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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 271 records · Page 15Linked to original sources
PubMed1999

Effect of FK506 on ATP-induced intracellular calcium oscillations in cow tracheal epithelium.

To elucidate the effect of FK506 on Ca2+ oscillations in airway epithelium, we investigated cultured cow tracheal epithelial cells with a Ca2+ image-analysis system. ATP (1 microM) induced long-lasting Ca2+ oscillations, having nearly constant peak values (300-400 nM) and intervals (20-40 s) in subconfluent cells but not in confluent cells. These responses were gradually attenuated and abolished by the addition of FK506. Rapamycin, which binds the FK506-binding protein (FKBP), likewise inhibited Ca2+ oscillations, whereas cyclosporin A, a calcineurin inhibitor, did not. Treatment of cells with FK506 decreased Ca2+ content in thapsigargin-sensitive stores, suggesting that the partial depletion of the stores causes the inhibition of Ca2+ oscillations. Immunocytochemistry revealed the existence of cytoplasmic FKBP-like immunoreactivities. The expression of a 12-kDa FKBP was greater in subconfluent cells than in confluent cells as determined by Western blotting, suggesting that the 12-kDa FKBP may be one of the factors that regulates Ca2+ oscillations. Therefore, FK506 possesses an inhibitory action on the Ca2+ response via intracellular FKBP but not via calcineurin, which may result in modification of airway epithelial functions.

Adenosine Triphosphate↗
PubMed1999

Effect of granulocyte/colony-stimulating factor on the onset of the adult respiratory distress syndrome.

To evaluate the effect of granulocyte/colony-stimulating factor (G-CSF) on the onset of the adult respiratory distress syndrome (ARDS), we investigated whether the incidence of ARDS due to pulmonary infection differed between the G-CSF group which received chemotherapy with G-CSF and historical controls without G-CSF. We evaluated 132 patients with hematological malignancy in complete remission without any main organ dysfunction who had been treated between April 1983 and December 1997. We compared the incidence of ARDS due to pulmonary infection between those who received G-CSF and those who did not. There was no remarkable difference in the number of patients, gender, age, or distribution of primary diseases between the two groups. The intensity of chemotherapy was not considered to significantly differ between the two groups, though the chemotherapy regimens administered differed slightly. In the G-CSF group, the duration of neutropenia was significantly shorter and the frequency of documented infection was significantly decreased. We could not find any relationship between ARDS due to pulmonary infection and any anticancer agent or antibiotics. There was no relationship between the kind of G-CSF and the incidence of ARDS due to pulmonary infection (per chemotherapy session; p > 0.10, per case; p > 0.30, chi2 test). The incidence of ARDS due to pulmonary infection per chemotherapy session was 4.21%, and showed a higher tendency in the G-CSF group (p < 0.100, chi2 test). The incidence of ARDS due to pulmonary infection per case was 25.4% and was significantly higher in the G-CSF group (p < 0.025, chi2 test). The incidence of ARDS due to pulmonary infection was higher in the G-CSF group than in the controls, suggesting that G-CSF promotes the development of ARDS due to pulmonary infection.

Adolescent↗
PubMed1999

Calcification in untreated non-Hodgkin's lymphoma of the jejunum.

A 69-year-old Japanese female was admitted to our hospital due to a 2-month history of vomiting after eating. Examination of the small intestinal tract revealed a tumor with calcification in the inner portion, from the horizontal portion to the ascending portion of the duodenum, and jejunojejunostomy was performed. The pathological findings of the tumor gave a diagnosis of non-Hodgkin's lymphoma, diffuse small cleaved cell (Working Formulation classification), B cell type, of the jejunum. Calcification is rarely found in untreated malignant lymphoma and 15 cases of untreated malignant lymphoma with calcification have been reviewed.

Adolescent↗
PubMed1999

Clinical study of brain metastasis of renal cell carcinoma.

OBJECTIVES: To evaluate the natural history and the efficacy of treatments for renal cell carcinoma (RCC) with brain metastasis, we reviewed 18 patients with this disease. METHODS: Out of 325 cases with RCC treated at Osaka University Hospital from 1957 to 1993, 18 (5.5%, male:female ratio 16:2) cases developed brain metastases. Median follow-up was 44 months after the initial treatment of the primary lesion. Twelve patients had surgical resection of brain metastases (surgical group), and 7 of them received adjuvant radiotherapy. Six patients with poor performance status were treated with supportive therapy alone (nonsurgical group). RESULTS: Of 18 RCC patients with brain metastasis, 16 were male and 2 female. All brain metastases except for 1 case were symptomatic. Median interval between the initial treatment of the primary lesion and the diagnosis of brain metastasis was 19 months. The most frequent metastatic site prior to brain was the lung, which was detected in 7 cases (38.9%). Median survival of the entire group, measured from the onset of brain metastasis, was 9.5 months. One-year survival rate after the diagnosis of brain metastasis was 43.2% (64.8% in surgical group, 0% in nonsurgical group), 3-year 18.5% and 5-year 0%. Among 109 metastatic RCC, 14 patients were treated by lymphokine-activated killer (LAK) therapy. Out of 14 metastatic RCC patients treated by LAK therapy, 3 (21.4%) developed brain metastases. On the other hand, out of 95 metastatic RCC patients without LAK therapy, 15 (15.8%) had brain metastases. There was no significant difference in the rate of brain metastases between these two groups. CONCLUSION: There was a trend for prognosis of the surgical group to be better compared to that of the nonsurgical group, although it is not statistically significant. The optimum treatment for brain metastasis of RCC remains undefined, but our data suggested surgical resection in selected patients might contribute to prolonged survival of patients with brain metastasis. LAK therapy was not necessarily the risk factor of the brain metastasis.

Adult↗
PubMed1999

Molecular mechanism for pore-formation in lipid membranes by the hemolytic lectin CEL-III from marine invertebrate Cucumaria echinata.

The pore-forming activity of CEL-III, a Gal/GalNAc specific lectin from the Holothuroidea Cucumaria echinata, was examined using artificial lipid membranes as a model system of erythrocyte membrane. The carboxyfluorescein (CF)-leakage studies clearly indicated that CEL-III induced the formation of pores in the dipalmitoyl phosphatidyl choline (DPPC)-lactosyl ceramide (LacCer) liposomes effectively but not in the DPPC-glucosyl ceramide (GlcCer) liposomes or DPPC liposomes. Such a leakage of CF was strongly inhibited by lactose, a potent inhibitor of CEL-III, suggesting that the leakage is mediated through the specific binding of CEL-III to the carbohydrate chains on the surface of the liposomes. The leakage of CF from the DPPC-lactosyl ceramide liposomes was pH-dependent, and it increased with increasing pH. The immunoblotting analysis and circular dichroism data indicated that upon interaction with liposomes, CEL-III associated to form an oligomer concomitantly with a marked conformational change. Furthermore, channel measurements showed that CEL-III has an ability to form small ion channels in the planar lipid bilayers consisting of diphytanoylphosphatidylcholine and human globoside (Gb4Cer)/LacCer.

Animals↗
PubMed1999

Detection and evaluation of asymptomatic myocarditis in schoolchildren: report of four cases.

STUDY OBJECTIVE: Data on the prevalence of myocarditis in children are limited. Autopsy studies have shown that myocarditis is often undiagnosed. We attempted to investigate the clinical features of asymptomatic myocarditis in four schoolchildren detected during a mass ECG screening in schoolchildren. DESIGN AND SETTING: To evaluate asymptomatic myocarditis, we clinically examined 12 schoolchildren who were referred to Shiga University of Medical Science Hospital, Otsu, Japan, because of abnormal ST or T waves detected during ECG screening. None of the 12 children had experienced any episodes suggesting cardiac disease or Kawasaki disease. Cardiac function and myocardial viability were assessed by two-dimensional echocardiography (2-DE), thallium-201 (201Tl) myocardial scintigraphy, and cardiac catheterization. Endomyocardial biopsy specimens were examined histologically. PATIENTS: Endomyocardial biopsy specimens revealed histologic evidence of myocarditis in 4 of the 12 children with abnormal ST or T waves. RESULTS: Abnormal tracer perfusion was observed on 201Tl myocardial scintigrams in these four children, but the results of coronary arteriography were normal. 2-DE showed left ventricular hypokinesis in one child and left ventricular enlargement in one of the four children with histologic evidence of myocarditis. A second endomyocardial biopsy specimen was obtained in two of four children, showing persistent myocarditis in one child. CONCLUSIONS: This type of screening program and indepth evaluation using 2-DE and 201Tl myocardial scintigraphy appear to be helpful in identifying children with myocarditis. The present histologic investigations suggested that even asymptomatic myocarditis might result in persistent heart damage.

Biopsy↗
PubMed1999

Human megakaryocyte ploidy.

We reviewed the literature concerning the history of determination of the ploidy of human megakaryocytes and its relationship with diseases. The ploidy of rabbit megakaryocytes was analyzed by microspectrophotometry in 1964, and the analysis of the ploidy in human megakaryocytes was first performed in 1968. Presently, microphotometry and flow cytometry are the primary methods for the evaluation of the ploidy, but they have their merits and demerits. In the ploidy of human megakaryocytes, a peak has often been reported at 16N in healthy individuals, and the next peaks have been observed at 32N and 8N. The results of ploidy analyses have been reported by many investigators to be comparable between patients with idiopathic thrombocytopenic purpura and normal subjects, but various shifts of the peaks have also been documented. The ploidy is often reported to shift to a larger ploidy class in polycythemia vera and essential thrombocythemia, but it has invariably been reported to shift to a smaller class in chronic myelogenous leukemia. In reactive thrombocytosis, the ploidy pattern was reported to be the same as that in normal individuals by some investigators but to shift to a larger ploidy by others. These differences are considered to be due to heterogeneity of the subjects. In myelodysplastic syndrome, the ploidy shifts mostly to a smaller class, but it may show various patterns. We also reviewed the ploidy in other rare hematological disorders, the relationships of the ploidy with diabetes mellitus and atherosclerotic disorders, and its changes in the ontogeny. Details of the mechanism of polyploidization and its biological significance remain unknown, and further advances in the studies of these topics are anticipated.

Animals↗
PubMed1999

Potassium channel openers antagonize the effects of class III antiarrhythmic agents in canine Purkinje fiber action potentials. Implications for prevention of proarrhythmia induced by class III agents.

We studied the effects of potassium channel openers (PCOs) on frequency dependent prolongations of action potential duration (APD), triggered activities and oscillatory action potentials (OSC) induced by E-4031 and dofetilide. The action potentials of canine Purkinje fibers were recorded by a glass microelectrode technique. The effects of E-4031 (10(-6)M) as well as that of additional nicorandil (2 x 10(-5) M) on the APD were examined. When abnormal automaticity was observed under perfusion of E-4031 (10(-5) M) or dofetilide (10(-5) M), action potentials were recorded continuously to estimate the sequential effects of additional perfusion of nicorandil (6 x 10(-5) M) or Y-26763 (10(-5) M) on triggered activities and OSC. APD prolongation by E-4031 at slower stimulation rates (cycle lengths > or = 1,000 msec) was suppressed by nicorandil in a dose dependent manner. Both nicorandil and Y-26763 abolished the train of early afterdepolarization (EAD) due to E-4031 or dofetilide with a shifting of the resting membrane potential to a more negative level. PCOs also normalized dofetilide induced abnormal automaticities (EAD, OSC). The antagonistic actions of PCOs on changes in action potential induced by class III antiarrhythmic agents may prevent the development of proarrhythmias produced by these agents.

Action Potentials↗
PubMed1999

Relationship between coronary blood flow velocity waveform and transmural distribution of myocardial blood flow in coronary artery.

It is important to know the transmural distribution of myocardial blood flow in assessing the severity of ischemia in coronary heart disease. We analyzed the relation between phasic waveform of epicardial coronary flow velocity with a Doppler flow probe in the left anterior descending artery in dogs and regional myocardial blood flow using a colored microsphere technique. Time-velocity integral in an average of 5 cardiac cycles was measured as an index of coronary blood flow during diastole (TVId) and systole (TVIs). The diastolic fraction of coronary blood flow (%DF) was defined as TVId/(TVId + TVIs). Myocardial specimens were divided into inner (subendocardial), middle, and outer (subepicardial) layers, and the inner layer to outer layer myocardial blood flow ratio (endo/epi ratio) was used as an index of transmural distribution of myocardial perfusion. The mean endo/epi ratio and the mean %DF decreased as the pressure gradient increased. There was a moderate but significant correlation (r = 0.57) between the endo/epi ratio and the %DF. In conclusion, analysis of the phasic pattern of coronary blood flow velocity provides some information about the transmural distribution of blood flow in the myocardium. The %DF may be a useful index for evaluating subendocardial ischemia.

Animals↗
PubMed1999

Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes.

The recently described variant of the human beta3-adrenergic receptor (AR) gene located mainly in visceral adipocytes is associated with earlier onset of NIDDM, abdominal obesity, insulin resistance, and an increased capacity to gain weight. We investigated whether lipolysis in human omental adipocytes induced by a potent and selective human beta3-AR agonist (L-755,507) was affected by the Trp64Arg mutation of the beta3-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy. The Trp64Arg mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Arg64 homozygous (n = 4) had a lower median effective concentration (EC50) and lower responsiveness compared with wild-type (n = 8) (EC50: -6.55 +/- 0.21 vs. -7.53 +/- 0.35 log mol/l, P = 0.007; responsiveness: 3.48 +/- 0.32 vs. 5.76 +/- 0.36 micromol x 10(5) cells(-1) x 90 min(-1), P = 0.014, respectively), although there was no difference in lipolysis induced by isoproterenol or CGP12177. Trp64Arg heterozygous (n = 6) also had a significantly lower EC50 and lower responsiveness (EC50: -6.18 +/- 0.09 log mol/l; responsiveness: 4.17 +/- 0.33 micromol x 10(5) cells(-1) x 90 min(-1)). We concluded that the Trp64Arg mutation of the beta3-AR gene is associated with lower lipolytic activities.

Adipose Tissue↗
PubMed1999

Pancreatic phospholipase A2 induces bacterial translocation in rats.

The importance of pancreatic enzymes, particularly phospholipase A2 (PLA2), for bacterial translocation, which is considered to be one of the aggravating causes of acute pancreatitis, was investigated. Male rats were administered an intraperitoneal or intravenous injection of normal saline, PLA2, or amylase. Four days later, the mesenteric lymph nodes (MLNs) and portal blood of the animals were cultured. None of the animals had a positive portal blood culture. The MLNs contained enteric bacteria in 78% of the animals given 50 mg/kg of PLA2 intraperitoneally. 5 mg/kg of PLA2 intraperitoneally, 50 mg/kg of amylase intraperitoneally, or 50 mg/kg of PLA2 intravenously showed positive cultures in 25%, 20%, and 11%, respectively. None of the animals given intraperitoneal or intravenous normal saline had positive cultures of their MLNs. Intraperitoneal injection of 25 mg/kg of nafamostat mesilate just before intraperitoneal PLA2 (50 mg/kg) resulted in a reduction of positive MLNs from 70% to 30%. The cecal myeroperoxidase (MPO) activity of animals administered 50 mg/kg of PLA2 intraperitoneally was significantly higher compared with animals administered saline intraperitoneally. These results indicate that intraperitoneal leakage of PLA2 plays an important role in bacterial translocation during acute pancreatitis and that administration of a protease inhibitor may be effective against the bacterial translocation.

Acute Disease↗
PubMed1999

Induction of lasting complete regression of preformed distinct solid tumors by targeting the tumor vasculature using two new anti-endoglin monoclonal antibodies.

Endoglin (EDG, CD105) is a proliferation-associated antigen on endothelial cells. In this study, two new anti-EDG monoclonal antibodies (mAbs) Y4-2F1 (or termed SN6j) and P3-2G8 (SN6k) were generated and used for treating distinct preformed tumors. These mAbs, both IgG1-kappa antibodies, cross-reacted weakly with mouse endothelial cells but defined epitopes different from the epitope defined by a previously reported anti-EDG mAb K4-2C10 (B. K. Seon et al., Clin. Cancer Res., 3: 1031-1044, 1997). SN6j and SN6k reacted strongly with human endothelial cells and vascular endothelium of malignant human tissues but showed no significant reactivity with tumor cells per se. The deglycosylated ricin A chain (dgRA) conjugates of the two mAbs showed a weak but specific cytotoxic activity against murine endothelial cells in vitro. In the therapeutic studies, severe combined immunodeficient mice were inoculated s.c. with MCF-7 human breast cancer cells and left untreated until palpable tumors of distinct size (4-6 mm in diameter) appeared. Mice with the distinct tumors were treated by i.v. administration of individual anti-EDG conjugates, unconjugated mAbs, or a control conjugate. Long-lasting complete regression of the tumors was induced in the majority of tumor-bearing mice (n = 8 for each conjugate) when 40 microg of the individual conjugates were administered three times via the tail vein. It is remarkable that the tumors remained regressed without further therapy for as long as the mice were followed (i.e., 100 days). Control conjugate did not induce regression of the tumors in any of the treated mice, although weak nonspecific effects were observed in some of the mice (n = 8). The effects of unconjugated mAbs were small with the dose used, i.e., 34 microg three times. The anti-EDG conjugates showed antiangiogenic activity in the dorsal air sac assay in mice. The results suggest good potential of these conjugates for the clinical application.

Animals↗
PubMed1999

[Burkitt's lymphoma originating in gluteal muscle tissue].

We report a case of Burkitt's lymphoma originating in gluteal muscle tissue. A 61-year-old Japanese man was admitted to our hospital due to painful swelling of the left femur and gluteal region in October 1996. A laboratory examination disclosed elevated levels of serum lactate dehydrogenase and soluble interleukin 2 receptor. Gallium scintigraphy demonstrated accumulations in the left femur and gluteal region. Magnetic resonance imaging yielded intense signals and disclosed swelling of muscle tissue in the same region. Pathological examination of biopsy specimens from the left femur revealed a starry-sky pattern, and a chromosomal analysis revealed t(2;8)(p11;q24). Heightened concentrations of antibody for Epstein-Barr virus were not detected. Non-African type Burkitt's lymphoma was diagnosed on the basis of these findings. CHOP therapy and irradiation of the affected region were initially effective, but the disease eventually became resistant to treatment. The patient died of cerebral hemorrhage. As far as we know, this is the first report in Japan of Burkitt's lymphoma originating in muscle tissue.

Burkitt Lymphoma↗
PubMed1999

[Development of cyroglobulinemia and polyneuropathy in a chronic myeloid leukemia patient during interferon-alpha treatment].

Neurological side effects and complications of cryoglobulinemia were observed during interferon-alpha (IFN-alpha) therapy in a patient with chronic myeloid leukemia (CML). A 50-year-old man was hospitalized because of leukocytosis and extramedullary tumors in the lumbar spine. In addition, the patient complained of dysesthesia in his feet. A diagnosis of accelerated phase CML was made. Administration of prednisolone, vincristine, hydroxyurea, and Ara-C and irradiation of the lumbar spine were started. Two months later, the patients achieved hematologic response and the size of his tumors decreased. Thereafter, we started IFN-alpha treatment (3-6 x 10(6) units daily) by intramuscular injection. After 8 weeks of this treatment, the patient complained of worsening dysesthesia in his feet. An axonal form of peripheral neuropathy was diagnosed by electrophysiological examination. Immunological studies revealed decreased complement levels and type III mixed cryoglobulinemia. Methylprednisolone pulse therapy alleviated the neurological symptoms and lowered the cryoglobulin levels. The clinical course suggested that mixed cryoglobulinemia was associated with CML and that the increase in cryoglobulin levels was caused by IFN-alpha and played a causative role in the worsening peripheral neuropathy. Therefore, to prevent these side effects, careful clinical assessment is necessary before starting IFN-alpha therapy.

Cryoglobulinemia↗