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Biomedical subjects

J M Murphy

Publications and source records attributed to J M Murphy.

At least 127 records · Page 7Linked to original sources
PubMed1995

Estrogen-induced guinea pig model for uterine leiomyomas: do the ovaries protect?

A guinea pig model was used to study the hormonal control of uterine leiomyomas. Twenty female guinea pigs were divided into four groups--young, old, ovariectomized (OVX), and non-OVX animals--and were given two estradiol-17 beta (E2) silastic implants each for 3-10 mo; another four older OVX animals served as controls and received empty implants. After 3 mo, 100% (8 of 8) of the OVX animals, but none of the OVX controls, developed tumors, mainly on the uterine serosa and the abdominal wall. Electron microscopy and desmin immunostaining demonstrated that the tumors were leiomyomas. In E2-treated animals, E2 levels in serum, leiomyomas, or leiomyoma-free uterine segments rose significantly while serum progesterone (P4) was negligible. Surprisingly, only 8% (1 of 12) of the non-OVX animals developed a tumor. This apparent "ovarian protection" was transient: after 6-9 mo, 50% of the remaining non-OVX animals developed leiomyomas, but these were smaller and fewer than in OVX animals. On the basis of this model, we propose the hypothesis that some factors from the ovaries suppress leiomyoma growth in response to estrogen but that as the ovaries age this protection is diminished, allowing the clinical development of leiomyomas.

Animals↗
PubMed1995

Screening for psychosocial dysfunction in pediatric inpatients.

Screening pediatric inpatients for psychosocial dysfunction offers physicians an opportunity to identify emotional and behavioral problems that might otherwise go unrecognized. In this study, the Pediatric Symptom Checklist (PSC), a brief, parent-completed questionnaire, which has been validated in a variety of outpatient settings, was used to screen 98 pediatric inpatients. Results indicated that the PSC can be easily administered in a busy inpatient setting and is well-tolerated by both house staff and patients' parents as a routine part of the admissions process. The percentage of children who screened positive with the PSC in this inpatient setting was similar to the percentages generated by using the PSC in outpatient settings. Routine use of the PSC in inpatient settings serves to heighten house staff awareness of psychosocial concerns and facilitate parent-physician discussion of pediatric mental health issues.

Adolescent↗
PubMed1995

Effects of the benzodiazepine inverse agonist RO19-4603 on the maintenance of tolerance to a single dose of ethanol.

The time course of the novel benzodiazepine inverse agonist, RO19--4603 (0.075 or 0.150 mg/kg) in antagonizing the depressant effects of ethanol (EtOH) (0.50, 1.0 and 1.5 g/kg) and the development of tolerance on locomotor behaviors (e.g., ambulatory count, total distance and stereotypy count) were investigated in Sprague-Dawley rats given EtOH injections spaced at 24-hr intervals. A single dose of RO19--4603 prevented the development of tolerance to the 0.50- and 1.0-g/kg EtOH doses 24-hr post-RO19--4603 administration on most locomotor behaviors. On Day 1, the 0.150-mg/kg RO19--4603 dose prevented the reduction of motor behaviors after the 1.0- and 1.5-g/kg EtOH doses, whereas the 0.075-mg/kg RO19--4603 dose prevented the reduction of motor behaviors only after the 1.5-g/kg EtOH dose. The 0.075- and 0.150-mg/kg RO19--4603 doses also prevented the EtOH-induced reduction of motor behaviors after the 1.5-g/kg EtOH dose 24-hr post-RO19--4603 administration. RO19--4603 was without effect on activity when given alone. These data suggest that the motor impairing effects of EtOH and the development of tolerance to them may involve gamma-aminobutyric acidA-benzodiazepine receptor mechanisms that when occupied, even briefly by certain benzodiazepine inverse agonists, produce long-lasting effects on locomotion and tolerance.

Animals↗
PubMed1994

Mechanisms of EGF receptor regulation in breast cancer cells.

Overexpression of the EGF receptor in breast cancer correlates with poor prognosis and failure on endocrine therapy for both ER-/EGFR+ and ER+/EGFR+ tumors, suggesting a role for EGFR in the progression to hormone independence. The identification of specific DNAse I hypersensitive site patterns for the EGFR gene in ER+ vs. ER- cells implicates regions of the EGFR first intron in up-regulation of EGFR, while estrogen regulation studies indicate the involvement of a repressor(s) in the maintenance of low levels of EGFR. Based on these findings, a multi-step model is proposed for the progression of breast cancer from a hormone-dependent, ER+/EGFR-phenotype to an aggressive, hormone-independent, ER-/EGFR+ stage.

Breast Neoplasms↗
PubMed1994

The benzodiazepine inverse agonist RO19-4603 exerts prolonged and selective suppression of ethanol intake in alcohol-preferring (P) rats.

The time course of the benzodiazepine (BDZ) inverse agonist RO19-4603 in antagonizing ethanol (EtOH) intake was investigated in alcohol-preferring (P) rats (n = 7) maintained on 24-h continuous free-choice access to EtOH (10% v/v), water, and food. After fluid intakes had stabilized over several weeks, animals were injected with Tween-80 vehicle solution or RO19-4603 (0.075, 0.150, and 0.30 mg/kg). EtOH and water intakes were determined at 8- and 24-h intervals. RO19-4603 caused a marked attenuation of EtOH drinking with each of the doses tested. EtOH intake during the 8-h following 0.075, 0.150, and 0.30 mg/kg RO19-4603 was decreased by approximately 36, 74, and 57%, respectively. Intakes during the 24-h interval were similar to the vehicle control condition. However, 32 h post-drug administration, EtOH intakes were reduced to approximately 27, 31, and 29% following the 0.075, 0.150 and 0.30 mg/kg doses, respectively. To further confirm the reliability of the RO19-4603 dose-response effect, and its selectivity for EtOH, the highest dose condition (0.30 mg/kg) was tested twice. The second 0.30 mg/kg dose condition exerted a profile of effects similar to the initial treatment; 8 h following administration, intake was decreased to 60% of the control level, and 32 h post-drug administration intake was decreased to approximately 46% of the controls. These decreases were evidently selective in comparison with water, since water drinking showed compensatory increases which paralleled the decreased EtOH consumption. Dose-response comparisons indicated that 0.150 mg/kg approaches the maximum effective dose, since the 0.30 mg/kg dose of RO19-4603 did not produce an additional decrease in EtOH intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Deterrents↗
PubMed1994

Consumption of sweet, salty, sour, and bitter solutions by selectively bred alcohol-preferring and alcohol-nonpreferring lines of rats.

To determine whether selective breeding for high or low oral ethanol consumption is associated with different preferences for nonpharmacological solutions with various flavors, the oral intake of a range of concentrations of sucrose (0.5-64.0 g/100 ml), NaCl (0.025-3.2 g/100 ml), citric acid (0.008-2.048 g/liter), and sucrose octaacetate (0.002-0.512 g/liter) was studied in alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. Separate groups of 7-8 rats from each line were tested for consumption of each of the four flavors. The flavored solutions were presented continuously with water and food always available, and the concentrations were doubled every 48 hr. Although rats from both lines showed a strong preference for the sucrose solutions, P rats consumed greater amounts than NP rats [F(7,98) = 5.57, p < 0.001]. Rats of the P line drank less of the NaCl solutions than NP rats [F(7,98) = 3.88, p < 0.001], but the effect was not as robust as the line differences seen with sucrose. The P and NP rats did not differ in citric acid or sucrose octaacetate intake at any of the concentrations tested. Selective breeding for high oral ethanol preference appears to be positively associated with consumption of sweet solutions and negatively associated with intake of salty solutions.

Alcohol Drinking↗
PubMed1994

Anthropology and psychiatric epidemiology.

Psychiatric epidemiologic research has been criticized by anthropologists for ignoring cultural variation in the definitions of psychiatric disorders. While recognizing the importance of this issue, it is suggested here that a considerable amount of ethnographic evidence indicates that many types of comparative effort can be carried out without cultural injustice. It is also urged that anthropologists provide a system for classifying cultures so as to foster an understanding of the ways in which shared beliefs and meanings can influence psychiatric illness. Categorizing populations as Western versus Non-Western or Developed versus Developing is inadequate as a basis for studying the cultural context of psychiatric illness in different parts of the world.

Anthropology, Cultural↗
PubMed1994

Mind and mood in modern art, II: Depressive disorders, spirituality, and early deaths in the abstract expressionist artists of the New York School.

This article documents the high prevalence of mood disorders in a group of 15 of the mid-twentieth-century Abstract Expressionist artists of the New York School. These artists, using the technique of psychic automatism (based on free association) in order to reveal unconscious material, created a psychologically and spiritually significant art that addressed the mythic themes of creation, birth, life, and death. Over 50% of the 15 artists in this group had some form of psychopathology, predominantly mood disorders and preoccupation with death, often compounded by alcohol abuse. At least 40% sought treatment and 20% were hospitalized for psychiatric problems. Two committed suicide; two died in single-vehicle accidents while driving; and two others had fathers who killed themselves. Many of these artists died early deaths, and close to 50% of the group (seven of 15) were dead before the age of 60. The material presented in this article suggests the following formulation and hypothesis. Depression inevitably leads to a turning inward and to the painful reexamination of the purpose of living and the possibility of dying. Thus, by bringing the artist into direct and lonely confrontation with the ultimate existential question, whether to live or to die, depression may have put these artists in touch with the inexplicable mystery that lies at the heart of the "tragic and timeless" art that the Abstract Expressionists aspired to produce.

Adult↗
PubMed1994

Genetic and neurobiological basis of alcohol-seeking behavior.

Through selective breeding, rat lines exhibiting high and low alcohol drinking preference have been developed as useful animal models for studying the neurobiological basis of alcohol-seeking behavior. The identified differences between lines in neurotransmitter functioning allows the evaluation of receptor agonist/antagonist compounds that might be efficacious in the treatment of alcohol craving and dependence.

Alcoholism↗
PubMed1993

Molecular characterization of maize extensin expression.

This study concerned the developmental regulation of wall-localized, hydroxyproline-containing proteins in maize tissues and organs. Silk and pericarp cell walls contained more peptidyl hydroxyproline than did walls of any vegetative tissue, although all tissues and organs accumulated these proteins as they matured. In many tissues, hydroxyproline-rich proteins are first associated with the wall in a soluble form before being insolubilized through covalent attachment to the matrix. Because hydroxyproline was more soluble earlier than later in development, it appears that insolubilization was occurring in maize tissues and organs as well. Tissue prints reacted with an anti-extensin antibody gave positive results, indicating the presence of a soluble form of this common hydroxyproline-rich glycoprotein (HRGP). Silk and pericarp cells actively synthesized this extensin from abundant transcripts. In vegetative tissues, extensin transcripts were somewhat more abundant in seedlings than in pre-anthesis or mature plants, but levels were much lower than in silk and pericarp. Southern blots of maize genomic DNA indicated that these extensin transcripts are encoded by a small multigene family. Potential roles for extensin in reproductive/protective tissues versus the embryo or vegetative tissues are suggested.

Cell Wall↗
PubMed1993

Molecular basis for extensin size heterogeneity in two maize varieties.

This study concerned the molecular basis for the protein size heterogeneity of extensin from two maize (Zea mays L.) varieties. We studied the physical properties of extensin, a hydroxyproline-rich glycoprotein (HRGP), from the silk and pericarp of Golden X Bantam (GXB) sweet corn and Japanese Hulless (JHL) popcorn. Extensin from GXB has a molecular mass of 66 kDa whereas extensins from JHL have molecular masses of 76 and 66 kDa. Treatment with anhydrous hydrogen fluoride to deglycosylate proteins reduced the size of all extensins by 5 kDa. Probing with a 500 bp fragment from a genomic clone of maize extensin identified two transcripts (1.9 and 1.5 kb) on northern blots. JHL contained both transcripts and GXB contained only the 1.5 kb transcript. The probe also hybridized to two larger transcripts (6.2 and 4.5 kb) that were found in both varieties. We immunoprecipitated two proteins (66 and 56 kDa) from translated RNA isolated from JHL and one protein (56 kDa) from GXB. These results demonstrate that these extensins differ in the size of their peptide moiety and not in their extent of glycosylation.

Amino Acid Sequence↗
PubMed1993

ADH resistance of LLC-pk1 cells caused by overexpression of cAMP-phosphodiesterase type-IV.

The studies of animal models of nephrogenic diabetes insipidus (NDI) suggest that abnormally high activity of cAMP phosphodiesterase (cAMP-PDE), may cause unresponsiveness to the diuretic effect of AVP. We explored whether overexpression of one of the cAMP-PDE type isozymes, PDE-IV, in [8-Arg]-vasopressin (AVP) sensitive renal epithelial LLC-PK1 cells can prevent the hormone-elicited cAMP increase. LLC-PK1 cells were stably transfected with ratPDE3.1 cDNA (which encodes for rolipram-sensitive PDE-IV), inserted in plasmid pCMV5 and then were compared with sham-transfected LLC-PK1 cells and wild LLC-PK1 cells. In the stably transfected clone (LLC-PK1-S #16), the rolipram-sensitive PDE-IV activity was about five times higher than in controls, whereas activities of other types of PDEs were not different. The presence of cognate mRNA for PDE-IV was confirmed by Northern blot. Whereas in the control cells (wild LLC-PK1 cells and sham-transfected LLC-PK1 cells), the incubation with 10(-7) M AVP increased cAMP more than tenfold, the LLC-PK1-S#16 cells with overexpressed cAMP-PDE were resistant to cAMP-increasing effects of AVP and forskolin. However, in the same LLC-PK1-S#16 cells the cGMP increases in response to nitroprusside were not diminished. The AVP-dependent cAMP accumulation in LLC-PK1-S#16 cells with overexpressed PDE-IV was restored by addition of roliprams which decreased cAMP-PDE activity to the levels similar to those in wild LLC-PK1 cells and sham-transfected LLC-PK1-#A1 cells. In contrast, inhibitors of other PDE isozymes (PDE-I or PDE-III) had little or no effect. Our findings show that excessive activity of cAMP-PDE, in this case of isozyme PDE-IV, can cause resistance to AVP which is analogous to that observed in collecting ducts of mice with hereditary nephrogenic diabetes insipidus.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

An experimental approach to understanding the genetic and neurobiological basis of alcoholism.

The development and characterization of an animal model to study mechanisms underlying abnormal alcohol-seeking behavior have been described. Raised by genetic means, it demonstrates the importance of genetic factors in this behavior. It has allowed the elucidation of neural pathways and neurotransmitter systems that subserve alcohol-seeking behavior. It offers the potential for screening new medications for the treatment of alcoholism, based upon these kinds of newly discovered knowledge.

Alcohol Drinking↗
PubMed1993

CNS mechanisms of alcohol self-administration.

Neurochemical and neuropharmacological studies were undertaken to examine the possible involvement of the ventral tegmental area (VTA) dopamine (DA) system and the dorsal raphe nucleus (DRN) serotonin (5-HT) system in regulating oral alcohol self-administration. In vivo microdialysis studies demonstrated that either i.p. ethanol administration (1.0-2.0 g/kg) or local perfusion with ethanol (100 mM) could enhance the extracellular concentrations of both DA and 5-HT in the nucleus accumbens (ACB). Furthermore, the effects of local perfusion with ethanol on DA release in the ACB could be blocked by co-perfusion with a 5-HT3 antagonist. In the selectively-bred alcohol preferring P line of rats, there appears to be abnormal 5-HT and/or DA systems in certain limbic structures, i.e., ACB, olfactory tubercles (OTU) and medial prefrontal cortex (MPF). This is indicated by (a) lower contents of DA and 5-HT; (b) fewer 5-HT immunostained fibers; (c) lower densities of 5-HT1B, 5-HT2 and D2 receptors; and (d) higher densities of 5-HT1A receptors in the CNS of P rats compared to the alcohol-nonpreferring NP line of rats. Neuropharmacological studies demonstrated that local microinfusion of the D2 antagonist, sulpiride, or, at low doses, the DA releaser, d-amphetamine, could increase alcohol drinking by P rats. Intracranial self-administration (ICSA) studies showed that the P line of rats, but not the NP line, will self-administer 50-150 mg% ethanol directly into the VTA. Overall, these results suggest an innate abnormal functioning of the VTA DA and DRN 5-HT systems may be key factors facilitating the rewarding actions of ethanol in the CNS of P rats.

Alcohol Drinking↗
PubMed1993

Identification and growth characteristics of pink pigmented oxidative bacteria, Methylobacterium mesophilicum and biovars isolated from chlorinated and raw water supplies.

Pink pigmented bacteria were isolated from a blood bank water purification unit, a municipal town water supply (tap water), and an island (untreated) ground water source. A total of thirteen strains including two reference strains of pink pigmented bacteria were compared in a numerical phenotypic study using 119 binary characters. Three clusters were derived, one major cluster of eleven strains was subdivided into two sub-clusters on the basis of methanol utilization. Five strains were facultative methylotrophs and were classified as Methylobacterium mesophilicum biovar 1. The other six strains did not utilize methanol, but on the basis of high phenotypic similarity of 83.6% were classified as M. mesophilicum biovar 2. The single reference strain comprising cluster 2 Pseudomonas extorquens NCIB 9399 was assigned to the genus Methylobacterium and classified as M. extorquens. Cluster 3 was the single reference strain Rhizobium CB 376.

Fresh Water↗
PubMed1992

Relations over time between psychiatric and somatic disorders: the Stirling County Study.

A longitudinal study of a general population in Atlantic Canada provided information on associations between two broad categories of illness: somatic disorders and disorders involving depression and/or anxiety. Prevalence was investigated in a sample of 1,003 adults selected in 1952 and another sample of 1,094 adults selected in 1970. Using a cohort of 618 survivors from the 1952 sample who were followed up in 1968, the authors studied prevalence at the beginning and end of the 16-year period. Incidence was also investigated so that the strength of associations between prior illness of one type and subsequent illness of the other type could be assessed. Data were obtained by interviewing subjects with the same structured schedule at each time of investigation. In prevalence enumerations, psychiatric disorders were found to be significantly associated with somatic disorders. Prior somatic disorder was significantly associated with subsequent incidence of depression and/or anxiety and vice versa. The results did not, however, show one direction of influence ("psyche-to-soma" or "soma-to-psyche") to be markedly stronger than the other. The results mainly support the concept of "generalized vulnerability" and draw attention to the importance of recognizing comorbidity in diagnosis and clinical practice.

Adult↗