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Biomedical subjects

T Koizumi

Publications and source records attributed to T Koizumi.

At least 91 records · Page 5Linked to original sources
PubMed2000

[Progression of refractory thrombocytopenia to chronic myelomonocytic leukemia accompanied by various inflammatory reactions].

A 51-year-old man was admitted for treatment of severe thrombocytopenia in May 1997. A diagnosis of MDS RA (refractory thrombocytopenia; RTC) was made by bone marrow examination, which revealed mild marrow hypoplasia and a reduced number of megakaryocytes accompanied by micromegakaryocytes and hypolobular megakaryocytes. Chromosome analysis demonstrated 46, XY, t(5;7) (q31;q22) in all 20 cells examined. The patient received only supportive therapy including platelet transfusion, until leukocytosis and monocytosis gradually developed in November 1998. In view of a marked increase in the number of monocytes (more than 3,000/microliter), a diagnosis of CMML was made in December 1998. As the leukocytosis progressed, various inflammatory symptoms such as facial erythema and endophthalmitis developed. Administration of interferon alpha (IFN alpha) unexpectedly worsened the leukocytosis and monocytosis, suggesting abnormal responses of these cells to IFN alpha. Detailed molecular analysis of these cells might reveal a novel mechanism of leukemogenesis associated with 5q31.

Disease Progression↗
PubMed2000

[Acute effects of oxygen on dyspnea and exercise tolerance in patients with pulmonary emphysema with only mild exercise-induced oxyhemoglobin desaturation].

The effects of oxygen on dyspnea and exercise tolerance during a 6-mimute walk test were examined in 10 patients with chronic pulmonary emphysema (CPE) who had only mild hypoxemia at rest (PaO2 > 60 Torr) and mild exercise-induced oxyhemoglobin desaturation (lowest SpO2 > 88%) on compressed air. As a whole, oxygen supplementation (2 l/min) resulted in a 7% increase in the distance walked in 6 min (6 MD), a 3% increase in the lowest SpO2, and an 8% decrease in the dyspnea score. In 6 of 7 patients with severe airflow limitation (one-second forced expiratory volume (FEV1) < 40% of predicted value), 6 MD (7-15%) increased significantly on oxygen, an improvement that correlated significantly with FEV1 (r = -0.65, p < 0.05). These results suggest that supplementary oxygen improves dyspnea and exercise tolerance in CPE patients with only mild exercise-induced hypoxemia despite severe airflow limitation. The long-term efficacy of oxygen in such patients needs further study.

Aged↗
PubMed2000

[Pulmonary Mycobacterium gordonae infection treated with clarithromycin].

We reported a case of 51-year-old female immunocompetent patient with pulmonary Mycobacterium gordonae infection. The patient complained persistent cough and sputum and occasionally hemosputum. Chest radiograph and computed tomography (CT) of the lung showed bronchiectasis and small nodules in middle lobe. Bronchofiberscopy was performed twice, and bronchial washing specimen repeatedly revealed acid-fast bacilli. The organism was identified as Mycobacterium gordonae by biochemical tests and direct sequence method. She was treated with clarithromycin (400 mg/day) over 6 months and the chest CT findings showed improvement. The case was considered to be sensitive to clarithromycin in vitro drug susceptibility test. The case suggested that clarithromycin was a useful therapeutic agent to Mycobacterium gordonae infection.

Clarithromycin↗
PubMed2000

[A case of limited Wegener granulomatosis with hypereosinophilia].

A 51-year-old female was admitted to Nagano Matsushiro General Hospital because of fever, cough and dyspnea on exertion. Her laboratory data revealed leukocytosis with hypereosinophilia, a high erythrocyte sedimentation rate and c-reactive protein. Chest radiography revealed an infiltration shadow with a cavity in the right upper lobe. A lung abscess was diagnosed and antibiotics were administered. Laboratory results showed improvement, but chest radiography continued to show cavities. She was admitted to our hospital because of fever, left pleural effusion and progression of cavities on chest radiographs. She showed no abnormalities of the upper airway or kidney, and was negative for c-antineutrophil cytoplasmic antibody (c-ANCA). Because a positive c-ANCA was seen on day 8 of hospitalization, L-type limited Wegener granulomatosis (WG) was diagnosed according to Gross et al. Prednisolone (PSL) was administered, which improved the anemia, eosinophilia and the cavities. On day 7 of PSL administration, of the left pneumothorax occurred as a complication caused by perforation of the left chest cavity, but her clinical course was good after a cavernectomy was performed. Some studies have reported that limited WG shows a negative c-ANCA, and that antibiotic therapy improves inflammation. The L-type of limited WG revealed a low-grade positive ratio and titer of c-ANCA. Moreover, L-type limited WG responds well to therapy. We therefore selected PSL administration only against L-type limited WG. We have reported L-type limited WG with eosinophilia and the negative effects of c-ANCA at an early clinical stage.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Endothelin receptor blockade attenuates air embolization-induced pulmonary hypertension in sheep.

We investigated the effects of two types of endothelin receptor antagonists on pulmonary hypertension induced by pulmonary air embolization in awake sheep. We prepared awake sheep with indwelling catheters inserted in blood vessels for continuous monitoring of pulmonary artery pressure, left atrial pressure and systemic arterial pressure. Cardiac output was measured every 30 min. The study consisted of two experiments, one with FR139317 (100 microg/kg/min; (R)2-[(R)-2-[(S)-2-[1-(hexahydro-1H-azepinyl)]-carbonyl]amino-4-++ +methy l-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl)amino-3-(2-pyr idyl)propionic acid), a selective endothelin ET(A) receptor antagonist, and the other with TAK-044 (100 microg/kg/h; cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-yl)carbonyl]-L-alanyl -L- alpha- aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium salt), an endothelin ET(A) and ET(B) receptor antagonist. In the paired experiments, air was continuously (4.06 ml/min) infused into the main pulmonary artery for 3 h after the baseline pressures were stabilized. Sheep were treated or not treated with FR139317 or TAK-044. Pulmonary artery pressure was significantly higher than the baseline pressure after the start of air infusion. Both FR139317 and TAK-044 significantly attenuated the increase in pulmonary artery pressure during air embolization. Plasma endothelin -1 levels in both pulmonary and systemic arteries were equally and significantly increased after the start of air infusion. The results indicate that endothelin-1 release is attributable to the development of pulmonary hypertension during the course of air embolization in awake sheep.

Animals↗
PubMed1999

Strain- and age-dependent loss of sarcoglycan complex in cardiomyopathic hamster hearts and its re-expression by delta-sarcoglycan gene transfer in vivo.

The delta-sarcoglycan (SG) gene is deleted in hamsters with hereditary cardiomyopathies. Immunological analyses of heart before, but not after, the progression of cardiomyopathy (CM) revealed that the BIO 14.6 strain, a model of hypertrophic CM, heterogeneously preserved alpha- and gamma-SG with loss of beta- and delta-SG. In contrast, the TO-2 strain, a model of dilated CM, did not show either SG. Furthermore, in vivo transfer of the full length delta-SG gene to TO-2 hearts expressed all four SGs. Thus, this age- and strain-dependent features suggest a more feasible setting for TO-2 than BIO 14.6 to verify both CM progression and the efficacy of gene therapy.

Age Factors↗
PubMed1999

Precise identification of gene products in hearts after in vivo gene transfection, using Sendai virus-coated proteoliposomes.

Both efficient gene transfer and the exact identification of gene product are required for gene therapy. Gene transfection of green fluorescence protein (GFP) might be useful for the reporter. After in vivo cotransfection of GFP and beta-galactosidase (beta-Gal) genes in Sendai virus-coated proteoliposomes to rat hearts, we compared the sensitivity and specificity of three methods: GFP detection, histochemical staining (HC) of beta-Gal activity, and immunostaining (IS) of the beta-Gal protein. Fluorescence microscopy and double staining of HC and IS revealed that both GFP and IS were equally sensitive and fourfold superior to HC at the peak of gene expression. However, different from skeletal muscle, the GFP of transfected cardiomyocytes showed two demerits: the fluorescence quenching due to the intense staining of beta-Gal activity, and nonspecific autofluorescence from myocardium. Thus, specific IS would be so far the most reliable to identify the gene product in heart.

Animals↗
PubMed1999

Interferon-alpha elevates pulmonary blood pressure in sheep--the role of thromboxane cascade.

We tested the effect of interferon-alpha on lung function to examine whether interferon-alpha causes some pathophysiological change in the lung. We prepared awake sheep with chronic lung lymph fistula, and measured the pulmonary hemodynamics, lung fluid balance and concentrations of prostanoid products. At 1 h after intravenous interferon-alpha administration (18 x 10(6) I.U.), pulmonary arterial pressure and pulmonary vascular resistance were significantly increased compared to the baseline values. The levels of thromboxane B2 in both plasma and lung lymph were increased concomitant with early elevation on pulmonary arterial pressure. In addition, OKY-046 [sodium-3[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid] (10 mg kg(-1)), a selective thromboxane synthase inhibitor, significantly prevented the interferon-alpha-induced pulmonary hypertension and thromboxane B2 production. While no evidence of increased pulmonary vascular leakage was observed. These findings suggest that a single infusion of interferon-alpha stimulates a thromboxane cascade and causes transient pulmonary hypertension. However, interferon-alpha itself or increased thromboxane A2 might not affect the pulmonary vascular permeability in sheep.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Species difference in simultaneous transport and metabolism of ethyl nicotinate in skin.

The objective of this research was to compare the characteristics of skin permeation and metabolism of ethyl nicotinate (EN) among humans and several animal models. In vitro simultaneous skin permeation and metabolism experiment of EN was done in side by side diffusion cells at 37 degrees C. An EN hydrolysis experiment was carried out using skin homogenate and kinetic parameters (Vmax and K(m)) were estimated by computer data-fitting to Michaelis-Menten equation. Both EN and a metabolite, nicotinic acid (NA), were detected in all receiver solutions in permeation studies and no significant chemical hydrolysis was found, indicating that enzymatic hydrolysis of EN occurred during the skin permeation process. Difference in total (EN + NA) flux, from EN-saturated solution, was less than double among various species. The ratio of NA flux to total flux was highest for rat (0.94) followed by hairless rat, mouse, human and hairless mouse (0.76, 0.23, 0.19 and 0.13), and thus a great species difference was found in skin esterase activity. Total flux increased linearly with increase in donor concentration for all species. For hairless rat, mouse and hairless mouse, NA fluxes increased with increase in EN donor concentration and reached a plateau, suggesting that metabolic saturation occurred in skin. Species difference in NA fluxes and EN donor concentration in which the NA flux reached a plateau were also found. In rats, kinetic parameters for EN hydrolysis using skin homogenate were significantly higher than those in mice. These results suggest that species difference in permeation profiles of EN might primarily reflect the difference in esterase activity. To predict skin permeability in human using an animal model, the species difference in skin metabolism should be taken into consideration.

Animals↗
PubMed1999

Soluble fas ligand in natural killer cell lymphoma.

We measured serum soluble Fas ligand (sFasL) in a patient with natural killer cell lymphoma, and investigated relationship between sFasL and liver dysfunction. An elevated level of sFasL was decreased after local radiation therapy, and liver function improved. When lymphoma relapsed, liver dysfunction reappeared and the level of sFasL increased parallelly. Lymphoma cells expressed mRNA of FasL. This suggested that this liver dysfunction was induced by some remote effectors, and sFasL was one of candidates of these effectors.

Adult↗
PubMed1999

Hepatitis C virus structural proteins induce liver cell injury in transgenic mice.

To develop an animal model of hepatitis C virus (HCV) infection, transgenic mice carrying part of the HCV cDNA (C980) encoding HCV-core and envelope proteins under control of the mouse class I major histocompatibility complex gene (H-2K) regulatory region were produced. HCV-C980 RNA and HCV-core protein were present in livers from line H36 as determined by RNase protection assay and immunostaining, respectively. More than 40 animals from line H36 were examined histologically. Most of these H36 mice after 10 months of age developed spontaneous focal infiltration of lymphocytes, hepatocyte necrosis, degeneration, and altered foci with mitotic hepatocytes. These pathological lesions were absent in livers from the age-matched control littermates. Liver cells from these H36 mice were sensitive to damage induced by intravenous administration of an anti-Fas antibody. It is suggested that HCV-C980 proteins by themselves may be one causative agent of liver cell injury in subjects with HCV infection.

Animals↗
PubMed1999

Intestinal blood-flow velocity in uncomplicated preterm infants during the early neonatal period.

BACKGROUND: Intestinal blood-flow changes after birth. Objective. To elucidate the factors influencing intestinal blood-flow velocity in preterm infants during the early neonatal period. MATERIALS AND METHODS: We measured blood-flow velocity in the superior mesenteric artery by pulsed Doppler US in 44 uncomplicated infants with a gestational age of less than 34 weeks and from 1 to 6 days of age. RESULTS: Time-averaged mean blood-flow velocity significantly increased with age from 1 to 6 days old. There was a significant correlation of time-averaged mean blood-flow velocity with birth weight at 1, 2, 4, 5 and 6 days of age and with the amount of enteral feeding from 4 to 6 days of age. Multivariate analysis showed that partial correlation of time-averaged mean blood-flow velocity with birth weight at 2 days of age and that with the amount of enteral feeding at 5 days of age were significant. End-diastolic blood-flow velocity was significantly lower at 1 day of age in infants with patent ductus arteriosus than those without it. CONCLUSIONS: Age, birth weight, the amount of enteral feeding and patent ductus arteriosus are included in the determinants of intestinal blood-flow velocity in preterm infants.

Aging↗
PubMed1999

Immunoblastic lymphadenopathy-like T-cell lymphoma complicated by multiple gastrointestinal involvement.

We report a rare case of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma complicated by multiple gastrointestinal involvement, which appeared to be ameliorated by chemotherapy but resulted in perforative peritonitis. A 66-year-old Japanese woman who had generalized lymphadenopathy and eruptions was admitted to our hospital because of bloody stool. Colonoscopic examination revealed hemorrhagic ulcers in the terminal ileum and a saucer-like ulcer in the cecum. Gastrointestinal endoscopy revealed several ulcerative or elevated lesions in stomach and duodenum. Biopsy specimens of these lesions and of a lymph node showed characteristic histological features of IBL-like T-cell lymphoma. The initial treatment with prednisolone (PSL) and cyclophosphamide (CPA) was effective. Six months after the treatment, however, she developed bloody stool again caused by multiple ulcerative lesions in the large intestine. The recurrence of the disease was determined histologically, and four courses of CPA, PSL, vinblastine sulfate and doxorubicin hydrochloride (CHOP) therapy were administered. One month after completing the CHOP therapy, she developed intestinal obstruction and then acute peritonitis resulting from perforation at an ulcer scar in the jejunum. Surgical treatment was successful, and histological examination demonstrated no lymphoma cells in the resected specimen. A gastrointestinal perforation should be recognized as a potential complication of IBL-like T-cell lymphoma, even during remission.

Aged↗
PubMed1999

Levels of soluble FasL and FasL gene expression during the development of graft-versus-host disease in DLT-treated patients.

Three patients with different clinical symptoms of graft-versus-host disease (GVHD) who had received donor lymphocyte transfusion (DLT) for the treatment of relapsed leukaemia after an allogeneic bone marrow transplantation (BMT) from HLA-matched sibling donors were analysed for the presence of soluble FasL (sFasL) in the sera and for the expression of the Fas ligand (FasL) gene in the peripheral blood mononuclear cells (PBMNC). Two patients who demonstrated liver damage with increased levels of serum bilirubin showed significantly increased levels of serum sFasL. The increase in the sFasL level was observed prior to the increase in the bilirubin during the clinical courses of both patients. The high dose of methyl predonisolone administered to one of these patients greatly reduced the levels of sFasL in the serum. The bilirubin levels were also reduced thereafter. The third patient (without liver damage) did not show any increase in the serum sFasL level. The expression of the FasL gene in the PBMNC of these three patients was examined. All three patients showed increased levels of the FasL gene expression during their clinical courses. However, only one patient showed a parallel alteration of FasL gene expression with sFasL in the serum. These cases provide evidence that the Fas/FasL system is closely associated with human GVHD, especially in the development of liver GVHD.

Adult↗
PubMed1999

A 21-aminosteroid, U-74006F, attenuates endotoxin-induced lung injury in awake sheep.

The purpose of the present study was to examine the efficacy of U-74006F, a 21-aminosteroid, on lung dysfunction induced by endotoxaemia in awake sheep with lung lymph fistula and haemodynamic monitoring. We measured pulmonary haemodynamics, lung lymph balance, circulating leucocyte count, arterial blood gas tensions, and levels of thromboxane (Tx) B2 and 6-keto-prostaglandin (PG) F1 alpha in plasma and lung lymph. We performed two experiments. In experiment 1 (n = 6), we intravenously infused Escherichia coli lipopolysaccharide endotoxin (1 microgram/kg) over 30 min and observed the parameters over 5 h. In experiment 2 (n = 6), we pretreated sheep with an intravenous bolus of U-74006F (2 mg/kg) 30 min before the infusion of endotoxin in the same manner of experiment 1, and continuously infused U-74006F (0.5 mg/kg per h) over 5 h after the bolus during the experiment. The U-74006F significantly suppressed the early pulmonary hypertension, the late increase in pulmonary permeability and the elevations of TxB2 and 6-keto-PGF1 alpha levels in plasma and lung lymph during the early period following endotoxaemia, although the compound did not change the time course of leucocytopenia and hypoxaemia. These findings suggest that the administration of U-74006F attenuates the lung dysfunction induced by endotoxaemia in awake sheep.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Prenatal and postnatal histories of very low birthweight infants who developed hepatoblastoma.

BACKGROUND: Hepatoblastoma in children of very low birthweight (< 1500 g) is increasing in Japan and this has suggested the presence of either a genetic or environmental etiology. This study was aimed at revealing common prenatal and postnatal histories, including family history of hepatoblastomas in children of very low birthweight. METHODS AND RESULTS: The medical records of 15 patients, nine boys and six girls, were reviewed. The patients were diagnosed at the age of 6-77 months (median 16 months). Their birthweight ranged from 560 to 1380 g (median 826 g) and the gestational age was 23-33 weeks (median 25 weeks). No parents were exposed to any occupational risk factors and there were no characteristic features in the parents' history or the maternal reproductive history, although one patient was born to a mother who had taken a contraceptive before she got pregnant with the patient as a result of in vitro fertilization. A ventricular septal defect and an atresia of the external auditory canal were congenital anomalies seen in the patients, but congenital anomalies associated with hepatoblastoma were not seen. Early postnatal illnesses included respiratory distress syndrome in six patients, symptomatic patent ductus arteriosus in three patients, chronic lung disease in seven patients, cytomegalovirus hepatitis in one patient and cholelithiasis in one patient. Oxygen therapy was given to 13 patients for a period of 4-508 days (median 112 days) and lengths of oxygen therapy and assisted ventilation were significantly longer in patients with a stage IIIB or IV tumor than those with a stage II or IIIA tumor (P = 0.0040 and 0.0190, respectively). Furosemide was used in 13 patients for a period of 6-460 days (median 88 days) and the length of the treatment was also significantly longer in patients with advanced tumors (P = 0.0420). Among the patients at 23-25 weeks of gestation, these treatments tended to be longer in patients with a stage IIIB or IV tumor than those with a stage II or IIIA tumor. CONCLUSIONS: These results suggest the presence of an environmental etiology, rather than a genetic one, which is responsible for the development of hepatoblastoma in children of very low birthweight. Close monitoring of the children after being discharged from the neonatal intensive care unit is essential and a case-control study is necessary to identify risk factors for hepatoblastoma in children of very low birthweight.

Child↗