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D Murphy

Publications and source records attributed to D Murphy.

At least 217 records · Page 12Linked to original sources
PubMed1993

Osmotic stimuli attenuate vasoactive intestinal peptide gene expression in the rat anterior pituitary gland.

Studies on vasoactive intestinal peptide (VIP) in the anterior pituitary gland have shown that it is synthesized locally, physiologically regulated, and may act as a paracrine/autocrine factor. We have now investigated the regulation of anterior pituitary VIP gene expression in rats during osmotic stimulation. Both salt-loading and dehydration resulted in a progressive and marked reduction in VIP mRNA levels as determined by Northern analysis, to 10% of control levels at 14 days of salt-loading. The 1.7 and 1.0 kb VIP RNA transcripts were equally affected. Since anterior pituitary VIP is partially localized in lactotrophs we also measured prolactin (PRL) mRNA levels. In contrast to VIP, PRL mRNA levels were increased during both osmotic paradigms, the mRNA levels being significantly raised after 5 days of salt-loading to 130% of controls. Further experiments, conducted to examine the mechanism by which VIP gene expression is down-regulated during osmotic stimulation, demonstrated that dopamine and angiotensin II do not appear to be involved. The results show dissociated regulation of VIP and PRL during osmotic stimulation and provide suggestive evidence of a role for anterior pituitary VIP in the animal's osmoregulatory responses. VIP may therefore be a paracrine factor with diverse functional roles.

Angiotensin II↗
PubMed1993

A randomised dose intensity study in ovarian carcinoma comparing chemotherapy given at four week intervals for six cycles with half dose chemotherapy given for twelve cycles.

BACKGROUND: The importance of dose intensity has not been clearly defined in ovarian cancer and we present a prospectively randomised trial of dose intensity in patients with ovarian cancer. PATIENTS AND METHODS: Ninety-nine patients with FIGO stage Ic, II, III and IV epithelial ovarian cancer were randomised to receive cycles of standard dose cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with adriamycin (50 mg/m2) and ifosfamide (5 G/m2) for 6 cycles at monthly intervals (49 patients) or cycles of half dose cyclophosphamide (300 mg/m2) and carboplatin (150 mg/m2) alternating with adriamycin (25 mg/m2) and ifosfamide (2.5 G/m2) for 12 cycles at monthly intervals (50 patients). Patients in each arm were well balanced for major prognostic factors. RESULTS: The combined clinical response rate (complete response and partial response) on the 6 month arm was 76% compared with 48% on the low dose intensity arm (p = 0.009). With a median follow up of 25.7 months the median survival on the low dose intensity arm is 20.9 months. The median survival point on the 6 month arm has not yet been reached. The median progression free interval on the 12 month arm was 19.8 months, the median value has not yet been reached on the standard arm. The amount of residual tumour following initial laparotomy was the only significant independent variable affecting survival (p = 0.0001). The mean received dose intensity of each drug was greater than 80% of the planned dose intensity. More patients had clinical disease progression during treatment on the low dose intensity arm (42%) when compared to the standard dose intensity arm (8%) (p = 0.0003). Fifteen patients on the standard dose arm experienced a total of 18 delays and 5 patients on the low dose arm experienced 17 delays. Nausea, vomiting and diarrhoea were similar for both standard and low dose cycles of chemotherapy with a consequent benefit for patients receiving fewer cycles even though these were of higher dose. CONCLUSIONS: The combination studied was more effective when given at the higher dose intensity and the improved response and survival was not accompanied by a significant increase in toxicity.

Adenocarcinoma↗
PubMed1993

Managing patient stress in endoscopy.

Most patients experience a certain degree of stress as they prepare for and undergo endoscopy procedures. The stress they experience is correlated to Hans Seyle's General Adaptation Syndrome theory in this article. Stressful events that occur pre-, intra-, and postprocedure are identified. Examples of patient coping skills are discussed. Several nursing interventions such as patient teaching, relaxation techniques, and communication skills are described. All of these interventions assist the nurse in promoting a positive outcome for the patient. As a patient experiences a positive outcome from a stressful event, coping mechanisms are strengthened and developed. These coping mechanisms enable the patient to adapt to future stressors.

Adaptation, Psychological↗
PubMed1993

In vitro regulation of rat prolactin messenger ribonucleic acid poly(A) tail length: modulation by bromocriptine.

Recent analysis of endocrine gene transcripts has revealed that several hormone mRNAs exhibit regulated size changes (due to alterations in length of the 3' poly(A) tail) which may function as an additional level of control in the determination of gene expression. We have now shown, through the novel application of an organ culture technique, that prolactin mRNA exhibits a similar regulated change in poly(A) tail length when rat anterior pituitary glands are explanted. The effect is observed in glands of either male or female rats and is specific with respect to growth hormone and alpha-tubulin mRNAs. Furthermore, we have also found that the size change in prolactin mRNA is attenuated in the presence of bromocriptine, indicating regulation through a dopaminergic pathway.

Animals↗
PubMed1993

Regulation of vasopressin (VP) gene expression in the bed nucleus of the stria terminalis: gonadal steroid-dependent changes in VP mRNA accumulation are associated with alterations in mRNA poly (A) tail length but are independent of the rate of VP gene transcription.

Forebrain vasopressin (VP) neurons of the bed nucleus of the stria terminalis (BNST) contrast with hypothalamic VP neurons in exhibiting nuclear gonadal steroid receptors which may directly effect steroid-induced changes in VP gene expression observed in BNST cells. A transcription and Northern mRNA analysis has been performed to determine the mechanism through which gonadal steroids regulate VP gene expression in the BNST. In addition to confirming a distinctive, sexually dimorphic pattern of VP mRNA expression in the BNST as compared with the hypothalamic supraoptic nuclear (SON), our results show that the marked decrease in BNST VP mRNA levels observed two weeks after castration is not associated with a change in transcriptional activity of the VP gene. Similarly, VP gene transcription is not increased, relative to castrated animals, in the BNST of castrated rats treated with testosterone which exhibit normal or somewhat elevated levels of VP mRNA in the BNST. A post-transcriptional mechanism therefore appears to underlie the gonadal steroid-regulated changes in VP gene expression in the BNST. Since modulation of mRNA size (due to changes in poly (A) tail length) was also observed following castration and testosterone treatment it is apparent that the post-transcriptional mechanism may involve regulated changes in VP mRNA poly (A) tail length. The present findings contrast with the osmotic up-regulation of VP mRNA levels in the SON which is primarily a transcriptional response, and provide a demonstration of the potential physiological importance of post-transcriptional mechanisms of hormonal gene regulation.

Animals↗
PubMed1993

Large DNA restriction fragment polymorphism in the Mycobacterium avium-M. intracellulare complex: a potential epidemiologic tool.

Mycobacterium avium-M. intracellulare complex (MAI) isolates were studied by comparing the large restriction fragment (LRF) patterns produced by digesting their DNAs with infrequently cutting restriction endonucleases and separating the resultant large fragments by pulsed-field gel electrophoresis. Four reference strains and 35 randomly selected clinical MAI isolates gave highly diverse LRF patterns when their DNAs were digested with XbaI or AsnI. The LRF patterns of random isolates identified to be the same species by DNA probe analysis were not similar. The LRF patterns of random isolates of the same serotype were also different. In contrast, all isolates recovered from the same patient gave identical patterns. This included 28 isolates from nine patients. One isolate from sputum, one isolate from bone marrow, and two isolates from blood recovered over a 27-month period from a patient with AIDS were identical. Seven isolates recovered from the sputum of a second patient over 37 months also had identical patterns. The LRF patterns of unrelated MAI strains are highly polymorphic, appear to be strain specific, are relatively stable, and offer exciting promise as epidemiologic markers for the study of MAI infections.

DNA, Bacterial↗
PubMed1993

Lateralizing signs in intractable partial epilepsy: blinded multiple-observer analysis.

We evaluated the accuracy and interobserver variability of selected ictal and postictal behavioral changes. Three observers, blinded to clinical history, EEG, and side of surgical resection, analyzed videotapes of 166 seizures in 38 patients, looking for lateralizing signs. Twenty-seven patients with temporal lobe resections were seizure-free for > or = 1 year postoperatively, and 11 with extratemporal resections had at least 90% reduction in seizures > or = 1 year postsurgery. The epileptogenic region (ER) was lateralized by analyzing lateralizing signs in 78% of patients; positive predictive value (PPV) was 94% (90% CI = 87% to 100%). Overall kappa was 0.68. Signs were considered present if seen by two or more observers. Forty-five percent had version, ie, forced and sustained head deviation (kappa = 0.76, PPV = 94%); 37% had dystonic posturing of the upper extremity (kappa = 0.47, PPV = 93%); and 34% had unilateral mouth deviation (kappa = 0.83, PPV = 92%). These signs indicated a contralateral ER. Twenty-one percent had unilateral upper extremity automatisms, all ipsilateral to the ER (kappa = 0.65, PPV = 100%); 21% had postictal dysnomia, indicating a dominant-hemisphere ER (kappa = 0.89, PPV = 100%); and 16% had ictal speech, usually indicating a nondominant-hemisphere ER (kappa = 0.75, PPV = 83%). Dystonic posturing, postictal dysnomia, ictal speech, and unilateral upper extremity automatisms may indicate a higher probability of temporal lobe epilepsy. Analysis of lateralizing signs shows good interobserver agreement and provides useful clinical information.

Arm↗
PubMed1993

Aerosol vaccination of pigs against Mycoplasma hyopneumoniae infection.

Aerosol vaccination is used effectively to immunize poultry against Newcastle disease, but to the authors' knowledge, this vaccination procedure is not well studied in other species. The efficacy of IM and aerosol vaccination of pigs against Mycoplasma hyopneumoniae infection was evaluated. Twenty-one pigs from a Mycoplasma-free herd were randomly allotted by litter and body weight into 3 groups. One group was given aerosolized phosphate-buffered saline solution (PBSS) by inhalation. The second group (AERO) was given aerosolized M hyopneumoniae vaccine by inhalation. The third group (IM) was given the same vaccine by IM injection. Vaccination by IM administration was repeated once, and aerosol vaccination was repeated twice at 2-week intervals. Two weeks after the last vaccination, all pigs were intratracheally challenge-exposed with 3 ml of broth culture containing 10(7) color-changing units (CCU) of a low-passage strain of virulent M hyopneumoniae. Pigs were observed daily for coughing. Four weeks after challenge exposure, all pigs were necropsied. Percentage of lung affected by gross pneumonia was measured, bronchioalveolar lavage fluid (BALF) cells were counted, and quantitative culture for mycoplasmas was performed on lung sections. Additionally, M hyopneumoniae-specific antibodies were measured in prevaccination, postvaccination, and postchallenge-exposure serum and BALF by use of indirect ELISA. Mean prevalence of persistent coughing in pigs of the AERO group (4.6 d/pig) was not different from that in pigs of the PBSS group (3.7 d/pig). Prevalence of coughing in IM vaccinated pigs (1.0 d/pig) was lower (P < 0.05) than that in pigs of the PBSS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1992

The identification of a cis-acting element involved in cyclic 3',5'-adenosine monophosphate regulation of bovine vasopressin gene expression.

Cyclic adenosine 3',5'-monophosphate (cAMP) has been implicated as an intracellular messenger mediating osmotic regulation of expression of the gene encoding the neuropeptide vasopressin (VP) in the hypothalamus. We have used a heterologous transient transfection system to demonstrate that cAMP regulates the bovine VP gene promoter following transfection into CV1 cells. Mutational analysis identified a bovine VP cAMP-responsive element (BVP-CRE) 120-112 base-pairs upstream of the start of transcription. DNase I footprint analysis using nuclear protein extract from CV1 cells showed protection at the site of the BVP-CRE. Protection of the BVP-CRE was also observed using purified AP1 protein, while there was a weak interaction with the BVP-CRE using purified rat CREB protein. Nuclear proteins purified from the rat supraoptic nucleus bind to the BVP-CRE. As transgenic mouse studies have shown that the bovine VP gene is subject to appropriate physiological regulation in the mouse hypothalamus (Ang, H. L., Funkhouser, J., Carter, D. A., Ho, M. Y., and Murphy, D. (1991) Soc. Neurosci. Abstr. 513, 12), these data indicate a role for the BVP-CRE element in mediating VP gene expression in vivo. These data demonstrate that cAMP regulates bovine VP gene expression in vitro via a cis-acting element within the VP promoter, and this activation may be mediated by members of the AP1/ATF/CREB family of transcription factors.

Animals↗
PubMed1992

Equine hyperlipaemia in the United Kingdom: clinical features and blood biochemistry of 18 cases.

The background, clinical signs, blood biochemistry and management of 18 cases of equine hyperlipaemia are described. Eleven of the animals were Shetland ponies, four were Welsh mountain ponies or their crosses, one was a fell pony and two were riding ponies of mixed breeding. Their average age was nine years. Fourteen of the cases were mares, of which nine were in foal and two were lactating; the remainder were geldings. Underlying or concurrent diseases were identified in only six animals, but in one other animal the hyperlipaemia appeared to have been precipitated by stress, and in another by undernutrition to prevent laminitis. Twelve of the animals were considered obese. There was no age, seasonal, or geographic bias to the distribution of cases. Plasma triglyceride concentrations were increased by between five- and 80-fold, and ranged from 4.7 to 78.8 mmol/litre. There was biochemical evidence of hepatic damage in 17 cases, of renal insufficiency in 15, and pancreatic pathology in three cases. Four animals were euthanased without therapy. The others were treated with oral glucose solutions, which were supplemented with injections of insulin and heparin in four cases, and insulin alone in two cases. Eight of the treated animals died, to give an overall mortality of 67 per cent. The outcome of the treatment was unrelated to the degree of hypertriglyceridaemia, to the presence and severity of hepatic, renal or pancreatic pathology or to the therapeutic regimen.

Alkaline Phosphatase↗
PubMed1992

Decrease in hypothalamic vasopressin mRNA poly(A) tail length following physiological stimulation.

1. The vasopressin mRNA in the adult male rat hypothalamus is modulated in two distinct ways by a dehydration stimulus. In addition to the well-established increase in transcript abundance, it has recently been demonstrated that the vasopressin mRNA poly(A) tail increases in length. 2. We have studied the ontogeny of poly(A) tail length modulation in neonates in response to milk deprivation and found that poly(A) tail length changes are age dependent. In neonates older than 12 days of age, the vasopressin mRNA poly(A) tail length increased with milk deprivation and this effect became more marked in older animals. However, in rats 5 to 9 days old, milk deprivation resulted in a detectable though not significant decrease in vasopressin mRNA poly(A) tail length. 3. As milk deprivation is a combination of dehydration and starvation, we investigated the effect of the latter stimulus in more mature animals. We found that starvation modifies the length of the vasopressin mRNA poly(A) tail in a manner opposite that due to dehydration. 4. Our data indicate a novel mode of regulation of the vasopressin mRNA, namely, poly(A) tail shortening. This system provides a model for future studies concerning the adaptive role of poly(A) tail length modulation in response to physiological stimuli.

Adaptation, Physiological↗
PubMed1992

Surgically created Wolff-Parkinson-White syndrome after Fontan operation.

The Wolff-Parkinson-White syndrome is caused by a congenital accessory connection between the atrium and ventricle. We describe a case of symptomatic Wolff-Parkinson-White syndrome that arose after a Björk modification of the Fontan operation. Invasive electrophysiologic and intraoperative mapping indicated that the surgically created atrioventricular connection was functioning as an accessory pathway. Surgical dissection and cryoablation abolished the symptoms and the preexcitation.

Adolescent↗
PubMed1992

Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors.

Some patients with thyrotropin (TSH)-producing pituitary tumors are more hyperthyroid than others despite similar TSH levels in serum, suggesting that qualitatively different TSH molecules with differing bioactivities may be secreted by different tumors. We used ricin and lentil lectin-affinity chromatography to test whether the TSH oligosaccharides varied among 12 patients with TSH-producing tumors. We found that each tumor secreted heterogeneous isoforms of TSH that differed in their extents of exposed galactose (Gal) residues, and their degrees of sialylation and core fucosylation. These biochemical parameters also varied markedly for TSH secreted by different tumors. Isoforms appeared to reflect poor sialyltransferase activity in two tumors and efficient sialyltransferase in the remainder. TSH secreted by tumors was more fucosylated than TSH secreted by control euthyroid persons. There was an inverse relationship between the sialylation and fucosylation of tumor TSH. No simple relationship between TSH oligosaccharide structures and bioactivity was evident, although mixtures of isoforms having the least and most sialylated TSH seemed to be the most bioactive clinically. In three patients from whom serum and medium TSH were both available, TSH in serum was more sialylated than TSH secreted by the tumor in vitro, perhaps reflecting slow clearance of sialylated isoforms from the circulation. Core fucosylation of serum TSH was less than that of medium TSH. These data prove that human tumors secrete TSH with heterogeneous oligosaccharide structures.

Adult↗
PubMed1992

Nuclear mechanisms mediate rhythmic changes in vasopressin mRNA expression in the rat suprachiasmatic nucleus.

Vasopressin (VP) gene expression in the rat suprachiasmatic nucleus (SCN) is subject to a cyclical mode of regulation which is indicative of a close association with the circadian clock intrinsic to this area of the hypothalamus. Previous studies show that both the amount and size (due to differential polyadenylation) of VP mRNA are reduced during the dark phase of the daily cycle. We have now identified the cellular site wherein these changes are mediated. By transcriptional run-on analysis of nuclei isolated at different time points from the SCN we have shown that an attenuation of transcriptional activity can account for the dark-phase reduction in VP mRNA levels; by comparison with other genes expressed in this tissue, a significant, VP gene-specific reduction was observed which resulted in dark-phase transcriptional activity at 30% of light-phase activity (P less than 0.005). A similar diurnal variation was not found in the supraoptic nucleus. In addition, by Northern analysis of sub-cellular RNA pools, we have demonstrated that the smaller, dark-phase-specific VP RNA species is located, in abundance, within the nuclear fraction. These results provide clear evidence that the cyclical changes in SCN VP mRNA expression are primarily regulated within the nucleus, indicating that any potential regulation in the cytoplasm is of secondary importance. Further analysis of the molecular components which mediate the cyclical changes in transcriptional activity of the VP gene may identify fundamental aspects of neuronal timing mechanisms.

Animals↗