Search PubMed⌕ Search

Biomedical subjects

M Freund

Publications and source records attributed to M Freund.

At least 289 records · Page 16Linked to original sources
PubMed1986

Homogeneously staining chromosomal region in a case of erythroleukaemia.

Cytogenetical analysis of bone marrow and peripheral blood cells in a case of erythroleukaemia revealed a complex karyotype with a stemline of 44 chromosomes. 1 marker chromosome bearing a homogeneously staining region (hsr) was found in each of the aneuploid cells examined. The hsr was localised to the chromosome regions 15q12 and 15p12. The possible function of amplified DNA sequences and the relationship of hsr to cell proliferation are discussed.

Aged↗
PubMed1986

Age adapted induction and intensified consolidation therapy in acute myelogenous leukemia.

52 patients entered a study for remission induction and intensified consolidation in AML. Group I (age less than or equal to 50 years) received a combination of DNR, ara-C and VP16-213 for induction and early consolidation and HDara-C/DNR for late consolidation. Of 34 evaluable patients (25 first diagnosis, 9 first relapse), 27 achieved CR. 13 patients received 1-2 courses of HDara-C/DNR. Toxic symptoms of HDara-C/DNR were severe myelosuppression, infections, skin reactions, diarrhea and hepatotoxicity. CNS toxicity was not observed. 2 patients died from infection. The duration of granulocytopenia (less than 500/microliter) was 7-43 days (range) and of thrombocytopenia (less than 25,000/microliter) 5-34 days (range). Patients of group II (age greater than 50 years) received a modified regimen with reduced toxicity. Their number is too small for evaluation as yet.

Aclarubicin↗
PubMed1986

Combination therapy with mitoxantrone and etoposide in refractory acute myelogenous leukemia.

We have investigated the efficacy of mitoxantrone in combination with etoposide in patients with refractory acute myelogenous leukemia. The regimen consisted of 10 mg/m2/day of mitoxantrone given iv on Days 1-5; and 100 mg/m2/day of etoposide as short infusion, initially on Days 1-3 and extended to Days 4 and 5 as appropriate. Of the 26 patients treated with this combination, nine (34.6%) have achieved complete remission and two have achieved partial remission. The median duration of continuous complete remission was 85 days (range, 21-183+). Toxicity was mild and only one case of early death was observed. This combination seems to be an active regimen in refractory acute myelogenous leukemia, and its incorporation in front-line therapy seems warranted.

Adult↗
PubMed1986

Ultrasound assessment of ductal closure, pulmonary blood flow velocity, and systolic pulmonary arterial pressure in healthy neonates.

Ultrasound Doppler was used to establish time of ductal closure, normal values for blood flow velocity in the pulmonary artery (PA), and time interval between pulmonary valve closure (Pc) and tricuspid valve opening (To) in 37 healthy neonates. Ductal closure had occurred in 23% of the children within 12 h after delivery and in 53% during the next 12 h. No open ductus was found after 30 h of age. Maximal blood flow velocity was 0.90 +/- 0.09 (SD) m/s during the first five days of life and 1.12 +/- 0.17 m/s at the age of 14-30 days. The Pc-To interval is known to reflect systolic PA pressure in adults. The Pc-To interval decreased significantly (p less than 0.01) from an average of 0.059 +/- 0.016 s at 3.5-12 h of age to 0.048 +/- 0.011 at 19-36 h of age and thereafter successively to 0.027 +/- 0.004 s at 20-30 days of age. This value is only slightly higher than that of 0.015-0.020 s for normal adults at comparable heart rates. These data suggest a rather sharp decline of systolic PA pressure during the first day of life and thereafter a slower decline; normal adult values are approached but not reached at 3-4 weeks of age. The Pc-To value seems to be of limited value in the early neonatal period, because even normal neonates have increased values with a large individual variation. After 3-4 weeks of age, an increased value should be taken as an indication of increased systolic PA pressure.

Blood Flow Velocity↗
PubMed1985

Treatment of acute myelocytic leukemia with a daunorubicin-cytarabine-6 thioguanine regimen without maintenance therapy.

The present study reports on the treatment of 44 patients with AML. 17 patients were male, 27 female. Mean age was 50.1 years. Treatment-regimen consisted of induction-therapy with daunorubicin 45 mg/m2 i.v. d 1-3, cytarabine 100 mg/m2 X 24 h continuous intravenous infusion (c.i.v.i.) d 1-7, 6 thioguanine 100 mg/m2 twice orally d 1-7. There were only two consolidation therapies with daunorubicin and cytarabine and no maintenance therapy. 30 patients (68%) achieved CR, 1 patient (2%) PR, 3 were non-responders (7%). There were 10 (23%) early deaths during or following induction therapy. Median disease-free survival was 6 months, median overall survival 7.5 months. We conclude, that the reported induction therapy is efficient though toxic. To improve long term results, consolidation and intensification therapy should be escalated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

The mechanism of action of lymphokines. VIII. Lymphokine-enhanced spontaneous hydrogen peroxide production by macrophages.

Oil-elicited guinea-pig peritoneal macrophages (MPs) cultured for 2-3 days in medium containing supernatant of concanavalin A-activated lymphocytes (lymphokine, LK) generated large amounts of hydrogen peroxide (H2O2), as detected by the horseradish peroxidase (HRP)-dependent oxidation of phenol red, in the absence of further stimulation. H2O2 production increased with the duration of exposure to LK and was evident at high dilutions of supernatant (1/64). Parallel cultures of MPs in medium or a supernatant of non-activated lymphocytes also increased their H2O2 production during culture but levels at all time intervals were significantly lower than those measured in LK treated cultures. The marked increase in H2O2 production was associated with only a moderate increment in superoxide (O-2) liberation and this was not specific for LK treated cells. Detection of LK-dependent H2O2 production was dependent on ongoing pinocytosis during the assay. This and other arguments suggest that the HRP-phenol red assay, as applied here, detects H2O2 generation occurring at the level of intracellular vesicles and it is concluded that LK elicits H2O2 production that is limited to the intracellular compartment. H2O2 is, apparently, derived by non-enzymatic dismutation of O-2 taking place within the cell; LK treatment of MPs also resulted in a significant reduction in catalase activity.

Animals↗
PubMed1984

Expression of an X-linked muscular dystrophy in a female due to translocation involving Xp21 and non-random inactivation of the normal X chromosome.

A young female was diagnosed as having X-linked muscular dystrophy of the Duchenne type. Chromosome studies, including trypsin-Giemsa banding, Quinacrine fluorescence, and nucleolus organizer region (NOR) silver staining revealed an X-autosome reciprocal translocation t(X;21) (p21;p12). Utilizing both [3H] thymidine autoradiography and the BrdU-Hoechst 33258-Giemsa technique, lymphocytes and fibroblasts were found to show a preferential inactivation of the normal X suggesting the presence of a single mutant gene on the translocated X. This patient is one of seven reported cases of an X-linked muscular dystrophy associated with an X-autosome translocation. In all seven cases the exchange point in the X chromosome is in band p21 at or near the site of the Duchenne gene.

Adult↗
PubMed1983

CNS manifestations in non-Hodgkin lymphomas (NHL).

In a group of 241 patients with non-Hodgkin lymphoma investigated retrospectively, CNS manifestations occurred in 8%, mainly as meningeosis lymphoblastomatosa. Lymphoblastic and immunoblastic NHL showed the highest risk of CNS infiltration (40.7% and 12.5% respectively). Further risk factors were disseminated stage of the disease, prior involvement of the bone marrow and juvenile age. Characteristic symptoms were eye muscle paresis, paresthesias and pareses of peripheral muscles. The most fruitful diagnostic measure was lumbar puncture. More than 80% of the patients observed with CNS manifestations died within one year. The factor limiting life was less the CNS infiltration itself than the systemic progression. CNS prophylaxis should be incorporated in the treatment plan in patients with lymphoblastic and immunoblastic non-Hodgkin lymphoma at an early stage. In contrast CNS prophylaxis is not justified in uncontrollable systemic non-Hodgkin lymphoma spread.

Adult↗
PubMed1983

Oral ISDN for the treatment of patients with acute myocardial infarction.

In a controlled randomized trial the effect of treatment with 60 mg orally administered ISDN in patients with acute myocardial infarction was studied. Besides the usual clinical investigations, hemodynamics were checked; pulmonary artery pressure and cardiac output during the first 4 days were measured. 509 patients were included in the trial. Based on other researchers' considerations about limitation of infarct size we formed a subgroup of 132 patients to be treated within 8 h after onset of symptoms. The mortality for the entire ISDN-group was not influenced compared with that for the control group. If treatment with ISDN was started within the first 8 h after onset of symptoms of acute myocardial infarction, mortality in this group was significantly lower than that in the control group. In the group of patients receiving treatment within the first 8 h we found positive effects: a fall of pulmonary artery pressure with consecutive rise of cardiac output, mainly in patients showing high left ventricular end-diastolic filling pressures. In the treated group we found a significant decrease in arrhythmias and angina pectoris. When left ventricular hemodynamics were tested before discharge from the hospital patients treated with ISDN during the first 8 h again showed favorable results. We conclude that treatment with ISDN in the early phase of acute myocardial infarction is beneficial particularly for patients with high left ventricular filling pressures.

Administration, Oral↗
PubMed1982

Considerations in selecting a postvasectomy semen examination regimen.

The criteria for declaring a vasectomized man sterile have been the subject of debate for many years, yet most suggested regimens differ. The problem lies in the remaining unanswered physiologic questions of such a fundamental nature as to frustrate attempts to formulate a regimen based strictly on medical considerations. The rates of disappearance of sperm following vasectomy vary considerably among men. The physiologic basis for these variations are herein discussed for the first time. At present, regimens reflect, for the most part, social considerations, according to the values and perceptions of the individual physician. The problems raised by postvasectomy residual sperm and current formulation of regimens are described.

Ejaculation↗
PubMed1981

Restriction and modification in Bacillus subtilis: two DNA methyltransferases with BsuRI specificity. I. Purification and physical properties.

Two S-adenosyl-L-methionine:DNA (cytosine 5)-methyltransferases, termed M.BsuRIa and M.BsuRIb, were purified 3,000- and 4,000-fold, respectively, from Bacillus subtilis strain OG3R (r+m+) by successive column chromatography. The molecular weights determined by gel filtration were 37,000 for M.BsuRIa and 40,000 for M.BsuRIb. The sedimentation coefficients s20,w were 3.55 for both enzymes as determined by glycerol gradient centrifugation, corresponding to molecular weights of 43,000. Analysis of the two methyltransferases by agarose gel electrophoresis under native conditions, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, showed correspondence of the M.BsuRIa activity with one protein band at a molecular weight of 41,000, whereas M.BsuRIb activity was associated with two protein bands with molecular weights of 42,000 and 39,000, respectively.

Bacillus subtilis↗
PubMed1981

Restriction and modification in Bacillus subtilis: two DNA methyltransferases with BsuRI specificity. II. Catalytic properties, substrate specificity, and mode of action.

The properties of two DNA methyltransferases, termed M. BsuRIa and M. BsuRIb, whose isolation was described in the preceding paper (Günthert, U., Freund, M., and Trautner, T. A. (1981) J. Biol. Chem. 256, 9340-9345) were compared. Both enzymes recognize the same target sequence in double-stranded DNA, leading to methylation of the internal cytosine: 5'GGCC. The enzymes have identical reaction constants with their substrates, DNA (km = 2.7 nM for the 5' GGCC sequence), and S-adenosyl-L-methionine (km = 0.7 microM). Initial rates of methyl group transfer were proportional to enzyme concentration over a range of 50-fold, indicating absence of aggregation. The enzymes are different in their ionic strength requirements using Tris-HCl, pH 8.4. M. BsuRIa is most active at 100 mM, M. BsuRIb at 440 mM. As measured by incorporation kinetics and heat inactivation, M. BsuRIa is the more stable enzyme of the two. Equilibrium dialysis was used to study the mode of methyl group transfer to the DNA with either enzyme. The data indicate that initially S-adenosyl-L-methionine binds to methyltransferase. This complex attaches to either modified or nonmodified DNA. The methyl group will then be transferred to a nonmodified target sequence, leading to the dissociation of enzyme and S-adenosyl-L-homocysteine from the DNA.

Bacillus subtilis↗