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Biomedical subjects

D E Sullivan

Publications and source records attributed to D E Sullivan.

10 recordsLinked to original sources

Conservation of hepatitis C virus 5' untranslated sequences in hepatocellular carcinoma and the surrounding liver.

Persistent infection by hepatitis C virus is a major risk factor for the development of hepatocellular carcinoma, but the mechanism of hepatocarcinogenesis is unknown. To study the association of hepatitis C virus with hepatocellular carcinoma, we sequenced part of the 5' untranslated region of hepatitis C virus from the tumor tissue and the surrounding nontumorous liver of three patients with hepatocellular carcinoma. No sequence differences between tumor-derived and liver-derived hepatitis C virus isolates were detected. The conservation of the 5' untranslated region of hepatitis C virus--not only in infected hepatocytes, but also in neoplastic cells--suggests that the regulatory elements at the 5' terminus of the viral genome play an important role in the pathobiology of hepatitis C virus.

Base Sequence

Quantitative polymerase chain reaction for hepatitis B virus DNA.

To monitor and compare the effect of drugs on hepatitis B virus (HBV) replication in hepatitis patients, an accurate quantitative method with high sensitivity is needed. Polymerase chain reaction (PCR) is the most sensitive method for the detection of HBV DNA, but because of sample to sample variability in amplification efficiency, the quantification of target nucleic acids by conventional PCR is inaccurate. Therefore, we developed a competitive PCR method with an internal standard which uses the same primers as the target HBV DNA. The standard was generated from the HBV S gene by PCR site-directed mutagenesis and differed from the native S gene by a single base which introduced an internal restriction enzyme site. For practical application, this method was used to quantitate the effect of the carbocyclic analogue 2'-deoxyguanosine (2'-CDG) on HBV DNA replication in 2.2.15 cells, an HBV transfected HepG2 cell line. A decrease of HBV DNA level in the attomole range was demonstrated by the assay in the media of 2.2.15 cells treated with 2'-CDG. The results were verified by conventional HBV DNA slot blot analysis followed by densitometric scanning. Competitive PCR proved to be a sensitive, accurate and reliable method for HBV quantitation.

Antiviral Agents

The nucleus-limited Hsr-omega-n transcript is a polyadenylated RNA with a regulated intranuclear turnover.

The Drosophila Hsr-omega puff, one of the largest heat shock puffs, reveals a very unusual gene, identified by heat shock but constitutively active in nearly all cell types. Surprisingly, Hsr-omega yields two transcription end-products with very different roles. The larger, omega-n, is a nuclear RNA with characteristics suggesting a new class of nuclear RNAs. Although it neither leaves the nucleus nor undergoes processing, omega-n RNA is polyadenylated, showing that polyadenylation is not limited to cytoplasmic RNA, but possibly has a function in the nucleus. The amount of omega-n within the nucleus is specifically regulated by both transcription and turnover. Heat shock and several other agents cause rapid increases in omega-n. A rapid return to constitutive levels follows withdrawal of the agents. Degradation of omega-n is inhibited by actinomycin D, suggesting a novel intranuclear mechanism for RNA turnover. Within the nucleus, some omega-n RNA is concentrated at the transcription site; however, most is evenly distributed over the nucleus, showing no evidence of a concentration gradient which might be produced by simple diffusion from the site of transcription. Previous studies suggested that omega-n has a novel regulatory role in the nucleus. The actinomycin D-sensitive degradation system makes possible rapid changes in the amount of omega-n, allowing the putative regulatory activities to reflect cellular conditions at a given time. Omega-n differs from the best studied nuclear RNAs, snRNAs, in many ways. Omega-n demonstrates the existence of intranuclear mechanisms for RNA turnover and localization that may be used by a new class of nuclear RNAs.

Animals

Tissue- and development-specific expression of HBGF-1 mRNA.

The gene for heparin-binding growth factor-1 (HBGF-1) encodes a 15.5-18 kDa polypeptide that affects the proliferation and differentiation of a broad range of mammalian cells and is widely distributed among normal adult tissues. In this study, we show that normal tissues of the adult rat express HBGF-1 transcripts in one of three patterns: a 4.4 kb mRNA was the predominant HBGF-1 transcript in brain, heart and lung; a 1.4 kb mRNA was the predominant transcript in the liver; approximately equal levels of the 1.4 and 4.4 kb mRNAs were found in the kidney. HBGF-1 expression was localized in two tissues: central nervous system expression of HBGF-1 was significantly higher in the brain stem compared to the cerebrum and cerebellum; renal expression of HBGF-1 was significantly higher in the medulla compared to the cortex. Analysis of the postnatal changes in HBGF-1 expression using the newborn rat kidney revealed that the level of HBGF-1 mRNA is low at birth and does not rise to adult levels until the seventh postnatal day. These findings demonstrate that HBGF-1 expression is specific for tissue type and stage of development.

Animals

The effect of topical 2.5% phenylephrine and 1% tropicamide on systemic blood pressure and pulse.

A prospective double-blind trial is described in which patients were given either 1% tropicamide, 2.5% phenylephrine, a combination of the two drugs, or a placebo. Blood pressure measurements and pulse rates were determined at 5, 10 and 15 minute intervals post-instillation. No significant change in systolic or diastolic blood pressures were determined for any of the treatment groups at any of the time intervals; however, a slight but significant decrease in pulse rate was noted in some of the treatment groups. The data are analyzed according to other variables. Factors which may have influenced the findings are discussed.

Adolescent

Injuries to the spine.

A spinal cord injury is a devastating event that occurs with a survival incidence of 30 to 40 per million. The percentage of complete neurologic injuries appears to be decreasing. This is thought to be attributable to a number of factors, including more and better trained paramedics, improved extrication and splinting techniques, earlier diagnosis, and transfer to an appropriate regional spinal cord injury center. The emergency department physician, whether in an urban or rural setting, plays a major role in the successful outcome of the spinal cord injured patient, by the application of early, appropriate management techniques, the insuring of proper spinal stabilization, and the use of all diagnostic services and personnel at his or her disposal. These measures guarantee that no further injury is likely to occur during this most crucial period of time.

Adolescent

"Staircase" closure of lower lip defects.

Attention is called to a previously described method of closing certain common surgical defects of the lower lip. Advancement flaps are used from one or both sides, resulting in a staircase configuration. The advantages, disadvantages, and applications of the method are described.

Carcinoma, Squamous Cell