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Biomedical subjects

T Katayama

Publications and source records attributed to T Katayama.

At least 127 records · Page 7Linked to original sources

An effective chemotherapy regimen for liver metastasis from retroperitoneal fibrosarcoma: report of a case.

Retroperitoneal fibrosarcoma is a rare disease that has proven difficult to treat due to its high incidence of postoperative local recurrence. We recently experienced a patient in whom retroperitoneal fibrosarcoma was followed by liver metastasis without local recurrence. A 34-year-old woman who initially presented with right upper quadrant pain was found to have a retroperitoneal tumor by diagnostic imaging techniques. Extirpation of the tumor was performed and the histopathological diagnosis was fibrosarcoma. A solitary metastasis was detected in the lateral segment 1 year after this operation and a lateral segmentectomy was carried out; however, a short time later, multiple liver metastases were found. Initially, ethanol injections were given with little effect, following which CYVADIC chemotherapy, consisting of cyclophosphamide, vincristine, farmorubicin, and dacarbazine was administered. An excellent responsiveness without severe toxicity was achieved after five cycles, with a significant reduction in tumor size, being estimated as a complete response. Thus, we consider that this chemotherapy regimen could be a promising mode of treatment for liver metastasis from retroperitoneal fibrosarcoma without local recurrence.

Adult↗

Daily wheel running activity modifies the period of free-running rhythm in rats via intergeniculate leaflet.

The period of free-running rhythms (tau) in rats, as measured using a running wheel, is different from that measured using an Automex. The aim of this work was to examine the effects of lesions of the intergeniculate leaflet (IGL) on the tau of these two activity rhythms. When blind rats were transferred from a cage with a running wheel to a cage without a running wheel, the tau lengthened. The tau of the wheel-running activity was associated with the number of wheel revolutions per day. A complete lesion of the IGL lengthened the tau of the wheel-running activity, and caused a reduction in the number of wheel revolutions per day in all rats. In rats housed in cages without a running wheel, locomotor activity was reduced by IGL lesions, although the tau was unaffected. When IGL-lesioned rats were transferred from a cage with a running wheel to a cage without a running wheel, no further change was observed. These results indicate that the tau is modified by the daily activity of wheel-running, but not by general locomotor activity, and that the IGL may be involved in this modification.

Animals↗

Overinitiation of chromosome replication in the Escherichia coli dnaAcos mutant depends on activation of oriC function by the dam gene product.

The activity of DnaA protein, the initiator of chromosome replication in Escherichia coli, is regulated by adenine nucleotide binding; the ATP-bound form, not the ADP-bound form, is active. DnaAcos is a mutant protein that is insensitive to negative regulation by ADP. Initiation of chromosome replication occurs excessively in the dnaAcos mutant at 30 degrees C, a restrictive temperature for growth. To determine the control factors that act independently of adenine nucleotide binding of DnaA, we analysed suppressors from the dnaAcos mutant isolated by Tn5 insertion mutagenesis. Three of the suppressors carried Tn5 in the aroK or aroB gene, the first two cistrons in the dam operon. Complementation tests revealed that the dam gene is responsible for the suppression. Over-replication of the chromosome was inhibited in the dnaAcos aroK::Tn5 double mutant, and initiation of chromosome replication in the dnaA+ aroK::Tn5 mutant was partially inhibited. The aroK(or B)::Tn5 cells contained DnaA molecules at a level similar to that in the parental aroBK+ strain. Moreover, dnaAcos suppression depended on the function of the seqA gene. Thus, Dam activity positively regulates initiation of chromosome replication in vivo. SeqA function seems to be distinguished from the control of DnaA protein by adenine nucleotide binding.

Adenosine Diphosphate↗

CedA is a novel Escherichia coli protein that activates the cell division inhibited by chromosomal DNA over-replication.

We isolated and characterized a new gene related to the control of cell division regulation in Escherichia coli. At 30 degrees C, the dnaAcos mutant causes over-replication of the chromosome, and colony formation is inhibited. We found that, at this temperature, the dnaAcos cells form filaments; therefore, septum formation is inhibited. This inhibition was independent of SfiA, an inhibitor of the septum-forming protein, FtsZ. To identify factors involved in this pathway of inhibition, we isolated seven multicopy suppressors for the cold-sensitive phenotype of the dnaAcos mutant. One of these proved to be a previously unknown gene, which we named cedA. This gene encoded a 12 kDa protein and resided at 38.9min on the E. coli genome map. A multicopy supply of the cedA gene to the dnaAcos cells did not repress over-replication of the chromosome but did stimulate cell division of the host, the result being growth of cells with an abnormally elevated chromosomal copy number. Therefore, the expression level of the cedA gene seems to be important for inhibiting cell division of the dnaAcos mutant at 30 degrees C. We propose that over-replication of the chromosome activates a pathway for inhibiting cell division and that the cedA gene modulates this division control. In the dnaA+ background, cedA also seems to affect cell division.

Amino Acid Sequence↗

Prognostic factors of hemophagocytic syndrome in adults: analysis of 34 cases.

Hemophagocytic syndrome (HPS) presents with fever, pancytopenia, liver dysfunction and increase in hemophagocytic histiocytes in various organs. Although there are two major classifications of HPS in adults, malignant and reactive histiocytosis, it is often very difficult to distinguish between these disorders. We analyzed the laboratory data of patients with HPS to evaluate prognostic factors. Of 34 patients, 14 survived, and 20 died. The median age of survivors was 29.6+/-11.5 yr significantly younger than those who died (54.7+/-17.8 yr). Twenty patients had no obvious underlying disease, the other 13 had hematological malignancies or viral infections. Comparison of laboratory data revealed that nonsurvivors had significantly lower Hb and platelet values on admission. During treatment, worsening of anemia and thrombocytopenia, increase of transaminase and biliary enzymes were similarly more prominent. Risk factors associated with death were: age over 30 yr, presence of disseminated intravascular coagulation, increased ferritin and beta2-microglobulin, anemia accompanied by thrombocytopenia and jaundice. Our data suggests that patients with HPS and any of these risk factors should be treated aggressively with sufficient chemotherapy and supportive care.

Adolescent↗

Decrease in expression of the master operon of flagellin synthesis in a dnaA46 mutant of Escherichia coli.

We examined the expression of the fliC, fliA and fihD genes in the dnaA46 mutant. In Northern blot analysis, the amounts of fliC, fliA, and flhD mRNA decreased in the dnaA46 mutant growing at 37 degrees C but not at 28 degrees C. The promoter activity of each gene also decreased in this mutant at 37 degrees C. The decrease in expression of the flh D gene was not related to the cAMP-catabolite activator protein (CAP) pathway. We tentatively conclude that DnaA protein is involved in the expression of the flhD gene by a mechanism independent of the cAMP-CAP pathway.

Blotting, Northern↗

Possible therapeutic effect of T-794, a novel reversible inhibitor of monoamine oxidase-A, on post-stroke emotional disturbances, assessed in animal models of depression.

Emotional disturbances, such as lack of motivation or depression, are common after stroke. The drugs mainly used to treat these syndromes in Japan are the cerebral metabolic enhancers whose biochemical and pharmacological profiles are similar to those of antidepressant drugs. In order to examine the possible therapeutic effect of T-794 [(5R)-3-(6-(cyclopropylmethoxy) 2-naphthalenyl)-5-(methoxymethyl) 2-oxazolidone], a new reversible inhibitor of monoamine oxidase (MAO) type A, on those emotional disturbances, its antidepressant activity was compared with those of major cerebral metabolic enhancers in rodents with or without treatment of cerebral ischemia. Oral administration of T-794 potently prevented reserpine-induced ptosis (ED50 = 4.41 mg/kg), akinesia (ED50 = 3.29 mg/kg), and hypothermia (minimum effective dose = 3 mg/kg) in mice. It was at least 3.7, 13.0, and 3.3 times more potent than cerebral metabolic enhancers tested (indeloxazine, bifemelane, amantadine and idebenone) in antagonism of the ptosis, the akinesia, and the hypothermia, respectively. Effect of T-794 was also examined in the behavioral despair test in rats subjected to forebrain ischemia. The ischemia was induced by a combination of bilateral common carotid artery occlusion (15 min) and systemic hypotension (sodium nitroprusside 5 mg/kg, s.c). From 13 d after the surgery, drugs were orally administered twice daily 7 times, and following the last administration rats were assessed for their behavior. T-794 reduced the duration of immobility in the behavioral despair test at 30 mg/kg without affecting spontaneous motor activity, whereas indeloxazine showed no significant effect. Antidepressant-like activity of T-794 was suggested in rodents with as well as those without cerebral ischemia. The results suggest that T-794 may make an important contribution to the treatment of emotional disturbances following stroke.

Animals↗

[Surgical treatment for patients with atypical mycobacteriosis].

We have been conducting surgical therapy for patients with atypical pulmonary mycobacteriosis (AM) since 1965 and have reported on the outcome of this approach to treatment. We have found that chemotherapy is not adequately efficacious against type III Mycobacterium avium complex (MAC), which suggests that surgical intervention may be the optimum approach for MAC. Among MAC patients who were treated surgically at our hospital in the period between 1966 and 1994, 74 cases on whom postoperative follow-up observation was possible served as the subjects of the present investigation. We report here on the outcome of treatment and related problems in these patients. Thirty-nine patients gave positive results for bacterial discharge on smear tests and all were positive on culture. Operation was performed on the right lung in 46 patients and on the left lung in 16. Pneumonectomy was conducted in 10 patients and lobectomy in 20. Other operative modes used included segmental resection in 9, pyothorax in 7, and thoracoplasty in 5 patients. Postoperative bacterial excretion was observed in 15 patients and was persistent bacterial discharge were advanced cases with lesions in another lobe, cases with a past history of tuberculosis, cases of cavitation with lesions on the contralateral side or cases with massive bacterial discharge prior to surgery. Postoperative death occurred in 5 patients: the cause of death was lung cancer in 1 case, serum hepatitis in 1 case, and respiratory failure evidenced by enlarged shadows in 3 cases. These findings pointed to a marked significance of surgical therapy for MAC patients. However, recurrent bacterial discharge has been observed occasionally in some patients even 5 years after surgery. This suggests the need for careful ongoing assessment of the efficacy of surgical therapy and long-term postoperative follow-up.

Adult↗

Identification of the anti-adhesive site buried within the heparin-binding domain of fibronectin.

We recently found that heparin-binding domain 2 (Hep 2) of fibronectin (FN) exhibits cryptic anti-adhesive activity. In order to locate the anti-adhesive site, a number of synthetic peptides which represents the primary structure of the Hep 2 domain were characterized as to their ability to decrease the adhesion of A375SM melanoma cells to FN substrate. Only one peptide (T-E-A-T-I-T-G-L-E-P-G-T-E-Y-T-I-Y-V-I-A-L, residues 1835-1855) (peptide III14-2), which is situated between the previously identified adhesive sites, FN-C/H-I and II, decreased the cell adhesion to FN. Assaying of the anti-adhesive activities of sub-peptides showed that the hydrophobic moiety of peptide III14-2 (underlined sequence) seems to be indispensable for the anti-adhesive activity. These results suggest that anti-adhesive activity is closely associated with the sequence, Y-T-I-V-I-A-L, that is usually buried within the Hep 2 domain structure because of its hydrophobic nature.

Amino Acid Sequence↗

[Tuberculosis in patients with human immunodeficiency virus infection].

Six men (mean age: 36.3 +/- 29 years) infected with the human immunodeficiency virus (HIV), four Japanese and two from Myammar, were admitted to our hospital for treatment of tuberculosis. In five, HIV positivity on serologic testing was first found when tuberculosis was diagnosed. The mean CD4 cell count was 37.3 +/- 29.6/microliters. Results of tuberculin skin tests were negative in 5 patients. One patient had pulmonary tuberculosis and 5 had miliary tuberculosis. Hilar and mediastinal lymphadenopathy was found on chest X-ray films in 4 patients and superficial lymphadenopathy was found in all patients. All patients had positive mycobacterial cultures of sputum and 2 patients had positive tests for acid-fast bacilli on smears of lymph-node aspirates. In one patient with tuberculosis meningitis, a culture of cerebrospinal fluid for acid-fast bacilli was positive. Epithelioid cell granulomas were found in samples of lung, liver, and bone marrow from 4 patients. Mycobacterium tuberculosis was isolated from all patients, and was not resistant to isoniazid, rifampicin, ethambutol, or streptomycin. Therefore all patients responded well to treatment of tuberculosis.

AIDS-Related Opportunistic Infections↗

[Coronary microvascular dysfunction in coronary artery disease associated with glucose intolerance].

Coronary flow reserve is used as an indicator to assess coronary microvascular function in the absence of obstructive coronary atherosclerosis. Diabetic patients, even with angiographically normal coronary arteries, show significantly reduced coronary flow reserve. This study evaluated coronary microcirculation in coronary artery disease complicated by glucose intolerance. Thirty-three patients with coronary artery disease were divided into three groups: Fourteen patients without glucose intolerance (control group), 8 with impaired glucose tolerance (IGT group), and 11 with noninsulin dependent diabetes mellitus (DM group). A Doppler guide wire was used to measure phasic coronary blood flow velocity in the left anterior descending artery without significant stenosis (> or = 40% diameter narrowing). Coronary flow reserve was determined by intracoronary 10 mg papaverine hydrochloride administration which induced maximal hyperemia. Coronary flow reserve was decreased in the DM group compared with the control group (2.1 +/- 0.6 vs. 3.1 +/- 0.9, p = 0.004), and that in the IGT group (2.5 +/- 0.9) did not show a significant difference compared with the other two groups. Vessel characteristics, such as infarct- or noninfarct-related artery and previous coronary angioplasty, did not have an influence on the results. Other coronary risk factors, left ventricular function, and hemodynamic findings were comparable in the three groups. This study demonstrates that diabetes mellitus may cause functional microvascular abnormalities in coronary artery disease.

Aged↗

[Congenital antithrombin III deficiency associated with pulmonary thromboembolism].

A 42-year-old man was admitted to the hospital because of sudden left-lateral chest pain and dyspnea. The chest roentgenogram on admission showed a string-like shadow and pleural effusion, and analysis of arterial blood gases revealed hypoxemia. Many bilateral segmental defects were seen on a radioisotope perfusion scan of the lungs, and the chest CT scan showed a low-density area in the trunk of the pulmonary artery. From these findings, pulmonary thromboembolism was diagnosed. The serum antithrombin III (ATIII) activity and the antigen value were low, and the patient's son's serum ATIII level was also low. Both the patient and his son were given the diagnosis of congenital ATIII deficiency. Gene analysis revealed two point mutations in exon 6 of the ATIII gene, so we classified this case as type IIc. The patient was treated with intravenous urokinase and heparin, and was then given warfarin. The arterial blood gas tensions improved, and the low-density area of the pulmonary artery on the CT scan disappeared, as did the pulmonary perfusion defect on the radioisotope scan. The clinical manifestations of members of 28 families with congenital ATIII deficiency reported in Japan were reviewed. Patients in whom many point mutations were detected in the ATIII gene were rare.

Adult↗

[Quality assurance for the measured values and quality control].

It is essential for us to build a liable quality control system in order to report excellent results assured of quality. For the purpose, not only the execution of quality control on laboratory side but also the recognition of quality control on clinical side are important. And more important matter is to record the error of measured values.

Laboratories↗

Alterations in glutathione peroxidase activity following reperfusion injury to rat liver.

Prevention of cellular damage after warm ischemia is of major importance in liver transplantation. In this study, we determined the extent to which lipid peroxides contribute to the pathogenesis of hepatic cell damage induced by transient warm ischemia with subsequent reperfusion. In addition, the function and immunohistochemical features of glutathione peroxidase, a potent physiological lipid peroxide scavenger of the liver, was assessed. Reperfusion following 15 or 30 minutes of warm ischemia resulted in a significant elevation in serum and liver lipid peroxidase (LPO) levels. In addition, necrosis of the hepatic periportal area accompanied with remarkable rises in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. In contrast, 30 min of ischemia without reperfusion caused minimal hepatocellular damage. The adverse changes after ischemia/reperfusion were minimized by pretreatment with superoxide dismutase (SOD). These results indicate that increased lipid peroxidation by production of radicals after reperfusion caused the liver cell damage. After ischemia/reperfusion, liver glutathione peroxidase (GSH-PO) activity was significantly decreased and its location altered in the damaged liver. These findings suggest that GSH-PO contributes significantly to the protection against hepatic reperfusion injuries.

Animals↗

Disruption of the hslU gene, which encodes an ATPase subunit of the eukaryotic 26S proteasome homolog in Escherichia coli, suppresses the temperature-sensitive dnaA46 mutation.

The Escherichia coli hslVU genes encode subunits of an ATP-dependent protease, a homolog of the eukaryotic 26S proteasome. We found that the hslU gene is required for the temperature (40 degrees C)-sensitive phenotype of the dnaA46 mutant, while other soluble ATP-dependent proteases, La (Lon) and Ti (Clp), were unrelated to this dnaA46 phenotype. Disruption of the hslU gene inhibited cell growth at high temperatures. These observations suggest a specific in vivo role for HslVU protease in denatured proteins. As the absence of HslU produces minicells in M9 medium, the protease may be involved in the cell cycle regulation.

ATP-Dependent Proteases↗