Search PubMed⌕ Search

Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 433 records · Page 24Linked to original sources

Factors associated with participation, attrition, and outcome in a smoking cessation program at the workplace.

Despite their growing popularity, worksite health-promotion programs have generally been characterized as having low participation rates, high attrition rates, and modest outcomes. This investigation identified the predictors of participation, attrition, and outcome of worksite smoking-cessation program. Subjects were regular cigarette smokers recruited from two worksites. Of 66 eligible smokers in the two worksites, 44 (67%) agreed to participate in the program. Fifty-five percent (24 of 44) of these completed the program. Of those completing the program, 29% had quit smoking by posttest and 17% were abstinent at the 6-month follow-up. Results indicated that a different set of variables predicted participation, attrition, and outcome. The significant predictors of smokers who participated were the length of cessation in previous abstinence attempts, the number of years they smoked, and the belief regarding personal vulnerability in contracting a smoking-related disease. Levels of pretest carbon monoxide along with attitudes regarding the adoption of smoking restrictions in the worksite predicted attrition. Posttest cessation was related to nicotine levels of cigarette brand smoked at pretest and pretest beliefs regarding postcessation weight gain. Abstinence at the 6-month follow-up was predicted by the number of co-workers who smoked and pretest concerns related to postcessation weight gain. The results are discussed in terms of future evaluation and intervention efforts.

Adult↗

Renal effects of dopamine in vascular surgical patients.

Low-dose dopamine (DA) is often used in surgical patients to induce diuresis when appropriate volume replacement is unsuccessful. Despite wide application, there are little objective data supporting any beneficial effects on renal hemodynamics in this patient population. To better define the response to dopamine in the clinical setting, we studied the renal effects of low-dose DA in 13 patients having vascular surgery. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by inulin and p-aminohippurate clearance, respectively. Group I (n = 8) included patients in stable condition after operation who were administered intravenous DA, 0.5 micrograms/kg/min, for 2 hours. RBF significantly increased from 579 +/- 85 to 726 +/- 114 ml/min/1.73 m2 (p less than 0.05). Increases were also observed in GFR (95.0 +/- 10.9 to 107 +/- 15.7 ml/min/1.73 m2), sodium excretion (164 +/- 35 to 239 +/- 53 mu Eq/min), and osmolar excretion (709 +/- 78 to 866 +/- 93 mu Osm/min). There were no changes in urine output (2.17 +/- 0.36 to 2.49 +/- 0.43 ml/min). Group II (n = 5) consisted of patients having abdominal aortic surgery who were treated with DA, 2.0 micrograms/kg/min, before and after surgery. Increases in RBF were seen in both the preoperative period (414 +/- 59 to 659 +/- 96 ml/min/1.73 m2, p less than 0.01) and postoperative period (439 +/- 60 to 623 +/- 94 ml/min/1.73 m2, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Diuresis↗

Seasonality in the sudden infant death syndrome.

Distinctive epidemiological features of the sudden infant death syndrome (SIDS) are its age at death distribution and pronounced winter excess. Whether or not these effects are independent of the month of birth of the infant is uncertain. We used a loglinear model to separate the effects of age at death, month of death and month of birth amongst 6229 infants who died from SIDS in England and Wales during the period 1979-1983. The results suggest that month of birth and month of death independently influence the risk of the infant dying from SIDS, the risk related to month of death being much greater.

Age Factors↗

Identification of the gene encoding the 65-kilodalton DNA-binding protein of herpes simplex virus type 1.

Hybrid arrest of in vitro translation was used to localize the region of the herpes simplex virus type 1 genome encoding the 65-kilodalton DNA-binding protein (65KDBP) to between genome coordinates 0.592 and 0.649. Knowledge of the DNA sequence of this region allowed us to identify three open reading frames as likely candidates for the gene encoding 65KDBP. Two independent approaches were used to determine which of these three open reading frames encoded the protein. For the first approach a monoclonal antibody, MAb 6898, which reacted specifically with 65KDBP, was isolated. This antibody was used, with the techniques of hybrid arrest of in vitro translation and in vitro translation of selected mRNA, to identify the gene encoding 65KDBP. The second approach involved preparation of antisera directed against oligopeptides corresponding to regions of the predicted amino acid sequence of this gene. These antisera reacted specifically with 65KDBP, thus confirming the gene assignment.

DNA-Binding Proteins↗

Purification of the herpes simplex virus type 1 65-kilodalton DNA-binding protein: properties of the protein and evidence of its association with the virus-encoded DNA polymerase.

Using a combination of conventional column chromatography and velocity sedimentation, we have purified the 65-kilodalton DNA-binding protein (65KDBP) encoded by herpes simplex virus (HSV) greater than 625-fold. The HSV type 1 (HSV-1)-encoded DNA polymerase (pol) cofractionated with 65KDBP through DEAE-Sephacel, Blue Sepharose, and Mono Q columns and was only separated from 65KDBP by sedimentation through a glycerol gradient. Immunoaffinity columns containing monoclonal antibody (MAb) 6898 immunoglobulin effectively bound most of the HSV-1 pol activity which coeluted with 65KDBP. The pattern of reactivities of HSV-1/HSV-2 recombinants with MAbs specific for HSV-1 65KDBP or the HSV-2-infected cell-specific protein ICSP34,35 strongly suggests that these two species are serotype equivalents of the same protein. Taken together, all these data indicate that 65KDBP is a pol-associated protein and the HSV-1 counterpart of HSV-2 ICSP34,35 previously reported to have similar properties (P. J. Vaughan, D. J. M. Purifoy, and K. L. Powell, J. Virol. 53:501-508, 1985). Purified preparations of 65KDBP were capable of binding to double-stranded DNA, as determined by filter retention and mobility shift assays. The protein-DNA complex formed with 65KDBP was distinct from that produced by pol and could be further shifted by the addition of immunoglobulin specific for 65KDBP. These results demonstrate that 65KDBP has been purified substantially free from pol and indicate that DNA binding is an inherent property of the protein.

Chromosome Mapping↗

Maternal drug histories and congenital malformations: limb reduction defects and oral clefts.

In a case control study, prescription data were examined for the three months before the last menstrual period and for the first trimester of pregnancy in (a) 115 mothers of children with limb reduction defects, (b) 676 mothers of children with oral cleft, and (c) an equal number of control mothers of normal babies from the same doctor's practice for each case. In the limb reduction study, the study mothers were prescribed more drugs generally although this did not reach statistical significance, nor were there significant differences between study and control mothers for individual groups of drugs. In the oral cleft study, significantly more drugs were prescribed to study mothers in the three months before the last menstrual period, and a similar trend, which did not reach statistical significance, was observed in the first trimester. Anticonvulsant drugs were prescribed significantly more frequently to study mothers during the whole period of the study. A significant association was also demonstrated between oral contraceptives taken in the three months before the last menstrual period and oral cleft, but doubt must remain concerning this relationship; the risk is not well understood and is likely to be nonspecific. A number of other significant associations were identified, although their importance in practice is uncertain in view of the confounding factors that may affect a study of this kind.

Abnormalities, Drug-Induced↗

A study of sulphatoxymelatonin excretion and gonadotrophin status during weight gain in anorexia nervosa.

To clarify a controversy as to whether melatonin secretion is related to body weight, urinary sulphatoxymelatonin (aMT6s) excretion was estimated in 10 patients with anorexia nervosa before and after weight gain, and compared with 10 age-matched controls. There was no change in aMT6s excretion after weight gain, and no significant difference between the patients and control groups at either point. Significant increases in plasma LH, FSH, and estradiol were detected after weight gain in anorexic patients, independent of aMT6s excretion.

Adult↗

Effects of recombinant tumor necrosis factor, lymphotoxin, and immune interferon on proliferation and differentiation of enriched hematopoietic precursor cells.

We compared the effects of recombinant (r) tumor necrosis factor (TNF) and lymphotoxin (rLT) on in vitro colony formation by erythroid, multipotential and granulocyte, monocyte (CFU-GM) precursor cells. Recombinant granulocyte, macrophage-colony stimulating factor and bone marrow preparations enriched for hematopoietic precursors were used in order to examine the direct effects of the cytokines on precursors in the absence of other soluble factors or mature cells that may influence colony formation. Both rTNF and rLT inhibited colony formation by erythroid and multipotential precursor cells. rTNF and rLT did not inhibit the more mature (day-7) CFU-GM, although a synergistic inhibition was observed when the cytokines were added to cultures together with recombinant interferon gamma (rIFN gamma). However, rTNF did inhibit day-7 CFU-GM when conditioned medium from the human bladder carcinoma cell line 5637 was used as a source of colony-stimulating activity. rTNF inhibited the more immature (day-14) CFU-GM regardless of the source of colony-stimulating activity used, and was a stronger inhibitor of day-14 CFU-GM than rLT, suggesting a difference in the biological effects of the two cytokines. Noninhibitory concentrations of rTNF or rIFN increased the number of monocyte colonies formed, identified by cytochemical staining. These data suggest a mechanism for TNF and IFN gamma-induced inhibition of CFU-GM through induction of monocyte differentiation rather than through a direct toxic effect.

Bone Marrow Cells↗

Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes.

We present evidence that human peripheral blood lymphocytes, free of contaminating monocytes, rapidly produce high levels of tumor necrosis factor (TNF) when stimulated with phorbol diester and calcium ionophore, and lower but significant levels of TNF when stimulated with mitogens. These two types of inducers act preferentially on T cells, both CD4+ and CD8+. NK cells produce TNF only when stimulated with phorbol diester and calcium ionophore, and they do so at a much lower level than T cells. The procedures used in the purification of lymphocytes and the differential ability to respond to various inducers allow us to exclude that monocytes or basophils contaminating the lymphocyte preparation participate in the production of TNF. In particular, LPS, a potent inducer of TNF production from monocytes, is unable to induce significant levels of TNF in the lymphocyte preparations. The TNF produced by lymphocytes has antigenic, physicochemical, and biochemical characteristics identical to those of the TNF produced by myeloid cell lines or monocytes upon stimulation with LPS. LT is also produced by lymphocyte preparations. Production of TNF and LT proteins in response to the different inducers is paralleled by accumulation of cytoplasmic TNF and LT mRNA. Both at mRNA and at protein levels, stimulation of T lymphocytes with phorbol diester and calcium ionophore preferentially induces TNF, whereas mitogen stimulation preferentially induces LT. Our data suggest that the TNF and LT genes, two closely linked genes encoding two partially homologous proteins with almost identical biological functions, are independently regulated in lymphocytes.

Calcimycin↗

The effects of cortical ablation on multiple unit activity in the striatum following dexamphetamine.

Bilateral removal of the fronto-parietal cortex of the rat resulted in decreased spontaneous multiple-unit activity recorded in the striatum of freely-moving rats. Cortical ablations changed the neuronal response in the striatum to systemic administration of dexamphetamine (2.5 mg/kg i.p.) from excitation in control animals (88%) to inhibition in ablated animals (61%). Furthermore, catalepsy, induced by haloperidol, but not by morphine, was markedly attenuated after cortical ablation. These changes were accompanied by a 23% decrease in the specific binding of [3H]spiperone in the striatum. The binding of [3H]met-enkephalin was unaffected by the cortical lesions. Levels of glutamate in the striatum decreased from 8.88 +/- 0.5 mumols/g in control animals to 6.93 +/- 0.37 mumols/g after bilateral cortical ablation. On the other hand, cortical ablations did not alter the content of either the gamma-aminobutyric acid or glutamine of the striatum. It is concluded that the excitatory response, observed in striatal neurons in freely-moving animals, is dependent upon an intact cerebral cortex and requires intact cortico-striatal afferents. The results further suggest that neurons in the striatum are under the tonic influence of glutamate, released from cortico-striatal afferents. Lastly, some dopamine D2 binding sites in the striatum are located on cortico-striatal afferent terminals and blockade of these striatal D2 sites may be involved in the induction of catalepsy by neuroleptic drugs.

Animals↗

Definition of a region required for transformation in E1a of adenovirus 12.

In order to define functionally important regions of the E1 a gene of adenovirus 12 (Ad12), a number of Ad12 mutants were studied. These mutants share an identical 69-bp deletion in the first exon of E1a as well as duplications of a long terminal repeat sequence at the end of the Ad12 genome. The mutants are fully competent for replication and growth in their normal hosts and have a host range extended to include the Vero cell line of African green monkey origin. The partially deleted E1a can stimulate the expression of all early adenoviral genes as well as the cellular heat shock gene, the transcription of which is stimulated by Ad5 E1a. However, plasmids containing the deleted E1a plus wild type E1b were unable to effect a transformation of either primary rat embryo fibroblasts or on an established cell line following transfection. Further, the mutant viruses were defective in generating tumors in newborn hamsters. We conclude that the deleted sequence of E1a described here is critical for transformation by E1a but is not necessary for multiplication of the virus or the transcriptional activating function of the gene.

Adenovirus Early Proteins↗

A set of monozygotic twins with Rett syndrome.

The case history of a set of twins with Rett syndrome is presented. The twins test as monozygotic by both blood groups and HLA titers. In a previous generation, the family had three females who died of an unknown degenerative disease on the paternal side of this family. The discussion includes a hypothesis about female genetic disease occurring in a recessive pattern on the X chromosome.

Brain Diseases↗

Rett syndrome: new observations.

Two elderly females with Rett syndrome are reported with evidence of a slowly progressive central and distal peripheral nervous system involvement. Thermography in 4 girls confirmed distal hypothermia of the extremities in a glove and stocking distribution. Unilateral sympathectomy during surgery for scoliosis in one of them resulted in increased warmth and physical growth of the foot and nails, compared to the uninjured side. This suggests increased sympathetic tone as the probable cause of distal hypothermia, vasomotor instability and dystrophy of the feet in this disorder. In an attempt to identify a marker, girls with clinically classical Rett syndrome had plasma and urinary cell evaluation for an unusual glycolipid. A blind study using a small number of patients failed to prove absolute specificity and additional studies are required to evaluate its validity as a marker for Rett syndrome.

Adult↗

Day to day care of Rett syndrome children.

Girls with Rett syndrome are profoundly handicapped and are incapable of an independent life. The basic living skills of feeding, toileting, dressing, mobilising and communication are examined and advice as to how these girls can best be helped in these areas is suggested. The changing impact of the diagnosis on parents, as the condition becomes more widely know, is mentioned, and the physicians' attention is directed to the parental and family stresses caused through the presence of a profoundly handicapped child in a family so that he or she may be careful in not adding to this stress by making further unrealistic demands, but rather be encouraged to act in a supportive and encouraging manner cognisant of the sometimes limited resources which are available to individual families.

Activities of Daily Living↗

Percutaneous transluminal angioplasty of stenotic coronary artery bypass grafts: 5 years' experience.

In a 60 month period (January 1981 to December 1985), 82 patients (79% male with a mean age of 60 years) had 83 saphenous vein grafts and 5 internal mammary artery grafts with a total of 101 stenotic sites treated with percutaneous transluminal coronary angioplasty. The mean time between bypass surgery and angioplasty was 51.2 months. The procedure was technically successful in 85% of patients, 86% of grafts and 85% of the sites attempted. In these cases, the mean diameter stenosis was reduced from 77 +/- 14 to 27 +/- 20% (p less than 0.001), the mean pressure gradient from 49 +/- 16 to 7 +/- 6 mm Hg (p less than 0.001). Emergency coronary artery bypass graft surgery was necessary in one patient (1.2%) whereas myocardial infarction occurred in three patients (3.6%). There were no hospital deaths. Clinical follow-up was obtained in all 82 patients. Before angioplasty, 23% were in Canadian Cardiovascular Society functional class II, 60% in class III and 17% in class IV. With a mean clinical follow-up period of 21.4 +/- 2.3 months, 71% are in class I, 17% in class II and 12% in class III. There were two deaths, 3 months or more after angioplasty, one probably due to graft closure. So far, angiographic follow-up (at 7.9 +/- 2.1 months) has been available in 26 patients. Ten patients (with 10 grafts) exhibited graft restenosis; six of them have had second successful repeat angioplasty. Among the many variables analyzed, statistically significant predictors of success were a higher measured balloon/graft ratio (p less than 0.001), smaller diameter graft (p less than 0.001), and shorter lesion length (p less than 0.01). The only predictor of complication was diffuseness of disease in the graft (p less than 0.05). The statistically significant predictors of recurrence were the residual stenosis after the initial angioplasty (p less than 0.01) and the measured balloon/graft ratio (p less than 0.01). Angioplasty of coronary artery grafts appears to be a feasible and efficacious procedure with a low complication rate. The technique is a satisfactory alternative to repeat surgery in selected patients.

Adult↗

Regulation of hematopoiesis by T lymphocytes and natural killer cells.

T lymphocytes and natural killer (NK) cells exert both stimulatory and suppressive effects that regulate growth and differentiation of hematopoietic cells. Activated T and NK cells have been demonstrated in different pathological states of bone marrow failure and are proposed to play a role in the pathogenesis of the disease. T and NK cells have also been shown to be responsible for bone marrow graft rejection in both allogeneic and syngeneic donor/recipient combinations. Lymphocytes can regulate hematopoietic cell growth by direct cellular contact or by releasing soluble factors, such as colony-stimulating factors, immune interferon, lymphotoxin, and tumor necrosis factor, active on hematopoietic precursor cells.

Anemia↗

Squamous and adenocarcinoma of the uterine cervix: a comparison using routine data.

We studied the clinical, demographic and survival characteristics of more than 5,000 women registered with either squamous or adenocarcinoma of the uterine cervix in South Thames Cancer Registry over the period 1968-81. There were similarities with respect to social class, smoking habit, oestrogen/oral contraceptive use and time trends in incidence but differences between the two cancers were found with respect to age distribution, parity, method of detection and survival. Some of the data are of limited value, having been obtained only from case notes, so the results need some caution in their interpretation. However the results are broadly consistent with those of studies performed in other countries on smaller samples. A methodological issue is also raised, viz. the appropriateness of a disease with well-known characteristics as a comparison group. From our results the likely size of various associations can be judged and used in the design of future studies to clarify the epidemiology of cervical adenocarcinoma.

Adenocarcinoma↗