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Biomedical subjects

J M Murphy

Publications and source records attributed to J M Murphy.

At least 19 recordsLinked to original sources
PubMed1996

Benzodiazepine receptor ligands with different intrinsic efficacies alter ethanol intake in alcohol-nonpreferring (NP) rats.

Benzodiazepine (BDZ) receptor ligands with varying intrinsic efficacies [RO19-4603, 0.02-0.15 mg/kg; FG 7142 1-16 mg/kg; DMCM, 1-8 mg/kg; RO16-6028 (bretazenil), 8-32 mg/kg] in modulating GABAergic activity were examined for the ability to alter palatability-induced ethanol (EtOH) intake in the alcohol-nonpreferring (NP) line of rats. NP rats on a 22-hour fluid-deprivation schedule were given 2-hour daily access to a 10% (v/v) EtOH/3% (g/v) polycose solution and water. Average EtOH intake was 2.1 +/- 0.2 g/kg/2 hours, and water intake was 17.1 +/- 0.9 ml/2 hours. During the initial 15 minutes of the 2-hour session, RO19-4603, the imidazothienodiazepine partial inverse agonist reduced EtOH intake to 19% of control values at 0.04 mg/kg and completely suppressed drinking of the EtOH solution at 0.15 mg/kg. Twenty-four-hour postdrug administration, the 0.08-mg/kg dose of RO19-4603 completely suppressed drinking of the EtOH solution at the 60-minute interval, and the 0.15-mg/kg dose reduced intake to 20% of control levels at the 15-minute interval. FG 7142, the partial beta-carboline inverse agonist reduced EtOH drinking at the 60-minute interval with the 1-mg/kg dose, and the 16-mg/kg dose reduced water intake at the 15-minute interval. DMCM, the full beta-carboline inverse agonist, significantly reduced water intake at 15 minutes (4 and 8 mg/kg), and the same doses caused a substantial increase in EtOH drinking at the 120-minute interval. The anxiolytic agent bretazenil (16 and 32 mg/kg) increased EtOH consumption during the initial 15 minutes to 270% to 425% of control levels, and water intake increased by the end of the 2-hour session to as much as 210% of control following administration of the 32-mg/kg dose. These findings support existing evidence suggesting that BDZ receptor ligands may modify neuronal processes that mediate some reinforcing and/or aversive properties of alcohol. They further demonstrate a potential importance of the GABAA-BDZ receptor complex in mediating palatability- (environmentally) induced EtOH drinking even in rats selectively bred for low alcohol preference.

Analysis of Variance↗
PubMed1996

Proline is synthesized from glutamate during intragastric infusion but not during intravenous infusion in neonatal piglets.

Glutamate is considered the primary precursor amino acid for proline synthesis in mammals. Evidence exists, however, suggesting that proline may be a dietary indispensable amino acid for 2.5-kg piglets due to inadequate synthesis. This hypothesis was tested by intravenous and intragastric infusion of radiolabeled amino acids in vivo. Piglets (3 to 4 d old) were surgically implanted with catheters in the femoral (infusion) and jugular (sampling) veins and in the stomach (feeding and infusion). Piglets were fed hourly, via the stomach catheter, a semi-purified diet containing 10% dried skim milk, 15% corn oil, amino acids, vitamins and minerals. Experiment 1 was a 2 X 2 factorial design, with 24 piglets adapted to either low or supplemental proline diets (1.3 and 16.4 g proline x kg(-1) respectively) for 7 d, then intravenously infused with either [U-14C]glutamate or [U-14C]proline (185 k Bq x kg(-1) prime; 370 kBq x kg(-1) x h(-1) constant) for 4 h. Experiment 2 followed similar protocols, with eight piglets adapted to the low proline diet for 7 d and [U-14C]glutamate or [U-14C]proline infused into the stomach catheter. Piglets infused intravenously with [U-14C]glutamate did not convert glutamate to proline. Radioactive label was recovered in proline in all of the piglets receiving intragastric infusion of [U-14C]-glutamate. The fractional synthesis rate of proline from intragastric glutamate was 125 microgram ol kg(-1) x h(-1), accounting for approximately 40% of the proline accumulated. These data provide conclusive evidence that intravenously infused glutamate is not used as a precursor for proline synthesis and that, although conversion of glutamate to proline occurs in the gastrointestinal tract, the rate is not sufficient to provide the proline accumulated.

Animals↗
PubMed1996

Three extracellular proteases from Cochliobolus carbonum: cloning and targeted disruption of ALP1.

Three extracellular serine proteases (Alp1a, Alp1b, Alp2) from Cochliobolus carbonum were purified and characterized. Of eight carbon/protein substrates tested, total protease activity was highest when the fungus was grown on medium containing collagen. Alp1a and Alp1b are members of the trypsin family (EC 3.4.21.4), and Alp2 is a member of the subtilisin family (EC 3.4.21.62). Alp1a, Alp1b, and Alp2 have monomer molecular masses of 25, 30, and 38 kDa respectively. Alp1b is glycosylated, whereas Alp1a is not. The gene encoding Alp1a, ALP1, was isolated using PCR primers based on two amino acid sequences: One obtained directly from the N-terminus of Alp1a and another that is highly conserved in other trypsins. The transcriptional start site was determined using RACE and the intron structure and polyadenylation site were determined from a cDNA clone. An internal fragment of ALP1 was used to create Alp1a null mutants by transformation-mediated gene disruption. Total protease activity in the mutants was reduced by 35% to 45%. By chromatographic analysis, the mutants had lost two peaks of UV absorption and the two protease activities corresponding to Alp1a and Alp1b, which, together with the biochemical data, indicates that Alp1a and Alp1b are products of the same gene. The in vitro growth and diseases phenotypes of the ALP1 mutants were distinguishable from the wild-type strain; therefore, ALP1 is not by itself required for pathogenicity.

Amino Acid Sequence↗
PubMed1996

Effects of taste aversion training on the acquisition of alcohol drinking in adolescent P and HAD rat lines.

Early alcohol drinking has been hypothesized to cause alcohol-related problems in adulthood. In addition, a potential role for genetic factors exist in the etiology of some types of alcoholism. The objective of the present study was to determine if taste aversion training to ethanol during adolescence in previously ethanol-naive, alcohol-preferring P and high-alcohol drinking HAD-1 lines of rats would retard or prevent the onset of high alcohol drinking. Taste aversion training began at 30 days of age. Male and female rat pups were fluid deprived for 24 hr before 30 min access to a 10% [v/v] ethanol solution, followed by an intraperitoneal injection of either saline or 0.15 M LiCl (10 ml/kg). A total of five training sessions were administered every other day with unrestricted access to water on intervening training days. Twenty-four hours after the last training trial, rats were given continuous free-choice between water and 10% ethanol for 4 weeks with food available and libitum. There were no obvious gender or line differences to the effects of taste aversion training. All LiCl-treated subjects avoided the usually preferred ethanol solution for the entire 4-week test period, whereas saline-treated rats steadily increased their alcohol intake to over 6.0 g/kg/day by week 4. Rats in the saline and LiCl-treated groups gained weight at comparable rates, and the groups did not differ in total fluid intake. The findings demonstrate that early environmental intervention can prevent the onset of high alcohol drinking in the selectively bred alcohol-preferring P and high-alcohol drinking HAD-1 lines of rats.

Age Factors↗
PubMed1995

The Pediatric Symptom Checklist. Support for a role in a managed care environment.

OBJECTIVES: To gather data based on studies of the Pediatric Symptom Checklist, identify risk factors associated with high levels of dysfunction in primary care pediatric settings, and explore the relationship between common risk factors and psychosocial problems identified by pediatricians. DESIGN: Retrospective review and cross-sectional, case-referent survey. SETTING: Subjects were selected from three primary care pediatric clinics in Massachusetts: a private practice in a predominantly white, middle-class suburb, an urban health maintenance organization clinic, and an inner-city clinic. PARTICIPANTS: Of 423 outpatients aged 6 to 12 years screened for psychosocial problems, 72 children and their families were seen for in-depth structured and clinical interviews (24 from each site). INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Children with a single parent and/or those who were economically disadvantaged were significantly more likely to show psychosocial impairment. The specificity of the Pediatric Symptom Checklist was 100% in samples with a lower socioeconomic status compared with 68% in middle-class samples, and sensitivity was 95% in middle-class samples compared with 80% in lower-class samples. Pediatricians identified psychosocial problems in eight of 15 children with a history of familial mental illness or substance abuse and seven of eight children with a history of physical or sexual abuse, but only six of 17 cases from single-parent families and four of 11 cases from poor families. CONCLUSIONS: Pediatricians should be sensitive to psychosocial dysfunction especially in single-parent and low-income families. Use of the Pediatric Symptom Checklist for psychosocial screening in a managed health care delivery system could target capitated resources efficiently by providing early identification and secondary prevention of psychosocial morbidity.

Affective Symptoms↗
PubMed1995

Operant response suppression induced with systemic administration of 5-hydroxytryptophan is centrally mediated.

Intracerebroventricular (ICV) administration of selective serotonergic agents was used to examine the extent of central mediation of 5-HTP-induced operant response suppression in rats. ICV administration of LY53857 (1.0, 3.75, or 7.5 micrograms/5 microliters/5 min) dose dependently blocked response suppression induced with systemically administered 5-HTP (25 mg/kg, IP), whereas ICV 0.9% saline (5 microliters over 5 min) had no significant effect on 5-HTP-induced response suppression. ICV ketanserin (7.5 micrograms/5 microliters/5 min) also blocked response suppression induced with systemically administered 5-HTP. ICV administration of the 5-HT2A/2C receptor agonist DOI (80 micrograms/5 microliters/5 min) induced significant periods of response suppression in this model, which was blocked with LY53857 (1.0 mg/kg, IP) pretreatment. These data demonstrate that central administration of 5-HT2A/2C antagonists potently attenuate operant response suppression induced with systemically administered 5-HTP or DOI and are in agreement with previous findings suggesting central mediation of 5-HTP-induced operant response suppression.

5-Hydroxytryptophan↗
PubMed1995

Placement outcomes of 206 severely maltreated children in the Boston Juvenile Court system: a 7.5-year follow-up study.

This study examines placement outcomes of 206 severely maltreated children 7.5 years after arraignment in Boston Juvenile Court (BJC) on Care and Protection Petitions. Sixty-seven percent (n = 138) of the sample had been permanently removed from their parents and 33% (n = 68) had their cases dismissed in the BJC. At time of this follow-up, 21% of the full sample (n = 44) were still in temporary custody awaiting permanent placement. In addition, 4% (n = 8) of children had "drifted" back to their abusive/neglectful parents despite prior permanent removal. The average time children in this sample spent in probate proceedings (awaiting permanent placement) had increased substantially to 2.1 years since the last overview study of this sample 4 years ago. The rate of court referral for incidences of reabuse (a C&P filing), or delinquency was significantly lower among children who had been permanently placed (p < .003). Rates of court-referral for reabuse charges were the same (16%) for children who were in temporary custody at the time of follow-up and children who had been dismissed back to the parent for whom the original C&P had been filed. Results are discussed in light of the urgent need to restructure time limits in juvenile court proceedings, integrate adequate tracking of child abuse and neglect cases through and across court and agency boundaries, and the use standardized assessments of abused and neglected children as a tool in the adjudication process.

Adolescent↗
PubMed1995

Arthroscopic Bankart suture repair for recurrent traumatic unidirectional anterior shoulder dislocations.

We report our experience with arthroscopic repair of the Bankart lesion following traumatic unidirectional anterior shoulder dislocation. Thirty consecutive patients (7 women, 23 men; average age, 26.5 years) were followed for an average of 38 months (minimum 2-year follow-up) after arthroscopic Bankart suture repair for recurrent shoulder dislocation. The study included patients who had pure shoulder dislocations (excluding those with instability secondary to subluxation, multidirectional instability, or an atraumatic origin), had experienced an initial frank shoulder dislocation (documented radiographically or requiring the assistance of medical personnel for reduction), and had a Bankart lesion, visualized arthroscopically. Clinical evaluation using the Rowe functional grading system showed 11 patients rated as excellent, 8 as good, 3 as fair, and 8 as poor. Six of 8 patients were rated as poor because they frankly redislocated following their arthroscopic shoulder stabilization. Our study shows a 27% failure rate in this group. Critical reevaluation of the transglenoid arthroscopic Bankart procedure is mandatory to identify the appropriate patient population for this procedure.

Adult↗
PubMed1995

Deltoid and supraspinatus muscle pressures following various arthroscopic shoulder procedures.

Twenty-four consecutive patients were monitored for pressure elevations in the supraspinatus and deltoid muscles following various arthroscopic shoulder procedures. All patients had clinically swollen shoulders and mild pressure elevations in both muscles immediately following each procedure. Muscle pressure elevations seen immediately postoperatively were clinically insignificant, as no ill effects were seen at follow-up. The extreme clinical swelling following various arthroscopic shoulder procedures appears to be related to the type of procedure performed, but more directly to the amount of irrigation fluid required.

Adolescent↗
PubMed1995

Implementing a parent-present induction program.

One of the greatest fears of children undergoing surgery is separation from their parents. Children for whom preoperative sedation is contraindicated often endure the distress of this separation and the beginning of anesthesia surrounded by masked strangers. Those who receive sedation often experience the invasiveness of a medication administered rectally or intramuscularly or the insertion of an IV line. Until recently, the doors to the operating room remained closed to family members. Like other hospitals throughout the country, however, Children's Hospital in Boston has responded to the concerns of parents and staff members by implementing a parent-present anesthesia induction program. As a result, the surgical experience for many children and families has changed significantly for the better.

Anesthesia↗
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↗