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Biomedical subjects

J Laszlo

Publications and source records attributed to J Laszlo.

At least 91 records · Page 5Linked to original sources
PubMed1979

Treatment of metastatic endocrine-unresponsive carcinoma of the prostate gland with multiagent chemotherapy: indicators of response to therapy.

Eighty-eight patients with metastatic and hormonally unresponsive carcinoma of the prostate gland were treated with a multiagent chemotherapy protocol. Because of the difficulty in evaluating the response of patients to therapy, data were collected in a prospective fashion and analyzed for clinical or laboratory changes that correlated with improved survivorship. Decrease of initially abnormal values of either acid or alkaline phosphotase into the normal range was associated with prolonged survival; weight gain of more than 10% was also associated with improved survival. Thirty-three patients demonstrated a fall of acid or alkaline phosphatase into the normal range or they increased their weight by at least 10%. The median survival time for this group of patients was 76.1 weeks as compared to 28.2 weeks for patients who failed to exhibit these changes. In future studies of the treatment of metastatic prostate cancer, these changes might be used as criteria of response to therapy.

Acid Phosphatase↗
PubMed1979

New dose-time relationships of folate antagonists to sustain inhibition of human lymphoblasts and leukemic cells in vitro.

In this study, three methods are utilized to analyze toxicity produced by methotrexate and the lipid-soluble antifolate, 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine, in human lymphoblasts (WIL-2) and leukemic cells. These methods detect increasingly severe metabolic damage; inhibition of deoxyuridine incorporation into DNA, the reversibility of inhibition of deoxyuridine incorporation by supplementation with formyltetrahydrofolate as Ca2+ leucovorin, and the ability of cells to form clones in soft agarose. The critical dose and exposure time for establishing and maintaining the metabolic toxicity of methotrexate is examined in detail. It is shown that, if an initial loading dose of methotrexate is of high enough concentration or is maintained for a sufficient period to achieve greater than 98% inhibition of deoxyuridine incorporation, this inhibition can be sustained by low concentrations of 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine or methotrexate. Concentrations of methotrexate or 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine that equal or exceed 0.1 microM are sufficient for maintenance of inhibition by an initial loading dose of methotrexate but escape from inhibition that occurs if lower levels of drug are used. The possible implications of these observations for in vivo protocols are discussed.

Cell Line↗
PubMed1979

Facilitated light microscopic cytochemical diagnosis of acute myelogenous leukemia.

Hydroperoxidase-positive Phi bodies and rods are much more prominent and prevalent than rods visualized with a Romanovsky-type stain (Auer rods) in immature leukocytes of patients with active acute myelogenous leukemia (AML). They are readily observed with the light microscope in peripheral blood or marrow films of AML patients stained to show their peroxidatic activity. In many of these patients, Auer rods, which apparently constitute only a small subpopulation of the hydroperoxidase-positive Phi bodies and rods, were detected with difficulty, if at all. The hydroperoxidase-positive Phi bodies and rods were observed in 92% of 36 patients with active disease. They were never observed in leukocytes of patients with other hematopoietic disorders or of normal individuals. Thus, they facilitated the distinction of AML from acute lymphocytic leukemia and chronic granulocytic leukemia in blast crisis. They were absent in full clinical remission after chemotherapy and were greatly diminished in partial remission. They were present in disease relapse and reappeared in five patients who had been in full remission. These results suggest that these hydroperoxidase-positive enlarged particles are pathognomonic of AML and that monitoring them with the light microscope may aid in guiding its clinical management.

Adolescent↗
PubMed1978

The light microscopic demonstration of hydroperoxidase-positive Phi bodies and rods in leukocytes in acute myeloid leukemia.

Unique fusiform or spindle-shaped particles (Phi bodies) and rods with hydroperoxidase (catalase and/or peroxidase) activity are present in human granulocyte precursors only in acute myelogenous leukemia (AML). These newly recognized particles are much more numerous and prominent than Auer rods. They may be rapidly and readily identified using the microscope in marrow or peripheral blood films when the procedures recommended in this paper for fixation, incubation for hydroperoxidase demonstration in 3,3'-diaminobenzidine (DAB)/H2O2 medium, copper salt treatment and counterstaining (optional) with the Papanicolaou method are employed. Films prepared in the same manner but treated with benzidine/H2O2 medium for myeloperoxidase did not reveal these particles. We believe that Phi bodies are pathognomonic of AML since they are almost invariably present in AML patients with active disease. Their presence serves to distinguish AML from acute lymphocytic leukemia and from chronic granulocytic leukemia in blast crisis. Since the particles disappear in disease remission and reappear upon relapse, the recommended procedure is not only useful in diagnosis but in guiding therapy. When a very rapid diagnosis is needed, it is not necessary to counterstain the preparations, but the nuclei, cytoplasm and plasmalemma can readily be observed in the granulocyte precursors when they are counterstained by the Papanicolaou method. This treatment does not diminish the clarity of the Phi bodies and rods which stain by virtue of their peroxidatic activity. This cytochemical diagnostic procedure should be considered for adoption by hematology laboratories.

Bone Marrow↗
PubMed1978

Activation of an inhibitory noradrenergic pathway projecting from the locus coeruleus to the cingulate cortex of the rat.

Repetitive stimulation of the locus coeruleus evoked strong inhibition of the firing rate of about 50% of cells of the cingulate rat cortex. Forty per cent of the cells were not affected and 9% were excited by stimulation of the locus coeruleus. Pretreatment of the rats with reserpine and alpha-methyl-p-tyrosine drastically reduced the percentage of cells inhibited by locus coeruleus stimulation. The cells inhibited in response to stimulation of the locus coeruleus as well as those not inhibited were depressed by microiontophoretically applied norepinephrine. This inhibitory action of NE was observed in rats anesthetized either with urethane, chloral hydrate or with Nembutal. The transsynaptically elicited, as well as the norepinephrine elicited, depression of the cells' discharge rate was antagonized by the microiontophoretically applied beta-receptor blocking drug MJ 1999. These data suggest that the inhibitory action on cingulate cortical cells of locus coeruleus stimulation is mediated by the dorsal ascending noradrenergic pathway.

Adrenergic Fibers↗
PubMed1978

Treatment of chronic granulocytic leukemia with melphalan.

Thirty-three patients with newly diagnosed chronic granulocytic leukemia (CGL) were treated with melphalan between 1968 and 1976. Within 3 mo of beginning therapy subjective and objective disease parameters improved. Disease control was easily maintained with this agent until hematologic exacerbation occurred. The median duration of disease control was 25.3 mo, and the median duration of survival was 28.6 mo. Serious side effects were not produced. Thus melphalan appears to be another agent that may be used to control the manifestations of CGL prior to hematologic exacerbation.

Adolescent↗
PubMed1978

Comparison of metoprine (DDMP) and etoprine (DDEP) by measuring the inhibition of deoxyuridine incorporation into the DNA of human leukemic cells 1,2,3.

In vitro studies were used to measure the incorporation of labeled deoxyuridine into the DNA of human leukemic cells in autologous plasma in order to compare the inhibitory effects of two diaminopyrimidines, metoprine and etoprine. The results indicate that these two lipid-soluble folate antagonists give similar qualitative and quantitative effects over a concentration range of from 1 to 100 micrometer. However, drug-induced inhibition of deoxyuridine incorporation into DNA was quite variable for cells obtained from different adult patients, even within a given morphologic type of leukemia. Despite these biologic varitions in leukemic sensitivity in vitro, both drugs gave virtually identical results on an equimolar basis.

Antineoplastic Agents↗
PubMed1978

Splenectomy for Felty's syndrome. Clinicopathological study of 27 patients.

The major clinical and pathological features and the long-term follow-up of 27 patients with Felty's syndrome who were treated with splenectomy for sever granulocytpenia and for acute, chronic, or recurrent infection were studied. Granulocyte counts rose within days in most patients, although slow responses and transient granulocytopenia did occur; only 12% of the patients had persistent or recurrent granulocytopenia. Infections resolved promptly in 77% of the patients, more slowly in the remainder, and only one patient had new problems of infection after aplenectomy. Splenic enlargement, present in all but one case, was attributable to expansion of the sinusoidal pulp. The most substantial pathological features of immune stimulation included germinal center hyperplasia and prominent clusters of plasma and preplasma cells within sinuses.

Adult↗
PubMed1976

Effects of nitrosoureas on human DNA polymerase activities from acute and chronic granulocytic leukemia cells.

In vitro DNA synthesis by isolated cytoplasmic DNA polymerases of human leukemic cells was found to be inhibited by 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methyl-cyclohexyl)-1-nitrosourea. 2-Chloroethyl isocyanate and cyclohexyl isocyanate, the decomposition products of 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, respectively, are as effective as their parent nitrosoureas in inhibiting the enzyme activity. Preincubation studies indicated that these compounds inhibit DNA synthesis primarily by altering the enzyme DNA polymerases without significantly affecting the DNA template activities.

Acute Disease↗
PubMed1976

Induction of DNA polymerase alpha during liver regeneration in rats on controlled feeding schedules.

The activity of 2 nonmitochondrial forms of DNA polymerase, designated DNA polymerases alpha and beta, was investigated during liver regeneration in regimented rats. In accord with Barbiroli and Potter, we observed that regimentation of rats with respect to temperature, light and darkness, and availability of food resolves the DNA synthesis response to partial hepatectomy into 2 peaks, one occurring at a fixed time after operation and the other entrained by the environmental conditions. The peaks can be fused or separated depending on the timing of the operation. For this study, operation times were selected to give both patterns of DNA synthesis as measured by the uptake of radioactive thymidine into DNA. For both operation times, DNA polymerase activity in the nuclear extract correlated temporally and qualitatively with radioactive thymidine uptake into DNA. At the times of maximal DNA synthesis and polymerase activity, the DNA polymerase was purified from extracts of isolated nuclei. DNA polymerase alpha represented 70% and DNA polymerase beta represented 30% of the recovered activity from the nuclear extract. This is in agreement with the previous observation in nonregimented rats that DNA polymerase alpha is the major activity in nuclei during liver regeneration. For both operation times, DNA polymerase activity in the postmicrosomal fraction was sedimentable and increased 3 to 4 times above the level observed with this same fraction from normal rat liver. This activity was shown to be due to DNA polymerase alpha only with this subcellular fraction. DNA polymerase alpha activity with this fraction peaked 4 to 6 hr after the time of maximal radioactive thymidine incorporation into DNA. DNA polymerase activity in the microsome fraction did not change significantly after partial hepatectomy. This activity has been shown to represent DNA polymerase beta. Prior administration of cycloheximide and actinomycin abolished the rise in DNA polymerase alpha activity in the nucleus and postmicrosomal fraction. Hydroxyurea did not prevent the rise in DNA polymerase alpha activity with those subcellular fractions but did inhibit over 90% of the uptake of radioactive thymidine into DNA. These data suggest, but do not prove, that DNA polymerase alpha activity is induced in response to the stimulus(i) for liver regeneration.

Animals↗