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Biomedical subjects

B Rose

Publications and source records attributed to B Rose.

At least 19 recordsLinked to original sources
PubMed2001

Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection.

Entecavir (ETV) is a guanosine nucleoside analogue with potent antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus. To explore the consequences of prolonged virus suppression, woodchucks received ETV orally for 8 weeks and then weekly for 12 months. Of the 6 animals withdrawn from therapy and monitored for an additional 28 months, 3 had a sustained antiviral response and had no evidence of hepatocellular carcinoma (HCC). Of the 6 animals that continued on a weekly ETV regimen for an additional 22 months, 4 exhibited serum viral DNA levels near the lower limit of detection for >2 years and had no evidence of HCC. Viral antigens and covalently closed circular DNA levels in liver samples were significantly reduced in all animals. ETV was well tolerated, and there was no evidence of resistant variants. On the basis of historical data, long-term ETV treatment appeared to significantly prolong the life of treated animals and delay the emergence of HCC.

Animals↗
PubMed2001

Pathogen testing of ready-to-eat meat and poultry products collected at federally inspected establishments in the United States, 1990 to 1999.

The Food Safety and Inspection Service (FSIS) conducted microbiological testing programs for ready-to-eat (RTE) meat and poultry products produced at approximately 1,800 federally inspected establishments. All samples were collected at production facilities and not at retail. We report results here for the years 1990 through 1999. Prevalence data for Salmonella, Listeria monocytogenes, Escherichia coli O157:H7, or staphylococcal enterotoxins in nine different categories of RTE meat and poultry products are presented and discussed. The prevalence data have certain limitations that restrict statistical inferences, because these RTE product-testing programs are strictly regulatory in nature and not statistically designed. The cumulative 10-year Salmonella prevalences were as follows: jerky, 0.31%; cooked, uncured poultry products, 0.10%; large-diameter cooked sausages, 0.07%; small-diameter cooked sausages, 0.20%; cooked beef, roast beef, and cooked corned beef, 0.22%; salads, spreads, and pâtés, 0.05%; and sliced ham and luncheon meat, 0.22%. The cumulative 3-year Salmonella prevalence for dry and semidry fermented sausages was 1.43%. The cumulative 10-year L. monocytogenes prevalences were as follows: jerky, 0.52%; cooked, uncured poultry products, 2.12%; large-diameter cooked sausages, 1.31%; small-diameter cooked sausages, 3.56%; cooked beef, roast beef, and cooked corned beef, 3.09%; salads, spreads, and pâtés, 3.03%; and sliced ham and luncheon meat, 5.16%. The cumulative 3-year L. monocytogenes prevalence for dry and semidry fermented sausages was 3.25%. None of the RTE products tested for E. coli O157:H7 or staphylococcal enterotoxins was positive. Although FSIS and the industry have made progress in reducing pathogens in these products, additional efforts are ongoing to continually improve the safety of all RTE meat and poultry products manufactured in federally inspected establishments in the United States.

Animals↗
PubMed2000

Analysis of Salmonella serotypes from selected carcasses and raw ground products sampled prior to implementation of the Pathogen Reduction; Hazard Analysis and Critical Control Point Final Rule in the US.

In July 1996, the US Department of Agriculture (USDA), Food Safety and Inspection Service (FSIS), published the Pathogen Reduction; Hazard Analysis and Critical Control Point (HACCP) Systems final rule to improve food safety of meat and poultry products. The final rule established, among other requirements, pathogen reduction performance standards for Salmonella for food animal carcasses and raw ground products. The final rule is to be fully implemented in three stages in successively smaller federally inspected meat and poultry slaughter and processing establishments. Implementation began in January 1998 and was completed in January 2000. Samples of carcasses of four species of food animals (cattle, swine, chickens, turkeys), and raw ground product from each of these species, were collected by FSIS from establishments prior to implementation of the final rule and cultured for Salmonella. This paper reports Salmonella serotype results of samples collected from June 1997 through August 1998. These results represent a baseline for future comparisons.

Animals↗
PubMed2000

Conservation of sequence and function of the pag-3 genes from C. elegans and C. briggsae.

The Caenorhabditis briggsae homologue of the Caenorhabditis elegans pag-3 gene was cloned and sequenced. When transformed into a C. elegans pag-3 mutant, the C. briggsae pag-3 gene rescued the pag-3 reverse kinker and lethargic phenotypes. The C. elegans pag-3 gene fused to lacZ was expressed in the same pattern in C. elegans and C. briggsae. Unlike many gene homologues compared between C. elegans and C. briggsae, extensive sequence conservation was found in the non-coding regions upstream of the pag-3 exons, in several of the introns and in the downstream non-coding region. Furthermore, the splice acceptor and splice donor sites were conserved, and the size of the introns and exons was surprisingly similar. The predicted protein sequence of C. briggsae PAG-3 was 85% identical to the protein sequence of C. elegans PAG-3. Because so much of the non-coding region of pag-3 was conserved, the control of pag-3 may be quite complex, involving the binding of many trans-acting factors. These results suggest the evolutionary conservation of the pag-3 gene sequence, its expression and function.

Amino Acid Sequence↗
PubMed2000

Collaborative angiographic patency trial of recombinant staphylokinase (CAPTORS).

BACKGROUND: We undertook an angiographic, dose-finding study of staphylokinase (SAK42D variant) to evaluate its efficacy and safety in patients with acute ST-segment myocardial infarction. METHODS AND RESULTS: Patients were studied within 6 hours of symptom onset and received SAK42D as a 30-minute infusion with 20% of the total dose given as a bolus. Eighty-two patients with a median age of 60 years (interquartile range 52 to 69 years), 84% male and 43% with an anterior myocardial infarction, were studied at a median time from symptom onset of 2.7 hours. There was a high degree of Thrombolysis in Myocardial Infarction (TIMI) 3 flow achieved with 15 mg of SAK42D, that is, 62%. Therefore after 21 patients had been studied at this dose the next dose of 30 mg was used and 65% TIMI 3 patency was achieved. At the peak dose of 45 mg, TIMI 3 90-minute patency was 63%. There were no allergic reactions, and no patient had intracranial hemorrhage. Four patients had major and 9 moderate bleeding during the study; 2 of the major and 5 of the moderate bleeding events occurred within 48 hours of commencement of treatment. The majority (62%) of these were related to vascular instrumentation, and there was no relation between the extent of bleeding and dose of SAK42D used. Forty-five minutes after cessation of SAK42D, there were small percent decrements in plasma fibrinogen and plasminogen levels that did not reach statistical significance. However, there were dose-related changes in alpha(2) anti-plasmin that revealed a borderline significant reduction that was dose related (P =.053). CONCLUSION: These data revealed similar fibrinolytic efficacy across a 3-fold increment in dose, indicating that this study operated on a flat portion of the dose-response curve. The favorable efficacy/safety profile achieved with staphylokinase is encouraging, and further investigation is warranted.

Aged↗
PubMed1999

Dynamics of gap junctions observed in living cells with connexin43-GFP chimeric protein.

To study the aggregation of cell-to-cell channels into gap junctions at individual cell-cell contacts, we transfected cells with an expression vector for a chimeric protein composed of the cell-to-cell channel protein connexin43 and a green fluorescent protein. The chimeric channel protein was visualized in the fluorescence microscope and was found to form gap junctions at the cell-cell contacts just like wild-type connexin43. Cells expressing the chimeric protein had functional cell-to-cell channels. Using timelapse videomicroscopy on live cells we observed individual gap junctions over long periods and recorded the time course of aggregation of the chimeric channel protein into gap junctions at newly formed cell-cell contacts. We found that individual small gap junctions were very dynamic, moving about or becoming assembled and disassembled in the course of minutes. Larger gap junctions were more stable than small punctate ones. In control condition, stable new gap junctions were not formed during observation times of 30 min or longer. But at elevated levels of cyclic adenosine monophosphate, the chimeric channel protein began aggregating at new junctions 5-10 minutes after cell-cell contact and continued to concentrate there for at least one hour. Also already established junctions grew in size. The fluorescent chimeric channel protein will be an excellent tool to investigate the regulation of trafficking of connexin from and to the membrane and the mechanism of connexin channel aggregation into gap junctions.

Animals↗
PubMed1998

Characterization of an HPV-negative cell line (FR-CAR) derived from a cervical squamous intraepithelial lesion.

A new cell line, FR-car, has been established from a biopsy of a low-grade human cervical squamous intraepithelial lesion (SIL). We confirmed the epithelial origin of the cells by keratin staining using polykeratin, AE1/AE3 and CAM 5.2 antibodies. Sixty percent to 80% of the cultured cells stained positive for proliferative cell nuclear antigen (PCNA) and Ki-67. There was no overexpression of p53. Karyotyping revealed that the cell line was hypodiploid with clonal abnormalities on chromosome 6 and 16. Sections of a biopsy adjacent to the lesion from which the culture was initiated tested positive for human papillomavirus (HPV) 18 DNA by the polymerase chain reaction, but cultured cells tested at several passages were HPV-negative by either type-specific or consensus PCRs. This HPV-negative SIL line may be useful in studies into the cell biology of dysplastic epithelium.

Adult↗
PubMed1998

Survey among survivors of the 1995 Ebola epidemic in Kikwit, Democratic Republic of Congo: their feelings and experiences.

This study describes experiences of the survivors of the 1995 Ebola epidemic in Kikwit, Democratic Republic of Congo. Most of the survivors in our sample had cared for a sick family member before becoming ill themselves, and most had never heard of Ebola before they developed symptoms and therefore did not suspect that they were infected by the virus. Fear, denial and shame were their principal initial feelings. After release from hospital, survivors were abandoned by family or friends more often than they had expected. Belief in god was an important aid to all of them. Their most negative experiences were witnessing other people dying in the isolation ward of the Kikwit General Hospital, and the reluctance of hospital personnel to treat them. During Ebola outbreaks more attention should be given to the psychosocial implications of such an epidemic. Information campaigns should include antidiscrimination messages and more psychosocial support should be given to patients and their families.

Democratic Republic of the Congo↗
PubMed1998

Point mutations in SP1 motifs in the upstream regulatory region of human papillomavirus type 18 isolates from cervical cancers increase promoter activity.

Evidence of the functional significance of two naturally occurring mutations at nt 40 or 41 in the Sp1 motif in the promoter proximal segment of the upstream regulatory region (URR) of human papillomavirus (HPV) type 18 is presented. In electrophoretic mobility shift assays, Sp1 protein bound more efficiently to the Sp1 mutant motifs than to the prototype; while in both HeLa and HT3 cells, luciferase activity controlled by the mutant URRs was upregulated 2- and 3-fold, or 4- and 6-fold, in comparison with the prototype URR or HeLa cell-derived URR respectively. The HeLa URR represents a more appropriate baseline for promoter activity, containing a series of point mutations representative of most HPV-18 cancer isolates, including one in the Yin Yang 1 (YY1) site at the P105 promoter. The effect of the Sp1 mutations was found to be largely maintained in the context of the HeLa URR containing the prototype YY1 site.

Alanine↗
PubMed1997

Urine glycosaminoglycan concentrations in mucopolysaccharidosis VI-affected cats following bone marrow transplantation or leukocyte infusion.

Urinary glycosaminoglycan (GAG) concentrations were determined in nineteen normal cats (eleven kittens and eight adult cats), eighteen mucopolysaccharidosis VI (MPS VI)-affected untreated cats (ten kittens and eight adult cats), thirteen cats MPS VI-affected cats following bone marrow transplants (BMT), and two MPS VI-affected cats following intravenous infusion of leukocytes from normal cats. Mucopolysaccharidosis VI-affected cats treated with BMT had a precipitous decrease in urinary GAG by day 7 post-BMT, then a transient increase just prior to engraftment, followed by a sustained decrease to within, or near, the range of urinary GAG concentration established for normal cats. The pre-engraftment changes in urinary GAG excretion were reproduced by leukocyte infusion. After infusion of comparable members of normal peripheral blood leukocytes, a significant decrease in urinary GAG concentrations, specifically dermatan sulfate (DS), was seen with a nadir at day 5 post-infusion, followed by a return by day 9 to pre-infusion values. Post-engraftment, a continued low urinary GAG concentration with a specific decrease in DS can be utilized to document successful autologous engraftment in MPS VI-affected cats.

Animals↗
PubMed1997

An inhibition of gap-junctional communication by cadherins.

The action of Ca(2+)-dependent cell-cell adhesion molecules (cadherins) on cell-to-cell channel-mediated intercellular communication was investigated in mouse L and rat Morris hepatoma cells. These cells fail to adhere to one another in aggregation assays and thus seem to lack cell adhesion molecules. Expression of exogenous cadherin induced strong cell-cell adhesion in both cell types, but had opposite effects of communication, causing inhibition in L cells and improvement in hepatoma cells. Both cells express the connexin43 cell-to-cell channel protein. By western blot we found no cadherin-specific changes in connexin43 protein in either cell type, but connexin43 gap junctional plaque staining, i.e. connexin43 localization to cell-cell junctions, was inhibited in L cells and facilitated in hepatoma cells. In addition we found that the inhibitory effect is largely abolished by blockers of glycosylation. Cadherin-cadherin interactions are known to trigger cell type-specific intracellular signal cascades resulting in diverse end effects, and gap junctional communication/plaque formation seems a further example of such cell type-specificity.

Animals↗
PubMed1996

Variability of the thrombin- and ADP-induced Ca2+ response among human platelets measured using fluo-3 and fluorescent videomicroscopy.

The intracellular free Ca2+ concentration ([Ca2+]cyt) of individual human platelets localized between siliconized glass cover slips was determined at rest and after stimulation with thrombin and ADP using the Ca2+ indicator fluo-3 (0.97 +/- 0.30 mmol/l cell volume) with fluorescence video microscopy. Resting [Ca2+]cyt in the presence of 2 mM external Ca2+ showed only small inter-platelet variability ([Ca2+]cyt = 86 +/- 30 (S.D.) nM). Resting [Ca2+]cyt of individual fluo-3-loaded platelets measured as a function of time had a S.D. of 10 nM or 12% (S.D./mean). Individual platelets showed no affinity for the siliconized support and their [Ca2+]cyt showed no tendency to oscillate in either the resting or in the activated state. When 0.2 U/ml thrombin or 20 microM ADP were added, all platelets showed a characteristic Ca2+ transient whereby [Ca2+]cyt increased to peak values within 8-12 sec and then declined. The Ca2+ transients measured with fluo-3 were in approximate synchrony but peak [Ca2+]cyt values showed large inter-platelet variability. The ensemble average peak [Ca2+]cyt for thrombin and ADP were 672 +/- 619 (S.D.) nM and 640 +/- 642 (S.D.) nM, respectively. Thus inter-platelet variations (S.D./mean) were 92% or 100% as large as the average measured values. Mathematically-constructed averages of the single platelet experiments agreed reasonably well with platelet-averaged values obtained in parallel experiments with stirred platelet suspensions in a plastic cuvette, measured with a conventional spectrofluorometer. Peak [Ca2+]cyt values reflecting dense tubular Ca2+ release alone (external Ca2+ removed) also showed large interplatelet variation (171 +/- 105 (S.D.) nM with thrombin and 183 +/- 134 (S.D.) nM with ADP). Dense tubular Ca2+ release induced by cyclopiazonic acid (a dense tubular Ca2+-ATPase inhibitor) gave peak [Ca2+]cyt of 289 +/- 170 nM. Thus the size of the dense tubular Ca2+ pool has an inter-platelet variation of 59% (S.D./mean). Variability of the dense tubular pool size accounts for some, but not all, of the large interplatelet variation in peak (Ca2+]cyt seen with thrombin and ADP activation.

Adenosine Diphosphate↗
PubMed1996

Comparison of body composition and bone mineral measurements from two DXA instruments in young men.

The purpose of this study was to compare body-composition and whole-body, lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle (WT) bone mineral measurements by using the Hologic QDR 1000W (DXAH) and the Lunar DPX-L (DXAL) dual-energy X-ray absorptiometry instruments. In addition, the ability of conversion equations to predict DXAH data from DXAL data were tested. Thirteen healthy young adult males (aged 22.2 +/- 3.6 y, 177.4 +/- 5.3 cm in height, and 72.7 +/- 9.6 kg in weight) were scanned on the same day by using DXAH and DXAL. Whereas measured body mass was not different (P > 0.05) between machines, whole-body fat mass [DXAH-DXAL (DXAdiff) = 1152 +/- 1395 g], percentage fat (DXAdiff = 1.5 +/- 1.7% of body mass), bone mineral density (BMD; DXAdiff = 0.016 +/- 0.023 g/cm2), and bone mineral content (BMC; DXAdiff = 316 +/- 50 g) were lower and whole-body fat-free soft tissue (FFST; DXAdiff = 1781 +/- 1859 g) was higher with DXAH than with DXAL. Lower fat mass (DXAdiff = 2145 +/- 855 g) and BMC (DXAdiff = 216 +/- 36 g) and higher FFST (DXAdiff = 1966 +/- 943 g) in the trunk were primarily responsible for the whole-body differences. Lower BMD and BMC values were found for LS (DXAdiff = 0.145 +/- 0.038 g/cm2 and 3 +/- 2 g, respectively), trochanter (DXAdiff = 0.100 +/- 0.044 g/cm2 and 1.7 +/- 1.0 g), and WT (DXAdiff = 0.195 +/- 0.061 g/cm2 and 1.93 +/- 0.51 g) with DXAH compared with DXAL. DXAH BMD of FN was also lower (DXAdiff = 0.141 +/- 0.032 g/cm2) than with DXAL. Only DXAH whole-body BMC and LS BMD were accurately predicted from DXAL with conversion equations. Predicted DXAH FN BMD was significantly lower than the actual DXAH value (P < or = 0.05), whereas the discrepancy between DXAH and DXAL actually increased for whole-body percentage fat and BMD (DXAdiff = 6.6 +/- 1.3% body mass and 0.020 +/- 0.025 g/cm2). In conclusion, lower whole-body fat mass, percentage fat, and BMC, and higher whole-body FFST with DXAH were due primarily to measurement differences in the trunk. Whereas conversion equations accurately predicted DXAH whole-body BMC and LS BMD from DXAL measurements in young adult males, they did not accurately predict DXAH, percentage fat, and BMD of the whole body and FN BMD.

Absorptiometry, Photon↗
PubMed1995

Inhibition of glycosylation induces formation of open connexin-43 cell-to-cell channels and phosphorylation and triton X-100 insolubility of connexin-43.

We transfected the cDNA for the cell-to-cell channel protein connexin-43 (Cx43) into Morris hepatoma H5123 cells, which express little Cx43 and lack gap junctional communication (open cell-to-cell channels). We found that cells overexpressing Cx43 nonetheless lacked open cell-to-cell channels, but that inhibition of glycosylation by tunicamycin induced open channels in these cells. Tunicamycin also induced biochemical changes in Cx43 protein; the level increased, and a considerable fraction became phosphorylated and Triton X-100 insoluble, in contrast to untreated cells where Cx43 was non-phosphorylated and Triton X-100 soluble. Although tunicamycin caused the formation of open channels, channels were not found aggregated into gap junctional plaques, as they are when they have been induced by elevation of intracellular cAMP. The results suggest that although Cx43 itself is not glycosylated, other glycosylated proteins influence Cx43 posttranslational modification and the formation of Cx43 cell-to-cell channels.

Alkaline Phosphatase↗
PubMed1995

Clustering of Cx43 cell-to-cell channels into gap junction plaques: regulation by cAMP and microfilaments.

Cell-to-cell channels are often seen clustered at cell-cell contacts into the so-called gap junction plaques. The mechanism of this clustering is unknown. We show that the clustering of cell-to-cell channels composed of connexin43 is induced by elevation of cyclic AMP. The cAMP-induced clustering is enhanced by inhibition of glycosylation and abolished by disruption of microfilaments. Channel clustering thus seems to be regulated by cAMP and glycosylation and to involve microfilaments.

Actin Cytoskeleton↗