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Interferon research abs 1 || Hemoglobin research abs || Stem cell research abs || Nucleic acid research abs || Herpes research abs || Bronchitis research abs || Schizophrenia research abs || Tuberculosis research abs

Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):241-6. Epub 2002 Dec 27.
Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium tuberculosis transcription pattern characteristic of nonreplicating persistence.

Shi L, Jung YJ, Tyagi S, Gennaro ML, North RJ.

Public Health Research Institute, Newark, NJ 07103, USA.

The lung is the primary target of infection with Mycobacterium tuberculosis. It is well established that, in mouse lung, expression of adaptive, Th1-mediated host immunity inhibits further multiplication of M. tuberculosis. Here, real-time RT-PCR was used to define the pattern of expression against time of lung infection of key genes involved in Th1-mediated immunity and of selected genes of M. tuberculosis. Inhibition of bacterial multiplication was preceded by increased mRNA synthesis for IFN-gamma and inducible NO synthase (NOS2) and by NOS2 protein synthesis in infected macrophages. Concurrently, the pattern of transcription of bacterial genes underwent dramatic changes. mRNA synthesis increased for alpha-crystallin (acr), rv2626c, and rv2623 and decreased for superoxide dismutase C (sodC), sodA, and fibronectin-binding protein B (fbpB). This pattern of M. tuberculosis transcription is characteristic of the nonreplicating persistence [Wayne, L. G. & Sohaskey, C. D. (2001) Annu. Rev. Microbiol. 55, 139-163] associated with adaptation of tubercle bacilli to hypoxia in vitro. Based on this similarity, we infer that host immunity induces bacterial growth arrest. In IFN-gamma gene-deleted mice, bacterial growth was not controlled; NOS2 protein was not detected in macrophages; sodC, sodA, and fbpB transcription showed no decrease; and acr, rv2626c, and rv2623 transcription increased only at the terminal stages of lung pathology. These findings define the transcription signature of M. tuberculosis as it transitions from growth to persistence in the mouse lung. The bacterial transcription changes measured at onset of Th1-mediated immunity are likely induced, directly or indirectly, by nitric oxide generated by infected macrophages.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12506197&dopt=Abstract

Swiss Med Wkly. 2002 Sep 7;132(35-36):517-22.
Outcome of treatment of pulmonary tuberculosis in Switzerland in 1996.

Helbling P, Medinger C, Altpeter E, Raeber PA, Beeli D, Zellweger JP.

Swiss Federal Office of Public Health, Bern. peter.helbinag.admin.ch

PRINCIPLES: Adequate treatment of pulmonary tuberculosis cures patients and reduces transmission. The study assesses treatment outcomes under current conditions in Switzerland. METHODS: Retrospective cohort study including all TB cases with positive sputum cultures notified to the national surveillance system between July 1996 and June 1997. Ten months after notification, treating physicians reported the outcomes using WHO categories. RESULTS: Of 265 patients, 209 (79%) completed at least 6 months' treatment, 3 (1%) were treatment failures, 23 (9%) died, 8 (3%) defaulted from treatment and 22 (8%) left the country. The proportion of successful treatments did not significantly differ between the 103 Swiss-born (80%) and the 162 foreign-born (78%) patients. There were 19 deaths (18%) in the Swiss-born and 4 (2%) in the foreign-born groups; death was caused by TB in two patients, 10 died of other causes (cause unknown in 11). In the foreign-born group there were 31 (19%) potentially unsatisfactory outcomes (treatment failure, default from treatment, transfer abroad) and in the Swiss-born group 2 (2%). Default from treatment involved 8 patients, 6 of whom were asylum seekers. In a multivariate analysis potentially unsatisfactory outcomes were not significantly associated with foreign origin but with status as a foreigner of irregular or unknown legal status (adj. OR 8.8; 95% CI 1.4 to 53.7). CONCLUSIONS: Overall treatment success rates are satisfactory and similar to those of other western European countries. Potentially unsatisfactory outcomes are more common in foreign-born persons of irregular legal status. Tracking of non-adherent patients by health workers could further improve outcomes.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12506334&dopt=Abstract

S Afr Med J. 2002 Nov;92(11):907-11.
Aetiology and outcome of severe community-acquired pneumonia in children admitted to a paediatric intensive care unit.

Delport SD, Brisley T.

Department of Paediatrics, Kalafong Hospital, University of Pretoria.

OBJECTIVE: To determine the aetiological agents and outcome of severe community-acquired pneumonia (SCAP) in children admitted to the paediatric intensive care unit (PICU) at Kalafong Hospital, Pretoria. PATIENTS AND METHODS: An audit was done after a protocol was implemented to identify the aetiological agents in children with life-threatening SCAP admitted to the PICU from the emergency room. The following investigations were done as per protocol: blood culture, culture of the tracheal aspirate, immunofluorescence and culture of the nasopharyngeal aspirate, microscopy and culture of the gastric juice for Mycobacterium tuberculosis, and determination of HIV status. The following data, documented prospectively, were obtained from patient records: date of admission, age, gender, weight, duration of ventilation, duration of stay in the PICU, survival or death, and severity of illness as determined by means of the score for acute neonatal physiology (SNAP) or paediatric risk of mortality (PRISM) score depending on the child's age. RESULTS: Twenty-three children were admitted over a 1-year period (1 November 1994-30 October 1995). Their median age was 10 weeks (range 2 weeks-5 years) and the sex distribution was equal. Two children were HIV-infected. Twenty children received mechanical ventilation for a median period of 6.5 days (range 2-16 days). Aetiological agents were identified in 15/23 children (65%). Respiratory syncytial virus (RSV) was the most common pathogen, identified in 7/23 children, Klebsiella pneumoniae was the most common bacterial pathogen, identified in 5 children (2 blood cultures and 3 tracheal aspirates). Tuberculosis was not diagnosed. The mean PRISM score was similar in survivors and children who died. The case fatality rate was 30%. The 7 children who died had a median arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) ratio of 94 (range 32-111) and the 16 survivors had a median ratio of 146 (range 51-252) (P = 0.01) on admission. Both HIV-infected children died and postmortem examination showed a pneumonia due to Pneumocystis carinii and cytomegalovirus. CONCLUSIONS: SCAP occurs in very young children. One or more pathogens were isolated in 65% of cases. Viral pathogens predominated, with RSV being the most common. The yield of positive blood cultures was low at 17%. Streptococcus pneumoniae and Haemophilus influenzae were not found. The case fatality rate was 30% and death was more likely with a low PaO2/FiO2 ratio on admission.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12506595&dopt=Abstract

Vopr Med Khim. 2002 Jul-Aug;48(4):361-7.
[Genetic heterogeneity of cytochrome CYP51 in clinical strains of Mycobacterium tuberculosis]

[Article in Russian]

Shavkunov AS, Lazarev VN, Chernausova LN, Kuz'min AV, Govorun VM.

Institute of Physico-Chemical Medicine, Malaya Pirogovskaya ul. la, Moscow, 119828 Russia. a_s_shavkunootbox.ru

Information on the complete genome sequences of a number of organisms available recently offers essentially new opportunities for the development of new, highly effective antimicrobial compounds. In particular, the search for new effective antituberculosis drugs remains an important problem, due to the recent increase of number of patients suffering with tuberculosis. In this respect considerable attention is paid to the cyp51-like gene Rv0764c encoding sterol-14 alpha-demethylase belonging to the cytochrome P450 superfamily, which has been discovered by computer analysis of the Mycobacterium tuberculosis genome sequence. We have screened 64 clinical isolates of M. tuberculosis for functionally relevant mutations in the coding sequence of the gene encoding Cyp 51-demethylase by single-strand conformation polymorphism analysis (SSCP) and sequencing of PCR-amplified gene fragments. Structural analysis of the gene in the isolates revealed no mutations leading to amino acid substitutions in the corresponding protein. 10 isolates had a silent nucleotide substitution 114 GCT-->GCC. Computer analysis of cyp51 sequence of the CDC1551 strain also revealed a similar nucleotide substitution, which has not been mentioned previously. The data obtained demonstrate that the sequence of the gene is highly conserved, supporting the advisability of M. tuberculosis Cyp51 protein to be considered as a molecular target for new antitubercular drugs. The SNP found in the gene coding sequence may be employed in the studies of M. tuberculosis population genetics.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12506611&dopt=Abstract

Zh Mikrobiol Epidemiol Immunobiol. 2002 Nov-Dec;(6):30-5.
[Genetic typing of Mycobacterium tuberculosis strains by spoligotyping and genome fingerprinting techniques]

[Article in Russian]

Shemiakin IG, Stepanshina VN, Korobova OV, Anisimova VA, Ivanov IIu, Lipin MIu, Lazarev AA, Skaldina AI, Chernavskaia LA, Tarasova TI.

State Research Center of Applied Microbiology, Obolensk, Moscow Region, Russia.

A total of 122 M. tuberculosis clinical drug-resistant strains isolated in Central Russia were studied by spoligotyping and genome fingerprinting techniques. According to spoligotyping results 77% of M. tuberculosis strains were distributed to 13 oligotypes, while 23% of these strains were found to form unique patterns. Most of them belonged to the families Beijing and Haarlem (43.4% and 13.9% respectively). The patterns of the strains of oligotype 12 (7F-7F-7E-0E-78-3E) were identical to those of the strains isolated in Brazil, France and the Netherlands. The strains of the spoligotype 22 (7F-1E-7F-7F-07-3E) had the patterns identical to those of the strains of group S13, also isolated in Brazil. According to genome fingerprinting 31.4% of the strains were found to belong to clusters with the similarity coefficient equal to 1. The strains belonging to genotypes W and A1 were found to prevail in the analyzed group.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12506624&dopt=Abstract

Hair loss is a problem in modern soceity. Examining the factors of hair growth may shed light on how hair loss might occur. How long can hair grow before it stops growing eventually if it does? Given that the hair growth rate is quite uniform and constant, somewhere between 0.3-0.5 millimeters per day, it's believed that the length of anagen, the growth phase, differs among individuals, and this is the major determinant to the maximum hair length. For some individuals, anagen may last ten years. Of course the length of the anagen is governed by genes, and the genetic background of the individuals. Non-genetic factors such as nutritional condition, weather, seasonal changes (hair may grow a bit faster during winter), taking medications, health condition may of course influence the rate of hair growth as well as hair loss. The shape of the hair, straight or curly, is dependent on the shape of the follicle. A circular or round hair follicle would generate straight hair, while the follicle with oval or elliptical shapes (in its cross-section) would produce a curly hair.

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