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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 271 records · Page 15Linked to original sources
PubMed1977

Genetics of colon carcinogenesis in mice treated with 1,2-dimethylhydrazine.

Genetic analysis of colon tumor induction by symmetrical 1,2-dimethylhydrazine (DMH) was undertaken in F1, F2, and reciprocal backcross hybrids derived from a cross between two inbred mouse strains, the 100% susceptible ICR/Ha and completely resistant C57BL/Ha. Mice, 12 to 14 weeks old, received 22 successive weekly s.c. injections of 0.35% aqueous solution of DMH buffered to pH 6.5. A dose of 15 mg/kg/mouse/week produced invasive colon adenocarcinomas in all ICR/Ha males and females (60 of 60) within 22 weeks. None of the 90 C57BL/Ha mice developed DMH tumors during 44 weeks of observation. Susceptibility to the carcinogen was dominant, as indicated by 100% colon tumor incidence in reciprocal ICR/Ha X C57BL/HaF1 hybrids (68 of 68) and in the susceptible backcross ICR/Ha X F1 (42 of 42). Tumor yield in F2 hybrids (94 of 120) was 78%, which is in close agreement with the 3:1 ratio expected if a single dominant DMH susceptibility gene is inherited via the F1 from the ICR/Ha grandparent. Likewise, tumor yield in resistant backcross mice of genotype C57BL/Ha X F1 (46 of 117) is not out of line with the anticipated 1:1 ratio in the latter type of test hybrids. Tests with five isozyme markers and two coat color genes have tentatively ruled out linkage of DMH susceptibility on seven autosomes. The 47% tumor incidence among 57 male resistant backcross hybrids, regardless of whether their single X chromosome was inherited from the ICR/Ha or C57BL/Ha strain, provides evidence against sex linkage.

Animals↗
PubMed1977

The value of liver scan in the follow-up study of patients with adenocarcinoma of the colon and rectum.

Seventy consecutive patients with adenocarcinoma of the colon and rectum had a liver scan followed by surgical exploration of the liver. Preoperatively, blood chemistry studies were done in addition to palpation of the abdomen. Surgical findings were correlated to results of the liver scans, function tests and palpation of the liver. The overall concordance of liver scans with surgical findings was 78 per cent. Thirty per cent had false-positive results and 15 per cent, false-negative results. The correlation of the liver scan with surgical findings was improved with increasing extent of metastases. When less than 25 per cent of the liver was replaced by tumor, there was a random correlation of scan to surgical findings. By combining liver scans and liver function tests, metastases could be predicted with increased reliability only in patients who had severe metastatic disease of the liver. It is strongly recommended that patients with liver scans suggestive of metastatic disease and with most liver function tests within normal limits undergo exploration to establish the diagnosis. Exploratory laparotomy seems to be the only way to avoid chemotherapeutic treatment of patients with false-positive scans and still allow detection and treatment of metastases to the liver to occur at earlier stages.

Adenocarcinoma↗
PubMed1976

Cosolvent-buffer mixtures as models for the cytoplasmic mileu: the enzymology of adenosine aminohydrolase.

Adenosine aminohydrolase from calf intestinal mucosa is sensitive to changes in its environment produced by small mole fractions of dimethylsulfoxide (DMSO). At a mole fraction of 0.1 where the dielectric constant is lowered from that of 78 of neat water to about 76.5, Vmax was reduced by 65% and affinity for substrate (adenosine) and the two competitive inhibitors, insine and N6-benzyladenosine, was decreased markedly. However, this decreased affinity was such that Ki/Km remained virtually constant for both inhibitors. DMSO itself showed the kinetics of a mixed inhibitor with Ki decreasing with increasing mole fraction. This cosolvent also decreased the heat stability of the enzyme which suggests that enzyme conformation is altered by DMSO. Comparison of data in the presence of DMSO with previously obtained data with dioxane shows that heat stability as well as Vmax, at a given value of dielectric constant, is independent of the amount or nature of cosolvent used to achieve that dielectric constant. However, cosolvent induced changes in Ki indicate that colligative as well as dielectric constant effects contribute to the observed changes in kinetic behavior. These experiments may be considered as models for the behavior of enzymes in the medium of lowered dielectric constant expected in the vicinity of cytoplasmic membranes. The results indicate that in such an environment, adenosine aminohydrolase would be expected to be less efficient a catalyst, but equally susceptible to product inhibition, as compared to media of dielectric constant approaching that of water.

Adenosine Deaminase↗
PubMed1976

Splenectomy or radiation and splenectomy for hypersplenism in lymphosarcoma.

This is a retrospective study of 14 patients with lymphosarcoma with hypersplenism. Eight patients received radiation to the spleen followed by splenectomy for recurrence of hypersplenism. Six patients underwent primary splenectomy for hypersplenism. Radiation decreases the size of the spleen but recurrence of hypersplenism is seen in an average of 8 mo. Splenectomy in these cases improves the hematological picture. Average postsplenectomy survival is 27.6 mo. Splenectomy alone in hypersplenism also improves the hematological picture. Postsplenectomy survival in this group is 13 mo. One case of primary lymphosarcoma of the spleen is reported.

Adult↗
PubMed1976

Adenosine-aminohydrolase activity in the erythrocytes, lymphocytes, and plasma of healthy subjects and kidney transplant recipients.

Adenosine-aminohydrolase activity in the red blood cells and lymphocytes of transplant patients were assayed by continuous flow analysis. This enzyme, which has been implicated in the ability of lymphocytes to mount an immune response, was evaluated in renal allografted patients immunosuppressed by azothiprine and methylprednisone. Red cell adenosine-aminohydrolase activity was depressed in all patients when compared to nontreated health controls. Adenosine aminohydrolase activity was raised in the lymphocytes of the renal allografted patients. Renal transplant patients' in vitro lymphocyte reactivity to antigens, mitogens, or skin testing to specific antigens, confirmed the depressive effects of immunosuppression observed in vivo. We conclude from these studies that red cell adenosine-aminohydrolase activity may be a more sensitive index of the state of immunoresponsiveness than the corresponding enzyme activity in the lymphocyte.

Adenosine Deaminase↗
PubMed1976

Splenectomy for palliation of chronic myelocytic leukemia.

Sixty patients with chronic myelocytic leukemia (CML) (most, in the "terminal phase" of the disease) were subjected to splenectomy because of symptomatic splenomegaly, thrombocytopenia or anemia for which they required frequent transfusions. Surgical morbidity and mortality were high when the procedure was performed on a "casual" basis, but both were reduced sharply after care of these patients was restricted to a single medical-surgical-nursing team and improved technics of surgery and perioperative management were developed. Significant hematologic and clinical benefit was achieved in half of the patients and temporary arrest of the disease was often observed, but in most patients, the basic evolution of CML was not greatly altered. In eight patients, however, long-lasting improvement (one to nine years) was recorded. Measurement of the doubling time of circulating leukemic cells and other observations were consistent with the hypothesis that, in some patients, the spleen contains a more rapidly proliferating and "more malignant" population of leukemic cells than the marrow. We conclude that splenectomy is often a useful palliative procedure in advanced stages of CML, and that it may be strikingly beneficial in 10 to 15 per cent of such cases.

Adolescent↗
PubMed1976

Extended therapy of stage D carcinoma of the prostate with oral estramustine phosphate.

We treated 50 patients with stage D carcinoma of the prostate with 15 mg. per kg. per day oral estramustine phosphate for 3 to 24 months. We are able to evaluate 44 patients. Objective remissions were induced in 8 of the 44 patients (19 per cent) and subjective remission occurred in all objective responders and in 7 additional patients for a subjective response of 15 of 44 (36 per cent). No hematologic or renal toxicity was encountered. Transient nausea occurred early in half of the patients and was dose limiting in 3 patients. One case of hepatic toxicity was seen. Oral estramustine phosphate is well tolerated and long-term therapy is feasible.

Administration, Oral↗
PubMed1976

Evaluation of splenectomy in chronic myelogenous leukemia.

Splenectomy was performed in 45 patients with chronic myelogenous leukemia; 23 were in the chronic phase and 22 in the acute phase. Indications for operation included inability to control the disease by chemotherapy or radiation therapy, severe thrombocytopenia, frequent need for blood transfusion and extensive splenomegaly causing discomfort. Median survival time for these patients was better than survival time of other reported groups of patients who did not have a splenectomy. According to our criteria, splenectomy was beneficial to 15 patients in the chronic phase as well as to eight in the acute phase of chronic myelogenous leukemia. Median survival time after splenectomy was higher in patients who had splenectomy within two years of the diagnosis as compared with those who had the operation after two years. Splenectomy did not prevent the future onset of fatal blastic crisis. Although significant abnormalities in coagulation studies were seen in 37 of the patients, intraoperative hemorrhage was not a major problem. Considering the poor general condition, inadequate healing and susceptibility to infection, the postoperative mortality and complication rates were comparable with those reported in series in which splenectomy was performed for other diseases. It seems that splenectomy benefits a selected group of patients with chronic myelogenous leukemia; however, a randomized series would furnish better data upon which to make decisions.

Adult↗
PubMed1975

Ferritin synthesis by splenic tumor tissue of Hodgkin's disease.

Increased ferritin synthesis by Hodgkin's disease splenic tumor tissue was demonstrated by incorporation of 14C-leucine and radioautography. This suggests that elevated tumor and serum ferritin concentrations found in patients with Hodgkin's disease is derived from tumor tissue per se.

Adolescent↗
PubMed1975

Clinical and experimental studies on adenine, various nucleosides and their analogs in hematology.

In red blood cells as well as in platelets there appears to be a decrease in adenine nucleotides during storage under blood bank conditions. This can be decreased by use of anticoagulant preservatives with higher phosphate content than the standard ACD solution, through the addition of adenine and inosine. Maintenance of higher ATP levels appears to be related to longer circulating life span after transfusion into patients in the case of red blood cells but not platelets. Inosine and more alkaline preservative medium also contribute to the maintenance of 2,3-DPG levels in red blood cells, and with it to the maintenance of normal hemoglobin dissociation curves and thus oxygen-carrying capacity. Certain nucleoside analogs may contribute to the preservation of platelets and of whole blood by their platelet-aggregation inhibitory activity. Platelet-aggregation inhibitors may also be useful in preventing thromboembolic episodes with potentially greater safety than anticoagulants.

Adenine↗
PubMed1975

Synthesis properties of the naturally occurring N-[(9-beta-D-ribofuranosylpurin-6-yl)-N-methylcarbamoyl]-L-threonine (mt-6A) and other related synthetic analogs.

The naturally occurring modified nucleoside, N-[(9-beta-D-ribofuranosylpurin-6-yl)-N-methylcarbamoyl]-L-threonine (mt6A), and the corresponding glycine analog mg6A were synthesized from N6-methyl-2',3',5'-tri-O-acetyladenosine and the appropriately blocked isocyanates derived from threonine and glycine. The natural mt6A isolated from Escherichia coli tRNA (F. Kimura-Harada et al. (1972), Biochemistry 11, 3910), from wheat embryo tRNA (R. Cunningham and M. W. Gray (1974), Biochemistry 13, 543), and from rat liver tRNA (Rogg et al. (1975), Eur. J. Biochem. 53, 115) was found to be identical with the synthetic mt6A in paper and thin-layer chromatography and electrophoresis. Several analogs of the parent 6-ureidopurine ribonucleoside, N-[(9-beta-D-ribofuranosylpurin-6-yl)carbamoyl]-L-thronine (t6A), were also prepared. Starting from 2',3',5'-tri-O-acetylguanosine and 2',3',5'-tri-O-acetylcytidine and the above isocyanates, the t6A analogs, N-[(9-beta-D-ribofuranosyl-6-oxo-1H-purin-2-yl)carbamoyl]-L-threonine (t2G) and N-[(1-beta-D-ribofuranosyl-2-oxypyrimidin-4-yl)carbamoyl]-L-threonine (t4C), were prepared. Also synthesized were the corresponding glycine analogs, g2G and g4C, from guanosine and cytidine, respectively. The 2'-deoxyribosyl analog, N-[(9-beta-D-2'-deoxyribofuranosylpurin-6-yl)carbamoyl]-L-threonine (2'-deoxy-t6A), and the arabinosyl derivative, N-[(9-beta-D-arabinofuranosylpurin-6-yl)carbamoyl]-L-threonine (t6AraA), were synthesized from the appropriate urethane and the requisite amino acid. The ureido group in mt6A could not be hydrolyzed by the enzymes urease, peptidase, and protease. Various chemical and biological properties of the naturally occurring mt6A and the related analogs are discussed.

Chromatography, Paper↗
PubMed1975

Splenectomy for hematologic depression in lymphocytic lymphoma and leukemia.

Fifty patients with lymphocytic lymphoma and chronic lymphocytic leukemia underwent splenectomy for various combinations of anemia, thrombocytopenia, and leukopenia. All of these patients had advanced lymphoproliferative disease, and most had infiltration of bone marrow by neoplastic cells. Good response in all hematologic parameters was obtained in 27 of 48 evaluable patients. An additional 13 patients responded in one or two parameters; there were only 8 complete failures. The over-all surgical mortality was 8%. The median duration of response was 4 months, and the mean, 7 months. Increased tolerance to further antitumor therapy and a decreased transfusion requirement were seen among responding patients. Those patients with anemia who had evidence of shortened erythrocyte survival and splenic sequestration of 51Cr-labelled erythrocytes uniformly responded with rises in hemoglobin. However, half of the patients with negative splenic sequestration also showed improvement of anemia. Preoperative diagnostic studies failed to predict favorable responses of patients with thrombocytopenia or leukopenia. The classical criteria for the diagnosis of hypersplenism are not applicable in many cases of neoplastic lymphoproliferative disease; splenectomy could have been considered "contraindicated" in most of the patients in this series. We conclude that splenectomy is worth undertaking in patients with lymphoproliferative disease complicated by hematologic depression regardless of marrow findings or the results of other diagnostic studies.

Adult↗