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Biomedical subjects

P Walker

Publications and source records attributed to P Walker.

At least 19 recordsLinked to original sources
PubMed1992

Induction of mucosal and systemic immunity to a recombinant simian immunodeficiency viral protein.

Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant, particulate SIV antigen. Vaginal, followed by oral, administration of the vaccine elicited three types of immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4+ T cell proliferation and helper function in B cell p27-specific IgA synthesis in the genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4+ T cell proliferative and helper functions in the circulating blood.

Administration, Oral↗
PubMed1992

Role of affect and personality in gastric acid secretion and serum gastrin concentration. Comparative studies in normal men and in male duodenal ulcer patients.

The role of mood state (affect) and personality on basal acid secretion and basal serum gastrin concentrations were examined in seven healthy men and eight patients with duodenal ulcer. In each subject, gastric secretion and affect were assessed simultaneously on 5 separate days. None of 10 self-reported affect variables correlated with daily fluctuations in basal acid secretion in either group. Three variables (tension, conflict, and anxiety) correlated significantly with serum gastrin fluctuations in normal subjects, but these relationships were not present in patients with ulcer, who were hypergastrinemic regardless of their affective state. The degree to which serum gastrin fluctuated was unrelated to personality, as assessed by Minnesota Multiphasic Personality Inventory. On the other hand, several Minnesota Multiphasic Personality Inventory scales correlated with the degree of variability in basal acid secretion, including scales that measured impulsivity and social isolation/alienation. These studies indicate that serum gastrin concentrations are related to affective state in normal men, that this relationship is altered in men with duodenal ulcer, and that certain personality traits, such as impulsivity and social isolation, are associated with more labile basal acid secretion rates.

Adult↗
PubMed1992

Thyroid hormone and androgen regulation of nerve growth factor gene expression in the mouse submandibular gland.

The nerve growth factor (NGF) content of the mouse submandibular gland (SMG) is under hormonal control and is modulated by both thyroid hormones (TH) and androgens. The sexual dimorphism of the gland is well documented. In the adult male mouse, the SMG contains 10 times more NGF compared to the female. Conversely, castration of male mice reduces the SMG NGF levels to those found in control females. In order to determine the locus at which androgens and TH exert their effect on NGF gene expression in the SMG, steady-state NGF mRNA levels were determined. Daily treatment of adult female mice with TH for 1 week increased NGF mRNA levels 6-fold. Androgen treatment produced a 20-fold increase in SMG NGF mRNA, which was comparable to levels detected in the control adult male SMG. The effect of TH on NGF mRNA levels was time-dependent and coincided with the increase in NGF protein concentrations. At 48 h after a single TH injection, NGF mRNA levels (measured in SMG total RNA) increased 2-4-fold, while heteronuclear (hn) RNA levels were increased 1.5-2-fold. The NGF gene transcription rate was determined by run-on assay following TH treatment. A small but significant 2-fold induction by TH of NGF gene transcription was found at 24-48 h. Cytoplasmic RNA prepared from the same SMGs used in the run-on experiments was tested by S1 nuclease protection; NGF cytoplasmic RNA was increased 7-fold in the SMGs of females treated with TH 48 h previously. These results demonstrate that the effect of TH on NGF gene expression is due in part to an induction of NGF gene transcription. The discrepancies observed between transcription rate and mRNA levels suggest that the major effect of TH is at the post-transcriptional level, possibly mRNA stabilization. The time required to observe an induction of TH on NGF gene transcription is suggestive of an indirect effect, possibly through the induction by TH of another protein which in turn activates the NGF gene.

Anabolic Agents↗
PubMed1992

Production and characterization of four anti-neuropeptide Y monoclonal antibodies.

Human neuropeptide Y (hNPY) is a potent vasoconstrictor peptide of 36 aminoacid residues. We isolated hybridomas secreting four monoclonal antibodies directed against various epitopes of neuropeptide Y and studied their cross-reactivity with peptide YY (PYY) and the pancreatic polypeptide (PP), two peptides sharing sequence homologies with hNPY (respectively 70% and 50%). The antibody NPY02 is an IgG1 with a Ka of 5.5 x 10(10) liters/mol. It binds to the 11-24 region of NPY (IC50 = 2 x 10(-7)M), does not recognize PP but cross-reacts weakly with PYY. Antibodies NPY03 and NPY05 are IgG2 with respective Ka's of 6.7 x 10(9) and 2.5 x 10(10) liters/mol. They interact with a C-terminal epitope on NPY (NPY 27-34, IC50 = 2 x 10(-9) M for NPY03 and NPY 32-36, IC50 = 1 x 10(-9) M for NPY05). These two antibodies cross-react with PYY whereas only NPY05 binds PP. NPY05 is unable to bind the free acid form of neuropeptide Y. The 32-36 COOH free subpeptide is recognized 50,000 less efficiently by NPY05 than its amidated form. Antibody NPY04 is an IgG3 with a Ka of 3.8 x 10(8) liters/mol. It recognizes a N-terminal epitope between aminoacids 1 and 12 (IC50 = 2.5 x 10(-6) M). NPY04 interacts weakly with PYY but not detectably with PP. These results obtained with 4 different monoclonal antibodies demonstrate the presence of at least four epitopes on hNPY, two of them being continuous. These antibodies will be used to study the interaction of NPY with its receptor and to develop sensitive and specific assays for determination of NPY concentrations in biological fluids.

Amino Acid Sequence↗
PubMed1992

Inhibitory effect of neuropeptide Y on stimulated renin secretion of awake rats.

1. (1-36)-NPY is a vasoconstrictor peptide widely distributed in sympathetic nerve terminals. This peptide exerts an inhibitory action on renin release induced by various stimuli. Post-synaptic neuropeptide Y (NPY) receptors show a high affinity for (1-36)-NPY as well as for the agonist (Pro34)-NPY, while presynaptic receptors bind preferentially (13-36)-NPY. 2. This study was undertaken to assess whether the NPY induced renin suppression in awake normotensive rats infused with the beta-adrenoceptor stimulant isoproterenol is mediated by activation of pre- or post-synaptic receptors. 3. Non-pressor doses of (1-36)-NPY and (Pro34)-NPY markedly attenuated the renin secretion triggered by isoproterenol whereas (13-36)-NPY had no effect. This suggests that the effect of NPY on renin release is due to the stimulation of post-synaptic receptors. However it remains unknown whether NPY acts directly on juxtaglomerular cells or indirectly by modifying intraglomerular haemodynamics.

Animals↗
PubMed1992

Thyroid hormones precociously increase nerve growth factor gene expression in the submandibular gland of neonatal mice.

The developmental regulation of the expression of nerve growth factor (NGF) was studied in the mouse submandibular gland (SMG). Having demonstrated that, in the neonatal mouse, maturation of the SMG can be accelerated by treatment with thyroid hormones, with the resulting induction in SMG content of NGF, studies were undertaken to further examine the locus of thyroid hormone action. Because of the sexual dimorphism of the SMG, both male and female neonatal mice were used. NGF messenger RNA levels were undetectable in SMGs from untreated immature mice, while hybridization to total RNA from T4-treated mice was easily observable for NGF complementary DNA. Treatment for 14 days compared to 7 days resulted in a 7-fold increase in SMG NGF mRNA levels. A signal was obtained in 21-day-old control mice using S1 nuclease protection analysis; T4 increased NGF mRNA levels by 100-fold in both male and female immature mice. Heteronuclear RNA levels were induced 20-fold by T4. No sex differences were readily observable. Determination of the effect of thyroid hormone treatment on SMG NGF gene expression by nuclear run-on assay demonstrated a significant transcriptional effect of T4. Initial experiments using the pmngf6 vector, which is a pBR322-derived probe containing the full length NGF cDNA, showed a 2.5-fold induction of gene transcription. When an internal fragment of pmngf6 was subcloned into pTZ18R, thus removing the dC/dG tails contained in pmngf6, the background hybridization was considerably reduced and a 12.5-fold induction in NGF gene transcription was obtained after T4 treatment of neonatal mice. The results show that thyroid hormones increase NGF gene expression in the SMG of the immature male and female mouse. This effect is due in part to a significantly enhanced rate of gene transcription.

Animals↗
PubMed1992

Energetic metabolism in hypothyroid skeletal muscle, as studied by phosphorus magnetic resonance spectroscopy.

Phosphorus nuclear magnetic resonance spectroscopy was used to investigate the muscle bioenergetics in different hypothyroid states. Using the thenar muscle group as reference, 2 patients with chronic and severe hormonal deficiency, 3 patients with subacute hypothyroidism, and 8 patients with moderate thyroid insufficiency with isolated high blood TSH levels were studied at rest, during exercise, and during subsequent recovery. The patients were compared with 15 control subjects. Only 1 patient presented a clinical myopathy. The intracellular pH and the relative measurements of inorganic phosphate, phosphocreatine, phosphodiesters, and ATP were directly calculated from phosphorus spectra. Resting muscle showed a significant rise in the inorganic phosphate to ATP ratio. In working hypothyroid muscle, a more important decrease in phosphocreatine levels was noted in patients with chronic and subacute thyroid deficiency, while the intracellular pH fall was greater in all hypothyroid patients than in control subjects. The phosphocreatine recovery rate was lower in all deficient patients, reflecting a probable mitochondrial metabolism impairment. These results are consistent with a defect of the high energy phosphate metabolism in hypothyroidism, even in moderate or recent hormonal deficiency.

Adenosine Triphosphate↗
PubMed1992

Analysis of clinical experience with a new twist lock connectology.

The DextroLyte II (Dex II) Peritoneal Dialysis System was designed to improve safety and convenience in dialysis therapy. Connectors introduced with this system have a threaded recessed male connector with a corresponding female counterpart. Products are provided for CAPD, Single Use Y, Long Life Y and CCPD. Safety and convenience features intended to reduce peritonitis rates and improve patient acceptance include the following: 1. Connectors with threaded male and corresponding female counterparts which provide a dual seal 2. Easy-to-break frangible which seals the solution bag until ready for use 3. A flange on the connector ensures proper hand placement by providing a safety shield to prevent contamination during connection 4. A hinged shield containing an impregnated povidone-iodine sponge easily snaps around the bag connector 5. A Quick Disconnect Clamp (QDC) provides external occlusion permitting safe disconnection for bagless techniques without opening the system 6. A standard medication port provides easy access for administration of intraperitoneal medication Results of a multicenter study performed in nine centers are as follows: Total patient participants 121 Total patient months 1207 Overall peritonitis rate 1 episode in 43 patient months We conclude that the Dex II peritoneal dialysis systems provide safe dialysis therapy as evidenced by the exceptional peritonitis rates. Patient acceptance has been excellent due to the inclusion of the safety and convenience features described.

Evaluation Studies as Topic↗
PubMed1992

Clinical experience and comparative analysis of the standard and fast peritoneal equilibration tests (PET).

The fast peritoneal equilibration test (PET) has been proposed as a substitute procedure for the standard PET because it is less expensive and less time consuming since fewer samples must be drawn. This study was undertaken to compare the fast and standard PETs to determine if the fast PET is a viable alternative. Fifteen patients participated in the study. Results from the standard PETs indicate 13 patients had average permeability and 2 patients had high transport. Corresponding fast PETs indicate 10 patients with average permeability, 2 patients with high transport, 1 patient had discrepancies between the D/P ratios and drain volume, and 2 patients were noncompliant and did not complete the fast PET. We conclude that the fast PET is a valid screening tool to evaluate peritoneal membrane permeability in patients who have previously undergone a standard PET. It is cost effective and timesaving. The test is easily invalidated if patients fail to comply with instructions for the test. The fast PET is primarily useful as a screening device to determine whether permeability has changed.

Adult↗
PubMed1992

[24-hour blood pressure measurement in children and adults with type I diabetes mellitus: relation to duration of diabetes, obesity, albuminuria].

Early antihypertensive therapy in patients with diabetes mellitus reduces cardiovascular risk and improves long-term prognosis. Therefore, mildly hypertensive patients have to be discriminated from patients with "white coat" hypertension. 24-h-blood pressure profiles were recorded in 153 patients (age 7.9-26 years, duration of diabetes 0-21 years). The fraction of elevated blood pressure readings allows to classify these profiles independent of the age of the patient. This parameter was not related to either duration of diabetes or nocturnal excretion of albumin. In contrast, blood pressure correlated significantly with age- und sex-adjusted weight (z-score). Among 38 patients with elevated blood pressure recordings during outpatient visits, 24 (63%) displayed a normal 24-h-profile (less than 30% of blood pressure values are above the 95% limit for the respective age). These data indicate that hypertension might be independent of the metabolic derangement during the first years of diabetes.

Adolescent↗
PubMed1991

Auto-immune spondylodiscitis associated with collagen induced arthritis in rats: high field MRI findings.

The spinal involvement of the tail was studied in Wistar Furth rats immunized with bovine native type II collagen. Focal caudal autoimmune spondylodiscitis occurred 5 weeks after sensitization, as assessed histopathologically. High field Magnetic Resonance Imaging (MRI) was useful in depicting these caudal abnormalities that were related to juxta-diskal enthesitis. The occurrence of such inflammatory enthesopathies could serve as an experimental approach for physiopathological and therapeutical studies of spondylarthropathies.

Animals↗
PubMed1991

Management of airway obstruction in the Pierre Robin sequence.

A 10-year retrospective study of the management of airway obstruction in 26 infants with Pierre Robin sequence was made. It was not possible when the infant was first seen to assess the future severity of the airway obstruction but later 3 distinct groups could be identified according to the airway management which had become necessary. The deaths from respiratory obstruction indicate the prime importance of airway management. Laryngoscopy for intubation or endoscopic evaluation was often difficult and sometimes could not be achieved. 'Awake intubation' without general anesthesia has proved to be safer and less difficult using a special purpose slotted laryngoscope. Airway management should be individualized following the progressive sequence of posturing in the prone position, nasopharyngeal tube, endotracheal intubation and tracheotomy until successful control is achieved as indicated by the clinical features and pulse oximetry.

Airway Obstruction↗
PubMed1991

The role of neuropeptide Y in cardiovascular regulation.

Neuropeptide Y (NPY) is a 36 amino acid peptide present in the brain, the adrenal medulla and peripheral sympathetic nerves. The localization and mode of release of NPY led to the proposal that this peptide plays an important role in modulating the contribution of the sympathetic nervous system to blood pressure control. In this paper Bernard Waeber and colleagues review the current knowledge about the mechanisms involved in NPY signal transduction and the different mechanisms whereby NPY, released by the peripheral nervous system, may influence vascular tone and cardiac function.

Animals↗
PubMed1991

The role of articulation in the parsing and retention of letter strings in tachistoscopic free recall.

In Mewhort and Campbell's (1981) model of visual word recognition, a scan-parse mechanism transfer information from a character buffer to a short-term store and is largely responsible for the familiarity effects observed in tachistoscopic free recall. Although Mewhort and Campbell do not elaborate on the role of articulation in this task, they do suggest that the scan-parse mechanism acts prior to any involvement of articulatory processes (see Mewhort & Campbell, 1980). However, proponents of working memory (see Baddeley, 1986) are clear that articulation is necessary for the transfer of visual information to a phonological short-term store. In order to clarify the role of articulation in the parsing and retention of letter string, we asked subjects to undertake a tachistoscopic free-recall task, involving first- and fourth-order letter strings, with and without articulatory suppression and/or unattended speech. Unattended speech was observed to interfere with recall, but only when subjects were free to articulate the strings. This implies that subjects were retrieving information from the phonological store and that articulation is necessary for the registration of visual information in this store. The lack of interaction between order-of-approximation and suppression supports the view that the scan-parse mechanism acts independently of articulation. It appears, therefore, that letter strings are parsed at a stage preceding their transfer of the pharmacological store. Finally, the results indicate that subjects are able to draw directly on a representation of the parsed components of a letter string and may do so when phonological storage is difficult.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗