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Human chromosome 12 is required for optimal interactions between Tat and TAR of human immunodeficiency virus type 1 in rodent cells.

Levels of trans activation of the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) by the virally encoded transactivator Tat show marked species-specific differences. For example, levels of transactivation observed in Chinese hamster ovary (CHO) rodent cells are 10-fold lower than those in human cells or in CHO cells that contain the human chromosome 12. Thus, the human chromosome 12 codes for a protein or proteins that are required for optimal Tat activity. Here, the function of these cellular proteins was analyzed by using a number of modified HIV-1 LTRs and Tats. Neither DNA-binding proteins that bind to the HIV-1 LTR nor proteins that interact with the activation domain of Tat could be implicated in this defect. However, since species-specific differences were no longer observed with hybrid proteins that contain the activation domain of Tat fused to heterologous RNA-binding proteins, optimal interactions between Tat and the trans-acting responsive RNA (TAR) must depend on this factor(s).

Animals↗

Congenital hypomegakaryocytic thrombocytopenia associated with bilateral absence of the radius - the TAR syndrome.

A case of the TAR syndrome is described which presented bilateral absence of the radius and pronounced thrombocytopenia at birth; when seen at the age of 6, growth and development was within normal limits, except for the upper extremities, and no signs of an haemorrhagic diathesis were seen. A careful family study brought 2 additional cases to light: a female second cousin was found to have bilateral absent radius, but no haematological abnormalities when seen at the age of 10. Her younger brother had died at the age of 3 months with severe thrombocytopenia and heavily malformed, flipper-like upper extremities. The broad clinical variation of the syndrome should be kept in mind in genetic studies and counselling.

Abnormalities, Multiple↗

Purification and partial characterization of a basic xylanase produced by thermoalkaliphilic Bacillus sp. strain TAR-1.

A basic xylanase was purified from the culture supernatant of thermoalkaliphilic Bacillus sp. strain TAR-1. Its molecular mass and isoelectric point were 23 kDa and > pH 9.3, respectively. The enzyme showed a broad pH profile and was optimally active at 70 degrees C. Analyses of xylan-degradation products and N-terminal amino acid sequence revealed that the enzyme would be a family 11/G endoxylanase.

Bacillus↗

Clinical predictors of respiratory failure and long-term outcome in black tar heroin-associated wound botulism.

STUDY OBJECTIVES: To our knowledge, the predictors of respiratory failure (RF) and long-term mechanical ventilation have not previously been examined in patients with wound botulism associated with black tar heroin use. DESIGN: Retrospective case series. SETTING: A large university hospital. PATIENTS: Twenty consecutive patients from 1991 to 1998 with a diagnosis of wound botulism associated with drug use as identified through chart records from a single institution. RESULTS: The predominant mode of drug use was subcutaneous (75%). Fifteen of 20 patients (75%) developed RF. The clinical presentation was similar in groups with RF and without RF. Of those patients who received antitoxin within 12 h of presentation, 57% required mechanical ventilation compared to 85% of patients receiving the antitoxin after 12 h. The median durations of mechanical ventilation were 11 days for those who received antitoxin within 12 h, and 54 days for those who did not receive antitoxin within 12 h. The duration of mechanical ventilation for patients receiving antibiotics within 12 h was 35 days vs 54 days for patients receiving antibiotics after 12 h. Early tracheostomy (< 10 days after initial intubation) was associated with a shorter duration of mechanical ventilation (median, 45 days vs 60 days, respectively). CONCLUSION: Early antitoxin administration may decrease the need for and duration of mechanical ventilation among patients with wound botulism. Early tracheostomy may be beneficial for patients with RF.

Adult↗

Selective Cleavage of the HIV-1 TAR-RNA with a Peptide-Cyclen Conjugate.

Covalent linkage of the arginine-rich fragment of the Tat protein to 1,4,7,10-tetraazacyclododecane (cyclen) results in the selective cleavage of the TAR-RNA of HIV-1 (see picture; the biotin at the 5' end acts as a label for the subsequent analysis of the cleavage fragments). The cleavage occurs at room temperature and is diminished when Eu(III) ions are present-at a concentration of about 1/10 of the concentration of the peptide-cyclen conjugate. The pH dependence indicates that two ammonium ions are responsible for the cleavage reaction. The white arrows in the schematic diagram mark the cleavage sites in RNase T1, and the black arrows the sites in the peptide-cyclen conjugate.

Journal Article↗

[TAR-cloning of the short arm of human chromosome 7 in yeast and search for terminal sequences].

A partial clone library of the short arm of human chromosome 7 was created in yeast artificial chromosomes (YAC) using TAR-cloning. The DNA of monochromosome somatic hybrid cells (mouse/human) RuRag 14-4-7-44 containing short arm human chromosome 7 was used for cloning. The clone library was screened for YACs with the human DNA; the mitotic stability of these YACs, the sizes of cloned fragments, and an independent clonal distribution in the chromosome were determined. Human YACs were tested for the presence of chromosome 7p telomeric sequences.

Animals↗

[Cytogenetic disorders in workers of coal-tar chemical industry].

The authors studied frequencies of chromosomal aberration (CA) and sister chromatid exchanges (SCE) in workers of coal-tar chemical plant (34 individuals). The studies revealed significant increase of CA frequency (7.97 +/- 0.63%), when compared with reference groups 3.37 +/- 0.39% and 3.64 +/- 0.37%.

Adult↗

Intracellular expression of multimerized antisense TAR-Core RNAs inhibit the replication of human immunodeficiency virus type 1 in human CD4+ T lymphocytes.

Gene therapy is one of several approaches that are being tested in the search for an effective anti-HIV treatment. In this strategy, a "resistant" gene would be introduced into target cells, rendering them resistance to the infection of HIV. The HIV-1 Tat protein transactivate HIV-1 gene expression at the transcriptional level by interacting with its response element (TAR) in the long terminal repeat (LTR). Previously, we have shown that antisense polyTAR-Core RNAs can inhibit the transactivation of HIV-1 Tat protein in transiently transfected Jurkat cells. To determine whether this antisense polyTAR-Core RNAs could inhibit HIV-1 replication in CD4+ T cells, we transfected the antisense polyTAR-Core gene to MT4 cells and challenged them with HIV-1 SF33 strain. Levels of HIV-1 p24gag antigen were reduced more than 4-fold in cultures of the transduced MT4/LR cells infected with HIV-1 SF33 strain. In contrast, cultures of nontransduced MT4 cells and control LX vector transduced MT4/LX cells infected with the same viruses had high levels of HIV-1 p24gag. Our work showed that antisense polyTAR-Core RNAs were able to inhibit HIV-1 replication in CD4+ T cells, and could be used as resistance gene in further studying for gene therapy against HIV-1.

Animals↗

Wound botulism among black tar heroin users--Washington, 2003.

During August 22-26, 2003, four injection-drug users (IDUs) in Yakima County, Washington, sought medical care at the same hospital with complaints of several days of weakness, drooping eyelids, blurred vision, and difficulty speaking and swallowing. All four were regular, nonintravenous injectors of black tar heroin (BTH), and one also snorted BTH. This report summarizes the investigation of these cases, which implicated wound botulism (WB) as the cause of illness.

Adult↗

Tetraphocomelia and bilateral femorotibial synostosis. A severe variant of the thrombocytopenia-absent radii (TAR) syndrome?

In this report we describe severe tetraphocomelia with complete femorotibial fusion in a second trimester male fetus. The association of severe tetraphocomelia-femorotibial synostosis has previously been reported in three patients as examples of a severe variant of the thrombocytopenia-absent radii (TAR) syndrome. In the present fetus no morphological abnormalities of the megakaryocytes were detected. This observation is not in favour of the hypothesis that abnormalities of the primordial megakaryocytes may be causally related with the pathogenesis of the limb malformations as present in this syndrome.

Ectromelia↗

Household context and youth smoking behaviour: prevalence, frequency and tar yield.

Labour Force Smoking Survey data were used to examine the impact of household environment on the smoking behaviour of youth and young adults. Three indicators of older adult smoking behaviour were used to classify the smoking environment of households. The indicators were smoking prevalence, the mean number of cigarettes smoked per day, and the mean tar yield of cigarettes. Within households, the probability that a young person smokes, how much they smoke, and the type of cigarette they smoke is closely associated with the smoking behaviour of older adults in the household. Household smoking patterns contribute to the overall exposure of family members to the hazards of cigarette smoking and may influence the outcome of smoking cessation programs. Smoking cessation and prevention programs should consider the potential effect of family and household environments.

Adolescent↗

[Thrombocytopenia with bilateral absence of the radius (TAR syndrome). Reports of 2 clinical cases].

Thrombocytopenia with bilateral absent radii (TAR syndrome) is a hereditary condition with a recessive autosomic character. It is characterised by a series of hematological, skeletal and cardiac alterations, and also by various clinical manifestations. The frequency of this syndrome is very low. During the first months of life, prognosis is related to the severity of hemorrhage, but it improves after two years. Diagnosis is at times complex owing to the similarity between this and other syndromes. Therapy, especially during the first year of life, is based on blood transfusion. The paper describes clinical findings in two subjects admitted to the Istituto di Clinica Pediatrica. The two cases presented diverse degrees of hematological and skeletal involvement and followed different clinical evolutions.

Female↗

[Thrombocytopenia and absent radii syndrome (TAR). Case report and literature discussion].

A girl is described with the thrombocytopenia and absent radii (TAR) syndrome. The literature concerning this rare, autosomal recessive inherited syndrome is discussed. The main characteristics are bilateral radius aplasia in which the thumbs are present in combination with a a- or hypomegakaryocytic thrombocytopenia. Many other anomalies and associated disorders are described in the literature, especially in the haematological, skeletal, cardiac and intestinal fields. The treatment is mainly directed to the haemorrhagic diathesis and the orthopaedic problems. It is suggested that the mortality-rate--mainly a consequence of haemorrhage--which used to be 30-40%, has diminished thanks to the evolution of platelet transfusion therapy.

Chromosome Aberrations↗

[Some remarks concerning the tissue-air-ratio (TAR) in the case of bilateral total body irradiation (author's transl)].

The TAR's resulting from the bilateral 60Co-irradiation of an homogeneous whole body phantom and of a quadratic phantom are measured in their midlines and at their surfaces of incidence. They are compared with measurements on a patient. The dose contributions of scattered radiation and its effective energy are determined by means of a simple water-phantom. Investigations concerning the influence of the "os ilium" on the midline dose showed that besides the former mentioned other bone structures too in the pelvic area are responsible for the low rectal dose in patients. Rectal doses therefore should not considered representative for the midline dose. The variation of the midline dose depending on the source distance is discussed.

Child↗