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Biomedical subjects

R Kirkpatrick

Publications and source records attributed to R Kirkpatrick.

At least 19 recordsLinked to original sources
PubMed2006

The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

Arabidopsis↗
PubMed2002

MR cholangiopancreatography in patients with primary sclerosing cholangitis: interobserver variability and comparison with endoscopic retrograde cholangiopancreatography.

OBJECTIVE: The purpose of our study was to determine the degree of interobserver variability and correlation between MR cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) for the presence of bile duct strictures in patients with primary sclerosing cholangitis. MATERIALS AND METHODS: For this retrospective study involving 26 patients with primary sclerosing cholangitis, 31 MR cholangiopancreatograms were compared with 30 endoscopic retrograde cholangiopancreatograms. The MR cholangiopancreatograms were independently interpreted by two abdominal radiologists in a blinded, randomized manner for overall image quality, extent of ductal visualization, and the presence and location of bile duct strictures. Unweighted multirater kappa coefficient values were estimated for each comparison. RESULTS: Visualization of more than 50% of the expected ductal length was possible in the extrahepatic, central intrahepatic, and peripheral intrahepatic bile ducts in 99%, 88%, and 69% of the MR cholangiopancreatograms and 100%, 86%, and 52% of the endoscopic retrograde cholangiopancreatograms, respectively. Strictures were detected in the extrahepatic, central, and peripheral ducts in 53%, 68%, and 87% of the MR cholangiopancreatograms and 73%, 67%, and 63% of the endoscopic retrograde cholangiopancreatograms, respectively. The interobserver agreement for stricture detection was 61% for MR cholangiopancreatography and 76% for ERCP. MR cholangiopancreatographic findings were consistent with ERCP findings for the presence of strictures in 69% of the cases. CONCLUSION: In patients with primary sclerosing cholangitis, MR cholangiopancreatography better shows the bile ducts and can depict more strictures, especially of the peripheral intrahepatic ducts, than ERCP. MR cholangiopancreatography can be used to noninvasively diagnose and follow up patients with primary sclerosing cholangitis.

Adult↗
PubMed2000

Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor.

Histone acetylation alters chromatin state by modifying lysines on histone and plays an important role in modulating gene transcription. A dynamic balance of histone acetylation/deacetylation is maintained by histone acetyltransferases and histone deacetylases. Emerging evidence suggests that a family of histone deacetylases may exist to regulate diverse cellular functions, including chromatin structure, gene expression, cell cycle progression, and oncogenesis. We describe here a novel human histone deacetylase, named HDAC8, cloned from human kidney. HDAC8 encodes 377 amino acid residues and shares extensive homology to several known HDACs, in particular a histone deacetylase from Arabidopsis thaliana. Northern blot analyses revealed that HDAC8 expression pattern for HDAC8 is distinct from that for HDAC1 and HDAC3, and expression of HDAC8 mRNA occurs in multiple organs including heart, lung, kidney, and pancreas. HDAC8 mRNA was also observed in several cell lines derived from cancerous tissues. When expressed in HEK293 cells, HDAC8 exhibited deacetylase activity toward acetylated histone, indicating that this protein is a bona fide histone deacetylase. Its histone deacetylase activity was inhibited by trichostatin and other known histone deacetylase inhibitors. Furthermore, active recombinant HDAC8 was expressed and purified from Escherichia coli. When ectopically expressed in cells, HDAC8 was found to be localized to the nucleus. Co-transfection experiments demonstrated that expression of HDAC8 repressed a viral SV40 early promoter activity. These results indicate that HDAC8 is a novel member of the histone deacetylase family, which may play a role in the development of a broad range of tissues and potentially in the etiology of cancer.

3T3 Cells↗
PubMed2000

Poly(sodium 4-styrene sulfonate): an effective candidate topical antimicrobial for the prevention of sexually transmitted diseases.

Presently marketed vaginal barrier agents are cytotoxic and damage the vaginal epithelium and natural vaginal flora with frequent use. Novel noncytotoxic agents are needed to protect women from sexually transmitted diseases. One candidate compound is a high-molecular-mass form of soluble poly(sodium 4-styrene sulfonate) (T-PSS). The antimicrobial activity of T-PSS was evaluated in primary culture systems and in a genital herpes murine model. Results obtained indicate that T-PSS is highly effective against herpes simplex viruses, Neisseria gonorrhoeae, and Chlamydia trachomatis in vitro. A 5% T-PSS gel protected 15 of 16 mice from vaginal herpes, compared with 2 of 16 mice treated with a placebo gel. Moreover, T-PSS exhibited little or no cytotoxicity and has an excellent selectivity index. T-PSS is an excellent candidate topical antimicrobial that blocks adherence of herpes simplex virus at low concentrations, inactivates virus at higher concentrations, and exhibits a broad spectrum of antimicrobial activity.

Animals↗
PubMed1999

Bile salts: natural detergents for the prevention of sexually transmitted diseases.

The development of new, safe, topical microbicides for intravaginal use for the prevention of sexually transmitted diseases is imperative. Previous studies have suggested that bile salts may inhibit human immunodeficiency virus infection; however, their activities against other sexually transmitted pathogens have not been reported. To further explore the potential role of bile salts in preventing sexually transmitted diseases, we examined the in vitro activities and cytotoxicities of select bile salts against Chlamydia trachomatis, herpes simplex virus (types 1 and 2), Neisseria gonorrhoeae, and human immunodeficiency virus in comparison to those of nonoxynol-9 and benzalkonium chloride using both primary cells and cell lines derived from the human female genital tract. We found that taurolithocholic acid 3-sulfate and a combination of glycocholic acid and taurolithocholic acid 3-sulfate showed excellent activity against all of the pathogens assayed. Moreover, taurolithocholic acid 3-sulfate alone or in combination was less cytotoxic than nonoxynol-9 and benzalkonium chloride. Thus, taurolithocholic acid 3-sulfate alone or in combination warrants further evaluation as a candidate topical microbicidal agent.

Bile Acids and Salts↗
PubMed1999

Neisseria gonorrhoeae mutants altered in toxicity to human fallopian tubes and molecular characterization of the genetic locus involved.

In an effort to identify potential cytotoxins expressed by Neisseria gonorrhoeae, we have identified a locus that, when mutated in the gonococcus, results in a significant increase in toxicity of the strain to human fallopian tube organ cultures (HFTOC). This locus, gly1, contains two open reading frames (ORFs) which are likely cotranscribed. ORF1 encodes a polypeptide of 17.8 kDa with a signal sequence that is recognized and processed in Escherichia coli and N. gonorrhoeae. The 15.6-kDa processed polypeptide has been observed in membrane fractions and filtered spent media from cultures of E. coli expressing gly1 and in outer membrane preparations of wild-type N. gonorrhoeae. The gly1 locus is not essential for bacterial survival, and it does not play a detectable role in epithelial cell adhesion, invasion, or intracellular survival. However, a gly1 null mutant causes much more damage to fallopian tube tissues than its isogenic wild-type parent. A strain complemented in trans for the gly1 mutation showed a level of toxicity to HFTOC similar to the level elicited by the wild-type parent. Taken together, these results indicate an involvement of the gly1 locus in the toxicity of N. gonorrhoeae to human fallopian tubes.

Amino Acid Sequence↗
PubMed1997

Measurement of immunoglobulin synthesis using the ELISPOT assay.

We describe a method for the detection of specific antibody-producing cells from either in vitro or in vivo immunization. These techniques are especially useful for detecting antibodies from developing hybridomas. We have successfully used the system to detect isotype-specific antibodies to a variety of bacterial antigens which were produced by heterohybridomas.

Antibodies, Monoclonal↗
PubMed1997

Sulfated carbohydrate compounds prevent microbial adherence by sexually transmitted disease pathogens.

Heparan sulfate (HS) serves as a receptor for adherence of herpes simplex viruses, Chlamydia trachomatis, Neisseria gonorrhoeae, and, indirectly, human immunodeficiency virus. Using primary human culture systems, we identified sulfated carbohydrate compounds that resemble HS and competitively inhibit infection by these pathogens. These compounds are candidates for intravaginal formulations for the prevention of sexually transmitted diseases.

Bacterial Adhesion↗
PubMed1997

Humoral immune response of cottontail rabbits naturally infected with Francisella tularensis in southern Illinois.

Cottontail rabbits (Sylvilagus floridanus) usually are thought to succumb to infection with Francisella tularensis. Reports of a rabbit population from southern Illinois (USA) with a high prevalence of F. tularensis antibodies suggested that some cottontails survived infection with this typically fatal bacterium. Our goal was to examine the humoral response of cottontails from a study area in southern Illinois for which multiple serum samples existed. Multiple sera were collected from 79 cottontails from 1986 to 1990 and 63% gained, lost, or maintained ELISA titers of IgM and IgG isotype antibodies. The typical pattern of antibody response appeared to be IgM isotype antibodies first, followed by IgG isotype antibodies, with both generally increasing to high titers. Negative culture attempts of liver tissue from 51 cottontails with varying antibody responses suggested that chronic infection did not occur in rabbits that developed antibody. The significance of the cottontail antibody response in resolution or prevention of tularemia infection remains unclear.

Animals↗
PubMed1996

Liver abscess secondary to intrahepatic perforation of the gallbladder, presenting as a liver mass.

We present an unusual case of a large pyogenic liver abscess containing multiple stones caused by perforation of a necrotic gallbladder and spread of the infection into the liver. It manifested by weakness, weight loss, and a palpable liver mass, pointing toward a neoplastic process. Workup for metastatic disease was negative, and tumor markers also were negative. Ultrasound and computerized tomography were inconclusive, and the diagnosis was established by laparoscopy. Open drainage and cholecystectomy were performed, with good outcome. In the literature, there have been very few reports of intrahepatic perforation of the gallbladder resulting in formation of hepatic abscess. The presentation, diagnosis, and management of liver abscesses, as well as the complications of acute cholecystitis, are discussed.

Acute Disease↗
PubMed1993

The dhod gene and deduced structure of mitochondrial dihydroorotate dehydrogenase in Drosophila melanogaster.

We have carried out experiments to determine the structural organization of dhod and its apparent dihydroorotate dehydrogenase (DHOdehase) product. Germline transformation with dhod genomic DNA sequences permitted assignment of the functional limits of the gene to a 5-kb region, providing an experimental system for detailed analysis of this gene, as well as the DHO dehase protein. As expressed in embryos, the gene is a simple transcriptional unit containing two exons totalling 1347 nucleotides (nt) and a single small 5' intron of 54 nt. Compared to the enzyme from microorganisms, the deduced DHOdehase protein of 405 amino acids shows strong similarities within the presumptive catalytic portions of the protein. However, the N-terminal portions of these proteins are highly dissimilar, presumably reflecting diversity in the intracellular localization of DHOdehase in the different organisms. The Drosophila melanogaster protein contains N-terminal sequences that are typical of other mitochondrial intermembrane space proteins in animal cells.

Amino Acid Sequence↗
PubMed1993

Structure of the rudimentary-like gene and UMP synthase in Drosophila melanogaster.

The last two steps of de novo UMP biosynthesis are performed by a bi-enzymic protein in animal cells, UMP synthase, that is encoded by the gene r-l in Drosophila melanogaster. Over 3.5 kb of genomic DNA spanning this gene were sequenced. Transcriptional organization of r-l has been determined by sequence analysis of two cDNA clones and by primer extension analysis of embryonic RNA. The DNA region 5' to the apparent transcription start point contains no known transcriptional control elements or sequences similar to those upstream from dhod, which encodes the metabolic pathway step preceding UMP synthase. The deduced protein of 53.5 kDa is similar to the UMP synthases of slime molds and humans. It contains the two enzymatic domains separated by an apparent bridge polypeptide sequence of over 30 amino acids, which is dissimilar among UMP synthases of different organisms. The r-l structure includes two introns, one of which occurs within the DNA region that encodes the interdomain bridge sequence of the protein.

Amino Acid Sequence↗
PubMed1992

Fulminant hepatic failure related to omeprazole.

Omeprazole is a new hydrogen-potassium adenosine triphosphatase antagonist with indications for severe reflux esophagitis and Zollinger-Ellison syndrome. Side effects involving the liver have consisted of minimal elevations of hepatocellular enzymes with higher dosages. We present what we believe is the first reported case of fulminant hepatic failure related to omeprazole.

Esophagitis, Peptic↗
PubMed1990

Endogenous and exogenous plasma catecholamine levels in cardiac arrest in swine.

The use of epinephrine in cardiac arrest remains an area of continuing controversy. This study was undertaken to characterize the effect of endogenous and exogenous epinephrine on plasma epinephrine levels, and the relationship between plasma epinephrine and norepinephrine and mean arterial pressure and diastolic arterial pressure. Nineteen young swine were anesthetized with ketamine and alpha-chloralose and instrumented with arterial and central venous lines. Ventricular fibrillation was induced by pacemaker. At 5 min post arrest cardiopulmonary resuscitation (CPR) was begun with a mechanical resuscitator. Animals were randomized to receive either saline placebo (n = 9), 0.01 mg/kg epinephrine (n = 5) or 0.1 mg/kg epinephrine (n = 5) via the central venous line. Plasma was drawn for high pressure liquid chromatographic analysis of catecholamines every 2 min. The resuscitation was carried on for 30 min after the arrest. Plasma epinephrine levels differed significantly between treated subjects and controls, as did mean arterial pressure and diastolic arterial pressure. There was a correlation between both mean arterial pressure and diastolic arterial pressure with plasma epinephrine and log epinephrine, but no correlation with plasma norepinephrine. The two doses of epinephrine did not differ in the degree to which they elevated the mean arterial pressure and diastolic pressure. We conclude that the endogenous catecholamine response to cardiac arrest while producing norepinephrine and epinephrine levels many times greater than those in the resting animal, is not sufficient to maintain blood pressure. There is a strong correlation between blood pressure and the log of the plasma epinephrine concentration, but epinephrine concentration alone does not solely account for changes in blood pressure during arrest.

Animals↗
PubMed1989

Molecular cloning and transcript mapping of the dihydroorotate dehydrogenase dhod locus of Drosophila melanogaster.

The dhod locus encodes dihydroorotate dehydrogenase, the fourth enzymatic step of de novo pyrimidine biosynthesis. This locus was cloned previously by a chromosome walk in cytogenetic region 85A. The location of dhod within 85A DNA has been determined by mapping two rearrangement mutations to a small DNA region. A nearly full-length cDNA clone of the dhod transcript was isolated and partially sequenced, to confirm its identity. The cDNA clone was also used to map the transcribed DNA. A 1.5 kb dhod RNA is described which is most abundant in embryos and displays minor length heterogeneity in pupae and adults. The developmental expression of this transcript is discussed relative to the expression of dihydroorotate dehydrogenase activity and other genes of the pyrimidine biosynthetic pathway.

Amino Acid Sequence↗