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Biomedical subjects

P Walker

Publications and source records attributed to P Walker.

At least 127 records · Page 7Linked to original sources
PubMed1994

The Dübendorf Study: a population-based investigation on normal values of blood pressure self-measurement.

There is evidence that self-measurement of BP increases precision, reproducibility and prognostic value of BP measurement. However, generally accepted normal values for BP values obtained by self-measurement are still missing. The present study was undertaken to investigate differences between office and self-measured blood pressure; 503 randomly selected inhabitants (265 men and 238 women, age 20-90 years, mean age 46.5 +/- 12.9 years) of the small town of Dübendorf in Switzerland were studied. The subjects were not preselected according their BP levels, only patients taking antihypertensive drugs were excluded. Self-measurement was performed at home by the subjects during 14 days in the morning between 6 and 8 am and in the evening between 6 and 8 pm (mean of 26.7 measurements). Office BP was taken before and after the two week period. Mean office BP (130.0 +/- 16.5/82.1 +/- 11.1 mmHg) was significantly (P < 0.01) higher than mean self-measured BP (123.1 +/- 14.6/77.6 +/- 10.7 mmHg). There was no significant difference between first and second office BP measurement. Morning self-measured BP was lower than evening pressure (delta 4.0/1.4 mmHg, both P < 0.01) and the mean was taken for comparison with office BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Fulminant ulcerative colitis in pregnancy.

Most pregnant women with a history of ulcerative colitis will have a normal pregnancy and deliver a healthy child. Medical therapy can usually control the disease in those patients who experience an exacerbation, and only a minority of women progress to severe colitis necessitating surgery in pregnancy. We describe a woman who developed colitis in the first weeks of pregnancy that initially responded to steroid enemas. She then relapsed and progressed to severe colitis requiring a sub-total colectomy in the 26th wk of pregnancy. This was complicated by intra-abdominal sepsis and an abscess that required drainage. She successfully completed pregnancy, to be delivered of a healthy daughter in the 32nd wk of pregnancy.

Adult↗
PubMed1993

T- and B-cell functions and epitope expression in nonhuman primates immunized with simian immunodeficiency virus antigen by the rectal route.

Transmission of human immunodeficiency virus (HIV) in North America and Europe occurs most commonly through the rectal mucosa during homosexual intercourse. The simian immunodeficiency virus (SIV) macaque model has been used to investigate rectal immunization. The vaccine used was a recombinant SIV gag p27 expressed as hybrid Ty virus-like particles (Ty-VLP). Sequential ororectal (OR) mucosal immunization was compared with i.m. immunization. Whereas both routes of immunization induced serum IgA and IgG p27 antibodies, only OR immunization induced rectal secretory IgA antibodies. Specific CD4+ T-cell proliferative responses to stimulation with p27 were found after i.m. immunization only in the blood and spleen, but after OR immunization they were found in the internal iliac and inferior mesenteric lymph nodes in addition to the blood and spleen. T-cell epitope mapping of the proliferative responses of short-term cell lines (STCLs) grown from peripheral blood or lymphoid cells revealed a major epitope within the polypeptide 121-150 after either route of immunization. Two minor T-cell epitopes were found within peptide 41-80 in STCLs from splenic and circulating cells. B-cell epitope mapping of serum or biliary IgA and IgG antibodies revealed two overlapping or adjacent immunodominant epitopes to the T-cell epitopes within the polypeptides 121-170 and 51-90. The results suggest that rectal augmented by oral immunization with a recombinant particulate antigen in nonhuman primates elicits secretory IgA and to a lesser extent IgG responses in the draining lymph nodes and the rectal mucosa, whereas systemic immunization targets predominantly splenic and circulating T- and B-cell responses. These findings may have important implications in the strategy of designing vaccines in prevention of homosexual transmission of HIV infection.

Administration, Rectal↗
PubMed1993

The effect of visual similarity on short-term memory for spatial location: implications for the capacity of visual short-term memory.

Evidence from the recency effect suggests that visual short-term memory is limited to preserving information about a single pattern. Three experiments explored the capacity of visual short-term memory using a task which involved presenting a series of patterns in a random spatio-temporal sequence and probing memory for the spatial location of one of them. Experiment 1 used sequences of quasi-random block patterns which were either visually similar or dissimilar. Serial position curves showed a single-item recency effect. However, there was also a deleterious effect of visual similarity for the earlier patterns, indicating that visual short-term memory was supporting their retention. Experiment 2 showed that performance was unaffected by articulatory suppression, confirming that phonological coding is not an important factor in the localisation task. Experiment 3 switched to letter stimuli and, because of the known tendency for this type of stimulus to be phonologically recoded, required articulatory suppression. Letters were shown in a customised form in sequences which were either visually similar or visually dissimilar. The results replicated experiment 1 in showing restricted recency combined with an effect of visual similarity extending across earlier list items. When the same letters were shown in standard form, the recency effect remained but the similarity effect disappeared, ruling out possible interpretations in terms of semantic as well as phonological coding. It is concluded that the recency effect gives a misleading indication of the capacity of visual short-term memory. The visual similarity effect suggests that it is capable of supporting the retention of several patterns.

Adult↗
PubMed1993

High level expression of human neuropeptide Y receptors in mammalian cells infected with a recombinant vaccinia virus.

Neuropeptide Y (NPY) is a 36 amino acid peptide present in the central and peripheral nervous system. Numerous studies point to a role of NPY in cardiovascular regulation. NPY effects are mediated through stimulation of specific cell surface G protein-coupled receptors. To allow biochemical studies of the receptor and of its interaction with the ligand, we have developed a potent expression system for NPY receptors using a recombinant vaccinia virus. A human NPY receptor cDNA was fused to a strong vaccinia virus promoter and inserted into the viral genome by homologous recombination. Recombinant viruses were isolated and tested for their ability to induce NPY binding site expression following infection of mammalian cell lines. Using saturation and competition binding experiments we measured a Bmax of 5-10 x 10(6) NPY binding sites per cell. The Kd for the binding of NPY is about 20 nM. Labelling of infected cells with a fluorochrome-labelled NPY indicated that the recombinant protein integrates into the cell membrane.

Base Sequence↗
PubMed1993

Failed extubation in the neonatal intensive care unit.

One of the roles of the pediatric otolaryngologist in the neonatal intensive care unit (NICU) is the assessment and management of the neonate who fails a trial of extubation. This paper reviews the recent 5-year institutional experience at The Hospital for Sick Children, Toronto, with neonates who failed extubation and who subsequently underwent diagnostic endoscopy. One hundred twenty-eight neonates from the NICU underwent diagnostic endoscopy. Of these, 58 neonates underwent diagnostic endoscopy for failure to extubate. Nine neonates were extubated after diagnostic endoscopy and retrial (16% of the series). Eleven neonates were extubated after additional endoscopic procedures (19% of the series). Twenty-four neonates underwent anterior cricoid split, of whom 20 or 83% (34% of the series) were eventually successfully extubated with no further airway intervention required during the study period (minimum 6 months' follow-up). Eleven neonates underwent tracheotomy (19% of the series). Four neonates underwent another external procedure to allow extubation (7% of the series). Three neonates died while still intubated (5% of the series). Our management of the neonate who fails a trial of extubation is discussed.

Clinical Protocols↗
PubMed1993

Identification of binding proteins for nuclear localization signals of the glucocorticoid and thyroid hormone receptors.

Nuclear entry of proteins the size of the glucocorticoid and thyroid hormone receptors appears to be mediated by an interaction of nuclear localization signals (NLSs) within the proteins and specific NLS-binding proteins. NLSs have been identified in the hinge region of both receptors. We have identified the cellular binding proteins of the glucocorticoid receptor NLS and the thyroid hormone receptor NLS after cross-linking of radiolabeled signal peptides to subcellular fractions. Two S49 lymphoma cytosolic polypeptides of 60 and 76 kilodaltons (kDa) were specifically bound to either the glucocorticoid or thyroid hormone receptor NLS. The two binding sites demonstrated saturable binding. A competitive binding assay showed that the binding sites were specific for NLSs and that a mutated NLS was a poor competitor for the binding of labeled glucocorticoid receptor NLS. However, competition studies with peptides unrelated to NLSs, yet resembling NLSs in that they had a net positive charge, revealed that the 60-kDa entity demonstrated greater specificity for binding to NLSs than did the 76-kDa polypeptide. Glucocorticoid receptor NLS and thyroid hormone receptor NLS-binding proteins of 60 and 76 kDa were also identified in nuclear fractions. Although the unoccupied glucocorticoid receptor resides in the cytoplasm, while the unoccupied thyroid hormone receptor is always found in the nucleus, the hinge NLS interactions do not specify these different localizations of the unoccupied receptors. Rather, the data support roles for the hinge NLS in general steps of nuclear import and the 60-kDa cross-linked product as a chaperone of both receptors into the nucleus. Its cellular localization also suggests a role for the 76-kDa cross-linked product as a chaperone, but its relatively less stringent binding specificity may indicate that this polypeptide has a different physiological function.

Adrenalectomy↗
PubMed1993

[Abnormalities of the muscular bioenergetics in Steinert's disease].

The thenar muscles and gastrocnemius of a patient with myotonic dystrophy were investigated, at rest, by phosphorus nuclear magnetic resonance spectroscopy. A decrease in phosphocreatine level and an increase in inorganic phosphate and phosphodiester levels were found in the gastrocnemius, which was clinically spared, whilst the thenar muscles, which were wasted and affected by myotonia, exhibited only an increased inorganic phosphate level and an elevated pH. These findings were comparable with those found in other muscular disorders, such as Duchenne's and Becker's dystrophies, as well as in limb girdle dystrophy. They suggested that the abnormalities observed were unrelated to myotonia or wasting, and the possibility of a secondary mitochondrial disorder in myotonic dystrophy, is to be considered.

Adult↗
PubMed1993

Low-frequency vibration emitted from unstable hip in human neonate.

Developmental dysplasia of the hip (DDH) continues to be an orthopedic enigma. Some authors still believe it is a purely birth phenomenon. Even with widespread birth screening, however, DDH continues to become evident later than three months of age, long after a satisfactory outcome can be guaranteed. In an effort to reduce the number of late manifestations, the authors have developed a noninvasive form of screening for DDH called vibration arthrometry. Five hundred neonates were examined in local maternity hospitals, according to the guidelines of Ortolani and Barlow. The new method involves the attachment of miniature accelerometers around the infant's pelvis. Using this method, it was possible to elicit vibration events from approximately one fourth (255 hips) of the hips tested; vibrations were recorded from normal hips (125), from "clicky" hips (128), and from unstable hips (two). Differences between "nil-felt" (clinically silent) and "click-felt" (palpable clicking on testing) were significant. Vibration testing can be seen as an aid in the manual palpation necessary to detect this crippling condition.

Female↗
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↗