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Biomedical subjects

M Sakai

Publications and source records attributed to M Sakai.

At least 541 records · Page 30Linked to original sources

[A case of surgical treatment of Budd-Chiari syndrome].

A 37-year-old man was admitted to our hospital for evaluation and surgical treatment of Budd-Chiari syndrome. He underwent a radical operation (endovenectomy and patch dilatation) with femoro-femoral assist bypass. The inferior vena cava (IVC) showed narrowing just below the diaphragm, and its lumen was completely obliterated with fibrous tissue. The fibrous strand was partially resected, and the IVC was closed by Xeno-medica pericardial patch. The patient has been doing well after the operation.

Adult↗

[Successful treatment of intrapericardial administration of carboplatin in a case of squamous cell lung cancer with malignant pericardial effusion].

A 74-year-old male developed cardiac tamponade due to malignant pericardial effusion six months after he was diagnosed as primary lung cancer. Carboplatin was administered into the pericardial cavity six times with the total dose of 1,100 mg. Pericardial effusion disappeared without severe toxicities and response duration was about three months. Upon recurrence, he was again successfully treated with single intrapericardial administration of 300 mg of carboplatin. He survived for seven months after being diagnosed as cardiac tamponade.

Aged↗

Phenotypic characteristics of T cells interacted with synovial cells.

We demonstrated the phenotypic characteristics of T cells interacted with synovial fibroblast-like cells. A small percentage of peripheral blood T cells adhered to synovial fibroblast-like cells. When synovial cells were treated with interferon-gamma or interleukin-1 beta, the percentage of T cells that adhered to the treated cells markedly increased in comparison with the value for untreated synovial cells. The kinesis of T cell adherence to treated synovial cells differed from that of HLA-DR antigen expression on synovial cells. T cell adherence was not blocked by mouse monoclonal anti-HLA-DR and anti-HLA-ABC antibodies. The phenotypes of the adherent and nonadherent T cells were investigated with a flow cytometer. The CD29 + subset was more adhesive than the CD45RA + subset to IL-1 beta-stimulated synovial cells. The proportions of high density lymphocyte function associated antigen (LFA)-1 alpha and LFA-1 beta were greater in the adherent than in the nonadherent T cells, and the mean fluorescence intensities of LFA-1 alpha, LFA-1 beta and CD2 molecules on adherent T cells were significantly higher than those on nonadherent T cells. Our results support the concept that an interaction between infiltrating lymphocytes and synovial cells occurs in the synovium, resulting in the initiation and perpetuation of immune responses in synovial tissue in rheumatoid arthritis.

Adult↗

[A case of combined septal perforation and cardiac rupture after acute myocardial infarction].

We experienced a rare surgical case of combined septal perforation and cardiac rupture after acute myocardial infarction. The patient was a 78-year-old woman, who had an extensive acute anterior myocardial infarction and underwent emergency PTCR and PTCA successfully. One hour later, she collapsed in a state of electro-mechanical dissociation and was transferred to the operating room. Emergency operation confirmed the diagnosis of free wall rupture of the left ventricle combined with septal perforation, which was successfully repaired. She recovered well during four weeks postoperatively, however she died due to septic shock following pneumonia on 32nd postoperative day. This report describes a clinical features of this rare case, and also reviews another six cases previously reported in the literature.

Aged↗

[Pharmacokinetics of lidocaine in perfused rat liver].

Lidocaine pharmacokinetics were studied using perfused rat livers under several conditions. 1) In the low perfusion group (perfusion rate = 1/2 of control group), the elimination rate constant and clearance of lidocaine in the first phase were reduced, but in the second phase, metabolism of lidocaine was more active than in other groups. 2) High albumin concentration in the perfusate did not significantly affect lidocaine metabolism. 3) Low pH of the perfusate (pH = 7.10) did not affect the metabolism of lidocaine. 4) Acute and chronic liver damage inhibited the lidocaine metabolism, which may be due to decreases in viable hepatocytes, effective hepatic blood flow and mitochondrial P-450. 5) Halothane in the concentration of 2.5% reduced the lidocaine metabolism. This was probably due to inhibition of hepatocyte activity by halothane because increases in GOT, LDH and lactate in the perfusate and a decrease in the O2 consumption by the rat liver were observed.

Animals↗

Thrombolytic properties of staphylokinase.

We evaluated the properties of recombinant staphylokinase in comparison with those of tissue-type plasminogen activator (t-PA) and streptokinase (SK). The presence of fibrin(ogen) fragment FCB-2 in the reaction mixture increased plasminogen activation by staphylokinase more than 20-fold. Such characteristics are similar to those of t-PA. On the other hand, SK was not affected by the presence of FCB-2. The thrombolytic properties of staphylokinase were studied in a system consisting of a radioactive human plasma clot (125I-fibrinogen-labeled) suspended in the circulating citrated plasma. Significant thrombolysis (50% in 3 hours) was obtained with 2 micrograms/mL of staphylokinase and 4.45 micrograms/mL t-PA, as compared with 12 micrograms/mL for SK. The relative molar potency of staphylokinase, calculated from the molecular weight, was about two times more effective than that of SK, but about half of that of t-PA. Systemic fibrinolytic activation and fibrinogen breakdown was not observed with staphylokinase or t-PA, but was observed with SK. The thrombolytic efficiency of staphylokinase, which was calculated as the ratio of the degree of thrombolysis/the degree of fibrinogenolysis, was about five times greater than that of SK, and about half of that of t-PA. These findings suggest that staphylokinase has higher specific thrombolytic properties and lesser fibrinogenolytic properties than those of SK.

Amino Acid Sequence↗

Expression of human glutathione S-transferases in Saccharomyces cerevisiae confers resistance to the anticancer drugs adriamycin and chlorambucil.

Adaptation and resistance to chemicals in the environment is a critical part of the evolutionary process. As a result, a wide variety of defence systems that protect cells against chemical insult have evolved. Such chemical resistance mechanisms appear to play a central role in determining the sensitivity of human tumours to treatment with chemotherapeutic drugs. The glutathione S-transferases (GST) are important detoxification enzymes whose over-expression has been associated with drug-resistance. In order to evaluate this possibility we have expressed the human Alpha-class and Pi-class GST cDNAs that encode GST B1B1 and GST pi in the yeast Saccharomyces cerevisiae. The expression of GST B1B1 or GST pi resulted in a marked reduction in the cytotoxic effects of chlorambucil, a bifunctional alkylating agent, and an anthracycline, adriamycin. These data provide direct evidence that the over-expression of GST in cells can confer resistance to anticancer drugs.

Alkylating Agents↗

Glutathione-S-transferase pi as a determinant of drug resistance in transfectant cell lines.

A series of glutathione S-transferase pi (GST-pi) transfectant cell lines have been constructed in activated c-H-ras-transformed NIH-3T3 cells (pT22-3) by using a pKOneo plasmid and an expression vector containing cDNA for GST-pi with a beta-actin gene promoter. From the wild type pT22-3 cells, two clones were selected and designated RGN1 and RGN2. The degree of overexpression of GST-pi was estimated by Northern and Southern blot analysis to be incrementally higher in RGN2 compared with RGN1. Translation of mRNA was estimated by Western blot analysis using isozyme-specific polyclonal antibodies and confirmed the relative GST-pi levels. Each cell line, including the wild type, expressed alpha and mu class isozymes to the same degree and had similar but negligible expression of the mdr 1 gene. Sensitivity to various anticancer drugs and radiation was estimated by a series of cytotoxicity assays. The data confirmed that GST-pi provided a degree of protection against the toxicity of ethacrynic acid and adriamycin, but sensitivity to alkylating agents such as chlorambucil, melphalan, and cis-platinum was not influenced by GST-pi. Similarly, the response to ionizing radiation was similar for each line. Since the levels of intracellular GSH were also not significantly different, the availability of co-substrate was not a factor in determining response. In creating the GST-pi transfectants, these data establish that while increased isozyme levels can play a role in determining sensitivity to some agents, the protective effect is selective.

Actins↗

Transient tyrosine hydroxylase-immunoreactive neurons in the region of the anterior olfactory nucleus of pre- and postnatal mice do not contain dopamine.

The transient appearance of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons in the anterior olfactory nuclear region of mice was investigated using TH-immunocytochemistry. In this region, a new cell group composed of a small number of neurons immunoreactive to TH was demonstrated for the first time from the embryonic stages of E16-E18. These cells were not shown using antisera against aromatic L-amino acid decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyl-transferase, dopamine or serotonin. TH-IR cells progressively increased in number until birth. After birth the numbers reached maximum at postnatal days 9-12 and decreased until 4 weeks old, and then mostly disappeared at 6 weeks. Only single TH-IR cells were occasionally observed in this brain area of adult mice. Ultrastructurally some of these TH-IR neurons had immature Golgi apparatus, only a few mitochondria and deformed nuclei along with thin cytoplasma. Some other TH-IR cells, however, had mature Golgi apparatus, many mitochondria and a round nucleus more closely resembling mature cells. These neurons do not belong to the dopaminergic neuron system, because they lack dopamine production, and may be tentatively involved in early limbic circuits.

Aging↗

[Experience of perioperative myocardial infarction with graft patency following coronary artery bypass graft surgery].

Coronary artery bypass graft surgery, with current operative mortality rates of one to three percent, is now an accepted treatment for coronary artery disease. However, perioperative myocardial infarction (PMI) is not a rare complication of this procedure, and the precise mechanism of its occurrence is not well elucidated. We experienced a case of 70-year-old man who had transmural hemorrhagic PMI in the distribution of the grafted vessel and died due to low output syndrome in spite of vigorous treatment. All five grafts were found to be well patent at autopsy. In this case, the cause of PMI was supposed to be inadequate intraoperative myocardial protection and reperfusion injury.

Aged↗

Drug resistance to cis-diamminedichloroplatinum (II) in Chinese hamster ovary cell lines transfected with glutathione S-transferase pi gene.

Establishment of Chinese hamster ovary (CHO) cell lines expressing human glutathione S-transferase-pi (GST-pi) was performed after cotransfection of pSV2-neo and human GST-pi cDNA-carrying plasmid p beta actGPi-2. About 30 G418-resistant clones were tested for their expression of GST-pi by Northern blot analysis. Two clones, beta 2-3 and beta 2-5, expressed a significant amount of GST-pi mRNA; and one clone, beta 1-1, that did not was also used for further study. Western blot analysis with anti-GST-pi antibody showed significant increases of GST-pi in beta 2-3 and beta 2-5, but not in beta 1-1. Northern blot analysis with the human GST-pi cDNA probe showed that the increase in the expression of GST-pi-mRNA in beta 2-3 and beta 2-5 was respectively 2- and 4-fold higher than that in beta 1-1. Southern blotting analysis showed that beta 1-1, beta 2-3 and beta 2-5 contained about one copy of the human GST-pi cDNA sequence. beta 2-3 and beta 2-5 were resistant to 1.4- and 3.0-fold higher doses of CDDP than CHO, respectively, but beta 1-1 was not. Increased expression of GST-pi might be associated with CDDP-resistance in CHO cells.

Animals↗

A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells.

We have identified a novel octamer binding factor (Oct-3) in P19 embryonal carcinoma cells. Oct-3, which recognizes the typical octamer motif (ATTTGCAT) as well as the AT-rich sequence TTAAAATTCA, is present in P19 stem cells but disappears when the cells are induced to differentiate by retinoic acid (RA). Cloned cDNA corresponding to Oct-3 encodes a protein of 377 amino acids. Oct-3 has a conserved POU domain, but the remaining part is distinct from other POU domain-containing proteins such as Oct-1 and Oct-2. mRNA of 1.5 kb coding for Oct-3 is abundant in P19 stem cells but is dramatically repressed during RA-induced differentiation. Repression of the 1.5 kb mRNA is rapid and specific to RA. In mouse, oct-3 mRNA is undetectable in all the adult organs examined. The N-terminal proline-rich region of Oct-3, when fused to the DNA binding domain of c-Jun, functions as a transcriptional activating domain. We suggest that Oct-3 is a novel octamer binding transcription factor that is developmentally regulated during mouse embryogenesis.

Amino Acid Sequence↗

Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonic stem cells.

We have recently identified an enhancer, termed GPEI, in the 5'-flanking region of the rat glutathione transferase P gene, that is composed of two imperfect TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive elements (TREs). Unlike other TRE-containing enhancers, GPEI exhibits a strong transcriptional enhancing activity in F9 embryonic stem cells. Mutational analyses have revealed that the high activity of GPEI is mediated by two imperfect TREs. Each TRE-like sequence has no activity by itself but acts synergistically to form a strong enhancer which is active even in the very low level of AP-1 activity in F9 cells. Furthermore, we show that synthetic DNAs containing two perfect TREs in certain arrangements have strong transcriptional enhancing activities in F9 cells and the activity is greatly influenced by the relative orientation and the distance of two TREs.

Animals↗

Lipoma of the esophagus--report of a case and review of the literature.

We report herein, a rare case of esophageal lipoma and review the Japanese literature on this subject. Lipoma of the alimentary tract is relatively uncommon but that of the esophagus is extremely rare with only 17 cases having been reported in Japan. The majority of these cases occurred in the cervical esophagus with the most serious symptom being regurgitation of the pedunculated tumor which lead to asphyxia and death in one case. Only 2 cases occurred in the thoracic esophagus and these tumors were small in size and resected endoscopically. This is the first reported case of an esophageal lipoma being located in the thoracic esophagus which was resected through a thorocotomy. The clinical features of esophageal lipoma are also described herein.

Aged↗

Thymic carcinoid--a case report and review of the literature.

We report herein a case of a patient with thymic carcinoid who was operated on twice and has been followed for 9 years. In 1979, the original tumor was removed through an emergency left thoracotomy incision done for a hemothorax caused by an anterior mediastinal biopsy. Tumor recurrence was found 6 years later and removal carried out through a median sternotomy. The patient has been working and enjoying life following radiation and chemotherapy for a total of 9 years after his first operation. Recurrent thymic carcinoid has been thought to carry a poor prognosis, but this successfully treated case has been followed up for a long time after the removal of his recurrent tumor. We present this case and discuss other such cases reported in the Japanese literature.

Carcinoid Tumor↗

Effects of midazolam on the threshold of lidocaine-induced seizures in the dog--comparison with diazepam.

The anticonvulsive effect of midazolam was compared with that of diazepam in ten dogs. Lidocaine-induced seizure waves on the electroencephalogram were used to observe the suppressive effect of the drugs. Midazolam, 0.2 mg.kg(-1), was found to possess a stronger suppressive effect against lidocaine-induced seizures than the same dose of diazepam. These two drugs showed to possess similar effects on cerebral and systemic circulations and cerebral metabolism during seizures.

Journal Article↗

Interactive alpha- and beta-adrenergic actions of norepinephrine in rat cardiac myocytes.

We investigated the effects of the physiological neurotransmitter norepinephrine on the contractile properties and Ca2+ dynamics of isolated cardiac myocytes, with particular emphasis on possible interactions between alpha- and beta-adrenergic effects. Individual rat ventricular myocytes were electrically stimulated at a frequency of 1 Hz. Norepinephrine (10(-9) to 10(-5) M) increased extent and velocity of shortening and decreased the contraction duration. beta-Adrenergic activation gave a greater enhancement of extent and velocity of shortening than did norepinephrine alone (i.e. alpha plus beta). Neither alpha 1 nor alpha 2 adrenergic activation individually produced a significant impact upon contraction. Using suspensions of myocytes loaded with Quin-2, we also studied resting levels of cytosolic Ca2+ ([ Ca2+]c), the increase of [Ca2+]c due to caffeine-addition (as an index of sarcoplasmic reticulum Ca2+ content) and the subsequent increase in [Ca2+]c due to depolarization with 30 mM K+ (as an index of sarcolemmal voltage-dependent Ca2+ channel activity). Norepinephrine decreased resting [Ca2+]c, increased sarcoplasmic reticulum Ca2+ content and increased Ca2+ channel activity. beta-Adrenergic activation produced the same effect on resting [Ca2+]c and sarcoplasmic reticulum content, but gave significantly greater activation of sarcolemmal Ca2+ channel activity, than did norepinephrine (alpha plus beta). By contrast, alpha-adrenergic stimulation had no effect on resting [Ca2+]c or sarcoplasmic reticulum Ca2+ content. We conclude that beta-mediated effects predominate in the action of the physiological agonist norepinephrine on cardiac myocytes. However, alpha (specifically alpha 1)-adrenergic effects are significant in diminishing the potentiation of the extent and velocity of shortening, and of depolarization-induced entry of Ca2+ into the cell, which is seen on beta-stimulation alone. Thus, there may be an intrinsic feedback effect in the actions of norepinephrine on the cardiac myocyte.

Animals↗

Expression of human alpha-fetoprotein in yeast.

Human alpha-fetoprotein (AFP) was expressed in Saccharomyces cerevisiae, with a plasmid containing the cDNA sequence for human AFP fused with the rat AFP signal peptide. The recombinant AFP was purified from the yeast lysate by DEAE-cellulose and immunoaffinity chromatography. The amino acid composition and the molecular weight of the recombinant AFP were similar to those of hepatoma AFP. N-terminal amino acids sequence analysis indicated that the signal peptide had been processed. The recombinant and hepatoma AFP reacted identically in Ouchterlony immunodiffusion and radioimmunoassay tests. These observations indicated that the yeast recombinant protein had the properties of native AFP.

Amino Acid Sequence↗