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Biomedical subjects

M Wasserman

Publications and source records attributed to M Wasserman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4.

Osmoregulation, inhibitory neurotransmission and pH balance depend on chloride ion (Cl-) flux. In intestinal epithelial cells, apical Cl- channels control salt and fluid secretion and are, in turn, regulated by agonists acting through cyclic nucleotides and internal calcium ion concentration ([Ca2+]i). Recently, we found that muscarinic pretreatment prevents [Ca2+]i increases from eliciting Cl- secretion in T84 colonic epithelial cells. By studying concomitant inositol phosphate metabolism, we have now identified D-myo-inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4), as the inositol phosphate most likely to mediate this uncoupling. A novel, membrane-permeant ester prepared by total synthesis delivers Ins(3,4,5,6)P4 intracellularly and confirms that this emerging messenger does inhibit Cl- flux resulting from thapsigargin- or histamine-induced [Ca2+]i elevations.

Atropine↗
PubMed1994

Comparative effects of GH, IGF-I and insulin on serum sex hormone binding globulin.

OBJECTIVE: The serum level of sex hormone binding globulin (SHBG) changes inversely with that of both insulin and insulin-like growth factor (IGF-I), during several nutritional conditions, as well as in response to GH treatment. However, with exogenous IGF-I administration, endogenous IGF-I increases, while insulin decreases. In order to study the separate roles of these hormones in controlling SHBG metabolism, we compared SHBG levels in patients treated with IGF-I and GH. DESIGN AND PATIENTS: Serum levels of IGF-I, insulin and SHBG were measured before and during the treatment of patients with IGF-I or GH. Blood samples were drawn in the fasting state, prior to and during therapy, 24 hours after drug administration. Sixteen children and adults with Laron syndrome (LS) received daily s.c. injections of IGF-I (120-150 micrograms/kg) for up to 5 months. Three adults with isolated GH deficiency (IGHD) received daily s.c. injections of GH (0.03-0.06 U/kg) for 16 months. Two groups of nine prepubertal children with constitutional short stature (CSS) received GH (0.1 U/kg/day) for 3 months. MEASUREMENTS: Serum levels of insulin and acid extractable IGF-I were determined by RIA, and that of SHBG by IRMA. RESULTS: Basal insulin and SHBG levels were within normal range in the LS, IGHD and CSS patients. IGF-I levels were low in LS and IGHD patients, and normal in the CSS children. The mean peak response to chronic therapy was as follows: in LS patients, IGF-I administration decreased insulin levels to 62%, and increased SHBG levels by 64% above basal values. Chronic GH therapy in IGHD caused a marked rise in both IGF-I levels (473%), and insulin levels (96%), and a gradual decline of SHBG to 75% of the basal concentration. In GH treated CSS patients, serum IGF-I peaked at 80% and insulin levels at 102% above the respective basal levels, while SHBG decreased to 83% after 5 days of treatment. CONCLUSION: The results obtained in Laron syndrome, isolated GH deficiency and constitutional short stature patients treated with IGF-I or GH, indicate that serum insulin had consistently an inverse relation with the levels of circulating SHBG. No relation was found between IGF-I and SHBG levels.

Adult↗
PubMed1993

Evolutionary cytogenetics of the Drosophila buzzatii species complex.

The salivary gland chromosomes of 10 species in the Drosophila mulleri subgroup (repleta group) have been re-analysed. These include the eight members of the South American buzzatti and martensis clusters, previously ascribed to the mulleri complex, and the two Caribbean species D. stalkeri and D. richardsoni, previously comprising the stalkeri complex. The chief results can be summarized as follows. Inversion 3a is not present in the martensis cluster. Hence, there is no cytological link between this cluster, or the buzzatii cluster, and the rest of the mulleri complex. Accordingly, a new species complex, the buzzatii complex, is established with the two South American clusters. D. stalkeri and D. richardsoni share at least two inversions with all the species in the buzzatii and martensis clusters, and produce hybrids in interspecific crosses with many of them. This indicates a close phylogenetic relationship. Therefore, D. stalkeri and D. richardsoni are incorporated as a cluster within the newly erected buzzatii complex. A phylogenetic tree illustrating the chromosomal evolution of the buzzatii complex is presented and all the previous cytological information concerning its members is reviewed.

Animals↗
PubMed1991

Effect of calpain inhibitors on the invasion of human erythrocytes by the parasite Plasmodium falciparum.

17 different proteinase inhibitors were screened for their effect on the erythrocyte invasion by the malaria parasite Plasmodium falciparum. The effect was tested when the inhibitors were present in the culture medium and when they were trapped into erythrocyte ghosts. A very strong inhibition of invasion was observed in the presence of calpain inhibitors, with IC50 in the order of 10(-7) M. Chymostatin, leupeptin, pepstatin A and bestatin also caused inhibition of the invasion, but with IC50 in the order of 10(-5) M. The results suggest that participation of various proteinases in the process and point to the possibility of a calpain-mediated proteolytic event. This study may explain previous observations on the role of calcium in the invasion of the human erythrocyte by Plasmodium falciparum.

Animals↗
PubMed1991

Effect of octreotide on 24-hour growth hormone and prolactin secretory patterns in acromegalics.

Four adult patients with active acromegaly underwent studies of their 24-hour secretory pattern of hGH and Prl prior to and at the end of 3 months of treatment with the octreotide (somatostatin analog SMS 201-995) 100 micrograms s.c. every 8 h. Blood was withdrawn at 30-min intervals with the aid of a constant withdrawal pump. The best fit cosinor method was used to define the following rhythm parameters: mesor, amplitude, acrophase and periodicity. Prior to treatment, hGH secretion was increased in all patients. The mean 24-hour ranged from 9-47 ng/ml with amplitude 5.2-23 and observed maximal pulse 41-95 ng/ml. Computed rhythms were circadian in 3 patients and ultradian in 1; in 2 patients the acrophases were shifted to daytime. hPrl secretion was altered in 3 of the patients. Two had elevated mean 24-hour of 17.7 and 22.2 ng/ml, while computed rhythms showed semicircadian periodicity in 1 of them and circadian periodicity with a shift of acrophase to daytime in the other. The third patient who had normal hPrl levels, showed ultradian 8-hour periodicity. At the end of treatment there was a marked reduction in hGH secretion in 1 patient and a lesser reduction in the other 3. The rhythm was influenced by the masking effect of the drug, to yield an 8-hour period with acrophases related to injection clock time having equal amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1990

Role of calcium and erythrocyte cytoskeleton phosphorylation in the invasion of Plasmodium falciparum.

The role of calcium in the invasion of the human erythrocyte by the parasite Plasmodium falciparum was studied. The intraerythrocytic and intraparasitic concentrations of Ca2+ were modified using calcium-ionophore A23187 and the chelator EGTA. The Ca2+ inside the parasite appeared to be necessary for the normal completion of invasion. We determined that in recently invaded erythrocytes (2 h), the Ca2+ concentration increased about 10 times. Merozoite invasion produced a decrease in beta-spectrin phosphorylation and an increase in the phosphorylation of a protein with band 4.1 mobility. These changes were similar to those produced by an ionophore-mediated Ca2+ influx in uninfected erythrocytes. These facts support the idea that a calcium influx into erythrocytes might precede or accompany merozoite invasion, triggering a series of molecular events, including phosphorylation and dephosphorylation of cystoskeletal proteins.

Animals↗
PubMed1990

Distribution of liposomes in tuberculous mice.

The dynamics of the distribution of liposomes for use as drug carriers for the treatment of tuberculosis is studied. While the free radiolabel injected into mice was rapidly excreted by the kidneys, the same label trapped within liposomes was retained for longer periods in the liver, spleen and lung. There were variations in the distribution and retention times of liposomes of different composition. When the distribution of liposomes in healthy and tuberculous mice was compared, a greater accumulation in the liver, spleen and lungs of healthy mice was observed, although the retention time in tuberculous mice was longer. These findings merit consideration in the design of therapies based on liposome-entrapped drugs as the dynamics of distribution and retention differ between normal and infected animals.

Animals↗
PubMed1990

Effect of oral clonidine, insulin-induced hypoglycemia and exercise on plasma GHRH levels in short-stature children.

Human growth hormone release is affected by a variety of pharmacological and physiological stimuli. We have studied the effect of oral clonidine, insulin hypoglycemia, and exercise on plasma hGH and GHRH levels in 31 healthy short-stature children. Thirteen underwent an oral clonidine test (0.15 mg/m2), 12 an iv. insulin test (0.1 U/kg), and 6 performed exercise (running for 10 min in a defined route). GHRH-1-44 was extracted from plasma on silica columns and determined by RIA. Although all three stimuli induced a marked increase in plasma hGH levels, only clonidine induced a significant increase in plasma GHRH levels. Maximal increment in GHRH during clonidine was 6.82 +/- 1.05 pmol/l (mean +/- SEM) as compared with 0.51 +/- 0.28 and 0.53 +/- 0.62 during hypoglycemia and exercise (p less than 0.0005 and p less than 0.005), respectively. An additional 24 subjects received TRH 0.2 mg/kg iv: 8 TRH alone, 8 TRH and insulin, and 8 TRH and clonidine. Only insulin potentiated the TRH-induced TSH response with a peak of 22.0 +/- 3.2 vs 16.0 +/- 0.8 and 15.3 +/- 1.5 mU/l (p less than 0.025) for TRH alone and TRH and clonidine, respectively. It is suggested that clonidine stimulates hGH secretion mainly through an enhancement of GHRH release, whereas stress stimuli such as hypoglycemia and exercise achieve hGH release by a different mechanism, possibly inhibition of somatostatin.

Administration, Oral↗
PubMed1989

Utility of fever, white blood cells, and differential count in predicting bacterial infections in the elderly.

A total of 221 elderly patients between the ages of 70 to 99 years who presented to a community-based teaching hospital emergency room were prospectively evaluated by assessing for fever (greater than or equal to 37.5 degrees C), leukocytosis (greater than or equal to 14,000/mm3) and bandemia (greater than 6%) as a screening method for predicting the presence of bacterial infection. Thirty-three patients had documented bacterial infections. Although with increasing body temperature the percent of patients who were infected increased, 48% of the infected elderly patients had no fever. In patients with fever, 39% had a bacterial infection compared to only 9% in the afebrile group. In patients with fever, leukocytosis, and bandemia, all patients were infected. Conversely, in the absence of fever, leukocytosis, and bandemia, only 6% had bacterial infection. All elderly patients who present with an acute or subacute change in health status or functional capabilities associated with fever, leukocytosis, or bandemia should be carefully assessed for the high probability of a bacterial infection.

Aged↗
PubMed1988

Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep.

Leukotrienes have been suggested to play a role in the endotoxin-induced changes of the pulmonary hemodynamics and airway mechanics. Since Ca2+ is necessary for contraction of airway and vascular smooth muscle as well as for activation of phospholipase A2 and 5-lipoxygenase enzymes, we wondered whether the calcium antagonist verapamil would modify the endotoxin-mediated pulmonary effects as well as the generation of circulating eicosanoids. In twelve conscious sheep, measurements of pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), lung resistance (RL), arterial PO2 (PaO2), leukocyte (WBC) count, arterial thromboxane B2 (TxB2), prostaglandin (PG) F2 alpha, and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentrations were obtained before and at predetermined intervals after a 10-min infusion of Escherichia coli endotoxin (0.3 microgram/kg). On separate occasions, the sheep received a bolus injection of verapamil (150 micrograms/kg) before endotoxin, followed by a continuous infusion of verapamil [10 micrograms.kg-1.min-1 (n = 5) or 20 micrograms.kg-1.min-1 (n = 7)] for up to 4 h post-endotoxin. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 326 and 276% of base line during phase I (0-1 h) and lesser increases to 177 and 157% of base line during phase II (1.5-4 h), respectively (P less than 0.05). SVR also showed biphasic increases of 44 and 42% during phase I and II, respectively. Mean PaO2 decreased by 16 Torr and WBC count decreased from 6.4 +/- 1.5 to 3.3 +/- 1.1 thousand/mm3, associated with marked increases in plasma TxB2, PGF2 alpha, and 6-keto-PGF1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Preservation of the glomerular capillary ultrafiltration coefficient during rat nephrotoxic serum nephritis by a specific leukotriene D4 receptor antagonist.

Leukotriene D4, a potent biologically active lipoxygenase derivative of arachidonic acid in activated leukocytes, depresses the glomerular capillary ultrafiltration coefficient (Kf) and contracts mesangial cells in culture. We therefore investigated its potential role in mediating the reduction in nephron filtration rate seen after induction of experimental nephrotoxic serum (NTS)-induced glomerulonephritis in the rat. Micropuncture measurements were performed in euvolemic Munich-Wistar rats 2 h after i.v. administration of 0.8 ml of rabbit serum (group 1, n = 6), 0.8 ml of rabbit anti-rat glomerular basement membrane antibody in the absence (group 2, n = 8), or presence (group 3, n = 7) of the new highly specific LTD4 receptor antagonist SK&F 104353. Quantitation of antibody binding and neutrophil infiltration revealed no differences between groups 2 and 3. Antagonism of endogenous LTD4 actions, however, was associated with prevention of the NTS-induced fall in SNGFR because of the abrogation of the fall in Kf which characterizes this form of experimental glomerulonephritis. Antagonism of endogenous LTD4 had no effect on the NTS-induced increases in pre- and postglomerular arteriolar resistances, and did not affect nephron plasma flow rate or net transcapillary hydraulic pressure difference. The observed highly localized protective action of the LTD4 antagonist on the glomerular capillary points to a possibly major functional role for intraglomerularly released LTD4, likely originating from infiltrating leukocytes, in the pathophysiology of this form of glomerulonephritis.

Acute Disease↗
PubMed1986

A simple technique for entrapping rifampicin and isoniazid into liposomes.

A method for the preparation of liposomes loaded with rifampicin and isoniazid is described. Optimal conditions were established; the lipid suspension was mixed with the aqueous solution of the drugs and was sonicated in a bath for 30 min at 50 degrees C. The optimum composition tested was phosphatidyl choline, cholesterol and cardiolipin in a molar ratio of 7:2:1. The separation of unloaded drug was performed by centrifugation through three successive Sephadex G-25 columns. The liposomes were multilamellar vesicles with a size ranging from 100-300 nm. The drugs were trapped in concentrations from 6.5-9.5 mg/ml. This method is suitable for preparation of liposomes in small laboratories.

Hot Temperature↗
PubMed1986

The use of rifampicin and isoniazid entrapped in liposomes for the treatment of Murine tuberculosis.

Liposomes loaded with rifampicin and isoniazid were used experimentally to treat mice with severe tuberculosis. The animals were distributed in four groups. The control group and the group treated with unloaded liposomes showed the severest disease. Both groups showed the lowest accumulated survival, about 50% after 30 days. The numbers of colony-forming-units (CFU) and root specific lung weight (RSLW) were the highest and the histopathology of the lung showed marked diffuse lesions. However, the group treated with unloaded liposomes showed significantly higher growth of M. tuberculosis compared with the control. The group treated with drug and drug loaded liposomes showed a higher survival, about 85% after 30 days, and the lowest values of CFU and RSLW. The lung histology revealed considerably less inflammation which was focal. The parameters evaluated indicated a significantly better response in the group of animals treated with rifampicin and isoniazid entrapped in liposomes.

Animals↗
PubMed1986

Inhibition by auranofin of pharmacologic and antigen-induced contractions of the isolated guinea pig trachea.

The effects of an orally active gold complex, auranofin, were investigated on the isolated guinea pig trachea contracted pharmacologically and antigenically. Pretreatment of the tracheal tissues for 15 minutes with auranofin (10(-5) and 10(-4) mol/L) produced a significant rightward shift of a histamine dose-response curve (p less than 0.001), whereas a 30-minute pretreatment with auranofin (10(-4) mol/L) inhibited LTD4-induced (but not LTC4-induced) contraction of the tracheal spirals. In tracheas from animals actively sensitized to ovalbumin, auranofin (10(-4) mol/L) significantly inhibited contractions elicited by 0.01 micrograms/ml of this antigen. Auranofin does not appear to behave like a nonspecific suppressant of tracheal muscle contraction since it failed to antagonize a potassium chloride-induced (6 X 10(-2) mol/L) contraction. Therefore, auranofin appears to alter the in vitro response of the guinea pig trachea not only to histamine but also, more importantly, to LTD4 and specific antigen. These results characterize and extend further the pharmacology of auranofin in airway tissue.

Animals↗
PubMed1985

Temporal relationships on macromolecular synthesis during the asexual cell cycle of Plasmodium falciparum.

The over-all synthesis of DNA, RNA and protein was studied during the asexual cell cycle of Plasmodium falciparum. A method for stringent synchronization of the culture was developed. Rates of synthesis of the three macromolecules were determined every four hours by labelling the parasites with radioactive precursors during 30 min pulses. There was a peak of synthesis of DNA at 44 hours. Between 33 and 45 hours the rate of synthesis of DNA was exponential. Maximum RNA synthesis was reached at 36 hours. For proteins there were two peaks, one at 24 and the other at 40 hours. Partial degradation of the RNA synthesized by schizonts was detected.

Cell Cycle↗