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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 379 records · Page 21Linked to original sources
PubMed1987

Hematologic problems in the preoperative patient.

A number of topics have been reviewed pertaining to hematologic problems in preoperative patients. Most if not all of the problems discussed can be evaluated reasonably well by history, physical examination, and a few simple laboratory tests. Because the morbidity arising from some of these abnormalities can be quite significant, evaluation and treatment should be completed prior to surgery whenever possible. It is also critical to recall that therapy for a number of hematologic problems involves the transfusion of blood or blood products. This therapy should not be taken lightly as both immediate reactions (fever, anaphalaxis, hemolysis) as well as delayed effects (allosensitization and viral infections) occur frequently. The prudent clinician should try to minimize his patients' exposure to these potentially toxic materials by using alternative therapies.

Hematologic Diseases↗
PubMed1987

Cromolyn sodium: a review of mechanisms and clinical use in asthma.

The cellular and clinical pharmacology of cromolyn sodium are reviewed. Cromolyn sodium inhibits the release of mediators of inflammation, induced by specific antigens as well as nonspecific mechanisms, such as exercise, from mast cells. Cromolyn may also inhibit the activity of other cell types that produce inflammation. It is the only antiasthmatic that blocks both early and late asthmatic responses induced by allergen inhalation and exercise. Consequently, cromolyn therapy can block the increase in bronchial hyperreactivity induced by chronic allergen exposure. Cromolyn is effective for controlling the symptoms of mild to moderate chronic asthma in 60 to 70 percent of patients. In comparative studies, cromolyn has been as effective as theophylline for controlling symptoms of chronic asthma with fewer side effects, and may be particularly suited for asthmatic patients with learning or behavioral problems. The combination of theophylline and cromolyn is often more effective than either agent alone. Because of the convenience of administration, cromolyn is preferred over theophylline for exercise-induced asthma. Cromolyn may allow the corticosteroid dosage to be reduced in severe steroid-dependent asthmatics, but it is primarily indicated for the prophylaxis of mild to moderate disease. Adverse reactions to cromolyn are uncommon to rare. Cromolyn is now available in a Spinhaler, a metered-dose aerosol, and a nebulizer solution. If taken properly all preparations appear to be equally effective. Attention to proper inhalation technique and appropriate education of the patient is essential to ensure a good outcome with cromolyn.

Asthma↗
PubMed1987

Lymphocyte interleukin 2 production and responsiveness are altered in patients with primary myelodysplastic syndrome.

Immunoregulatory T and B cell functions in 15 patients with primary myelodysplastic syndrome (MDS) were studied by measuring the proliferative and the stimulatory capacity of T and B cells, respectively, in autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR). T cell proliferation in the auto MLR was 25% of the control (P less than .02), whereas proliferation in the allo MLR was normal. When control T cells were stimulated by MDS B cells, their proliferative response was only 57% of the control (P less than .01). The mechanism responsible for these abnormalities was studied by determining the capacity of MDS and normal T cells to produce interleukin 2 (IL 2) and to generate IL 2 receptors (IL 2R) following stimulation with control and MDS B cells. In the auto MLR of MDS patients, only 3% +/- 2% of T cells developed IL 2R positivity, whereas in control cultures 12% +/- 2% of T cells were positive, as determined by immunofluorescence, using a monoclonal antibody (MoAb) directed against the IL 2R, and FACS analysis. When MDS T cells were stimulated by control B cells, IL 2R generation and the production of IL 2 were within normal limits. In contrast, when control T cells were stimulated by MDS B cells or control B cells, the MDS B cells induced production of only 26% of IL 2 as compared with control B cells. In parallel experiments, IL 2R generation in control T cells stimulated by either MDS or control B cells was similar. We conclude that in the primary MDS, T and B cell interactions are impaired. Although MDS T cells develop normal quantities of IL 2R and produce normal amounts of IL 2 when stimulated by control B cells, they are markedly impaired when stimulated by self B cells. Similarly, MDS B cells can induce IL 2R generation in control T cells but not in MDS T cells. Myelodysplastic B cells are also defective in inducing IL 2 production by normal T cells in an allo MLR. These in vitro abnormalities strongly suggest that generation of lymphocytes with immunoregulatory functions is impaired in patients with MDS.

B-Lymphocytes↗
PubMed1987

ACTH-related peptides, kindling and seizure disorders.

Very small amounts of pituitary hormones and their peptide fragments can profoundly affect learning, memory and other behaviors in both rodents and humans. In addition, several potent pituitary hormone analogs have been developed (e.g. ORG-2766) which retain the behavioral but not the endocrine properties of the parent hormone. The abilities of these peptides to influence nervous system functions suggested that they also may be capable of modifying seizure activity. This possibility is supported by the fact that treatment with adrenocorticotropic hormone (ACTH) represents a major effective therapy for at least one clinical convulsive disorder, infantile spasm. This contention also is reinforced by our findings that ORG-2766 markedly reduces both the behavioral severity and the spread of seizure potentials in an animal model of epilepsy, the kindled rat. By contrast, arginine vasopressin and its non-endocrine desglycyl fragment (DGAVP) facilitates the seizure process in this animal model. Our research also suggests that the behavioral and physiological effects of certain anterior and posterior pituitary hormone fragments depend, in part, on their abilities to modulate permeability mechanisms in brain vasculature. In addition, and especially significant from the standpoint of etiology, is the observation that the kindling process itself appears to alter cerebrovascular permeability. In the kindled rat, "permanent" decreases in permeability (60-75%) are found selectively in the hypothalamic and hippocampal regions, weeks after the last seizure. Several lines of evidence indicate that disruption of normal cerebrovascular function occurs following epileptiform seizures. We propose that an immediate increase in cerebral blood flow and cerebrovascular permeability occurs following a single, acute seizure, and that repeated chronic seizures lead to damage to the cerebrovascular system. Sustained damage would be expected to contribute to the development and maintenance of a chronic seizure focus. Such observations suggest a link between important cerebrovascular disturbances associated with seizures and the existing known and proposed electrophysiological, metabolic and neuropathological substrates of epilepsy. They also point to new strategies for the treatment of seizure disorders by focusing on ways to reduce or prevent cerebrovascular damage.

Adrenocorticotropic Hormone↗
PubMed1987

Cystic fibrosis in adults: diagnosis and management.

Once regarded as a disease of infants and young children, cystic fibrosis now also must be considered a disease of adolescents and young adults. Disease complications and management, including hemoptysis, pneumothorax, sinusitis, pancreatic deficiency, and intestinal obstruction, are discussed in this review. In addition, a practical approach to the clinical evaluation, follow-up, and treatment of the older cystic fibrosis patient is presented for the physician who has not had extensive experience in managing these patients. Current research in identifying the CF gene, basic defect, and the use of heart-lung transplants is discussed.

Adult↗
PubMed1987

Familial bleeding disorder associated with deficiencies in platelet signal processing and glycoproteins.

Aggregation responses to low concentrations of ADP, epinephrine, collagen and cationophore A23187 in platelets from two family members with marked bleeding tendencies were virtually absent, whereas shape change with ADP was normal. The contribution to factor X activation by collagen-treated platelets was markedly decreased. Glycoproteins IIb and III were also significantly reduced. The patients' platelets had normal stores of secretable constituents, but secretion of adenine nucleotides and acid hydrolases in response to low concentrations of thrombin and A23187 was drastically reduced compared to normal platelets; secretion of platelet factor 4 was normal. Agonist concentrations that normally produce maximal responses induced only partial aggregation and secretion in the patients' platelets. After prelabelling with [3H]arachidonate thrombin caused less changes in the [3H]phosphatidylinositol, [3H]phosphatidylcholine and free [3H]arachidonate in platelets from the patients than in platelets from normals. We conclude that the patients' platelets have an impairment in part of the signal processing mechanism that is common for all agonists and responses. This platelet abnormality, which has a superficial resemblance to thrombasthenia, represents a hitherto undescribed qualitative platelet disorder.

Adenosine Diphosphate↗
PubMed1986

Astrocyte glutamate receptor activation promotes inositol phospholipid turnover and calcium flux.

Astrocyte-enriched cultures prepared from the neonatal rat cortex were prelabelled with either [3H]myoinositol or 45Ca2+ and then exposed to various excitatory amino acids. This resulted in an increase in both the breakdown of membrane inositol phospholipids and Ca2+ flux with the following rank order of efficacy: quisqualate greater than or equal to glutamate (Glu) greater than kainate much greater than N-methyl-D-aspartate. Experiments performed with the Ca2+ ionophore A23187 and in the absence of medium Ca2+ suggested that Glu-evoked 45Ca2+ efflux was primarily the result of an increased influx of extracellular Ca2+. However, Glu-stimulated inositol lipid metabolism was found to be only partially dependent on extracellular Ca2+. The quisqualate-preferring receptor antagonist gamma-glutamylaminomethylsulphonic acid was found to be effective in reversing both Glu-evoked inositol lipid breakdown and Ca2+ flux. The results presented are suggestive of some form of interaction between Glu receptors coupled to inositol lipid turnover and Ca2+ channel opening in astrocytes.

Amino Acids↗
PubMed1986

A sequence upstream from the coding region is required for the transcription of the 7SK RNA genes.

We have isolated and characterized two recombinant lambda phages containing sequences homologous to 7SK RNA which code for a RNA 330 nucleotides long in an "in vitro" transcription system. S1 mapping of the transcript shows that this RNA corresponds to the 7SK RNA obtained from human cells, indicating that the two recombinant phages contain genes coding for 7SK RNA. The transcription of these genes is polymerase III dependent. Sequences upstream from the start of transcription are essential for "in vitro" synthesis of 7SK RNA, suggesting that internal promoter elements, if present, are not sufficient to support the synthesis of 7SK RNA. A region of homology with the upstream sequences of the genes for U6 RNA, 7SL RNA and Bombyx mori alanine tRNA is found within 50 bp from the transcription start point. Within the homologous region a motif common to the four genes is a "TATA"-like box, placed at position -30 to -25 of the 7SK RNA gene, which is typical of the polymerase II promoter region.

Base Sequence↗
PubMed1986

Receptor-mediated inositol phospholipid hydrolysis in astrocytes.

Astrocyte-enriched cultures of the neonatal rat cortex were incubated for 24 h with [3H]inositol to prelabel the membrane inositol phospholipids. Exposure of the cultures to either noradrenaline or carbachol in the presence of Li+ produced a time- and dose-dependent accumulation of intracellular [3H]inositol phosphates. The separation of the individual inositol phosphates formed in response to receptor stimulation revealed that the major 3H-metabolite accumulated under these conditions was inositol monophosphate but that at least some of this was due to the initial formation of inositol trisphosphate. The use of selective receptor antagonists showed that noradrenaline- and carbachol-induced [3H]inositol phosphate accumulation was the result of the activation of alpha 1-adrenoceptors and muscarinic acetylcholine (probably of the M1 subtype) receptors respectively. Agonist-evoked [3H]inositol phosphate accumulation were found to be additive but the simultaneous addition of agonists and the Ca2+ ionophore A23187, which also promoted inositol phospholipid hydrolysis, was not. Agonist-induced [3H]inositol phosphate accumulation was only partially dependent on extracellular Ca2+, whilst that elicited by A23187 was entirely Ca2+-dependent. The results suggest that alpha 1-adrenoceptors and muscarinic acetylcholine receptors in these cultures are present either on the same cells and linked to separate inositol lipid pools or associated with different subpopulations of astrocytes in these cultures. Moreover, inositol lipids other than phosphatidylinositol 4,5-bisphosphate may be hydrolysed in response to agonist stimulation.

Animals↗
PubMed1986

Astrocytes have both M1 and M2 muscarinic receptor subtypes.

In astrocytes, carbachol evoked the turnover of membrane inositol phospholipids prelabelled with [3H]inositol, as revealed by [3H]inositol phosphate accumulation in the presence of 5 mM lithium. This effect was blocked by atropine and by pirenzepine (IC50 2.2 nM and 56 nM, respectively). Carbachol partially attenuated the isoproterenol-stimulated cyclic adenosine 3',5'-monophosphate production in astrocytes by a direct effect on adenylate cyclase, an effect blocked by atropine and pirenzepine. These results suggest that astrocytes express muscarinic receptor subtypes.

Animals↗
PubMed1986

Platelet dysfunction in uremia. II. Correction by arachidonic acid of the impaired exposure of fibrinogen receptors by adenosine diphosphate or collagen.

Previous studies showed that platelets from patients with uremia have a marked decrease in their aggregation response to adenosine diphosphate (ADP) and collagen as single agents or as a pair. It is known that small amounts of arachidonic acid can enhance the sensitivity of platelets to concentrations of ADP or collagen that do not cause aggregation when used singly. Stimulation of platelets by certain agonists induces the formation of fibrinogen receptors on the platelet surface. The binding of fibrinogen that follows is essential for platelet aggregation. The platelet membrane glycoprotein IIb-IIIa complex appears to be the site of the fibrinogen receptor. Therefore, we investigated the binding of iodine 125-labeled fibrinogen to uremic platelets exposed to ADP, collagen, or arachidonic acid as single agents and as pairs. When aggregation and binding were studied in response to ADP, collagen, or the combination of ADP with collagen, uremic platelets had reduced aggregation and bound abnormally low amounts of fibrinogen. In contrast, platelets from patients with uremia bound as much 125I-fibrinogen and aggregated as well as controls when ADP or collagen were used in combination with low concentrations of arachidonic acid. Studies with a monoclonal antibody (B 79.7) suggested that the number of glycoprotein IIb-IIa molecules is the same in uremic and normal platelets. We conclude that uremia impairs the exposure of fibrinogen receptors on platelets in response to ADP or collagen without affecting the glycoprotein IIb-IIa complex quantitatively. Correction by arachidonic acid of the impaired aggregation and exposure of fibrinogen receptors by ADP or collagen suggests that abnormal release of endogenous arachidonic acid plays a role in the dysfunction of platelets in uremia.

Adenosine Diphosphate↗