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Biomedical subjects

E Henderson

Publications and source records attributed to E Henderson.

At least 163 records · Page 9Linked to original sources
PubMed1982

Combinations of methotrexate (COP or CHOP) in the treatment of previously untreated and treated lymphomas.

A regimen consisting of two courses of methotrexate (MTX) with leucovorin rescue followed 1 week later by cyclophosphamide, vincristine, and prednisone (MTX-COP) was studied in ten patients with disseminated diffuse non-Hodgkin's lymphoma who had had no prior chemotherapy. A similar regimen with the addition of doxorubicin (MTX-CHOP) was used for patients who had had previous chemotherapy: 11 with diffuse non-Hodgkin's lymphoma and two with Hodgkin's disease. The response rate to initial MTX administration was 55%, and the clinical onset of effect was usually observed within 48 hours. Responses were observed in previously treated and untreated patients. The remission rate was 100% with both regimens. There were seven complete remissions with MTX-COP and six with MTX-CHOP. The median durations of remission were 23 and 13 months, respectively; median survival was not reached in either group. MTX was well-tolerated by both groups of patients without serious toxic effects. Overall, significantly more hematologic toxicity was observed in previously treated patients; however, no life-threatening toxic effects were observed in either group. The incorporation of MTX and other antimetabolites into schedules of chemotherapy for previously treated and untreated patients with non-Hodgkin's lymphoma is well tolerated and deserved further exploration.

Adult↗
PubMed1981

Dehydroepiandrosterone and 16 alpha-bromo-epiandrosterone: inhibitors of Epstein-Barr virus-induced transformation of human lymphocytes.

Dehydroepiandrosterone (DHEA), a major adrenal secretory product in men and women, is a potent inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Long-term treatment with this steroid has previously been found to suppress spontaneous breast cancer development in C3H mice. DHEA is now shown to inhibit Epstein-Barr virus (EBV)-induced morphologic transformation and stimulation of DNA synthesis in human lymphocytes. 16 alpha-Br-epiandrosterone, a DHEA analog that is about 60 times as potent as DHEA as an inhibitor of G6PDH, is much more effective as an inhibitor of EBV-induced transformation.

Androsterone↗
PubMed1981

The prognostic value of submaximal exercise testing with radionuclide ventriculography before hospital discharge in patients with recent myocardial infarction.

To test the hypothesis that patients at risk of future cardiac events can be identified by sub-maximal exercise testing with radionuclide ventriculography (RVG), 61 patients were studied a mean of 19 +/- 1.0 days (+/- SEM) after acute myocardial infarction (MI). RVGs were used to measure left ventricular ejection fraction (LVEF), wall motion score (WMS), end-diastolic volume (EDV) and end-systolic volume (ESV), and the ratio of systolic blood pressure to ESV (P/V index) at rest and during submaximal exercise. Frank lead ECGs were analyzed for ST-segment change and arrhythmias. These patients were followed for a mean of 9.6 months (60 for 6 months or more and one for 3 months) to determine the incidence of cardiac death, recurrent MI, unstable or medically refractory angina, persistent congestive heart failure (CHF) or limiting angina; these problems were considered to be important cardiac events. At the 6-month follow-up, 37 patients had important complications: four patients died, five had MI, seven had unstable or medically refractory angina, 11 had persistent CHF and 10 had severe limiting angina. The sensitivity and specificity of RVG in predicting the important postinfarct complications listed above were 95% and 96% for failure to increase LVEF by at least 5 units, 95% and 96% for an increase in ESV of more than 5%, 97% and 88% for failure of the P/V index to increase by more than 35%, and 81% and 88%, respectively, for a decrease in WMS. The sensitivity and specificity of the ECG in predicting important complications were 54% and 58%, respectively. The rest and submaximal exercise RVG variables, the ECG, a history of MI, the location of the infarction, Killip class III, age, sex, and maximal work load performed were analyzed statistically to determine the best predictors of prognosis. The change with exercise in LVEF, ESV and the P/V index were most significant variables in predicting prognosis during the 6-month follow-up period. When patients with subsequent cardiac events were separated into those with death, recurrent MI and unstable or medically refractory angina as major cardiac events, and patients with persistent CHF and limiting angina as less important ("minor") cardiac events, only the peak submaximal exercise LVEF and history of MI were significant in distinguishing these groups. In patients without important cardiac events during the 3- and 6-month follow-up, 70% and 88%, respectively, no abnormality in the responses of LVEF, ESV, or P/V index to submaximal exercise. These results suggest that submaximal exercise testing with RVG is a highly sensitive means of classifying patients at the time of hospital discharge after MI according to the likelihood of having cardiac events during the ensuing 6 months.

Adult↗
PubMed1980

Colony morphology, cell growth and viral radiosensitivity as parameters for detecting strain differences in Epstein-Barr virus (EBV).

Several parameters of two lymphocyte-transforming Epstein-Barr viruses (EBVs), B95-8 and Olare, derived from infectious mononucleosis (IM) and African Burkitt's lymphoma (BL), respectively, were compared to determine if there were biological differences between Epstein-Barr viral strains. Morphology of transformed colonies, growth of transformed cell lines, sensitivity to UV light and X-irradiation, as well as EBV-related, antigens were investigated in autochthonous cell lines. The morphology of transformed colonies was found to differ consistently both in new transformants and in lines which had been continuously growing in culture for almost 1 year. The BL transformants grew to greater density than did the IM transformants, and BL-derived virus was more sensitive to both UV light and X-irradiation. No immunologic differences were noted in the strains in assays performed for EBV-related antigens.

Cell Line↗
PubMed1979

Surface markers and size of lymphocytes in human umbilical cord blood stimulated into deoxyribonucleic acid synthesis by Epstein-Barr Virus.

We characterized subpopulations of lymphocytes in human umbilical cord blood which are stimulated into deoxyribonucleic acid synthesis by Epstein-Barr virus. Lymphocytes were examined simultaneously for deoxyribonucleic acid synthesis by autoradiography and for surface markers by rosette formation with sheep erythrocytes or erythrocytes coated with antibody and mouse complement (EAC). The subpopulation which incorporated [3H]thymidine after exposure to virus consisted mainly of cells which formed rosettes with EAC. Lymphocytes were enriched or depleted of thymus-derived lymphocytes (T cells), null cells, or cells forming rosettes with EAC. The extent of sensitivity of the cells to stimulation by Epstein-Barr virus correlated with the proportion of the population which formed rosettes with EAC. When mononuclear cell populations were depleted of T lymphocytes and then fractionated by size, small lymphocytes showed higher rates of deoxyribonucleic acid synthesis after virus exposure and higher transformation frequency than did larger cells or unfractionated cells. Thus, the cells which are stimulated into deoxyribonucleic acid synthesis by Epstein-Barr virus appear to be the same as cells which are ultimately transformed.

DNA↗
PubMed1978

Radiobiological inactivation of Epstein-Barr virus.

Lymphocyte transforming properties of B95-8 strain Epstein-Barr virus (EBV) are very sensitive to inactivation by either UV or X irradiation. No dose of irradiation increases the transforming capacity of EBV. The X-ray dose needed for inactivation of EBV transformation (dose that results in 37% survival, 60,000 rads) is similar to the dose required for inactivation of plaque formation by herpes simplex virus type 1 (Fischer strain). Although herpes simplex virus is more sensitive than EBV to UV irradiation, this difference is most likely due to differences in the kinetics or mechanisms of repair of UV damage to the two viruses. The results lead to the hypothesis that a large part, or perhaps all, of the EBV genome is in some way needed to initiate transformation. The abilities of EBV to stimulate host cell DNA synthesis, to induce nuclear antigen, and to immortalize are inactivated in parallel. All clones of marmoset cells transformed by irradiated virus produce extracellular transforming virus. These findings suggest that the abilities of the virus to transform and to replicate complete progeny are inactivated together. The amounts of UV and X irradiation that inactivate transformation by B95-8 virus are less than the dose needed to inactivate early antigen induction by the nontransforming P(3)HR-1 strain of EBV. Based on radiobiological inactivation, 10 to 50% of the genome is needed for early antigen induction. Inactivation of early antigen induction is influenced by the cells in which the assay is performed. Inactivation proceeds more rapidly in EBV genome-free cells than in genome carrier Raji or in P(3)HR-1 converted EBV genome-free cells clone B(1). These results indicate that the resident EBV genome participates in the early antigen induction process. Variation in radio-biological killing of B95-8 and P(3)HR-1 EBV is not attributable to variations in the repair capacities of the cells in which the viruses were assayed, since inactivation of HSV was the same in primary lymphocytes and in all lymphoid cell lines tested.

Animals↗
PubMed1978

Differences in expression of surface marker characteristics on Epstein-Barr virus-transformed human and simian lymphoid cell lines.

Human lymphoblastoid cell lines transformed in vitro by the Epstein-Barr virus (EBV) had receptors for fixed complement detectable by a rosette test. EBV transformed cells derived from cotton-topped marmoset leukocytes did not express this receptor. Evidence is presented that both human and marmoset cell lines arose from precursor cells which have complement receptors. Our findings suggest that transformation of marmoset leukocytes by EBV results in the loss of a differentiated surface marker.

Animals↗
PubMed1978

Combination chemotherapy plus methanol extracted residue of bacillus Calmette-Guérin or Corynebacterium parvum in stage III lung cancer.

Seventy-six patients with stage III bronchogenic carcinoma were treated with monthly adriamycin, cyclophosphamide, cis-dichlorodiammineplatinum(II), and vincristine. In addition, they were randomized to receive either no immunotherapy, the methanol extracted residue of bacillus Calmette-Guérin (MER), or Corynebacterium parvum (C. parvum). Age, histology, extent of disease, prior therapy, and performance status were comparable in the three treatment groups. Twelve patients (16%) died having received only one treatment cycle. Sixty-four of the 76 patients received two or more treatments and were evaluable for response. There were no patients with complete responses, 14 patients (18%) with partial responses, 28 patients (37%) with no change, and 22 patients (29%) with progressive disease. Survival among patients receiving C. parvum is significantly longer (P less than 0.05) than that of patients receiving either MER or no immunotherapy.

Adult↗
PubMed1977

Host-determined differences in expression of surface marker characteristics on human and simian lymphoblastoid cell lines transformed by Epstein-Barr virus.

In an attempt to account for differences in the biologic behavior of Epstein-Barr virus in different primate species, we studied lymphocyte surface markers on primary and transformed cells. Among primary leukocytes, the distribution of cells with characteristics of bone-marrow-derived cells (B cells) was similar in humans, wooly monkeys, and cotton-top marmosets. However, after transformation by Epstein-Barr virus, cells from each species were characterically different. Transformed human umbilical cord cells expressed the complement receptor; monkey cells exhibited both this receptor and the receptor for IgG Fc (EA7S); and marmoset cells did not have either surface marker. We measured the transformation efficiency of human and marmoset leukocyte subpopulations enriched or depeleted in cells with the complement receptor. In both species the highest efficiencies of transformation were found in populations with the greatest numbers of cells with the receptor. The data therefore suggest that, in all species, a cell with the complement receptor is susceptible to transformation but that this receptor is not expressed on transformed marmoset cells. Thus, in Epstein-Barr virus-induced transformation it is necessary to distinguish between transformation of growth properties (immortalization) and transformation of cell surface properties.

Animals↗
PubMed1975

The nature of the alkylation lesion in mammalian cells.

Methylating agents may produce as many as nine alkylated purine and pyrimidine adducts in DNA, as well as forming phosphotriesters and inducing apurinic sites and strand breaks. Although some of these products are formed in proportionately small amounts, there are sufficient sites affected in the DNA of a mammalian cell to make even the most minor product of potential biological significance. It is not possible to specify the exact reaction sites resulting in biological damage, but it is possible to quantitate the excisiion-repair of such damage both in the bulk of the DNA and at DNA growing points. Excision-repair can be measured in the bulk of the DNA by determining the specific activity of the NaCl eluate of a benzoylated naphthoylated DEAE-cellulose column of extracts of cells after treatment and incubation in the presence of hydroxyurea and labeled thymidine. The average number of nucleotides inserted per methyl methanesulfonate-induced methyl group is 0.1, per apurinic site is 9. Repair in growing-point regions after methyl methanesulfonate treatment occurs to approximately the same extent as in the bulk of the DNA.

Alkylating Agents↗
PubMed1975

The measurement of chemically-induced DNA repair synthesis in human cells by BND-cellulose chromatography.

Repair synthesis in human cells in tissue culture can be readily separated from semi-conservative DNA synthesis with the aid of a benzoylated naphthoylated DEAE cellulose (BND-cellulose) column. Cells are incubated with a radioactive DNA precursor during treatment with a repair-inducing agent. An inhibitor of semi-conservative DNA synthesis (hydroxyurea) is added to slow the progression of the DNA growing point. The cells are lysed and after treatment with ribonuclease and pronase the lysates are sheared and passed through a BND-cellulose column. Native DNA is eluted with I M NaCl. Any increase in radioactivity in the native DNA is due to repair synthesis and the specific repair activity (nucleotides inserted per mug of DNA) can be determined from radioactivity and absorbancy measurements. Repair can also be measured in the region of the DNA growing point by fractionation of the material eluted from BND-cellulose with 50% formamide. Repair was not detected in N-acetoxy-2-acetylaminofluorene (AAAF)-treated lymphoblasts derived from an individual with xeroderma pigmentosum although methyl methanesulfonate (MMS)-induced repair was observed in these cells.

Benz(a)Anthracenes↗