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At least 361 records · Page 20Linked to original sources
PubMed2002

A physical map of the mouse genome.

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.

Animals↗
PubMed2006

Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid.

Isoniazid is a key drug used in the treatment of tuberculosis. Isoniazid is a pro-drug, which, after activation by the katG-encoded catalase peroxidase, reacts nonenzymatically with NAD(+) and NADP(+) to generate several isonicotinoyl adducts of these pyridine nucleotides. One of these, the acyclic 4S isomer of isoniazid-NAD, targets the inhA-encoded enoyl-ACP reductase, an enzyme essential for mycolic acid biosynthesis in Mycobacterium tuberculosis. Here we show that the acyclic 4R isomer of isoniazid-NADP inhibits the M. tuberculosis dihydrofolate reductase (DHFR), an enzyme essential for nucleic acid synthesis. This biologically relevant form of the isoniazid adduct is a subnanomolar bisubstrate inhibitor of M. tuberculosis DHFR. Expression of M. tuberculosis DHFR in Mycobacterium smegmatis mc(2)155 protects cells against growth inhibition by isoniazid by sequestering the drug. Thus, M. tuberculosis DHFR is the first new target for isoniazid identified in the last decade.

Cell Proliferation↗
PubMed1998

Oral white sponge naevus: response to antibiotic therapy.

White sponge naevus is a rare benign inherited disorder of the mucous membranes, principally the oral mucosa. Although the condition is painless, patients are often symptomatic, complaining of an altered texture of the mucosa or that the lesions are unaesthetic. No standard treatment for the condition exists although numerous treatments have been tried. We now report on six patients who were prescribed systemic antibiotic therapy; three were adult men aged 24 years, 32 years, and 52 years, one an 11-year-old woman, one a 6-year-old woman (daughter of the 32-year-old man) and an 18-month-old boy (son of the 24-year-old man). Four responded as judged by clinical examination, although not the 6-year-old female or the 18-month-old male; the discontinuation of therapy then resulted in clinical recurrence in those who had responded, but long-term low dose treatment maintained the remission.

Adult↗
PubMed2002

Healthcare for older persons, a country profile: Nigeria.

The Nigerian population is undergoing demographic transition, with an increasing population of older people. Nuclear and extended family members traditionally care for older persons at home. We have observed changes in home living conditions due to reduced family size, and urban migration for economic reasons are likely to affect the care of older people. The inadequately funded healthcare system has placed little emphasis on the care of older people because there are more-pressing health problems and funding for older people is limited. This paper advocates improved attention to the health needs of older people through improved budgetary allocation, revision of the training curriculum of all cadres of health staff to include geriatrics, and utilization of primary healthcare facilities.

Aged↗
PubMed2004

Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes.

We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphilis-causing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function.

ATP-Binding Cassette Transporters↗
PubMed2002

The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts.

The 3.31-Mb genome sequence of the intracellular pathogen and potential bioterrorism agent, Brucella suis, was determined. Comparison of B. suis with Brucella melitensis has defined a finite set of differences that could be responsible for the differences in virulence and host preference between these organisms, and indicates that phage have played a significant role in their divergence. Analysis of the B. suis genome reveals transport and metabolic capabilities akin to soil/plant-associated bacteria. Extensive gene synteny between B. suis chromosome 1 and the genome of the plant symbiont Mesorhizobium loti emphasizes the similarity between this animal pathogen and plant pathogens and symbionts. A limited repertoire of genes homologous to known bacterial virulence factors were identified.

Alphaproteobacteria↗
PubMed1987

Quantitative studies of human cardiac metabolism by 31P rotating-frame NMR.

We have developed 31P NMR spectroscopic methods to determine quantitatively relative levels of phosphorous-containing metabolites in the human myocardium. We have used localization techniques based on the rotating-frame imaging experiment and carried out with a double-surface coil probe. Information is obtained from selected slices by rotating-frame depth selection and from a complete one-dimensional spectroscopic image using phase-modulated rotating-frame imaging. The methods collect biochemical information from metabolites in human heart, and we use the fact that the phosphocreatine/ATP molar ratio in skeletal muscle at rest is higher than that in working heart to demonstrate that localization has been achieved for each investigation. The phosphocreatine/ATP molar ratio in normal human heart has been measured as 1.55 +/- 0.20 (mean +/- SD) (3.5-sec interpulse delay) in six subjects using depth selection and as 1.53 +/- 0.25 (mean +/- SD) in four subjects using spectroscopic imaging. Measurement of this ratio is expected to give a useful and reproducible index of myocardial energetics in normal and pathological states.

Adenosine Triphosphate↗
PubMed2003

Biological variation in Trichinella species and genotypes.

At present, the genus Trichinella comprises seven species of which five have encapsulated muscle larvae (T. spiralis, T. nativa, T. britovi, T. nelsoni and T. murrelli) and two do not (T. pseudospiralis and T. papuae) plus three genotypes of non-specific status (T6, T8 and T9). The diagnostic characteristics of these species are based on biological, biochemical and genetic criteria. Of biological significance is variation observed among species and isolates in parameters such as infectivity and immunogenicity. Infectivity of Trichinella species or isolates is determined, among other considerations, by the immune status of the host in response to species- or isolate-specific antigens. Common and particular antigens determine the extent of protective responses against homologous or heterologous challenge. The kinetics of isotype, cytokine and inflammatory responses against T. spiralis infections are isolate-dependent. Trichinella spiralis and T. pseudospiralis induce different dose-dependent T-cell polarizations in the early host response, with T. spiralis initially preferentially promoting Th1-type responses before switching to Th2 and T. pseudospiralis driving Th2-type responses from the outset.

Animals↗
PubMed2006

Validation of the Edinburgh Postnatal Depression Scale as a screening tool for depression in late pregnancy among Nigerian women.

This study aimed to examine the validity of the Edinburgh Postnatal Depression Scale (EPDS) as a screening tool for depression in late pregnancy among Nigerian women. A total of 182 women in late pregnancy (32-36 weeks) completed either the English or the translated Yoruba language version of the EPDS and a proportion of them were then assessed for the presence of DSM-IV major and minor depressive disorders using the MINI International Neuropsychiatric Interview. A cut-off score of 10 on the EPDS was found to be the best for screening for both major and minor depression (sensitivity = 0.867, specificity = 0.915, Diagnostic Likelihood Ratio for a positive result = 10.200). When screening for major depression only, a cut-off of 12 was found to the most appropriate (sensitivity = 1.000, specificity = 0.961, Diagnostic Likelihood Ratio for a positive result = 25.641). The EPDS is a valid and useful instrument in screening for depression in late pregnancy among Nigerian women.

Adult↗
PubMed2006

Microcapsules formulated in the enteric coating copolymer Eudragit L100 as delivery systems for oral vaccination against infections by gastrointestinal nematode parasites.

Microcapsules using the copolymer of methacrylic acid (Eudragit L100) were formulated for oral delivery of vaccines against the enteral/parenteral nematode parasite Trichinella spiralis. Antigenic preparations from first stage larvae (L1) of T. spiralis were microencapsulated in Eudragit L100. The microcapsules prepared by the spray drying method were resistant to acid pH, although the antigen was rapidly released under neutral and basic environmental conditions. The native protein conformation and biological activity was preserved in the microcapsules, as assessed by SDS-PAGE and ELISA. When administered to NIH mice, the antigen loaded microcapsules protected against infection by T. spiralis at both the intestinal and muscular levels, the worm burden diminishing by 45.58 and 53.33%, respectively. Furthermore, following administration of the microparticles an increase of the serum IgG1 response, a marker for the Th2 type response, was evident. These results indicate that microcapsules formulated with anionic biocompatible polymers such as Eudragit may be useful for oral vaccination against nematode infections.

Administration, Oral↗
PubMed1999

Preparation and characterization of albendazole beta-cyclodextrin complexes.

Albendazole (ABZ), mebendazole (MBZ), and ricobendazole (RBZ) are low-soluble anthelmintic benzimidazole carbamate drugs. To increase their aqueous solubility, three different types of beta-cyclodextrins (CyDs): beta-cyclodextrin (CD), hydroxypropyl-beta-cyclodextrin (HPCD), and methyl-beta-cyclodextrin (MCD) were used. Solubility depended on the type of CyDs. Increased solubility was obtained when the more substituted CyDs (HPCD or MCD) were used instead of nonsubstituted CD. Stability constants were calculated assuming a 1:1 stoichiometry. Calculated stability constant values depended on initial solubility of drug and pH of the medium. Solid ABZ complexes were prepared by coprecipitation and freeze-drying methods. These products were compared with physical mixtures of ABZ and CyDs. The characterization of these products was made by differential scanning calorimetry (DSC) and drug release studies. True inclusion complexes were obtained only by the freeze-drying method. Drug release studies showed that the freeze-dried inclusion complexes increased the solubility rate of ABZ, although a supersaturation effect was observed when drug release studies were performed in nonsink conditions. A bioavailability study on mice was done with a formulation of ABZ:HPCD complex and was compared to a conventional ABZ suspension. A significantly (p < .05) shorter Tmax of absorption was obtained by using the complex formulation. Greater and significant (p < .05) differences for AUC and Cmax were observed.

Albendazole↗
PubMed2004

Low genetic diversity despite hyperendemicity of hepatitis B virus genotype E throughout West Africa.

Sub-Saharan Africa suffers from an excessively high endemicity of hepatitis B virus (HBV), but little is known about the prevalent genotypes. In this study, we investigated the PreS1/PreS2/S genes of 127 viruses obtained from 12 locations in Mali, Burkina Faso, Togo, Benin, Nigeria, Cameroon, and the Democratic Republic of Congo. Except for those obtained from the Cameroon HIV cohort (18/22 HBV genotype A), 96 of 105 sequences belonged to HBV genotype E (HBV/E), and viral DNA was very similar (1.67% diversity) throughout this vast HBV/E crescent, which spans 6000 km across Africa. The low diversity suggests that HBV/E may have a short evolutionary history. Considering a typical mutation rate of DNA viruses, it would take only 200 years for the strain diversity of HBV/E viruses to develop from a single introductory event. The relatively recent introduction of HBV/E into humans would also explain its conspicuous absence in the Americas, despite the forced immigration of slaves from west Africa, until the early 19th century. Infection during infancy is mostly associated with chronic carrier status, and this combination can account for the explosive spread of virtually identical viruses within a community, but whether other routes of long-range transmissions must be considered becomes an important question.

Adolescent↗
PubMed2002

AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis.

The inhibition of apoptosis is a critical event in the development of colorectal malignancies, although the mechanism(s) remain incompletely understood. The anti-apoptotic proto-oncogene, AKT, has been implicated in the molecular pathogenesis of a variety of human malignancies; however, no data exist on the role of AKT in colon carcinogenesis. We therefore evaluated the presence of AKT in human and experimental colon neoplasms by immunohistochemistry. Normal colonic mucosa and hyperplastic polyps exhibited no significant AKT expression, in marked contrast to the dramatic AKT immunoreactivity seen in colorectal cancers (57% positive) and in both human colorectal cancer cell lines examined. Importantly, AKT was also detected in 57% of the adenomas examined, implicating overexpression of this proto-oncogene as an early event during colon carcinogenesis. Moreover, in the rodent-carcinogen model, azoxymethane (AOM)-treatment induced AKT expression in premalignant rat colonocytes. Tumors that evolve via different genetic pathways displayed a lower incidence of AKT overexpression. Indeed, only 22% of mismatch repair defective tumors and 42% of AOM-induced rodent tumors upregulated AKT. Staining with an antibody specific for AKT 2 duplicated findings with the AKT 1&2 antibody, suggesting that AKT 2 was the predominant isoform involved in colon carcinogenesis. Furthermore, utilizing an antibody that specifically recognizes the serine-473 phosphorylated form of AKT, we observed that activated AKT was detectable in the neoplastic but not normal epithelium. In summary, our immunohistochemical analysis indicates AKT overexpression occurs frequently during human colon carcinogenesis, but is less common in colon cancers with microsatellite instability. The early inhibition of apoptosis during sporadic colon carcinogenesis may be related, at least partly, to the overexpression of AKT.

Animals↗
PubMed2002

At issue: predicting drug-free treatment response in acute psychosis from the Soteria project.

Although an estimated 25 to 40 percent of acute psychoses remit without antipsychotic drug treatment, only limited efforts have been made to identify individuals in early episodes who might be able to recover without medications. This retrospective exploratory study uses baseline information from the Soteria project (young, unmarried, first and second episode DSM-II schizophrenia, n = 179) to develop a preliminary model for this purpose. Forty-three percent of experimentally treated subjects received no antipsychotic medications during the 2-year followup period and were designated "drug-free responders." At followup, this group had better outcomes (+ 0.82 of a standard deviation [SD]) on a composite outcome scale (representing rehospitalization, psychopathology, independent living, social and occupational functioning). A predictive model using three variables (age, the Goldstein Adolescent Social Competence Scale score, and number of diagnostic symptoms) correctly identified this subgroup 79 percent of the time (boot-strapped 95% confidence interval [CI], 65-90%). Predicted drug-free responders exhibited moderately better outcomes (effect size: 0.38 to 0.61 of an SD) when treated at Soteria. These data advance the hypothesis that an identifiable subgroup of individuals with early episode psychosis might fare better when receiving specialized psychosocial intervention and minimal or no use of antipsychotic medications.

Acute Disease↗
PubMed2005

Medication-free research in early episode schizophrenia: evidence of long-term harm?

This study investigates the question of whether short periods of medication-free research in early episode schizophrenia result in demonstrable long-term harm to human subjects. A meta-analysis of published quasi-experimental and random assignment studies that had a majority of first- or second-episode schizophrenia spectrum subjects, at least 1 initially unmedicated group, and a minimum of 1-year results was conducted. Only 6 studies, with 623 subjects, met inclusion criteria. The initially unmedicated groups showed a small, statistically nonsignificant long-term advantage (r = -0.09). Incorporating only random assignment studies into a composite effect size produced a similar near-zero result (r = 0.01). Good-quality evidence is inadequate to support a conclusion of long-term harm resulting from short-term postponement of medication in early episode schizophrenia research. A categorical prohibition against such research should be reconsidered.

Antipsychotic Agents↗