Cross-protection in NYVAC-HIV-1-immunized/HIV-2-challenged but not in NYVAC-HIV-2-immunized/SHIV-challenged rhesus macaques.

Objectives: Immunization with attenuated poxvirus-HIV-1 recombinants followed by protein boosting had protected four of eight rhesus macaques from HIV-2SBL6669 challenge. The present study was designed to confirm this result and to conduct the reciprocal cross-protection experiment.

Methods: Twenty-four macaques were primed with NYVAC (a genetically attenuated Copenhagen vaccinia strain) recombinants with HIV-1 and HIV-2 env and gag-pol or NYVAC vector alone and boosted with homologous, oligomeric gp160 proteins or adjuvant only.

Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromcyin: a case review and cohort study.

Background: In February, 1999, a local US health department identified a cluster of pertussis cases among neonates born at a community hospital and recommended oral erythromycin for post-exposure prophylaxis for about 200 neonates born at that hospital between Feb 1 and Feb 24, 1999. We investigated a cluster of seven cases of infantile hypertrophic pyloric stenosis (IHPS) that occurred the following month among the neonates who had received erythromycin.

Methods: We obtained a masked, independent review of the IHPS ultrasonography diagnoses, calculated the monthly IHPS incidence, and compared index and historical (1998-99) IHPS cases with respect to several characteristics including erythromycin exposure.

Rat cytochromes P450 (CYP) specifically contribute to the reductive bioactivation of AQ4N, an alkylaminoanthraquinone-di-N-oxide anticancer prodrug.

1. The bioreductive activation of the alkylaminoanthraquinone di-N-oxide prodrug AQ4N has been characterized in rat hepatic tissue using HPLC. 2.

Effects of AQ4N and its reduction product on radiation-mediated DNA strand breakage.

Supercoiled plasmid pBR322 DNA was irradiated in phosphate buffer by 60Co gamma-rays at a dose rate 19.26 Gy/min and total dose of 10 Gy in the presence of a bioreductive antitumour prodrug namely 1,4-bis [¿2-(dimethylamino-N-oxide)ethyl¿ amino] 5, 8-dihydroxyanthracene-9,10-dione (AQ4N) and its DNA affinic reduction product 1,4-bis[¿2(dimethylamino)ethyl¿ amino] 5,8-dihydroxyanthracene-9,10-dione (AQ4) under air and nitrogen. AQ4N and AQ4 were found to protect against radiation-induced plasmid single and double strand breakage as assessed by agarose gel electrophoresis.

A novel cell permeant and far red-fluorescing DNA probe, DRAQ5, for blood cell discrimination by flow cytometry.

The deep red fluorescing agent (DRAQ5) is a synthetic anthraquinone with a high affinity for DNA and a high capacity to rapidly enter living cells or stain fixed cells. DRAQ5 is optimally excited by red-light emitting sources and yields a deep red emission spectrum which extends into the low infra-red. DRAQ5 shows excitation at sub-optimal wavelengths including the 488 nm line and the multi-line UV wavelengths emitted by argon-ion lasers.

Molecular analysis of the klarsicht gene and its role in nuclear migration within differentiating cells of the Drosophila eye.

Background: The temporally regulated, cell-type-specific transport of organelles has great biological significance, yet little is known about the regulation of organelle transport during development. The Drosophila gene klarsicht is required for temporally regulated lipid droplet transport in developing embryos and for the stereotypical nuclear migrations in differentiating cells of the developing eye. Klarsicht is thought to coordinate the function of several molecular motors bound to a single lipid droplet or to facilitate the attachment of dynein to the cargo, but it is not known whether Klarsicht affects motors directly or indirectly.

Carriage of multidrug-resistant Streptococcus pneumoniae and impact of chemoprophylaxis during an outbreak of meningitis at a day care center.

Three cases of meningitis due to multidrug-resistant serotype 14 Streptococcus pneumoniae occurred at a day care center (DCC) over 5 days. Cultures of nasopharyngeal samples were done at the index DCC, 2 comparison DCCs, and a pediatrics practice. Isolates were serotyped and subtyped by pulsed-field gel electrophoresis (PFGE) with SmaI.

Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and fos responses to vagal satiety signals.

To test the possible role of N-methyl-D-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10-30 min, 8.9 +/- 1.

Free radicals in irradiated drugs: an EPR study.

Exposure of dry powder forms of the drugs nitrendipine, nifedipine, felodipine, and nimodipine to gamma-radiation results in the formation of free radicals detected by electron paramagnetic resonance (EPR) spectroscopy. The four structurally related drugs show qualitatively identical EPR spectral features in terms of g-values, the qualitative descriptive parameter. These radicals are very stable, surviving long periods of time in excess of 9 months and possibly beyond conventional shelf-life of the drugs.

Cu/Zn superoxide dismutase in excretory-secretory products of the human hookworm Necator americanus. An electron paramagnetic spectrometry study.

EPR spectrometry was used to investigate the effect of excretory/secretory product from Necator americanus on superoxide radical anions generated by xanthine/xanthine oxidase as a measure of excretory/secretory product superoxide dismutase activity. Using 1,1',5,5'-dimethylpyrollidine-N-oxide (DMPO) as a superoxide spin-trapping agent a 12-line EPR spectrum characteristic of the DMPO-OOH adduct was observed to decrease in the presence of excretory/secretory product. Superoxide dismutase activity was proportional to excretory/secretory protein concentration, was inhibited with cyanide treatment and was progressively destroyed with increasing time of heat denaturation of excretory/secretory product.

Latex anaphylaxis causing heart block: role of ranitidine.

Purpose: Treatment with H2 receptor antagonists may cause the heart to be more susceptible to atrioventricular conduction delay when exposed to an overwhelming insult by histamine released during an anaphylactic reaction. We present the case of a woman, pretreated with ranitidine, who developed 3:1 heart block secondary to latex anaphylaxis. We propose that H2 antagonist premedication alone in patients susceptible to anaphylaxis increases their risk of heart block.

Factors associated with slow disease progression in macaques immunized with an adenovirus-simian immunodeficiency virus (SIV) envelope priming-gp120 boosting regimen and challenged vaginally with SIVmac251.

Rhesus macaques were immunized with a combination vaccine regimen consisting of adenovirus type 5 host range mutant-simian immunodeficiency virus envelope (Ad5hr-SIVenv) recombinant priming and boosting with native SIV gp120. Upon intravaginal challenge with SIVmac251, both persistently and transiently viremic animals were observed (S. L.

Postmortem retrieval of total joint replacement components.

Improved understanding of the clinical outcomes of orthopedic implants requires the study of implants at the end of their service life. Previous studies focused on the retrieval of so-called failed implants during surgical revision. Interest is now moving to the study of successful implants, which are those still in place at the patient's death.

Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group.

Objectives: The purpose of this open-label study extension was to assess the long-term safety and efficacy of finasteride in the treatment of men with benign prostatic hyperplasia (BPH).

Methods: A Phase III North American BPH trial originally enrolled 895 men, 297 of whom were randomized to receive finasteride 5 mg. An enlarged prostate gland by digital rectal examination, symptoms of urinary obstruction, and a maximal urinary flow rate of less than 15 mL/s were required for entry.

Newly recognized focus of La Crosse encephalitis in Tennessee.

La Crosse virus is a mosquito-borne arbovirus that causes encephalitis in children. Only nine cases were reported in Tennessee during the 33-year period from 1964-1996. We investigated a cluster of La Crosse encephalitis cases in eastern Tennessee in 1997.

Metal release and excretion from cementless titanium alloy total knee replacements.

Concentrations of titanium, aluminum, and vanadium were measured in the serum and urine of patients with titanium alloy cementless primary total knee arthroplasty components. Patients were categorized in one of five groups. In Group 1, the patellar and tibial articulating surfaces were made of carbon fiber reinforced ultrahigh molecular weight polyethylene.

Intra and intermolecular charge effects on the reaction of the superoxide radical anion with semi-oxidized tryptophan in peptides and N-acetyl tryptophan.

The reaction of the superoxide radical anion (O2-*), with the semi-oxidized tryptophan neutral radical (Trp*) generated from tryptophan (Trp) by pulse radiolysis has been observed in a variety of functionalized Trp derivatives including peptides. It is found that the reaction proceeds 4-5 times faster in positively charged peptides, such as Lys-Trp-Lys, Lys-Gly-Trp-Lys and Lys-Gly-Trp-Lys-O-tert-butyl, than in solutions of the negatively charged N-acetyl tryptophan (NAT). However, the reactivity of O2-* with the Trp* radical is totally inhibited upon binding of these peptides to micelles of negatively charged SDS and is reduced upon binding to native DNA.

Involvement of human cytochromes P450 (CYP) in the reductive metabolism of AQ4N, a hypoxia activated anthraquinone di-N-oxide prodrug.

Purpose: To establish the role of the human cytochromes P450 (CYPs) in the reductive metabolism of the novel anthraquinone di-N-oxide prodrug AQ4N.

Methods And Materials: Metabolism of AQ4N was conducted in a panel of 17 human phenotyped liver microsomes. AQ4N and metabolites were detected by reverse phase isocratic HPLC.

Vaccine protection against a heterologous, non-syncytium-inducing, primary human immunodeficiency virus.

Vaccine-induced protection of chimpanzees against laboratory-adapted and syncytium-inducing, multiply passaged primary human immunodeficiency virus type 1 (HIV-1) isolates, but not against non-syncytium-inducing, minimally passaged ones, has been demonstrated. Following challenge with such an isolate, HIV-15016, we obtained complete protection in one of three chimpanzees previously protected against low- and high-dose HIV-1SF2 exposures after immunization with an adenovirus-HIV-1MN gp160 priming-HIV-1SF2 gp120 boosting regimen. At challenge, the protected chimpanzee exhibited broad humoral immunity, including neutralizing antibody activity.

Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study.

Unlabelled: There is an increasing recognition that, in the long term, total joint replacement may be associated with adverse local and remote tissue responses that are mediated by the degradation products of prosthetic materials. Particular interest has centered on the metal-degradation products of total joint replacements because of the known toxicities of the metal elements that make up the alloys used in the implants. We measured the concentrations of titanium, aluminum, cobalt, and chromium in the serum and the concentration of chromium in the urine of seventy-five patients during a three-year prospective, longitudinal study.

Reduction of the indoloquinone anticancer drug EO9 by purified DT-diaphorase: a detailed kinetic study and analysis of metabolites.

DT-diaphorase has been implicated in the activation and mechanism of cytotoxicity of the investigational indoloquinone anticancer drug EO9. Here, we have used a highly purified DT-diaphorase isolated from rat Walker tumour cells to provide unambiguous evidence for the ability of this enzyme to catalyze reduction of EO9 and to provide a more detailed characterization of the reaction. Under the conditions used hypoxia had no effect on the initial rate of this reduction but did effect the nature and stability of metabolites formed.

Enzymology of tirapazamine metabolism: a review.

The enzymology of triapazamine (TPZ, SR 4233, WIN 59075, 3-amino-1,2,4-benzotriazene 1,4-dioxide, Tirazone) has been extensively studied in rodents and to a lesser extent in human systems. While it is clear that the initial reductive step in TPZ activation is enzyme-mediated, there is limited consensus in the published literature as to the relative contributions of the cellular reductases involved. Moreover, not only is the importance of subcellular localization for these putative activating reductase(s) far from clear, but their activity profiles in vivo are poorly defined.

Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. PLESS Study Group. Proscar Long-term Efficacy and Safety Study.

Objectives: To evaluate prostate cancer detection and prostate-specific antigen (PSA) among men with benign prostatic hyperplasia treated with finasteride.

Methods: Three thousand forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were randomized in a double-blind, placebo-controlled trial to finasteride (n = 1524) or placebo (n = 1516) for up to 4 years. A prerandomization biopsy negative for prostate cancer was obtained in 98% of patients with a screening PSA of 4.

Differential expression and function of cadherin-6 during renal epithelium development.

The cadherin gene family encodes calcium-dependent adhesion molecules that promote homophilic interactions among cells. During embryogenesis, differential expression of cadherins can drive morphogenesis by stimulating cell aggregation, defining boundaries between groups of cells and promoting cell migration. In this report, the expression patterns of cadherins were examined by immunocytochemistry and in situ hybridization in the embryonic kidney, during the time when mesenchymal cells are phenotypically converted to epithelium and the pattern of the developing nephrons is established.