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Biomedical subjects

S Misawa

Publications and source records attributed to S Misawa.

At least 145 records · Page 8Linked to original sources
PubMed1994

[B-lymphoma arising in the temporal muscle].

B cell lymphoma arising in skeletal muscle is described with the review of literature. A 72-year-old man visited our hospital on September 21st 1992, because of a right temporal mass which had grown gradually since one year previously. A CT scan and MRI showed a soft tissue mass adjacent to the temporal muscle expanding from the right temporal to infratemporal fossa. Physical examination on admission revealed that the mass at the right temporal region, was non-tender, elastic soft, and 5 x 2 cm in diameter. Some elastic hard masses at the right infraauricular region, approximately 1.5 x 1.2 cm in diameter, were also found. Histological examination of a biopsied specimen obtained from the temporal mass revealed B cell lymphoma, diffuse medium-sized cell type. Tests for surface markers using tumor cell suspension showed positive results for CD5, CD19, CD20, SmIg mu, delta, lambda, but negative for CD10. Chromosomal analysis revealed clonal aberrations, and the defining karyotype as 51, X, +X, -Y, +2, +3, +4, +8, +12. The patient achieved a complete remission after treatment with combination chemotherapy including doxorubicin, cyclophosphamide, vincristine, etoposide, vindesine, procarbazine, and prednisolone.

Aged↗
PubMed1994

[Clinical effects of a combination treatment with fosfomycin and clavulanic acid/ticarcillin for infections in patients complicated with hematological disorders].

We evaluated clinical effects and toxicities of a combination of fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) for treatment of infections complicated with hematological disorders in 61 patients. Fifty-eight patients were evaluable, including 40 with acute leukemia, 13 with malignant lymphoma and 5 with other hematological disorders. Clinical efficacies were excellent in 21 cases, good in 13 cases, fair in 2 cases and poor in 22 cases. The efficacy rate was 58.6% (34 cases/58 cases). This treatment was also effective in 12 of 20 cases in which granulocyte counts were less than 500/microliters through the course of administration. No subjective side effects were observed. Abnormal values in laboratory tests were noted in 1 case. Mild elevations of GOT and GPT were observed. Thus, the combination of FOM and CVA/TIPC is an effective and safe regimen for the treatment of infections in patients complicated with hematological disorders.

Adolescent↗
PubMed1994

N-ras mutation and karyotypic evolution are closely associated with leukemic transformation in myelodysplastic syndrome.

We performed a longitudinal analysis of the karyotypes and N-ras gene configuration of bone marrow cells in 35 patients with myelodysplastic syndrome (MDS). Karyotypic evolution was found in eight patients, and was associated with disease progression, including leukemic transformation, in all the patients. We identified N-ras mutations in six patients, using a polymerase chain reaction (PCR) technique, in which oligonucleotide primers were constructed with induced mismatches, followed by endonuclease digestion. Direct sequencing confirmed single base substitutions at codon 12 in two patients and at codon 13 in four. The incidence of N-ras gene mutations was significantly higher in the karyotypically evolved group (five of eight patients) than in the stable group (one of 27 patients). All of five patients harboring both karyotypic evolution and an N-ras mutation showed concomitant disease progression to overt leukemia or refractory anemia with excess of blasts in transformation (RAEB-T). Two of four patients with either karyotypic evolution or N-ras mutation and six of 26 patients without any of these alterations also progressed to overt leukemia. Our results indicate that the accumulation of these genetic alterations is closely associated with leukemic transformation of MDS, although other genetic alterations may also play a key role in the remaining patients.

Adult↗
PubMed1994

Pressor effect of recombinant human erythropoietin: results of home blood pressure measurements in hemodialysis patients.

We investigated whether the treatment of anemic hemodialysis patients with a low dose of recombinant human erythropoietin (rHEpo) for a short period would increase the blood pressure (BP). Home BP measurements were used to detect minute increases in BP. Fifty-one anemic patients on maintenance hemodialysis with a hematocrit of 25% or less received rHEpo at the dose of 4500 IU/week by the intravenous route for 8 weeks. Overall, rHEpo did not increase the BP whether measured at home or in the clinic (causal BP). Hemoglobin concentration increased significantly from 7.1 +/- 0.7 to 8.8 +/- 0.7 g/dl. Patients were classified into two groups according to the change in mean (M) home BP induced by rHEpo: a pressor group (delta MBP > or = 5 mmHg, n = 17) and a non-pressor group (delta MBP < 5 mmHg, n = 34). The hemoglobin concentration rose significantly in both groups, but there was no change in casual BP. Home blood pressure measurements showed a gradual and continuous rise in BP in the pressor group, but not in the non-pressor group. Patients administered antihypertensive medications before rHEpo treatment accounted for 88% of the former and 50% of the latter groups. Two patients with malignant nephrosclerosis were included in the pressor group. The findings indicate that rHEpo, even given at a low dose for a short period, elevates the BP, as determined by home BP measurement, but not by casual measurements obtained in the clinic.

Adult↗
PubMed1994

[Translocation t(11;14) (q13;q32) in six patients with lymphoid malignancies of mature B-cell phenotype].

We described six patients with t(11;14)(q13;q32) in lymphoid malignancies. Based on the histologic or morphologic findings of these patients, malignant lymphoma diffuse large cell (ML-DL) was diagnosed in two patients, small lymphocytic (SL) in one, mantle zone lymphoma (MZL) in one, prolymphocytic leukemia (PLL) in one, and chronic lymphocytic leukemia with > 10% prolymphocytes (CLL/PL) in one. Three cases showed involvement of the gastro-intestinal tract, and four were leukemic. Five cases were dead 12 to 25 months after the time of chromosomal analysis. Immunological studies revealed that all the patients were positive for CD5, CD20, HLA-DR, and only one was weak positive for CD10. Using probe b, SstI-Sst I segment, Southern blot analysis showed the rearrangement of BCL-1 gene in a patient with MZL. Our results suggested that t(11;14) is found in lymphoid malignancies with mature B-cell phenotype and that hepatosplenomegaly, gastrointestinal involvement, leukemic manifestation, and poor prognosis are common clinical features.

Aged↗
PubMed1994

Analysis of mutations and expression of GAP-related domain of the neurofibromatosis type 1 (NF1) gene in the progression of chronic myelogenous leukemia.

We investigated mutations in the GTPase activating protein-related domain of the neurofibromatosis type 1 gene (NF1-GRD) and its expression in each phase of chronic myelogenous leukemia (CML). Samples from 45 cases in chronic phase (CP), 41 in acute phase, and four CML cell lines were examined for mutations in the NF1-GRD by single-strand conformation polymorphism (SSCP) analysis and allele specific restriction analysis (ASRA). No mutations were detected in the exon where frequent mutations have recently been reported in human tumors, namely the FLR exon. We also examined for point mutations of the N-ras gene but found no mutations either. In 23 samples from CML cases and four CML cell lines, expression of two types of the NF1-GRD transcripts, type I and type II, were examined by NF1-GRD-specific polymerase chain reaction-based densitometric analysis and by the quantitative assay with coamplification of the NF1-GRD and beta-actin transcripts. Consequently, although expression level of type I transcripts varied among the samples, type II expression was increased in CML cell lines and a minor increase in type II expression was observed in the samples in acute phase compared with CP. However, this difference in type II expression between CP and acute phase was so small that changes of NF1-GRD transcripts as well as NF1-GRD or N-ras mutations might not be responsible for the progression of CML.

Alleles↗
PubMed1993

CX-397, a novel recombinant hirudin analog having a hybrid sequence of hirudin variants-1 and -3.

To elucidate the differential roles of N- and C-terminal halves of hirudins in thrombin inhibition, we produced novel recombinant hirudin analogs, CX-397 and CX-397R, having a hybrid amino acid sequence of hirudin variants-1 (HV-1) and -3 (HV-3). CX-397 is composed of the N-terminal half of HV-1 (HV-11-36) combined with the C-terminal half of HV-3 (HV-337-66). CX-397R is the opposite combination. Their anti-thrombin activity was determined by a fluorogenic enzyme assay and compared with that of recombinant HV-1 (rHV-1) and rHV-3. The order of the magnitude of dissociation constants (Ki) of these four hirudin analogs in thrombin inhibition was as follows: CX-397R (0.294 pM) > rHV-1 (0.148 pM) > rHV-3 (0.0593 pM) > CX-397 (0.0433 pM), indicating that CX-397 is the strongest inhibitor among them.

Amino Acid Sequence↗
PubMed1993

Effects of cicletanine on the urinary excretion of prostanoids and kallikrein, and on renal function in man.

The effects of cicletanine, a new antihypertensive agent, on the prostaglandin-kallikrein system and the renin-angiotensin system were studied. A single oral dose of 200 mg cicletanine or placebo was administered to 9 healthy male volunteers, with samples of blood and urine obtained before and 2 hours after drug administration. Cicletanine increased the urine flow, urinary excretion of sodium, and fractional excretion of sodium by 47%, 115%, and 104%, respectively. While the excretion of 6-keto-prostaglandin-F1 alpha was enhanced significantly, urinary excretion of thromboxane-B2, prostaglandin-E2, and kallikrein were unchanged. Cicletanine also did not alter plasma renin activity, plasma aldosterone concentration, or creatinine clearance. These observations suggest that cicletanine may suppress sodium reabsorption at the nephron, and it may stimulate prostacyclin generation with no effect on that of thromboxane-A2. Thus cicletanine may be beneficial in the management of cardiovascular disorders in which the equilibrium between prostacyclin and thromboxane is disturbed.

Administration, Oral↗
PubMed1993

Effects of paraquat on Mg(2+)-ATPase activity in rat liver.

Intraperitoneal injection of paraquat (70 mg/kg) elicited a significant decrease of 20% in activity of Mg(2+)-ATPase in hepatic mitochondria, which is always surrounded by a high concentration of oxygen, in rats. The decrease of mitochondrial Mg(2+)-ATPase activity was completely abolished by pretreatment with vitamin E, which is a scavenger of oxygen radicals. On the other hand, paraquat administration did not change the Mg(2+)-ATPase activity in endoplasmic reticulum, which exists in an anaerobic condition in living cells. When liver microsomes were incubated with 1 mM paraquat under aerobic conditions, the Mg(2+)-ATPase activity was decreased by 42%. The decrease of Mg(2+)-ATPase activity was completely eliminated by pretreatment with vitamin E. Furthermore, lipid peroxidation in microsomes was tremendously increased by the addition of 1 mM paraquat under aerobic conditions. The increase of lipid peroxidation was completely abolished by preadministration of vitamin E in rats. The results suggest that the inhibition of Mg(2+)-ATPase activity induced by paraquat may be mediated by active oxygen, which is produced by the reaction of paraquat radicals; molecular oxygen may be involved in the induction of hepatic cell injury.

Animals↗
PubMed1993

Trimethadione metabolism as a probe drug to estimate hepatic oxidizing capacity in rats.

1. Trimethadione (TMO) has the properties required of probe drugs for the evaluation of hepatic oxidizing capacity in vivo. 2. TMO is demethylated to dimethadione (DMO), its only metabolite, in the liver after oral administration. 3. In rats with various types of hepatic intoxicated-, induced- and partially hepatectomized-rats, the serum DMO/TMO ratios, which were measured on blood samples obtained by a single collection 2 hr after oral administration of TMO, correlated well with the degree of hepatic damage or induction. 4. This finding suggests that TMO may be used as a probe drug in the rapid determination of the functional reserve mass of the liver as well as the hepatic oxidizing capacity.

Animals↗
PubMed1993

Hypotensive effect of losartan, a nonpeptide angiotensin II receptor antagonist, in essential hypertension.

We examined the chronic effects of losartan (DuP 753), a novel orally active angiotensin II receptor antagonist, on blood pressure and renal function in eight hospitalized patients with essential hypertension. After a control period of 1 week, losartan was administered orally once a day for 2 to 4 weeks in increasing doses of 12.5, 25, 50, and 100 mg, until blood pressure in the supine position decreased more than 20 mm Hg (systolic) and 10 mm Hg (diastolic) (or 13 mm Hg in mean blood pressure). The average dose of losartan was 59.4 +/- 43.7 (mean +/- SD) mg/day. Systolic, diastolic, and mean blood pressures, according to 24 h monitoring, fell significantly, from 151.9 +/- 6.8 to 137.2 +/- 7.9 mm Hg, from 90.6 +/- 3.7 to 81.0 +/- 3.7 mm Hg, and from 111.1 +/- 4.6 to 99.7 +/- 5.0 mm Hg, respectively (mean +/- SE, P < .01 for each), with no change in circadian rhythm or variability of blood pressure. Reduction in blood pressure was slightly greater during daytime than during sleep time. Unlike peptide angiotensin II antagonists, losartan did not exert pressor action. No significant alterations were observed in body weight, serum electrolytes, creatinine clearance, urine volume, or urinary excretion of sodium. Losartan significantly lowered serum uric acid concentration from 5.5 +/- 0.4 to 4.8 +/- 0.3 mg/dL (P < .05). Urinary excretion of uric acid increased significantly from 498.9 +/- 64.4 to 540.6 +/- 66.6 mg/day (P < .05). Plasma renin activity rose significantly but plasma aldosterone concentration did not change with the losartan treatment. These results suggest that losartan has a long-acting hypotensive effect with a hypouricemic action in essential hypertension.

Adult↗
PubMed1993

Chemical modification by polyethylene glycol of the anti-tumor enzyme arginine deiminase from Mycoplasma arginini.

Amino acid-degrading enzymes are known to inhibit the growth of tumor cells in culture by depleting amino acids in the medium. Here we demonstrate that arginine deiminase (EC 3.5.3.6) from Mycoplasma arginini had stronger growth-inhibitory activity against all 4 kinds of tumor cell lines tested than L-asparaginase and arginase, which are well-known anti-tumor enzymes. Next, chemical modification of the arginine deiminase molecule with polyethylene glycol was shown to enhance its potency as an anti-tumor enzyme. The percentage of modified amino groups per molecule was estimated to be 51% of the total amino groups, and the average molecular weight was estimated to be about 400,000 by gel-filtration HPLC. The enzymic activity of the modified enzyme was 25.5 units/mg protein, which was equivalent to 57% of that of the native enzyme. The modified enzyme strongly inhibited growth of a mouse hepatoma cell line, MH134, at a concentration of more than 10 ng/ml, showing almost the same dose-response curve as the native enzyme. When a bolus of 5 units of the modified enzyme was intravenously injected into male BDF1 mice, L-arginine in the blood completely disappeared within 5 min, and remained undetectable for more than 8 days. On the other hand, in the case of bolus injection of the same number of units of native enzyme, the plasma L-arginine level recovered up to 66% of the control level at 8 days. These results suggest that this modified enzyme has a longer plasma clearance time and may be more effective as a new anti-tumor agent than the native enzyme.

Animals↗
PubMed1993

[Clinical effects of a combination treatment with cefodizime and minocycline for infections in patients complicated with hematological disorders].

We evaluated clinical effects and toxicities of a combination in treatment with cefodizime (CDZM) and minocycline (MINO) for infections complicated with hematological disorders in 67 patients. Fifty-nine patients were evaluable, including 32 with acute leukemia, 15 with malignant lymphoma, and 12 with other hematological disorders. Clinical efficacies were excellent in 17 cases, good in 24 cases, fair in 2 cases, and poor in 16 cases. The efficacy rate was 69.5% (41 cases/59 cases). This treatment was also effective in 8 of 12 cases in which granulocyte counts were less than 500/microliter through the course of administration. No subjective side effects were observed. Abnormal values in laboratory tests were noted in 5 cases. Mild elevations of GOT, GPT, Al-P and bilirubin were observed, but none was serious. Thus, the combination of CDZM and MINO is an effective and safe regimen for the treatment of infections in patients complicated with hematological disorders.

Adult↗
PubMed1993

[Efficacy of fluconazole on systemic mycosis associated with hematologic malignancies and a study on diagnostic value of plasma beta-D-glucan levels].

Efficacy of fluconazole (FLCZ), an anti-fungal agent of triazole derivatives, was evaluated in patients with systemic mycoses and suspected mycoses associated with hematologic malignancies including leukemia, myelodysplastic syndrome and malignant lymphoma. Plasma beta-D-glycan levels, the differences between the levels determined toxicolor test and in endospecy test, were also investigated. Fourteen patients with systemic mycoses and 31 patients with suspected mycotic infections were treated with intravenous administration of FLCZ at a daily dose of 400 mg. Excellent to good responses were observed in 4 of the 14 patients (28.6%) with definitive diagnosis of mycosis, and in 18 of the 31 patients (58.1%) with suspected fungal infections, with an overall efficacy rate of 48.9% (22/45). Levels of plasma beta-D-glycan correlated well with efficacies of FLCZ in 19 of 30 patients. In several cases, however, plasma beta-D-glucan levels were low during the entire course of treatment. Even in 10 cases of definite mycosis, 4 cases showed low levels of plasma beta-D-glucan (below 15 pg/ml by repeated determinations). The results indicate that FLCZ is an effective agent for the treatment of severe systemic fungal infections in patients with hematologic disorders. Deep seated mycosis cannot be ruled out even when its plasma levels of beta-D-glucan are low.

Adolescent↗
PubMed1993

Establishment and characterization of a human neuroblastoma cell line derived from a brain metastatic lesion.

We encountered a case of abdominal primary stage IV neuroblastoma which recurred in the central nervous system. A neuroblastoma cell line, designated KP-N-NS, was established from this brain metastatic lesion. This is considered to be the first neuroblastoma cell line established from a brain metastatic lesion. In culture, KP-N-NS exhibited N(neuroblastic) type cell morphology with neurite-like processes and small cell bodies. This cell line revealed karyotypic abnormality, 46, XX, -1, +der (1)t(1;?)(p36.1;?), and twelve-fold amplification of MYCN DNA (twice as much in primary bone marrow tumor cells). Integrin study indicated high expression levels of alpha 1 beta 1 and alpha 4 beta 1, but alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1, alpha 6 beta 4, and alpha v beta 3 were barely detectable by fluorescence-activated cell sorting (FACS) analysis. Compared with 8 other previously established N-type neuroblastoma cell lines, no significantly characteristic integrin expression was detected in this cell line. KP-N-NS will provide a useful tool for the study of metastasis and relapse in the central nervous system in neuroblastoma patients.

Brain Neoplasms↗
PubMed1993

Changes in hepatic copper distribution leading to hepatitis in LEC rats.

Copper (Cu) accumulating in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats due to a hereditary metabolic disorder is assumed to cause acute hepatitis with severe jaundice or chronic hepatitis leading to cancer. Changes in concentrations and distributions of Cu, zinc and iron in the liver of LEC rats were determined to find the relationship between the chemical forms and the toxicity. Female rats after delivery were used because of high susceptibility to acute hepatitis. They were divided into four stages according to the development of jaundice. Cu concentrations in the whole liver and the supernatant decreased with development of jaundice. Distribution profiles of Cu, zinc, iron and sulfur on a gel filtration column by HPLC-ICP showed that Cu in the liver supernatant was mostly bound to metallothionein (MT) before jaundice (stage 1), high molecular weight proteins and MT at the beginning of jaundice (stages 2 and 3), and then mostly to MT at severe jaundice (stage 4) though the concentration of Cu at this stage was decreased to about 50% of stage 1. The results suggest that Cu accumulating as MT in the liver is liberated drastically after exceeding the capacity of MT synthesis, and the liberated Cu causes acute hepatitis.

Animals↗
PubMed1993

Changes in copper distribution in the plasma and kidneys of LEC rats following acute hepatitis.

Copper (Cu) accumulating bound to metallothionein (MT) in the liver of LEC (Long-Evans with cinnamon-like coat color) rats due to a hereditary metabolic disorder is assumed to lead to acute hepatitis with severe jaundice. The metal was shown to be present in the liver in a form not bound to MT at the beginning of hepatitis after first delivery and lactation. Following this change in the distribution of Cu from MT-bound to non-MT bound form in the liver, changes in the concentrations and distributions of Cu, zinc (Zn) and iron in the plasma and kidneys of LEC rats were also observed. Cu plasma distribution on a gel filtration column by HPLC-ICP revealed that the holo-form of ceruloplasmin (Cp) was present before hepatitis and increased with its development, indicating the availability of Cu for Cp by hepatitis. Cu-binding proteins migrating at the same retention times as those of hepatic Cu-MT and Cu,Zn-superoxide dismutase (SOD) were detected in plasma during hepatitis. Albumin was largely present in the form of nonmercaptoalbumin, reflecting that the bloodstream was under oxidative stress. A sudden increase in the concentration of Cu in the kidneys occurred with hepatitis, and the metal came to be distributed more to high molecular weight proteins with its development.

Acute Disease↗