Ontogenesis of serotonin 'receptors' in different regions of rat brain.
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Age Factors↗
Biomedical subjects
S Murphy
Publications and source records attributed to S Murphy.
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↗
Neutrophil chemiluminescence defect in pediatric patients with recurrent pneumonias.
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Blood Bactericidal Activity↗
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↗
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↗
Platelet storage at 22 degrees C: effect of type of agitation on morphology, viability, and function in vitro.
Recovery in vivo after 51Cr labeling, platelet morphology, and platelet aggregation were studied with platelet concentrates (PC) stored for transfusion under carefully controlled conditions. PC were prepared to a final volume of 50 ml from whole blood anticoagulated with citrate-phosphate-dextrose (CPD). The platelet count was kept between 0.8 and 1.6 X 10(12) platelets/liter. The PC were stored in bags constructed of polyvinylchloride (PVC) or polyethylene (PE) at 22 degrees C for 72 hr. The bags were placed on a horizontal shaker or a ferris wheel for agitation during storage. No significant changes in pH or platelet count were observed during storage. PC stored on the wheel showed moderate loss of viability and a marked deterioration of platelet morphology and aggregation compared to the shaker. PC stored on the shaker in bags made of PE showed better aggregation with ADP and thrombin but had the same viability and morphology as PC in bags constructed of PVC. Maintenance of normal platelet morphology as determined by phase-contrast microscopy, extent of shape change response, and the size distribution according to the Coulter Counter correlated with recovery in vivo.
Blood Platelets↗
Template bleeding time and clinical hemorrhage in myeloproliferative disease.
In 32 patients with myeloproliferative disorders (MPD), correlations were made among clinical observations of hemorrhagic tendency, template Ivy bleeding time, and platelet aggregation studies. Bleeding time was commonly prolonged, particularly in myelofibrosis. In two cases, this prolongation appeared to reflect a defect in platelet function, which resulted in clinical bleeding. Prolongation of bleeding time did not correlate with degree of thrombocytosis. Two patients with thrombocytosis had serious clinical bleeding at a time when bleeding time was normal. Of the patients, 35% had abnormal findings from aggregation studies, but there was no correlation between aggregation studies and prolongation of bleeding time or clinical hemorrhage. We conclude that bleeding in MPD arises either from a defect in platelet function, which is reflected in a prolonged bleeding time, or from thrombocytosis.
Blood Cell Count↗
Harvesting of platelets for transfusion and problems of storage.
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Aspirin↗
Microscopic platelet size and morphology in various hematologic disorders.
Microscopic evaluation of apparent platelet size and morphology was examined in a variety of hematologic disorders. The time of preparation of the blood smear was important. An artifactual increase in platelet size was noted on blood films from 20 normal individuals that were prepared either immediately or 180 min after venipuncture. The clearest differentiation of patient categories was obtained with smears prepared 60 min after venipuncture using blood anticoagulated with K3EDTA. Under these conditions, normal size and morphology values were found in thrombocytopenic patients with aplasia or with increased splenic pooling. In contrast, large size values were a reliable finding in idiopathic thrombocytopenic purpura patients, whose platelet counts were less than 50,000/microleter. Large size values were also noted in patients with infiltrated bone marrows or myeloproliferative syndromes regardless of the platelet count. The last two groups usually showed abnormal platelet morphology with greater than 10% hypogranular platelets. Normal platelet size and morphology were observed in patients with iron-deficiency and megaloblastic anemias and in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus who had normal platelet counts.
Anemia, Hypochromic↗
Immunotherapy of leukemia and lymphoma.
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Antigens, Neoplasm↗