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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 415 records · Page 23Linked to original sources
PubMed1984

DNA sequences complementary to human 7 SK RNA show structural similarities to the short mobile elements of the mammalian genome.

A complementary DNA clone of 7 SK RNA from HeLa cells was used to study the genomic organization of 7 SK sequences in the human genome. Genomic hybridizations and genomic clones show that 7 SK is homologous to a family of disperse repeated sequences most of which lack the 3' end of the 7 SK RNA sequence. Only few of the genomic K sequences are homologous to both 3' and 5' 7 SK probes and presumably include the gene(s) for 7 SK RNA. The sequence of four genomic 7 SK clones confirms that they are in most cases pseudogenes. Although Alu sequences are frequently found near the 3' and 5' end of K DNA, the sequences immediately flanking the pseudogenes are different in all clones studied. However, direct repeats were found flanking directly the K DNA or the K-Alu unit, suggesting that the K sequences alone or in conjunction with Alu DNA might constitute a mobile element.

Base Sequence↗
PubMed1984

Cerebrovascular permeability to 86Rb in the rat after exposure to pulsed microwaves.

Microwaves (pulsed, 2,450 MHz) at an average power density of 3 W/cm2 were applied directly to the head for 5, 10, or 20 min, producing a peak specific absorption rate of 240 W/kg in the brain, which, after a 10-min exposure, resulted in brain temperatures in excess of 43 degrees C. A bolus of 86Rb in isotonic saline was injected intravenously and an arterial sample was collected for 20 s to determine cardiac output. Compared with unexposed controls, uptake of 86Rb increased most in those regions directly in the path of the irradiation, namely, the occipital and parietal cortex, as well as the dorsal hippocampus, midbrain, and basal ganglia. In a separate group of animals, regional brain-vascular spaces were found to increase with brain temperature. These results support previous observations indicating that reliably demonstrable increases of blood-brain barrier permeability are associated with intense, microwave-induced hyperthermia, and that the observed changes are not due to field-specific interaction.

Animals↗
PubMed1984

Concanavalin A binding glycoproteins in subcellular fractions from the developing rat cerebral cortex.

Synaptic plasma membrane (SPM) and mitochondrial fractions were prepared from 3-50-day rat cerebral cortex and their purity assessed. The fractions were subjected to electrophoresis on slab gels, stained for protein, and overlaid with 125I-concanavalin A (ConA). ConA binding glycoproteins (CABGs) were revealed by autoradiography. In the SPM fraction CABGs of MW 25,000, 63,000, 80,000, 115,000, 174,000, and 239,000 increased while those of MW 47,000, 75,000, and 190,000 decreased developmentally. In the mitochondrial fraction, CABGs of MW 25,000, 44,000, 115,000 and 174,000 increased while those of 34,000, 43,000, 47,000, 51,000, 80,000, 107,000, and 195,000 decreased developmentally. CABGs of MW 32,000, 63,000, 88,000, 153,000, 190,000, and 239,000 appear to be unique to the SPM fraction and those of MW 34,000, 107,000, and 195,000 are unique to the mitochondrial fraction.

Aging↗
PubMed1984

Effects of neonatal medroxyprogesterone acetate on postnatal sexual differentiation of female rats.

Medroxyprogesterone acetate (MPA), 5 micrograms/g body wt, was given to lactating female rats 1 day after parturition. Group 1 females suckled 10-12 young, with equal numbers of males and females, while Group 2 females each suckled 10 female young. The young were weaned at 21 days of age. Exposure to MPA advanced the day of vaginal opening by 1 day, and increased anogenital distance in Group 2 young. At autopsy between 80 and 100 days of age, the clitoris of Group 2 females was significantly greater than in controls, and ovarian and adrenal weights were reduced.

Adrenal Glands↗
PubMed1984

Neonatal exposure to a progestin via milk alters subsequent LH cyclicity in the female rat.

Medroxyprogesterone acetate (MPA; 5 micrograms/g body wt) or norethisterone oenanthate (NET-OEN; 4 micrograms/g body wt) was given to lactating female rats by subcutaneous injection 1 day after parturition. Each female suckled ten female pups which had been randomly allocated to her and at 21 days of age the pups were weaned. In this way female pups were exposed to either MPA or NET-OEN via milk during suckling. The patterns of LH and progesterone secretion at pro-oestrus were investigated using radioimmunoassay. When these pups reached adulthood it was found that neonatal exposure to MPA via milk significantly reduced the pro-oestrous LH peak by 45% as well as the total amount (by 27%) of LH secreted during pro-oestrus. Neonatal exposure via milk to NET-OEN had no effect on LH secretion during pro-oestrus. Pro-oestrous progesterone secretion was unaffected by either MPA or NET-OEN treatment.

Animals↗
PubMed1984

gamma-Glutamyl transpeptidase activity can be altered by kainic acid and related compounds.

The effect of kainic acid and related compounds, gamma-D-glutamylglycine, cis-2,3-piperidine dicarboxylic acid and DL alpha-aminoadipic acid, was investigated on purified and membrane bound gamma-glutamyl transpeptidase [GGT]. All four compounds suppressed enzyme activity to an extent which depended upon the presence of a gamma-glutamyl moiety acceptor. Of the amino acid and dipeptide acceptors used, glycyl-glycine was the most affected. These compounds may be useful probes in determining the physiological role of gamma-glutamyl transpeptidase. The relationship between GGT, the gamma-glutamyl cycle and the toxicity of kainic acid is discussed.

2-Aminoadipic Acid↗
PubMed1984

Late allergic reactions: the skin and the lung.

The late allergic response appears to be simply a sequel of an IgE-mediated mast cell-dependent allergic reaction which has a greater inflammatory component. Late responses in the skin and the bronchi share many similarities. Pharmacologic modification of the late allergic response is especially important because these reactions may be more severe and prolonged than immediate allergic reactions.

Adult↗
PubMed1984

Heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia.

Samples of leukemic cell DNA from 14 children with acute nonlymphocytic leukemia (ANLL) and 4 human myeloid leukemia cell lines were analyzed for rearrangement in the heavy chain region of the immunoglobulin gene. The diagnosis of ANLL was confirmed in all patients by morphological, cytochemical, and immunologic studies. By restriction endonuclease digestion and hybridization with cloned heavy chain immunoglobulin gene probes for the constant (Cmu) and joining (JH) regions, the DNA of 2 patients and 1 cell line (ML-1) was found to contain rearrangements. The DNA from the remaining 12 patients and 3 cell lines was not rearranged (germline configuration). Both patients with apparent immunoglobulin gene rearrangement achieved complete remission on therapy for ANLL. Immunoglobulin gene rearrangement in phenotypically defined ANLL suggests (1) that such changes may not be limited to lymphoid leukemia of B cell lineage, or (2) that, in some patients, the leukemic transforming event may involve stem cells capable of both B cell and myeloid differentiation.

Acute Disease↗
PubMed1984

Platelet metabolism during storage of platelet concentrates at 22 degrees C.

The development of methods for storing platelet concentrates (PCs) at 22 degrees C for transfusion has been predominantly empiric, with minimal knowledge of metabolic events occurring during storage. It is known that a decrease in pH due to accelerated production of lactic acid in hypoxic conditions is a major cause for loss of platelet viability. In the current studies, we have measured metabolic parameters such as O2 and glucose consumption rates and CO2 and lactic acid production rates. We have also determined the O2 and CO2 transport capacities of various containers and the buffering capacity of plasma. The O2 consumption rate was 1.10 +/- 0.16 (SD) nmol/min/10(9) platelets. In well-oxygenated systems, lactic acid formation was 1.74 +/- 0.12 nmol/min/mL PC for PCs with a platelet count of 1 to 2 X 10(9)/mL; and 0.52 mol of glucose was consumed per 1 mol lactic acid produced. In a completely oxygen-free system, lactic acid production increased 5-8-fold. These calculations suggest that 85% of energy generation is derived through oxidative metabolism and that glucose may not be the primary substrate for this metabolism. Bicarbonate concentration, initially 22.1 +/- 1.6 mEq/L, decreased 1.41 +/- 0.18 nEq/min/mL PC for PCs with counts 1 to 2 X 10(9) platelets/mL. The loss of bicarbonate was caused by displacement by lactic acid and as a consequence of spontaneous CO2 efflux from the container. CO2 production, 2.3 +/- 0.4 nmol/min/10(9) platelets, was derived from oxygen consumption and the CO2 liberated from bicarbonate as it was consumed. A rapid fall in pH to levels below 7.0 (22 degrees C) took place when the bicarbonate concentration fell below 5 mEq/L as lactate concentrations reached 20 to 25 mmol/L. A further increase in lactate concentration from 25 mmol/L to 40 mmol/L correlated with a further fall in pH to 5.8. Thus, the ultimate storage life of a PC is determined by continuous lactate production and the fixed buffering capacity of plasma and by the glucose concentration of the PC. With knowledge of these parameters, methods for predicting pH as a function of time, platelet count, and O2 and CO2 transport capability of the container have been developed as guidelines for future work.

Bicarbonates↗
PubMed1984

Studies of the platelet density abnormality in myeloproliferative disease.

We have previously shown that the extinction (optical density) of normal fresh platelets correlates closely with their apparent volume as determined with the Coulter counter and that platelets from patients with myeloproliferative disorders (MPD) have a decrease in extinction relative to their apparent volume. In this study we show that the reduction in extinction of MPD platelets correlates with a decrease in platelet density and with a decrease in the refractive index of the platelet hyaloplasm. To explore the abnormality of the hyaloplasm, we incubated normal and MPD platelets in plasma from blood anticoagulated with K3-ethylenediaminetetraacetate (EDTA). Normal platelets responded with marked swelling, as shown by an increase in apparent Coulter volume and by corresponding decreases in density, extinction, and refractive index of hyaloplasm. The magnitude of these changes was markedly less with MPD platelets. Ultrastructural studies by others have indicated that the swelling effect of EDTA results from dilatation of intracellular channels such as the surface-connected canalicular system and that these structures occupy more of the interior of MPD platelets than in the case of normal platelets. One hypothesis to explain our findings is that MPD platelets circulate with dilated internal channels that are unable to dilate further with EDTA. In addition, we previously found that MPD platelets display an increased dispersion (geometric standard deviation) of their apparent Coulter volumes. In this study we show that the dispersion abnormality correlates with the density abnormality and that the increase in dispersion is not confined to a subpopulation of abnormal light platelets; rather, it is present in all density subpopulations. All of our data are consistent with the view that the abnormalities in density and dispersion originate at the time of shedding from the megakaryocyte.

Blood Platelets↗
PubMed1983

Effect of intravenous carbenicillin, cefoxitin and cefamandole on ADP-induced platelet aggregation and shape change.

The effect of a large daily dose of i.v. carbenicillin, cefoxitin and cefamandole on platelet aggregation with adenosine diphosphate (ADP) and the effect of carbenicillin on ADP induced shape change were evaluated. Six volunteers received carbenicillin 100 mg/kg every 4 hours. Three of them also received cefoxitin 3 gm every 6 hours and cefamandole 2 gm every 4 hours. All treatments were separated by 14 days. Prior to treatment, as well as 1 and 24 hours after the last dose of antibiotic, citrated platelet-rich plasma was tested for the extent of aggregation at a series of ADP concentrations. As previously reported by several groups, carbenicillin decreased the sensitivity of platelets in their aggregation response to ADP. Thus, the concentration of ADP needed to obtain 50% of maximal aggregation response was increased 3.5 +/- 1.7 (S.D.) fold. In addition, when measured separately, the sensitivity of platelets in their shape change response to ADP was decreased to a similar degree. The concentration of ADP needed to produce 50% of maximal shape change response was 2.8 +/- 1.6 (S.D.) fold higher after carbenicillin treatment. The results are in accordance with previous in vitro studies suggesting that carbenicillin interferes with the initial phase of platelet activation. Cefoxitin and cefamandole had no apparent effect on platelet aggregation.

Adenosine Diphosphate↗