Search PubMed⌕ Search

Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 739 records · Page 41Linked to original sources
PubMed1993

Late rupture of left ventricular true aneurysm after acute myocardial infarction.

Left ventricular (LV) free wall rupture complicated with acute myocardial infarction (AMI) usually occurs in the early phase of AMI. True aneurysm of the LV is sometimes a complication of AMI but rarely ruptures. In our patient, a 72-year-old woman, the LV free wall ruptured on Day 49 after the onset of AMI and the ruptured site was the thinnest wall of large true aneurysm of the LV. The large aneurysmal formation probably was due to corticosteroids used for pericarditis. More attention should be paid to late cardiac rupture and the use of corticosteroids.

Adrenal Cortex Hormones↗
PubMed1993

[A clinicopathological study of a patient with paraneoplastic limbic encephalitis, myelitis, sensory neuropathy and cerebellar degeneration, associated with a unique antineuronal antibody].

Clinicopathological and immunohistochemical studies were performed in a patient with paraneoplastic limbic encephalitis, myelitis, sensory neuropathy and cerebellar degeneration secondary to small cell lung cancer. A 67-year-old male smoker developed orthostatic dizziness 6 months prior to admission. Over the following months, his wife noticed that he became forgetful and confused. Over the next three weeks, he became unable to sit or stand unaided and admitted to our service. On admission, he was lethargic and disoriented in time and place. Neurological examination revealed marked limb weakness with distal dominant muscle atrophy. A chest radiograph demonstrated a mass in the right middle lobe and a bronchial biopsy revealed a small cell carcinoma. CT scan and MRI of the brain revealed abnormalities in the bilateral medial temporal lobes and putamen. He was treated with anti-cancer chemotherapy, but died of respiratory failure after 13 months illness. Postmortem examination showed a mass in the right middle lobe of the lung. No tumor metastases were noted in the nervous tissue. Microscopical examinations of the nervous system revealed neuronal loss, astrogliosis and perivascular and parenchymatous lymphocytic infiltration in the hippocampus, subiculum, amygdala, putamen, medulla oblongata, spinal cord and dorsal root ganglia. Loss of Purkinje cells was also seen in the cerebellum without lymphocytic infiltration. Immunohistochemical analysis of the patient's serum and CSF by the use of adult rat brain revealed immunoreactivity at the hippocampal pyramidal neurons CA3 and CA4. At the higher dilution, neuronal nuclei were specifically stained.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[In vivo autoradiographic benzodiazepine receptor imaging with 125I-iomazenil (Ro 16-0154)].

The biodistribution of 125I-Iomazenil (Ro 16-0154), a benzodiazepine receptor antagonist, was examined using in vivo autoradiography of gerbil brain. 125I-Iomazenil was administrated i.v. into male gerbils, and autoradiography was prepared from coronary sections of the animals decapitated at 5, 60, 120 and 180 min after injection. Initial uptake images (5 min) of 125I-Iomazenil were thought to show blood flow distribution. On the images obtained 120-180 min after administration, high activity of 125I-Iomazenil was observed in the cerebral cortex, amygdala, hippocampus, globus pallidus, thalamus, hypothalamus, superior colliculus, substantia nigra and cerebellar cortex in the areas of which benzodiazepine receptor concentration was reported to be high. However, low activity was observed in the caudate-putamen. Accumulation of 125I-Iomazenil was blocked by pre-administration of flumazenil. 123I-Ro 16-0154 has a high potentiality for benzodiazepine receptor mapping by SPECT.

Animals↗
PubMed1993

[Combination therapy of high dose doxifluridine (5'-DFUR)+mitomycin C (MMC) for advanced or recurrent colorectal cancer. Joint Research Group in the Osaka Area for Combination Therapy of 5'-DFUR with Other Drugs].

A co-study was conducted on treatment with high dose 5'DFUR+MMC in order to determine its effectiveness as a systemic chemotherapy in patients with advanced and recurrent colorectal cancers. The treatment schedule included 5'-DFUR given orally at a dose of 1,600 mg/body/day for five consecutive days, a two-day discontinuation, then repeated medication with the above, and MMC injected intravenously at a dose of 6 mg/m2 once every four weeks. One course consisted of four weeks, and courses were repeated as long as tolerated by the patients. Twenty-nine patients were registered for the study and 28 cases were perfectly capable of anti-tumor responses. The response rate was 25.5%, including: CR, 2; PR, 5; NC, 11; and PD, 10 cases. Responding cases were found in metastases to the lung, cervical lymph node and abdominal wall. Response rate was especially high in pulmonary metastases at 41.7% (5/12 cases). The slight side effects were mostly gastrointestinal in nature and did not necessitate drug discontinuance. The results suggest that treatment with high dose 5'-DFUR+MMC is useful for advanced and recurrent colorectal cancers, especially those with pulmonary metastases.

Administration, Oral↗
PubMed1993

[Effect of intra-venous hyperalimentation on hepatic energy metabolism after hepatic resection in the cirrhotic rat].

We evaluated experimentally the effect of administration of glucose on hepatic energy metabolism, mitochondrial functions and lipid metabolism after hepatic resection. The 75% hepatic resection was performed on thioacetamide induced cirrhotic rat. Glucose solution with 30 Cal/kg/day (group I) or 200 Cal/kg/day (group II) was administrated intravenously for 48 hours after hepatic resection. Blood levels of ketone bodies and glucagon, tissue activities of ATP synthesis and tissue content of adenine nucleotides were measured in both groups. Hepatic energy charge was significantly decreased in group II, comparing with group I. When fatty acid was used as a substrate for respiratory system, the activity of ATP synthesis on mitochondria after hepatic resection rose, while in case pyruvate was used as a substrate the value was declined. On the levels of serum free fatty acids and ketone bodies, there were no remarkable changes in group I, while in group II, obvious declines were investigated. It is suggested that the overload of glucose in the early stage after hepatic resection is unfavorable to hepatic energy metabolism because of decline of serum free fatty acid by hyperinsulinemia and suppression of fatty acid oxidation by decline of blood glucagon.

Animals↗
PubMed1993

Hypotensive effects and influence on serum lipids of SQ29,852, a new angiotensin converting enzyme inhibitor, in patients with essential hypertension: a comparison with atenolol.

The effects of SQ29,852 (n = 24), a new angiotensin converting enzyme inhibitor, and atenolol (n = 22), monotherapies were compared in 46 patients with mild to moderate essential hypertension. Both SQ29,852 (mean dose 15.0 +/- 5.1 mg/day) and atenolol (mean dose 37.5 +/- 18.5 mg/day) significantly decreased both systolic and diastolic blood pressures. There were no significant changes in serum lipids, apolipoproteins, lipoproteins or atherosclerotic indices after both SQ29,852 and atenolol. There were also no significant inter-group differences. There were no serious side effects or abnormal laboratory tests in both treatment groups. It is concluded that SQ29,852 is an effective antihypertensive drug without adverse effect on lipid metabolism.

Adult↗
PubMed1993

[A study of crossed cerebellar diaschisis on 123I-IMP SPECT images and its redistribution phenomenon].

Crossed cerebellar diaschisis (CCD) is interpreted as a functional deactivation, presumably caused by a loss of excitatory or inhibitory afferent inputs on the corticopontocerebellar pathway and others. A redistribution phenomenon (RD) is usually observed in the contralateral cerebellum with CCD on delayed images of 123I-IMP SPECT. This phenomenon was analyzed in a view point of rCBF measurement in 24 patients with brain tumor, infarction and so forth. Regional CBF was measured by the microsphere method with 123I-IMP and a delayed-to-early counts ratio (D/E ratio) was used. As a result, there was no relation between rCBF and the D/E ratio in the cerebellum, which means that RD is occurred by other factors except for rCBF in the cerebellum. Regional CBF and the D/E ratio in the contralateral and ipsilateral cerebellum was 46.3 ml/100 g/min, 1.01 and 57.0 ml/100 g/min, 0.86, respectively. These results mean that the high activity of IMP gradually decreased in the ipsilateral cerebellum, while, the low activity in the contralateral cerebellum was almost stable, and the difference of both activity reduced after 5 hours and RD was observed on the delayed image. The data indicate that retention mechanism of IMP and vascular permeability are not affected in the cerebellum with CCD.

Adolescent↗
PubMed1993

[Clinical significance of micromegakaryocytes in de novo AML].

Bone marrow specimens obtained from 54 patients with de novo AML and 7 patients with AML evolving from MDS were retrospectively examined for the presence of micromegakaryocytes defined as cells of less than 30 microns in diameter with one or two nuclei. At least 25 megakaryocytes were counted in each patient. Micromegakaryocytes were found in 17 cases (31%), M1:1/11, M2:5/18, M3:0/4, M4:5/12, M5:1/4, M6:4/4, M7:1/1. The median age of the patients was higher in de novo AML with micromegakaryocytes (57 years) than in de novo AML without micromegakaryocytes (41 years) (p = 0.014). Chromosomal analysis revealed that deletion of 5 or 5q-, 7 or 7q- was recognized only in the group of de novo AML with micromegakaryocytes and that t(15;17), t(8:21) and inv (16) were not recognized in this group. Micromegakaryocytes were identified in each bone marrow specimen obtained from 9 of 10 patients with de novo AML with trilineage myelodysplasia. The complete remission rate was significantly lower in de novo AML with micromegakaryocytes (33%) than in de novo AML without micromegakaryocytes (86%) (p = 0.001). The duration of survival of the patients with de novo AML with micromegakaryocytes was shown to be shorter than that of the patients with de novo AML without micromegakaryocytes (p = 0.017). Micromegakaryocytes were recognized in all of 7 patients with AML evolving from MDS. The presence of micromegakaryocytes in bone marrow of the patients with AML indicates a subset of AML with poor prognosis that may be closely associated with myelodysplastic syndrome.

Adolescent↗
PubMed1993

Unilateral conjugate gaze palsy due to a lesion of the abducens nucleus. Clinical and neuroradiological correlations.

We report a case of left-sided horizontal gaze palsy, ipsilateral adduction weakness, and left peripheral facial weakness, all of which indicate the lesion in the left median pontine tegmentum. The enhanced MRIs revealed a discrete left median pontine tegmental lesion, involving the abducens nucleus, MLF, and facial nerve knee. This lesion spared the area of the left PPRF. Among these structures, the area of the abducens nucleus seems to be responsible for the unilateral horizontal gaze palsy. We are not aware of any previous precise neuroradiological documentation of unilateral paralysis of conjugate gaze due to a lesion of the abducens nucleus by sagittal and horizontal MRIs.

Aged↗
PubMed1992

Thrombin-induced human platelet aggregation is inhibited by protein-tyrosine kinase inhibitors, ST638 and genistein.

We have investigated the involvement of protein-tyrosine kinases in thrombin-induced aggregation of human platelets, using ST638 and genistein which are known inhibitors of protein-tyrosine kinase. Preincubation of platelets with 50 microM of ST638 or 25 micrograms/ml of genistein completely blocked the platelet aggregation induced with 0.05 unit/ml of thrombin. The increase of protein-tyrosine phosphorylation bands (135-, 124-, 76-, 64-, and 60-kDa) induced with thrombin was also inhibited by these inhibitors in a dose-dependent manner. These inhibitors also blocked the platelet aggregation and protein-tyrosine phosphorylation induced with thrombin in aspirin-treated platelets. Increase of the intracellular Ca2+ concentration induced by thrombin was also inhibited by higher concentrations of genistein. These results suggest that the protein-tyrosine phosphorylation plays a certain role in platelet activation having some relation to the intracellular Ca2+ concentration.

Amino Acid Sequence↗
PubMed1992

Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein.

A novel trypsin-like protease associated with rat bronchiolar epithelial Clara cells, named Tryptase Clara, was purified to homogeneity from rat lung by a series of standard chromatographic procedures. The enzyme has apparent molecular masses of 180 +/- 16 kDa on gel filtration and 30 +/- 1.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Its isoelectric point is pH 4.75. Studies with model peptide substrates showed that the enzyme preferentially recognizes a single arginine cleavage site, cleaving Boc-Gln-Ala-Arg-4-methylcoumaryl-7-amide most efficiently and having a pH optimum of 7.5 with this substrate. The enzyme is strongly inhibited by aprotinin, diisopropylfluorophosphate, antipain, leupeptin, and Kunitz-type soybean trypsin inhibitor, but inhibited only slightly by Bowman-Birk soybean trypsin inhibitor, benzamidine, and alpha 1-antitrypsin. Immunohistochemical studies indicated that the enzyme is located exclusively in the bronchiolar epithelial Clara cells and colocalized with surfactant. An immunoreactive protein with a molecular mass of 28.5 kDa was also detected in airway secretions by Western blotting analyses, suggesting that the 30-kDa protease in Clara cells is processed before or after its secretion. Proteolytic cleavage of the hemagglutinin of influenza virus is a prerequisite for the virus to become infectious. Tryptase Clara was shown to cleave the hemagglutinin and activate infectivity of influenza A virus in a dose-dependent way. These results suggest that the enzyme is a possible activator of inactive viral fusion glycoprotein in the respiratory tract and thus responsible for pneumopathogenicity of the virus.

Amino Acid Sequence↗
PubMed1992

Inhibition of the acidification of endosomes and lysosomes by the antibiotic concanamycin B in macrophage J774.

The antibiotic concanamycin B was found to inhibit oxidized-low-density-lipoprotein(LDL)-induced accumulation of lipid droplets in the macrophage J774 at a concentration of 5-10 nM. Concanamycin B inhibited cholesteryl-ester synthesis from [14C]oleate by 50% at 14 nM without affecting the synthesis of triacylglycerol and polar lipids. Degradation of internalized oxidized 125I-LDL was inhibited by about 80% in cells treated with 25 nM concanamycin B, while cell-surface binding of oxidized 125I-LDL at 4 degrees C, uptake of surface-bound oxidized 125I-LDL and microsomal acyl-CoA:cholesterol acyltransferase activity were not significantly affected by the antibiotic at 25 nM. When J774 cells were treated with 25 nM concanamycin B at 37 degrees C for 60 min, there was a reduction of about 50% in the activity of cell-surface receptors. This reduction appeared to be due to partial trapping of the receptors within the cells. Concanamycin B significantly inhibited ATP-dependent acidification of endosomes and lysosomes of the J774 cells at a concentration of 4 nM. Since acidic condition of these organelles is required for receptor recycling and hydrolysis of lipoproteins, the results demonstrate that concanamycin-B inhibition of oxidized-LDL-induced accumulation of lipid droplets and cholesteryl esters in macrophages J774 is associated with reduced ATP-dependent acidification of these organelles.

Adenosine Triphosphate↗
PubMed1992

Concentrations and molecular forms of human brain natriuretic peptide in plasma.

Using a highly sensitive radioimmunoassay (RIA) system for human brain natriuretic peptide (BNP), immunoreactive (ir-) human BNP was found to be present in plasma, in addition to heart and brain tissue. Plasma concentrations of ir-BNP were 0.17-0.74 fmol/ml (mean: 0.35 fmol/ml) in normal young men, being about 1/17 of the plasma concentration of human atrial natriuretic peptide (ANP). In patients with heart disease, plasma concentration of ir-BNP increased about 100-fold (5.00-177.37 fmol/ml), being nearly comparable to that of ir-ANP, even though ANP concentration also increased about 7-fold. Two molecular forms of ir-BNP in plasma were identified as BNP-32 and gamma-BNP (pro-BNP), which are also found in cardiac atrium. In normal human plasma, gamma-BNP is the predominant molecular form, while the main form in cardiac atrium is BNP-32. These results suggest that biosynthesis and secretion of BNP are augmented in heart disease and that human BNP has a unique processing and metabolic system distinct from that of ANP.

Chromatography, Affinity↗
PubMed1992

Inhibition of the accumulation of lipid droplets in macrophage J774 by bafilomycin B1 and destruxin E.

Two microbial metabolites, bafilomycin B1 and destruxin E, have been found to inhibit significantly the oxidized low density lipoprotein (LDL)-induced accumulation of lipid droplets at 3 nM and 0.5 microM, respectively, in macrophage J774. The incorporation of [14C]oleate into cholesteryl esters in the cells incubated with oxidized LDL was inhibited to the same extent by the two compounds. Both compounds had no effect on the cell surface binding at 4 degrees C and the internalization of oxidized 125I-LDL as well as on the activity of acyl-CoA:cholesterol acyltransferase. However, when incubated with these compounds at 37 degrees C, receptors for oxidized LDL were partially trapped within the cell. In accordance with receptor accumulation, ATP-dependent acidification of endosomes and lysosomes was significantly inhibited by 50 nM bafilomycin B1 and 1 microM destruxin E, respectively. From these results it was concluded that the inhibition of ATP-dependent acidification of endosomes and lysosomes by bafilomycin B1 and destruxin E resulted in the reduction of oxidized LDL-induced synthesis of cholesteryl ester and thereby caused a reduced accumulation of lipid droplets in macrophage J774.

Animals↗
PubMed1992

Occurrence of an allosteric transition in the modification of papain with L-1-acetyl-2,3-dihydropyrrolo[2,3-b]-indole-2-carboxamide.

When papain was reacted with L-1-acetyl-2,3-dihydropyrrolo[2,3-b]indole- 2-carboxamide at pH 8.0, inactivation occurred accompanied by modification of Cys-25 in the active site. Plots of pseudo first-order rate constants against the reagent concentrations yielded an anomalous sigmoidal curve, suggesting that papain responded to this reagent in an allosteric manner. This is supported by the fact that the presence of a moderate concentration (a twenty-fold molar excess) of N alpha-acetyl-L-tryptophanamide over papain accelerated the inactivation.

Amino Acids↗
PubMed1992

AlgR2 is an ATP/GTP-dependent protein kinase involved in alginate synthesis by Pseudomonas aeruginosa.

The exopolysaccharide alginate is a major virulence factor in the pathogenicity of Pseudomonas aeruginosa infecting the lungs of cystic fibrosis (CF) patients. Alginate synthesis by P. aeruginosa is believed to occur in response to environmental signals present in the CF lung. Transcription of a critical alginate biosynthetic gene, algD, is triggered by environmental signals and is known to be controlled by regulatory proteins AlgR1, AlgR2, and AlgR3. AlgR1 is a member of the family of response regulators of the phosphorylation-dependent two-component bacterial signal transduction systems. In this report, we describe the characterization of AlgR2 as the kinase involved in phosphorylation of AlgR1. AlgR2, an 18-kDa soluble protein undergoes rapid autophosphorylation in the presence of either ATP or GTP and transfers the phosphate to AlgR1. AlgR2 retains high affinity for both ATP and GTP with an apparent Km of 137 and 249 nM, respectively, for phosphorylation by these two substrates. ADP and GDP exhibit competitive inhibition with an apparent Ki of 94 and 314 nM, respectively, during phosphorylation by ATP and 481 and 273 nM during phosphorylation by GTP. AlgR1 and AlgR2 can be isolated in the form of an 80-kDa complex that is capable of undergoing phosphorylation and intracomplex phosphotransfer in vitro. A 16-kDa AlgR2 analog, capable of autophosphorylation in the presence of ATP or GTP and transferring the phosphate moiety to AlgR1, has been characterized in Escherichia coli.

Adenosine Triphosphate↗