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Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 37 records · Page 2Linked to original sources

Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation.

A 5-year-old boy received CD34-positive HLA haplo-identical bone marrow transplantation from his father as treatment for refractory advanced neuroblastoma. He had residual disease in the para-aortic lymph nodes and multiple bones after the transplant. However, all of his residual disease had disappeared completely 3 years later. He developed grade I acute graft-versus-host disease (GVHD) but had no symptoms of chronic GVHD or any other complications. This case demonstrates the possibility of a graft-versus-tumor effect against neuroblastoma by HLA-mismatched allogeneic hematopoietic stem cell transplantation.

Bone Marrow Transplantation↗

The effect of hematopoietic growth factors on the risk of graft-vs-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis.

The effect of hematopoietic growth factors on neutrophil recovery after allogeneic transplantation is well-recognized. Recent laboratory studies demonstrated that these cytokines may also modify T-cell and dendritic cell function, but whether the effect is strong enough to alter the risk of GVHD is unclear. We performed a meta-analysis to determine the effect of G-CSF or GM-CSF on the risk of nonhematopoietic outcomes after allogeneic transplantation. A search of the literature from 1986 to present yielded 18 publications in which data were provided for cohorts receiving growth factor vs either placebo or no therapy. These included nine prospective randomized studies, eight retrospective cohort studies, and one case-control study comprising a total of 1198 patients. The publication types were heterogeneous with regard to demographic and treatment characteristics, although within publications, comparative groups were generally balanced. The pooled risk ratio estimates with use of growth factor was 1.08 (95% CI 0.87-1.33, P=0.48) for grades 2-4 acute GVHD, 1.22 (95% CI 0.80-1.86, P=0.99) for grades 3-4 acute GVHD, and 1.02 (95% CI 0.82-1.26, P=0.87) for chronic GVHD. This analysis did not detect a significant change in the risk of acute or chronic GVHD after allogeneic hematopoietic stem cell transplantation when hematopoietic growth factors were used to shorten the initial period of neutropenia.

Bone Marrow Transplantation↗

Langerhans' cells in the murine oral mucosa in the inductive phase of delayed type hypersensitivity with 1-chloro-2, 4-dinitrobenzene.

We created a murine model of delayed-type hypersensitivity (DTH) to 1-chloro-2, 4-dinitrobenzene (DNCB). Using this murine model, we compared oral mucosal sensitization and skin sensitization for the difference in reaction during the elicitation phase. Evaluation of sensitizability, using the mouse ear swelling test (MEST) after oral mucosal or skin sensitization, showed that the ear swelling response peaked 24 h after challenge. The optimal induction concentration was 1.0% in both oral mucosal and skin sensitization, resulting in a positive reaction rate of 100%. However, the ear swelling response 24 h after challenge with the optimal concentration of DNCB (1.0%) was significantly lower in oral mucosal than in skin sensitization. We compared the oral mucosal and skin sensitization sites for the number of Langerhans' cells (LC) and the antigen-presenting capability in the induction phase. The numbers of F4/80+ major histocompatibility complex (MHC) class II+ LC before induction did not differ significantly between the oral mucosa and the skin. After induction, F4/80+ MHC class II+ LC increased in number, but the increase was significantly smaller in the oral mucosa than in the skin. MEST on anti-CD86 antibody-administered mice showed that ear swelling was similarly suppressed after oral mucosal or skin sensitization. In murine models of DTH after oral mucosal sensitization, the number of F4/80+CD86+ LC increased after induction, but the increase was significantly smaller than that in murine models of DTH after skin sensitization. This study showed that, in murine models of DTH, oral mucosal sensitization elicited a weaker reaction than skin sensitization. This was presumably because oral mucosal sensitization induced fewer LC, resulting in lower antigen-presenting capability.

Animals↗

What cause of mortality can we predict by cholesterol screening in the Japanese general population?

OBJECTIVE: In a population with a markedly lower coronary mortality such as in Japan, the benefit of cholesterol screening may be different from Western populations. We attempted to assess the importance of cholesterol screening in Japan. DESIGN: A 13.2-year cohort study for cause-specific mortality. SETTING: Three hundred randomly selected districts throughout Japan in which the National Survey on Circulatory Disorders 1980 was performed. SUBJECTS: A total of 9216 community dwelling persons aged 30 years and over, with standardized serum cholesterol measurement and without a past history of cardiovascular disease. RESULTS: There were 1206 deaths, which included 462 deaths due to cardiovascular disease with 79 coronary heart diseases. Hypercholesterolemia (>6.21 mmol L-1) showed a significant positive relation to coronary mortality (relative risk; 2.93, 95% confidence interval; 1.52-5.63) but not to stroke. Although hypocholesterolemia (<4.14 mmol L-1) was significantly associated with an increased risk of liver cancer, noncardiovascular, noncancer disease and all-cause mortality, these associations, except for liver cancer, disappeared after excluding deaths in the first 5 years of the follow-up. The multivariate adjusted attributable risk of hypercholesterolaemia for coronary disease was 0.98 per 1000 person-years, which was threefold higher than that of hypocholesterolemia for liver cancer: 0.32 per 1000 person-years. The attributable risk percentage of hypercholesterolaemia was 66% for coronary heart disease. CONCLUSION: Similar to Western populations, it is recommended to provide screening for hypercholesterolaemia in Japan, especially for males, although its attributable risk for coronary disease might be small.

Adult↗

Tentorial schwannoma: a case report.

A rare case of tentorial schwannoma in a 29-year-old male is described. The schwannoma was located within the leaves of the tentorium. MRI showed a wedge-shaped enhancing tumour. Exact nerve of origin of the tumour could not be identified. We speculate that the tumour arose from the tentorial branch of the trigeminal nerve. The literature concerning intracranial schwannoma unrelated to a major cranial nerve is reviewed.

Adult↗

Detection of a pineoblastoma with large central cyst in a young child.

THE PATIENT: We present the very rare case of a pineoblastoma with large central cyst in a 7-year-old boy who presented with a short history of gradually worsening headache and upward gaze palsy. IMAGING INVESTIGATIONS: On CT and MRI studies, it was seen as a peripherally calcified, irregularly shaped mass with heterogeneous low signal intensity on T1-weighted images and ringed enhancement after gadolinium administration; there was homogeneous high signal intensity on T1-weighted images. DISCUSSION: We discuss differential diagnosis for several types of cystic tumors in the pineal region, including pineoblastomas.

Brain Diseases↗

Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation: comparison of an antigenemia assay and quantitative real-time polymerase chain reaction.

Cytomegalovirus (CMV) antigenemia and quantitative real-time polymerase chain reaction (PCR) were compared for monitoring of CMV reactivation after allogeneic stem cell transplantation. The number of CMV antigen-positive cells by the antigenemia assay and the level of CMV DNA by real-time PCR correlated well. The sensitivity and specificity of the antigenemia assay was 55.4% and 95.5%, respectively, using real-time PCR as the reference standard. The probability of positive antigenemia at day 100 was 76.5%, with a median of first detection at day 37 in 51 patients, compared with a positive PCR of 84.3% and day 33, respectively. When HLA-identical sibling donor transplant recipients and other donor transplant recipients were analyzed separately, there was no difference between the two tests. However, temporal patterns of first detection of CMV antigen-positive cells and CMV DNA differed between HLA-identical and alternative recipients; patients without CMV (29%) or with sporadic positive PCR results (14%) were more common in HLA-identical sibling transplants, whereas patients with simultaneous antigenemia and positive PCR occurred more in alternative transplants (48%). Two of 51 patients (4%) developed CMV colitis despite antigenemia-guided prophylaxis, but both were successfully treated with ganciclovir. Although PCR is more sensitive than antigenemia, both tests are useful in the early detection of CMV after allogeneic stem cell transplantation.

Adolescent↗

A simple method to estimate populational 24-h urinary sodium and potassium excretion using a casual urine specimen.

In order to estimate the salt and potassium intake in a population and to compare their annual trends, we developed a simple method to estimate population mean levels of 24-h urinary sodium (24HUNaV) and potassium (24HUKV) excretion from spot urine specimens collected at any time. Using 591 Japanese data items from the INTERSALT study as a gold standard, we developed formulas to estimate 24-h urinary creatinine (24HUCrV), 24HUNaV and 24HUKV using both spot and 24-h urine collection samples. To examine the accuracy of the formulas, we applied these equations to 513 external manual workers. The obtained formulas were as follows: (1) PRCr (mg/day) = -2.04 x age + 14.89 x weight (kg) + 16.14 x height (cm) -2244.45; (2) estimated 24HUNaV (mEq/day) = 21.98 x XNa (0.392); (3) estimated 24HUKV (mEq/day) = 7.59 x XK(0.431); where PRCr = predicted value of 24HUCr, SUNa = Na concentration in the spot voiding urine, SUK = K concentration in the spot voiding urine, SUCr = creatinine concentration in the spot voiding urine, XNa (or XK) = SUNa (or SUK)/SUCr x PRCr. In the external group, there was a significant but small difference between the estimated and measured values in sodium (24.0 mmol/day) and potassium (3.8 mmol/day) excretion. In every quintile divided by the estimated 24HUNaV or 24HUKV, the measured values were parallel to the estimated values. In conclusion, although this method is not suitable for estimating individual Na and K excretion, these formulas are considered useful for estimating population mean levels of 24-h Na and K excretion, and are available for comparing different populations, as well as indicating annual trends of a particular population.

Adult↗

[A case report of ross operation and ventricular septal defect closure following correction of type A interruption by modified Blalock-Park, pulmonary artery banding and patent ductus arteriosus division].

A 2-year-old boy who had undergone a correction of a type A interruption using a modified Blalock-Park operation, pulmonary artery banding and the division of a patent ductus arteriosus, underwent a Ross operation and closure of ventricular septal defect (VSD). Although a pre-operative echo cardiogram revealed a bicuspid aortic valve, and a Doppler echocardiogram showed only 10 mmHg of pressure gradient across the aortic valve, Ross procedure was performed as a procedure accompanying the closure of a total conus VSD. The total conus VSD was closed with a Dacron patch using pledget mattress sutures. In addition, a running suture was applied over the denuded aortic root and the cranial margin to achieve water tight closure. An aortic root replacement procedure was our first choice for the Ross operation. After both coronary buttons were re-implanted into pulmonary sinuses, a pulmonary artery autograft was wrapped around by the remaining aortic wall for reinforcement to prevent future dilatation. The main pulmonary artery was reconstructed using a bicuspid pericardial valve conduit with a diameter of 24 mm. A post-operative echocardiogram showed no neoaortic valve regurgitation, good coaptation of tri-leaflets, mild regurgitation of pericardial valve and good cardiac performance.

Abnormalities, Multiple↗

[A modified Fontan operation in the presence of a supracardiac total anomalous pulmonary venous connection].

We report a case of 2-year-old girl with asplenia syndrome who successfully underwent modified Fontan procedure and concomitant repair of supracardiac total anomalous pulmonary venous connection (TAPVC). The preoperative diagnosis included a common atrioventricular canal (type C), a double outlet right ventricle, a common atrium, common atrioventricular valve regurgitation, pulmonary stenosis, and a bilateral superior vena cava (SVC). Cardiac catheterization revealed a Qp/Qs of 1.3, mean PA pressure of 16 mmHg and an Rp of 1.3. The TAPVC drained to left SVC (LSVC) at a position proximal to the hemiazygos vein with an ostium of 5 mm in diameter. The LSVC was divided distal to its connection to the common pulmonary vein (CPV). The TAPVC ostium was cut back into the CPV, then it was anastmosed with posterior aspect of the atrial wall in an effort to provide a wide anastomosis. The postoperative course was uneventful and the patient was discharged from hospital on the 35th postoperative day.

Abnormalities, Multiple↗

Superior outcome of infant acute myeloid leukemia with intensive chemotherapy: results of the Japan Infant Leukemia Study Group.

This study analyzed data on 35 infants with acute myeloid leukemia (AML) who were treated with intensive chemotherapy between 1995 and 1998 in Japan. The incidence of boys, younger age (< 6 months old), and hyperleukocytosis at onset was high in patients with the M4/M5 subtype (n = 23) in the French-American-British classification, compared with the non-M4/M5 subtype (n = 12). Thirteen (56%) and 16 (70%) patients with the M4/M5 subtype also showed 11q23 translocations and MLL gene rearrangements, respectively, whereas only one patient with the non-M4/M5 subtype had this rearrangement. All 35 patients were treated with the ANLL91 protocol consisting of etoposide, high-dose cytarabine, and anthracyclines. Overall survival and the event-free survival (EFS) rates at 3 years of all patients were 76% (95% confidence interval [CI], 61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no significant difference between 2 subgroups divided by age, gender, presence of the MLL gene rearrangements, and white blood cell count at onset; EFS in patients with the M4/M5 subtype tended to be better than those with the non-M4/M5 subtype. Although all 6 patients who underwent allogeneic stem cell transplantation (SCT) have been in complete remission, no benefit of SCT was confirmed. These findings suggest that the intensive chemotherapy with the ANLL91 protocol might have been responsible for the observed good outcome of infant AML, even without SCT. The presence of the MLL gene rearrangements or the age at onset had no impact on the outcome of infant AML.

Aclarubicin↗

Phosphorylation of proteins and apoptosis induced by c-Jun N-terminal kinase1 activation in rat cardiomyocytes by H(2)O(2) stimulation.

Cytokines and various cellular stresses are known to activate c-Jun N-terminal kinase-1 (JNK1), which is involved in physiological function. Here, we investigate the activation of JNK1 by oxidative stress in H9c2 cells derived from rat cardiomyocytes. H(2)O(2) (100 microM) significantly induces the tyrosine phosphorylation of JNK1 with a peak 25 min after the stimulation. The amount of JNK1 protein remains almost constant during stimulation. Immunocytochemical observation shows that JNK1 staining in the nucleus is enhanced after H(2)O(2) stimulation. To clarify the physiological role of JNK1 activation under these conditions, we transfected antisense JNK1 DNA into H9c2 cells. The antisense DNA (2 microM) inhibits JNK1 expression by 80% as compared with expression in the presence of the sense DNA, and significantly blocks H(2)O(2)-induced cell death. Consistent with the decrease in cell number, we detected condensation of the nuclei, a hallmark of apoptosis, 3 h after H(2)O(2) stimulation in the presence of the sense DNA for JNK1. The antisense DNA of JNK1 inhibits the condensation of nuclei by H(2)O(2). Under these conditions, the H(2)O(2)-induced phosphorylation of proteins with molecular masses of 55, 72, and 78 kDa is blocked by treatment with the antisense DNA for JNK1 as compared with the sense DNA for JNK1. These findings suggest that JNK1 induces apoptotic cell death in response to H(2)O(2), and that the cell death may be involved in the phosphorylations of 55, 72, and 78 kDa proteins induced by JNK1 activation.

Animals↗

Ischemic preconditioning attenuates cardiac sympathetic nerve injury via ATP-sensitive potassium channels during myocardial ischemia.

BACKGROUND: During myocardial ischemia, massive norepinephrine (NE) is released from the cardiac sympathetic nerve terminals, reflecting the sympathetic nerve injury. A brief preceding ischemia can reduce infarct size; this is known as ischemic preconditioning (PC). The effect of PC on sympathetic nerves, however, including its underlying mechanisms in dog hearts, has remained unclear. Thus, this study was designed to elucidate whether the activation of ATP-sensitive potassium (K(ATP)) channels is involved in the mechanism of cardiac sympathetic nerve protection conferred by PC. METHODS AND RESULTS: Interstitial NE concentration was measured by the in situ cardiac microdialysis method in 45 anesthetized dogs. Five minutes of ischemia followed by 5 minutes of reperfusion was performed as PC. In the controls, the dialysate NE concentration (dNE) increased 15-fold after the 40-minute ischemia. PC decreased dNE at 40-minute ischemia by 59% (P<0.01), which was reversed by glibenclamide. A K(ATP) channel opener, nicorandil (25 microg. kg(-1). min(-1) IV), decreased dNE at 40 minutes of ischemia by 76% (P<0.01), which was also reversed by glibenclamide. During the PC procedure, no significant increase in dNE was detected, even with the uptake-1 inhibitor desipramine. CONCLUSIONS: Cardiac sympathetic nerve injury during myocardial ischemia was attenuated by PC via the activation of K(ATP) channels, but the trigger of the PC effect is unlikely to be NE release in dog hearts.

Adenosine Triphosphate↗

Clinical and virologic characteristics of chronic active Epstein-Barr virus infection.

Thirty patients with chronic active Epstein-Barr virus (CAEBV) infection were analyzed. The study group included 18 male and 12 female patients, ranging in age from 5 to 31 years with a mean age of 14.2 years. Not all patients had high titers of EBV-specific antibodies, but all patients had high viral loads in their peripheral blood (more than 10(2.5) copies/microg DNA). Fifty percent of the patients displayed chromosomal aberrations, and 79% had monoclonality of EBV. Patients were divided into 2 clinically distinct groups, based on whether the predominantly infected cells in their peripheral blood were T cells or natural killer (NK) cells. Over a 68-month period of observation, 10 patients died from hepatic failure, malignant lymphoma, or other causes. Patients with T-cell CAEBV had a shorter survival time than those with NK-cell type of disease.

Adolescent↗

Relatively selective neuronal nitric oxide synthase inhibition by 7-nitroindazole in monkey isolated cerebral arteries.

The selectivity of 7-nitroindazole in inhibiting endothelial and neuronal nitric oxide synthases (eNOS and nNOS) was investigated by comparing its inhibitory action on relaxations mediated by nitric oxide (NO) in response to stimulation of perivascular nerves and in response to histamine in monkey cerebral artery strips. 7-Nitroindazole at 2 x 10(-5) M moderately attenuated the response to transmural electrical stimulation and to nicotine, but did to alter the endothelium-dependent relaxation in response to histamine in cimetidine-treated strips. Raising the concentration of 7-nitroindazole to 10(-4) M abolished the neurogenic response, partially inhibited the histamine-induced relaxation, but did not affect the response to NO. It is concluded that 7-nitroindazole is a relatively selective nNOS inhibitor; however, at high concentrations, it inhibits eNOS in monkey cerebral arteries.

Animals↗