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Biomedical subjects

D R Bell

Publications and source records attributed to D R Bell.

At least 91 records · Page 5Linked to original sources
PubMed1989

Comparison of western blot analysis and immunocytochemical detection of P-glycoprotein in multidrug resistant cells.

A sensitive immunocytochemical technique was developed to detect a 170,000 dalton cell membrane glycoprotein (P-gp) in cell lines resistant to vincristine and vinblastine with varying degrees of resistance. P-gp was shown very clearly using the C219 monoclonal antibody and immunocytochemical detection with either antialkaline phosphate or peroxidase-antiperoxidase with silver gold intensification. There was good correlation between the results obtained with immunocytochemical detection of P-gp in single cells and Western blot analysis. The technique is easily performed and can detect P-gp in relatively small numbers of cells that Western blot analysis could miss and is suitable for clinical application.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

High flow attenuates relaxation by acetylcholine in isolated perfused canine femoral arteries.

The effect of changes in flow on endothelial-dependent and -independent dilation of isolated perfused arteries was determined. Femoral arteries from ten dogs were excised and mounted in a vessel bath containing a physiological salt solution (PSS) at 37 degrees C, bubbled with 95% O2-5% CO2. The vessel outer diameter was measured using an ultrasonic crystal dimension system. Arteries were perfused with PSS at a steady flow of 1 ml/s at 90 mmHg. Tone was induced in the arteries by the addition of phenylephrine to the vessel bath. Acetylcholine (six dogs) and sodium nitroprusside (four dogs) were added to the perfusate in a cumulative fashion and changes in vessel diameter were recorded until maximum vasodilation was achieved. Dose-response relationships to the agents were determined with each vessel perfused at 1 and 4 ml/s. Sensitivity to each agent was measured as the ED50 value calculated from the respective dose-response relationships. Sensitivity to acetylcholine, but not sodium nitroprusside, was significantly decreased in arteries perfused at 4 ml/s versus 1 ml/s [acetylcholine ED50: 1 ml/s = (0.79 +/- 0.31) x 10(-8) mol/l, 4 ml/s = (1.55 +/- 0.60) x 10(-8) mol/l, P less than 0.05; sodium nitroprusside ED50: 1 ml/s = (2.57 +/- 0.12) x 10(-7) mol/l, 4 ml/s = (2.69 +/- 0.60) x 10(-7) mol/l, not significant]. We conclude that high flow decreases sensitivity to acetylcholine in canine femoral arteries and suggest that vascular reactivity to this agent may be modified by changes in shear on the vascular endothelium.

Acetylcholine↗
PubMed1988

Cisplatin plus VP 16-213 in advanced ovarian carcinoma.

Thirty-five patients with advanced epithelial ovarian carcinoma (24 untreated, 11 previously treated with alkylating agents) were treated with a combination of cisplatin and etoposide (VP16-213). Tumor response (i.e., complete response and partial response) was seen in 16 of the 35 patients (i.e., 46%), with 5 complete responses. The response rate in previously untreated patients was 54%, but only 27% in previously treated patients. The median survival was 42 weeks. The toxicity of this regimen was severe. Twelve patients became severely myelosuppressed, including one septic death while severely neutropenic. Treatment with cisplatin and etoposide produces only average tumor response rates and patient survival, but is associated with severe toxicity. There is no evidence of synergy between cisplatin and VP16 in this study.

Adult↗
PubMed1988

Identification of a multidrug resistance associated antigen (P-glycoprotein) in normal human tissues.

The multidrug resistance (NDR) phenotype describes a pattern of cross-resistance to unrelated compounds observed in mammalian cell lines selected in vitro for resistance to a single agent. Overexpression of a 170,000 dalton cell membrane glycoprotein (P-glycoprotein) is associated consistently with this phenotype in these cell lines. Recently, several human tumours have been shown to contain P-glycoprotein and expression was greatest in tumours exhibiting clinical drug resistance. To explore further the significance of P-glycoprotein, we examined normal human tissues obtained at autopsy by polyacrylamide gel electrophoresis and immunoblotting using a monoclonal antibody directed against P-glycoprotein. We showed expression of P-glycoprotein in normal liver and small bowel mucosa but not in other organs examined. This suggests there may be significant expression of P-glycoprotein in certain normal human tissues and any plan to exploit P-glycoprotein clinically must take these findings into account.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Initial equilibration of albumin in rabbit hindpaw skin and lymph.

We compared initial plasma to extravascular and plasma to lymph equilibrations of 125I-labeled rabbit albumin in hindpaw heelskin of anesthetized rabbits during control conditions, increased venous pressure (IVP), and intra-arterial infusions of papaverine or bradykinin. Plasma tracer concentrations were maintained constant during the experiments. Control prenodal lymph specific activity relative to plasma specific activity (L*/P*) was significantly greater (P less than 0.01) than extravascular specific activity relative to plasma specific activity (M/P) following 3, 5.5, and 11 h of tracer infusion. Papaverine increased lymph flow and lymph albumin flux (LCL) 2.4-fold, without significantly changing the extravascular albumin mass (MA). IVP increased LCL 2.5-fold and decreased MA 25%. L*/P* at 3 h was twice control following papaverine. M*/P* at 3 h was not significantly affected by papaverine or IVP. Bradykinin increased LCL 10-fold and MA 2.3-fold. L*/P* and M*/P* were 3.1 and 4.3 times control, respectively. The data are consistent with extravascular albumin distributing into two pools that equilibrate with plasma at different rates. Papaverine and IVP affect the faster pool, whereas bradykinin affects both pools.

Albumins↗
PubMed1988

External auditory canal stenosis and atresia: dual flap surgery.

Surgical correction of the severely stenosed or atretic external canal still remains a difficult surgical challenge. As more and more techniques are described, it is apparent that the main thrust and emphasis is to prevent late cicatrization or stenosis. The essential principles are to create a wide canal and cover as much raw surface as possible with skin, preferably full-thickness and with an intact blood supply. The following technique, using dual flaps, has been used successfully in 10 consecutive problem ears with unusual underlying pathologies. With follow-up ranging from seven months to four years, there have been no cases of restenosis to date.

Adolescent↗
PubMed1987

Detection of a multidrug resistant phenotype in acute non-lymphoblastic leukaemia.

Most adult patients with acute non-lymphoblastic leukaemia (ANLL) relapse with drug resistance. Overexpression of a plasma membrane protein, P-glycoprotein, correlates with multidrug resistance in human and animal cell lines. We have detected a multidrug resistance phenotype in two patients with drug resistant ANLL by an immunocytochemical assay using a monoclonal antibody to P-glycoprotein. Sequential analysis of peripheral blood samples from both patients showed a progressive increase in both the intensity of staining and the proportion of leukaemic cells that bound antibody as the disease progressed. The assay is simple, and may have prognostic and therapeutic implications.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1987

Randomised study of ticarcillin, cefamandole with or without tobramycin in febrile, neutropenic patients with solid tumors.

A prospective randomised study was conducted comparing the efficacy and toxicity of the antibiotics ticarcillin and cefamandole (TC) with or without tobramycin (TCT) in 100 febrile neutropenic patients with solid tumours undergoing conventional chemotherapy. In this study, neutropenia less than 100/microliter was noted in 31% of 106 evaluable infectious episodes and neutrophil counts less than 1,000/microliter persisted for a median 4 days. Infection was microbiologically documented in 42% of episodes (bacteremia 24%) with gram-negative organisms responsible for 63% of bacterial isolates. Overall, 65% of episodes responded to TC and 76% to TCT (p greater than 0.05). Patients with initial shock bacteremia, pulmonary infection, or gram-negative sepsis responded relatively poorly. Neutrophil nadir and pathogen susceptibility did not influence outcome. Antibiotic toxicity was minimal with no tobramycin-related nephrotoxicity. These results are broadly comparable to those observed with leukemic patients, but the relatively short duration of neutropenia in the solid-tumour patients appears to minimize the need for additional antibiotics provided there is adequate antimicrobial coverage with the initial choice of antibiotics.

Adult↗
PubMed1987

Chromosomal location of human P-glycoprotein gene sequences.

Nonresponse to chemotherapy may result from the acquisition of multidrug resistance by malignant cells. Overexpression of the 170,000 dalton cell surface P-glycoprotein is associated with this phenotype and this appears to result from amplification of a multigene family coding for this protein. A cDNA encoding a conserved portion of P-glycoprotein has been cloned from hamster cells, and this was used in the present study to localize human P-glycoprotein gene sequences to chromosome 7q36.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1987

Angiosarcoma of the heart.

The case of a woman with angiosarcoma of the right atrium is reported. The tumor was inoperable, and the patient was treated with chemotherapy. There was no response to treatment.

Aged↗
PubMed1987

Albumin and IgG in skin and skeletal muscle after plasmapheresis with saline loading.

The acute effect of removing plasma equivalent to 1.7% body wt and replacing it with saline equivalent to 10% body wt on the extravascular distribution of water, albumin, and immunoglobulin G (IgG) in skin and skeletal muscle was studied in anesthetized rabbits. The plasma protein concentration decreased by 43%. Prenodal lymph was collected from hindpaw skin or skeletal muscle. The extracellular and plasma volumes in excised tissue samples were measured using 51Cr-labeled ethylenediaminetetraacetic acid and 125I-labeled albumin, respectively. The protein spaces were calculated from measurements of endogenous albumin and IgG concentrations using immunochemical techniques. Lymph flow from both tissues increased more than twice control, whereas the lymph total protein concentration decreased to less than one-half control. Three to six hours after the saline infusion, the skin interstitial volume was 30% greater than control, whereas the extravascular masses of albumin and IgG were 20% greater than control. For muscle, the interstitial volume was twice the control value, whereas the extravascular masses of albumin and IgG were not significantly altered. There was a large decrease in the lymph protein concentration after acute plasmapheresis. However, there was not an acute decrease in the extravascular albumin or IgG masses from skin or skeletal muscle. This may be due to the presence of the collagen matrix and edema fluid.

Animals↗
PubMed1987

Decreased intraocular pressure in dogs with one-kidney, one wrapped hypertension.

We examined the relationship of intraocular pressure and the development of one-kidney, one wrapped (perinephritic) hypertension in the dog. Conscious femoral arterial pressure (direct arterial puncture) and intraocular pressure (Schiotz tonometer) were measured weekly before and after the surgical induction of hypertension in 11 healthy male mongrel dogs and before and after unilateral nephrectomy in 15 normotensive control dogs. Preoperative mean arterial pressure (102 +/- 5 vs 99 +/- 8 [SD] mm Hg, hypertensive vs control dogs) and intraocular pressure (18.1 +/- 2.5 vs 17.7 +/- 2.1 mm Hg, hypertensive vs control dogs) were similar in both groups. In normotensive control dogs, mean arterial pressure and intraocular pressure averaged over the postoperative period (4-8 weeks) did not differ significantly from preoperative values. In contrast, during the same period arterial pressure significantly increased and intraocular pressure significantly decreased in hypertensive dogs (arterial pressure, 163 +/- 8 mm Hg; intraocular pressure, 11.9 +/- 4.0 mm Hg; p less than 0.001 for both values compared with corresponding values in control dogs). Intraocular pressure was inversely related to arterial pressure in hypertensive dogs (r = 0.56, p less than 0.01). These observations indicate that intraocular pressure decreases with the development of canine one-kidney, one wrapped hypertension. The mechanism of this decrease may be related to abnormalities in Na+,K+-adenosine triphosphatase activity found in this form of hypertension.

Animals↗
PubMed1987

A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis.

Forty-four patients with documented meningeal carcinomatosis (small-cell lung carcinoma [SCLC], 29%; breast carcinoma, 25%) were treated in a prospective randomized trial with intrathecal methotrexate (MTX) 15 mg or MTX plus cytosine arabinoside (Ara-C) 50 mg/m2. Most patients received intrathecal hydrocortisone (HC) each treatment to minimize arachnoiditis. Overall response was 55%. Seven patients achieved complete response. Response to MTX was superior to combined MTX/Ara-C, but not significantly so (61% v 45%; P greater than .10). Response was more frequent if drugs were administered via Ommaya reservoir than by lumbar puncture (65% v 48%; P greater than .10). Concurrent radiotherapy to the CNS was associated with significantly better response (73% v 35%; P less than .05). Small-cell lung carcinoma patients showed the best response (69%). Overall median survival for the whole group was 8 weeks, but responders fared better than nonresponders (median survival, 18 v 7 weeks; P less than .05). Nausea and vomiting were the most common toxicities encountered (45%), but rarely proved limiting. An unusual, previously undocumented reaction to intrathecal HC was noted. MTX is moderately effective in nonleukemic meningeal carcinomatosis, but the addition of Ara-C does not appear to improve results. Pretreatment factors did not predict outcome in this trial.

Adult↗
PubMed1987

P-glycoprotein in human sarcoma: evidence for multidrug resistance.

Overexpression of an immunologically conserved, cell-surface glycoprotein (P-glycoprotein) is consistently associated with multidrug resistance in cell lines in vitro. A preliminary survey of specimens from 12 solid tumor types in our laboratories indicates significant overexpression of P-glycoprotein in some sarcomas. When tested by immunoblotting with monoclonal antibodies directed against P-glycoprotein; tumors from six of 25 sarcoma patients displayed elevated levels of P-glycoprotein. Three of the sarcoma patients exhibiting P-glycoprotein had not previously been exposed to chemotherapy, implying that overexpression of this marker and possible concomitant multidrug resistance may not depend only on selection during prior drug treatments. The P-glycoprotein overexpression in the sarcoma specimens is evidence for the presence of multidrug resistant cells in these tumors; thus, our data suggest that this mode of resistance may have clinical significance in sarcoma patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗