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Biomedical subjects

B Rose

Publications and source records attributed to B Rose.

At least 19 recordsLinked to original sources
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↗
PubMed1994

Groin dissection in malignant melanoma.

BACKGROUND: There is controversy about the extent of groin dissection necessary (whether superficial or radical) and about its utility when the deep nodes are affected. METHODS: A total of 198 groin dissections (1977-1991) were reviewed; 94 (48%) were superficial and 104 (52%) were radical dissections. Of 72 patients with palpable positive inguinal nodes, 31 (43%) had involvement of the deep nodes; of 39 patients with nonpalpable, histologically positive inguinal nodes, seven (18%) had or later manifested involvement of the deep nodes. RESULTS: The mean number of positive nodes (median) in the group with clinically palpable disease was six (two), and in the group with occult disease the number was two (one). The estimated overall (disease-free) 5-year and 10-year survival rates for patients with negative nodes were 73% (67%) and 64% (58%), respectively, and for those with positive nodes they were 36% (27%) and 30% (23%), respectively. Survival was significantly poorer for patients with positive nodes (p < 0.0001). The respective 5-year and 10-year survival rates for patients with positive nodes and involvement of the inguinal nodes only were 41% (33%) and 36% (29%), and for those with involvement of the inguinal and deep nodes the rates were 28% (17%) and 19% (13%). Survival was significantly poorer for patients with deep node involvement (p = 0.006). CONCLUSIONS: The survival rates after therapeutic groin dissection are substantial and unattainable with any other treatment at the present time. Incontinuity dissection of the deep nodes is advisable in the presence of palpable inguinal nodes, since the incidence of deep node involvement is considerable and the survival rate appreciable after removal of involved deep nodes.

Adult↗
PubMed1994

Barbiturate therapy for status epilepticus in the postanesthesia care unit.

Although rare, status epilepticus refractory to conventional therapy may require the initiation of pentobarbital anesthesia and intensive monitoring in the PACU. Barbiturate therapy mandates that the nurse be able to perform mechanical ventilation and advanced cardiopulmonary monitoring as well as be familiar with electroencephalographic monitoring. Careful attention to the potential side effects of barbiturate therapy and anticipation of end-organ complications can increase the likelihood of seizure termination and recovery of status epilepticus patients.

Barbiturates↗
PubMed1993

Gap-junction protein gene suppresses tumorigenicity.

Prompted by the notion that the membrane channels in gap junctions conduct growth-regulating signals from cell to cell, we transferred the alpha 1 gene for the channel protein (connexin43) of rat heart to tumorigenic mouse MCA-10 cells. Upon incorporation into the cell genome, this exogenous gene was expressed, resulting in functional channels and normal growth regulation: cell-cell communication, determined with a channel-permeant 400-dalton fluorescent tracer, was increased and tumorigenicity, determined in nude mice, was suppressed.

Animals↗
PubMed1992

A chimeric mouse/human anti-IL-2 receptor antibody with enhanced biological activities.

A chimeric mouse/human MAb against the human p55 IL-2R was constructed from Ig genes isolated from a mouse hybridoma cell line, designated AHT107. AHT107 binds to a different epitope on p55 than IL-2, and similar to observations made for other rodent anti-IL-2R antibodies that do not recognize the same or spatially related epitope as IL-2, murine AHT107 did not efficiently inhibit proliferation of T-lymphocytes in mitogen and MLR PBMC stimulation assays. In contrast, the chimeric AHT107 antibodies containing a human IgG-1 constant region had substantially more anti-proliferative activity than their murine IgG-I counterparts. Our results indicated that the human constant region of the chimeric antibodies interacted more efficiently than the murine constant region with effector components present in the PBMC cultures. This conclusion was supported by our observation that F(ab')2 generated from the chimeric antibodies did not efficiently inhibit proliferation in the PBMC assays, and the chimeric antibodies did not inhibit proliferation of an antigen specific, IL-2 dependent human T-cell clone stimulated in the absence of PBMC.

Amino Acid Sequence↗
PubMed1992

The cell-cell channel in the control of growth.

Several lines of evidence indicate that the cell-cell channels in gap junction are conduits for growth-regulating signals. Experimental upregulation of the channels by retinoids causes inhibition of cellular growth and, conversely, their downregulation by oncogenes, e.g. activated src, stimulates growth. In either direction, the extent of growth correlates tightly with the degree of communication. Cogent evidence of the channel's function in growth regulation is now on hand: incorporation of a channel-protein gene into the genome of a transformed communication-deficient cell line normalizes communication and growth. The current data conform to a model of growth control with discrete regulatory centers.

Animals↗