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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 217 records · Page 12Linked to original sources
PubMed1994

A comparison of monoclonal antibody productivity in different hollow fiber bioreactors.

Cell culture in hollow fiber bioreactors has been used as a method for large-scale production of monoclonal antibodies, viruses, cell-associated proteins and cancer antigens. We have examined an important variable in culturing cells in hollow fiber bioreactors: bioreactor composition. Eight different bioreactor designs which varied in nominal molecular weight cutoff, surface area, fiber material and ultra filtration rate were compared in large-scale hollow fiber cultures. A standard protocol utilizing the hybridoma 3C11 (ATCC HB 8511) or African green monkey kidney cells (Vero cells, ATCC CRL 1587) was designed so that the only variable examined was the hollow fiber bioreactor in use. The results suggest that surface area has little effect on antibody productivity, while fiber composition and ultrafiltration rate may play an important role. Vero cell growth was affected by both fiber composition and ultrafiltration rate.

Animals↗
PubMed1994

Astrocyte-derived lipoxygenase product evokes endothelium-dependent relaxation of the basilar artery.

The goal of this study was to examine the possible production of vasoactive factors by astrocytes. We consistently observe that rat astroglial cells in suspension produce marked relaxation when added to precontracted rings of intact (but not endothelium-denuded) rabbit basilar artery. The ultimate mediator of this relaxation was endothelium-derived nitric oxide whose synthesis is activated by an as yet unidentified factor(s) produced tonically by astrocytes. The factor is relatively stable, and is not arachidonate, or a product of cyclooxygenase or P450 metabolism. Based upon studies with selective inhibitors, the factor appears to result from 12- or 15-lipoxygenase metabolism, the products of which are known to be vasoactive. In a separate series of experiments, astrocyte-conditioned medium stimulated the production of citrulline from L-arginine by nitric oxide synthase in bovine aortic endothelial cells. The possible significance for central nervous system (CNS) pathophysiology of an astrocyte-derived vasodilator is discussed.

Amino Acid Oxidoreductases↗
PubMed1994

Nitric oxide limits transcriptional induction of nitric oxide synthase in CNS glial cells.

Nitric oxide (NO) can modulate directly and indirectly the activity of a variety of enzymes, including nitric oxide synthase (NOS). In addition, it appears that the NO formed by astroglial cells in which transcriptional induction of NOS has been evoked by cytokines affects NOS mRNA level. We have observed that induction in the presence of NOS inhibitors or NO-trapping agents amplifies NOS mRNA expression and that this effect is reversed by an NO donor. Rather than promoting mRNA instability, NO appears to inhibit the transcriptional induction of NOS. This effect of NO on induction of the NOS gene provides a mechanism by which the temporal and perhaps spatial production in the nervous system of NO, a reactive and potentially toxic mediator, can be finely regulated.

Amino Acid Oxidoreductases↗
PubMed1994

Effect of hypoxia and reoxygenation on the activity of transglutaminase in brain of newborn piglets.

The transglutaminase activity in five regions of the brain of newborn piglets was measured and the effects of hypoxia and posthypoxic period on this activity evaluated. Enzyme activity was measured in homogenates from cortex, hippocampus, striatum, thalamus and midbrain. The control activities were 7.2, 6.2, 6.0, 5.7 and 4.6 pmol/mg protein/min, respectively. The activities at the end of an 18 min period of hypoxia induced by an FiO2 of 9% were not significantly different from control activities. By 3 h after the hypoxic episode, however, the transglutaminase activities were significantly above control levels in all five regions of the brain. Measurements of the kinetic constants of tranglutaminase indicated that increases in enzyme activity were associated with an increase in Vmax with no significant change in the apparent affinity of the enzyme for the substrate, putrescine. The increased activity of transglutaminase during the posthypoxic period, with no changes immediately after hypoxia, suggest that the increases could be due to increased enzyme synthesis rather than activation of existing enzyme. The rise in transglutaminase activity subsequent to a hypoxic episode may contribute significantly to the long-term disturbances in cellular metabolism in the immature brain induced by hypoxic episodes.

Animals↗
PubMed1994

Milk consumption and bone mineral density in middle aged and elderly women.

OBJECTIVES: To study the effects of historical milk consumption on current bone mineral density at the hip and spine. DESIGN: Cross sectional study. SUBJECTS: 284 community based women aged 44-74 years recruited from four general practice age-sex registers in Cambridge. Subjects categorised their average milk consumption up to age 25, from age 25-44, and from age 44 to the present time as > or = 1 glass/day, < 1 glass/day but > 1 glass/week, or < 1 glass/week. MAIN OUTCOME MEASURES: Bone mineral density at the hip and spine measured by dual energy x ray absorptiometry. RESULTS: Data on milk consumption up to age 25 years were available for 252 women. There was a consistent upward trend in bone mineral density at all sites with increasing historical milk consumption (total hip, femoral neck, trochanter, intertrochanter, P < 0.05; Ward's triangle, P = 0.005). Adjustment for age and body size did not alter these trends. Milk consumption up to age 25 was a significant independent predictor of bone mineral density at all sites in multiple linear regression analyses controlling for age, body mass index, menopausal status, smoking, ever use of hormone replacement therapy or oral contraceptives, physical activity, and alcohol intake. The effects of milk consumption from age 25-44 and from age 44 to the present were similar in direction though not statistically significant. CONCLUSION: Frequent milk consumption before age 25 favourably influences hip bone mass in middle aged and older women.

Absorptiometry, Photon↗
PubMed1994

Decline of erythromycin resistance of group A beta-hemolytic streptococci in Japan. Comparison with worldwide reports.

OBJECTIVE: To determine the current prevalence of erythromycin resistance and penicillin tolerance of group A beta-hemolytic streptococci (GABHS) in Japan. RESEARCH DESIGN: One hundred four isolates of GABHS from the civilian community in Tokyo and 101 isolates from the military population at the US Air Force Base in Yokota, Japan, were tested for erythromycin susceptibility and penicillin susceptibility and tolerance. SETTING: US Army Medical Center. RESULTS: Of the Japanese civilian isolates, two were moderately susceptible and none were resistant to erythromycin; of the military isolates, none were moderately susceptible and one was resistant, for an overall resistance rate of 0.49%. All isolates were exquisitely susceptible to penicillin, and no evidence of penicillin tolerance was found. CONCLUSIONS: Comparison with similar studies world-wide shows that erythromycin susceptibility of GABHS in Japan is now among the lowest in the world, while just over a decade ago it was the highest. These observations mandate constant monitoring of erythromycin resistance of GABHS wherever this drug is used to treat patients with infections due to this organism.

Drug Resistance, Microbial↗
PubMed1994

Comparison of neonatal nurse practitioners, physician assistants, and residents in the neonatal intensive care unit.

OBJECTIVE: To compare patient care delivery by neonatal nurse practitioners and physician assistants with that of pediatric residents in the intensive care setting. DESIGN: Retrospective chart review after developing specific performance criteria, namely, patient management, outcome, and charges. METHODS/MATERIALS: Charts for 244 consecutive admissions to a neonatal intensive care unit in Jacksonville, Fla, were reviewed. Patients were cared for by one of two teams, one staffed by residents and the other by neonatal nurse practitioners and physician assistants. Similar patients were cared for by the two teams, as determined by patient background characteristics and diagnostic variables. Performance of the two teams was assessed by comparison of patient management, outcome, and charges. Management variables included data on length of critical care and hospital stay, ventilator and oxygen use, total parenteral nutritional use, number of transfusions, and the performance of various procedures. Outcome variables included the incidence of air leaks, bronchopulmonary dysplasia, intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity, and number of infants who died. Charge variables included hospital and physician charges. MAIN RESULTS: Results demonstrated no significant differences in management, outcome, or charge variables between patients cared for by the two teams. CONCLUSION: Neonatal nurse practitioners and physician assistants are an effective alternative to residents for patient care in the neonatal intensive care unit.

Florida↗
PubMed1994

Roles for protein kinases in the induction of nitric oxide synthase in astrocytes.

Lipopolysaccharide (LPS) or a combination of interferon (IFN)-gamma and interleukin (IL)-1 beta can induce a calcium-independent nitric oxide synthase (iNOS) in astrocyte cultures (Simmons and Murphy: J Neurochem 59:897, 1992; Eur J Neurosci 5:825, 1993; Galea et al: Proc Natl Acad Sci USA 89:10945, 1992). This induction can be measured by assaying cyclic GMP levels in the cultures, which correlates with, but is more sensitive than, measurement of nitrite accumulation. To study potential second-messenger systems involved in the induction of iNOS, phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, and various protein kinase inhibitors were employed. PMA induced a time-, dose-, and L-arginine-dependent increase in cyclic GMP, which could be inhibited by dexamethasone or actinomycin D. This induction could be dramatically increased by concurrent treatment with IFN-gamma. The presence of iNOS mRNA could be demonstrated by hybridization with a specific cDNA probe. H7 (a non-specific serine/threonine kinase inhibitor) but not H89 (a more specific PKA inhibitor) prevented induction by all agents. However, downregulation of PKC or pretreatment with the PKC inhibitor calphostin C did not prevent the induction by LPS or cytokines, suggesting that PKC is not necessary for iNOS induction by these mediators. Additionally, genistein (a nonspecific tyrosine kinase inhibitor) could prevent induction by all agents, but the more specific inhibitor, tyrphostin, attenuated only NOS induction by LPS. These results suggest that activation of PKC can lead to, but is not necessary for, the induction of NOS in astrocytes and that there is a potential role for tyrosine kinases in NOS induction by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Effect of neurocatin on the activity of monoamine oxidase B in rat brain synaptosomes.

Neurocatin, a small (about 2,000 Dalton) neuroregulator isolated from mammalian brain, is a powerful effector of monoamine oxidase B in rat brain synaptosomes. Incubation of intact synaptosomes with neurocatin caused an inhibition of the enzyme dependent on the concentration of neurocatin. This inhibition became statistically significant at a neurocatin concentration of 10 ng/200 microliters and was significant at all higher neurocatin concentrations. At 40 ng/200 microliters, neurocatin inhibited monoamine oxidase B activity by about 60%. This inhibitory effect was almost completely abolished by breaking the synaptosomal membrane by hypotonic buffer prior to incubation with neurocatin. In addition, incubation of the synaptosomes in calcium free medium almost completely abolished the inhibitory effect of neurocatin on monoamine oxidase B. The inhibition appeared to involve covalent modification of the enzyme mediated by a neurocatin receptor(s). Measurements of the kinetic parameters of the enzyme showed that 20 ng of neurocatin caused a statistically significant decrease in Vmax (by 20%) with no significant change in KM, compared to controls. Inhibition of monoamine oxidase by neurocatin is potentially of great clinical importance because this enzyme plays a major role in catabolism of the biogenic amines and alterations in its activity is believed to contribute to several neurological disorders.

Animals↗
PubMed1994

Parity and bone mineral density in middle-aged women.

A retrospective study was carried out to determine the relationship between parity and bone mineral density (BMD) in middle-aged women. Eight hundred and twenty-five woman aged 41-76 years were recruited from four general practice registers in Cambridge. Subjects were unselected as to their health status. Each subject completed a detailed health questionnaire. Participation rate was 50%. The main outcome measure was BMD measured at the spine (L2-4, n = 825) and hip (neck, intertrochanter and Ward's triangle; n = 817) by dual-energy X-ray absorptiometry (DXA) using the Hologic QDR-1000 densitometer. It was found that the unadjusted mean BMD was significantly higher at all sites among the parous women (p = 0.031 to < 0.00001), and remained significantly higher at the femoral neck (p = 0.025), intertrochanter (p = 0.001) and Ward's triangle (p = 0.045) after adjusting for age and body mass index (BMI). Similar findings were seen after stratifying for potential confounding variables. There was a consistent upward trend of BMD with increasing parity at all sites. Parity remained a significant independent predictor of BMD at all sites after controlling for age, BMI, menopausal status, oral contraceptive and hormone replacement therapy use, smoking status and breast-feeding status in multiple linear regression analyses. There was, on average, a 1.0% increase in BMD per live birth. Our findings therefore suggest a positive relationship between parity and bone mass.

Adult↗
PubMed1994

Primary spontaneous pneumothorax in children.

In the absence of pediatric data, spontaneous pneumothorax is managed according to adult guidelines. Fifty-eight patients with primary spontaneous pneumothorax (PSP) were treated in our center over the last 20 years. The median age was 16.7 years, and the male:female ratio was 1.9:1. A total of 102 PSP were treated; 63% were left-sided. The risk of recurrence was 51% after one PSP and 56% after two. There were four metachronous bilateral PSP. Nonoperative management included tube drainage in 57% of the cases (mean extent of PSP, 53%). Forty percent of patients were treated by supplemental oxygen and observation, without drainage (mean extent of PSP, 23%). Eleven patients were treated as outpatients, with Heimlich valves (mean extent of PSP, 64%). Fourteen patients (28%) underwent bullectomy, with or without pleurodesis. Thirteen of the surgically treated patient had experienced at least two episodes of PSP. Primary spontaneous pneumothorax in children has male predominance. The risk of recurrence after one episode is greater than that for adults. Operative management by bullectomy, with or without pleurodesis, carries little morbidity, has a high success rate, and is recommended after the first recurrence. It is safe to manage younger children conservatively because the chance of recurrence is lower; thoracotomy was not necessary in children under 9 years of age.

Adolescent↗
PubMed1994

Report of three gastric tumors in children.

The literature concerning gastric tumors in children is mainly limited to case studies. The authors reviewed 1,403 histological reports of pediatric gastric pathology (covering 10 years) at their institution. There were three gastric tumors of benign histology and no malignant tumors. The first patient was a 9 1/2-year-old boy who presented with several months of symptomatic, pH-probe-confirmed gastroesophageal reflux. He underwent placement of a Toupet antireflux valve. During laparotomy, a submucosal mass was discovered incidentally, on the greater curvature of the stomach. The mass was excised. Pathological examination showed heterotopic pancreas. The second patient, a 15-month-old girl, presented with a short period of vomiting. Results of an upper gastrointestinal series showed gastric outlet obstruction. She underwent laparotomy and was found to have an intussusception of a gastric polyp into the proximal jejunum, and an associated malrotation. Ladd's procedure, gastroduoduodenostomy with reduction of the intussuscepted polyp, and excision of the polyp were performed. Histological examination of the tumor showed hamartoma with hyperplastic elements. The tumor was benign but was regarded as difficult to classify. The third patient, a 6-year-old boy, presented with microcytic anemia. Endoscopy showed multiple friable bleeding gastric masses. He underwent laparotomy, with partial gastrectomy and pyloroplasty. Histological examination showed the tumor to be plasma cell granuloma. The tumor recurred, and the patient required subsequent operative procedures. The authors confirm that gastric tumors in children are rare. Although the tumor histology may be benign, excision of the tumor may require major operative resection.

Child↗
PubMed1994

Minimally conjoined omphalopagi: a consistent spectrum of anomalies.

Omphalapagus twins constitute less than one third of all siamese twins. Most omphalopagi are attached by a skin bridge that often contains hepatic tissue. Only four cases of omphalopagi attached by an intestinal bridge have been reported. The authors present two additional cases of conjoined twins minimally attached by a small bowel and bladder bridge. In both instances, the spectrum of anomalies included a ruptured omphalocele and imperforate anus with cloacal anomalies. The attachment consisted of an open urachal remnant joining the two bladders, and the short small bowel of twin A attached to the terminal ileum of twin B. Separation was uneventful. For one set of twins, the case part of the proximal colon of twin B was used to lengthen the bowel of twin A. Three of the twins survived and underwent additional procedures for repair of the cloacal anomalies. All four previously reported cases of minimally conjoined omphalopagi presented with a remarkably similar spectrum of anomalies. All had ruptured omphaloceles, imperforate anus with cloacal anomalies, and urachal anomalies. Intestinal connection was consistently at a point corresponding to the Meckel diverticulum site of twin B, with blood supply to the small bowel of twin A, probably via the vitelline artery. The consistent spectrum of anomalies encountered with minimally conjoined omphalopagi allows planning of separation. Caution is required to avoid overlooking the patent urachus, and intestinal lengthening procedures based on the vitelline artery become an important consideration.

Anus, Imperforate↗
PubMed1994

Growth hormone-binding protein levels: studies of children with short stature.

A high-affinity growth hormone-binding protein (GHBP) in serum is derived from the extracellular domain of the GH receptor. In an attempt to investigate the differences in GHBP levels in various conditions of poor growth, we measured GHBP levels by two methods--an Ultrogel chromatographic technique and a ligand-mediated immunofunctional assay (LIFA). The following three groups of children were studied: Turner's syndrome (n = 7), idiopathic and/or familial short stature ([ISS] n = 15), and organic or idiopathic hypopituitarism (n = 19). All groups were similar in age (Turner's syndrome, 10.1 +/- 0.9 years; ISS, 10.0 +/- 0.7; hypopituitarism, 11.5 +/- 1.0) and height SEM score (Turner's syndrome, -2.9 +/- 0.3; ISS, -3.0 +/- 0.4; hypopituitarism, -2.3 +/- 0.4). Their values were compared with those values of GHBP in healthy controls of similar age. Immunofunctional assay values for GHBP were as follows: Turner's syndrome, 235.4 +/- 26.0 pmol/L; ISS, 122.4 +/- 11.0; and hypopituitarism, 157.1 +/- 23.0. These results were significantly different in subjects with ISS and hypopituitarism as compared with a group of healthy controls between the ages of 9 and 12 years (N = 255; GHBP = 287.9 +/- 10.9 pMol/L; P < .001 compared with both ISS and hypopituitarism). Similar changes were found using Ultrogel chromatography. This difference in GHBP levels is still significant even when more stringent criteria are applied to define hypopituitarism (ie, peak GH responses to stimuli < 6.0 ng/mL, instead of < or = 10 ng/mL originally).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Modulation of inducible nitric oxide synthase expression in astroglial cells.

Nitric oxide is produced in the CNS by both constitutive and inducible isoforms of nitric oxide synthase. Once nitric oxide synthase is transcriptionally induced in astrocytes in vitro, these cells release large amounts of nitric oxide tonically. Glial cell-derived nitric oxide can be toxic to neurons and oligodendrocytes and is implicated in a variety of neuropathologies, suggesting that the expression of nitric oxide synthase in glia must be finely regulated. From northern and western blot analysis we have identified various agents (transforming growth factor-beta, nitric oxide, receptor agonists) that modulate cytokine-induced expression of nitric oxide synthase mRNA in astrocytes. This suggests that the magnitude and duration of nitric oxide production from activated astrocytes in vivo may be determined by signals from adjacent neurons and microglial cells.

Amino Acid Oxidoreductases↗
PubMed1994

The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat.

Recent studies have suggested that glia might play a more active role in synaptic function than previously thought. Therefore, the present studies have evaluated the potential role of spinal cord glia in acute nociceptive processing and in the thermal and mechanical hyperalgesia produced by peripheral injury. In the present experiments, we found that: (1) selective inhibition of glia metabolism with intrathecal (i.t.) administration of fluorocitrate (1 nmol) results in a marked, but reversible, attenuation of the persistent thermal and mechanical hyperalgesia produced by intraplantar zymosan (5 mg); (2) selective inhibition of the inducible form of nitric oxide synthase (iNOS) with i.t. aminoguanidine (1 pmol-1 nmol) resulted in a dose-dependent inhibition of the persistent thermal, but not mechanical hyperalgesia produced by intraplantar zymosan (5 mg); (3) i.t. coadministration of interleukin 1 beta (IL1 beta; 10 ng) and interferon gamma (IFN; 1000 U) resulted in expression of the message for iNOS 8 hr after administration assessed using reverse-transcription polymerase chain reaction (RT-PCR) and Southern blot analysis; and (4) i.t. administration of lipopolysaccharide (LPS; 150 micrograms) produced a time-dependent thermal hyperalgesia compared with saline treated-rats (15 microliters). There was no change in mechanical withdrawal thresholds over time following any treatment, except fluorocitrate. We have previously shown that NO plays a significant role in mechanisms of hyperalgesia. In the present experiments we have extended these observations and have now shown a role for iNOS, expressed by glia, in mechanisms of hyperalgesia. These results suggest an unexplored avenue for the development of potential new and novel therapies for pain control.

Amino Acid Oxidoreductases↗