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Biomedical subjects

M Ruben

Publications and source records attributed to M Ruben.

At least 19 recordsLinked to original sources

Dysregulated expression of IFN-gamma and IL-10 and impaired IFN-gamma-mediated responses at different disease stages in patients with genital herpes simplex virus-2 infection.

Cell-mediated T-helper type-1 (Th1) responses play a vital role in the immunopathogenesis of genital infections caused by herpes simplex virus 2 (HSV-2). We investigated the role of Th responses in HSV-2 infection at different disease stages by analysing the production of Th cytokines in HSV-stimulated peripheral blood mononuclear cells (PBMCs). IFN-gamma production decreased over time following a recurrence, whereas levels of IL-10, and to a lesser extent IL-2, remained elevated during this period. In addition, PBMCs from asymptomatic seropositive individuals produced high levels of IFN-gamma and low levels of IL-10, in contrast to individuals with a history of genital ulcers. Following a recurrence, virus copy number in the genital lesions decreased progressively over time, in a manner similar to IFN-gamma production by HSV-2-stimulated PBMCs. Enhanced production of IFN-gamma may modulate HSV replication and B7 expression on monocytic cells of HSV-infected individuals. In contrast to seronegative controls, IFN-gamma failed to enhance B7 expression on monocytic cells of HSV-infected individuals. In addition, monocytic cells from HSV-2-infected individuals with recurrent disease supported greater HSV replication than did those of HSV-infected asymptomatic individuals or seronegative controls. Furthermore, addition of IFN-gamma resulted in enhanced HSV replication in monocytic cells of HSV-infected individuals with recurrent disease, in contrast to the inhibition observed in HSV-seropositive asymptomatic individuals and seronegative controls. Taken together, our results suggest that dysregulated production of IFN-gamma at different disease stages and the impaired ability of monocytic cells to respond to IFN-gamma may play a role in the pathogenesis of recurrent genital herpes disease.

Case-Control Studies↗

Dengue viruses in the Caribbean. Twenty years of dengue virus isolates from the Caribbean Epidemiology Centre.

The first isolate of a dengue virus in the Americas was obtained in Trinidad and Tobago in 1953, and several dengue virus isolates were obtained in subsequent years. However, the systematic isolation and typing of dengue viruses in support of virus surveillance and outbreak investigations did not start until the creation of the Caribbean Epidemiology Centre (CAREC) in 1975. Since then, over two thousand viral isolates have been obtained and typed from many countries in the English and Dutch-speaking Caribbean. In this communication, virological data from 17 countries between 1977 and 1996 are presented and analyzed together for the first time with available epidemiological data. Types 1, 2 and 4 were isolated over the period, and geographic and temporal patterns in the distribution of the most prevalent strains are presented. The historical surveillance data is critically assessed. A temporal correlation with reported dengue incidence and rainfall data in Trinidad and Tobago is reported. Recent changes in epidemiological patterns are described, including reference to two large later outbreaks. Risk assessment of complicated forms of dengue virus infections in the Caribbean has been attempted, with some success. The importance of ongoing systematic surveillance is discussed.

Age Distribution↗

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from three Caribbean countries: Trinidad, Guyana, and St. Vincent.

BACKGROUND: The percentage of Neisseria gonorrhoeae isolates resistant to antimicrobial agents commonly used for treatment is unknown in many Caribbean countries. GOAL: To determine the antimicrobial susceptibility of N gonorrhoeae isolates from Trinidad (144 isolates), Guyana (70 isolates), and St. Vincent (68 isolates) so baseline data can be established for further studies, and to assist in establishing effective treatment guidelines. STUDY DESIGN: Consecutive urethral and endocervical specimens from several clinics were collected and identified as N gonorrhoeae. Isolates of N gonorrhoeae were tested for their susceptibility to penicillin, tetracycline, ceftriaxone, ciprofloxacin, spectinomycin, and azithromycin. The presumptive identification of penicillinase-producing N gonorrhoeae and/or tetracycline-resistant N gonorrhoeae isolates based on MIC was confirmed by plasmid and tetM content analysis. RESULTS: High percentages of penicillin and/or tetracycline resistance were observed in N gonorrhoeae isolates from Guyana (92.9%), St. Vincent (44.1%), and Trinidad (42.4%). Isolates from all three countries were susceptible to ceftriaxone, ciprofloxacin, and spectinomycin. One penicillinase-producing N gonorrhoeae/tetracycline-resistant N gonorrhoeae from Guyana had an MIC of 0.5 microg/l to ciprofloxacin. This and nine other isolates from Guyana also were resistant to azithromycin (defined as MIC > or = 2.0 microg/ml) as well as penicillin and tetracycline. A reduced susceptibility to azithromycin was displayed by 16% of the isolates from St. Vincent and 72% of the isolates from Guyana (MIC, 0.25-1.0 microg/ml). Most penicillinase-producing N gonorrhoeae isolates carried Africa-type plasmids (61/90), with 28 of 90 having Toronto-type plasmids and a single isolate carrying an Asia-type plasmid. The tetM determinant in tetracycline-resistant N gonorrhoeae isolates was predominantly of the Dutch type (68/91). CONCLUSIONS: The high prevalence of N gonorrhoeae isolates from 3 of 21 English- and Dutch-speaking Caricom countries in the Caribbean with either plasmid-mediated or chromosomal resistance to penicillin and tetracycline supports international observations that these drugs should not be used to treat gonococcal infections. The detection of isolates with reduced susceptibility to drugs such as azithromycin, which currently are recommended for treatment in the region, attest to the importance of the continued monitoring of gonococcal antimicrobial susceptibility for the maintenance of effective treatment guidelines.

Anti-Bacterial Agents↗

[Nutritional status of preschool children in Ciudad de La Habana from 1972 to 1993].

Two anthropometric surveys of children and adolescents have been carried out in Cuba with national samples. A third study done in the province of Ciudad de la Habana provided information on the physical characteristics of the population in that area and a baseline for the periodic evaluation of its nutritional status. This article compares the weight and height results obtained in these surveys for children 0 to 5 years old who lived in this province with the international reference standards proposed by WHO. The results show that, despite the economic difficulties the country has faced, the prevalence of malnutrition is low. In 1993, the prevalence of low height-for-age was 3.1%; that of low weight-for-height, 0.4%; and that of low weight-for-age, 1.5%. Overweight was the most common type of malnutrition, with a prevalence of 5.2%. Between 1972 and 1993, the prevalence of chronic malnutrition fell 32.6%, acute malnutrition was reduced by 69.2%; malnutrition of all types decreased by 44.4%; and overweight fell 48.5%.

Anthropometry↗

Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes.

Culture of infectious virus, PCR amplification of viral DNA, and the appearance of genital skin lesions were used as markers to study the course of a recurrence of genital herpes in 40 patients treated with famciclovir or placebo. The highest frequency of patients with skin lesions occurred within the first 36 h following the onset of a recurrence, which also corresponded to the peak in the production of virus. While the timing of the peak in skin lesions was independent of the type of treatment, the frequency of lesions and the release of virus at the lesion site were both reduced by famciclovir treatment. Furthermore, patients receiving this antiviral agent showed a more rapid recovery time and a shorter period during which viral DNA could be detected at the lesion. PCR and then Southern blot hybridization greatly enhanced our ability to detect herpes simplex virus at the lesion site. This procedure proved to be of greater diagnostic value in assessing genital herpes than the standard culture method currently used. In addition, PCR was more sensitive in evaluating treatment effectiveness.

2-Aminopurine↗

Regulated expression of a transfected human cardiac actin gene during differentiation of multipotential murine embryonal carcinoma cells.

P19 embryonal carcinoma (EC) cells are multipotential stem cells which can be induced to differentiate in vitro into a variety of cell types, including cardiac muscle cells. A cloned human cardiac actin (CH-actin) gene was transfected into P19 cells, and stable transformants were isolated. Low levels of CH-actin mRNA were present in transformed EC cells, but a marked increase in the level of CH-actin mRNA was found as these cells differentiated into cardiac muscle. The accumulation of CH-actin mRNA paralleled that of the endogenous mouse cardiac actin mRNA. A chimeric gene, which consisted of the CH-actin promoter linked to the herpes simplex virus thymidine kinase coding region, was constructed and transfected into P19 cells. In these transformants, the thymidine kinase protein was located almost exclusively in cardiac muscle cells and was generally not detectable in EC or other nonmuscle cells. These results suggest that the transfected CH-actin promoter functions in the appropriate developmental and tissue-specific manner during the differentiation of multipotential EC cells in culture.

Actins↗

An integrated software system for microcomputer management of recombinant DNA data.

A database-oriented system (pCP123) is described for the manipulation of recombinant DNA data. This system was developed within the context of an integrated software package with spreadsheet, database, graphing and programming capabilities. The system includes two databases, one of sites and another of regions, coordinately handled by a series of macro-programs operated from four user-define menus. A distinctive feature of the system is the possibility of handling both ends of defined functional or structural regions in situations of simulated deletions or insertions.

Computers↗

Contact lenses.

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Aged↗

Corneal epithelial response of the primate eye to gas permeable corneal contact lenses: a preliminary report.

The comparative corneal epithelial effects of rigid gas permeable and soft contact lenses are reported in the present preliminary study using two bush baby monkeys (Galago senegalensis). Both types of lenses produced early cell death among the surface squamous cells while internally the epithelium and its nerve fibers remained normal. Sporadically small abnormal groups of cells involving two to three of the surface layers were observed in both the hard and soft lens wearing corneas. It was concluded that this represented superficial punctate keratitis (SPK). Small superficial intracellular epithelial cysts with membranous contents were infrequently noted in the gas permeable lens wearing cornea and it is suggested here that they were mild forms or precursors of those seen clinically in human corneas. Since the gas permeable lens met the corneal oxygen requirement it is postulated that the traumatic effect of the rigidity of the lens caused the cystic formation to occur. The relative hypoxia induced by the soft contact lens resulted in a mild superficial epithelial edema.

Animals↗

Covalently closed circles of adenovirus 5 DNA.

The genome of adenoviruses is a double-stranded linear DNA molecule with inverted terminal repeats about 100 base pairs (bp) in length and a terminal protein covalently linked to the 5' nucleotide of each strand. Both of these features permit the formation of DNA circles, the inverted repeats allowing the circularization of single-stranded DNA and the terminal protein the joining of one or more molecules to yield double-stranded circles or concatemers. However, although the existence of covalently closed circles has been postulated, double-stranded viral DNA purified from virions or infected cells by conventional methods (that is, using proteases and phenol or chloroform) has always been obtained in a linear form. Here, we present evidence for the existence in adenovirus 5 (Ad5) infected cells of novel structures resulting from covalent head-to-tail joining of viral DNA molecules and show that these structures are due at least in part to the formation of covalently closed circles.

Adenoviridae↗

Integration and expression of viral DNA in cells transformed by host range mutants of adenovirus type 5.

Group I host range (hr) mutants of adenovirus type 5 are unable to transform rat embryo or rat embryo brain cells but induce an abnormal transformation of baby rat kidney cells. We established several transformed rat kidney cell lines and characterized them with respect to the transformed phenotype and the structure of the integrated viral DNA. The hr mutant-transformed cells, unlike wild-type virus transformants, were fibroblastic rather than epithelial, failed to grow in soft agar, and were also less tumorigenic in nude mice. Studies on the structure of the integrated viral DNA sequences showed that hr-transformed cells always contained the left end of the adenovirus DNA, but the size of the integrated DNA fragment varied among different lines, and a high percentage of the lines contained the entire viral genome colinearly integrated. The patterns of integration were maintained after prolonged growth in culture and after subcloning. Attempts to rescue infectious virus from lines which contained the entire genome were unsuccessful. Using immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we analyzed the viral proteins expressed in hr-transformed cells. Results of these studies indicated that, like wild type-transformed cells, hr transformants expressed E1B proteins of molecular weight 58,000 and 19,000.

Adenoviridae↗