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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 487 records · Page 27Linked to original sources

A membrane defect in cystic fibrosis: decreased red cell permeability to water.

The abnormally high concentrations of electrolytes and organic solutes found in the glandular secretions of individuals with cystic fibrosis may arise from decreased water content rather than perturbed solute transport. Thus, it is possible that the abnormalities insolute concentrations are a result of a reduced water movement into the secretory product. It is our hypothesis that if an abnormality exists in the transport of water across secretory cell membranes, this defect may also be expressed in nonsecretory cell membrane permeability to water. We report here osmotic water permeability measurements on red cells and 11 cystic fibrosis patients ranging in age from 2 to 20 years and eight normal individuals. The mean hydraulic conductivity for the patients of 1.23 +/- 0.13 cm3/dyne sec is significantly less (P < 0.001) than that of normal individuals who have permeabilities of 1.45 +/- 0.11 cm3/dyne sec. Analysis showed that the osmotic water permeability correlates well with the Shwachman score (r = 0.76). Patients who are in the poorest clinical condition show the lowest hydraulic conductivities.

Body Water↗

Pulmonary echinococcosis: a pediatric disease of the Southwestern United States.

Three cases of pulmonary echinococcosis in native American children emphasize the need to consider the diagnosis in the differential diagnosis of mass lesions of the chest when the appropriate environmental conditions are present. Two children presented with a non-productive cough, while one was asymptomatic. Surgery is the treatment of choice for pulmonary echinococcal cysts. All three children did well after thoracotomy, and one child has a normal roentgenogram six years after surgery. Recent evidence seems to indicate that transmission of the Echinococcus among native Americans in the Southwest is increasing, and thus human echinococcal disease may be of increasing clinical importance.

Child, Preschool↗

Efficacy of a 12-hour sustained-release preparation in maintaining therapeutic serum theophylline levels in asthmatic children.

The purpose of this study was to determine whether a new sustained-release theophylline preparation TheoDur could maintain therapeutic serum theophylline levels in asthmatic children on a 12-hour dosage regimen. Twenty asthmatic children aged 6 to 18 years with a mean of 11.4 years who required continuous theophylline therapy for control of their asthma were enrolled in the study. Each patient's dosage was titrated to achieve a six-hour postdose serum theophylline level between 10 and 20 microgram/ml. The patients required a mean +/- SEM dose of 10.0 +/- 0.54 mg/kg every 12 hours which gave a mean +/- SEM six-hour postdose serum theophylline level of 15.65 +/- 0.72 microgram/ml. At the end of five days on this dosage, the patients were admitted and serum theophylline levels were determined every three hours for 24 hours. The mean +/- SEM difference between maximum and minimum serum theophylline levels (delta TL) for the group was 4.5 +/- 0.3 microgram/ml. There was not a significant difference in the delta TL between the two age groups (6 to 9 years, 4.5 +/- 0.5 microgram/ml and 10 to 18 years 4.5 +/- 0.4 microgram/ml). In conclusion, TheoDur will maintain therapeutic serum theophylline levels with minimal fluctuations in asthmatic children on a 12-hour dosing schedule.

Adolescent↗

Host defense deficiency in hairy cell leukemia and its correction by leukocyte transfusion.

A similar defect host defense mechanisms in hairy cell leukemia was defined in two patients. Surface-adherent monocytes were not detected in the peripheral blood nor were monocytes that mediate antibody-dependent cell-mediated cytotoxicity (ADCC) to isoantibody-coated human erythrocytes. In addition, lymphocytes of both patients failed to show blastogenic responses to concanavalin A (Con-A) and pokeweed mitogen (PWM) but showed a vigorous response to phytohemagglutinin (PHA). Other immunologic abnormalities were present but were either moderate in degree or were not present in both patients. In vitro lymphocyte blastogenic responses were fully restored by incubation of patients' leukocytes with a normal donor's adherent monocytes. One patient received daily allogeneic leukocyte transfusion for 4 days. This resulted in complete normalization of monocyte adherence and ADCC that persisted for several months after transfusion and was associated with hemotalogic improvement. Therapy in case 1 resulted in correction of the blastogenic responses to Con-A and PWM. Thus, a host defense defect in hairy cell leukemia has been defined in 2 patients and a preliminary result suggests that therapy with leukocyte transfusions may be useful in the postsplenectomy patient with an infectious complication and should be explored further.

Antibody-Dependent Cell Cytotoxicity↗

TLC? Forget it.

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Consumer Behavior↗

Cerebral blood flow after treatment with ORG-2766, a potent analog of ACTH 4--9.

Regional cerebral blood flows (rCBF) were measured in conscious, male rats at 10, 30, 60 min and 24 hr after intravenous administration of a potent, behaviorally active analog of ACTH/MSH 4--9 (ORG-2766). Flows in the basal ganglia, hippocampus, septal area and frontal cortex were depressed significantly throughout the 60 min postinjection period. HYpothalamic and parietal flows were depressed at 10 and 30 min, but recovered by 60 min, whereas flow to the cerebellum was depressed between 30 and 60 min postinjection. The least changed and therefore relatively better perfused area throughout the first 60 min period was the occipital cortex. By contrast, at 24 hr, when perfusion of all brain regions had returned to near control levels, flow to the occipital cortex was elevated. During the first hour after treatment with either ORG-2766 or alphaMSH the patterns of regional circulation in the brain were qualitatively the same. The data suggest that ORG-2766 and, probably, alpha MSH trigger serially linked neurophysiologic changes in the brain lasting at least 24 hr, which organize the behavioral actions of this class of peptides on memory and attentional processes.

Adrenocorticotropic Hormone↗

Polycythemia vera. Increased expression of normal committed granulocytic stem cells in vitro after exposure of marrow to tritiated thymidine.

In previous studies of two patients with polycythemia vera (PV) and heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G-6-PD), only type A isoenzyme was found in non-lymphoid hematopoietic cells. However, some granulocytic and erythrocytic colonies grown in vitro had type B G-6-PD and therefore arose from presumably normal progenitors. In this study we exposed marrow cells from these same two patients to high-specific activity tritiated thymidine (3HTdR) before culture to kill cells actively synthesizing DNA. Individual granulocytic colonies were plucked and tested for G-6-PD after 14 d of culture. The frequency of type B colonies rose after exposure to 3HTdR from 8/101 to 11/36 in patient 1 and from 0/32 to 6/31 in patient 2 (P less than 0.003). No increase in the frequency of normal erythroid bursts after 3HTdR exposure was seen, implying that in PV, early granulopoiesis, and erythropoiesis are regulated differently. The results demonstrated that only type A granulocytic colonies, arising from the abnormal clone, were removed by the 3HTdR. In addition, for patient 2, statistical analysis indicated there was an absolute increase in normal granulocytic colonies detected in culture. Thus, PV clonal colony-forming units in culture (CFU-C) cycle more rapidly than do normal CFU-C and may suppress proliferation of normal CFU-C in vitro.

Cell Division↗

Synthesis of DNA and lecithin in tissue culture and oestrogen receptor activity in rat mammary tumours dependent on and independent of the ovary.

Dimethylbenz(alpha)anthracene (DMBA)-induced and transplanted rat mammary tumours (2 lines) were examined for oestrogen receptor activity, and for sensitivity to hormones in vivo (by ovariectomy) and in vitro (by tissue culture). In vivo, the growth of all tumours induced by the administration of DMBA in random-bred Sprague-Dawley rats was found to be dependent on the ovary, whilst in all transplanted tumours (12 TG-3 and six TG-5 lines), maintained in an inbred strain of Sprague-dawley rats, growth was found to be independent of the ovary. In vitro, the capacity for DNA synthesis in DMBA-induced tumours was better maintained after 24 h when insulin (10 microgram/ml) and corticosterone (5 microgram/ml) or insulin, corticosterone and prolactin (each 5 microgram/ml) were present in the medium (five out of 12 and eight out of 11 tumours respectively); no effect of hormones in the media was detected after 48 h. In the transplanted tumours, no effect of hormones on DNA synthesis was detected after either 24 or 48 h of culture. Synthesis of lecithin was not detectably influenced by the presence of hormones in either DMBA-induced or transplanted tumours. Oestrogen receptor concentrations were, on average, significantly higher in the DMBA-induced tumours than in either line of transplanted tumour. For 22 DMBA-induced tumours and 15 transplanted tumours, the effect of hormones in vitro ('response') was directly correlated with receptor concentration at time 0 (Spearman's rho = +0.59) and inversely correlated with the rate of DNA synthesis ('basal') at time 0 (Spearman's rho = -0.62). No single parameter or pair of parameters permitted accurate distinction between the tumour types.

9,10-Dimethyl-1,2-benzanthracene↗

Postnatal amino acid uptake by the rat small intestine. Changes in membrane transport systems for amino acids associated with maturation of jejunal morphology.

The uptake of a number of amino acids by the developing small intestine of the rat was investigated in vitro. L-valine, L-leucine, L-methionine, L-phenylalanine, L-arginine and L-lysine were all taken up by active transport and concentrated within the jejunal mucosa. GABA was not actively transported by the jejunum. The kinetics of carrier transport of amino acids was determined from birth to maturity. The Michaelis constant (Km) of the L-leucine, L-methionine, L-arginine and l-lysine transport systems was found to be low postnatally and increased with age, particularly after the time of weaning. The rate of l-leucine, L-methionine, L-phenylalanine and L-lysine transport (Vmax) was high postnatally but decreased after weaning. Neutral amino acids were transported at higher rates than basic amino acids. l-arginine was poorly transported by the jejunum. The specificity of transport systems for amino acids was investigated in inhibition studies. Amino acid transport systems appeared to be polyfunctional in the postnatal period but were more specific in post-weaned animals. The changes in kinetics and specificity of amino acid transport in the small intestine are discussed with reference to their possible functional significance and to the maturational changes in the jejunum, particularly with the appearance of a functionally distinct absorptive cell lining the intestinal villi during the third postnatal week (the time of weaning).

Aging↗

The effectiveness of rubidazone in hairy cell leukemia (leukemic reticuloendotheliosis).

Two patients with hairy cell leukemia treated with the anthracycline antibiotic rubidazone are presented. One achieved a complete remission and the other a good partial hematologic and bone marrow remission. Neither has relapsed (at 20 and 13 mo, respectively), and neither has been retreated. Intensive supportive measures were required during the prolonged myelosuppression that followed treatment. The relative youth of the patients (ages 24 and 39 yr) may have contributed to their ability to survive until normal marrow recovered. Chemotherapy should not be employed in the initial management of hairy cell leukemia. However, if life-threatening granulocytopenia and thrombocytopenia occur secondary to bone marrow replacement by leukemic cells, and improvement does not occur using alternative methods of therapy, consideration could be given to chemotherapy with rubidazone. Facilities for intensive supportive care should be available.

Adult↗

Serum theophylline levels in asthmatic children receiving sustained-release theophylline tablets.

Serum theophylline levels produced in asthmatic children by sustained-release theophylline tablets (TheoDur) were studied. Nineteen patients received for 14 days a dose of 5.5 to 13.1 mg/kg (mean 9.1 mg/kg) of amhydrous theophylline (as sustained-release TheoDur tablets) every 12 hours. Theophylline serum levels were assayed, by cation-exchange high-performance liquid chromatography, immediately before and at 4, 6 and 10 hours after the first day-five dose. Symptoms of asthma and theophylline toxicity were recorded. Mean peak-trough difference for the 6-to-10-years age group (4.5 +/- 1.6 microgram/ml) was not significantly different than that of the 11-to-17-year age group (5.2 +/- 3.2 micrograms/ml) (p greater than 0.1). Therapeutic serum theophylline levels (8 to 20 micrograms/ml) were maintained throughout a 12-hour period in 12 patients. Two patients had side effects possibly attributable to theophylline. Four patients reported asthamtic symptoms on two or more evenings; none required emergency treatment. The study suggests that sustained-release theophylline tablets administered every 12 hours can maintain therapeutic serum levels in children.

Adolescent↗

Postnatal amino acid uptake by the rat small intestine. Energetics of membrane transport systems for amino acids in the developing jejunum.

The energetics of amino acid uptake by the developing small intestine was investigated in vitro. L-valine, L-leucine, L-phenylalanine, L-methionine, L-lysine and L-arginine were all actively transported by the newborn rat jejunum. Metabolic inhibitors (e.g. 2,4-dinitrophenol) significantly reduced uptake of all amino acids but uptake against a concentration gradient was not totally abolished. Uptake of all amino acids was reduced at low[Na+]. Inhibition of transport of neutral amino acids by reduced luminal [Na+] was greater than that of basic amino acids, and the tissue was barely able to concentrate the neutral amino acids. [Na+] affected the Michaelis constant (Km) of neutral transport systems for their substrates; for the basic amino acids Km values were unaffected by the presence or absence of Na+. Ouabain significantly inhibited neutral amino acid uptake but had no effect on L-lysine or L-arginine uptake. These results are discussed in terms of the Na+ gradient hypothesis for amino acid transport, and the site of energy input to active transport. The role of glycolysis in providing energy for intestinal transport in the neonatal rat and the efficiency of Na+ dependent and independent transport mechanisms are considered. It is concluded that the energetics of amino acid transport systems in neonatal and adult rats are essentially similar.

Amino Acids↗

Stroke.

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Cerebrovascular Disorders↗

Age-dependent variations in polymorphonuclear leukocyte chemiluminescence.

Polymorphonuclear leukocytes from 46 adults (age 18 to 35), 19 adults (age 70 to 91), 10 children (age 1 to 3), and 22 neonates (cord blood samples) were tested for their chemiluminescence response to opsonized zymosan. Results indicated that both cord blood leukocytes and those from individuals over 70 were significantly lower (P less than 0.05) in their chemiluminescence response. Furthermore, when the latter group was divided into two subsets, one containing subjects over 80 years of age and the other containing subjects between 70 and 80 years of age, those over 80 showed a chemiluminescence response significantly lower (P less than 0.05) than those between 70 and 80. The kinetics of the chemiluminescence response was similar with all samples except the neonatal cells, where the response appeared to peak and subside more slowly. These data demonstrate that polymorphonuclear leukocyte chemiluminescence is depressed in the very young and the very old.

Adolescent↗

Polycythemia vera. The in vitro response of normal and abnormal stem cell lines to erythropoietin.

Bone marrow cells from two glucose-6-phosphate dehydrogenase (G-6-PD) heterozygotes with polycythemia vera were cultured to determine whether progenitors which wre not of the polycythemia vera clone were present, and, if present, which cell lines contributed to the increase in erythroid colonies observed in response to added erythropoietin (ESF). To accomplish this, the G-6-PD isoenzyme activity of individual erythroid colonies was determined. All of the erythroid colonies analyzed in cultures without added ESF, contained the G-6-PD isoenzyme type characteristic of the abnormal clone. With higher ESF concentrations in the culture, however, there was an increase in the colonies that were not of the polycythemia vera clone. Analysis of the ratio of the various types of colonies indicated that normal and polycythemia vera cells are capable of responding to ESF in vitro. In selected patients, this technique permits analysis of the ratios of normal to abnormal cells during the course of the disease, in response to therapy and during late complications, such as myelofibrosis or leukemic transformation.

Clone Cells↗