Quantitative autoradiographic mapping of mu-, delta- and kappa-opioid receptors in knockout mice lacking the mu-opioid receptor gene

Mice lacking the mu-opioid receptor (MOR) gene have been successfully developed by homologous recombination and these animals show complete loss of analgesic responses to morphine as well as loss of place-preference activity and physical dependence on this opioid. We report here quantitative autoradiographic mapping of opioid receptor subtypes in the brains of wild-type, heterozygous and homozygous mutant mice to demonstrate the deletion of the MOR gene, to investigate the possible existence of any mu-receptor subtypes derived from a different gene and to determine any modification in the expression of other opioid receptors. Mu-, delta-, kappa1- and total kappa-receptors, in adjacent coronal sections in fore- and midbrain and in sagittal sections, were labelled with [3H]DAMGO (D-Ala2-MePhe4-Gly-ol5 enkephalin), [3H]DELTI (D-Ala2 deltorphinI), [3H]CI-977 and [3H]bremazocine (in the presence of DAMGO and DPDPE) respectively. In heterozygous mice, deficient in one copy of the MOR gene, mu-receptors were detectable throughout the brain at about 50% compared to wild-type. In brains from mu-knockout mice there were no detectable mu-receptors in any brain regions and no evidence for mu-receptors derived from another gene. Delta-, kappa1- and total kappa-receptor binding was present in all brain regions in mutant mice where binding was detected in wild-type animals. There were no major quantitative differences in kappa- or delta-binding in mutant mice although there were some small regional decreases. The results indicate only subtle changes in delta- and kappa-receptors throughout the brains of animals deficient in mu-receptors.     

The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily

The mAb A33 detects a membrane antigen that is expressed in normal human colonic and small bowel epithelium and > 95% of human colon cancers. It is absent from most other human tissues and tumor types. The murine A33 mAb has been shown to target colon cancer in clinical trials, and the therapeutic potential of a humanized antibody is currently being evaluated. Using detergent extracts of the human colon carcinoma cell lines LIM1215 and SW1222, in which the antigen is highly expressed, the molecule was purified, yielding a 43-kDa protein. The N-terminal sequence was determined and further internal peptide sequence obtained following enzymatic cleavage. Degenerate primers were used in PCRs to produce a probe to screen a LIM1215 cDNA library, yielding clones that enabled us to deduce the complete amino acid sequence of the A33 antigen and express the protein. The available data bases have been searched and reveal no overall sequence similarities with known proteins. Based on a hydrophilicity plot, the A33 protein has three distinct structural domains: an extracellular region of 213 amino acids (which, by sequence alignment of conserved residues, contains two putative immunoglobulin-like domains), a single hydrophobic transmembrane domain, and a highly polar intracellular tail containing four consecutive cysteine residues. These data indicate that the A33 antigen is a novel cell surface receptor or cell adhesion molecule in the immunoglobulin superfamily.     

Characterization of a tunable optical parametric oscillator laser system for multielement flame laser excited atomic fluorescence spectrometry of cobalt, copper, lead, manganese, and thallium in buffalo river sediment

A pulsed (10 Hz) optical parametric oscillator (OPO) laser system based on beta-barium borate (BBO) crystals and equipped with a frequency-doubling option (FDO) was characterized for use in laser excited atomic fluorescence spectrometry (LEAFS). This all-solid-state laser has a narrow spectral line width, a wide spectral tuning range (220-2200 nm), and a rapid, computer-controlled slew scan of wavelength (0.250 nm s-1 in the visible and infrared, and 0.125 nm s-1 in the ultraviolet). The output power characteristics (15-90 mJ/pulse in the visible, 1-40 mJ in the infrared, and 1-11 mJ in the ultraviolet), laser pulse-to-pulse variability (3-13% relative standard deviation, RSD, of the laser pulses), conversion efficiency of the FDO (2-17%), and spectral bandwidth in the visible spectrum (0.1-0.3 cm-1) were measured. The laser was used as the excitation source for a flame LEAFS instrument for which rapid, sequential, multielement analysis was demonstrated by slew scan of the laser. The instrument allowed about 640 measurements to be made in about 6 h, with triplicate measurements of all solutions and aqueous calibration curves, which yielded accurate analyses of a river sediment (National Institute of Standards and Technology, Buffalo River Sediment, 2704) for five elements with precisions < 5% RSD. Comparable or improved flame LEAFS detection limits over literature values were obtained for cobalt (2 ng mL-1), copper (2 ng mL-1), lead (0.4 ng mL-1), manganese (0.2 ng mL-1), and thallium (0.9 ng mL-1) by flame LEAFS.     

Tricuspid valve surgery and intraoperative echocardiography: factors affecting survival, clinical outcome, and echocardiographic success

BACKGROUND: The impact of echocardiographic-guided treatment on outcome after tricuspid valve (TV) surgery is not well defined. OBJECTIVES: The purpose of this study was to determine clinical and echocardiographic factors associated with adverse outcomes after TV surgery and determine the role of intraoperative echo (IOE) in facilitating successful outcomes after TV surgery. METHODS: Four hundred and one patients (279 females, mean age 60 years) underwent TV surgery and other concomitant cardiac surgery at a single institution and were followed clinically and by echocardiography during a 10-year period. RESULTS: Decreased survival after TV surgery was associated with: preoperative increased New York Heart Association (NYHA) functional classification (relative risk [RR]=2.02), increased left ventricular dysfunction by echocardiography (RR=1.28), and use of a TV replacement strategy (RR=2.92). Decreased event-free survival after TV surgery was associated with concomitant coronary artery bypass grafting (RR=2.97). Late echocardiographic failure (3 to 4+ tricuspid valve regurgitation [TR]) after TV surgery was associated with increased severity of TR on preoperative echocardiogram (odds ratio [OR]=1.91). Decreased late echocardiographic failure after TV surgery was associated with the use of a TV annuloplasty ring with a repair strategy (OR=0.40). The surgical plan was altered at the time of surgery to insure a successful outcome in 32 (10%) of 335 patients based on IOE findings. CONCLUSIONS: Adverse outcomes after TV surgery can be predicted by several preoperative clinical and echocardiographic variables. IOE is useful in improving immediate, but not late, outcomes after TV surgery.     

Mortality in geriatric psychiatric inpatients

OBJECTIVE: To report current information about invasive pneumococcal infections, capsular types and antimicrobial resistance in Canada. DESIGN: Retrospective analysis. SETTING: Canada. PATIENTS: A total of 976 patients from whom Streptococcus pneumoniae was isolated from blood or cerebrospinal fluid between Jan. 1, 1992, and Dec. 31, 1995. OUTCOME MEASURES: Capsular type and antimicrobial susceptibility. RESULTS: Twenty types accounted for 90.8% of the isolates from patients over 5 years of age; all but type 15A are covered by the currently available 23-valent vaccine. Nine types accounted for 92% of the isolates recovered from children 5 years and less. Reduced susceptibility to penicillin was found in 7.8% of the collection and was associated with types 6B, 9V and 19A. Full resistance to penicillin was observed most frequently during 1995 and was associated with type 9V. Rates of reduced susceptibility over one 12-month period were 19.5% for trimethoprim-sulfamethoxazole and 4.5% or less for each of cefotaxime, ceftriaxone, chloramphenicol, erythromycin, ofloxacin and tetracycline. CONCLUSIONS: Over 90% of invasive pneumococcal infections are covered by the currently available vaccines (for people over 2 years of age) and the pneumococcal protein-polysaccharide conjugate vaccines under development for young children. The high frequency of antimicrobial resistance observed requires more complete investigation and confirmation; however, taken from a global perspective, it supports the need to develop better control strategies, including greater use of new and existing vaccines.     

Single-specimen bile cytology: a prospective study of 80 patients with obstructive jaundice

The interaction between drugs (tolbutamide (1), 1-butyl-3-(methylsulfonyl)urea (2)) and human serum albumin (3) was investigated by equilibrium dialysis and NMR spectroscopy. The binding of 1 and 2 to 3 was concluded to be hydrophobic and hydrophilic, respectively, on the basis of the dependence of the binding constants on temperature, ionic strength, and chain length of fatty acid added. In 1H-NMR spectra of 1, there were no significant shifts with change in concentration or addition of 3. The spin-lattice relaxation time (T1) and spin-spin relaxation rate (1/T2) of the respective protons of 1 were independent of concentration, but depended on the concentration of 3 added. The binding position was determined from the ratio of 1/T2 of 1 bound to 3 and free 1. 1 and 2 were found to bind to 3 through the tolyl group and sulfonylurea group, respectively. The binding property of 1 was considered to be governed by the competition between the hydrophobic effect of the tolyl group and the hydrophilic effect of the sulfonylurea group in the molecule.     

All-trans-retinoic acid down-regulates elastin promoter activity elevated by ultraviolet B irradiation in cultured skin fibroblasts

OBJECTIVE: Little research has evaluated maternal experience with fetal pulse oximetry for fetal surveillance. The purpose of this study was to compare maternal perceptions of labor with intrapartal cardiotocography with or without fetal pulse oximetry in a research setting. METHODS: One hundred women with vaginal, vertex deliveries and uncomplicated fetal outcomes were enrolled. The study group was a subset of 50 mothers who had participated in a pulse oximetry trial. The control group of 50 mothers was monitored by cardiotocography only. Both groups were matched for age, parity, weeks of gestation, epidural anesthesia use, and duration of labor. A global measure of maternal perception of labor was established by experience with labor, general attitude toward monitoring devices, satisfaction with monitoring, nursing and medical care, and anxiety, each of which was evaluated separately. The mothers in the study group were also interviewed about aspects related to the fetal pulse oximetry research setting, such as information, movement restriction, discomfort, care, privacy, and safety. The questionnaires were based on a standardized rating scale model, and the interviews were conducted two to four days after delivery. The results were analyzed by chi-squared, paired t test, and ANOVA. RESULTS: No significant differences were observed between the study and control participants in any parameter concerning the maternal perception of labor. Mothers' experiences with pulse oximetry as assessed by interview was overwhelmingly positive. CONCLUSIONS: Fetal monitoring by pulse oximetry in a research setting did not affect maternal perceptions of labor. Mothers' experiences with pulse oximetry were highly positive, suggesting that research in fetal pulse oximetry need not compromise maternal perceptions of labor.     

Improved survival with resection after transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma

Three patients with malignant blue nevus are reported-one on the right side of the body, one on the right arm, and one on the face. The criteria and difficulty of histopathological diagnosis are considered as well as the differential diagnoses for this tumor. The therapy is described, and the possible relations between malignant blue nevus and certain other tumors (e.g., atypical or locally aggressive cellular blue nevus) are explored. A review of the literature reveals that there is current disagreement about the exact prognosis for these tumors and indicates the need to collect data for all patients observed.     

Molecular analysis of rifampin-resistant Mycobacterium tuberculosis isolated from Korea by polymerase chain reaction-single strand conformation polymorphism sequence analysis

The production of and sensitivity to bacteriocin-like activity among 44 strains of black-pigmented anaerobes isolated from periodontal sites were evaluated by both an overlay and an agar diffusion method. The species studied were Porphyromonas gingivalis, Prevotella intermedia and the closely related species Pr. nigrescens. Pr. intermedia strains (90%) produced bacteriocin-like activity against Pr. nigrescens and all Pr. nigrescens were active against Pr. intermedia. Both species showed a high degree of activity against P. gingivalis, whereas only one P. gingivalis strain produced bacteriocin-like activity against either of the other two species. Both Pr. nigrescens and Pr. intermedia showed some activity (40% and 20%, respectively) against other strains of the same species. Such bacteriocin production might be expected to influence the distribution of these black-pigmented species in vivo. Of 224 periodontal sites sampled, only 2.6% yielded mixed cultures of black-pigmented species and of these only one strain, a P. gingivalis isolate, produced bacteriocin-like activity against any of the other strains isolated from these sites. These data support the concept that local production of bacteriocin-like activity in vivo may contribute to the selection of the black-pigmented bacterial profile in subgingival sites.