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Biomedical subjects

B J Roth

Publications and source records attributed to B J Roth.

At least 145 records · Page 8Linked to original sources
PubMed1988

Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide.

STUDY OBJECTIVE: To determine the efficacy of the addition of ifosfamide to cisplatin plus etoposide (VIP), or vinblastine (VeIP), in patients with recurrent germ cell tumors. DESIGN: Nonrandomized, prospective phase II trial. SETTING: Tertiary referral university hospital. PATIENTS: Fifty-six of fifty-eight entered patients with measurable and progressive recurrent germ cell tumors of testicular (46 patients), ovarian (1 patient), and extragonadal (9 patients) origin were evaluable for response after not being cured with cisplatin, vinblastine, and etoposide regimens. INTERVENTIONS: Patients were administered cisplatin (20 mg/m2 body surface area daily for 5 days), ifosfamide (1.2 g daily for 5 days), plus either etoposide (75 mg daily for 5 days) or vinblastine (0.11 mg/kg body weight on days 1 and 2). In addition, vigorous intravenous hydration therapy with normal saline (100 to 125 mL/h) was administered during the treatment course. Uroepithelial protective agents, N-acetylcysteine (orally) or mesna (intravenously), were administered. Four courses were administered to responding patients every 3 weeks. When complete excision was feasible, surgical resection of residual tumor was done approximately 6 to 8 weeks after chemotherapy. MEASUREMENTS AND MAIN RESULTS: Twelve of fifty-six evaluable patients had a complete remission with chemotherapy alone, whereas 8 additional patients were free of disease after resection of teratoma (3 patients) or carcinoma (5 patients) for a total disease-free rate of 36% (95% CI, 23.4 to 49.6). The 95% CI median duration of remission for these patients is 34 months (range, 3 to more than 42; 95% CI, 9 months to infinity), and the median survival for all eligible patients is 12.7 months (95% CI, 10 months to 26 months), with 15 of the 20 patients who achieved disease-free status alive 18 to 53 months or more. Nine of fifty-eight patients remain free of disease, including 7 patients for 2 years or longer. Hematologic and nephrotoxicity were the predominant drug-related toxicities, with one drug-related death secondary to pneumonia. CONCLUSIONS: Ifosfamide combination chemotherapy as third-line or greater therapy can produce durable complete remissions in heavily pretreated patients with recurrent germ cell tumors.

Adolescent↗
PubMed1988

Relation of proliferative activity to survival in patients with advanced germ cell cancer.

Patients with advanced disseminated germ cell tumors of the testis, retroperitoneum, and mediastinum have impaired survival compared to other patients with disseminated germ cell tumors having less bulky metastatic disease. Among patients with advanced disseminated germ cell tumors, we currently lack adequate predictors of long-term survival. Flow cytometric analysis of the paraffin-embedded, formalin-fixed tumor blocks of 50 of these patients suggests that proliferative activity is significantly correlated with survival (p less than 0.001) in multivariate analysis. Log (beta-human chorionic gonadotropin) is the only other useful predictor of long-term survival in multivariate analysis of prognostic factors in this group of patients. Flow cytometric DNA analysis may be useful in predicting survival in patients with advanced disseminated germ cell tumors.

Cell Cycle↗
PubMed1988

The electrical potential produced by a strand of cardiac muscle: a bidomain analysis.

Analytic expressions are derived relating the transmembrane potential to the intracellular, interstitial and external potentials in a cylindrical strand of cardiac muscle lying in a saline bath. The bidomain model is used to account for the anisotropy and interstitial space in the tissue. The implications of this model for interpreting potential data from strands of cardiac muscle are discussed.

Action Potentials↗
PubMed1988

Magnetic determination of the spatial extent of a single cortical current source: a theoretical analysis.

In this paper a model, originally developed for calculating the magnetic field produced by a single nerve fiber, is used to compare the ability of two magnetometers with different spatial resolutions to map the magnetic field distribution from a highly localized current source in the cerebral cortex. It is concluded that whenever the source-to-coil distance is much larger than the dimensions of the source it will be difficult, if not impossible, to use an inverse calculation to determine the spatial extent of the source from the magnetic field. When the source-to-coil distance is comparable to the extent of the source, an inverse calculation can provide information regarding the axial length of a localized dipolar current source.

Cerebral Cortex↗
PubMed1988

Cisplatin as first-line therapy for metastatic breast cancer.

Cisplatin has had only minimal activity when used as second- and third-line chemotherapy for metastatic breast cancer (MBC). There have been no phase II studies in the United States evaluating cisplatin in patients with MBC with no prior chemotherapy. We therefore treated 20 consecutive patients with cisplatin 30 mg/m2/d for four days every 3 weeks for a maximum of six courses. We obtained partial responses in nine of 19 evaluable patients (47%), with responses in liver, lung, and soft tissue indicator lesions. Our data suggest that cisplatin has substantial single-agent activity as front-line therapy in MBC, and should be considered for inclusion in first-line combination chemotherapy regimens.

Adenocarcinoma↗
PubMed1988

Cisplatin-based combination chemotherapy for disseminated germ cell tumors: long-term follow-up.

A retrospective analysis of the initial 229 cases of disseminated germ cell tumors treated at Indiana University with cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin revealed 146 patients who are alive and disease-free with a minimum follow-up of 6 years and a median follow-up of 8.5 years. At 12 years, the estimated probability of survival is 65.0%, and the estimated probability of relapse-free survival for complete responders is 83.5%. Long-term complications, such as clinically significant organ toxicity or therapy-related second malignancies, have not been observed. The functional status of survivors is maintained, with 95% returning to their pretherapy status, of which 88% are fully employed. Of patients receiving chemotherapy without abdominal surgery, 35% have fathered healthy children posttherapy. Achievement of complete remission (CR) in disseminated germ cell tumors with cisplatin-based combination chemotherapy translates to long-term disease-free survival and cure for the majority of patients, with preservation of functional status.

Adolescent↗
PubMed1988

Analysis of phorbol ester stimulated human megakaryocyte development.

Megakaryocytes are relatively rare components of human bone marrow, making the study of their maturation difficult. Phorbol esters can act as differentiating agents in a number of cell systems including murine megakaryocytes. We report the effects of phorbol esters on the previously described long-term human megakaryocytic leukemia cell culture, EST-IU. While two nontransforming phorbols fail to affect these cells, the transforming phorbol 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a phenotype with characteristics of more mature megakaryocytes in a dose-related manner. This phenotype includes an increased adherence to untreated plastic or glass, polyploidization, an increase in cell size, and increased expression of both platelet glycoproteins and factor VIII-related antigen. Two-color flow cytometric analysis allowed simultaneous determinations of DNA content and the expression of surface membrane antigens or alpha-granule constituents, providing evidence that nuclear, membrane, and cytoplasmic maturation occur in parallel in this cellular system. TPA-induced maturation of EST-IU cells provides an important new cellular model for the further study of human megakaryocyte development.

Antigens↗
PubMed1987

Purification and characterization of a high molecular weight type 1 phosphoprotein phosphatase from the human erythrocyte.

The major Mn2+-activated phosphoprotein phosphatase of the human erythrocyte has been purified to homogeneity from the cell hemolysate. It is sensitive to both inhibitors 1 and 2 of rabbit skeletal muscle, preferentially dephosphorylates the beta subunit of the phosphorylase kinase, and dephosphorylates a broad range of substrates including phosphorylase a, p-nitro-phenyl phosphate, phosphocasein, the regulatory subunit of cyclic AMP-dependent protein kinase, and both spectrin (Km = 10 microM) and pyruvate kinase (Km = 18 microM) purified from the human erythrocyte. The purified enzyme is stimulated by Mn2+ and to a lesser extent by higher concentrations of Mg2+. The purification procedure was selected to avoid any change in molecular weight, hence subunit composition, between the crude and purified enzyme. Maintenance of the original structure is demonstrated by non-denaturing gel electrophoresis and gel filtration chromatography. Gel filtration of the purified holoenzyme shows a single active component with a Stokes radius of 58 A at a molecular weight position of 180,000. Sedimentation velocity in a glycerol gradient gives a value of 6.1 for S20, w. Together these data indicate a molecular weight of about 135,000. Two bands of equal intensity appear on sodium dodecyl sulfate-gel electrophoresis at molecular weights of 61,700 and 36,300, suggesting a subunit composition of two 36,000 and one 62,000 subunits. The 36-kDa catalytic subunit can be isolated by freezing and thawing the holoenzyme or by hydrophobic chromatography of the holoenzyme. The catalytic subunit shows unchanged substrate and inhibitor specificity but altered metal ion activation.

Animals↗
PubMed1987

A comparison of two models for calculating the electrical potential in skeletal muscle.

We compare two models for calculating the extracellular electrical potential in skeletal muscle bundles: one a bidomain model, and the other a model using spatial and temporal frequency-dependent conductivities. Under some conditions the two models are nearly identical. However, under other conditions the model using frequency-dependent conductivities provides a more accurate description of the tissue. The bidomain model, having been developed to describe syncytial tissues like cardiac muscle, fails to provide a general description of skeletal muscle bundles due to the non-syncytial nature of skeletal muscle.

Animals↗
PubMed1987

Flow cytometry derived DNA content of the primary lesions of advanced germ cell tumours.

We currently lack good prognostic indicators for patients with advanced disseminated germ cell tumours (GCT). An analysis of archival tumour samples of forty-nine patients with advanced GCT for flow cytometry derived DNA content suggests an inverse relationship between tumour proliferative activity and patient survival. The great majority of patients with advanced GCT have aneuploid tumour subpopulations. This analysis suggests that the survival of patients with advanced GCT may depend in part on kinetic variables present in the primary tumour.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Electrically silent magnetic fields.

There has been a significant controversy over the past decade regarding the relative information content of bioelectric and biomagnetic signals. In this paper we present a new, theoretical example of an electrically-silent magnetic field, based on a bidomain model of a cylindrical strand of tissue generalized to include off-diagonal components in the conductivity tensors. The physical interpretation of the off-diagonal components is explained, and analytic expressions for the electrical potential and the magnetic field are found. These expressions show that information not obtainable from electrical potential measurements can be obtained from measurements of the magnetic field in systems with conductivity tensors more complicated than those previously examined.

Action Potentials↗
PubMed1986

Establishment in long term culture of megakaryocytic leukemia cells (EST-IU) from the marrow of a patient with leukemia and a mediastinal germ cell neoplasm.

Megakaryocytes are the bone marrow cells that generate platelets. They are relatively rare cells, comprising between 0.03 and 0.06% of all nucleated marrow cells (R. L. Berkow et al., J. Lab. Clin. Med., 103: 811-818, 1984). The study of human megakaryocyte differentiation and function has been hampered by the small number of these cells available for study. Recently we have established a human cell line (EST-IU) from the marrow of a patient with an acute nonlymphocytic leukemia and a mediastinal germ cell tumor. While this cell line seems to express many of the phenotypic characteristics of human megakaryocytes, it does not appear to express any phenotypic properties associated with cells of the erythroid, lymphoid, granulocytic, or monocytic lineages. Transmission electron microscopy demonstrates frequent multinucleated cells. Staining for platelet peroxidase reactivity revealed darkening of the perinuclear envelope and the endoplasmic reticulum, a characteristic of cells of the megakaryocytic lineage. Indirect immunofluorescence assays reveal that EST-IU expresses reactivity with anti-platelet glycoprotein antisera, anti-Factor VIII-related antigen antisera, anti-Factor V antisera, anti-thrombocyte antisera, Tab (monoclonal anti-platelet glycoprotein IIb-IIIa), and anti-fibronectin antisera. Flow cytometry-derived DNA histograms demonstrate populations with multiple ploidies, ranging from approximately 4N to 32N. Based upon morphological and histochemical characteristics, antigenic expression, and nuclear characteristics, EST-IU cells appear to have a phenotype that closely resembles human megakaryocytes. This cell line should be useful in the further cell study of the molecular and cell biology of human megakaryocytopoiesis.

Acute Disease↗
PubMed1985

The magnetic field of a single axon. A comparison of theory and experiment.

The magnetic field and the transmembrane action potential of a single nerve axon were measured simultaneously. The volume conductor model was used to calculate the magnetic field from the measured action potential, allowing comparison of the model predictions with the experimental data. After analyzing the experiment for all systematic errors, we conclude that the shape of the magnetic field can be accurately predicted from the transmembrane potential and, more importantly, the shape of the transmembrane potential can be calculated from the magnetic field. The data are used to determine ri, the internal resistance per unit length of the axon, to be 19.3 +/- 1.9 k omega mm-1, implying a value for the internal conductivity of 1.44 +/- 0.33 omega -1 m-1. Magnetic measurements are compared with standard bioelectric techniques for studying nerve axons.

Action Potentials↗
PubMed1985

Predictors of myocardial infarction in emergency room patients.

To develop a decision rule to aid in the diagnosis of myocardial infarction, we evaluated clinical and ECG data on 540 adults treated in an urban hospital emergency room for acute chest pain. Of 62 (11.5%) patients who had acute infarctions, 54 were admitted to intensive care (sensitivity 87%); 103 of 478 patients without infarctions were also admitted to intensive care (specificity 78%). Thirty-four percent of all patients admitted had infarctions. Multivariate analysis identified only four clinical variables which carried independent information predicting infarction: two from the ECG and two from the clinical history. A predictive model based on these four variables had significantly greater specificity (86% vs. 78%, p = .003) and accuracy of overall patient classification (88% vs. 79%, p = .013) but somewhat lower sensitivity (81% vs. 87%, p = .46) than physician judgments. However, a decision rule which would have admitted to intensive care those patients with a high probability of infarction who were not admitted by the emergency room physicians, would have increased the sensitivity for detecting infarction to 95% with no appreciable decrease in specificity or yield of infarctions among patients admitted to intensive care.

Adult↗