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Biomedical subjects

M Tanabe

Publications and source records attributed to M Tanabe.

At least 199 records · Page 11Linked to original sources

Expression of neuronal src mRNA as a favorable marker and inverse correlation to N-myc gene amplification in human neuroblastomas.

Neuron-specific src mRNA, which is expressed in human brain tissue by alternative splicing, is associated with neural differentiation. Neuronal c-srcNI expression may be associated with the ability of neuroblastomas to mature; furthermore, c-srcN2 mRNA is induced in chemically differentiated neuroblastoma cells in vitro. The prognosis of a patient with a neuroblastoma is strongly affected by the ability of the tumor to differentiate in vivo. In order to clarify the relationship between neuronal src mRNA expression and the clinical outcome of a neuroblastoma, we analyzed the expression of src mRNA in neuroblastoma tissues from 28 patients by SI-nuclease-protection assay. N-myc gene amplification was also examined by Southern blot hybridization. The clinical significance of neuronal src mRNA expression and its relevance to N-myc gene amplification was also investigated. A high ratio (more than 10%) of c-srcN2 mRNA expression was observed in all early-stage tumors and in advanced neuroblastomas with a favorable prognosis. In contrast, in advanced neuroblastomas with an aggressive clinical phenotype, c-srcN2 mRNA expression was found at a low ratio (below 10%). Genomic amplification of the N-myc gene and expression of c-srcN2 mRNAs were inversely correlated. When combined with other prognostic markers such as N-myc gene amplification, the expression of c-srcN2 mRNA may be a new biological marker to predict the prognosis of patients with neuroblastomas.

Blotting, Southern↗

Combined immunosuppressive therapy with low dose FK506 and antimetabolites in rat allogeneic heart transplantation.

Following rat heterotopic heart allotransplantation, low to lethal doses of the antimetabolites mizoribine (MIZ), RS-61443 (RS), and AZA were given alone or in combination with subtherapeutic doses of FK506 (0.04 mg/kg/day) for 14 days after transplantation. With the median effect analysis of Chou and Kahan for quantitative drug interactions, substantial therapeutic synergism was demonstrated between FK506 and non-toxic doses of MIZ (2.5, 5, and 10 mg/kg/day) or AZA (5, 30, and 45 mg/kg/day), which was particularly evident with the lowest dose MIZ (2.5 mg/kg/day). When FK506 was used in combination with MIZ or AZA but not with RS, the maximum effect (peak median graft survival) was enhanced significantly from 15 days (MIZ alone) to 26 days (P < 0.05), and from 19 days (AZA alone) to 32 days (P < 0.01). In contrast, RS interacted with FK506 no more than additively. Although RS was the most powerful single antimetabolite, the best overall survival was obtained by combining AZA and FK506. The addition of FK506 did not significantly increase the percent mortality and LD50 of the antimetabolites.

Animals↗

[Experimental investigation of 201TlCl-scintigraphy in evaluating therapeutic effect of hyperthermia].

We investigated the usefulness of 201Tl-scintigraphy in the evaluation of therapeutic effect of hyperthermia. Satoh's experimental lung cancer tumors implanted in the right thighs of donryu rats were treated with hyperthermia using water bath. Tumors were heated at 44 degrees C or 46 degrees C for 15 min. 201Tl-scintigraphy was obtained before, immediately after and 24 hrs after treatment. Counts ratio of the tumor to the normal muscle (T/N ratio) was measured by gamma camera. We examined blood flow of the tumor, and relative tumor growth rate, and performed autoradiogram and histopathological examination of the tumor after 201Tl-scintigraphy. Immediately after hyperthermia, T/N ratio and blood flow of the tumor significantly decreased (p < 0.05). Autoradiogram showed that the accumulation of 201TlCl in the tumor decreased diffusely. Histopathological finding showed congestion, thrombosis, and swelling of endothelial cells. These results suggest that the decrease in T/N ratio may be caused by the vascular damage due to hyperthermia. The T/N ratio recovered 24 hrs after hyperthermia but was still lower than that for the control. Autoradiogram showed that 201TlCl greatly accumulated in the viable tumor tissue but was hardly seen in the necrotic tumor tissue. These results suggest that the decrease in T/N ratio may be caused by increase of necrotic areas. The T/N ratio 24 hrs after hyperthermia correlated (r = 0.83) with relative tumor growth rate on 7th day after hyperthermia and, therefore, can be used as an indicator of relative tumor growth rate. 201Tl-scintigraphy can be useful for prediction of therapeutic effect of hyperthermia.

Animals↗

[The effect of PTA on cerebral vessels in experimental vasospasm: a histopathological study].

Although the percutaneous transluminal angioplasty (PTA) is an useful procedure for the treatment of symptomatic vasospasm after subarachnoid hemorrhage, the morphological changes in spastic intracranial vessels after PTA are not yet clear. The purpose of this study was to evaluate the effects of PTA angiographically and histologically. Chronic cerebral vasospasm was induced by producing a blood clot in the subarachnoid space around the top of internal carotid siphon in Japanese monkey. After angiographic recognition of vasospasm, PTA was carried out with silicone microballoon at 1 atmosphere, 3 times for 10 seconds. Angiography after PTA disclosed significant dilatation at the site of PTA, without any significant dilatation of distal spastic vessels. Papaverine hydrochloride was then infused intra-arterially, which resulted in significant dilatation of distal spastic vessels. Upon histological examination, deformation and some denudation of endothelial cells were noted in the intimal layer. At the site of denudation, attachment of platelets was observed despite generalized heparinization. Internal elastic lamina and the media were also stretched and myocytes were deformed and arranged irregularly. These changes were not uniform all over the vascular walls. We conclude that the prolonged effect of PTA may be caused by mechanical damage of endothelial cells and myocytes, and the nonuniformity of histological changes in vascular wall may be a leading cause of its rupture during PTA.

Angioplasty, Balloon↗

Changes in body core temperatures and heat balance after an abrupt release of lower body negative pressure in humans.

Changes in body core temperature (T(cor)) and heat balance after an abrupt release of lower body negative pressure (LBNP) were investigated in 5 volunteers under the following conditions: (1) an ambient temperature (Ta) of 20 degrees C or (2) 35 degrees C, and (3) Ta of 25 degrees C with a leg skin temperature of 30 degrees C or (4) 35 degrees C. The leg skin temperature was controlled with water perfusion devices wound around the legs. Rectal (T(re)), tympanic (T(ty)) and esophageal (T(es)) temperatures, skin temperatures (7 sites) and oxygen consumption were measured. The intensity of LBNP was adjusted so that the amount of blood pooled in the legs was the same under all conditions. When a thermal balance was attained during LBNP, application of LBNP was suddenly halted. The skin temperatures increased significantly after the release of LBNP under all conditions, while oxygen consumption hardly changed. The release of LBNP caused significant falls in T(cor)s under conditions (1) and (3), but lowered T(cor)s very slightly under conditions (2) and (4). The changes in T(es) were always more rapid and greater than those of T(ty) and T(re). The falls in T(ty) and T(re) appeared to be explained by changes in heat balance, whereas the sharp drop of T(es) could not be explained especially during the first 8 min after the release of LBNP. The results suggest that a fall in T(cor) after a release of LBNP is attributed to an increase in heat loss due to reflexive skin vasodilation and is dependent on the temperature of venous blood returning from the lower body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Isolation and characterization of Streptoverticillium anticoagulant (SAC), a novel protein inhibitor of blood coagulation produced by Streptoverticillium cinnamoneum subsp. cinnamoneum.

Three Streptoverticillium anticoagulants, SAC I, II, and III, which strongly inhibit human intrinsic blood coagulation, were each isolated in a homogeneous form from a culture fluid of Streptoverticillium cinnamoneum subsp. cinnamoneum IFO 12852. SAC I, II, and III are simple proteins with molecular weights of around 12,000, and with isoelectric points of 9.7, 9.7, and 9.9, respectively. Their amino acid compositions are similar and each SAC possesses two disulfide bonds. The COOH-terminal residue of each of these proteins is phenylalanine. Together with the similarity of their protein chemical properties, the results of NH2-terminal amino acid sequence analysis of these SAC proteins strongly suggested that the deletion of Ser-Leu and Ser-Leu-Tyr from the NH2-terminus of SAC I (Ser-Leu-Tyr-Ala-Pro-...) results in the generation of SAC II and III, respectively. The amount of each SAC necessary to double the partial thromboplastin time was around 5 micrograms/ml. SAC I inhibited activated human factor XII and human plasma kallikrein. It also inhibited, but to a lesser extent, activated factor X. The inhibition constants (Ki) of SAC I toward activated factor XII and plasma kallikrein were 5.3 x 10(-8) and 7.2 x 10(-9) M, respectively. The SACs also inhibited some microbial serine proteases such as subtilisin Carlsberg and, to a lesser extent, mammalian serine proteases including bovine trypsin and alpha-chymotrypsin. Of these three inhibitors, only SAC I inhibited metalloproteases such as thermolysin in addition to these serine proteases.

Amino Acid Sequence↗

Primary structure and reactive site of Streptoverticillium anticoagulant (SAC), a novel protein inhibitor of blood coagulation produced by Streptoverticillium cinnamoneum subsp. cinnamoneum.

The complete amino acid sequence of SAC I, a novel protein inhibitor of blood coagulation produced by Streptoverticillium cinnamoneum subsp. cinnamoneum IFO 12852, was determined. Automated Edman degradation was employed for its fragment peptides, which were obtained by specific cleavage procedures including tryptic, chymotryptic, and peptic digestions, and cyanogen bromide treatment. SAC I is composed of 110 amino acid residues with a molecular weight of 11,642. It has two intramolecular disulfide bonds, Cys31-Cys46 and Cys68-Cys98, but no cysteine residues. The overall sequence homology of SAC I is 58% to plasminostreptin, a protein protease inhibitor produced by Streptomyces antifibrinolyticus, and 52% to S-SI, Streptomyces subtilisin inhibitor, produced by Streptomyces albogriseolus. Subtilisin [EC 3.4.21.14]-modified SAC I, which was prepared by incubating SAC I with subtilisin, had a newly-generated amino terminal sequence, Glu71-Trp72-Asn73-, in addition to the original amino terminal sequence, and a newly-generated carboxyl terminal arginine in addition to the original phenylalanine. These results clearly show that the Arg70-Glu71 bond was specifically cleaved on the limited proteolysis with subtilisin and that the bond is the relative site for subtilisin.

Amino Acid Sequence↗

Improved method of preparation of inflated-fixed lung for radiologic-pathologic correlation.

The technique of inflation and fixation of the lung with polyethylene glycol is useful for specimen radiography and radiologic-pathologic correlation, but it is limited by poor histologic staining of the fixed tissue. To improve staining we used formalin to distend and fix the lung before standard fixation with a polyethylene glycol mixture. In this preliminary study, canine and infant lungs, and lungs from three cases of lung cancer were examined. The modified technique provided high-quality staining and satisfactory specimen radiography in all cases except one of the lung cancers; in this case excessive shrinkage occurred and degraded radiographic quality. We conclude that the new method of preparation permits both specimen radiography and high quality staining of the fixed tissue.

Adult↗

von Recklinghausen's disease with diencephalic syndrome in an adult. Case report.

The case of a 39-year-old man with von Recklinghausen's disease, presenting with emaciation and a marked increase in serum growth hormone concentration, is presented. Neuroradiological and histological examination confirmed anaplastic astrocytoma in the optic chiasm-hypothalamic region. This is a rare case of diencephalic syndrome and von Recklinghausen's occurring together in an adult.

Adult↗

Remarkable elevation of interleukin 6 and interleukin 8 levels in the bone marrow serum of patients with rheumatoid arthritis.

OBJECTIVE: Characteristic cellular changes have previously been reported in the bone marrow of patients with rheumatoid arthritis (RA). We investigated the levels of various cytokines in RA bone marrow. METHODS: We studied 25 patients with RA (22 women and 3 men) and 10 trauma patients (7 women and 3 men) as non-RA controls. Twelve kinds of cytokines [interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor, tumor necrosis factor (TNF)-alpha, and TNF-beta] were assayed by ELISA in iliac bone marrow serum (BMS), tibial BMS, and peripheral blood serum. RESULTS: Markedly elevated levels of IL-6 and IL-8 were detected in iliac BMS, and much lower levels were found in tibial bone marrow and peripheral blood serum. The levels of IL-6 and IL-8 in iliac BMS showed a close relationship to the extent of synovial proliferation. CONCLUSION: Iliac bone marrow may be an important site for the production or accumulation of IL-6 and IL-8 in RA, and these cytokines may influence synovial proliferation in patients with polyarthritis.

Adult↗

Phenotypic characteristics of bone marrow cells in patients with rheumatoid arthritis.

OBJECTIVE: Our previous study showed the presence of abnormal myeloid lineage cells in the epiphyseal bone marrow adjacent to joints affected with severe rheumatoid arthritis (RA). Now, we investigated whether there were any changes of other marrow cell populations related to RA, and whether there were any pathologically characteristic changes in the iliac bone marrow, which is one of the major systemic hematopoietic organs. METHODS: 2-Color flow cytometry was carried out to analyze the phenotypes of mononuclear cells (MNC) fractions in bone marrow aspirates and venous blood from 56 patients with RA and 7 non-RA controls. RESULTS: The absolute number of MNC in the iliac bone marrow was increased by 3-fold in the RA patients compared with the non-RA controls. In contrast, no significant increase of MNC was observed in the tibial epiphyseal bone marrow or peripheral blood. The ratio of each MNC fraction in the iliac bone marrow did not differ significantly between the RA patients and the non-RA controls. In lymphocyte subsets, the percentage of HLA-DR+CD8+ cells to all CD8 cells in the iliac bone marrow increased significantly in the RA patients compared with the non-RA controls. Abnormal myeloid cells (MX-GA+MY4+ cells), specific to severe RA, were found to be more concentrated in the iliac bone marrow than in the tibial epiphyseal bone marrow. CONCLUSION: Characteristic pathologic changes of the iliac bone marrow suggest an important role of systemic bone marrow in the progression of RA.

Adult↗

[Chagas' disease among blood donors in Bolivia].

A questionnaire survey of blood donors at Santa Cruz General Hospital, Bolivia, showed that while there were no seropositive cases of syphilis, HBsAg, and HIV, the prevalence of Chagas' disease was very high (23%) among the 225 blood donors who responded to this questionnaire. Actual cases of Chagasic seropositive blood being used for blood transfusion were seen, including the urgent need for a program for Chagas' disease in Bolivia. From the results of this study, it is recommended that for blood donors from South American countries, the presence/absence of Chagas' disease should be confirmed.

Adolescent↗

Effect of acute lung injury and coexisting disorders on plasma concentrations of atrial natriuretic peptide.

OBJECTIVE: To clarify how plasma atrial natriuretic peptide concentrations vary with the severity of acute lung injury. The influence of coexisting diseases which trigger acute lung injury was also examined. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Fifty patients who had standard risk factors for acute lung injury including sepsis syndrome, major surgery, prolonged hypotension, aspiration of gastric contents, and burns. Twenty-five of these patients had acute lung injury (group 3) caused by these disorders; the remaining 25 patients had risk factors only (group 2). Ten age-matched normal volunteers were selected as controls (group 1). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Plasma atrial natriuretic peptide concentration was measured in these patients and compared with the severity of acute lung injury. In group 3, a significant increase in the mean plasma atrial natriuretic peptide concentration was observed (188 +/- 78 pg/mL, p < .01) compared with group 2 (54 +/- 28 pg/mL) and the age-matched control group (30 +/- 8 pg/mL). This increase was related to the onset of acute lung injury and returned to control concentrations after recovery. Plasma atrial natriuretic peptide concentrations in group 3 correlated highly with a lung injury score representing the severity of acute lung injury (r2 = .45, p < .01), but did not correlate with other cardiopulmonary variables. CONCLUSION: The results suggest that severity of lung injury, but not other predisposing disorders, may be the key factor leading to the increase in plasma atrial natriuretic peptide concentrations observed in these patients.

Analysis of Variance↗

[anorexia nervosa; an association with certain types of soft tissue emphysema].

A 17-year-old female with anorexia nervosa developed pneumomediastinum, subcutaneous emphysema, retroperitoneal emphysema, interstitial pulmonary emphysema and epidural emphysema (epidural emphysema; air between the dura mater and the vertebral arch). She had no history of bronchial asthma. The mechanism was presumed to be weakness of the alveolar wall due to malnutrition, leading to rupture of alveoli, followed by air entering the interstitium and dissecting along perivascular sheaths (interstitial pulmonary emphysema) into the mediastinum. A further increase in mediastinal pressure may bring about opening of the fascial planes along great vessels and allow air to penetrate into subcutaneous tissues and the spinal canal. These types of emphysema have been reported in bronchial asthma cases and in those on positive pressure breathing. To our knowledge, there are no previous reports of anorexia nervosa associated with these phenomena.

Adolescent↗