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Biomedical subjects

M Kurosawa

Publications and source records attributed to M Kurosawa.

At least 19 recordsLinked to original sources
PubMed2005

Genetic diagnosis of sex chromosome aberrations in horses based on parentage test by microsatellite DNA and analysis of X- and Y-linked markers.

REASONS FOR PERFORMING STUDY: Sex chromosome aberrations are often associated with clinical signs that affect equine health and reproduction. However, abnormal manifestation with sex chromosome aberration usually appears at maturity and potential disorders may be suspected infrequently. A reliable survey at an early stage is therefore required. OBJECTIVES: To detect and characterise sex chromosome aberrations in newborn foals by the parentage test and analysis using X- and Y-linked markers. METHODS: We conducted a genetic diagnosis combined with a parentage test by microsatellite DNA and analysis of X- and Y-linked genetic markers in newborn light-breed foals (n = 17, 471). The minimum incidence of sex chromosome aberration in horses was estimated in the context of available population data. RESULTS: Eighteen cases with aberrations involving 63,XO, 65,XXY and 65,XXX were found. The XO, XXY (pure 65,XXY and/or mosaics/chimaeras) and XXX were found in 0.15, 0.02 and 0.01% of the population, respectively, based solely on detection of abnormal segregation of a single X chromosome marker, LEX003. CONCLUSIONS AND POTENTIAL RELEVANCE: Detection at an early age and understanding of the prevalence of sex chromosome aberrations should assist in the diagnosis and managment of horses kept for breeding. Further, the parental origin of the X chromosome of each disorder could be proved by the results of genetic analysis, thereby contributing to cytogenetic characterisation.

Animals↗
PubMed2005

Acute pancreatitis possibly caused by allergy to bananas.

We are reporting a forty-seven year old female who had three attacks of acute pancreatitis after having; eaten bananas. She was treated with a light diet and intravenous fluids during each of her admissions. The treatment concluded with the disappearance of clinical symptoms such as epigastralgia, nausea, vomiting and diarrhea within a few days. In addition, elevated serum and urine amylase levels returned to normal values in parallel with the clinical symptoms. The data during her three attacks of acute pancreatitis were as follows: serum total IgE level = 644 IU/mL, specific IgE to bananas = 2.18 UA/ml. No remarkable abnormalities were present in sonography, computed tomography, magnetic resonance imaging of the abdomen, and magnetic resonance cholangiopancreatography. Endoscopic examination of the upper digestive tract showed the ampulla of Vater swollen and edematous, thus a biopsy was performed. Toluidine blue staining and immunohistochemical staining against human mast cell tryptase with the biopsy specimens showed mast cells accumulating in mucosa and submucosa. By avoiding consumption of bananas, she has not suffered from any additional attacks of pancreatitis since the third attack in the last thirty-four months up to this day of December 10, 2004.

Acute Disease↗
PubMed2002

Megakaryoblastic transformation of polycythemia vera with hypercalcemia.

Polycythemia vera (PV) is known to occasionally transform into acute leukemia. Administration of alkylating agents seems to be associated with an increased risk of leukemic transformation of PV. Hypercalcemia is a serious complication of malignancies, but it is uncommon in acute leukemia. In the majority of malignancies with hypercalcemia, elevated parathyroid hormone-related protein (PTHrP) is thought to be the main cause of hypercalcemia. We report a rare case of megakaryoblastic transformation of PV with hypercalcemia. A 62-year-old man was diagnosed as having PV in 1983, and he had received ranimustine and busulfan. He developed acute megakaryoblastic leukemia 17 years after the initial diagnosis of PV. Serum calcium was elevated, the serum level of intact parathyroid hormone (PTH) was suppressed, and the level of intact PTHrP was slightly elevated. He had no lytic bone lesions; however, uncoupling of bone turnover due to an increase in bone resorption and a decrease in bone formation was detected by using biochemical markers. Since the level of PTHrP was slightly elevated from the normal value, we speculated that PTHrP produced in the local field by leukemic cells might have been more abundant than circulating PTHrP. Pamidronate and adrenocortical hormone were effective in reducing the serum calcium level. However, the patient died shortly after the start of induction chemotherapy. The prognosis of cases of PV that has transformed into acute leukemia is generally poor because the majority of such cases are refractory to chemotherapy.

Adrenocorticotropic Hormone↗
PubMed2002

del11(p11-13) with overexpression of Wilms' tumor gene during leukemic transformation of myelodysplastic syndrome.

We report a case of leukemic transformation from myelodysplastic syndrome (MDS) with a sole chromosome abnormality of del11(p11-13). The patient had been diagnosed as having MDS (refractory anemia with excess of blast cells, RAEB) in May 1998. At that time, cytogenetic analysis of bone marrow cells showed a normal karyotype. The patient received sequential chemotherapy with low-dose cytosine arabinoside (AraC) and macrophage colony-stimulating factor (M-CSF). Complete remission was obtained with this treatment, but the disease gradually progressed after June 1999. Cytogenetical analysis showed del11(p11-13) in 6 of 40 cells analyzed at that time, and the disease had evoluted to overt leukemia in December 1999 with a gradual increase in the abnormal clone. Furthermore, mRNA of the WT1 gene located at chromosome 11p13 was overexpressed during leukemic transformation, whereas it was not detected at the time of the initial diagnosis of MDS (RAEB) in May 1998. It was thought that this chromosome deletion and overexpression of WT1 resulted in the leukemic transformation in this patient. This is the first case report of del11(p11-13) being considered to be the primary cause of leukemic transformation from MDS.

Blast Crisis↗
PubMed2001

Determination of bufalin-like immunoreactivity in serum of humans and rats by time-resolved fluoroimmunoassay for using a monoclonal antibody.

The existence of a mammalian natriuretic substance or endogenous digitalis-like factor, which inhibits Na+,K+-ATPase and thereby regulates body fluid volume, has been speculated for a long time but has yet to be defined. We established in the present study a simple and highly sensitive procedure to measure bufalin, a constituent of toad venom preparation and a specific inhibitor of Na+,K+-ATPase by time-resolved fluoroimmunoassay (TR-FIA) and using a monoclonal antibody. The antibody was specific to bufalin and resembled bufadienolides but showed no cross-reactivity with digitoxin and ouabain. A bufalin-like immunoreactivity was detectable in serum of humans and rats by the proposed TR-FIA. The levels of bufalin-like immunoreactivity in serum of healthy volunteers were significantly correlated with their systolic blood pressure. Moreover, bufalin-like immunoreactivity in serum of Dahl-S rats increased in parallel with a period of high-salt diet. These results suggest that increased bufalin-like immunoreactivity may be associated with certain types of hypertension.

Animals↗
PubMed2001

Cepharanthine activates caspases and induces apoptosis in Jurkat and K562 human leukemia cell lines.

Cepharanthine (CEP) is a known membrane stabilizer that has been widely used in Japan for the treatment of several disorders such as anticancer therapy-provoked leukopenia. We here report that apoptosis was induced by low concentrations (1-5 microM) of CEP in a human leukemia T cell line, Jurkat, and by slightly higher concentrations (5-10 microM) in a human chronic myelogenous leukemia (CML) cell line K562, which expresses a p210 antiapoptotic Bcr-Abl fusion protein. Induction of apoptosis was confirmed in both Jurkat and K562 cells by DNA fragmentation and typical apoptotic nuclear change, which were preceded by disruption of mitochondrial membrane potential and were induced through a Fas-independent pathway. CEP treatment induced activation of caspase-9 and -3 accompanied by cleavage of PARP, Bid, lamin B1, and DFF45/ICAD in both Jurkat and K562 cells, whereas caspase-8 activation and Akt cleavage were observed only in Jurkat cells. The CEP-induced apoptosis was completely blocked by zVAD-fmk, a broad caspase inhibitor. Interestingly, CEP treatment induced remarkable degradation of the Bcr-Abl protein in K562 cells, and this degradation was prevented partially by zVAD-fmk. When used in combination with a nontoxic concentration of herbimycin A, lower concentrations (2-5 microM) of CEP induced obvious apoptosis in K562 cells with rapid degradation or decrease in the amount of Bcr-Abl and Akt proteins. Our results suggest that CEP, which does not have bone marrow toxicity, may possess therapeutic potential against human leukemias, including CML, which is resistant to anticancer drugs and radiotherapy.

Alkaloids↗
PubMed2001

Exfoliative esophagitis early after autologous peripheral blood stem cell transplantation.

Two patients with non-Hodgkin's lymphoma (NHL) suffered from hematemesis due to exfoliative esophagitis early after autologous peripheral blood stem cell transplantation (PBSCT). The chemotherapy regimens used for these 2 patients were the same and consisted of high-dose ranimustine, carboplatin, etoposide, and cyclophosphamide (MCVC regimen), which have been widely used in autologous PBSCT for NHL in Japan. Esophageal bleeding in both patients was stopped by conservative treatment without any special endoscopic manipulations. Gastrointestinal bleeding after hematopoietic stem cell transplantation is usually caused by viral infections, graft-versus-host disease, or conditioning chemo-radiotherapy. Although severe esophagitis is common in patients receiving stem cell transplantation, the exfoliative form detected by endoscopic examination has not been reported. We conclude that high-dose chemotherapy and frequent vomiting during treatment are risk factors for lower-esophageal bleeding in these cases.

Adult↗
PubMed2001

Peripheral T-cell lymphoma in a patient with osteopetrosis.

Osteopetrosis is a rare genetic disorder in which the function of osteoclasts is defective, resulting in impaired bone resorption. This disease is usually accompanied by myelosuppression due to decreased marrow space and by osteomyelitis, especially in the submandibular bone. We report the case of a 72-year-old woman with an autosomal dominant form of osteopetrosis who suffered from peripheral T-cell lymphoma. Accurate clinical and pathological diagnoses and staging were difficult due to nonspecific reactive hyperplasia of the lymph nodes, even though we used several scintigraphic techniques and [18F]fluorodeoxyglucose positron emission tomography. We also paid special attention to myelosuppression and exacerbation of osteomyelitis after combination chemotherapy. Severe infectious complications were avoided by early administration of G-CSF for leukocytopenia and by continuous oral administration of antibiotics. The patient achieved complete remission after four courses of chemotherapy and this status has been maintained for 6 months.

Aged↗
PubMed2001

Chronic eosinophilic leukemia with t(6;11)(q27;q23) translocation.

We report a rare case of chronic eosinophilic leukemia (CEL) with a chromosomal abnormality of t(6;11)(q27;q23). The patient was diagnosed as having thyroid cancer with metastases to the lung and cervical lymph nodes in 1993. Percutaneous ethanol injection therapy (PEIT), total thyroidectomy, and radiotherapy were performed. The patient was also diagnosed as having prostatic cancer with bone metastasis in July 1999, and hormonal therapy was performed. At the time of the diagnosis of prostatic cancer, leukocytosis with eosinophilia was also revealed. Thereafter, cytogenetical analysis and reverse transcriptase polymerase chain reaction (RT-PCR) analysis of bone marrow showed t(6;11)(q27;q23) translocation and MLL/AF6 fusion products, respectively. No transcripts of the BCR/ABL chimeric gene were found by RT-PCR in bone marrow. Analysis of serum cytokines revealed a slight elevation of GM-CSF but no elevation of IL-3 or IL-5. Tissue damage due to infiltration of eosinophils was not observed throughout the clinical course. On the basis of the cytogenetic and molecular abnormality, the patient was diagnosed as having CEL, rather than reactive eosinophilia due to thyroid or prostatic cancer or other reactive inflammation. This is the first case report of CEL with t(6;11)(q27;q23) translocation.

Aged↗
PubMed2001

Cholecystokinin-8 (CCK-8) has no effect on heart rate in rats lacking CCK-A receptors.

Heart rate responses to i.v. administration of cholecystokinin-8 (CCK-8) were investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-A receptors and control Long-Evans Tokushima Otsuka (LETO) rats. The heart rate decreased after i.v. administration of 3 nmol.kg(-)(1) of CCK-8 in LETO rats, but not in OLETF rats. Bradycardia in the LETO rats disappeared after treatment with MK-329, but not after treatment with L-365,260. The expression of CCK-A receptor precursor mRNA was found exclusively in the atrium in LETO rats. These results suggest that CCK-8 decreases heart rate via CCK-A receptors located in the atrium of the rats.

Animals↗
PubMed2001

Distinct PKC isozymes regulate bufalin-induced differentiation and apoptosis in human monocytic cells.

Bufalin, an Na(+)-K(+)-ATPase inhibitor, simultaneously induced cell differentiation and apoptosis in human monocytic leukemia THP-1 cells. In this study, we investigated the regulatory role of protein kinase C (PKC) isozymes in bufalin-induced cell differentiation and apoptosis. A PKC-specific but isozyme-nonselective inhibitor, Ro-31-8220, and a cPKC selective inhibitor, Gö-6976, caused significant attenuation of bufalin-induced interleukin-1beta (IL-1beta) gene expression, a mature monocytic marker, indicating that cPKC participates in the bufalin-induced cell differentiation. On the other hand, cPKCbeta- and nPKCdelta-defective THP-1/TPA cells displayed strong resistance to the bufalin-induced DNA ladder formation. Rottlerin, an nPKCdelta-specific inhibitor, partially attenuated preapoptotic effects of bufalin, such as the limited proteolysis of nPKCdelta and poly(ADP-ribose) polymerase and the cell staining by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, suggesting that nPKCdelta is involved, at least in part, in bufalin-induced apoptosis. In contrast, Gö-6976 and rottlerin significantly augmented bufalin-induced apoptosis and differentiation, respectively. The findings suggest that bufalin-induced cell differentiation and apoptosis are interlinked and that distinct PKC isozymes are involved in the fate of the cell.

Apoptosis↗
PubMed2001

Primary lymphoma of spermatic cord.

Primary lymphomas of spermatic cord are extremely rare. In a review of the world medical literature, until now, only fourteen cases of spermatic cord lymphoma have been reported, and, furthermore, they have a poor prognosis even in patients with stage I disease. Herein, we report a new case of primary non-Hodgkin's lymphoma of the spermatic cord. In August, 1993, 76-year-old man visited an urological hospital with a compaint of a right intrascoral mass, and underwent orchiectomy. Macroscopically no invasive lesion in the testis was observed, and the tumorous lesion was restricted to the epididymis. The histopathological study indicated that he suffered from primary malignant lymphoma of the spermatic cord (B-cell, diffuse medium-sized cell type). As radiographic investigations showed no other invasive lesion, the patient was diagnosed to be in stage IE. He was followed only with clinical observation, and, in August, 1996, relapsed with extensive disease in the abdoninal cavity, and was transferred to our hospital. Fourty months after the orchiectomy, he died of progression of disease irrespective of the salvage radio-chemotherapies given to him.

Aged↗
PubMed2001

Expression of adhesion molecules on cord-blood-derived, cultured human mast cells and effect of dexamethasone on intercellular adhesion molecule-1 expression on the mast cells treated by phorbol myristate acetate.

BACKGROUND: Increase in mast-cell number at sites of allergic inflammation has been observed, and glucocorticoids applied to the sites have been shown to result in a significant reduction in mast cells. However, the expression of adhesion molecules on cultured human mast cells and their regulation by glucocorticoids is poorly understood. METHODS: Cultured human mast cells were raised from human umbilical cord-blood cells, and the expression of adhesion molecules on the mast cells was analyzed by flow cytometry. The cells were also incubated with 10 ng/ml phorbol myristate acetate (PMA) for the indicated time, and the effect of dexamethasone on adhesion molecule expression on PMA-treated, cultured human mast cells was examined. RESULTS: Cord-blood-derived, cultured human mast cells constitutively expressed intercellular adhesion molecule-1 (ICAM-1), very late antigen-4 (VLA-4), and macrophage-1 antigen (Mac-1). Weak expression of lymphocyte function-associated antigen-1 (LFA-1) was observed on the cells, whereas they failed to express vascular cell adhesion molecule-1 (VCAM-1). Kinetic studies showed that after a transient downregulation reaching a minimum at 8 h, the expression of ICAM-1 was markedly upregulated on PMA-treated mast cells after a 24-h incubation. In contrast, the expression of VLA-4 and Mac-1 was decreased after the incubation with PMA for 24 h. The PMA-induced upregulation of ICAM-1 was inhibited by dexamethasone in a concentration-dependent manner. CONCLUSION: Our results indicate that cord-blood-derived, cultured human mast cells constitutively express integrins and ICAM-1, but not VCAM-1, and demonstrate for the first time that dexamethasone inhibits the upregulation of ICAM-1 on PMA-treated, cultured human mast cells.

Anti-Inflammatory Agents↗
PubMed2000

Effect of interleukin-1beta on subdiaphragmatic vagal efferents in the rat.

Interleukin-1beta (IL-1beta) is an important mediator of fever and illness. Recent studies have demonstrated that IL-1beta (2 microg kg(-1)) increases gastric vagal afferent activity. The peripheral mechanisms of the action of lower doses were studied by recording the mass efferent and afferent activity of the gastric branch of the ventral vagal nerve in anesthetized rats. Twenty min after i.v. administration of IL-1beta (1 microg kg(-1)) the efferent activity of the vagal nerve was decreased to 62+/-6% in totally but not in partly vagotomized rats. Preadministration of indomethacin (5 mg kg(-1)) 30 min before IL-1beta blocked this reduction. Administration of 1 microg kg(-1) of IL-1beta had no effect on the afferent activity of the gastric branch of the vagal nerve. The present results suggest that the subdiaphragmatic vagal afferents modulate the parasympathetic efferent outflow in response to IL-1beta partly through prostaglandin dependent mechanisms and that supradiaphragmatic afferents or central sites are more sensitive to the low doses of IL-1beta which becomes evident after elimination of the subdiaphragmatic vagal input.

Animals↗
PubMed2000

Effects of systemic injection of interleukin-1beta on gastric vagal afferent activity in rats lacking type A cholecystokinin receptors.

We have shown that systemic administration of interleukin-1beta (IL-1beta) excites gastric vagal afferent activity in part via stimulation of type A cholecystokinin (CCK-A) receptors in rats. The present study was undertaken to determine whether the response of the gastric vagal afferent nerve to systemic IL-1beta is altered in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which lack CCK-A receptors. The response was compared with that of the control strain, Long-Evans Tokushima Otsuka (LETO) rats. All animals were anesthetized with pentobarbital and artificially ventilated. Intravenous administration of 4 microg/kg of IL-1beta increased gastric vagal afferent activity in both LETO and OLETF rats, whereas a smaller dose of 2 microg/kg of IL-1beta increased activity only in the OLETF rats. The present results demonstrate that the response of the gastric vagal afferent activity in CCK-A receptor deficient OLETF rats was more sensitive to intravenous administration of IL-1beta than was in control LETO rats.

Animals↗