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Biomedical subjects

M Braddock

Publications and source records attributed to M Braddock.

13 recordsLinked to original sources

A population-based study of motorcycle injury and costs.

STUDY OBJECTIVE: To provide a population-based injury and cost profile for motorcycle injury in Connecticut. DESIGN: Population-based retrospective epidemiologic review of Connecticut death certificates, hospital discharge data, and police accident reports. RESULTS: Connecticut death certificates identified 112 deaths from motorcycle injuries for an annual death rate of 1.2 per 100,000 persons. Death rates were highest among 20- to 24-year-old men. Nonhelmeted motorcyclists were 3.4-fold more likely to die than were helmeted riders (P less than .05). An estimated 2,361 motorcycle-related hospital discharges resulted in an annual hospitalization rate of 24.7 per 100,000 persons. Head, neck, and spinal injuries accounted for 22% of all injuries. Total costs exceeded $29 million; 29% of hospitalized patients were uninsured, and 42% of the cost was not reimbursed to the hospitals. CONCLUSION: Motorcycle injuries contribute significantly to Connecticut's mortality, morbidity, and medical costs. Our study suggests that a uniform helmet law would save an estimated ten lives and prevent more than 90 nonfatal injuries in Connecticut each year at a cost savings to the state of $5.1 million. These data are crucial in advocating re-enactment of motorcycle helmet laws.

Abbreviated Injury Scale

An adenosine at position 27 in the human immunodeficiency virus type 1 trans-activation response element is not critical for transcriptional or translational activation by Tat.

Tat protein binds to the trans-activation response (TAR) element of human immunodeficiency virus type 1 RNAs and activates gene expression at the level of transcription in mammalian cell lines and translation in Xenopus oocytes. Certain residues within TAR are important for Tat binding in vitro, including residue A-27, which appears to be able to be modified in a Tat-dependent manner in Xenopus oocytes (L. Sharmeen, B. Bass, N. Sonenberg, H. Weintraub, and M. Groudine, Proc. Natl. Acad. Sci. USA 88:8096-8100, 1991). Activation by Tat in oocytes occurs via a covalent modification of TAR-containing RNA. We have found that in both mammalian cells and Xenopus oocytes, conversion of A-27.U-38 or C-27.G-38 or C-27.G-38 reduces activation. However, conversion to G-27.U-38 or G-27.C-38 had little or no effect on activation, and in oocytes, these mutant RNAs were still covalently modified. These data exclude a specific role for the adenosine at residue 27 for Tat activation but suggest a requirement for a purine at this position.

Adenosine

Work-related injury among Connecticut minors.

Work-related injuries have recently been shown to be a significant cause of morbidity among adolescents. This study represents a population-based work-related injury profile for Connecticut minors. Review of 796 worker compensation reports for adolescents from 14 through 17 years of age submitted over 12 months revealed an overall age-specific injury rate of 15 per 1000 employed 16- and 17-year-olds; frequency of injury increased with age. Social and recreational workers had an injury rate of more than 20%, predominantly sprains and contusions. Among all other occupations and industries, cuts were the major type of injury (34%); more than one third of cutting injuries were associated with use of case cutters, another third with knives. There were no work-related deaths among minors in this study. Minors in the workplace are at high risk of injury compared with adults. This study suggests that identification of specific patterns of work-related injury could lead to targeted intervention strategies.

Accidents, Occupational

Blocking of Tat-dependent HIV-1 RNA modification by an inhibitor of RNA polymerase II processivity.

Human immunodeficiency virus gene expression is regulated transcriptionally and post-transcriptionally by the virally encoded tat protein (Tat). Tat functions through an RNA target sequence located in the untranslated region at the 5' end of viral transcripts. In Xenopus oocytes, translation of RNA containing the target sequence is specifically activated by Tat. This activation only occurs if the RNA is injected into the nucleus, and might be due to Tat-dependent, nucleus-specific chemical modification of the RNA which somehow facilitates translation. Here we demonstrate that Tat activation of its target RNA in the nucleus involves a Tat-dependent covalent modification. The modified RNA is competent for translation after reinjection into either the nucleus or the cytoplasm in the absence of Tat. Furthermore, we find that the nucleoside analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, which inhibits processivity of RNA polymerase II (ref. 9), blocks this Tat-dependent modification.

Animals

Child pedestrian injury: a population-based collision and injury severity profile.

Linked multiple data sources were analyzed to provide a population-based collision and injury severity profile among pedestrians under 20 years of age struck by a motor vehicle during 1986-1987 in Hartford, Connecticut. Data sources included police accident reports, medical examiner records, and hospital charts. There were 234 motor vehicle-pedestrian collisions reported to the police in the study period. Of these, 213 were Hartford residents resulting in an annual age-specific pedestrian collision rate of 22.8 per 10,000 persons. A spot map of collision location reveals several well-defined geographic areas, which includes nearly half (45%) of the motor vehicle-pedestrian collisions. We reviewed 143 of 192 medical charts (75%) and 6 medical examiner records. The case fatality rate was 4.2% and the mean Injury Severity Score was 4.4. These findings will be useful for designing, implementing, and evaluating a targeted child pedestrian safety program.

Accidents, Traffic

Population, income, and ecological correlates of child pedestrian injury.

Pedestrian injury is a significant health problem among urban children. This study is an analysis of the role of population, income, and ecological factors in the occurrence of child pedestrian collisions. One hundred and ninety-eight motor vehicle collisions occurring in Hartford, Connecticut involving pedestrians younger than 15 years old were reported to police during 1986 through 1987. Collision locations were abstracted from police reports and assigned a census tract. Census tracts were classified as "high frequency" (8+ collisions), "moderate frequency" (3 to 7 collisions), or "low frequency" (0 to 2 collisions). High-frequency census tracts had greater proportions of children and of nonwhite residents than moderate- or low-frequency tracts. They also were characterized by high proportions of households headed by females living below the poverty line. High-frequency tracts had a greater number of children per acre than moderate or low tracts. Children per acre had the strongest association with collision frequency (R = .72) and remained the most consistent when other variables were controlled. The number of children per acre is a potentially useful predictor of census tracts at risk for child pedestrian collisions. This may be useful in developing focused prevention strategies within an urban environment.

Accidents, Traffic

A nuclear translational block imposed by the HIV-1 U3 region is relieved by the Tat-TAR interaction.

Replication of HIV-1 depends on the viral Tat protein, which functions via a target sequence, TAR, present in the proviral long terminal repeat (LTR) and at the 5' end of viral mRNAs. We have shown that Tat potentiates the expression of TAR-containing RNAs, but only when Tat and the TAR-containing RNA are present in the nucleus. We now show that a small change in the TAR loop abolishes nuclear potentiation by Tat. Furthermore, the HIV-1 U3 region induces expression incompetence in mRNA synthesized by this promoter. RNAs of identical structure are, however, translated efficiently when produced from the CMV-IE promoter. The Tat-TAR system appears, therefore, to rescue the expression potential of HIV-1 LTR-directed RNA.

Animals

HIV-1 TAT "activates" presynthesized RNA in the nucleus.

Replication of the human immunodeficiency virus (HIV-1) depends upon the viral TAT protein. TAT stimulates gene expression via a target response sequence (TAR) located within the HIV-1 LTR. As TAR is located in the transcribed region it could act as a signal in either the DNA, the RNA, or both. To test whether TAT acts on transcription and/or posttranscriptionally, we produced TAT in yeast and monitored its activity after microinjection into the nucleus or cytoplasm of Xenopus oocytes. The TAT protein stimulated TAR-dependent expression, but this activation was not inhibited by transcriptional inhibitors. Furthermore, TAR-containing RNA, produced in vitro, was "activated" by TAT after coinjection into oocytes. This activation only occurred, however, when the RNA was injected into the nucleus and not into the cytoplasm. Our data indicate, therefore, that in the Xenopus system TAT acts on presynthesized RNA and that the nucleus is involved in this action.

Animals

HIV expression strategies: ribosomal frameshifting is directed by a short sequence in both mammalian and yeast systems.

The pol gene of the human immunodeficiency virus (HIV-1) is expressed as a gag:pol fusion, arising from a ribosomal frameshift that brings the overlapping, out-of-phase gag and pol genes into translational phase. In this study, we show that HIV frameshifting is mediated by a very short sequence in the viral RNA. We demonstrate the importance of a homopolymeric run within this sequence and conclude that HIV frameshifting is not dependent on stem-loop structures downstream from the frameshift site. Our analysis also indicates that the sequence requirements are identical in mammalian and yeast systems.

Animals

Synthesis of a gene for the HIV transactivator protein TAT by a novel single stranded approach involving in vivo gap repair.

The synthesis of a gene for the HIV TAT protein is described using a novel approach that capitalises on the ability to synthesise oligonucleotides of greater than 100 bp in length. It involves the synthesis of large oligomers covering one strand of the desired gene in its entirety and the use of small complementary bridging and adapter oligonucleotides to direct the assembly and cloning of the large oligomers. After ligation to the cloning vector the partially single stranded intermediate is transformed directly into the recipient bacterial host where the plasmid is repaired. The synthetic tat gene has been expressed in HeLa cells and is shown to trans-activate TAR+ but not TAR- HIV LTR-CAT constructs.

Amino Acid Sequence

Cloning of cDNA to rat mammary-gland fatty acid synthase mRNA. Evidence for the expression of two mRNA species during lactation.

A cDNA library was constructed in the expression vector lambda gt11, by synthesizing cDNA from size-selected poly(A) RNA from lactating rat mammary gland, using random hexanucleotide primers. Using this library we identified two recombinants which, on addition of a lac z inducer, produced proteins recognized by affinity-purified anti-fatty-acid synthase antibody, and which, therefore, contained fatty acid synthase coding sequences. The inserts were subcloned, were shown to be between 500 and 600 base pairs in size, and to cross-hybridize. The cloned DNA was then used in Northern hybridizations with mRNA isolated at various stages throughout lactation. Two mRNA species were identified of approx. 9.7 and 10.4 kilobases, which increased and decreased in parallel during lactation, reaching a peak at 12-13 days. Both mRNA species disappeared rapidly if the pups were removed prematurely. This study provides evidence that, during hormonal induction in lactation, regulation of the level of fatty acid synthase protein can be accounted for by variation in the level of mRNA.

Animals