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T Kitani

Publications and source records attributed to T Kitani.

At least 145 records · Page 8Linked to original sources

Amylase-producing plasmacytoma cell lines, AD3 and FR4, with der(14)t(8;14) and dic(8)t(1;8) established from ascites.

We established two human plasma cell lines, FR4 and AD3, from ascitic fluid in a patient with IgA k plasmacytoma (PC). Aberrant amylase production was found in this patient. Both AD3 and FR4 were free of Epstein-Barr virus, and both produced Ig A k in vitro. They produced amylase of the salivary type in vitro. This was confirmed by the demonstration of amylase mRNA comigrating with salivary gland mRNA. These cell lines commonly had unusual chromosomal abnormalities der(14)t(8;14) and dic(8)t(1;8). AD3 had additional chromosomal abnormalities compared with FR4. This suggests that AD3 is a subline of FR4. The oncogene c-myc is rearranged in most case of Burkitt's lymphoma with t(8;14). However, neither rearrangement nor amplification of the c-myc allele was detected in our PC lines. These lines expressed c-myc of 2.4 kb. There were no structural changes in the amylase genes of AD3 and FR4 detectable with Southern blotting analysis. As these lines were authentic PC lines, they would be useful for the future study of the relationship between the mechanism of oncogenesis and the rare tumor aberration, amylase production.

Aged↗

Expression of decay-accelerating factor on hematopoietic progenitors and their progeny cells grown in cultures with fractionated bone marrow cells from normal individuals and patients with paroxysmal nocturnal hemoglobinuria.

Decay-accelerating factor (DAF), a complement-regulating glycoprotein, has been shown to be expressed on hematopoietic progenitors and their progeny cells in normal individuals but not on abnormal cells in patients with paroxysmal nocturnal hemoglobinuria (PNH). Fluorescence histograms of bone marrow cells showed the heterogeneity of DAF expression on their cell membranes, suggesting mixed hematopoietic cell populations in PNH. We have previously shown that DAF is a maturational protein expressed on normal hematopoietic cells. In order to elucidate the relationship between DAF expression and cell maturity in PNH, we fractionated bone marrow cells according to amount of DAF and cultured these cells in methylcellulose for clonal assay of erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM), followed by reanalysis of DAF expression on their progeny. The matured cells from the bursts/colonies in cultures with DAF-negative PNH marrow cells had no or little DAF, but those grown from DAF-positive PNH progenitors showed nearly as much of this factor as those grown from normal progenitors. These results clearly indicate that there are at least two distinct populations of hematopoietic progenitors with respect to the membrane expression of DAF and that abnormalities occur at the level of the stem cell in PNH.

Bone Marrow↗

Molecular analysis of T cell receptor and CD3 genes in CD3- large granular lymphocytes (LGLs): evidence for the existence of CD3- LGLs committed to the T cell lineage.

Seven patients with CD3- lymphoproliferative disorder of granular lymphocytes (LDGL) were analyzed for rearrangement of the T cell receptor (TCR) delta and alpha as well as gamma and beta genes. Among those patients six showed the germline configuration of all known rearranging TCR genes. Two analyzed patients of them lacked CD3-gamma transcripts and expressed nonfunctional TCR-beta transcripts. Meanwhile, TCR-delta gene rearrangement accompanied by expression of full-length TCR-delta transcripts was observed in one patient with CD3- LDGL. In addition, the cells from this patient transcribed the CD3-gamma gene which is one of the earliest events restricted to cells committed to the T cell lineage. These findings indicate that CD3- LGLs include not only cells belonging to the NK cell lineage but also precursor cells committed to the T cell lineage.

Antigens, Differentiation, T-Lymphocyte↗

Randomized trial of combination antibiotic therapy in patients with hematological disorders. Hanshin Study Group of Hematopoietic Disorders and Infection.

A 3 arm prospective randomized trial was designed to compare the effectiveness of aztreonam (AZT) + clindamycin (CLDM), amikacin (AMK) + AZT and CLDM + AMK as antibiotic therapy for fever in patients with hematological disorders. Between July 1987 and June 1988, one hundred and sixty of the 199 febrile episodes entered in this study were evaluated for response. Underlying diseases were hematological malignancies in 88.8% of the subjects, and there was no statistically significant differences in incidences of the diseases among the 3 groups. Efficacy rates were 64.2% in the AZT + CLDM group, 52.8% in the AMK + AZT group and 35.2% in the CLDM + AMK group. Efficacy rates in those with neutrophil counts was less than 500/microliters before starting the antibiotics were 53.3%, 43.8% and 25.0%, respectively, in the 3 groups. The combination of AZT + CLDM was found to be the most effective even in the treatment of infections associated with febrile neutropenic patients.

Adolescent↗

Association of protein tyrosine phosphorylation with B cell differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA).

We have assessed whether tyrosine protein kinase (TPK) is involved in B cell differentiation. In vitro phosphorylation of an endogenous substrate in B cell leukemias showed that leukemic B cells at different stages of differentiation had specific endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. To clarify the relationship between TPK and the process of B cell differentiation, we studied protein tyrosine phosphorylation in two kinds of leukemic B cells, which showed distinct responses to TPA (12-O-tetradecanoylphorbol-13-acetate) in B cell differentiation. TPA-treated leukemic B cells from patients with B cell chronic lymphocytic leukemia (B-CLL) differentiated into cytoplasmic immunoglobulin (clg)+ plasmacytoid cells, while TPA-treated leukemic B cells from patients with hairy cell leukemia (HCL) did not differentiate into clg+ cells, but showed a peculiar morphological change, spreading. Untreated B-CLL cells and HCL cells showed similar TPK activities and tyrosine protein phosphorylation. When treated with TPA, enhanced phosphorylation was seen in B-CLL cells, while a clear reduction in phosphorylation was found in HCL cells. However, using 4-hydroxycinnamide derivatives which reduce TPK activity, we found that only the reduction of TPK activity did not lead HCL cells to spreading. These data suggest that protein tyrosine phosphorylation and/or dephosphorylation might be involved in B cell differentiation, but only the change of TPK activity in HCL cells is not sufficient to induce effects.

B-Lymphocytes↗

[A multicenter clinical study of oral topical administration of G-512 on chemotherapy-associated intraoral mucosal lesions of patients with hematological malignancies. G-512 Therapeutic Study Group for Intraoral Mucosal Lesions].

We evaluated the usefulness of PGE2 on chemotherapy-associated oral mucosal lesions of the patients with hematological malignancies and compared the efficacy of the troche with that of the tablet. One hundred and fifty three patients were given 0.5 mg of these PGE2 topically three times daily. One hundred and fourty five cases were evaluable (Tablet; 85, Troche; 60). 1) Symptoms and signs were improved in 102/144 (70.8%) and 102/145 (70.3%), respectively. The overall response rate was 70.3%. 2) The improvement rates were 77.5% (55/71), 85.7% (6/7) and 62.7% (32/51) in leukocyte count-increased, -unchanged and -decreased patients, respectively. 3) No background factor of the patients except performance status affected the improvement rate. 4) Higher improvement rate was noted in the PGE2 early starting group (within 5 days after the appearance of oral lesions) than the late group (6 days and thereafter) (76.5% v.s. 55.8%: U-test p less than 0.1, chi2-test p less than 0.05). 5) There was no difference in the efficacy rate between the tablet and the troche. 6) Mild side effects were seen in 10 cases. These results suggest that topical administration of PGE2 is safe and useful for improving chemotherapy-associated oral mucosal lesions of patients with hematological malignancies.

Administration, Oral↗

[Clinical evaluation of combination therapy with aspoxicillin and ceftazidime for severe infections complicating hematological disorders].

Clinical effects of a combination therapy using aspoxicillin (ASPC) and ceftazidime (CAZ) were investigated in 88 patients with severe infections which were complicating hematological disorders. ASPC and CAZ were administered intravenously at daily doses of 8 g and 4 to 6 g, respectively, in 2 to 4 divided doses for at least 3 days. The treatment was markedly effective in 20 cases; effective in 31; fairly effective in 4; and ineffective in 33 cases. Seventy-seven patients with whom detailed data were obtained showed an efficacy rate of 63.6%. Bacteria were detected in 9 patients, from whom 10 strains were isolated. The results of bacteriological effects were: 3 strains disappeared, 1 decreased, 3 unchanged, and 3 unclear. The bacteriological eradication rate was 42.9%. Of the detected 10 strains, 3 were identified as Pseudomonas aeruginosa, with 2 of the 3 strains eradicated and 1 decreased. An evaluation of the relationship between clinical efficacies and neutrophil counts before and after the ASPC-CAZ combination therapy showed that the patients with 500/mm3 or higher neutrophil counts before the therapy or those with increased neutrophils after the therapy tended to be more responsive to the therapy. Side effects were observed in 4 patients, but all of them disappeared upon discontinuation of the therapy. The combination therapy with ASPC and CAZ appears to be useful for the treatment of severe infections complicating hematological disorders.

Adolescent↗

Different membrane anchors of Fc gamma RIII (CD16) on K/NK-lymphocytes and neutrophils. Protein- vs lipid-anchor.

Fc gamma RIII (CD16), the type three receptor for the Fc portion of IgG, is expressed on neutrophils, killer (K)/NK lymphocytes and macrophages. K/NK lymphocyte Fc gamma RIII, which plays a role in antibody-dependent cellular cytotoxicity, is an efficient signal transducing molecule, whereas neutrophil Fc gamma RIII, which plays a role in immune-complex clearance, seems less efficient in signal transduction. Neutrophil Fc gamma RIII has been reported to be a glycan-phosphatidylinositol-anchored membrane protein. Our studies suggest that K/NK lymphocyte Fc gamma RIII is protein-anchored rather than glycan-phosphatidylinositol-anchored. That is, K/NK lymphocyte Fc gamma RIII was resistant to phosphatidylinositol-specific phospholipase C and surface expression of Fc gamma RIII was not affected on K/NK lymphocytes from patients with paroxysmal nocturnal hemoglobinuria, a disorder of hemopoietic stem cells resulting in deficient expression of glycan-phosphatidylinositol-anchored proteins. Different membrane anchoring mechanisms of the Fc gamma RIII may account for different consequences of the ligand binding to two cell types.

Antigens, Differentiation↗

Purification and characterization of antizyme inhibitor of ornithine decarboxylase from rat liver.

A protein inhibiting a protein inhibitor (antizyme) to ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) (ODC), antizyme inhibitor, was purified from the liver cytosol of thioacetamide-treated rats by procedures including antizyme affinity chromatography. Overall purification was roughly estimated to be about 17,000,000-fold and recovery was about 2.4%. The purified preparation showed one major protein band and a faint band corresponding in mobility to molecular weights of 51,000 and 53,500, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Judging from the ornithine decarboxylase activity of the final preparation, the faint band may be ornithine decarboxylase. The apparent molecular weight of antizyme inhibitor estimated by gel filtration on Sephacryl S-200 was approx. 62,000, indicating that antizyme inhibitor may be composed of a single polypeptide chain. In order to examine the question of whether antizyme inhibitor is a protein derived from ornithine decarboxylase, an inactive ornithine decarboxylase, in an immunotitration study and analysis of the binding to antizyme were investigated. The results indicate that antizyme inhibitor may be a protein distinct from ornithine decarboxylase.

Animals↗

Antianoxic action of evodiamine, an alkaloid in Evodia rutaecarpa fruit.

In order to determine the antianoxic potential of evodiamine, its effects were compared to those of vinpocetine (VPT), using a series of animal models of anoxia. In mice, evodiamine was equivalent to VPT in the KCN-induced anoxia model but was greater than VPT in the low-pressure-induced anoxia model. Its effectiveness was increased by combined treatment with physostigmine, suggesting the involvement of a cholinergic mechanism in the antianoxic action of evodiamine.

Alkaloids↗

Antianoxic action and active constituents of evodiae fructus.

In order to develop new drugs from natural products, constituents of natural medicines were examined for their effectiveness in the KCN-induced anoxia model in mice. Methanol extract from a Chinese medicine, evodia (fruits of Evodia rutaecarpa Benth. or E. officinalis Dode), had a significant effect in the KCN-induced anoxia model in mice and therefore the active constituents were further examined. The results indicated that the antianoxic action of evodia was found in the fraction containing evodiamine. Further analysis of the active constituent indicated that evodiamine and rutaecarpine, indole-alkaloids found in large amounts in the Chinese medicine evodia, were mainly responsible for the antianoxic action.

Animals↗

[Therapeutic effects of imipenem/cilastatin sodium against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

One hundred ninety-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 182 patients in whom efficacies are evaluable, responses were excellent in 50 patients, good in 52, fair in 21 and poor in 59, and the efficacy rating was 56.0%. 2. The efficacy rating in 87 patients who had failed to respond to prior treatment with other antibiotics was 58.6%. 3. There were significant differences in efficacy ratings when patients were grouped according to differences the number of neutrophils after treatment, less than 100, 101 approximately 500 and over 501/mm3. 4. The eradication rate in 38 patients from whom causative organisms were isolated was 75.8%. 5. Out of 197 patients in whom the safety was evaluable, side effects were observed in 19 patients (9.6%) and abnormal laboratory test values in 15 (7.6%).

Adolescent↗

[Ceftriaxone as a single agent in empirical therapy of infection in patients with hematologic disorders. Hanshin Infection Study Group].

For seventy episodes of infection in hematologic disorders mostly during the phase of severe granulocytopenia, a trial was designed to evaluate the efficacy of a new third-generation cephalosporin, ceftriaxone (CTRX). The regimen consisted mainly of drip infusion of CTRX 2 g every 12 hours. The overall response rate achieved was 54.3 percent. Two episodes of an outpatient with malignant lymphoma were effectively treated by CTRX at a dose of 2-4 g once a day, reflecting its long biological half-life. Gastrointestinal symptoms, hypersensitivity reactions and elevation of hepatic enzyme levels occurred rarely (6.4 and 5.1 percent of the patients, respectively), and these abnormalities were mild and reversible. Thus, CTRX may be recommended as an effective monotherapy in the treatment of infections in immunocompromised patients with hematologic disorders.

Adolescent↗

[Mycotic liver and spleen abscesses successfully treated by intraportal and intrahepatosplenic arterial administration of antimycotic drugs in two cases with acute leukemia].

Case 1. A 34-year-old male was admitted in July, 1986 with a diagnosis of AML (M2). Two courses of BHAC-DMP regimen induced complete remission in October, while marked pyrexia resistant to antibiotics remained. An ultrasonography (US) and computed tomography (CT) revealed multiple liver and spleen abscesses suspected of mycotic etiology. Administration of amphotericin B (AMPH-B) by intravenous injection was difficult owing to its severe side effect. Multiple abscesses increased in the size and number despite treatment with Miconazole (MCZ) and Ketoconazole. Exploratory laparotomy was performed with splenectomy, and splenic specimens were found to contain Candida organisms. Soon AMPH-B was administered through a catheter inserted into the portal vein at the same time. A side effect by AMPH-B was tolerable and his fever resolved to normal in 2 weeks after institution of this therapy, and the sizes of abscesses were markedly reduced. The patient remained in remission through 23 months, free of fungal infection. Case 2. A 23-year-old female was admitted for relapse of ALL (L2), in April, 1987. Reinduction therapy with BHAC-L-AVP achieved again in May but fever unresponsive to antibiotics occurred. Since multiple liver-spleen abscesses were showed by US and CT suspected mycotic etiology, antimycotic therapy with Miconazole and AMPH-B was performed but clinical findings were deteriorated. AMPH-B was administered through a catheter inserted into the hepatic artery for two weeks, following into the splenic artery for a week. Splenic abscesses were resolved in a week and liver abscesses were markedly reduced at three weeks after initiation of intra-arterial antifungal treatment. Through the analysis of these case studies we confirmed the usefulness of intraportal and intrahepatosplenic arterial administration of AMPH-B.

Abscess↗

Inhibition of human natural killer activity by antiserum against vitamin D-binding protein, a group-specific component (Gc).

An anti-Gc antiserum (anti-Gc) was prepared by immunizing rabbits with purified Gc, a major vitamin D-binding protein in human serum. Gc is expressed on the surfaces of a small proportion of resting T cells and almost all B cells are natural killer (NK) cells. We investigated the effects of anti-Gc on NK activity of normal peripheral blood lymphocytes. Both anti-Gc and purified IgG isolated from anti-Gc prominently inhibited human NK activity in vitro. Inhibition of anti-Gc was dependent on the concentration of the antiserum employed. Competition assay showed that purified Gc significantly blocked the inhibitory effect of anti-Gc. The inhibition of NK activity in the cells treated with anti-Gc was restored time-dependently by being cultured in anti-Gc free medium. Anti-Gc-treated NK cells retained their capacity to bind to target cells. These findings suggest that mGc is associated with the process of the NK cytolysis on the post-binding cytolytic phase.

Cytotoxicity Tests, Immunologic↗

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on leukemic cells from chronic B cell leukemia.

It is not clear whether cells from various chronic B cell leukemias including B-chronic lymphocytic leukemia (CLL), CLL in prolymphocytoid transformation (CLL-PLT), B-prolymphocytic leukemia (PLL), and hairy cell leukemia (HCL) simply represent different stages of a single B cell differentiation pathway. Furthermore, it is not known whether cells from any given B cell leukemia are characterized by the same population during the differentiation process. Differentiation of various B cell leukemic cells was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and the resulting changes in their morphology, cytoplasmic immunoglobulin (clg), and cytochemistry were evaluated. With respect to peculiar morphological change, i.e. extending long thin processes (spreading) and the appearance of clg, each sample showed different responses. According to these two indices samples were classified into three groups; spread+ clg- samples (one case of CLL-PLT, all HCL), spread+ clg+ samples (one of CLL, one of CLL-PLT), and spread- clg+ samples (a majority of CLL, one of CLL-PLT, and all PLL). Unexpectedly, both CLL and CLL-PLT consisted of heterogenous populations as to the reactivity to TPA. In the process of TPA-induced differentiation in CLL cells, features similar to those of HCL cells were not found. Since three different TPA-induced response patterns were observed in each chronic B cell leukemia type, it was not possible to sequentially assign each of these leukemias along a single B cell differentiation pathway. In order to explain this result, we introduced the hypothesis that these groups might be divided into different lineages in B cell differentiation. Since TPA-induced spreading cells were present in the B cell fraction of normal peripheral blood mononuclear cells, this morphological change should not be associated with malignant transformation.

B-Lymphocytes↗