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Biomedical subjects

W Sato

Publications and source records attributed to W Sato.

At least 55 records · Page 3Linked to original sources
PubMed1995

Reversal of multidrug resistance by a novel quinoline derivative, MS-209.

MS-209, a novel quinoline derivative, was examined for its reversing effect on multidrug-resistant tumor cells. MS-209 at 1-10 microM completely reversed resistance against vincristine (VCR) in vitro in multidrug-resistant variants of mouse leukemia P388 cells (VCR-resistant P388/VCR and Adriamycin (ADM)-resistant P388/ADM) and human leukemia K562 cells (VCR-resistant K562/VCR and ADM-resistant K562/ADM). MS-209 at 1-10 microM also completely reversed resistance against ADM in vitro in P388/VCR cells, K562/VCR cells, and K562/ADM cells. In ADM-resistant P388 (P388/ADM) cells, however, ADM resistance was only partially reversed at the MS-209 concentrations tested. MS-209 enhanced the chemotherapeutic effect of VCR in P388/VCR-bearing mice. When MS-209 was given p.o. at 80 mg/kg twice a day (total dose, 160 mg/kg per day) with 100 micrograms/kg VCR, a treated/control (T/C) value of 155% was obtained. MS-209 also enhanced the chemotherapeutic effect of ADM in P388/ADM-bearing mice. The most prominent effects were obtained when MS-209 was given with 2 mg/kg ADM, yielding T/C values of 150%-194% for the combined treatment at an MS-209 dose of 200-450 mg/kg. MS-209 inhibited [3H]-azidopine photolabeling of P-glycoprotein efficiently. Furthermore, the accumulation of ADM in K562/ADM cells was increased more efficiently by MS-209 than by verapamil. These results indicate that MS-209, like verapamil, directly interacts with P-glycoprotein and inhibits the active efflux of antitumor agents, thus overcoming multidrug resistance in vitro and in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Detection of neoplastic clone in the hypoplastic and recovery phases preceding acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor delta chain gene.

This study assessed the clonality of hypoplastic and subsequent recovery phases before the development of overt leukemia by molecular genetic analysis. We describe a boy who had transient granulocytopenia and anemia before the development of acute lymphoblastic leukemia (ALL). Initially, his bone marrow was hypocellular with 23.6% of lymphoblastic cells, whereas subsequent marrow after the administration of granulocyte colony-stimulating factor (G-CSF) appeared almost normal without any lymphoblasts. At diagnosis, we found the rearrangement of T cell receptor (TCR) delta gene in the leukemic cell DNA by Southern blot hybridization. The junctional sequence of the V delta 2-D delta 3 recombination of leukemic cells obtained by polymerase chain reaction (PCR) was used for a clonospecific probe. Using the probe, the presence of leukemic clone in the materials before and after diagnosis was examined. We found that the clonospecific probe could detect one leukemic cell in 10,000 normal cells, and we demonstrated the presence of the leukemic clone at the initial hypoplastic and the subsequent recovery phase. The PCR method is very useful to confirm the presence of leukemic clone even in a retrospective analysis using low-quality materials and may be helpful to understand the pathogenesis of a smoldering preleukemic phase.

Bone Marrow↗
PubMed1995

Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease.

Types A and B Niemann-Pick disease (NPD), an autosomal recessive lysosomal storage disorder, are caused by deficiency of acid sphingomyelinase (ASM). The recent identification of mutations in ASM gene causing types A and B NPD has led to the investigation of the phenotypic heterogeneity and the ethnic distribution of this disease, especially in Ashkenazi Jewish population. To characterize the mutations causing NPD in Japanese population, we analyzed the genomic sequence of ASM from a Japanese patient with type A NPD by PCR amplification and sequencing. A new mutation, Y446C, was identified. The authenticity of this lesion was demonstrated by the expression of the Y446C allele in COS-1 cells. No residual ASM activity was detected from the expression of the Y446C.

Amino Acid Sequence↗
PubMed1995

Isolation of cDNA encoding the human liver phosphorylase kinase alpha subunit (PHKA2) and identification of a missense mutation of the PHKA2 gene in a family with liver phosphorylase kinase deficiency.

X-linked liver glycogenosis (XLG) due to liver phosphorylase kinase (PHK) deficiency is the most frequent liver glycogen storage disease. The affected patients present in early childhood with hepatomegaly and growth retardation. We isolated and determined the structure of human liver alpha subunit of PHK (PHKA2) cDNA. The 3705 base pair open reading frame encodes a polypeptide of 1235 amino acid residues, and the deduced amino acid sequence shows 93 and 68% homology to that of rabbit liver alpha subunit of PHK and human muscle alpha subunit of PHK, respectively. We identified a missense mutation, a valine substitution for glycine at amino acid 193, in the PHKA2 gene of a family with XLG.

Amino Acid Sequence↗
PubMed1995

[Milrinone suppresses TNF-alpha and IL-1 beta release in mouse peritoneal macrophages].

Tumor necrosis factor-alpha (TNF-alpha) exerts a wide spectrum of biological activities and contributes to the pathophysiology of septic shock. We studied whether milrinone suppresses TNF-alpha and IL-1 beta releases from mouse peritoneal macrophages. Mouse peritoneal macrophages were stimulated for 18 hr with lipopolysaccharide and different doses of milrinone. TNF-alpha release was suppressed in a dose-dependent fashion with milrinone, reaching half-maximal inhibition at 30 microM. Release of IL-1 beta was not suppressed with 25 microM of milrinone, but it was suppressed with 250 microM of milrinone. We conclude that TNF-alpha release is suppressed by therapeutically administered milrinone.

Animals↗
PubMed1995

[The effect of isoflurane on the secretion of TNF-alpha and IL-1 beta from LPS-stimulated human peripheral blood monocytes].

The cytokines such as tumor necrosis factor and interleukin-1 secreted from macrophages/monocytes proved to play important roles in the pathogenesis of endotoxemia, severe pancreatitis and other surgical injuries. However, it is still unclear how inhalational anesthetic agents influence the secretion of these cytokines from macrophages/monocytes. We investigated the effects of isoflurane on TNF-alpha and IL-1 beta secretions from human peripheral blood monocytes stimulated by lipopolysaccharide. TNF-alpha and IL-1 beta secretions increased after LPS stimulation and this increase was inhibited by isoflurane in dose-dependent fashion. The inhibitory action of isoflurane disappeared between 1 and 3 hours after stopping isoflurane inhalation. We concluded that isoflurane could inhibit TNF-alpha and IL-1 beta secretions from peripheral blood monocytes stimulated by LPS in a dose-dependent fashion and that the inhibitory action of isoflurane was reversible.

Anesthesia, Inhalation↗
PubMed1994

Cardiomyopathy and angiopathy in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.

In four patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) in which mutated mitochondrial deoxyribonucleic acid was seen, hypertrophic cardiomyopathy and angiopathy was demonstrated by echocardiography, dipyridamole stress scintigraphy, and cardiac catheterization. On stress scintigraphy with dipyridamole, three patients showed hypoperfusion in the early image and a "filling-in" pattern in the late image. However, coronary angiography did not demonstrate narrowing of the large vessels in these patients. Light and electron microscopy of endomyocardial biopsy specimens indicated abnormal mitochondria, with marked increase in the number and size of mitochondria in endothelium. Modified Gomori's trichrome staining in biopsied endomyocardial specimens revealed a red-purple deposit similar in appearance of the ragged-red fibers in skeletal muscle, a characteristic finding of mitochondrial disease. Deterioration of complex I in the mitochondrial electron transfer system, which is widely observed in various mitochondrial diseases, appeared in biopsied skeletal muscle of our patients, indicating deficiency of some subunits of complex I. These results indicate that mitochondrial diseases such as MELAS show not only cardiomyopathy but also angiopathy. We speculate that proliferation of mitochondria leads to narrowing of the lumen of arterioles, which might be responsible for the ischemic findings observed scintigraphically.

Adolescent↗
PubMed1994

A mitochondrial tRNA(Leu)(UUR) mutation at 3,256 associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

Enzymatic and molecular analyses were conducted on the muscular tissue of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Significant decreases in activity of complexes I and IV were found and three nucleotide substitutions in the mitochondrial tRNA genes were detected. Two of the substitutions were detected in unaffected members of the family and in some healthy controls. A C-to-T transition mutation at the nucleotide position 3,256 in the mitochondrial tRNA(Leu)(UUR) gene was detected only in the patient and not in unaffected members of the family or 100 healthy controls. The data strongly suggest that this mutation at nucleotide position 3,256 in the mitochondrial tRNA(Leu)(UUR) gene is associated with MELAS.

Adult↗
PubMed1994

[Prostaglandin E1 does not inhibit production of TNF and IL-1 by mononuclear cells after head-neck surgery].

We studied whether human blood mononuclear cells could produce tumor necrosis factor (TNF) and interleukin 1 (IL-1) by surgical stimuli, and if so, prostaglandin E1 (PGE1) could inhibit their increases before and following operation in patients undergoing head-neck surgery. The patients were randomly allocated into 2 groups; no PGE1 infusion group (control group, n = 6) and PGE1 infusion group (PGE1 group, n = 6). PGE1 group was infused intravenously with PGE1 at a rate of 30 ng.kg-1 x min-1 during surgery and at a rate of 10-30 ng.kg-1 x min-1 after surgery. Peripheral blood was withdrawn into heparinized syringes from these patients immediately before surgery and on the 1st postoperative day. Production of TNF on the 1st postoperative day increased 1.5 fold in control group and 1.4 fold in PGE1 group compared with those before surgery. Production of IL-1 on the 1st postoperative day increased 1.7 fold in control group and 1.1 fold in PGE1 group compared with those before surgery. Also, there were no significant differences between 2 groups in both productions of TNF and IL-1. These data indicate that human blood mononuclear cells would produce TNF and IL-1 by surgical stimuli and PGE1 could inhibit their production by surgical stimuli. It also provides evidence that PGE1 does not inhibit the body's defense response to surgical stimuli.

Aged↗
PubMed1994

[Prostaglandin E1 suppresses hypersecretion of antidiuretic hormone induced by surgical stress].

We studied the effects of prostaglandin E1 (PGE1) on decrease in urine output during surgery in patients for radical total hysterectomy under general anesthesia. The patients were randomly allocated into two groups. Five patients (control group) were given no PGE1 and served as control. Seven patients (PGE1 group) were given continuous infusion of PGE1 at a rate of 50 ng.kg-1 x min-1 after first measurement (baseline). Urine output in control group decreased by 68%, but in PGE1 group it did not change from the baseline. Urine sodium and fractional sodium excretion in control group decreased, but in PGE1 group they increased. Creatinine clearance increased from the baseline in both groups. Antidiuretic hormone in control group increased by 30%, but in PGE1 group decreased by 53%. Plasma renin activity, angiotensin I, angiotensin II in both groups increased, and those in the control group were higher than those in PGE1 group. However, aldosterone in the control group was lower than that in PGE1. These results indicate that diuretic effect of PGE1 could be mediated by suppression of antidiuretic hypersecretion induced by surgical stress, inhibition of the action of antidiuretic hormone, and suppression of sodium and water reabsorption in proximal and distal tubules. Also, PGE1 did not directly stimulate renin-angiotensin system.

Adult↗
PubMed1993

Tissue distribution of mutant mitochondrial DNA in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

We analysed the distribution of mutant mitochondrial DNA (mtDNA) with A-to-G substitution mutation of tRNA(Leu)(UUR) in various autopsied tissues from a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). There was no significant difference in the proportion (76-86%) of mutant mtDNA in many tissues, except in the lung and spleen. Unequal partitioning of mtDNA in somatic cells appears less prominent than that in germ cells.

Adult↗
PubMed1993

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) decrease in diastolic left ventricular function assessed by echocardiography.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are known to be associated with cardiomyopathy. Systolic and diastolic left ventricular functions were assessed by M-mode and Doppler echocardiography in four patients with MELAS and in 14 normal controls. The interventricular septal thickness and left ventricular posterior wall thickness were greater (11.0 +/- 1.6 mm vs. 5.8 +/- 0.7 mm and 11.0 +/- 2.2 mm vs. 5.9 +/- 0.8 mm) in patients with MELAS than in a control group. Parameters of systolic left ventricular functions (ejection fraction, shortening fraction, systolic time intervals, and mean Vcf) and left ventricular dimensions were not significantly different between the two groups. To assess the diastolic function, blood flow velocity across the mitral valve was measured by Doppler echocardiography and various indexes were obtained. In patients with MELAS, the impairment of diastolic left ventricular filling was demonstrated by decrease in the following indexes: peak flow velocity in the early passive filling period (E) (0.76 +/- 0.10 m/s vs. 0.94 +/- 0.09 m/s), integrated velocity for total E (10.2 +/- 1.3 vs. 13.0 +/- 0.9), the ratio of E and late atrial filling integrated velocities (1.72 +/- 0.06 vs. 2.49 +/- 0.29).

Adolescent↗
PubMed1993

Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene.

P0, a major structural protein of peripheral myelin, is a homophilic adhesion molecule and maps to chromosome 1q22-q23, in the region of the locus for Charcot-Marie-Tooth neuropathy type 1B (CMT1B). We have investigated P0 as a candidate gene in two pedigrees with CMT1B and found point mutations which are completely linked with the disease (Z = 5.5, theta = 0). The mutations, glutamate substitution for lysine 96 or aspartate 90, are located in the extracellular domain, which plays a significant role in myelin membrane adhesion. Individuals with CMT1B are heterozygous for the normal allele and the mutant allele. Our results indicate that P0 is a gene responsible for CMT1B.

Alleles↗
PubMed1993

[Effects of DbcAMP on tumor necrosis factor and interleukin-1 production in human monocytes].

Recent reports have shown that dibutyryl cAMP (DbcAMP) blocks endotoxin-induced lung injury. To determine whether DbcAMP suppresses the production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in human monocytes, we measured the levels of TNF and IL-1 in response to E. Coli lipopolysaccharide (40 micrograms.ml-1) in vitro. We now show that DbcAMP suppressed dose-dependently the production of TNF in human monocytes, and DbcAMP totally suppressed it at the dose above 5 x 10(-4) M. However, DbcAMP did not suppress the production of IL-1 even at the dose of 5 x 10(-3) M in human monocytes. These data suggest that the productive mechanism of IL-1 may be different from that of TNF. Further, suppression of TNF by DbcAMP may contribute to the beneficial effects in animal models of septic shock or lung injury and this may have clinical implications.

Bucladesine↗
PubMed1992

Isolation and sequence determination of cDNA encoding PMP-22 (PAS-II/SR13/Gas-3) of human peripheral myelin.

A full length cDNA of PMP-22 (PAS-II/SR13/Gas-3) of peripheral myelin has been isolated from a cDNA library of human fetus spinal cord. The clone is 1823 base pairs (bp) in length and contains a 480 bp open reading frame encoding a polypeptide of 160 residues. The deduced amino acid sequence is highly homologous to PMP-22 from bovine (PAS-II), rat (SR13) and mouse (Gas-3).

Amino Acid Sequence↗