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P Murphy

Publications and source records attributed to P Murphy.

At least 217 records · Page 12Linked to original sources
PubMed1989

Segment-specific expression of a homoeobox-containing gene in the mouse hindbrain.

The process of segmentation, in which the developing embryo is divided into repetitive structures along its antero-posterior (A-P) axis, as a means of organizing and coordinating the body plan is found in a wide range of organisms. In Drosophila, homoeotic genes are involved in all levels of segmental organization and in determining segment identity. The roles of these genes in segmentation have been found mainly by mutational studies, but also by in situ hybridization, which has shown their domains of expression. In contrast to Drosophila, however, embryonic expression of homoeobox-containing genes in vertebrate organisms has not been found to follow a segmental pattern. Vertebrate segmentation can be clearly seen in the mesodermal somites, but repetitive morphological structures in the central nervous system (neuromeres) have only recently been shown to have developmental significance. Neuromeres in the hindbrain (rhombomeres) have been defined as segmental units by their pattern of nerve formation in the developing chick and by the alternating expression of Krox-20, a gene encoding a zinc-finger DNA-binding protein, in the 9.5-day-old mouse. Here we report that a mouse homoeobox-containing gene, Hox-2.9, is expressed in a segment-specific manner in the developing mouse hindbrain. This expression is in a region which is flanked by the regions of expression of Krox-20, and is precisely contained within a single neuromere, rhombomere 4.

Animals↗
PubMed1989

The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion.

About 60% of both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) is due to deletions of the dystrophin gene. For cases with a deletion mutation, the "reading frame" hypothesis predicts that BMD patients produce a semifunctional, internally deleted dystrophin protein, whereas DMD patients produce a severely truncated protein that would be unstable. To test the validity of this theory, we analyzed 258 independent deletions at the DMD/BMD locus. The correlation between phenotype and type of deletion mutation is in agreement with the "reading frame" theory in 92% of cases and is of diagnostic and prognostic significance. The distribution and frequency of deletions spanning the entire locus suggests that many "in-frame" deletions of the dystrophin gene are not detected because the individuals bearing them are either asymptomatic or exhibit non-DMD/non-BMD clinical features.

Adolescent↗
PubMed1989

The role of the nurse on hospital ethics committees.

Sound decisions are characterized by assurance of adequate information, multiple perspectives, sufficiently deliberate thought, emotional support for all decision makers, and legal acceptability. Each of these features can be enhanced by appropriate involvement of the nurse on an ethics committee. As a result, the nurse will be helping to assure patient, family, and professional participants that they have done their best under difficult constraints. Serving as a member of a hospital ethics committee is time consuming and challenging. Yet, it is one of the most important ways nurses can function in the role of patient advocate. The ethics committee can be the answer to the frustration that nurses confront every day when faced with increased technology, legislative inaction, and medical paternalism. Even competent patients are often manipulated when they want to refuse treatment. Patients and families frequently have the illusion of choice but no real choice at all. If an ethics committee can provide some meaningful avenue for the exercise of patients' and families' rights, then they are worth the effort.

Ethics↗
PubMed1988

Tumorigenic and molecular characterization of novel phorbol ester-resistant and -sensitive lines of mice.

Two outbred lines of CD-1 mice were developed using males and females in an initiation (dimethylbenz[a]anthracene; DMBA), promotion (12-O-tetradecanoylphorbol-13-acetate; TPA) challenge, posttumorigenesis breeding protocol. Our results indicate that the phorbol ester-sensitive (PESTI) line developed tumors at a rate 4.1 times faster than the CD-1 parental line, while the phorbol ester-resistant (PERTI) line developed tumors at a rate 36 times slower than the CD-1 parents. The average number of tumors per mouse reached levels of 27.5 at 12 wk in the PESTI line, 0.1 at 16 wk in the PERTI line, and 6.7 at 16 wk in the CD-1 line. Biochemical tests showed that the PESTI line had both a high basal level and an enhanced epidermal ornithine decarboxylase (E.C. 4.1.1.17) response to TPA, the latter being nine times that of the PERTI line at their maximum dosages. An autoradiographic analysis of in vivo epidermal cell protein phosphorylation indicated marked differences in basal protein phosphorylation profiles (with high phosphate incorporation, PERTI, 112.7, 95.5, 64.4, 40.8, 18.6, 17.4, and 12.3 kDa; PESTI, 64.4, 40.8, 31.8, and 12.3 kDa) as well as TPA-dependent changes in these profiles (difference from basal levels, PERTI, 31.8 and 12.8 kDa; PESTI, 139.6, 126.3, 37.2, and 18.6 kDa). These heterogeneous profiles indicate strong genetic segregation of these protein kinase C target substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Preferential growth of blood-borne cancer cells at sites of trauma--a growth promoting role of macrophages.

Carcinoma and sarcoma after gaining access to the venous circulation are completely trapped in the organs of first encounter, i.e. the lung and vertebrae for cancers draining into the vena cava, or liver for tumours with portal drainage. Systemic dissemination of carcinomas and sarcomas derives from cancer growing in the lung and can be mimicked in experimental rats by injecting cancer cells intra-arterially via the left ventricle. These emboli are arrested in different tissues in proportion to the cardiac output they receive, but the probability of a cancer embolus introduced in this way causing a lesion varies by several orders of magnitude for different tissues. Traumatising tissues by procedures such as surgical incision of the abdomen, gut anastomosis, placing a stitch in the kidney or chemical or surgical partial hepatectomy, greatly enhances the likelihood that a cancer cell trapped in the tissues develops into a metastasis. While several factors contribute to making a wound a more favourable "soil" for metastasis a major mechanism is the release of growth factors from macrophages that have infiltrated the wound.

Animals↗
PubMed1988

Mechanisms of organ selective tumour growth by bloodborne cancer cells.

The sites of tumour development for 6 rat tumours injected into syngeneic rats via different vascular routes was determined. Xenografts of human tumours were also injected intra-arterially (i.a.) into immunosuppressed rats. Following intravenous (i.v.) and intraportal (i.ptl.) injection of cells tumour colonies localized in lung and liver respectively due to tumour cell arrest. Arterially injected radiolabelled cells disseminated and arrested in a similar distribution to cardiac output and did not 'home' to any organs. Following arterial injection of unlabelled tumour cells colonies grew in many organs. While the pattern of growth for a particular tumour varied with the cell dose, the 'arterial patterns' for all of the tumours studied followed a similar pattern. Some organs (eg adrenals, ovaries and periodontal ligament) were consistently preferred, others (eg skin and skeletal muscle) only supported tumour growth following the delivery of large numbers of cells, while in some tissues (eg spleen and intestines) tumour never grew. Viable tumour cells could be demonstrated by bioassay in many organs for up to 24h after i.a. injection. However tumour growth only occurred in certain organs and the pattern of this growth was not related to the number of tumour cells arrested or their rate of autolysis. This site preference could be expressed quantitatively as the probability of an arrested cell developing into a tumour and was considered a 'soil effect'. Site preference was not directly related to organ vascularity. Organ colonisation was promoted by steroid treatment but the mechanism was unclear and was not secondary to T-cell immunosuppression or prostaglandin synthesis suppression. The adrenal glands were preferred sites of tumour growth but pharmacological manipulation of adrenal function did not alter tumour growth to this organ. Sites of injury and healing were preferred sites of tumour colonisation and this could not be accounted for by increased delivery of tumour cells to these regions. The possibility that the macrophage component of the inflammatory response promoted tumour growth was suggested from studies in which the interval between trauma and inoculation of tumour cells was varied as well as by promotion of intraperitoneal (i.p.) tumour growth by a macrophage infiltrate.

Animals↗
PubMed1988

Further evidence supporting a cause and effect relationship between blood transfusion and earlier cancer recurrence.

Studies of associations between perioperative blood transfusions and later recurrence of solid tumors have yielded conflicting results. A previous analysis of transfused patients suggested that recurrence was associated with transfusion of whole blood as opposed to red blood cell concentrates. Additional analyses were performed on patients with cancers of the colon, rectum, cervix, and prostate to determine if patients receiving whole blood, red blood cells only, or no transfusions had differing outcomes. Patients receiving 1 unit or more of whole blood had uniformly poor outcomes compared with nontransfused patients (p less than 0.001). In contrast, patients receiving only red blood cells had progressively worse recurrence and death rates with increasing numbers of transfusion, suggesting the presence of a dose-effect relationship. Employing multivariate techniques, blood transfusion of less than or equal to 3 units that included any whole blood were independently and significantly associated with earlier recurrence (p = 0.003) and death due to cancer (p = 0.02). Transfusions of less than or equal to 3 units of blood comprised solely of red blood cell concentrates were associated with no greater risk of recurrence than that seen in patients receiving no transfusion (p = 0.50). These results provide a potential explanation for the disparate results reported in studies of blood transfusion and cancer outcome. The marked difference in outcome seen between patients receiving a few units of red blood cells and comparable patients receiving even one unit of whole blood are consistent with the hypothesis that transfusion of stored blood plasma causes earlier tumor recurrence in some instances. Strategies for reducing these risks might include avoidance of whole blood transfusions when only 1-3 units are required, more conservative transfusion practice, use of autologous blood transfusions, and perhaps, use of red blood cells washed free of plasma and white cell debris. Clinical trials to test these hypotheses are urgently needed.

Colonic Neoplasms↗
PubMed1988

Purification and partial characterization of a plasminogen activator inhibitor from the human glioblastoma, U138.

A plasminogen activator inhibitor was purified to apparent homogeneity from conditioned media of U138 cells. The inhibitor is a glycoprotein with a pI of 5.4 and an apparent molecular weight of 45,000. The inhibitor forms sodium dodecyl sulfate-stable complexes with plasminogen activators and trypsin but not with plasmin, thrombin, or pancreatic kallikrein. Some biochemical and immunochemical characteristics of the U138 inhibitor distinguish it from other known plasminogen activator inhibitors. The expression of this inhibitor by U138 cells could be modulated by incubation in phorbol myristate acetate, interleukin-1, tumor necrosis factor, and gamma interferon, but not in beta interferon. Thus, the expression of the plasminogen activator inhibitor can be influenced by biological response modifiers known to be active in the brain and in the neural response to inflammatory stimuli. Therefore, this inhibitor, along with protease nexin, may be involved in brain development and regulation.

Autoradiography↗
PubMed1987

Behavioural hypertension in sodium-loaded dogs is accompanied by sustained sodium retention.

Instrumented dogs were presented with two daily avoidance conditioning sessions during 12 days of continuous saline infusion (1.3 l/day). Avoidance conditioning of sodium-loaded dogs resulted in progressive 24-h hypertension over the 12-day conditioning periods (systolic, 21 +/- 3 mmHg; diastolic, 15 +/- 1 mmHg) accompanied by a decreased 24-h heart rate (-14.8 +/- 4.0 beats/min). Under these conditions, renal excretion of sodium decreased relative to sodium intake (-88 +/- 19 mmol/12 days) while urine volume was increased relative to water intake (0.18 +/- 0.07 l/day). The sodium retention was accompanied by increased plasma sodium levels (1.8 +/- 0.7 mmol/l) and decreased plasma calcium levels (-1.2 +/- 0.2 mmol/l). Daily creatinine clearance decreased during the development of hypertension (-53 +/- 13% per day). Subsequently, each dog was exposed to 12 days of saline infusion in the absence of avoidance sessions. Under these conditions, arterial pressure and sodium balance remained stable. It was concluded that the rapidly developing and reversible hypertension occurring in sodium-loaded dogs exposed to recurrent behavioural stress is mediated by increased levels of total body sodium.

Animals↗
PubMed1987

Oxidative stress and growth temperature in Bacillus subtilis.

Pretreatment of Bacillus subtilis with low concentrations of hydrogen peroxide protected the cells against the lethal effects of higher levels of oxidative stress. During the period of adaptation, eight proteins were induced, as detected by one-dimensional gel electrophoresis. Four of these proteins were the same size as four of the proteins induced by the temperature upshift. The range of proteins synthesized in response to an elevation in temperature depended both on the starting (lower) temperature and on the temperature to which the cells were shifted. Both catalase and superoxide dismutase were present at high levels in B. subtilis, but neither was induced by oxidative stress or temperature upshift. In fact, catalase activity was reduced after the temperature upshift.

Bacillus subtilis↗
PubMed1987

Relationship among oxidative stress, growth cycle, and sporulation in Bacillus subtilis.

The sensitivity of Bacillus subtilis to hydrogen peroxide (oxidative stress) was found to vary with the position of the culture in the growth cycle. The most dramatic change occurred at the stationary phase, when the cells became totally resistant to 10 mM H2O2, in contrast to the loss of 3 to 4 log units of viability when treated at the early log phase. Two of the eight proteins induced by a protective concentration of H2O2 (50 muM) were also induced (in the absence of oxidative stress) on entry into the late log phase of growth. The response of five isogenic spo0 mutants (spo0B, spo0E, spo0F, spo0H, and spo0J) to oxidative stress was identical to that of the wild-type parental strain. In an isogenic spo0A strain, mid-log-phase cells were 100-fold less sensitive to 10 mM H2O2 than was the wild type. Pretreatment with 50 microM H2O2 induced little further protection, suggesting that the response is constitutive in this strain. By comparison of proteins induced by 50 microM H2O2 in the wild-type, spo0A, spo0H, and spo0J strains, four proteins were identified that may be essential for protection against lethal concentrations of H2O2. The presence of multiple copies of the spo0H gene in a spo0A background converted the stress phenotype of the spo0A mutant to that of the wild type but left the sporulation phenotype unaltered.

Bacillus subtilis↗