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Biomedical subjects

N Nakazawa

Publications and source records attributed to N Nakazawa.

At least 37 records · Page 2Linked to original sources

[Clinical evaluation of panipenem/betamipron as a second line chemotherapy in severe infections associated with hematological disorders].

Thirty three patients with severe infections associated with hematological disorders were treated with panipenem/betamipron as a second line chemotherapy. Of these, 30 patients were evaluated for effectiveness. An excellent response was obtained in 14 patients (46.7%) and a good response in 5 (16.7%), and the overall efficacy rate was 63.3%. Efficacy rates were 3/6 in patients with sepsis, 68.4% (13/19) in patients with fever of undetermined origin, 2/4 in patients with pneumonia. In patients whose peripheral granulocyte count was below 100/microliter at the start of chemotherapy, the efficacy rate was 3/7. Side effects were observed in 5 of 33 patients (15.2%). These results show that PAPM/BP is useful as a second line chemotherapy for the treatment of severe infections in patients with hematological disorders.

Adult↗

The Ig heavy chain gene is frequently involved in chromosomal translocations in multiple myeloma and plasma cell leukemia as detected by in situ hybridization.

Chromosome rearrangement of 14q32.33 has recurrently occurred with variable partner sites, including 11q13.3, 8q24.1, 18q21.3, and 6p21.1 in multiple myeloma (MM). To assess the actual incidence of 14q32.33 translocation and to elucidate its implication in the pathogenesis of MM, we studied 42 patients with MM, plasma cell leukemia, or plasmacytoma and 5 with monoclonal gammopathy with undetermined significance (MGUS) by G-banding and molecular cytogenetic methods. Using double-color fluorescence in situ hybridization (DCFISH) with 2 Ig heavy chain (IgH) gene probes, a yeast artificial chromosome (YAC) clone containing variable region, and a phage clone containing gamma constant region, 14q32.33 translocation was detected as split signals of the IgH gene in 31 patients with plasma cell malignancies and 3 with MGUS. In contrast, of 40 patients who were assessed by G-banding, 3 (7.5%) showed the 14q+ chromosome. DCFISH detected a split of the IgH gene on interphase nuclei in 34 (73.9%) of 46 patients analyzed, whereas on metaphase spreads, it was in 22 (51.2%) of 43 patients analyzed. Interphase DCFISH was particularly useful to detect 14q32.33 translocation in 17 (65.4%) of 26 patients with normal karyotypes. Donor sites were identified in 11 of 22 patients demonstrated as carrying 14q32.33 translocation by metaphase FISH. Chromosome t(11;14)(q13.3; q32.33) was detected in 5 patients, t(8;14)(q24.1;q32.33) in 2, t(14;18)(q32.33;q21.3) in 2, and t(7;14)(q32.1;q32.33) in 1. A complex 14q32.33 translocation involving 3q and 16q24 was detected in 1 patient. Myeloma cells with t(7;14) showed myelomonocytoid surface antigen. Because rearrangements of 14q32.33 were closely associated with translocation of proto-oncogenes into the IgH gene, our findings indicate that 14q32.33 translocation with various partner chromosomes is a critical event in the pathogenesis of MM and MGUS.

Adult↗

[Laminin-dependent growth arrest of human hepatic carcinoma cell line, HuH-7, in association with expression of p21/WAF-1 protein].

Laminin-overlay to the culture of a human hepatocellular carcinoma cell line, HuH-7, resulted in changes in the cell behavior; suppression of the cell growth, conversion of the cell morphology, and the elevated secretion of cellular AFP in the culture medium, implying that the cells had undergone apparent differentiation in vitro. Together with the behavioral changes, the cells showed positive immunohistochemical staining of the anti-p 21/WAF 1 antibody over the cell nucleus and the amount of p 21/WAF-1 proteins was increased in the cells. p53 protein was detected both in the control cells and the cells with the laminin overlay. These findings indicate that the laminin-dependent changes in the cell behavior are closely associated with the activation of the cyclin-dependent kinase inhibitor, p 21/WAF-1, and that? is uncoupled with the p 53 expression.

Carcinoma, Hepatocellular↗

[Predisposition of subclones of pancreatic carcinoma cells, AsPC-1, to changes in functional and histopathological features of xenograft tumors with response to extracellular matrix].

We cloned two characteristics subclones from a human pancreatic carcinoma cell line, AsPC-1, according to their distinctive cell shapes; one an epithelial morphology and designated as "Beto-1" and the other a fibroblastic morphology and designated as "Fib-1". Fib-1 grew faster than Beto-1, but the growth rate of the cells on plastics was as high as that of the cells on the extracellular matrix extracts, matrigel. The pancreatic tumor-marker proteins, alpha-amylase, insulin, CEA, POA, PP, and AFP, but not CA 19-9, were positive in both subclones. Type IV collagen, fibronectin, and laminin, were all positive in both subclones; furthermore, the integrin adhesion receptor molecules, alpha 2 beta 1-subunit, alpha 5-subunit, and alpha 6-subunit, were also positive. The intercellular adhesion molecules, E-cadherin and ICAM-1, were detected in Beto-1 and Fib-1, respectively. Although both subclonal cells attached to type IV collagen, fibronectin, and laminin in a concentration-dependent manner. Beto-1 adhered most strongly to type IV collagen and Fib-1 attached most strongly to fibronectin. Beto-1 showed morphological differentiation on matrigel and in the tumor xenografts. Further, there was more fibroblast infiltration and type IV collagen production in Beto-1 tumor tissues, and more lymphocyte and neutrophil infiltration in tumors of Fib-1 which expressed ICAM-1 proteins. This study indicated that the histological diversity observed in the pancreatic carcinoma was evolved from the composition of the tumor cells which express the specific adhesion receptors.

Animals↗

[The influence of pregnancy and delivery on the climacteric symptoms].

This study was undertaken to investigate the influence of past pregnancy and delivery on the perimenopausal status in 144 women (48-52 years of age). Individual interviews to ascertain the personal profile, medical history, events at pregnancy, delivery and puerperium, and the kind and severity of climacteric symptoms were held. The subjects were divided into two groups by means of a simplified menopausal index (SMI): group A had climacteric symptoms (SMI > 50) and those in group B had mild symptoms (SMI < or = 50). The analysis of the principal components, and the correlation among the variables revealed that three factors--the impression and events at past pregnancies and deliveries, reproductive functions, and the psycho-character properties--had a significant influence on the status at the perimenopause, but the social-environmental factors appeared to have no significant influence on the severity of climacteric symptoms.

Climacteric↗

A possible role of estrone produced in adipose tissues in modulating postmenopausal bone density.

Estrogen deficiency in postmenopausal women is a major contributing factor to bone loss occurring after menopause. Although serum estradiol levels decrease conspicuously, a considerable amount of estrone still exists in women after natural menopause. Since most of the estrone is converted from androgens in adipose tissues, we attempted to seek interrelationship among serum estrone levels, fat mass and bone mineral density (BMD) in postmenopausal women. Thirty women who underwent natural menopause at the age between 45 and 53 were examined for BMD of head, arms, trunk and legs, as well as total body fat and total lean body mass using a Lunar DPX, a dual energy X-ray absorptiometer. Serum estrone concentration in each subject was measured by RIA. BMD of all sites of bones examined showed a positive correlation with relative fat mass (total body fat/body weight). Serum estrone levels were positively correlated with BMD of arms, trunk and legs, as well as relative fat mass. Multiple regression analysis further demonstrated that relative fat mass and serum estrone levels were significantly related to BMD of both arms and trunk, and BMD of trunk, respectively. These results suggest that estrone produced in adipose tissues may have, if only in part, a role in modulating the loss of bone mass occurring after menopause.

Adipose Tissue↗

[Ultrasonographic diagnosis of athero- and arterio-sclerosis].

Modalities to depict atherosclerotic lesion, have recently been rich in approaches, such as angiography, computed tomography, ultrasonography, radionuclide imaging and magnetic resonance imaging. Although the angiography is still one of the gold standards for diagnosing athero- and arteriosclerotic changes, recent developments in interventional catheterization and medical treatments necessitate the detailed characterization of the vascular wall. High-frequency ultrasonography now expands the observation toward the structure and composition of the vascular wall which can not be obtained in angiography. The higher the frequency of ultrasound is, the better the resolution of the echo imaging improves. However, the adequate depth for echo observation from the probe becomes narrower with the increase of the probe frequency. Accordingly, we have to choose an adequate approach for the vessel of interest. For example, transesophageal echocardiography is useful to evaluate the atherosclerotic changes of the descending aorta. Peripheral ultrasonography is useful for the superficial arteries, including carotid arteries, femoral arteries and branchial arteries. The advantages of the peripheral body surface approach are non-invasiveness and repeatability. Intravascular ultrasonography requires invasive technique, but it provides novel information regarding the presence and the extent of atherosclerosis and its characterization such as calcification. Intravascular ultrasonography is a necessary modality for evaluating the effect of the directional coronary atherectomy.

Arteriosclerosis↗

GDP inhibits the activity of the centrosome to nucleate microtubules.

Microtubule-nucleating ability of the centrosome in the isolated mitotic apparatus was investigated under the condition that the centrosomal fragment was preincubated with guanine nucleotides or its derivatives. GTP and non-hydrolyzable GTP analogues such as GTP-gamma S or GMP-PNP consistently supported high activity of the centrosome to nucleate microtubules. On the other hand, GDP substantially suppressed the microtubule-nucleating activity of the centrosomes. Evidence has been presented that this is not simply due to the inhibitory effect of GDP on microtubule assembly. This result is consistent with the idea that GTP binding proteins such as 51 kDa protein and gamma-tubulin localized to the pericentriolar materials in the centrosome are competent for the nucleation of microtubules when it is saturated with GTP.

Animals↗

Ethanol-elicited structural and biochemical alterations in mitochondrial ATPase in cultured myocardial cells.

The effects of ethanol (12.5-500 mM for up to 24 h) on mitochondrial structure including that of ATPase particles in cultured ventricular myocardial cells were studied using negative-stain electron microscopy. The activity of mitochondrial ATPase after ethanol treatment was also examined cytochemically and biochemically. At 5 min after the addition of all the concentrations of ethanol examined, some mitochondrial cristae were expanded and the arrangement of mitochondrial ATPase particles on these cristae was disordered. At and after 30 min the cristae decreased in number and some were expanded, vesiculated or fragmented. ATPase particles also decreased in number, particularly after the application of ethanol in concentrations of more than 50 mM. All the mitochondria had broadened and translucent cristae, and lacked ATPase particles with 200 and 500 mM ethanol at 24 h, although with 12.5 and 50 mM ethanol some mitochondria had similar negatively stained images but others had ATPase particles on broadened cristae. The enzymatic activity of the mitochondrial ATPase was unchanged with 200 and 500 mM ethanol at 24 h, compared with controls. The cytochemical technique also detected enzyme activity with all the concentrations of ethanol examined at 24 h. The discrepancy between the structural and biochemical alterations in mitochondrial ATPase induced by ethanol is discussed.

Adenosine Triphosphatases↗

[Correlation between adherence ability and construction of basement membrane-like scaffold of HeLa-S3 cells in nude mouse tumor].

We selected a subclone of HeLa-S3 cells to depict the relationship between cellular adherence to the extracellular matrix and pathological features of tumors derived from these cells. The selected subclone (PA cells) adheres poorly to type-IV collagen as compared to the wild type cells (EA cells) which attach easily to type-IV collagen. In vitro, it was confirmed that PA cells adhered poorly to type-IV collagen even after a long term of culture and showed weaker chemotactic activity toward this BM component. Injected into nude mice, PA cells formed smaller tumors than EA cells. Histologically, both derived tumors showed construction of basement membrane-like scaffolds that stained positively for type-IV collagen and laminin. EA cell tumors demonstrated frequent absence of and thinning and gaps in their basement membrane, which shows the invasive activity of the tumors. PA cell tumors showed a more regular basement membrane with predominant desmoplasia.

Animals↗

Interactions of elastin and microfibrils in elastogenesis of human pulmonary fibroblasts in culture.

The interaction of elastin and microfibrils in elastogenesis in vitro was investigated with electron microscopy and immunohistochemistry. Fetal human pulmonary fibroblasts were cultured with or without beta-aminopropionitrile (BAPN). One week after seeding, the extracellular microfibrils were loosely arranged without elastin deposition. Two and six week culture in controls, mature elastic fibers and microfibril bundles were formed. In cultures with BAPN, the microfibrils were loosely arranged, and a few microfibril bundles and no amorphous components were formed. Immunoelectron microscopy for elastin showed the reaction at the outer zones of amorphous components in controls, though the loosely-arranged microfibrils reacted diffusely in cultures with BAPN. Six week culture with BAPN, aggregated masses of elastin, which were dissociated from microfibrils, were found. In conclusion, deposition and maturation of elastin on microfibrils are necessary to form the microfibril bundles in normal elastogenesis, and vaguely outlined aggregated masses of elastin are formed under the inhibition of lysyl oxidase.

Aminopropionitrile↗

Calcification in human osteoblasts cultured in medium conditioned by the prostatic cancer cell line PC-3 and prostatic acid phosphatase.

A medium that had been conditioned by PC-3 cells stimulated the calcification of a human osteoblastic cell line, Tak-10, in a nonmitogenic culture. The calcification of the osteoblasts was stimulated maximally at a 25% concentration of the conditioned medium. Calcification activity was markedly enhanced by the addition of both prostatic acid phosphatase (PAP) and its substrate, alpha-glycerophosphate, to the medium; however, PAP added alone did not enhance this activity. These results suggest that human prostatic carcinoma cells produce a factor that stimulates the calcification of the human osteoblasts. Results have also suggested that PAP is a requisite for osteogenesis provided that its substrates are abundant in the medium.

Acid Phosphatase↗

AAR2, a gene for splicing pre-mRNA of the MATa1 cistron in cell type control of Saccharomyces cerevisiae.

We have isolated a class of mutants, aar2, showing the alpha mating type due to a defect in a1-alpha 2 repression but with alpha 2 repression activity from a nonmater strain of Saccharomyces cerevisiae expressing both a and alpha mating-type information in duplicate. Cells of the aar2 mutant and the aar2 disruptant also show a growth defect. A DNA fragment complementing the aar2 mutation contains an open reading frame consisting of 355 amino acid codons. Northern hybridization showed that cells of the aar2 mutant and disruptant contained alpha 1 and alpha 2 transcripts of the MAT alpha gene (or HML alpha in sir3 cells), but their a1 transcript of MATa (or HMRa in sir3 cells) migrated more slowly than that of the wild-type cells on gel electrophoresis and gave a diffused band. Primer extension analysis showed that the aar2 mutant and disruptant have a defect in splicing two short introns of the a1 pre-mRNA but not in splicing pre-mRNA of ACT1. The alpha mating type, but not the slow-growing phenotype, of the aar2 mutant was suppressed by introduction of an intronless MATa1 DNA. Thus, the AAR2 gene is involved in splicing pre-mRNA of the a1 cistron and other genes that are important for cell growth. The AAR2 locus was mapped on chromosome II beside the SSA3 locus, with a 276-bp space, but was not allelic to either PRP5 or PRP6, which are both located on chromosome II and function in splicing pre-mRNA of ACT1.

Amino Acid Sequence↗

[Combined valvular and coronary artery surgery].

Combined valvular and coronary surgery were performed on 9 patients between 1973 and 1986. Valve replacements were consist of 5 AVR (including 1 translocated AVR and 1 Bentall operation), 2 MVR and 2 double valve replacement. Coronary surgery were of 6 aorto-coronary bypass using great saphenous veins, 1 innominate artery-coronary bypass using a Dacron prosthesis, 1 punch-out of coronary ostium and 1 dilatation of the left coronary ostium with a vein patch. Retrograde infusion of cardioplegic solution from the coronary sinus were done in patients with coronary ostial stenoses. One emergency case with acute cardiac failure died immediately after operation, and one with double valve and one with mitral valve replacement died of hepatic failure and multiple organ failure respectively within 1 year after surgery. Combined valvular and coronary surgery are necessary for patients with both diseases. Although the results of double valve replacement were not satisfactory, they would be improved using intra-aortic balloon pump and ventricular assist devices actively.

Adult↗

[Progress of radiation therapy in malignant lymphomas].

Radiation therapy is keeping an important role on treating stage I, II and III A Hodgkin's disease. Several prognostic factors influencing treatment result were discovered recently even though patients conditions belong to the same stage. Owing to rapid progress of multi-anticancer drug chemotherapy, indication of radiotherapy of non-Hodgkin's lymphoma has become narrower than 10 years ago. However, radiotherapy is important to cure both stage I and early stage II non-Hodgkin's lymphoma with low or intermediate grade histological malignancy.

Adolescent↗