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Biomedical subjects

T Anderson

Publications and source records attributed to T Anderson.

At least 271 records · Page 15Linked to original sources
PubMed1979

Competitive binding radioassay for 5-fluorodeoxyuridine 5'-monophosphate in tissues.

A competitive binding radioassay has been developed for 5-fluorodeoxyuridine 5'-monophosphate, based on the tight binding of this potent inhibitor to thymidylate synthetase (EC 2.1.1.45). Unbound ligand may be separated from that bound to enzyme by precipitating the intact inhibitor-enzyme complex with trichloroacetic acid. Scatchard plot analysis using a two-site model for binding yielded apparent dissociation constants of 1.2 x 10(-11) and 1.7 x 10(-10) M from a least-squares computer fit of the data. 5-Fluorodeoxyuridine 5'-monophosphate could be detected in the range of 0.02 to 2.0 pmol with no apparent interference by other substances. Assay of 5-fluorodeoxyuridine 5'-monophosphate levels in L1210 ascites tumor following 5-fluorouracil in vivo revealed peak levels occurring within the first hr with a subsequent disappearance half-life of 3.9 hr. Close agreement was found between the previously described enzyme inhibition assay and the more rapid and sensitive competitive binding method.

Animals↗
PubMed1979

DNA-protein and DNA interstrand cross-linking by cis- and trans-platinum(II) diamminedichloride in L1210 mouse leukemia cells and relation to cytotoxicity.

The effects of cis- and trans-platinum(II) diamminedichloride on L1210 cells were investigated using the technique of DNA alkaline elution. Both agents produced reductions in alkaline elution rates which were partially or, in some cases, almost completely reversed by incubation of the cell lysates with proteinase K. The proteinase-sensitive component of this effect is taken to reflect DNA-protein cross-linking, while the proteinase-resistant component of this effect may include interstrand cross-links. The cytotoxicity of the two agents did not correlate with the extent of DNA-protein cross-linking but did appear to correlate with the extent of proteinase-resistant cross-linking; therefore, there may be a relationship between cytotoxicity and interstrand cross-linking.

Animals↗
PubMed1978

Clinical relevance of the histopathological subclassification of diffuse "histiocytic" lymphoma.

Because diffuse "histiocytic" lymphoma, which is an immunologically heterogeneous disease, responds well to chemotherapy in some but not all patients, we attempted to identify the morphologic features that might correlate with its behavior and prognosis. We identified five histopathological categories in 66 patients: one with an excellent prognosis (large, cleaved cell, six of eight patients surviving for two years); two with an intermediate prognosis (large, noncleaved and mixed follicular-center cell, nine of 18 and eight of 17, respectively, surviving for two years); and two with a poor prognosis (blastic and pleomorphic pyroninophilic, one of 10 and two of 13, respectively, surviving for two years). The differences among categories were significant (P less than 0.02) and not dependent on stage (P greater than 0.20). Tumors of follicular-center origin had a better prognosis than tumors of nonfollicular-center origin (P less than 0.01). Differences in survival were due to differences in complete response rate. Morphologic subclassification of diffuse "histiocytic" lymphoma may be useful in predicting response to chemotherapy and survival.

Adult↗
PubMed1978

Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy.

Eighty patients with advanced ovarian adenocarcinoma were treated in a prospective, randomized trial comparing a four-drug combination--hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil--with the oral alkylating agent, melphalan. Treatment with the four-drug combination was associated with a significantly increased overall response rate (75 vs. 54 per cent) (P less than 0.05), more complete remissions (33 vs. 16 per cent) and longer median survival (29 vs. 17 months) (P less than 0.02) but more severe toxicity than occurred with melphalan. Patients with minimal residual disease had a significantly higher overall response rate than patients with extensive residual disease (84 vs. 53 per cent) (P less than 0.05). Patients with advanced disease who achieved a complete remission documented by peritoneoscopy or laparotomy (or both) have a median survival that will exceed three years. The four-drug regimen is more effective than melphalan in the management of advanced ovarian adenocarcinoma.

Adenocarcinoma↗
PubMed1978

Excretion of MHPG in normal subjects: implications for biological classification of affective disorders.

Exretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured repeatedly in 17 normal subjects. The amount of MHPG excreted over a 24-hour period was fairly stable over a period of three consecutive 24-hour samplings, but stability was rather poor over subsequent periods of several weeks, suggesting that execretory patterns are not traits. A normal range of MHPG excretion was estimated to be 900 to 3,500 micrograms/24 hr. This range covers the majority of persons with affective disorders whose excretion patterns have been measured, although comparisons of absolute values between laboratories must be made cautiously. Further, substantial changes within this range may occur in normal subjects with no accompanying change in affect. A slight but definite diurnal pattern of excretion was found, with a peak at the period of 1600 to 1800 hours. No clear relationship to MHPG excretion to state of physical activity, recent consumption of foods or beverages, or prevailing affective state was defined in those subjects living under normal conditions. While MHPG excretion may yet prove useful for categorizing depressed patients and predicting response to drugs, any inferences drawn regarding the pathogenesis of affective disorders must be guarded.

Adolescent↗
PubMed1978

Activity of the epipodophyllotoxin VP-16 in the treatment of combination chemotherapy-resistant non-Hodgkin lymphoma.

Twenty patients with several histologic subtypes of non-Hodgkin lymphoma who had become resistant to combination chemotherapy were treated with a five-day course of the epipodophyllotixin VP-16. Of 19 evaluable patients, 8 (42%) responded to treatment with 1 complete response and 7 partial responses. The median duration of response was 5.5 months. Seven of the responders had a diffuse lymphoma and 1 had a nodular lymphoma. Of the responders who had diffuse histiocytic lymphoma (DHL), diffuse mixed lymphoma (DML), and diffuse undifferentiated lymphoma (DUL)--the more aggressive histologies in the Rappaport classification--6 of 13 (46%) evaluable patients responded to therapy. Responses were seen in node-dominant, skin-dominant, and marrow-dominant disease. Toxicity was mainly hematopoietic, 53% of patients experiencing leukopenia ( less than 2,000 cells per cu mm) and 68% of patients experiencing thrombocytopenian 2,000 cells per cu mm) and 68% of patients experiencing thrombocytopenia ( less than 100,000 platelets per cu mm). There were two deaths attributable to profound leukopenia with sepsis. The activity of VP-16 in patients who have previously been extensively treated with multiple drugs including vincristine supports its activity in the lymphomas and suggests its lack of cross-resistance with vincristine. The inclusion of VP-16 in primary treatment protocols in the diffuse lymphomas should be considered.

Blood Cell Count↗
PubMed1978

The role of the radioimmunoassay of serum alpha-fetoprotein and human chorionic gonadotropin in the intensive chemotherapy and surgery of metastatic testicular tumors.

Quantitative measurement of serum alpha-fetoprotein and human chorionic gonadotropin by double antibody radioimmunoassays reflects the efficacy of surgical, radiation and/or chemotherapeutic regimens in patients with bulky disseminated testicular tumors. When these therapies are effective they produce an immediate decrease in serum levels of these markers that reflects the decrease in tumor size and could be as rapid as the catabolic decay rate for alpha-fetoprotein or human chorionic gonadotropin. The alpha subunit of human chorionic gonadotropin has a short half-life (20 minutes) and has been used for the first time to localize a recurrent metastatic testicular tumor. Cellular localization of these markers by immunochemical techniques has helped us to understand the natural history of this cancer and the cell types responsible for production of the markers.

Adult↗
PubMed1978

Kinetics of formation and disappearance of a DNA cross-linking effect in mouse leukemia L1210 cells treated with cis- and trans-diamminedichloroplatinum(II).

cis- and trans-diamminedichloroplatinum(II) (PDD) produced a DNA cross-linking effect in mouse leukemia L1210 cells, which was demonstrable after subtoxic treatments with the DNA alkaline elution technique. Cross-linking effects developed following treatments with concentrations as low as 1 micron for cis-PDD and 5 micron for trans-PDD, which permitted over 80% survival of colony-forming ability. The maximum cross-linking effect by cis-PDD required about 12 hr of posttreatment incubation before it was fully developed, whereas the cross-linking effect of trans-PDD was fully developed at the end of the 1-hr drug exposure. The cross-linking effects of both agents were reversed upon further incubation of the cells.

Animals↗
PubMed1977

The treatment of Hodgkin's disease: emphasizing programs at the Clinic Center, National Institutes of Health.

During the past 10--15 years there has been a dramatic improvement in the prognosis of patients with Hodgkin's diases. More than 80% of all patients now will live 5+ years, many of them free from disease. The well-recognized immediate complications of therapy discussed above, are insignificant compared to the tremendous improvement in patients' survival. The fact that they now probably will survive long enough to potentially be at risk of such long-term complications is a testament to the efficacy of modern-day aggressive therapy.

Adult↗
PubMed1977

Peritoneoscopy: a technique to evaluate therapeutic efficacy in non-Hodgkin's lymphoma patients.

Peritoneoscopy was performed in 22 patients with non-Hodgkin's lymphoma as a re-staging technique to rule out relapse or persistence of active disease after intensive chemotherapy and/or radiotherapy. Fifteen patients with previous hepatic involvement achieved a complete clinical remission; however, five patients (33%) had persistent disease proved by biopsy at peritoneoscopy. In seven patients suspected to have a clinical relapse, peritoneoscopy biopsies documented relapse in three patients (43%), including two patients with negative percutaneous liver biopsies. Because of its low morbidity rate (4%), peritoneoscopy can be utilized to re-stage hepatic involvement by non-Hodgkin's lymphoma patients more accurately than percutaneous liver biopsies and with less morbidity than laparotomy.

Humans↗