emptied by 6 h in 45 of 46 experiments. In contrast, not all of the solid radiopaque markers emptied from the stomach by 6 h in 16 of 26 experiments in patients with diabetes mellitus (p less than 0.001 vs. healthy controls). In some experiments, 99mTc-labeled scrambled eggs were added to the meal so that emptying of this digestible solid, assessed by scintigraphy, could be compared with emptying of liquids and solid radiopaque markers. In healthy subjects, the digestible solid emptied more slowly than the liquid (t 1/2 = 154 +/- 11 min vs. 30 +/- 3 min, p less than 0.001), but emptying of digestible solid was significantly faster than the emptying of the indigestible solid radiopaque markers. In diabetics, emptying rates for the digestible solid and liquid were close to normal (t 1/2 = 178 +/- 5 min and 40 +/- 3 min, respectively), whereas indigestible solid markers were retained in the stomach 6 h after the meal in 50% of the patients. Radiopaque markers proved to be a simple method for measuring gastric emptying of indigestible solids in humans. Using this technique, patients with insulin-dependent diabetes mellitus had a high incidence of abnormally slow gastric emptying of indigestible solids; the method may be a more sensitive indicator of gastric motor dysfunction than radionuclide scintigraphy.

Adult↗

PubMed1984

Nonorganophilic, hematogenous dissemination in the presence of positive lymph nodes of a malignant tumor in rabbits.

An animal model has been devised which for the first time allows direct investigation of the roles of vascular dynamics, hematogenous versus lymphatic pathways, and involved regional lymph nodes in malignant dissemination. The VX2 anaplastic carcinoma growing in the hindlimb of rabbits normally metastasizes exclusively to the lungs, yet in this study was made to metastasize exclusively to the liver by construction of a cavoportal shunt prior to tumor transplantation. This technique also provided separation of the tumor's venous and lymphatic outflow. Normal and shunted animals with forelimb transplantation of the tumor, which acted as controls for the effects of the shunt operation itself, showed the same metastatic pattern as normal rabbits bearing hindlimb tumors. These results are direct evidence that a primary tumor metastasizes according to non-organophilic circulation dynamics and that lymphatic pathways, including metastatic regional lymph nodes, have no role in distant metastasis.

Animals↗

PubMed1984

Macrophage-hybridomas: generation, structure, and function.

We report the generation of macrophage-hybridomas, obtained by somatic cell fusion between macrophage-enriched C3H.eB spleen cell population, and a drug-resistant MPC-11 myeloma cell line, designated as 4T00.1L1 clone. Screening for hybridomas possessing macrophage properties was carried out by assaying the presence of two macrophage-specific enzymes: lysozyme and nonspecific esterase. Two hybridomas, E2-7 and E2-10, were selected for further studies. We found that clones of E2-7 (E2-7.7) did not express Fc receptors but possessed cell-surface Ia molecules. In contrast, clones of E2-10 (E2-10.20) possessed Fc receptors but were devoid of Ia molecules. E2-7.7 did, however, express Fc receptors after mitomycin treatment, whereas E2-10.20 eliminated the expression of Fc receptors after treatment with mitomycin C. Opsonized erythrocytes were phagocytized by E2-10.20 cells, but not by E2-7.7. Phagocytosis was thus correlated with the possession of Fc receptors. Testing the response of KLH-primed lymph node cells to KLH-pulsed hybridoma cells, we found that E2-7.7 cells caused antigen-specific lymphoproliferative response, whereas E2-10.20 did not. Thus, antigens could be presented by E2-7.7 but not by E2-10.20 cells. The response was shown to be mediated by T but not by B lymphocytes. The difference in antigen-presenting capacity could not be attributed to differences in antigen uptake by the different hybridomas, because the two hybridomas manifested the same level of pinocytosis. Both hybridomas produced IL1. The differences in the properties of the two hybridomas may indicate that the normal partners represent two distinct subpopulations of macrophages. The segregation of functional properties among the hybridoma clones may lead to a clarification of the dependence of distinct functions on defined molecular structures.

Animals↗

PubMed1983

Peptide fragments from the tuftsin containing domain of immunoglobulin G synthesis and biological activity.

Peptides corresponding to sequences of the Fc-portion of immunoglobulin G (IgG) surrounding and containing the tuftsin molecule were synthesized. The compounds were assayed for their ability to compete with [3H-Arg4]tuftsin in binding to mouse peritoneal macrophages and to stimulate the cell's capacity to phagocytize. Despite the sensitivity that tuftsin has demonstrated to various chemical modifications and structural alterations which usually cause reduction or total loss of biological activity, IgG-related analogs possess potent tuftsin-like activity. The activity is not caused by enzymatic breakdown and release of tuftsin. The fact that the elongated tuftsin analogs can specifically be attached to and activate macrophages may indicate a possible connection between Fc and tuftsin's receptors.

Amino Acid Sequence↗

PubMed1983

MHC imbalance and metastatic spread in Lewis lung carcinoma clones.

Imbalance in the Kb and Db region encoded molecules is observed in Lewis lung carcinoma clones. The uncloned metastatic population and the D122 high-metastatic clone show no expression of H-2Kb products, while the nonmetastatic A9 clone expresses Kb products. Twenty-nine new subclones of 3LL and A9 were analyzed for D-end and K-end membrane expression, primary growth rate and metastatic spread. We show that the imbalance in H-2Kb to H-2Db is correlated with metastatic properties of a given clone, but local tumor growth is not. A "low Kb/low Db" phenotype is nonmetastatic as is a "high Kb/high Db" phenotype; a "low Kb/high Db" is highly metastatic and a "medium Kb/high Db" is moderately metastatic. We find support for this notion of imbalance in experiments on MHC modulation by interferon and retinoic acid. Interferon increases both Kb and Db expression of A9 and D122 clones yet the net increase of Db was greater than Kb. This was associated with an increase in metastasis formation. Retinoic acid increases the expression of the Db gene product on the nonmetastatic A9, clone, without apparent changes in Kb expression. This treatment shifts the A9 to a high-metastatic phenotype. The significance of this imbalance to the tumor--host relationship is discussed.

Animals↗

PubMed1983

Phenotypic diversity within clones of human normal T cells.

Human normal T cells were selected for in vitro cloning according to the expression of T4, T8 or T10 antigens on individual cells. Clones were produced from each of these cells irrespective of the antigenic phenotype of the parental cell. The cloned progeny manifested, in many cases, shifts in antigen expression. Thus, T4+T8- cells gave clones expressing predominantly T4-T8+ and vice versa. The clonal expression of T4 and T8 seemed to be mutually exclusive. Antigenic shifts were recorded also in clones derived from T4-T8-T10- cells, resulting in T10+ clones which were also either T4+ or T8+ and from T4+T8-T10+ cloned cells yielding clones of either T4+ or T8+ cells. Testing functional properties we found that NK activity was mediated not only by T10+ cells but also, in some cases, by T4+ and T8+ cells. Moreover, TCGF production, which may reflect helper activity, was mediated not only by T4+ cells. Only the cytotoxic (CTL) activity seems to be confined to the T8 phenotype. Thus, it appears that T antigens, which seemed to be molecular markers of differentiation, are not markers for terminal differentiation and do not always reflect defined functional properties. These conclusions are drawn from cloning of normal T cells which manifest properties different from those of T-cell lines or T hybridomas.

Antibodies, Monoclonal↗

PubMed1983

Interaction of ribonuclease A with estrogen receptor from rat mammary tumor MTW9.

Incubation of crude estrogen receptor preparations from mammary tumor cytosol with RNase A increases the sedimentation coefficient of the receptor from 9.7 S to 10.4 S. The effect is not obtained with other low molecular weight basic proteins (lysozyme, cytochrome c, or histone H2B). Nonenzymically active RNase A derivatives such as performic acid oxidized RNase A, fully reductively methylated RNase A, carboxymethyl-His-119-RNase A, and RNase S-protein were ineffective. RNase T1, an acidic endoribonuclease, was also without effect. However, enzymically active RNase S', prepared from a mixture of RNase S-protein and S-peptide, shifted the sedimentation to 10.4 S. The increased sedimentation is not accompanied by a change in the Stokes radius of the receptor (74 A) or buoyant density in metrizamide (1.24 g/ml). The effect of RNase A on the sedimentation of the receptor can be reversed by subsequent incubation with human placental RNase inhibitor or with rabbit anti-RNase A antibodies. Direct interaction was shown by chromatography of the receptor on RNase A Sepharose. Thus, the shift in sedimentation results from binding of RNase A to the receptor and, although this requires that the enzyme active site be available, enzymic activity is not responsible for the effect. The interaction of RNase A with the receptor occurs at low ionic strength; it does not occur at elevated ionic strength or after activation of the receptor by precipitation with ammonium sulfate.

Animals↗

PubMed1983

Human normal CTL clones: generation and properties.

This study reports the production of clones of human killer T cells grown in the presence of TCGF4 following sensitization in MLC against (1) allogeneic cells, (2) autologous Bebv+ lymphocytes, or (3) autologous lymphoma cells. Sensitization against the tumor cells required the addition of macrophages. The expression of the cytotoxic activity of the cloned T lymphocytes required re-stimulation with the specific stimulator cells. The cytotoxic activity seemed to be MHC-restricted, since (1) cloned allosensitized CTL lysed their corresponding allogeneic targets, but did not lyse autologous Bebv+ cell or K562 cells; (2) cloned CTL sensitized against autologous Bebv+ cells lysed their autologous targets but not allogeneic Bebv+ targets or K562 cells; and (3) cloned CTL sensitized against autologous Burkitt lymphoma cells lysed their corresponding lymphoma targets or autologous Bebv+ targets but did not lyse allogeneic lymphoma cells or Bebv+ cells from the same allogeneic lymphoma cells or Bebv+ cells from the same allogeneic donors. The cloned CTL were homogeneous in expressing the OK T8 molecules and in being negative for T4, T10 or M1. At any given time, 25-45% of the cloned cells manifested lytic activity. The ultrastructural properties and cell surface OK T markers were different from those of cloned human NK cells. Emphasis is focused on the differences between the structural, functional and culture characteristics of CTL clones produced by direct isolation of MLC responder cells forming conjugates with specific target cells and those of clones from transformed T-cell lines or from T hybridomas.

Antigens, Surface↗

PubMed1983

Beta-endorphin and the endocrine pancreas. Studies in healthy and diabetic human beings.

Beta-endorphin is present in the endocrine pancreas, suggesting that endorphins may have a role in islet-cell function. To evaluate this possibility, we infused synthetic human beta-endorphin intravenously in healthy volunteers and in insulin-dependent diabetic patients. In both groups, beta-endorphin increased plasma glucagon concentrations, and this rise was accompanied by a significant increase in plasma glucose concentrations. In nondiabetic subjects, beta-endorphin also increased plasma insulin concentrations. The threshold dose of beta-endorphin for producing increased plasma concentrations of glucose and glucagon was 0.005 mg--a dose that acutely increased plasma concentrations of beta-endorphin by approximately 40-fold. Glucose, glucagon, and insulin responses to beta-endorphin could not be blocked by intravenous naloxone. These studies suggest that endorphins may be involved in gluco-regulation, that their hyperglycemic action is mediated at least in part by glucagon, and that the effect of beta-endorphin on islet-cell function is relatively resistant to naloxone.

Adult↗

PubMed1983

Applications of carbon dioxide laser surgery and radiation. A preliminary report.

Ten patients with advanced or recurrent squamous cell carcinomas of the upper airway were treated with a combination of carbon dioxide laser surgery and radiation therapy to evaluate the tolerance to rapid sequencing of both modalities in a variety of clinical situations. Other considerations were to accurately stage infiltrating tumors, to provide cytoreduction for T3 and T4 tumors, and to facilitate the optimal placement of intracavitary radium applicators. Because of minimal postoperative pain or dysfunction associated with the laser, patients were able to receive irradiation considerably sooner than with conventional surgery. Local tolerance was good to excellent in seven of the ten patients treated and, based on preliminary results, the combination would appear to offer advantages in curative approaches to advanced head and neck tumors.

Adult↗

PubMed1983

Splenic B cells function as immunogenic antigen-presenting cells for the induction of effector T cells.

Previous studies performed in our laboratory have revealed that an ordered, sequential, tricellular interaction is obligatory for the antigen-driven induction of a specific effector memory T cell. Thus, it was found that antigen-pulsed peritoneal macrophages signal, in spleen cells, the generation of antigen-specific initiator lymphocytes. These lymphocytes, following injection to syngeneic recipients, recruit, in the draining lymph nodes, "virgin" antigen-reactive T lymphocytes. Although the nature of the first and last cell in the interacting sequence was well characterized, the identity of the intermediary initiator splenic cell was obscure. Studies were carried out to characterize the nature of the splenic initiator cells. It was found that spleen cells from nu/nu, adult thymectomized and neonatal thymectomized, or spleen cells from normal donors which had been subjected to cytolysis using anti-Thy-1.2 antibodies in the presence of complement, did generate, following interaction with keyhole limpet hemocyanin (KLH)-fed macrophages, specific initiator cells. Carrageenan impairment of spleen macrophages did not affect the generation of initiator cells, nor did the depletion of dendritic cells from the spleen. On the other hand highly enriched B cell, but not highly enriched T cell populations, when seeded on KLH-pulsed macrophages, generated antigen-specific initiators, which, in vivo, recruited antigen-reactive T cells. It thus appeared that B lymphocytes can function as intermediary obligatory antigen-presenting cells and actively transfer immunogenic signals from peritoneal antigen-presenting cells to T lymphocytes. These findings may therefore suggest that antigen-specific B cells do not function solely as antibody-producing cells, but, once activated by macrophages, may control the induction and differentiation of some antigen-reactive T cell subsets. Thus, one can view the B cell as an important regulatory cell of both cellular and humoral immune functions. The significance of this observation with regard to Ir gene control at the level of B lymphocytes is discussed.

Animals↗

PubMed1983

Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice. II. Anti-mu treatment affects the initiation and recruitment of T cells.

Mice injected from day of birth onwards with rabbit anti-mouse IgM (antim-mu) antibodies were found to be B cell-deficient and defective for the induction of antigen-reactive proliferating T cells (TPRLF). This defective induction was not due to the absence of circulating antigen-specific antibodies since the daily injections of such antibodies during exposure to antigen did not restore the ability of anti-IgM treated animals to generate TPRLF. Analyzing the cellular events implicated in the induction of virgin antigen-reactive T cells, anti-mu-treated mice manifested impairment of the three interacting cell types involved in the induction of TPRLF. Thus, peritoneal and splenic antigen-presenting cells from such animals were impaired in their capacity to signal a primary antigen-specific T cell reaction. Their splenic lymphocytes could not function as initiator cells in transferring immunogenic signals to recruit TPRLF in normal recipients. Potent antigen-specific splenic initiator cells failed to induce the recruitment of specific TPRLF in anti-mu-treated mice. The defective induction of TPRLF in anti-mu-treated mice may be due to a functional impairment of cells expressing membrane-bound IgM molecules which seemingly play a central role in the transfer of immunogenic signals for the recruitment of antigen-specific circulating T cells. We suggest that splenic B cells function as initiators in the transfer of antigen-induced signals from peritoneal antigen-presenting cells to T cells. These seems to be the primary targets of anti-mu treatment.

Animals↗

PubMed1983

Differences in the metastatic potential of two sublines of tumor 3LL selected for resistance to natural NK-like effector cells.

Normal syngeneic spleen cells were found to inhibit the local growth of the Lewis lung carcinoma (3LL) when injected together with the tumor cells at a ratio of 100:1 (spleen to tumor cells). The repeated injection of the tumor cells together with spleen cells eventually led to the selection of a tumor cell population whose growth could no longer be inhibited by normal spleen cells. In a previous report from this laboratory, a tumor subpopulation obtained in this manner was shown to display an increased metastatic potential, as well as a decreased sensitivity to natural resistance mechanisms in vivo and NK lysis in vitro. In the present study, we attempted to characterize the spleen cell population which mediated this selection process. We found that spleen cells depleted of T cells, B cells, or adherent macrophages retained their ability to inhibit tumor growth and select a resistant line in vivo. Subsequently, two tumor sublines derived by continuous in vivo passage of the parental tumor line with either unfractionated or nylon wool-non-adherent spleen cells were characterized. It was found that whereas both sublines were resistant to growth inhibition by normal spleen cells, only the subline derived from continuous passage with unfractionated spleen cells showed a reduction in the density of H-2b molecules expressed on the cell surface and an enhanced metastatic potency. These results suggest that the resistance of a tumor line to natural killer cells may not always result in an increase in its metastatic potential.

Animals↗