Emergence of resistance to protease inhibitor amprenavir in human immunodeficiency virus type 1-infected patients: selection of four alternative viral protease genotypes and influence of viral susceptibility to coadministered reverse transcriptase nucleoside inhibitors.

Previous data have indicated that the development of resistance to amprenavir, an inhibitor of the human immunodeficiency virus type 1 protease, is associated with the substitution of valine for isoleucine at residue 50 (I50V) in the viral protease. We present further findings from retrospective genotypic and phenotypic analyses of plasma samples from protease inhibitor-naïve and nucleoside reverse transcriptase inhibitor (NRTI)-experienced patients who experienced virological failure while participating in a clinical trial where they had been randomized to receive either amprenavir or indinavir in combination with NRTIs. Paired baseline and on-therapy isolates from 31 of 48 (65%) amprenavir-treated patients analyzed demonstrated the selection of protease mutations.

Patient and carer satisfaction with 'hospital at home': quantitative and qualitative results from a randomised controlled trial.

Background: 'Hospital At Home' schemes are set to increase in the United Kingdom (UK) in response to the NHS Plan. To date, little detailed work has been done on the acceptability of these schemes to patients and their carers.

Aim: To compare Hospital at Home patient and carer satisfaction with hospital care.

Is the U.S. experiencing an incipient epidemic of hallucinogen use?

NHSDA and MTF survey data indicate "epidemic"-like growth in hallucinogen use from 1992-1996 and associated increases in cocaine, crack, heroin and amphetamine use. These trends might have resulted from a proliferation of raves and dance clubs in the U.S.

Use of coisogenic host blastocysts for efficient establishment of germline chimeras with C57BL/6J ES cell lines.

Gene targeting in embryonic stem (ES) cells allows the production of mice with specified genetic mutations. Currently, germline-competent ES cell lines are available from only a limited number of mouse strains, and inappropriate ES cell/host blastocyst combinations often restrict the efficient production of gene-targeted mice. Here, we describe the derivation of C57BL/6J (B6) ES lines and compare the effectiveness of two host blastocyst donors, FVB/NJ (FVB) and the coisogenic strain C57BL/6-Tyr(c)-2J (c2J), for the production of germline chimeras.

Meiotic linkage mapping of 52 genes onto the canine map does not identify significant levels of microrearrangement.

In an effort to extend our understanding of the evolutionary relationship between the canine and human genomes, we have developed and positioned 52 new gene-associated polymorphic markers on the canine meiotic linkage map. Canine-specific PCR primers were developed from the consensus of published sequences of several mammalian genomes and were designed to span intronic regions, thus optimizing the probability that a polymorphic site was included. The resulting markers were analyzed on a panel of three-generation canine reference families and the data were incorporated into the current meiotic linkage map.

Erythrocyte membrane ATP binding cassette (ABC) proteins: MRP1 and CFTR as well as CD39 (ecto-apyrase) involved in RBC ATP transport and elevated blood plasma ATP of cystic fibrosis.

In addition to the better-known roles of the erythrocyte in the transport of oxygen and carbon dioxide, the concept that the red blood cell is involved in the transport and release of ATP has been evolving (J. Luthje, Blut 59, 367, 1989; G. R.

Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer.

Purpose: The goal of the computer program Adjuvant! is to allow health professionals and their patients with early breast cancer to make more informed decisions about adjuvant therapy.

Methods: Actuarial analysis was used to project outcomes of patients with and without adjuvant therapy based on estimates of prognosis largely derived from Surveillance, Epidemiology, and End-Results data and estimates of the efficacy of adjuvant therapy based on the 1998 overviews of randomized trials of adjuvant therapy. These estimates can be refined using the Prognostic Factor Impact Calculator, which uses a Bayesian method to make adjustments based on relative risks conferred and prevalence of positive test results.

Plakoglobin regulates the expression of the anti-apoptotic protein BCL-2.

Plakoglobin is a cytoplasmic protein and a homologue of beta-catenin and Armadillo of Drosophila with similar adhesive and signaling functions. These proteins interact with cadherins to mediate cell-cell adhesion and associate with transcription factors to induce changes in the expression of genes involved in cell fate determination and proliferation. Unlike the relatively well characterized role of beta-catenin in cell proliferation via activation of c-MYC and cyclin D1 gene expression, the signaling function of plakoglobin in regulation of cell growth is undefined.

Differential morphometric and ultrastructural remodelling in the left atrium and left ventricle in rapid ventricular pacing-induced heart failure.

Background: Heart failure induced by rapid ventricular pacing (RVP) is associated with left atrial (LA) but not left ventricular (LV) hypertrophy.

Objective: To determine whether differences in wall tension correlate with the differential ultrastructural remodelling in the LA and LV chambers, changes in ultrastructure, systolic function and wall tension (an index of wall stress) were compared in dogs after RVP (n=7) and with no RVP (n=9).

Results: Compared with dogs with no RVP (controls), dogs with RVP had increased collagen volume fraction (5.

Forensic aspects of ocular injury.

A case of homicidal stabbing resulting in bilateral penetrating ocular injuries is described. The case is noteworthy in that it highlights an unusual mechanism of death in homicidal stabbing. Disturbances in heart rhythm including asystole can be ascribed to the so-called oculocardiac or trigeminocardiac reflex.

Use of a sperm analyzer for evaluating broiler breeder males. 2. Selection of young broiler breeder roosters for the sperm quality index increases fertile egg production.

Previous research has shown that the sperm quality index (SQI) of rooster semen is indicative of overall semen quality. The objectives of the present experiments were to determine the correlation of the SQI with semen characteristics and fertility and to determine if selection of young males for the SQI would improve fertility. In Experiment 1 semen was collected from 35 Peterson males and was analyzed individually for sperm concentration and viability.

Sensitive method for detection of human herpesviruses 6 and 7 in saliva collected in field studies.

To facilitate studies of the epidemiology and natural history of human herpesviruses 6 and 7 in infants, a practical method for collecting and quantifying the DNA of these viruses was developed. Saliva was collected using small strips of filter paper, and virus was detected using a real-time quantitative fluorescent-probe PCR assay. The sensitivity and specificity of this method even after prolonged drying of the specimens compared favorably to those of our traditional method of collecting and assaying saliva.

Economic evaluation of hospital at home versus hospital care: cost minimisation analysis of data from randomised controlled trial.

Objectives: To compare the costs of admission to a hospital at home scheme with those of acute hospital admission.

Design: Cost minimisation analysis within a pragmatic randomised controlled trial.

Setting: Hospital at home scheme in Leicester and the city's three acute hospitals.

Randomised controlled trial of effectiveness of Leicester hospital at home scheme compared with hospital care.

Objective: To compare effectiveness of patient care in hospital at home scheme with hospital care.

Design: Pragmatic randomised controlled trial.

Setting: Leicester hospital at home scheme and the city's three acute hospitals.

Human hepatic glyceraldehyde-3-phosphate dehydrogenase binds to the poly(U) tract of the 3' non-coding region of hepatitis C virus genomic RNA.

The unique poly(U/UC) tract, the middle part of the tripartite 3' non-coding region (3'NCR) of hepatitis C virus (HCV) genomic RNA, may represent a recognition signal for the HCV replicase complex. In this study, several proteins binding specifically to immobilized ribooligonucleotide r(U)(25) mimicking this structure were identified using cytosolic extracts from HCV-negative or -positive liver explants, and a prominent 36 kDa protein was studied further. Competition experiments including homoribopolymers revealed binding affinities in the order: oligo/poly(U)>(A)>(C)>(G).

Ontogeny of hepatitis C virus (HCV) hypervariable region 1 (HVR1) heterogeneity and HVR1 antibody responses over a 3 year period in a patient infected with HCV type 2b.

Hypervariable region 1 (HVR1) sequences of 96 clones at six time-points representing 27 variants in two major and one minor group were identified in a patient with chronic hepatitis C virus (HCV) infection over 3 years. Major and selected minor variants were used to design synthetic peptides corresponding to the HVR1 C terminus. Peptide ELISA reactivity with IgG was plotted against the corresponding clone frequency, and three patterns emerged: (1) three peptides were unreactive; (2) antibodies against two peptides followed emergence of the corresponding variant, suggesting isolate-specificity; (3) antibodies against four peptides preceded the appearance of the corresponding variant, indicating cross-reactivity or previous exposure.

Development of fumonisin-induced hepatotoxicity and pulmonary edema in orally dosed swine: morphological and biochemical alterations.

The fumonisin (FB) mycotoxins induce liver injury in all species but induce fatal pulmonary edema (PE) only in pigs. They inhibit ceramide synthase in the sphingolipid biosynthetic pathway. To study the pathogenesis of PE, we examined the early events in the development of FB-induced PE and hepatotoxicity in pigs.

Analysis of recombinant human platelet-derived growth factor by reversed-charge capillary zone electrophoresis.

Reversed-charge capillary zone electrophoresis (RC-CZE) has been developed as a clipping (proteolysis) assay for homodimeric protein recombinant human platelet-derived growth factor (rhPDGF-BB), a major serum mitogenic factor involved in subcutaneous wound healing. When expressed in yeast, the protein is excreted as a fully folded homodimeric protein consisting of two antiparallel B chains held together by two interchain disulfide bonds. During fermentation, internal proteolysis (clipping between residues Arg32 and Thr33) and C-terminal truncation (Arg32 and Thr109) may occur.

Use of a sperm analyzer for evaluating broiler breeder males. 1. Effects of altering sperm quality and quantity on the sperm motility index.

A new instrument for assessing mammalian semen attributes, the Sperm Quality Analyzer, was evaluated as a potential tool for determining rooster sperm quality. The Sperm Quality Analyzer measures the "activity" of sperm in a semen sample as the sperm motility index (SMI). The SMI is defined as the number and amplitude of deflections in a light path per second as a result of sperm movement within a capillary tube.

Plakoglobin induces desmosome formation and epidermoid phenotype in N-cadherin-expressing squamous carcinoma cells deficient in plakoglobin and E-cadherin.

Pg is a homologue of beta-catenin and Armadillo, the product of the Drosophila segment polarity gene and has been shown to have both adhesive and signaling functions. It interacts with both classic and desmosomal cadherins. Pg interaction with the desmosomal cadherins is essential for desmosome assembly.

Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a multicenter review.

Background: Endoscopic therapy of biliary tract leaks was uncommon before laparoscopic cholecystectomy. Studies have demonstrated the efficacy of endoscopic drainage by endoscopic sphincterotomy or stent placement. Various endoscopic therapeutic modalities and long-term follow-up of this problem were studied.