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Biomedical subjects

T Kitani

Publications and source records attributed to T Kitani.

At least 217 records · Page 12Linked to original sources

[Investigation of the preventive effect of CoQ10 against the side-effects of anthracycline antineoplastic agents].

This study was designed to evaluate the usefulness of Coenzyme Q10 (CoQ10) in the prevention of side effects due to anthracycline agents-Adriamycin (ADM) and Daunorubicin (DNR)-by comparing the preventive effect between CoQ10-treated and non-treated groups. The subjects were 79 patients, 55 of whom had malignant lymphoma. The age range was from 16 to 77 years with a mean age of 45.4 years. CoQ10 was administered by intravenous drip at 1 mg/kg/day the day before ADM or DNR administration, on the day and for a further 2 days after administration. In mean total dose, complete remission rate and mortality, no significant differences were observed between the 2 groups. Although there were also no significant differences in the degree of alopecia, fever, nausea and vomiting, the incidences of diarrhea and stomatitis were significantly (p less than 0.10 and p less than 0.05, respectively) reduced in the CoQ10-treated group. Depression of ST waves (more than 0.05 mV) and changes in T waves (R/10 greater than T, flat, inversion) on ECG were regarded as a parameter of aggravation. Such ECG aggravation was found in 20 of 40 patients given CoQ10 (50.0%) and in 18 of 25 receiving none (72.0%); a cardiotoxicity-inhibiting tendency was thus evident (p less than 0.10). In heart rate, tachycardia was noted in the nontreated group when the period of use of anthracycline agents exceeded 8 weeks. Twenty nine patients received ADM or DNR for 8 weeks or more, and, of them, 17 were treated with CoQ10; 11 of the 17 (64.7%) showed ECG aggravation, while 11 of 12 patients (91.7%) not treated with CoQ10 showed ECG aggravation. A tendency to depress ECG aggravation was thus observed in the treated group (p less than 0.10).

Adolescent↗

Forskolin-induced cyclic AMP production and gastric acid secretion in dispersed rabbit parietal cells: novel evidence for a major role of cyclic AMP in acid release.

Forskolin, a unique diterpine which is a direct activator of cyclic AMP-generating systems, stimulated both cyclic AMP and acid production in dispersed rabbit parietal cells. This agent was also capable of augmenting the action of histamine on both cyclic AMP and acid production at a low concentration. These findings provided novel evidence for a major role of cyclic AMP in gastric acid secretion.

Animals↗

Purification and properties of ornithine decarboxylase from rat liver.

Ornithine decarboxylase was purified to homogeneity, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and polyacrylamide gel electrofocusing, about 710,000-fold with a 35% yield from the liver cytosol of thioacetamide-treated rats. The final specific activity was approximately 24,400 nmol/min/mg of protein. The apparent molecular weight of the enzyme determined by gel filtration analyses on Sephacryl S-200 was 55,000 in the presence of 0.25 M NaCl and 145,000 in its absence. The minimum molecular weight of the enzyme was determined to be 54,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric point of the enzyme was estimated as 5.7 in the presence of 8 M urea. Some catalytic properties of the enzyme were also studied.

Animals↗

A human B lymphocyte antigen (P-76) shared by B-cell chronic lymphocytic leukemia cells and hairy cell leukemia cells.

A membrane antigen with an apparent specificity to B lymphocytes was detected with immunochemical techniques and its properties were analyzed. Anti-B-CLL serum was raised in a rabbit by immunization with B-cell chronic lymphocytic leukemia (B-CLL) cells. This anti-B-CLL serum was absorbed with erythrocytes, liver homogenate and insolubilized immunoglobulins. After further absorption with T-CLL cells, chronic myelocytic leukemia (CML) cells and acute myelocytic leukemia (AML) cells, the anti-B-CLL serum still reacted with peripheral blood B lymphocytes, B-CLL cells and hairy cell leukemia (HCL) cells. In contrast, no reactivity was seen with peripheral blood T lymphocyte or monocytes, or leukemia cells of non-B cell origin. An immunoprecipitation of radiolabeled cell surface proteins was attempted using the anti-B-CLL serum in the presence of Staphylococcus Aureus Cowan 1 (SaCl), and the precipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A membrane antigen with an apparent molecular weight of 76,000 daltons (P-76) was immunoprecipitated with the anti-B-CLL serum from the lysates of normal B lymphocyte, B-CLL cells and HCL cells. The antigen (P-76) is not composed of disulfide-linked subunits and has no structural relationship with HLA-DR (Ia-like) antigens or other known antigens. These results suggest that this antigen is B-lymphocyte specific, and favour the B-lymphocyte nature of HCL cells.

Antibody Specificity↗

Ultrastructural analysis of membrane-bound polysomes in mouse "nonsecretory" myeloma (nonproducing type).

Using our electron microscopic method of polysome analysis we ascertained the numbers of membrane-bound polysomes and their constituent ribosomes in myeloma cells of J 606 (IgG3) and MOPC315 (IgA) parent cell lines and in their variants that did not produce and, accordingly, secrete either H- or L-chains. Both variants had far fewer membrane-bound polysomes than the respective parent lines. The polysome distribution curve drawn for each of these variants showed one peak at 5-6 ribosomes. In contrast to this finding, the distribution curves for the J 606 and MOPC315 parent lines gave two peaks. These observations on mouse myelomas strongly resembled those on human myelomas.

Animals↗

Congenital dyserythropoietic anemia type I: a freeze-fracture and thin section electron microscopic study.

Congenital dyserythropoietic anemia type I was diagnosed in a Japanese patient. Electron microscopic examination of thin sections revealed the features of erythroblasts peculiar to CDA type I; namely "spongy appearance" of nucleus and "internuclear chromatin bridge" etc. However, the widening of nuclear pores, which has been reported as another peculiar feature of CDA type I erythroblasts, were not confirmed. Aberrations of erythroblast nuclear membrane which have not been hitherto noticed were as follows: The nuclear envelopes of erythroblasts frequently lacked heterochromatin application in wide areas where they often showed a marked invagination or evagination. This is associated with the invasion of cytoplasmic organelles into the nuclear territory and occasionally with the extrusion of the nucleolus into the cytoplasm. There were no nuclear pores on the invaginated or the evaginated portions of the nuclear envelope where the perinuclear cistern was compressed to lose the cisternal space, or widened to contain some membrane debris. The findings with thin sectionings were confirmed with freeze-fracturing. Both findings suggest that an aberration may reside in the erythroblast nuclear membrane itself, but not in nuclear pores.

Adult↗

Successful embolization for uterine hemorrhage in a patient with acute promyelocytic leukemia.

A successful embolization for life-threatening uterine hemorrhage is described in a patient with acute promyelocytic leukemia and disseminated intravascular coagulation. On admission the patient was in the 6th week of gestation with incomplete abortion and uterine hemorrhage. In addition to combination chemotherapy and anticoagulant therapy, dilatation and curettage were also performed. After the operation the uterine hemorrhage was progressively increased in amount and was not responsive to usual measures. Embolization of bilateral uterine arteries using Gelfoam was performed with a dramatic improvement of the hemorrhage.

Abortion, Incomplete↗

Ultrastructure of normal human T cell subpopulations. Parallel tubular arrays in T gamma lymphocytes and clustered dense bodies in T mu lymphocytes.

Ultrastructures of normal T-cell subpopulations, T gamma and T mu cells, were studied. T gamma cells were isolated and identified by repeating the rosetting method; firstly, by E rosette formation with neuraminidase-treated sheep red blood cells (SRBC), and next by EA gamma-rosette formation with ox red blood cells coated with IgG antibody (EAox). Before EAox rosetting, SRBC on isolated T cells were lysed by autologous plasma instead of ammonium chloride solution. Normal T gamma cells were heterogeneous with regard to their granules; the majority of T gamma cells had parallel tubular arrays (PTA) and a few had electron-dense granules. When ammonium chloride solution was employed to lyse SRBC, PTA were never observed; PTA in normal T gamma cells and in chronic lymphocytic leukemia cells with T gamma character both seemed to change into electron-dense granules after ammonium chloride treatment. In contrast to T gamma cells, T mu cells were characterized by clustered dense bodies, i.e. focal aggregates of electron-dense granules.

Ammonium Chloride↗

In vitro platelet phagocytosis in idiopathic thrombocytopenic purpura.

In vitro phagocytosis of platelets from patients with idiopathic thrombocytopenic purpura (ITP) (direct assay) and phagocytosis of normal platelets sensitized with patient serum (indirect assay), using normal peripheral blood leukocytes, were studied to find out whether the degree of phagocytosis reflects the severity of ITP. Phagocytosis was measured by the uptake of 51Cr-labeled platelets. Among patients whose platelet count was below 10 X 10(4)/microliters, 92% showed an increase in the phagocytosis ratio by the direct assay and 67% by the indirect assay. There was a highly significant inverse correlation between the direct phagocytosis ratio and the platelet count (p less than 0.001), but not between the indirect phagocytosis ratio and the platelet count. The amount of platelet-associated IgG (PAIgG) measured in patients whose platelets were used for the direct assay also showed an inverse correlation with the platelet count (p less than 0.05). Vincristine administration provoked a reduction in the direct phagocytosis ratio and PAIgG value. We propose that both the direct assay and PAIgG measurement reflect the severity of ITP, and PAIgG might be responsible for platelet phagocytosis.

Adolescent↗

[Therapeutic effect of cefotaxime against severe infections in patients with hematopoietic diseases].

Seventy-five patients with severe infection accompanying hematologic disorder, including leukemia and malignant lymphoma, were treated with cefotaxime (CTX). CTX was administered by intravenous drip infusion at a daily dose ranging from 4 to 16 g for terms of 3 to 21 days. The total doses were ranged from 12 to 226 g. The results obtained were as follows: Clinical effects: Excellent in 20 cases, good in 21 cases, fair in 7 cases and poor in 27 cases. The efficacy rate was 54.7% (41/75). Clinical effectiveness on isolated organisms (27 cases): In single infection (21 cases), the efficacy rates were 80% for Gram-positive cocci, including S. aureus and 63.6% for Gram-negative bacilli other than P. aeruginosa. In mixed infection (6 cases), the rate was 50.0%. There were no significant differences in the efficacy rates for those patients who were grouped by the initial number of neutrophil (less than 100, 101--500 and over 501/mm3). There were no significant difference in the efficacy rates for those patients who were grouped by the initial number of lymphocyte (less than 500 and over 501/mm3). Side effects and abnormal laboratory findings: One case of skin rash and 2 cases of elevated GOT and GPT were observed. CTX was therefore considered as a clinically useful antibiotic for the severe infections even in neutropenic state in patients suffering from malignant hematological diseases.

Adolescent↗

[Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].

A total of 117 cases with hematological malignancies were treated with MCNU at doses of 70-100 mg/m2. Following are the results obtained. 1. MCNU showed a marked depression of cells in the cases with CML, polycythemia vera and thrombocythemia. The low level of cells was maintained for 2 to 7 months. 2. A good response was observed in several cases with blastic crises of CML. 3. No response was observed in two cases with acute leukemia. 4. Although a fair response was observed in several cases with malignant lymphoma or multiple myeloma, moderate bone marrow suppression was observed in a majority of the cases.

Adult↗

[Cooperative studies on clinical effect of cefotetan for severe infections combined with hematologic disorders].

Seventy-six patients with severe infection accompanying hematologic disorders including leukemia and lymphoma were treated with intravenous drip infusion of cefotetan (CTT). Of the 66 cases in whom the efficacy could be evaluated, 22 cases responded markedly and 16 cases moderately, the effective rate being 57.6%. It is impressed that more cases responded markedly to CTT than to any other antibiotics previously studied. None of the cases revealed serious side effects attributable to CTT. These results indicate that CTT is an effective and safe antibiotic for the treatment of severe infection accompanying hematologic disorders. As CTT was administered to special cases under marked decrease of neutrocyte, the importance of neutrocyte in the treatment of infection was also indicated.

Adolescent↗

Hairy cell leukemia: a report of 10 cases in Japan and characterization of anti-hairy cell sera.

A series of 10 cases of hairy cell leukemia (HCL) in native Japanese patients was studied. The clinicopathological features and the phenotype of the leukemic cells were compared with those of HCL in Western countries. The clinical pictures were similar to those in Western countries but some hematological findings were different. The Japanese patients had more marked leukocytosis, less granulocytopenia and thrombocytopenia, and no dry tap on bone marrow aspiration. The phenotype of hairy cells was much the same in both areas. Two kinds of anti-hairy cell sera were raised in rabbits. One (AHS 406) was obtained from rabbits immunized by injecting whole hairy cells. The other (alpha HC-G and alpha HC-M) was obtained by injection of membrane glycoproteins partially purified from hairy cells. The reactivity of the former antiserum (AHS 406) against leukemic cells from a variety of leukemias including HCL and B-cell chronic lymphocytic leukemia was studied by an immunoprecipitation technique. AHS 406 defined three cell surface antigens on HCL, P-30, P-35 and GP-135 (30,000, 35,000 and 135,000 daltons respectively). These three components are expressed only on neoplastic B lymphocytes. Quantitative differences in expression were observed in different types of leukemia, although all three antigens were most strongly expressed in HCL. alpha HC-G showed reactivity similar to that of OKIa-1. alpha HC-M reacted with hairy cells but not with other leukemic cells except mature granulocytes of chronic myelocytic leukemia. It also reacted with most granulocytes and a few mononuclear cells in normal peripheral blood. Preliminary immunochemical studies suggest that alpha HC-M reacts with a glycoprotein with a molecular weight of 26,000.

Adult↗

[Clinical evaluation of high dose intravenous injection of fosfomycin on the severe infections associated with the treatment of haematological disorders].

Fosfomycin (FOM) was administered intravenously to 65 cases of severe infections complicated with 62 cases of several haematological disorders. Out of 65 cases, 45 were treated with high doses FOM, i.e., 8 g per day or more. Another 20 cases were treated in usual doses of 4--6 g per day. Causative organisms were isolated from 52 cases of which 32 cases were Gram-negative bacilli and 19 cases were Gram-positive cocci. The effective rate of FOM was 57.8% in the high-dose treatment group (26/45) and 45.0% in the usual-dose treatment group (9/20), but the significant difference was not defined. Among 32 cases with Gram-negative bacilli infections, including Pseudomonas aeruginosa or Serratia marcescens, 15 cases were effective (47%). On the contrary, 14 out of 19 cases with Gram-positive cocci infections were effective (74%). Thirteen cases (50.0%) were effective even in which neutrophils were less than 500/cmm before FOM administration. Severe side effects were not observed, without 2 cases. One was skin eruption due to drug allergy and the other was suspected to be interstitial pneumonitis, but not confirmed pathologically. These data suggest that high dose treatment of FOM were useful for the severe infections even in neutropenic state in haematological disorders.

Adolescent↗

[Phase I study on oral administration of methyl-6-[[[(2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU)].

A total of 48 patients with various malignant disorders, mostly from hemopoietic organs, entered to phase I study of MCNU given orally. Fifty-six percent of the patients given MCNU at the doses of 50-125 mg/m2 complained of gastrointestinal symptoms including nausea and vomiting, which were however mild and well tolerated. In the following study employing administration of 50 mg/day of MCNU for consecutive 2-6 days, the gastrointestinal toxicities were reduced to 26.1%, and hematological toxicities of delayed leukopenia and thrombocytopenia were derived 4-6 weeks after oral intake of the drug. The hematological recovery required 1-2 weeks after the nadir of leukocyte and thrombocyte count. A recommended dose for phase II study of MCNU by the route of oral administration was 50 mg/body/day for consecutive 4-6 days in every 8 weeks interval. The peak value of blood concentration of MCNU was obtained 60-120 minutes after p.o. administration at the doses of 50-100 mg. Elimination half-life was estimated to be 40-45 minutes. No concentration of the drug was detected in blood 24 hours after the administration.

Administration, Oral↗

Immunoglobulin production and secretion in Bence Jones protein myeloma and "nonsecretory" myeloma. Ultrastructural and immunofluorescence study.

Using our electron microscopic method for polysome analysis and an immunofluorescent technique we studied Ig production and secretion by tumor cells in seven BJP myeloma patients and seven "nonsecretory" myeloma patients. In BJP myeloma Ig production and secretion is of three types: Type 1, only L-chains are synthesized and secreted; Type 2, the myeloma cells show fluorescence for H-chains, but upon polysome analysis there is no peak at polysomes corresponding H-chain production; Type 3, the myeloma cells show fluorescence for H-chains, and polysome analysis shows two peaks corresponding to L- and H-chain production. Polysome analysis of "nonsecretory myelomas show the presence of only very few membrane-bound polysomes and their distribution curves are entirely different from those of "ordinary" myeloma. Furthermore, the distribution patterns vary among seven cases. Results obtained by polysome analysis and immunofluorescent technique suggest that the "nonsecretory" myeloma could be divided into several subtypes.

Bence Jones Protein↗