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Biomedical subjects

H Nonaka

Publications and source records attributed to H Nonaka.

At least 91 records · Page 5Linked to original sources

Effect of dextran sulfate on renal accumulation of gentamicin.

The effect of dextran sulfate of three molecular weights (1000, 5000, and 90,000) on the accumulation of gentamicin in rat kidney was investigated using a continuous infusion technique. During the infusions of both gentamicin and gentamicin-dextran sulfate mixtures, the gentamicin plasma concentration was maintained at 10 microgram/ml. The renal cortical accumulation of gentamicin was significantly lower when dextran sulfate (1000, 5000) was coadministered. The inhibition of cortical gentamicin accumulation increased with increasing dextran sulfate dose, and it was proportional to the amount of dextran sulfate excreted into the urine. Analysis by electrophoresis on cellulose acetate membrane indicated that gentamicin binds to dextran sulfate in rat urine. Therefore, gentamicin-dextran sulfate binding within the lumen of the proximal tubules may reduce the renal reabsorption and possibly the renal toxicity of gentamicin.

Animals↗

[Comparison of ciprofloxacin with polymyxin B for infection prophylaxis in neutropenic patients with acute non-lymphocytic leukemia].

Twenty-four neutropenic patients receiving intensive chemotherapy for acute non-lymphocytic leukemia were studied in a randomized trial comparing ciprofloxacin with polymyxin B for prevention of infections. Both groups (12 patients each group) received amphotericin B for antifungal prophylaxis. 20 febrile episodes occurred in 22 courses of oral prophylactic ciprofloxacin and 22 occurred in 24 courses of oral prophylactic polymyxin B. Patients receiving ciprofloxacin had a mean time to the first infection-related febrile episode of 7.2 days, compared with 4.3 days for the polymyxin B group (p less than 0.01). Patients receiving ciprofloxacin also had fewer days of fever (average 6.5 days versus 9.8 days for the polymyxin B group, p less than 0.02). Duration of administration of parental antibiotics were also shorter in the ciprofloxacin group (p less than 0.001). Although modifications of the empiric antibiotic regimen were required more frequent in patients receiving polymyxin B, this did not reach statistical significance. These results suggest that ciprofloxacin is a more efficacious oral antimicrobial agent than polymyxin B for the prevention of infections in neutropenic patients with acute non-lymphocytic leukemia.

Administration, Inhalation↗

[Treatment of acute lymphoblastic leukemia in adults by the modified protocol of L-10M (Sloan-Kettering)].

We have treated 20 adult patients with acute lymphoblastic leukemia (ALL) and 2 patients with lymphoblastic lymphoma with a protocol modified from L-10M of the Memorial Sloan Kettering Cancer Center. Eighteen patients (81.8%) entered complete remission (CR). Eight of them eventually relapsed (only 1 patient had a meningeal relapse) and died. Median CR duration was 19 months (median overall follow-up of 35 months and 50% remission duration was not yet determined. Median overall survival was 19 months. Three patients died of sepsis during remission induction, but all of other deaths were due to resistant or relapsed leukemia. The four patients who completed 3.5 year's modified L-10M protocol were free from relapse for 6-11 months (mean 8.7). Although further follow-up is necessary, we suggest that modified L-10M protocol is effective for adult ALL and long-term survival may be available.

Adolescent↗

[A case of cardiac amyloidosis showing the ischemic change by exercise Tl-201 myocardial scintigraphy].

A case of cardiac amyloidosis, which was recognized as an ischemic change by exercise Tl-201 myocardial scintigraphy, was studied. The case was 41 year-old woman, whose initial symptom was pretibial edema and died of ventricular fibrillation. Ischemic change was ascertained by the treadmill exercise test and exercise Tl-201 myocardial scintigraphy, however, the significant coronary stenotic lesion was not detected by coronary angiography. Our data suggested that ischemic change may be related with the disturbance of microcirculation caused by deposit of amyloid in the vessels and/or around the vessels from the pathological findings.

Adult↗

[Study on pathophysiology of the myelodysplastic syndromes (MDS)--pattern of dysmegakaryopoiesis related to leukemic transformation].

A series of 116 patients with MDS consisted of 74 cases of RA, 10 cases of RARS, 14 cases of RAEB, 9 cases of RAEB-T and 9 cases of CMML, were studied on the quantity and morphological abnormalities of megakaryocytes in relation to over all survival and leukemic change. The amount of megakaryocytes was graded into four groups; marked hypoplasia (O), moderate hypoplasia (L), normoplasia (N) and hyperplasia (H), RA cases showed heterogeneous pattern; containing 14 cases (18.9%) of group (O), 18 cases (24.3%) of group (L), 31 cases (41.9%) of group (N) and 11 cases (14.9%) of group (H). RARS, RAEB, RAEB-T and CMML cases were classified into group (N) or group (H). The heterogeneous pattern of RA did not relate to leukemic change, but over all survival tended to be shorter in group (N) cases. A significant number of young female cases of RA were involved in group (O). Morphological abnormalities of MDS megakaryocytes were classified into five types; I, mononuclear micromegakaryocytes, II, binuclear micromegakaryocytes, III, mononuclear small megakaryocytes, IV, multiseparated-nuclear megakaryocytes and V, megakaryocytes with bizzare nuclei. RAEB and RAEB-T cases uniformly showed marked dysmegakaryopoiesis ranging from type I to V. whereas RA, RARS and CMML cases showed mild dysmegakaryopoiesis. Only five cases (6.4%) of RA cases had type I micromegakaryocytes. Eight RA cases with type I on diagnosis or obtaining it during the clinical course tended to develop acute myeloid leukemia (5 cases) or to transform to RAEB sooner or later. In two cases of RAEB in which hematological improvement was obtained with low dose cytosine arabinoside regimen, disappearance of type I micromegakaryocytes was noted. A female case with 5q-anomaly surviving more than 10 years showed marked megakaryocyte hyperplasia and almost exclusively type III and IV megakaryocytes. These findings indicated that pattern of dysmegakaryopoiesis, especially appearance of type I, was closely related to leukemic change in MDS. Thus quantitative and qualitative evaluations of MDS megakaryocytopoiesis seemed important to understand the further heterogeneity of pathophysiology in MDS subtypes.

Aged↗

[Marked dysmyelopoiesis after induction chemotherapy in a case of acute myelomonocytic leukemia (M 4) with t(6; 11)].

A case of AML (M 4) with t(6; 11) showed recovery to myelodysplastic syndrome (MDS)-like bone marrow after one course of DCMP regimen. Dysplastic changes of three cell-lineages were observed and micromegakaryocytes were markedly increased in number. Recovering hematopoiesis was incomplete. During MDS-like phase, t(6; 11) disappeared, reverting to normal karyotypes. Low dose ara-C regimen did not show any effect. AML soon relapsed with reappearance of t(6; 11). MDS-like abnormal hematopoiesis has recently been reported to occur after remission induction therapy or at the time of relapse. G-6PD isozyme study revealed in a remission case of AML that hematopoiesis still consisted of abnormal clone in spite of karyotypic normalization. The abnormal hematopoiesis observed in our case can be referred to such a clonal disorder predominating after disappearance of blastic component of AML. It seems important to reveal what proportion of de novo AMLs shows such an abnormal hematopoiesis and to establish suitable therapeutic approach.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical study on alcoholic pancreatitis in alcoholics (especially in ERP findings)].

The pancreatic functions (PFD test and 75g GTT), pancreatic enzymes (serum-amylase, urine-amylase, serum-elastase I and serum-lipase), alcohol consumption histories, clinical symptoms, histological findings in the liver and ERP findings have been examined in 66 alcoholic patients. Fourty two out of 66 cases (64%) showed abnormal ERP findings which were compatible with chronic pancreatitis. But among these 42 cases, only 9 cases (21%) showed clinical symptoms such as epigastralgia, back pain, diarrhea and emaciation which suggest the existence of chronic pancreatitis. The degree of liver damage, alcohol consumption have no significant correlation with ERP findings. Furthermore, the severe alcoholic pancreatitis occurred in patients having mild liver injury more than those having severe liver injury such as cirrhosis. And the data of pancreatic functions and enzymes could not confirm ERP findings especially in patients with mild and moderate pancreatic injury when compared to normal ERP findings. We concluded that asymptomatic alcoholic pancreatitis occurred more frequently in painless alcoholic. It may be not suitable for only using the normal pancreatic functions test to diagnose the alcohol induced chronic pancreatitis.

Adult↗

[A trial for prolongation of chronic phase of chronic myeloid leukemia--maintenance of leukocyte counts within normal range with busulfan].

To prolong the survival of patients with chronic myeloid leukemia (CML), 19 patients were treated with busulfan to keep their leukocyte counts within normal range by controlling bone marrow hyperplasia. The duration of chronic phase in these patients was significantly longer than that in historical controls who were treated conventionally with busulfan. This prolongation was not ascribable to the difference in such prognostic factors between the two therapy groups as splenomegaly, leukocyte count and percentage of peripheral blasts. There was a significant difference again in the duration of chronic phase between the two therapy group even when restricted to each 11 patients with intermediate relative risk (0.7-1.5) according to Sokal et al. Four patients showed thrombocytopenia less than 5 x 10(4)/microliters, but all these patients recovered within 4 months and there was no further critical side effect except subcutaneous bleeding. This study suggests that maintenance of leukocyte count within normal range and suppression of granuloid hyperplasia in bone marrow with busulfan may prolong chronic phase of CML. Probability of clonal evolution may be decreased by reducing the total leukemic cell mass and suppressing cellular turnover of primitive CML stem cells. Another possibility is that prolongation of chronic phase might be dependent on the appearance of normal karyotype clone after long-term bone marrow suppression just like after intensive chemotherapy or alpha-interferon therapy.

Adolescent↗

A B-cell line having chromosome 14 aberration at break band q11 derived from an adult T-cell leukemia patient.

A B-cell line having translocations of chromosome 14 at break band q11 (the assigned locus of the alpha-chain gene of the T-cell antigen receptor) and chromosome 3 at break band p25 (the assigned locus of the c-raf-1 oncogene) was established from peripheral blood leukocytes of an adult T-cell leukemia (ATL) patient. The same chromosome 14 aberration at break band q11 and chromosome 3 aberration at break band p25 were also found in fresh T-cell leukemia cells. The B-cell line is surface immunoglobulin (sIg)+, immunoglobulin gene rearrangement+, ATL-specific antigen (ATLA)+, HTLV-1 proviral genome+, Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA)+ and the EBV DNA genome+. The fresh T-leukemic cells were T-cell receptor gene rearrangement+, the HTLV-1 proviral genome+ and EBV DNA genome.

B-Lymphocytes↗

Specific abnormalities of chromosome 14 in patients with acute type of adult T-cell leukemia/lymphoma.

Chromosome analysis was performed on 1 patient with diffuse lymphoma of mixed type by histologic diagnosis and on 7 patients with the acute type of adult T-cell leukemia (ATL). Specific abnormalities in chromosome 14 at break band q11 with the assigned locus of the alpha-chain gene of the T-cell antigen receptor were identified in 6 of 8 patients. Inv(14) (q11q32) was found in 2 patients and translocation of chromosome 14 at break band q11 was observed in 4. Donor chromosomes involved in translocation of the 14q11 varied, i.e., chromosomes 3, 7 or X, with the exception of one patient whose donor chromosome origin could not be determined. The breakpoint in chromosome 3 was in band p25, a region reported to include the locus of the c-raf-I oncogene. In chromosome 7, it was in band p11, a region reported to include the locus of the c-erb-B oncogene, and in the sex chromosome X, it was in band q11. One patient also had a chromosome 14 aberration at break band q32. Of the 2 remaining patients, one had lost chromosome 14 and the other had an isochromosome 14q. Our observation and other reported findings suggest that the rearrangement of chromosome 14 at break band q11 is specific for lymphoma-type or acute-type ATL patients, and aberrations of proto-oncogene expression or the coding sequence by recombination involving a T-cell antigen receptor gene due to chromosome inversion or chromosome translocation may play an important role in T-cell neoplasia including ATL.

Adult↗

A study on the microvasculature of the cerebellar cortex. The fundamental architecture and its senile change in the cerebellar hemisphere.

The arterial structure of the cerebellar cortex was studied by vascular stain and in diaphanized specimens after intra-arterial barium injections. A scanning electron microscope study on the corrosion cast of the arteries was also performed. Arteries distributed in the cerebellar hemisphere are classified into cortical, subcortical, and medullary arteries. The patterns of arterial distribution are similar to those in the cerebral cortex. The cortical arteries are subclassified into superficial, middle, and deep cortical branches. The superficial branches are very fine, forming capillary networks in the molecular layer. The middle cortical branches terminate in the Purkinje cell layer, by dividing into several branches extending parallel to the plane of this layer. These branches connect with capillaries in both the molecular and the granular layers. The deep cortical branches give off some collaterals along the Purkinje cell layer and terminate in the granular layer, by breaking up into capillary networks. The Purkinje cell layer is marked by arterial branches ramified from the middle and deep cortical branches and no particular dense capillary networks are formed in the Purkinje cell layer. The brains of older patients show intertwining of the middle and deep cortical branches, some forming "rope-like" appearance. These patterns are similar to those seen in the cerebral cortex, but they were found, in older people, in the cerebrum.

Aged↗

Dysmegakaryocytopoiesis in acute leukaemias: its predominance in myelomonocytic (M4) leukaemia and implication for poor response to chemotherapy.

Megakaryocytopoiesis was morphologically investigated in 129 adults with de novo acute leukaemia. Three types were identified: type I (84 cases), no detectable megakaryocytes; type II (32 cases), quantitatively preserved megakaryocytes with normal morphology; type III (13 cases); quantitatively preserved megakaryocytes but with distinct dysplastic changes such as micromegakaryocytes and megakaryocytes with multiple small separated nuclei. Type III was found in M1 (one out of 21 cases), M2 (one out of 20 cases). M4 (eight out of 24 cases), M6 (two out of four cases) and hypoplastic leukaemia (one out of 13 cases). M3 cases were all classified into type I. Most of acute lymphoid leukaemia cases (21 cases) belonged to type II. Among AML cases, the complete remission (CR) rate by intensive chemotherapy with daunorubicin and cytosine arabinoside was significantly lower in type III (11%) than in types I (87%) and II (71%). Among M4 cases, CR rates in type III (14%) was also significantly lower than those in type I (75%) and II (100%). Thus, the present study indicates the importance of recognizing dysmegakaryocytopoiesis in AML for clarification of the heterogeneous biology or pathophysiology of acute leukaemias and formulation of an appropriate therapeutic strategy.

Acute Disease↗

Cytogenetic and cytochemical studies on progenitor cells of primary acquired sideroblastic anemia (PASA): involvement of multipotent myeloid stem cells in PASA clone and mosaicism with normal clone.

By cytogenetic and cytochemical analyses of individual hematopoietic colonies, we investigated clonality in progenitor compartments of primary acquired sideroblastic anemia (PASA). Two of our four subjects had reduced but countable numbers of CFU-E, BFU-E, and GFU-GM in methylcellulose culture. In one patient with cytogenetic abnormality of 47, XX, +8 in 67% of the bone marrow cells, cytogenetic analysis of individual erythroid bursts and granulocyte/macrophage colonies demonstrated two populations with and without 8 trisomy, the trisomy clone being 38% in BFU-E and 50% in CFU-GM. These findings indicate involvement of multipotent stem cells in PASA clone and mosaicism of two distinct populations in erythroid as well as granulocyte/macrophage progenitor compartments, the abnormal PASA clone and probably the normal clones. In another case with no cytogenetic abnormality, repeated iron staining showed that 31% to 40% of CFU-E and 25% to 54% of BFU-E had erythroblasts with heavy iron deposits. An ultrastructural analysis of 25 individual erythroid bursts revealed that 32% had highly dysplastic erythroblasts with marked ferruginous iron accumulation in the mitochondria. The other 68% and 15 normal bursts from a healthy control did not have noticeable dysplastic changes and iron deposits in the mitochondria. This cytochemical/ultrastructural mosaicism seems to be compatible with the cytogenetic mosaicism. However, whether the BFU-E derived from abnormal PASA clone selectively manifest iron accumulation in the mitochondria or whether the PASA clone itself shows variable degrees of abnormal iron metabolism remains to be determined by simultaneous performance of ultrastructural and cytogenetic analysis for single bursts.

Adult↗