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Biomedical subjects

M Sakai

Publications and source records attributed to M Sakai.

At least 181 records · Page 10Linked to original sources
PubMed1999

[Usefulness and safety of intravenous thrombolytic therapy for elderly patients with acute myocardial infarction: relationship with cardiac rupture].

The usefulness and safety of intravenous thrombolytic therapy were investigated in 298 patients older than 65 years (145 males, 153 females, mean age 78 years) with acute myocardial infarction from 1984 to 1993. These patients were divided into 2 groups of 88 patients younger than 74 years (Group A) and 210 patients older than 75 years (Group B). Seventy patients received thrombolytic therapy with urokinase (UK) or tissue-plasminogen activator [t-PA (UK96 X 10(4)U: 57 patients, t-PA 30-40 X 10(4)U/kg: 12, UK + t-PA: 1)] within 6 hours after the onset of acute myocardial infarction (Group TL). Two hundred twenty-eight patients received conventional therapy (Group C). There were no differences in the frequencies of the site of myocardial infarction, Killip class, admission within 6 hours after the onset of acute myocardial infarction or thrombolytic therapy between the 2 age groups. In-hospital mortality was significantly higher in Group B than in Group A (43% vs 24%, p < 0.01). In Groups A and B, in-hospital mortality was 20% lower in Group TL compared with Group C (20% vs 25% in Group A, 36% vs 45% in Group B). In Group B, the mortality from pump failure including shock and congestive heart failure was half in Group TL compared with Group C (13% vs 30%). Cardiac rupture was found in 11 patients of Group TL and 7 patients of Group C. Therefore, the mortality from cardiac rupture was fivefold higher in Group TL compared with Group C (8% vs. 1.6% in Group A, 20% vs 3.6% in Group B). Of 11 patients with cardiac rupture in Group TL, 8 patients suffered rupture in the early phase within 12 hours after the onset of acute myocardial infarction and the tear was present near the center of infarcted area in all 7 autopsy cases. The case of recanalization of the infarct-related coronary artery in Group TL revealed moderate to massive hemorrhagic infarction at autopsy. This indicates that the mechanisms involved in cardiac rupture are different in thrombolytic therapy and conventional therapy. Intravenous thrombolytic therapy is effective for the reduction of mortality from pump failure in elderly patients with acute myocardial infarction older than 75 years. However, it must be evaluated as one of the risk factors of cardiac rupture in elderly patients.

Age Factors↗
PubMed1999

[Metastatic endometrial sarcoma of the right ventricular outflow tract associated with disseminated intravascular coagulopathy].

A case of myocardial metastasis of endometrial sarcoma to the right ventricular outflow tract is described. A 56-year-old woman was admitted with ecchymoses of lower limbs in September in 1995. Laboratory findings included thrombocytopenia and an increase of fibrinogen degradation products due to disseminated intravascular coagulopathy (DIC). Transesophageal echocardiography (TEE) demonstrated a large mass both in the right ventricular outflow tract and the proximal pulmonary artery. The mass was excised including base of the stalk. Cryoablation was employed on the endocardium where the stalk was originated. With pathological examination, the mass was identified to be endometrial sarcoma. The patient achieved an uneventful recovery and DIC was improved dramatically in a week after operation. Thirty-three months after the surgery, she has been well and free from local recurrent tumor.

Disseminated Intravascular Coagulation↗
PubMed1999

[Evaluation of cranial CT findings of patients with muscular dystrophy: with a reference to cerebral vascular disease and cardiac complications].

We evaluated cranial CT findings of 160 patients with various type of progressive muscular dystrophy (PMD). Significant brain atrophy was observed in 21 out of 63 cases of Duchenne muscular dystrophy (DMD), 7 out of 15 Becker muscular dystrophy (BMD), no case of 2 female dystrophinopathy (F-dyst), 11 out of 21 limb-girdle muscular dystrophy (LG), all cases of 10 Fukuyama type congenital muscular dystrophy (FCMD), 2 out of 5 fascioscapulohumeral muscular dystrophy (FSH), and 32 out of 44 myotonic dystrophy (MyD). Genetical degenerative process and vascular insufficiency seemed to cause brain atrophy in these disease. The intracranial calcification was observed in one DMD, one LG and seven MyD. One LG patient showed focal atrophy in left temporal lobe, and one MyD demonstrated right temporal meningioma. The trace of cerebral vascular accident was disclosed in eleven patients with PMD (1 DMD, 2 BMD, 1 F-dyst, 2 LG, 5 MyD). In these cases, 2 patients had dilated cardiomyopathy, 6 patients with decreased left ventricular ejection fraction, 3 with atrial fibrillation, 1 with cardiac arrest followed by pacemaker instillation, 1 with Adam-Stokes attack, and 3 with 1 degree AV-block. Diffuse low density in the white matter was seen in a patient with F-dyst, a FCMD patient, and 8 MyD patients. Cardiac emobolism, severe arrythmia, cardiogenic shock and hemodynamic disorder were seemed to cause cerebral vascular disease in PMD.

Adult↗
PubMed1999

[An autopsy case of amyotrophic lateral sclerosis/parkinsonism-dementia complex with family history and living history in the Kii Peninsula focus].

The patient was 68 year-old woman with an 8-year history of parkinsonism which was followed by psychiatric symptoms and neurogenic amyotrophy 5 years after the onset. She had a family history of parkinsonism associated with dementia in all of her three siblings. They grew up in Hobara village, a focus of amyotrophic lateral sclerosis (ALS) in the Kii Peninsula of Japan, in their childhood. Their parents were neither consanguineous nor natives of the Kii Peninsula. The brain weight was 1,040 g, and there were mild frontal lobe atrophy, moderate atrophy of pes hippocampi, decoloration of the substantia nigra and locus ceruleus, and anterior spinal root atrophy. The microscopic examinations revealed degeneration of CA 1 portion of the hippocampus to parahippocampal gyrus, substantia nigra, locus ceruleus and spinal anterior horn with Bunina body. The spinal pyramidal tracts also degenerated mildly. The neurofibrillary tangles (NFT) were observed in the cerebral cortex, especially in the cortices through hippocampus to lateral occipitotemporal gyri, basal nucleus of Meynert, basal ganglia, thalamus, substantia nigra and widespread regions of the central nervous system through the brainstem to the spinal cord including the nucleus of Onufrowicz. In spite of a few amount of the senile plaques in the cerebral cortex and Lewy bodies in the substantia nigra and locus ceruleus, abundant NFT distributed mainly in the third layer of the cerebral cortex, which is the characteristic finding of amyotrophic lateral sclerosis/Parkinsonism-dementia Complex (ALS/PDC) in the island of Guam. Thus this was verified ALS/PDC case outside the Guam island. The high incidence of neurological disease in her siblings and their history of living in the focus region in childhood suggest the genetic factor of ALS/PDC which is sensitive to certain environmental agents in the early stage of the life.

Aged↗
PubMed1999

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer].

A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.

Adenocarcinoma↗
PubMed1998

Genetic analysis of protein C deficiency in nineteen Japanese families: five recurrent defects can explain half of the deficiencies.

We have been studying the molecular basis of protein C deficiency. In this study, we determined the molecular defects of protein C deficiency in 19 Japanese families by using a strategy combining polymerase chain reaction (PCR) and single-strand conformational polymorphism (SSCP) analysis. We identified 10 missense mutations, 1 in-frame deletion, 1 frameshift deletion, 1 frameshift addition, and 1 splice site mutation, 5 of which were novel. From the results of genetic analysis of 67 Japanese families with protein C deficiency reported in this and previous studies, the recurrent defects including Phe139Val and Met365Ile substitutions and a Lys150 d letion, a G8857 deletion, and a splice site mutation of G3079A were only found in Japanese subjects and seemed to be a founder effect. In contrast, Arg169Trp, Arg286His, Val297Met, and Asp359Asn substitutions, all occurring at CG dinucleotides, were commonly observed in not only Japanese but also Western populations, indicating that these are hot spots for mutation in the protein C gene. These 9 recurrent molecular defects were found in 43 families in total, accounting 64% of Japanese families with protein C deficiency. In particular, the recurrent defects of Phe139Val, Arg169Trp, Va1297Met, and Met36-4Ile substitutions and a G8857 deletion were found in 33 families in total, accounting for 49% of Japanese families with protein C deficiency. For the identification of the genetic defect in Japanese patients with protein C deficiency, screening of these recurrent defects by using restriction enzyme cleavage is a rational method.

Exons↗
PubMed1998

Induction of murine macrophage growth by oxidized low density lipoprotein is mediated by granulocyte macrophage colony-stimulating factor.

We have examined whether certain secreted factor(s) is involved in oxidized low density lipoprotein (Ox-LDL)-induced murine macrophage growth. An antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) effectively inhibited Ox-LDL-induced macrophage growth by >80%. Ox-LDL as well as phospholipase A2-treated acetylated LDL enhanced mRNA levels and protein release of GM-CSF from macrophages, while neither acetylated LDL nor lysophosphatidylcholine (lyso-PC) showed such effects. The maximal induction of GM-CSF by Ox-LDL was noted at 4 h, followed by a time-dependent decrease to a basal level within 24 h. Ox-LDL-induced macrophage growth was inhibited by 75% by replacement of the culture medium at 24 h by a fresh medium containing the same concentration of Ox-LDL, when GM-CSF had already returned to the basal level. Thus, a cytokine(s) other than GM-CSF is also expected to participate in Ox-LDL-induced macrophage growth in a later phase. The Ox-LDL-induced GM-CSF release was inhibited by calphostin C, a protein kinase C inhibitor, and was significantly reduced in macrophages from the knockout mice lacking class A, type I and type II macrophage scavenger receptors (MSR-AI/AII). These results taken together indicate that effective endocytosis of lyso-PC of Ox-LDL by macrophages through MSR-AI/AII and subsequent protein kinase C activation have led to GM-CSF release into the medium which may play a priming role in conjunction with other cytokines in Ox-LDL-induced macrophage growth.

Animals↗
PubMed1998

Anti-emetic effects of a novel NK-1 receptor antagonist HSP-117 in ferrets.

We have developed a non-peptide compound, HSP-117, antagonist of the tachykinin NK-1 receptor. Binding of 3H-substance P (SP) to the membranes of IM-9 cells was inhibited by the antagonists HSP-117 and CP-99,994, the inhibitory activity of HSP-117 being about 50-fold that of CP-99,994. The SP-induced firing responses of single neuron activity in slices of the nucleus tractus solitarius of ferrets were inhibited by 10 microM HSP-117. Intracerebroventricular injection of HSP-117 significantly inhibited retching and vomiting induced by copper sulphate and morphine and the inhibitory effect of HSP-117 on emesis was greater than that of CP-99,994. These results indicate that (1) HSP-117 is a potent anti-emetic agent, blocking NK-1 receptors in the nucleus tractus solitarius and (2) NK-1 receptors in the nucleus tractus solitarius play an important role in emesis induced by broad-spectrum emetic stimuli.

Animals↗
PubMed1998

Complete sequence and gene organization of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3.

The complete sequence of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3, has been determined by assembling the sequences of the physical map-based contigs of fosmid clones and of long polymerase chain reaction (PCR) products which were used for gap-filling. The entire length of the genome was 1,738,505 bp. The authenticity of the entire genome sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2061 open reading frames (ORFs) were assigned, and by similarity search against public databases, 406 (19.7%) were related to genes with putative function and 453 (22.0%) to the sequences registered but with unknown function. The remaining 1202 ORFs (58.3%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs in the genome provided evidence that a considerable number of ORFs were generated by sequence duplication. By similarity search, 11 ORFs were assumed to contain the intein elements. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 46 tRNA genes including two with the intron structure. All the assigned ORFs and RNA coding regions occupied 91.25% of the whole genome. The data presented in this paper are available on the internet at http:@www.nite.go.jp.

Chromosomes, Archaeal↗
PubMed1998

Electrostatic stabilization in methionine aminopeptidase from hyperthermophile Pyrococcus furiosus.

The thermostability of methionine aminopeptidase from a hyperthermophile P. furiosus (PfMAP) was extremely high: the denaturation temperature was 106.2 degreesC at pH 10.2. To explore the contribution of electrostatic interaction to the superior thermostability of PfMAP, the thermostability of PfMAP was examined by differential scanning calorimetry (DSC) in various salt concentrations in the acidic region far from the isoelectric point of PfMAP. (1) In 20 mM glycine buffer, the DSC curve of PfMAP exhibited a single peak. Transition temperatures (Tm) were lowered with decreasing pH from 4 to 3. The heat denaturation of PfMAP was not reversible. (2) Denaturation enthalpy (DeltaH) measured at different pHs linearly correlated with Tm up to 102 degreesC, suggesting that the denaturation heat capacity (DeltaCp) for PfMAP is constant up to 100 degreesC. DeltaCp was estimated to be 0.82 J K-1 g-1. (3) In the presence of 10-100 mM KCl at pH 3.2, two peaks appeared on the DSC curves. The first peak shifted to lower temperatures with increasing concentration of KCl and, oppositely, the second one to higher temperatures. It was found that the first and second peaks originated from the heat denaturation of the native form of PfMAP and the melting of the non-native associated form having molten globule-like structure, respectively, judged from the CD spectra and ultracentrifugation analyses. This indicates the following: first, the attractive electrostatic interaction is an important factor in stabilizing the native form of PfMAP; second, the presence of KCl stimulates the formation of the molten globule-like state of PfMAP and stabilizes it. (4) In a comparison of the sequence and crystal structure of PfMAP, which has been recently determined (1xgs.pdb), with those of MAP from Escherichia coli (EcMAP), it was predicted that the extra four short-range ion pairs less than 3 A involved in PfMAP are crucial candidates as determinants for the superior thermostability of PfMAP.

Aminopeptidases↗
PubMed1998

Rat maf-related factors: the specificities of DNA binding and heterodimer formation.

maf is a family of genes encoding bZIP transcription factors. We isolated two cellular maf-related cDNAs, maf-1 (mafB) and maf-2 (c-maf), from rat and determined the specificities of DNA binding and heterodimer formation. Although both Mafs strongly bind to MARE, the consensus Maf recognition sequence (MARE, -TGCTGACTCAGCA-), originally identified by v-Maf protein Maf-1, recognizes a number of sequences containing only the first half of the MARE, -GCTGAC-. On the other hand, no such consensus short sequence could be determined for Maf-2. We determined the specificities of heterodimer formation with all members of the Jun and Fos family. In contrast to v-Maf which forms heterodimers with all Jun and Fos proteins, Maf-1 heterodimerizes with all four Fos proteins, but not at all with the three Jun proteins. Maf-2 heterodimerizes with c-Fos. We have also found that heterodimer formation of Maf-2 with c-Fos dramatically changes the specificity of DNA binding and trans-activation activity from that of the Maf-2 homodimer. These results show that Maf-1 and Maf-2 have significantly different properties and they might have different target genes and functions, in spite of the similarity of their bZip domain structure.

Animals↗
PubMed1998

Molecular heterogeneity of Vicia villosa-recognized perineuronal nets surrounding pyramidal and nonpyramidal neurons in the guinea pig cerebral cortex.

Of three monoclonal antibodies (mAbs Cat 301, 1B5 and 473) which recognize epitopes on perineuronal nets (PnNs), only mAb 473 displayed considerably varied degrees of staining intensity on Vicia villosa-labeled pyramidal (P) neurons (5%, intensely; 54%, very weakly; and 41%, unstained). These results indicate the heterogeneity on molecular structure or composition of the terminal N-acetylgalactosamine-containing PnNs within P class as well as between P and nonpyramidal classes.

Animals↗
PubMed1998

Molecular cloning of human D-dopachrome tautomerase cDNA: N-terminal proline is essential for enzyme activation.

D-Dopachrome tautomerase converts 2-carboxy-2,3-dihydroindole-5,6-quinone (D-dopachrome) into 5,6-dihydroxyindole. This protein has an amino acid sequence that is highly homologous with that of macrophage migration inhibitory factor (MIF), which has the potential to catalyze D-dopachrome to 5,6-dihydroxyindole-2-carboxylic acid and is an important cytokine for T-lymphocyte activation. We isolated and sequenced a 566 bp-long cDNA encoding human D-dopachrome tautomerase. The cDNA contains an open reading frame encoding 118 amino acids, including the initiator methionine. The amino acid sequence of the protein shares 80% homology with that of the rat enzyme. Northern blot analysis demonstrated that mRNA of D-dopachrome tautomerase is expressed in a large amount in the liver, and to lesser extent in other organs, including the heart, lung and pancreas. After purification of D-dopachrome tautomerase expressed in E. coli, we confirmed that the recombinant protein catalyzes the conversion of D-dopachrome to 5,6-dihydroxyindole. Its catalytic mechanism is not well understood. We found that the protein completely lost the enzyme activity when the N-terminal proline residue was replaced with alanine by site-directed mutagenesis. This fact suggests that the N-terminal proline is essential for the catalytic mechanism. Although the precise pathophysiological function of D-dopachrome tautomerase remains to be elucidated, the present results could contribute to further understanding of isomerase activity in relation to the immune response.

Amino Acid Sequence↗
PubMed1998

DNA ploidy, proliferative activities, and immunophenotype of malignant lymphoma: application of flow cytometry.

BACKGROUND: To explore the flow cytometric diagnosis of malignant lymphoma, we examined the deoxyribonucleic acid (DNA) ploidy, proliferative activities, and immunophenotype of surgical biopsy- and fine-needle aspiration (FNA)-derived materials. Our goal was to determine the possibility of making a diagnosis of malignant lymphoma by flow cytometric analysis of FNA-derived materials. METHODS: The DNA ploidy and proliferative indices including the percentage of S-phase fraction (SPF), G2 + M fraction (G2M), and Ki-67-positive fraction (Ki-67) were analyzed on the fresh materials from 84 consecutive patients with suspected malignant lymphoma. Flow cytometric analysis of surface antigens was simultaneously performed. Fourteen of the patients underwent FNA and subsequent surgical biopsy of the same lymph nodes for flow cytometric analysis. RESULTS: The proliferative indices of intermediate-grade non-Hodgkin's lymphomas (NHL) (n = 28) and high-grade NHL (n = 23) were significantly higher than those of the reactive hyperplasia (n = 25). The total for SPF + G2M of 6% was a satisfactory threshold for differentiating these NHL from reactive hyperplasia (sensitivity of 84%, specificity of 88%, and accuracy of 86%). However, low-grade NHL (n = 3) and Hodgkin's lymphoma (HL, n = 5) could not be discriminated by employing this parameter. DNA aneuploidy was seen in 13 of the 28 intermediate-grade NHL and 8 of the 23 high-grade NHL, whereas it was not seen in 25 reactive hyperplasia, 3 low-grade NHL, and 5 HL. The percentage of CD19-positive cells in B-cell NHL or CD3-positive cells in T-cell NHL was significantly higher compared with those for reactive hyperplasia. The percentage of CD16 + CD56-positive cells in natural killer (NK) cell NHL was extremely high, with a mean of 91.8%. Flow cytometric results for FNA-derived materials showed excellent correlation with those for surgical biopsy-derived specimens. CONCLUSIONS: Analyses of DNA ploidy, proliferative activities, and immunophenotype by flow cytometry (FCM) are useful for diagnosing intermediate- and high-grade NHL. Fine-needle aspiration is a less invasive approach than surgical biopsy, and, when combined with FCM, it may have a place in the diagnosis of NHL.

Biopsy, Needle↗
PubMed1998

Terminal ileal transposition procedure in ileoanal anastomosis following proctocolectomy.

We introduced a terminal ileal transposition procedure (TITP) in ileal pouch-anal anastomosis, in which a 50 to 70 cm isolated ileal segment 20 to 40 cm from the ileocecal valve was interposed between the terminal ileum and the anus. Twelve patients underwent this procedure in two or three-staged operations. Mean stool frequency per 24 hours was 4.4 +/- 1.7, and stool consistency was formed and soft in all patients at the mean of 13 months after TITP. We observed neither surgical technique-related complications nor metabolic disorders, except for iron deficiency anemia, during and after the operations. The serum level of vitamin B12 significantly increased after the operation in eight patients (P < 0.05). TITP has advantages such as preventing the terminal ileum from metabolic dysfunction due to pouchitis, avoiding sacrifice of the terminal ileum in the two-staged operation, and obviating the need for reconstruction of ileostomy in the three-staged operation. It may also promote intestinal absorption and reduce late metabolic complications.

Adolescent↗
PubMed1998

Upper motor neuron predominant degeneration with frontal and temporal lobe atrophy.

The autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. He showed slowly progressive spasticity, pseudobulbar palsy and character change, and died 32 months after the onset of symptoms. Autopsy revealed severe atrophy of the frontal and temporal lobes, remarkable neuronal loss and gliosis in the precentral gyrus, left temporal lobe pole and amygdala, mild degeneration of the Ammon's horn, degeneration of the corticospinal tract, and very mild involvement of the lower motor neurons. The anterior horn cells only occasionally demonstrated Bunina body by cystatin-C staining, and skein-like inclusions by ubiquitin staining. This is a peculiar case with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease predominantly affecting the upper motor neuron.

Aged↗