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Biomedical subjects

A Goodman

Publications and source records attributed to A Goodman.

At least 109 records · Page 6Linked to original sources

Development of a cytochrome P-450 monooxygenase system in clonogenic hemopoietic cells.

We characterized the presence of the monooxygenase arylhydrocarbon-hydroxylase (AHH), in mouse bone marrow cells taken directly from animals and from bone marrow colony culture. Using a standard radio-isotopic assay it was found that AHH activity was present in mouse bone marrow cells and that there was demonstratable activity in preparations taken directly from differentiated erythroid and myeloid colony cultures. Murine colonies of erythroid (CFU-E) and granulocytes (CFU-GM) were grown and AHH activity determined in non-induced and 3-methylcholanthrene (3-MC) induced cultures. Addition of 3-MC to erythropoietin dependent CFU-E was found to induce AHH activity above controls in a dose dependent manner, with 75 micrograms generating a maximal effect. CFU-E taken from different incubation periods (1-4 days) revealed that AHH was maximal in 2 1/2 day cultures and thereafter declined. In contrast, maximal AHH activity was obtained from 6-7 day CFU-GM and 40 micrograms of 3-MC stimulated the activity by 88%. These results demonstrate that AHH is present in normal mouse bone marrow cells and developing hemopoietic colonies, and that induction of AHH may indicate an important role for these cytochrome P-450 monooxygenases in cell development and differentiation as well as in the metabolism of various drugs.

Animals↗

Human antibodies to the antineoplastic drug elliptinium: characterization and structure-activity relationships.

Immune-mediated hemolytic disease is a phenomenon rarely encountered with cancer chemotherapeutic agents. Elliptinium, a tetracyclic ammonium compound used in breast and kidney cancer, can induce antibodies that may result in clinical hemolysis. This study reports the characterization of the elliptinium haptenic determinant by use of two different methodologies: a hemagglutination test and a radioimmunoassay. Binding of 12 analogues or derivatives of elliptinium was also studied. Good correlation between the two methods was obtained, indicating that the determinant is most likely located on the quaternary ammonium-containing ring. Furthermore, the hydrophilicity of the drug appears to be an important factor in the antibody reaction. The mechanism of the binding of elliptinium to its antibodies is discussed.

Alkaloids↗

Ellipticine derivatives interact with muscarinic receptors.

Ellipticine derivatives or analogues, tetracyclic alkaloids used in human cancer treatment, have been evaluated with regard to their interaction with several neurotransmitter receptors, in order to explain or to predict the side effects which occur in man. These drugs were recently found to be reversible non-competitive inhibitors of cholinesterases. In this study, we have shown that ellipticines are also potent muscarinic antagonists, only 100-fold less active than atropine in inhibiting 50% of the specific binding of (3H) quinuclidinyl benzilate on rat brain preparation of muscarinic receptors. That the interaction with muscarinic receptors is quite unique has been demonstrated by the lack of interaction with three other neurotransmitter receptors. Tertiary amines show relatively less blockade of muscarinic receptors, while substituted ammonium ions are better inhibitors of the QNB binding. The possible mechanisms of in vivo action of these alkaloids is discussed.

Alkaloids↗

Phase II study of daunorubicin in previously untreated patients with advanced colorectal carcinoma.

Fourteen patients with advanced measurable colorectal cancer were treated with daunorubicin hydrochloride (DNR). The drug was administered at a dose of 15 mg/m2 on day 1 through 3 and 8 through 10. After a 4-day rest period DNR was given in weekly injections of 15 mg/m2. There were no partial or complete responses. This study failed to confirm the previously reported therapeutic activity of this agent in colorectal carcinoma, using an identical dose and schedule. We have initiated a phase 1 study of daunorubicin to identify a maximum tolerated dose using an every 3-week schedule for future phase II trials in solid tumors.

Adenocarcinoma↗

The thermomechanical properties of gutta-percha. Part V. Volume changes in bulk gutta-percha as a function of temperature and its relationship to molecular phase transformation.

A variety of gutta-percha materials was subjected to dilatometric analysis to measure volume changes which take place with heating and cooling. The volume changes were found to be related directly to the molecular transformation kinetics of the polymer material and to the temperature ranges within which they take place. If the gutta-percha in the apical segment is not elevated above 45 degrees C, molecular transformation is avoided and the ultimate volume changes which accompany temperature cycling are small, predictable, and controllable.

Chemical Phenomena↗

Drug-induced antibodies during 2-N-methyl-9-hydroxyellipticinium acetate (NSC-264137) treatment: schedule dependency and relationship to hemolysis.

Drug-dependent antibodies were investigated in patients treated with elliptinium acetate, a cytostatic drug with activity in advanced breast cancer. Retrospective analysis of 83 patients, receiving weekly intravenous elliptinium, showed a high incidence of anti-elliptinium antibodies (20%). Hemolysis occurred among antibody-positive patients, apparently related to the antibody titer. The predictability of anti-elliptinium antibodies for hemolysis and the schedule dependency of antibody development was examined prospectively. Among 42 patients treated weekly for at least three courses, 40% developed antibodies. Of 30 patients receiving elliptinium daily for three days every three weeks, none developed either antibodies or hemolysis. Only antibody positive patients, with titers greater than or equal to 32 were at risk for hemolysis. The possible mechanisms are discussed.

Alkaloids↗

Two unusual causes of jaundice with similar ultrasound and CT findings.

The ultrasound and CT patterns of multilocular cystic areas in the liver in two jaundiced patients are presented. In one case the pattern represented a choledochal cyst and in the other an hydatid cyst of the liver. This unusual pattern, although nonspecific, should suggest one of these two diseases.

Adolescent↗

Fine-needle aspiration biopsy of malignant tumours of the abdomen.

Our initial experience of 50 patients who underwent fine-needle aspiration biopsy for suspected abdominal malignant disease confirms the safety and effectiveness of the technique. A positive diagnosis of malignant tumour was made in 36 out of 42 patients who were finally shown to have malignant disease. The correct diagnosis was made on 13 out of 17 patients with a pancreatic tumour; in 17 out of 17 with a liver tumour; in 3 out of 3 with renal masses; and in 3 out of 5 with other malignant lesions. Ultrasound was used for localization of the aspiration site in 38 patients, angiography in 11 patients and direct puncture in 2. During the biopsy of 55 sites, the needle was inserted into the abdomen 190 times and the only significant complication was the development of retroperitoneal haematoma in 2 patients.

Abdominal Neoplasms↗