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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 199 records · Page 11Linked to original sources
PubMed1996

Evidence that guanylate cyclase is involved in modulating the resting tension and neurally-induced contraction of the guinea pig tracheal muscle.

Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, a guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-1-methylxanthine, which promotes cyclic guanosine monophosphate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Synthesis using a Fmoc-based strategy and biological activities of some reduced peptide bond pseudopeptide analogues of dynorphin A1.

Eight analogues of Dyn A(1-11)-NH2 incorporating the enzymatically stable psi(CH2-NH) isosteric peptide bond replacement were synthesized and tested for binding affinity at the central opioid mu, delta, and kappa receptors in guinea pig brain (GPB) homogenates and for activity at the peripheral kappa (and mu) receptors in the guinea pig ileum (GPI). The peptidic analogues were synthesized by solid phase techniques using a Fmoc/tert-butyl strategy, and the psi(CH2-NH) bond, or reduced bond, was introduced via reductive alkylation of the N-terminal amino group of the growing peptide with a Fmoc-N(alpha)-protected amino aldehyde. The synthesis of Fmoc-N(alpha)-protected amino aldehydes also is described. Several other peptides have been previously synthesized incorporating this modification and showed for instance increased enzymatic stability and antagonist properties. Results obtained in the GPB show that modifications of the peptide bond in the address site (analogues 4-9) do not affect the binding at the kappa receptor and, with a few exceptions, at the mu and delta receptors. On the other hand, analogues 2 and 3, modified in the message segment of Dyn A(1-11)-NH2, show a decrease in binding affinity at all three receptors. In the GPI, the results are more varied as the influence of the peptide bond modification seems to be more important than in the GPB. Finally, selected analogues were tested with no indication for antagonist activity at the kappa peripheral receptor.

Amino Acid Sequence↗
PubMed1995

Antisense DNA downregulation of the ERBB2 oncogene measured by a flow cytometric assay.

A causal role has been inferred for ERBB2 overexpression in the etiology of breast cancer and other epithelial malignancies. The development of therapeutics that inhibit this tyrosine kinase cell surface receptor remains a high priority. This report describes the specific downregulation of ERBB2 protein and mRNA in the breast cancer cell line SK-BR-3 by using antisense DNA phosphorothioates. An approach was developed to examine antisense effects which allows simultaneous measurements of antisense dose and gene specific regulation on a per cell basis. A fluorescein isothiocyanate end-labeled tracer oligonucleotide was codelivered with antisense DNA followed by immunofluorescent staining for ERBB2 protein expression. Two-color flow cytometry measured the amount of both intracellular oligonucleotide and ERBB2 protein. In addition, populations of cells that received various doses of nucleic acids were physically separated and studied. In any given transfection, a 100-fold variation in oligonucleotide dosage was found. ERBB2 protein expression was reduced greater than 50%, but only in cells within a relatively narrow uptake range. Steady-state ERBB2 mRNA levels were selectively diminished, indicating a specific antisense effect. Cells receiving the optimal antisense dose were sorted and analyzed for cell cycle changes. After 2 days of ERBB2 suppression, breast cancer cells showed an accumulation in the G1 phase of the cell cycle.

Base Sequence↗
PubMed1995

Probes for narcotic receptor-mediated phenomena. 20. Alteration of opioid receptor subtype selectivity of the 5-(3-hydroxyphenyl)morphans by application of the message-address concept: preparation of delta-opioid receptor ligands.

Derivatives of racemic and optically active 5-(3-hydroxyphenyl)-2-methylmorphan (5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonane, 1) were synthesized containing additional aromatic moieties, as an application of the message-address concept targeted at producing delta-opioid receptor selective ligands. In vitro radioreceptor binding studies in rat brain revealed that both of the parent enantiomers, (-)- and (+)-1, had a high affinity for the mu-opioid receptor (21 nM), a slight affinity for kappa 1-opioid receptors (approximately 800-900 nM), and less than 1000 nM affinity for the delta-opioid receptor (mu/delta IC50 ratio of < 0.02 for both). A derivative of (-)-1 containing an indole moiety fused at the C6-C7 position of the phenylmorphan nucleus, (-)-11, displayed a > 180-fold increase in affinity for the delta-opioid receptor with an IC50 value of 6 nM. The parent compound (-)-1 had only 26% agonist activity at 30 microM in the mouse vas deferens (delta) bioassay, whereas compound (-)-11 had an IC50 of 393 nM in this preparation, indicating the importance of the indole moiety in imparting delta-opioid agonist activity to the phenylmorphan (-)-11. A structure-activity relationship (SAR) study of N-alkyl derivatives of the racemic nor 11 indicated similarities between the interaction of various derivatives with the mu- and delta- but not the kappa 1-opioid receptor. As studies on the molecular basis of the interaction of opioid ligands with their respective receptors continue to gain momentum, the SAR data described herein for the synthetic phenylmorphans will prove useful for further studies.

Animals↗
PubMed1995

Precision and accuracy of clinical and radiological signs in premature infants at risk of patent ductus arteriosus.

OBJECTIVE: To determine the precision (interobserver agreement) and accuracy (agreement with criterion standard) of clinical and radiological signs in premature infants at risk of patent ductus arteriosus (PDA) with left-to-right shunting. DESIGN: Masked comparison of clinical and radiological examination with Doppler flow echocardiography (criterion standard). SETTING: Neonatal intensive care unit. PATIENTS: One hundred infants with birth weights less than 1750 g were studied once between days 3 and 7 of life. A third of the cohort was intubated at the time of study. INTERVENTION: Five independent observers noted the presence or absence of an increased pulse volume, an active precordium, a heart murmur, a cardiothoracic ratio greater than 60%, increased pulmonary vascular markings on a concurrent chest x-ray film, and a relative increase of the cardiothoracic ratio compared with that from the previous chest x-ray film. Pulsed and color flow Doppler echocardiography was performed within 4 hours. All 100 tapes were reviewed by a second pediatric cardiologist. RESULTS: Twenty-three infants had a PDA with left-to-right shunting. The precision of clinical signs was modest, with average kappa values of 0.15 for pulse volume, 0.32 for precordium, and 0.41 for murmur. Pulse quality (43%) and murmur (42%) had the highest mean sensitivities. Corresponding specificities were 74% for pulse volume and 87% for murmur. The combination of a cardiac murmur with an abnormal pulse volume had the highest positive predictive value (77%). The radiological examination did not improve the observers' ability to distinguish between patients with and without PDA. CONCLUSIONS: The precision and accuracy of clinical and radiological signs of a PDA with left-to-right shunting are unsatisfactory. Therefore, Doppler flow echocardiography is required to diagnose PDA confidently in preterm infants between days 3 and 7 of life.

Ductus Arteriosus, Patent↗
PubMed1995

Cutaneous manifestations of Taxol therapy.

Taxol is a novel chemotherapeutic agent that has produced substantial responses in early clinical studies [1]. Taxol has excellent activity in a number of malignancies based on recently completed clinical trials, including a 30% response rate in platinum-refractory ovarian cancer patients [2-5]. We are currently conducting trials of dose-intense taxol with granulocyte colony stimulating factor (G-CSF) support in relapsed or refractory ovarian cancer patients. Such dose intensification produces a major response rate in 50% of patients with this disease [6]. Taxol was supplied in 5 ml ampules (6 mg/ml) in polyethoxylated castor oil (Cremophor EL) 50% and dehydrated alcohol and the dose was diluted in either 0.9% sodium chloride or 5% dextrose at concentrations of 0.6 to 1.2 mg/ml. We have noted 3 patients with previously unreported cutaneous manifestations which we believe are taxol related and also report our overall complication rate with the administration of taxol by peripheral intravenous lines.

Antineoplastic Agents, Phytogenic↗
PubMed1995

The synthesis and opioid receptor binding affinities of analogues of dermorphin and its N-terminal tetrapeptide fragment with dibasic acids in position 2.

Analysis of possible mu opioid receptor active conformations for dermorphin suggested that the topographical location of the tyramine moiety of the N-terminal tyrosine can be simulated with the phenol of tyrosine or desamino-tyrosine (4-hydroxyphenylpropionic acid) and a basic group located on the side chain of a dibasic acid residue located in position 2. The biological properties of respective analogs with D- or L-arginine, and D- or L-lysine in the position 2 of dermorphin or desamino-dermorphin and their N-terminal tetrapeptide fragments, has provided evidence in support of this prediction, and questions the dogma that an N-terminal tyrosine is a necessary element for opioid agonist peptides.

Amino Acid Sequence↗
PubMed1995

Adolescents and Norplant: preliminary findings of side effects.

PURPOSE: The purpose of this study was to investigate side effects such as menstrual irregularities, weight gain, and blood pressure changes among adolescent females who had been implanted with Norplant eight or more months. METHOD: A retrospective chart review was completed on adolescents who received care through an outpatient adolescent gynecology service. Subjects (n = 110) with an average age of 17.2 years were implanted with Norplant between March 1991 and February 1992. The mean length of time since implantation was 12.7 months and 64% were African-American. Data collected included: dates of all medical visits; presence of acne, mood changes, and menstrual patterns following implantation. Measurements of blood pressure and weight were taken at implantation and at all subsequent visits. RESULTS: Weights for Caucasian females at the last visit were significantly higher than at baseline (P < .02). With regard to the African-American females' weight, significant differences were found between baseline weight and each follow-up visit. Although we could not determine the bleeding patterns in 22% of our study sample, almost 40% of the adolescent females followed reported their bleeding to be light as well as regular and cyclic. CONCLUSION: Weight gain was the most frequently observed side-effect of Norplant in adolescents in this study.

Adolescent↗
PubMed1995

Maternal influence on the decision to adopt Norplant.

PURPOSE: To examine maternal influence and related variables on adolescents' decision to adopt Norplant. METHODS: A prospective study of 121 adolescent females who received Norplant through a hospital-based outpatient adolescent gynecology service. Each patient completed self-report questionnaires about her decision process, sexual behaviors and standardized measures of depression and anxiety at their insertion appointment or first-follow-up appointment. RESULTS: Almost 40% of the sample reported that their mother significantly influenced their decision to use Norplant and 61% of all patients stated that they had informed their mother of their choice of this contraceptive method. Through logistic regression, six variables were found to be significantly associated with mother as the most important decision source. These included: obtaining information about Norplant from a parent, maintaining the same sexual partner, past pill use, and not knowing other adolescents who boast about using the Norplant system. CONCLUSION: These data suggest that when parental consent is not required, adolescent females disclose sensitive information regarding choice-making to their mothers when they decided to adopt Norplant.

Adolescent↗
PubMed1995

Rational prescribing and interpractitioner variation. A multilevel approach.

There are marked geographical variations in rates of medical and surgical intervention at every level of aggregation and in every aspect of medical practice. These data raise a range of important theoretical, methodological, and policy issues. Much the same pattern of variation characterizes the prescription and consumption of therapeutic drugs. Data from a survey of general practice in New Zealand confirm the existence of extensive variability in prescribing. Multilevel techniques are deployed to isolate the specific interpractitioner element in this variability. Controlling for patient, diagnostic, and practitioner variables improves the predictive power of the model but does not reduce the extent of interpractitioner variability in prescribing rates. The existence of such variability raises questions about the role of clinical uncertainty and professional autonomy in the promotion of rational therapeutics in medical practice.

Adolescent↗
PubMed1995

Nuclear and cytoplasmic dynamics of sperm penetration, pronuclear formation and microtubule organization during fertilization and early preimplantation development in the human.

This report describes spatial and temporal aspects of sperm penetration and intracytoplasmic migration, pronuclear evolution and the specificity of presyngamic opposition, stage-specific changes in cytoskeletal organization and the relative contribution of maternal and paternal components to mitotic spindle formation. These studies involved observations of living human oocytes during conventional insemination in vitro and after intracytoplasmic deposition of spermatozoa, analysis of chromatin organization and distribution during pronuclear evolution, and detection of actin and alpha-, beta- and gamma-tubulin by confocal immunofluorescence microscopy. Immature and mature oocytes, penetrated but unfertilized oocytes, fertilized but arrested eggs, and cleavage-stage embryos from normal and dispermic fertilizations were examined. The results demonstrate that sperm nuclear migration to the maternal perinuclear region is rapid and linear, occurs in the absence of a detectable cytoskeletal system and appears to be assisted by an unusual configuration of the sperm tail principal piece which results from either retained intracytoplasmic motility or the process by which the sperm tail is progressively incorporated into the oocyte. Our findings also show a specificity of pronuclear alignment that is associated with a polarized distribution of both maternal and paternal chromatin, and with the position of the sperm centrosome and the presence of microtubules nucleated from this structure. The results also indicate that a maternal microtubule nucleating capacity is present in the immature oocyte but is apparently inactive until spindle formation. The poles of the first mitotic spindle appear to be derived from the sperm centrosome, although some maternal contribution cannot be excluded. The sperm tail and centrosome persist in a single cell through the cleavage stages, and the latter serves as a prominent site of cytoplasmic microtubule nucleation. The results provide a detailed understanding of the cellular and nuclear morphodynamics of the human fertilization process and indicate subtle defects that may be responsible for early developmental failure.

Cell Nucleus↗
PubMed1995

Evolution of the sperm aster after microinjection of isolated human sperm centrosomes into meiotically mature human oocytes.

This study examined the feasibility of isolating and transferring the centrosome-containing region of spermatozoa to mature human oocytes. The findings demonstrate that individual sperm centrosomes can be transferred and are capable of nucleating maternal tubulin to form a well-developed sperm aster in the recipient oocyte. The results are discussed with respect to centrosome function in early human development and applications in clinical in-vitro fertilization in the treatment of certain forms of male factor infertility.

Cell Fractionation↗
PubMed1995

Letter from abroad.

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Ambulatory Care Facilities↗
PubMed1995

Characterization of symptoms in children with recurrent abdominal pain: resemblance to irritable bowel syndrome.

We sought to prospectively characterize and compare the symptoms of children > or = 5 years of age with recurrent abdominal pain to previously established criteria for irritable bowel syndrome (IBS) in adults. For all eligible subjects, a detailed questionnaire concerning characteristics of abdominal pain and defecatory pattern was completed at presentation. In addition, a battery of screening tests was performed and additional evaluation was done at the discretion of their physician. In all, 227 subjects fulfilled the entrance criteria, but 56 were subsequently excluded because of diagnoses of inflammatory bowel disease (nine cases), lactose malabsorption (46 cases), or celiac disease (one case). Of the remaining 171 patients, 117 had IBS symptoms. In the IBS subjects, lower abdominal discomfort (p < 0.001), cramping pain (p < 0.0009), and increased flatus (p < 0.0003) were more common, whereas dyspeptic symptoms such as epigastric discomfort (p < 0.003), pain radiating to the chest (p < 0.009), and regurgitation (p < 0.02) were more common in the non-IBS subjects. Our study not only confirms the clinical heterogeneity of children with recurrent abdominal pain but also concomitantly demonstrates that most children with this disorder have symptoms that fulfill the standardized criteria for IBS in adults. The identification of subgroups of children with recurrent abdominal pain can provide a framework for the diagnosis of functional bowel disease as well as establish the need for invasive and expensive tests.

Abdominal Pain↗
PubMed1995

Clinical evaluation of various selected ELISA kits for the detection of anti-DNA antibodies.

Fifty four coded sera, 38 from eight patients with systemic lupus erythematosus (SLE), four from one patient with systemic vasculitis, one from one patient with polyarthritis and 11 normal controls were tested for anti-dsDNA antibodies using seven commercial enzyme linked immunosorbent assays (ELISA) and the radioimmunoassay method (RIA) routinely used in our unit. Sensitivity, specificity and predictive values were tested for both SLE diagnosis and disease activity. Using anti-dsDNA antibodies as a diagnostic test for SLE there were differences in sensitivity (from 66% to 95%), specificity (from 75% to 100%), predictive positive values (from 89% to 100%) and predictive negative values (from 50% to 87%) among ELISA kits. The RIA method was either more specific or equal to ELISA kits. Using 'equivocal' values as positive values an increase in sensitivity was observed but at the expense of specificity. Similar differences and trends were observed when the results were used as a measure for disease activity. This suggests that there are differences in sensitivity, specificity and predictive values among ELISA kits both in the diagnosis of SLE as well as in the determination of disease activity.

Adolescent↗
PubMed1995

Anticardiolipin antibodies in two elderly subpopulations.

Previous studies have reported that the prevalence of certain autoantibodies is nonspecifically elevated in elderly subjects due to immunoscenescence. This study was undertaken to assess the prevalence of anticardiolipin antibodies (aCL) in two elderly subpopulations: Two hundred and eighteen elderly were included in this study; 63 healthy elderly had a prevalence of anticardiolipin antibodies of zero; 155 unselected frail elderly were prospectively evaluated and the prevalence of anticardiolipin antibodies in this group was found to be significantly increased at 18.7%. Subdivision of this group into those elderly clinically assessed as suffering from dementia showed a prevalence of 26.5% and stroke a prevalence of 31.6%. Both were found to be statistically significantly increased when compared with both the healthy and frail elderly population. Subdivision of the dementia patients into those suffering from multi-infarct type dementia (MID) and those suffering from Alzheimer's type dementia (AD) showed an association of 44% and 20%, respectively. The association of MID with aCL was significant. This study demonstrates therefore that anticardiolipin antibodies are not nonspecifically elevated in elderly subjects but are significantly elevated in elderly subjects with strokes and multiple infarct dementia.

Aged↗