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Biomedical subjects

D Murphy

Publications and source records attributed to D Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1991

Rapid changes in poly (A) tail length of vasopressin and oxytocin mRNAs form a common early component of neurohypophyseal peptide gene activation following physiological stimulation.

The time course of acute changes in vasopressin (VP) and oxytocin (OT) mRNA size and level during dehydration has been studied in rats. Total RNA was extracted from samples of the supraoptic nucleus at various intervals after water deprivation, subjected to northern blotting, and probed with oligonucleotides specific for VP and OT mRNA. The VP and OT mRNA size, shown previously to reflect 3'-poly (A) tail length, was consistently increased 2 h after dehydration, prior to significant changes in plasma osmolality or haematocrit. Intraperitoneal administration of hypertonic saline resulted in a similarly rapid VP and OT mRNA size response, in some cases within 1 h of treatment. The effect of a discrete hypovolaemic stimulus was investigated with intraperitoneal injections of polyethylene glycol; again, the VP and OT mRNA size was rapidly increased. No significant changes in mRNA level were observed in any of the experimental groups. The results show that an increase in VP and OT mRNA poly(A) tail length forms an acute and general response to activation of the hypothalamo-neurohypophyseal system. The rapidity of the poly (A) tail response, which appears to be independent of physiological signalling mechanisms associated with increases in mRNA accumulation (observed after 2 days of dehydration), provides a paradigm for the investigation of novel modes of neuronal gene regulation.

Animals↗
PubMed1991

Testicular oxytocin gene expression in seminiferous tubules of cattle and transgenic mice.

We are using transgenic mice to study the regulation of the bovine vasopressin (VP) and oxytocin (OT) genes. Prompted by the observation that mice bearing a bovine OT transgene express bovine OT RNA in their testes, we investigated the expression of the VP-OT locus in normal mice and cattle. Normal wild-type mice do not have detectable levels of either VP or OT RNA in their testes. Normal cattle are also devoid of detectable VP transcripts, but have relatively high levels of testicular OT RNA. Additionally, OT, but not VP, peptide is detectable by HPLC. In situ hybridization to RNA in bovine testicular tissue sections localized OT transcripts to seminiferous tubules, with a distribution similar to that of alpha-inhibin, suggesting expression in Sertoli cells. Interestingly, the bovine OT RNAs in the transgenic mouse testes were also shown by in situ hybridization to have the same distribution. These data suggest that the cis-acting regulatory sequences responsible for expression of the OT gene in bovine Sertoli testis reside within the limits of the transgene used in this study. Further, the trans-acting factors present in murine testicular cells are able to recognize these elements, although they do not express the endogenous mouse OT gene in this tissue.

Animals↗
PubMed1991

Vasopressin and oxytocin gene expression in rat testis.

The vasopressin (VP) gene is expressed as three different transcripts in the rat testis. Using polymerase chain reaction (PCR) analysis we have been able to identify a VP RNA that is identical in exonic structure to that found in the hypothalamus. However, the abundance of this form is very low, and it cannot be detected by Northern blotting. Two VP RNAs with a novel structure, as shown using exon-specific probes, are present in higher abundance. By differential hybridization, sequencing of a cDNA clone, and PCR we have deduced the structure of these novel transcripts. Both of the novel testicular VP RNA species share two exons with the classical hypothalamic RNA. However, the testicular VP gene-derived RNA lacks the first exon of the hypothalamic transcript, the exon that contains the sequence information for the VP nonopeptide hormone. Instead, it has novel sequence that are derived from at least two unique testis-specific exons, one of which is located 7-10 kilobase up-stream of the brain-specific start of transcription. These two unusual transcripts are probably derived by alternative splicing of at least two up-stream exons. Sequence and polysome analyses indicate that the testicular VP RNAs are probably not translated. Northern blotting revealed that the VP gene-derived RNA species are tightly regulated during postnatal development, becoming apparent by 40 days of age, although they subsequently fail to respond to a variety of physiological perturbations. Oxytocin gene transcripts are not detectable by Northern hybridization, but the authentic hypothalamic-type RNA can be detected in the rat testis using PCR analysis.

Adrenal Glands↗
PubMed1991

The practice outcomes of a course in flexible sigmoidoscopy for primary care physicians.

A mail survey of 430 participants in a 2-day course on flexible sigmoidoscopy presented over the past 6 years was conducted to determine the extent to which flexible sigmoidoscopy was subsequently utilized in physician practice. Eighty percent of respondents performed the procedure in their practices on a regular basis. Two-thirds of the patients underwent sigmoidoscopy for screening. The course in flexible sigmoidoscopy appears to potentiate the motivation of primary care physicians to incorporate complete colorectal cancer screening in their practice.

Education, Medical, Continuing↗
PubMed1991

Differential expression of p62c-yes in normal, hyperplastic and neoplastic human epidermis.

The protein product of the c-yes proto-oncogene, p62c-yes, is highly expressed in a variety of mammalian cell types, including neurons, spermatozoa, platelets, and epithelial cells. In order to understand the function of p62c-yes in epithelial cells, the expression and localization of p62c-yes was studied in cultured human epidermal keratinocytes and in normal, hyperplastic, and neoplastic human epidermis. Human keratinocytes in culture produce a single 4kb c-yes mRNA and a 62kd protein product, p62c-yes, which is active as a protein tyrosine kinase. Using affinity-purified antibodies generated to the amino-terminus of the human c-yes protein, the expression of p62c-yes was localized to keratinocytes in the basal epidermal layer of normal neonatal and adult epidermis. There was a marked reduction in expression of p62c-yes by suprabasal keratinocytes undergoing progressive differentiation. By immunofluorescence microscopy, p62c-yes was localized to the plasma membrane and to a perinuclear cytoplasmic area in cultured keratinocytes. The apparent association of p62c-yes with plasma membranes was particularly evident in suprabasal keratinocytes from hyperplastic epidermis. Neoplastic keratinocytes in basal cell carcinomas showed a marked reduction in p62c-yes expression compared to normal basal keratinocytes in epidermis or to proliferating cultured keratinocytes. Thus the expression of p62c-yes by one epithelial cell type, the keratinocyte, is altered by cellular differentiation and neoplastic transformation. Keratinocytes provide a normal epithelial cell model in which the biochemical function of p62c-yes can be studied.

Cell Transformation, Neoplastic↗
PubMed1990

Vasopressin mRNA in parvocellular neurons of the rat suprachiasmatic nucleus exhibits increased poly (A) tail length following water deprivation.

Dehydration is associated with altered vasopressin (VP) gene expression in the rat hypothalamus; an increase in both arginine-vasopressin mRNA abundance and size (due to 3' poly(A) tail extension) has been observed previously. We have now shown that the effects of dehydration are not restricted to the magnocellular AVP neuronal systems since VP mRNA in the suprachiasmatic nucleus (SCN) exhibits a progressive increase in poly(A) tail length during dehydration. No significant increase in VP mRNA abundance was found. Similar kinetics of poly(A) tract extension in the SCN and magnocellular supraoptic nucleus implies a common regulatory mechanism which appears to be distinct from osmotic upregulation of VP transcript abundance.

Animals↗
PubMed1990

Regulation of c-fos and c-jun expression in the rat supraoptic nucleus.

1. We have investigated induction of the nuclear proto-oncogenes c-fos and c-jun in the rat supraoptic nucleus (SON) during physiological stimulation. 2. Dehydration (0-24 hr) was associated with modest, but significant increases in both c-fos and c-jun mRNA at 8 hr and 16 hr as determined by Northern analysis of total RNA extracted from microdissected SON. Prior to 8 hr, and beyond 24 hr, no consistent changes in c-fos and c-jun mRNA were found. Levels of c-fos and c-jun mRNA in the hippocampus were not altered over 24 hr of dehydration. 3. Acute stimulation with hypertonic saline (1.5 M, i.p.) resulted in a marked increase in SON c-fos mRNA at 1 hr (6-fold) and 2 hr (3.5-fold). Small increases in SON c-jun mRNA were observed at these time points. Treatment with a similar volume of 0.9% saline did not elevate SON c-fos and c-jun mRNA levels. 4. Analysis of transcriptional activity with a nuclear run-on assay showed that activation of transcription appears to mediate the induction of c-fos and c-jun mRNA following acute hypertonic saline treatment. During dehydration transcriptional activation is apparent for c-jun but is not well defined for c-fos. 5. The results are discussed with reference to the hypothesis that products of c-fos and c-jun may mediate adaptive changes in hypothalamic gene expression.

Animals↗
PubMed1990

Continuous cerebral electrical impedance monitoring in sick preterm infants.

Cerebral electrical impedance (dZ) and intra-arterial blood pressure were measured continuously during the first 48 h after birth in 26 sick ventilated preterm infants with a birth weight less than 1500 g. The aim was to establish whether any patterns of dZp or the variability of either blood pressure or dZp would allow identification of those infants who developed intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) or a poor neurological outcome. IVH and PVL were diagnosed by ultrasound image obtained every 6 h. Cerebral electrical impedance recordings were unsuitable for analysis in three patients and a further three died within 14 h of birth. In the remaining 20 patients, no step changes that may have been related to the onset of IVH or PVL were evident and whilst three patterns of dZp were identified, they were not useful in distinguishing between normal infants or those who developed IVH, PVL or had a poor neurological outcome. Using multiple linear regression, the coefficient of variation of dZp was significantly associated with both IVH and outcome, as was the coefficient of variation of blood pressure. Continuous measurement of cerebral electrical impedance, whilst technically feasible in sick preterm infants, was not found useful as a method of identifying those who developed IVH, PVL or had a poor neurological outcome.

Blood Pressure Determination↗
PubMed1990

Preference for denotative as opposed to connotative meanings in schizophrenics.

Twenty schizophrenics, 20 manics and 20 subjects with a depressive illness were asked to select the pair of words from a group of three which went together best. The groups of words were arranged such that potential pairings reflected shared denotative (e.g., linked by being antonyms) or shared connotative meaning (e.g., linked at a metaphorical level). The measure "denotative-based--connotative-based selections" was significantly lower in schizophrenics than manics and just failed to significantly distinguish schizophrenics from depressives. In a second experiment schizophrenics were significantly different from the depressives in showing less inclination to select a metaphorical meaning to an ambiguous adjective in a sentence. It is suggested that these results arise because the schizophrenic relies more on their left hemisphere lexicon in carrying out such semantic tasks.

Adult↗
PubMed1990

Pancreatitis after rectal administration of 5-aminosalicylic acid.

A patient treated with sulfasalazine for new-onset ulcerative colitis developed self-limited pancreatitis. Rechallenge with 5-aminosalicylic acid (5-ASA) in enema form (Rowasa) again induced pancreatitis. Recent case reports suggest that the salicylate component of sulfasalazine can lead to the development of pancreatitis with oral 5-ASA administration. This patient's course demonstrates further that rechallenge with 5-ASA in a rectal form may also lead to pancreatitis.

Administration, Rectal↗
PubMed1990

The management of primary fallopian tube carcinoma.

The outcome of 30 patients with primary fallopian tube carcinoma is described. Treatment varied over the 22 year period of accrual and included combinations of surgery, radiotherapy and chemotherapy. There was an apparent increase in stage at treatment with time which was probably related to more precise staging at laparotomy and the greater use of computerized tomography. The median survival for all patients was 28 months and the 5-year survival was 18%. Ten patients received postoperative chemotherapy for residual disease with an overall response rate of 80% and median progression-free and overall survival times of 14 and 21 months respectively. The pattern of relapse was similar to that seen in ovarian carcinoma, with all but one patient having the pelvis or abdomen as the main site of recurrence. Primary fallopian tube carcinoma has a response to treatment and a tumour biology similar to that of ovarian carcinoma. It is recommended that the management of this uncommon malignancy should continue to be along the lines of ovarian carcinoma, with initial treatment by cytoreductive surgery followed by chemotherapy or radiotherapy for residual disease.

Adult↗
PubMed1990

Prosodic comprehension and expression in schizophrenia.

Schizophrenics, manics, depressives and normal subjects (15 in each group) were tested for their ability to understand and express the prosodic quality of speech. Sentences in which one word was stressed (stress prosody comprehension) or in which a particular emotion was conveyed (emotional prosody comprehension) were taped and played to subjects to test their comprehension. Subjects were then asked to read out a list of sentences either stressing a nominated word (stress prosody expression) or conveying a nominated emotion (emotional prosody expression), and their efforts were rated by a panel of normal raters. The main results were 1) that schizophrenics were significantly inferior to the normal group, but equivalent to manics and depressives on emotional prosody comprehension; 2) schizophrenics were significantly inferior to all other groups on emotional prosody expression; and 3) all four groups were equivalently proficient on stress prosody comprehension and expression. The results are interpreted as lending support for the idea that there is an underlying right hemisphere dysfunction in schizophrenia.

Adult↗
PubMed1990

Long-term follow-up of children with Down syndrome with cardiac lesions.

Two hundred and eighty four patients with Down Syndrome (DS) were seen between 1951-1989. One-hundred and fourteen (40.1%) had a [corrected] cardiac murmur at presentation. A definitive cardiac diagnosis was established in 47 (41%) patients, of which 38 had long term follow-up. Fifteen (33%) patients had atrioventricular canals. There were 21 males and 17 females, with a mean age of 5.3 years. Fifteen (39%) patients were in functional class (FC) I, 16 (42%) in FC II, six (15%) in FC III, and one patient in FC IV at the time of presentation. There were 18 survivors (13 in the surgical group and five in the nonsurgical group) and 20 nonsurvivors (four in the surgical group and 16 in the nonsurgical group). Causes of death in the nonsurgical group included congestive heart failure, pneumonia, and pulmonary vascular disease, and occurred at a mean age of 8.4 years. Post-operative complications accounted for deaths in three of the four surgical patients. The survivors in the surgical group are presently in FC I/II. In the nonsurgical group, there was increased mortality, especially in those who presented in an earlier era, and a deterioration in functional class on follow-up due to the development of pulmonary vascular disease. Our data suggest that a) patients with Down syndrome and heart disease are helped by cardiac surgery with stabilization and improvement of their functional class; b) deterioration in functional class is seen in patients with Down syndrome with cardiac lesions who are managed nonsurgically [corrected] and c) mortality remains high in such patients treated nonsurgically due to development of pulmonary vascular disease and congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Impaired ability of schizophrenics, relative to manics or depressives, to appreciate social knowledge about their culture.

Twenty schizophrenics, 20 manics, and 20 depressives were given two sets of multiple choice questions, one testing the subject's social knowledge of how people tend to act in a social situation and the other tapping their knowledge of events or objects which are relatively free of a social component. Schizophrenics were significantly impaired on the former set of questions relative to manic, and were significantly worse on both than depressives. It is suggested that these results represent an objective measure of the social naïvete of schizophrenics. The significant difference from manics indicates that the results are not merely the general effects of psychosis, particularly because the manics performed worse on an attentional test than the schizophrenics.

Adult↗
PubMed1990

Dopaminergic mediation of physiological changes in proopiomelanocortin messenger ribonucleic acid expression in the neurointermediate lobe of the rat pituitary.

POMC mRNA levels in the intermediate lobe of the pituitary are known to be regulated by osmotic stimuli. Salt loading with 2% saline causes a decrease in POMC mRNA levels in the IL without affecting levels in the anterior lobe. We have investigated possible mediators of this effect and attempted to elucidate the mechanism by which the changes in mRNA levels are brought about. The dopamine D2 receptor antagonist domperidone blocked the inhibitory effect of salt load on POMC mRNA in the neurointermediate lobe, while the D2 agonist bromocriptine mimicked the effect of salt load. Pharmacological agents affecting D1 receptors, beta-adrenoceptors, and endogenous serotonin levels did not block the decrease in POMC mRNA levels after a salt load. The level of transcription of the POMC gene in the neurointermediate lobe was investigated using a nuclear run-on transcription assay. Transcription of POMC was found to be unchanged after a salt load, indicating that an osmotic stimulus does not decrease POMC mRNA levels by a specific change in the level of transcription.

Actins↗
PubMed1990

Vasopressin gene expression in the rodent hypothalamus: transcriptional and posttranscriptional responses to physiological stimulation.

The neuropeptide vasopressin (VP) is expressed in the supraoptic nucleus, a discrete group of neurons in the hypothalamus that respond to osmotic stimuli. In the rat the pattern of expression of VP mRNA changes in two ways as a consequence of the physiological stimulation of these neurons. Firstly, there is an accumulation of VP mRNA, and secondly, the poly(A) tail of the VP mRNA increases in length. We asked whether the increase in VP mRNA level is a consequence of transcriptional or posttranscriptional mechanisms. We present evidence from nuclear run-on assays that increases in the transcription of the rat VP gene are sufficient to account for the accumulation of VP mRNA observed in chronically stimulated animals. However, we note that in acutely stimulated animals there are rapid and relatively large increases in VP gene transcription that do not correlate with increases in the VP mRNA level, but coincide with the appearance of a homogeneous class of VP mRNAs with elongated poly(A) tails. We suggest that immediately after the onset of an acute osmotic stimulus, there is a rapid destruction of preexisting VP mRNAs and their replacement with new transcripts bearing longer poly(A) tails. We have also addressed the question of the function of the elongated VP mRNA poly(A) tail. It is unlikely that the poly(A) tail extension is involved in RNA stability; the transcriptional changes observed are sufficient to account for the increase in VP mRNA level, and we show that in the mouse similar increases in VP mRNA level are observed without concomitant changes in poly(A) tail length. We did not observe a change in the polysome distribution of the VP mRNA after osmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗