Molecular characterisation of novel receptors for PACAP and VIP.
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Biomedical subjects
Publications and source records attributed to K West.
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We evaluated a modified TDx-fetal lung maturity (FLM) test for estimating surfactant in small volume tracheal aspirates in 140 infants requiring mechanical ventilation. Respiratory distress syndrome was present in 75 infants, and 68 had TDx FLM less than 60 mg/dL (sensitivity, 90.6%). Respiratory distress was absent in 65 infants, 56 had TDx FLM more than 60 mg/dL (specificity, 86.1%). The modified TDx-FLM assay is highly automated, has a fast turn-around time (less than 30 minutes), has high reproducibility, and is less expensive than other available methods. This method has potential routine application in the diagnosis of surfactant deficiency, and the assessment of surfactant replacement and mechanical ventilation therapies.
Epidermoid carcinomas were induced in hamster buccal pouches with use of 7.12 dimethylbenz[a]anthracene (DMBA). In five animals that served as tumor controls (Group 1), right buccal pouches were painted with DMBA (0.5% solution in mineral oil) thrice weekly for 14 weeks. In five animals (Group 2), right buccal pouches were painted with DMBA and reduced glutathione (GSH) was administered systemically by mouth. Five animals (Group 3) received vitamin E instead of glutathione. An additional 20 animals (Groups 4, 5, 6, and 7) were untreated, vehicle, glutathione, and vitamin E controls, respectively. Glutathione and vitamin E were given in doses of 10 mg/kg in 0.5 ml of mineral oil thrice weekly on days alternate to DMBA painting. Treatment by GSH and vitamin E reduced the number and size of tumors that were formed. Histopathologically, there were also fewer sites of dysplasia, carcinoma in situ, and early invasive epidermoid carcinoma than in the tumor control animals. The formalin-fixed and paraffin-embedded buccal pouch sections were stained immunohistochemically with use of monoclonal antibodies for cytokeratins. These included high-molecular-weight keratins (50,000-68,000 mol wt) 10, 13, and 8 (k10, k13, and k8, respectively). Oral carcinomas and dysplastic sites exhibited basal and suprabasal (spinous layer) high levels of k10, k13, and k8 staining. Treatment with GSH or vitamin E increased the suprabasal staining for high-molecular-weight keratins and reduced the protein expression for k10, k13, or k8. This pattern of staining was observed in dysplastic as well as in carcinoma sites. These results indicate that cytokeratin protein expression could contribute to a common biomarker analysis for chemoprevention.
Infection Control policies/procedures are written to reduce the risk for patient and HCW infection. But, if the policy or procedure is not practical, feasible or up-to-date, compliance will be low and risk may increase. Risk assessment within the community and evaluation of exposures to create changes using new technologies will help to protect the HCW. The ED should develop an open working relationship with the ICP and participate through active membership on the infection control committee. The ICP should spend time in the ED observing or, better yet, by spending some time walking in their shoes. Working together, sharing data on risk and exposures, compliance with PPE recommendations, and cleaning routines are ways to bring about a more risk-free environment for both patient and care provider.
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The possible association of human papilloma viruses (HPV) with laryngopharyngeal squamous cell carcinoma is under investigation. Recent work suggests regional differences in the prevalence of HPV infection in the hypopharynx. The present study investigates the prevalence of HPV in tissue obtained from a series of piriform fossae. Piriform fossa epithelium was harvested from 12 autopsy cases free of local disease. DNA was obtained by SDS/Proteinase K digestion. Evidence of HPV infection was documented by the polymerase chain reaction using oligonucleotide primers complementary to sequences in the E6 region of HPV types 11, 16 and 18. All the specimens were positive for beta-globin. HPV11 was isolated from two patients. None were positive for HPV16 or HPV18. An 18% prevalence rate for HPV11 in the normal human hypopharynx was found.
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Heterotrimeric guanine nucleotide-binding proteins (G-proteins) function as signal transducers for a variety of hormone-coupled enzyme and ion transport systems in eukaryotic cells. The expression of pertussis toxin-sensitive G-proteins (Gi) which couple their cognate receptors and effectors are regulated by cell cycle-dependent events in porcine LLC-PK1 renal epithelial cells. G alpha i-2 and G alpha i-3 isoforms are detected in these cells, and like G alpha i-2 (Holtzman, E. J., Soper, B. W., Stow, L. L., Ausiello, D. A., and Ercolani, L. (1991) J. Biol. Chem. 266, 1763-1771), we now demonstrate that G alpha i-3 mRNA and protein is coordinately expressed in these cells during differentiation. To gain further insights into these events, the porcine G alpha i-3 gene minimal promoter was characterized and found 67 base pairs upstream from the major transcription start site. The 56-base pair minimal promoter lacked TATAAA and GC boxes but did contain a sequence GGAAGTG conserved in both the human and porcine gene that could potentially bind an adenovirus E4TF1 transcription factor. In cells stably transfected with G alpha i-2 or G alpha i-3 gene 5'-flanking sequences fused to firefly luciferase cDNA reporter, temporal 10-15-fold transcriptional activation of both genes occurred before cellular polarization. Utilizing mobility shift assays which compared nuclear extracts from cells before and after cell polarization, a motif in the 5' region of the gene promoter GTACTTCCGCT was identified that bound an induced nuclear protein complex during transcriptional activation. In polarized cells complemented with the human glucocorticoid receptor, dexamethasone decreased G alpha i-2 but increased G alpha i-3 basal transcription and mRNA content 3-fold. These studies demonstrate that both G alpha i genes are dynamically regulated in LLC-PK1 cells by both growth, differentiation, and hormone signals.
A scale is developed for measuring the overprotecting vs. optimal developmental stimulation tendencies for parents of physically "vulnerable" children. A series of items were administered to parents whose parenting techniques had been rated as either highly overprotective or as optimal by a group of MDs and other professionals. Correlations were estimated between each of the items and parental tendencies as rated by professionals. Twenty-eight items were selected that provided maximum prediction of over-protection. The resulting R2 was extraordinarily high (.94). Coefficient alpha and test-retest coefficients were acceptable. It is hoped that release of the new instrument (VCOPS) at this time will allow others to join in determining the clinical and experimental validity of this scale.
Children undergoing long-term peritoneal dialysis are at risk for membrane injury, necessitating conversion to hemodialysis. We analyzed the incidence and risk factors for membrane failure (inadequate ultrafiltration with or without peritoneal adhesions and decreased peritoneal surface area) in 68 children maintained with peritoneal dialysis for more than 3 months at our institution. The overall incidence of membrane failure was 16.2% (11/68). Kaplan-Meier estimates of peritoneal membrane survival were 88% at 24 months, 72% at 36 months, 65% at 48 months, and 52% at 60 months. Logistic regression analysis demonstrated that the risk of membrane failure increased with the number of episodes of peritonitis (odds ratio 1.61). The rate of peritonitis was 1 per 7.02 patient months in children who developed membrane failure compared with 1 per 9.18 patient months in children without membrane failures but the rate of peritonitis was not predictive of membrane failure (P = 0.09). Multiple logistic regression analysis demonstrated that peritonitis caused by Pseudomonas aeruginosa or alpha streptococcal organisms were independent predictors of membrane failure. We conclude that peritoneal membrane survival declines substantially with time on peritoneal dialysis and that membrane failure is associated with peritonitis, particularly peritonitis caused by Pseudomonas aeruginosa and alpha streptococcal organisms. The mechanism(s) of membrane injury are unknown but may be related to the inflammatory response initiated during peritonitis.
We reported previously that adoptive immunization with an influenza A virus NS1-specific H-2Ld-restricted, cross-reactive, CTL clone A-11 established by stimulation with A/PR/8/34 virus (H1N1) reduced lung virus titers in mice challenged with virus in vivo (Virology 178:174-179, 1990). Using a set of recombinant vaccinia virus constructs containing truncated portions of the NS gene we have localized this cross-protective CTL epitope to the N-terminal region of the NS1 protein. This region of NS1 is active in inducing CD8+ CTL in vivo because virus-stimulated BALB/c immune spleen cells in bulk cultures also recognized the N-terminal region of the NS1 protein.
Lymphoma arising in the liver is uncommon in adults and rare in children. A 12-year-old boy with hepatomegaly and jaundice had a calcified intrahepatic large-cell lymphoma of B-cell origin that expressed bcl-2 protein and had near-tetraploid chromosome number with a t(8;14) (q24;q32) and a homogeneously staining region (HSR). This tumor, only the fourth example of primary hepatic lymphoma in a child, has the rare finding of an HSR before treatment and is the first human lymphoma with t(8;14) that expresses bcl-2 protein. In addition, the demonstration of extensive calcification in the tumor by computed tomography scan is highly unusual for lymphoma. Lymphoma must be considered in the differential diagnosis of primary liver tumors in children and adults, especially if the serum alpha-fetoprotein level is normal.
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