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Biomedical subjects

D Murphy

Publications and source records attributed to D Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effect of verapamil on daunorubicin accumulation in lymphocytes isolated from patients undergoing chemotherapy.

Verapamil was shown to be capable of increasing intracellular daunorubicin levels in normal lymphocytes isolated from patients undergoing chemotherapy for epithelial ovarian cancer. The extent of the increase in daunorubicin accumulation was variable, occurring in the range of 0-123% as compared with intracellular daunorubicin levels attained in the absence of verapamil. No similar effect was seen in lymphocytes isolated from healthy volunteers. A tentative explanation of these data may be the induction of multidrug resistance (mdr)-like characteristics in normal lymphocytes following cytotoxic chemotherapy.

Daunorubicin↗
PubMed1991

Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones.

Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin- 5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e] [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.

Aggression↗
PubMed1991

Metallothionein levels in ovarian tumours before and after chemotherapy.

The metallothionein content of ovarian tumours is considerably higher than that found in normal ovaries (greater than 100-fold differences in mean values, P less than 0.001). There was no difference between the metallothionein content of tumours from patients who had completed chemotherapy, usually with a regimen containing a platinum drug, and tumours from untreated patients. Similarly, the level of metallothionein was not influenced by response to therapy, age, stage, histology, or tumour cell differentiation state. These data do not support the hypothesis that metallothionein content is a major determinant of tumour sensitivity in ovarian cancer.

Adult↗
PubMed1991

Changes in blood pressure during the normal menstrual cycle.

1. Changes in blood pressure during the normal menstrual cycle are not well documented, and previous studies have given conflicting results. 2. Thirty normotensive women and ten mildly hypertensive women measured their blood pressure at home each morning for 6 weeks, under standardized conditions, using a UA-751 semi-automatic sphygmomanometer. All had normal menstrual cycles and subjects entered the study at different phases of the cycle. 3. Blood pressure was higher at the onset of menstruation than at most other phases of the cycle (systolic blood pressure, P less than 0.05; diastolic blood pressure, P less than 0.001). Adjusted diastolic blood pressure was higher in the follicular than in the luteal phase (mean difference 1.23 mmHg, P less than 0.001). Similarly, blood pressure was lower during days 17-26 than during the remainder of the cycle (adjusted mean difference in systolic blood pressure -0.65 mmHg, P = 0.07; adjusted mean difference in diastolic blood pressure -1.19 mmHg, P less than 0.001). 4. Similar patterns were seen in normotensive and hypertensive subjects, and changes in plasma 17 beta-oestradiol and progesterone concentrations were also similar in the two groups.

Adult↗
PubMed1991

Anti-Leu3a induces combining site-related anti-idiotypic antibody without inducing anti-HIV activity.

Development of a vaccine for acquired immunodeficiency syndrome (AIDS) has proven difficult, and so alternative approaches such as idiotypic manipulation have been suggested. As applied to AIDS, this approach could involve immunizing with an anti-CD4 antibody resembling gp120, to induce anti-idiotypic antibodies which would bind to gp120. The CD4 binding site on gp120 is conserved, and so, such an immune response should protect against all variants. Induction of anti-human immunodeficiency virus (HIV) immunity has been reported using anti-Leu3a, and this result has led to testing in humans. Negative results obtained by others have been attributed to differences in immunization protocols. Because of the importance of this question, we reinvestigated the potential of anti-Leu3a to induce anti-HIV antibodies, compared with control immunizations with OKT4A (another anti-CD4 antibody) and the irrelevant Ig MOPC-21. Responses to anti-Leu3a showed induction of high-titer anti-idiotypic activity, and included combining-site-related activity. Yet sera showed no binding to gp160 above controls and no detectable neutralizing activity in a sensitive HIV plaque assay, so the anti-idiotypes induced were not internal images of CD4. We conclude that the pronounced anti-HIV responses reported with anti-Leu3a cannot be generalized, and thus that anti-Leu3a does not offer promise as an HIV vaccine. However, these results do not negate the promise of the idiotypic approach, and a vaccine for AIDS based on idiotype manipulation remains a possibility.

Animals↗
PubMed1991

Delivery in an obstetric birth chair: a randomized controlled trial.

OBJECTIVE: To determine whether nulliparae whose second stage of labour is conducted in an obstetric birth chair have a lower incidence of instrumental delivery than those using a conventional delivery bed. DESIGN: Randomized controlled trial using sealed, opaque envelopes for allocation. SETTING: Delivery ward in a busy teaching hospital. PATIENTS: 1250 nulliparae with a singleton live fetus with cephalic presentation, without epidural anaesthesia, who had achieved full dilatation. INTERVENTION: Intention to conduct second and third stages of labour in either the Birth-EZ chair or the conventional delivery bed, as randomly allocated. MAIN OUTCOME MEASURES: Primary measure: vaginal operative delivery; principal secondary measures: duration of second stage, perineal trauma, blood loss, women's views, and neonatal status. RESULTS: Delivery in the birth chair did not result in a reduction in operative delivery, overall. However, there was a reduction in vaginal operative delivery for fetal heart rate abnormality. There was no beneficial effect on perineal trauma or puerperal perineal pain. Post-partum haemorrhage was more frequent in the birth chair group. CONCLUSIONS: Delivery in the birth chair does not offer any obvious advantage to women over delivery on a bed.

Consumer Behavior↗
PubMed1991

A predominant group-specific neutralizing epitope of human immunodeficiency virus type 1 maps to residues 342 to 511 of the envelope glycoprotein gp120.

Recombinant native human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins gp160 and gp120 (residues 1 to 511) expressed in insect cells quantitatively adsorbed the group-specific neutralizing antibodies found in human sera. However, these antibodies were not adsorbed by envelope fragment 1 to 471 or 472 to 857 or by both fragments sequentially, even though together they add up to the full-length gp160 sequence. A hybrid envelope glycoprotein was constructed with residues 342 to 511 of the HIV-1 sequence and residues 1 to 399 of the simian immunodeficiency virus type 1 sequence to vary the HIV-1 sequence while preserving its conformation. This hybrid glycoprotein quantitatively adsorbed human neutralizing antibodies, while native simian immunodeficiency virus type 1 envelope glycoprotein did not. These results identify a new neutralizing epitope that depends on conformation and maps to residues 342 to 511 of gp120. It overlaps the extended CD4-binding site but is distinct from the V3 loop described previously (K. Javaherian et al., Proc. Natl. Acad. Sci. USA 86:6768-6772, 1989; J. R. Rusche et al., Proc. Natl. Acad. Sci. USA 85:3198-3202). Since it is conserved among diverse HIV-1 isolates, this new epitope may be a suitable target for future vaccine development.

Amino Acid Sequence↗
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↗