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Biomedical subjects

K West

Publications and source records attributed to K West.

At least 37 records · Page 2Linked to original sources
PubMed2000

Overexpression of the human VPAC2 receptor in the suprachiasmatic nucleus alters the circadian phenotype of mice.

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, and growth hormone-releasing hormone. Microinjection of VIP or PACAP into the rodent suprachiasmatic nucleus (SCN) phase shifts the circadian pacemaker and VIP antagonists, and antisense oligodeoxynucleotides have been shown to disrupt circadian function. VIP and PACAP have equal potency as agonists of the VPAC(2) receptor (VPAC(2)R), which is expressed abundantly in the SCN, in a circadian manner. To determine whether manipulating the level of expression of the VPAC(2)R can influence the control of the circadian clock, we have created transgenic mice overexpressing the human VPAC(2)R gene from a yeast artificial chromosome (YAC) construct. The YAC was modified by a strategy using homologous recombination to introduce (i) the HA epitope tag sequence (from influenza virus hemagglutinin) at the carboxyl terminus of the VPAC(2)R protein, (ii) the lacZ reporter gene, and (iii) a conditional centromere, enabling YAC DNA to be amplified in culture in the presence of galactose. High levels of lacZ expression were detected in the SCN, habenula, pancreas, and testis of the transgenic mice, with lower levels in the olfactory bulb and various hypothalamic areas. Transgenic mice resynchronized more quickly than wild-type controls to an advance of 8 h in the light-dark (LD) cycle and exhibited a significantly shorter circadian period in constant darkness (DD). These data suggest that the VPAC(2)R can influence the rhythmicity and photic entrainment of the circadian clock.

Amino Acid Sequence↗
PubMed2000

Adjuvant use of epsilon-aminocaproic acid (Amicar) in the endovascular treatment of cranial arteriovenous fistulae.

We report our experience with the use of the antifibrinolytic agent epsilon-aminocaproic acid (EACA), Amicar, as an adjuvant to endovascular treatment of cranial arteriovenous fistulae. We also review applications of antifibrinolytic agents to neurovascular disorders and discuss the mechanism of action, dosing strategy, contraindications, and possible complications associated with the use of EACA. We identified 13 patients with cranial arteriovenous fistulae (five direct carotid cavernous fistulae [CCF], seven dural arteriovenous fistulae [DAVF], and one vein of Galen malformation) who received EACA as an adjunct to endovascular treatment. In all cases embolic coils were the primary embolic agent. We reviewed the modes of initial endovascular therapy and angiographic findings immediately thereafter and the response to EACA. Two direct CCF and two DAVF were completely thrombosed on follow-up angiography, and two DAVF demonstrated diminished flow after EACA therapy. Seven fistulae did not respond to EACA. Four of eight tightly coiled fistulae thrombosed, while none of five loosely coiled fistulae thrombosed. None of four cases with a residual fistula separate from the coil mass underwent thrombosis with EACA, while four of nine cases without a separate fistula thrombosed. There was no morbidity related to EACA therapy. EACA may thus be useful as an adjunct to endovascular treatment of cranial arteriovenous fistulae. Loose or incomplete coil packing of the fistula predicts a poor response to EACA therapy.

Adolescent↗
PubMed2000

Is the grass greener? Early results of the Nuss procedure.

BACKGROUND/PURPOSE: Minimal access surgery (MIS, Nuss Procedure) is gaining acceptance rapidly as the preferred method for pectus excavatum repair. This shift in operative management has followed a single institution's evaluation of the procedure. This report describes an additional experience with the Nuss procedure. METHODS: Twenty-one patients with pectus excavatum underwent repair by the Nuss Procedure. The patients ranged in age from 5 to 15 years (average, 8.2 years). There were 19 boys and 2 girls. RESULTS: In 1 patient (age 5 years) the MIS procedure was aborted because of persistence of chest wall asymmetry. The other 20 patients had completion of their procedure without intraoperative complication. The operating times ranged from 45 to 90 minutes; however, there was an additional anesthetic set-up time (average, 45 minutes). All cases utilized a single support bar (11 to 17 inches). Patients underwent extubation in the operating room and were admitted to a ward bed with an epidural catheter in place for pain control and received intravenous analgesia. The hospital stay ranged from 4 to 11 days and averaged 4.9 days. Early postoperative complications included ileus (n = 1), bilateral pleural effusion (n = 2), atelectasis (n = 1), fungal dermatitis (n = 1), pneumothorax (n = 1), and flipped pectus bar (n = 2). Delayed complications included flipped pectus bar (n = 2), marked pectus carinatum requiring bar removal (n = 1), mild carinatum (n = 1), mild bar deviation (n = 1), progressive chest wall asymmetry (n = 3) with 1 requiring bar removal and open pectus repair, pleural effusion (n = 1), and chronic persistent pain requiring bar removal (n = 1). The length of follow-up is 3 to 20 months with an average of 12.3 months. CONCLUSIONS: The Nuss Procedure is quick, minimally invasive, and a technically easy method to learn; however, our data indicate there is a significant learning curve. Although previous reports suggest that few complications occur, we believe further assessment of patient selection regarding age, presence of connective tissue disorder, and severe chest wall asymmetry are still needed. Long-term follow-up also will be required to assure both health professionals and the public that this is the procedure of choice for patients with pectus excavatum.

Adolescent↗
PubMed2000

Osseous morphology and spatial relationships of the temporomandibular joint: comparisons of normal and anterior disc positions.

The objective of this study was to determine differences in spatial relationships and osseous morphology between temporomandibular joints with normal and anterior disc positions. Magnetic resonance imaging was employed to determine disc position in 335 temporomandibular joints in 175 subjects (106 female and 69 male) between the ages of 7.27 years and 20.0 years (mean age: 13.08 years). Twelve tomographic variables were measured from preorthodontic tomograms of the same individuals. Tomographic data were cross-referenced with MRI data for those with normal and full anterior disc displacement. Independent sample t-tests revealed significant differences for all measures of joint space, condylar position, and morphology of the articular eminence (P < .05) between joints with normal disc position and with full anterior disc displacement. This study indicated that measures of joint space and eminence morphology might provide diagnostic information for the assessment of joint status in the adolescent population.

Adolescent↗
PubMed2000

After the call. The latest post-exposure medical management info.

Ensuring proper post-exposure medical evaluation and treatment remains essential for the health and wellness of your personnel, risk management and OSHA compliance. Departments must ensure that the medical provider designated to manage post-exposure treatment knows the current post-exposure medical treatment protocols and that the medical facilities involved offer the most up-to-date, fastest testing methods available. With all the new recommendations and testing methods, HCWs can receive accurate information post-exposure in a 24-hour time-frame. The HIV issue can be resolved in less than one hour. This is exciting progress.

Anti-HIV Agents↗
PubMed1999

The efficacy of modified-live bovine respiratory syncytial virus vaccines in experimentally infected calves.

The efficacy of modified-live (MLV) bovine respiratory syncytial virus (BRSV) vaccines and the correlates of vaccine-induced immunity were investigated in calves using a virulent experimental infection. Clinical disease and pulmonary pathology were significantly reduced, relative to unvaccinated controls, in calves vaccinated according to label directions with commercial multivalent MLV BRSV vaccines. In vitro assays of cellular immunity were more consistent correlates of vaccine associated protection than presence of post vaccination serum antibody. Most vaccinated calves shed virus, but peak virus titre was suppressed compared to unvaccinated controls, with clearance coincident with the simultaneous appearance of mucosal antibody, cytotoxic cells in the lung and anamnestic or primary serum antibody responses. Virus clearance in unvaccinated calves was coincident with the appearance of BRSV specific cytotoxic cells, before mucosal antibody was detected.

Animals↗
PubMed1999

Structure of the human VIPR2 gene for vasoactive intestinal peptide receptor type 2.

The VPAC(2) (vasoactive intestinal peptide (VIP)(2)) receptor is a seven-transmembrane spanning G protein-coupled receptor which responds similarly to VIP and pituitary adenylate cyclase activating polypeptide (PACAP) in stimulating cAMP production. Recently, we reported the localisation of the human VPAC(2) receptor gene (VIPR2) to chromosome 7q36.3 (Mackay, M. et al. (1996) Genomics 37, 345-353). Here, we describe the characterisation of the VIPR2 gene structure and promoter region. The VIPR2 gene is encoded by 13 exons, the initiator codon of the 438 amino acid open reading frame is located in exon 1 and the termination signal and a poly-adenylation signal sequence are located in exon 13. The 5' untranslated region extends 187 bp upstream of the initiator codon and is extremely GC-rich (80%). The poly-adenylation signal is located 2416 bp downstream of the stop codon. Intron sizes range from 68 bp (intron 11) to 45 kb (intron 4) and the human gene spans 117 kb.

5' Untranslated Regions↗
PubMed1999

Neoral monitoring by simplified sparse sampling area under the concentration-time curve: its relationship to acute rejection and cyclosporine nephrotoxicity early after kidney transplantation.

BACKGROUND: Cyclosporine (CsA) dosing is traditionally based on trough blood levels (C0) rather than area under the concentration-time curve (AUC), although AUC correlates better with posttransplantation clinical events. For Neoral, AUC based on limited sampling correlates closely with full 12-hr AUC. The purpose of our study was to correlate C0 with AUC based on CsA levels at 0, 1, 2, 3, and 4 hr after dose (PK0-4) and to compare this AUC with C0 in predicting acute rejection (AR) and acute cyclosporine nephrotoxicity (CsANT) in de novo first kidney transplant patients. METHODS: PK0-4 was done 2-4 days after starting Neoral for 156 patients. All received CsA-based triple-drug immunosuppression without antibody induction. AUC was calculated as projected 12-hr (AUC0-12) and actual 4-hr (AUC0-4) from the PK0-4 using the parallel trapezoid rule. Neoral dosing was based on C0 not AUC. AUC was retrospectively compared with C0 as a predictor of AR and CsANT during the first 90 days. RESULTS: C0 correlated poorly with AUC0-12 and AUC0-4 (r=0.61 and r=0.42). C0 (mean+/-SEM) levels were not significantly different in 34 patients with and 109 without AR (293+/-21 vs. 294+/-11 microg/L, P=0.95). AUC0-12 and AUC0-4 were significantly lower in patients with than without AR (AUC0-12 9090+/-598 vs. 10608+/-336 microg x h/L, P=0.01; AUC0-4 3934+/-306 vs. 4802+/-166 microg.h/L, P=0.006). In stepwise regression analysis only AUC0-12 or AUC0-4 (P=0.03/P=0.02) and delayed graft function (P=0.007) predicted AR. AUC0-12, AUC0-4, and C0 were all significantly higher in patients with CsANT than without CsANT (AUC0-12 11746+/-650 vs. 10023+/-301 microg x h/L, P=0.01; AUC0-4 5270+/-358 vs. 4474+/-150 microg x h/L, P=0.01; C0 343+/-18 vs. 287+/-10 microg/L, P=0.01), but in stepwise regression analysis C0 was not an independent predictor of CsANT. Patients with AUC0-12 in the range of 9500 to 11500 microg x h/L or AUC0-4 between 4400 and 5500 microg x h/L had the lowest incidence of AR (13% and 7%, respectively) without significantly higher risk for CsANT. CONCLUSION: C0 correlates poorly with AUC based on PK0-4. Early AUC based on PK0-4 is more closely associated with AR and CsANT than is C0. Our data suggest that a target AUC0-12 of 9500-11500 or AUC0-4 of 4400-5500 microg x h/L may provide optimal Neoral immunosuppression.

Acute Disease↗
PubMed1999

The effect of formalin-inactivated vaccine on respiratory disease associated with bovine respiratory syncytial virus infection in calves.

The effect of vaccination with a formalin-inactivated, alum-precipitated (FI), bovine respiratory syncytial virus (BRSV) vaccine on BRSV induced respiratory disease in calves was investigated. Six month old BRSV-naive calves were vaccinated with either a FI, a modified live virus (MLV), or virus antigen negative control vaccine (n = 4 per group). One month after the second vaccination, the calves were aerosol challenged with lung wash from a newborn calf infected with a field isolate of BRSV. Moderate to severe clinical disease occurred in all calves. Calves that received FI vaccine had a significantly earlier (day 2 vs. day 4-5) onset of pyrexia and dyspnea (P < 0.05). Pulmonary lesions, consisting of cranioventral atelectasis and dorsal emphysema, occurred in all groups. Two calves that received MLV, and three that received FI vaccine, had reduced pneumonic lung area relative to controls. Vaccination with the FI vaccine resulted in more rapid onset of clinical disease, but ultimately, reduced pulmonary pathology in most recipients.

Animals↗
PubMed1999

Domains determining agonist selectivity in chimaeric VIP2 (VPAC2)/PACAP (PAC1) receptors.

1 The VPAC2 and PAC1 receptors are closely related members of the Group II G protein-coupled receptor family. At the VPAC2 receptor, VIP is equipotent to PACAP-38 in stimulating cyclic AMP production, whereas at the PAC1 receptor PACAP-38 is many fold more potent than VIP. In this study, domains which confer this selectivity were investigated by constructing four chimaeric receptors in which segments of the VPAC2 receptor were exchanged with the corresponding segment from the PAC1 receptor. 2 When expressed in COS 7 cells all the chimaeric receptors bound the common ligand [125I]PACAP-27 and produced cyclic AMP in response to agonists. 3 Relative selectivity for agonists was determined primarily by the amino terminal extracellular domain of the PAC1 receptor and the VPAC2 receptor. The interchange of other domains had little effect on the potency of PACAP-38 or PACAP-27. 4 For chimaeric constructs with a PAC1 receptor amino terminal domain, the substitution of increasing portions of the VPAC2 receptor decreased the potency of VIP yet increased that of helodermin. 5 This suggests that the interaction of VIP/helodermin but not PACAP with the PAC1 receptor may be influenced (and differentially so) by additional receptor domains.

Amino Acid Sequence↗
PubMed1999

Human opsonins induced during meningococcal disease recognize transferrin binding protein complexes.

Patient serum opsonins against transferrin binding protein A+B (TbpA+B) complexes from two Neisseria meningitidis strains (K454 and B16B6, with 85- and 68-kDa TbpB, respectively) were quantified by a functional phagocytosis and oxidative burst assay. TbpA+B complexes adsorbed to fluorescent beads were opsonized with individual acute and convalescent sera from 40 patients infected by a variety of meningococcal strains. Flow cytometric quantitation of leukocyte phagocytosis products (PP) demonstrated that disease-induced serum opsonins recognized TbpA+B, and the highest anti-TbpA+B serum opsonic activities were found between admission to hospital and 6 weeks later. The PP values obtained with TbpA+B from strain B16B6 (PP(B16B6)) were higher than those obtained with TbpA+B from strain K454 (PP(K454)), with both acute and convalescent sera (P < 0.0001), and correlated positively with higher immunoglobulin G enzyme-linked immunosorbent assay titers against TbpA+B from strain B16B6 than from strain K454 (P < 0.001). In spite of considerable variations between individuals, significant correlations were found between the PP(B16B6) and PP(K454) values, and the PP values did not depend on the variability of the TbpB proteins of the disease-causing strains. Simultaneously measured oxidative burst activity correlated closely with the PP values. We conclude that highly cross-reactive anti-TbpA+B serum opsonins are produced during meningococcal disease. The anti-TbpA+B opsonic activities were not affected by the variability of the TbpB proteins of the disease-causing strains, which further adds to the evidence for the vaccine potential of meningococcal TbpA+B complexes.

Adolescent↗
PubMed1999

Lack of evidence of conserved lentiviral sequences in pigs with post weaning multisystemic wasting syndrome.

In order to investigate the role of retroviruses in the recently described porcine postweaning multisystemic wasting syndrome (PMWS) serum and leukocytes were screened for reverse transcriptase (RT) activity, and tissues were examined for the presence of conserved lentiviral sequences using degenerate primers in a polymerase chain reaction (PCR). Serum and stimulated leukocytes from the blood and lymph nodes from pigs with PMWS, as well as from control pigs had RT activity that was detected by the sensitive Amp-RT assay. A 257-bp fragment was amplified from DNA from the blood and bone marrow of pigs with PMWS. This fragment was identical in size to conserved lentiviral sequences that were amplified from plasmids containing DNA from several lentiviruses. Cloning and sequencing of the fragment from affected pigs, however, did not reveal homology with the recognized lentiviruses. Together the results of these analyses suggest that the RT activity present in tissues from control and affected pigs is the result of endogenous retrovirus expression, and that a lentivirus is not a primary pathogen in PMWS.

Amino Acid Sequence↗