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Biomedical subjects

K Nakai

Publications and source records attributed to K Nakai.

At least 19 recordsLinked to original sources

Brain abscess following intracerebral haemorrhage.

We report two cases of brain abscess, which developed at the site of an intracerebral haemorrhage (ICH) in a 75-year-old man and a 32-year-old-man. The patients recovered after surgical treatment and systemic antibiotic therapy. The route of infection could not be detected in either case. The literature contains only 13 reported cases of brain abscess as a complication of ICH. Although the interval from initial ICH to abscess formation ranged from 4 to 20 weeks, almost all patients had episodes of high fever, indicating the presence of systemic infection and bacterial seeding, 0-14 days after the onset of their ICH. Therefore, abscess formation appears to be caused by haematogenous seeding of infection in patients with ICH. Abscess formation should be considered when a patient deteriorates clinically with a febrile episode after an ICH.

Adult↗

A minimally invasive endoscopic transsphenoidal approach with an endonasal septal pushover technique by using a modified nasal speculum.

Whereas the endoscopic endonasal transsphenoidal approach has been applied in patients with pituitary lesions as a potentially efficacious and less invasive surgical technique, the sinonasal step of a series of the surgical procedures is generally not well known to neurosurgeons. This is one of the reasons why the endoscopic technique has not been fully been adopted as a routine surgical procedure approaching towards the sella. The present paper describes the technical details of a purely endoscopic approach using an endonasal septal pushover technique. We also present a newly designed nasal speculum specialized for this endoscopic endonasal technique. As compared to the endoscopic endonasal approach previously reported, the surgical procedure required for sphenoidotomy with the aid of the modified speculum was simplified and thereby less time-consuming. This technique has been performed in 40 patients with several types of pituitary lesions. All patients recovered rapidly without significant rhinological complications. Despite a limited number of cases, our experience suggests that this simplified endoscopic technique could encourage a more routine use of endoscopes in the endonasal approach for pituitary lesions.

Adenoma↗

Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.

Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

Adolescent↗

IL-4-producing CD8(+) T cells may be an immunological hallmark of chronic GVHD.

Chronic graft-versus-host disease (cGVHD) occurs in approximately 60-80% of those who survive over 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the pathophysiology of cGVHD is poorly understood. To gain more insight into the immunological mechanism of cGVHD, we examine cytokine production of peripheral blood T cells from 19 patients in the chronic phase of allo-HSCT. The percentage of IFN-gamma-producing CD8(+) T cells among CD8(+) T cells was significantly higher in patients with or without cGVHD than in normal control subjects (P<0.001). On the other hand, the percentage of IL-4-producing CD8(+) T cells among CD8(+) T cells was significantly higher in patients with cGVHD (mean 3.3%; range 1.3-8.2%) than in patients without cGVHD (mean 1.2%; range 0.8-1.7%) and normal control subjects (mean 1.1%; range 0.1-1.6%) (both P<0.001). By contrast, the percentage of IL-4-producing CD4(+) T cells was not different among patients with and without cGVHD and normal controls. These findings suggest that IL-4-producing CD8(+) T cells may be an immunological marker of cGVHD.

Adolescent↗

Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease.

Disease-free survival in Philadelphia chromosome-positive ALL (Ph + ALL) is very poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph + ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (P < 0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (P < 0.0001, P < 0.0001, P = 0.0301, P = 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others.

Adolescent↗

Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for myelodysplastic syndrome (MDS). The object of this study was to evaluate the impact of chemotherapy before allo-SCT. We analyzed the data of 283 patients who underwent allo-SCT from an HLA-identical sibling donor for MDS that were reported to the Japan Society for Hematopoietic Cell Transplantation. The cumulative incidence of grade II-IV acute GVHD was 33%. Overall survival (OS) at 5 and 10 years was 48.8 and 42.5%, respectively. Multivariate analyses identified karyotype, FAB classification, and the history of chemotherapy before allo-SCT as significant predictors for OS. OS at 5 years was 57% for patients who underwent allo-SCT as a primary treatment for refractory anemia with excess blasts in transformation (RAEB-t) or secondary acute myeloid leukemia (AML) and 54% for those who underwent allo-SCT in remission after induction chemotherapy (P=0.81). The proportion of patients with a poor karyotype was equivalent between the two groups (P=0.44). Although only a randomized controlled trial will be able to establish a definite conclusion, these results do not support the administration of induction chemotherapy for patients with RAEB-t or secondary AML before allo-SCT.

Adolescent↗

Trial of remote telemedicine support for patients with chronic respiratory failure at home through a multistation communication system.

To create and test a multistation telemedicine support system, three remote locations were connected: the homes of two patients with chronic respiratory failure, the hospital of the attending physician, and the hospital of the pulmonary specialist. Real-time connections were set up between the three locations. Medical history and biologic variables were noninvasively recorded, including blood pressure, arterial oxygen saturation, three-lead electrocardiogram, and end-tidal carbon dioxide. Both physicians shared in these data real-time. If necessary, the respiratory specialist could provide medical advice to the attending physician based on the patient's condition. The trial program resulted in the same information being exchanged remotely using the multi-station telemedicine system that would be exchanged in a direct, face-to-face encounter. This result, together with the improvement in quality of life and the establishment of appropriate treatment and cooperation between the respiratory specialist and attending physician, suggests our system can be considered useful and promising for further use.

Aged↗

Bayesian joint prediction of associated transcription factors in Bacillus subtilis.

Sigma factors, often in conjunction with other transcription factors, regulate gene expression in prokaryotes at the transcriptional level. Specific transcription factors tend to co-occur with specific sigma factors. To predict new members of the transcription factor regulon, we applied Bayes rule to combine the Bayesian probability of sigma factor prediction calculated from microarray data and the sigma factor binding sequence motif, the motif score of the transcription factor associated with the sigma factor, the empirically determined distance between the transcription start site to the cis-regulatory region, and the tendency for specific sigma factors and transcription factors to co-occur. By combining these information sources, we improve the accuracy of predicting regulation by transcription factors, and also confirm the sigma factor prediction. We applied our proposed method to all genes in Bacillus subtilis to find currently unknown gene regulations by transcription factors and sigma factors.

Bacillus subtilis↗

Combination of boron and gadolinium compounds for neutron capture therapy. An in vitro study.

In neutron capture therapy, the therapeutic effect of the boron compound is based on alpha particles produced by the B(n, alpha) reaction while with the gadolinium compound the main radiation effect is from gamma rays derived from the Gd(n, gamma) reaction. The uptake and distribution within the tumor may be different among these compounds. Thus, the combination of the boron and gadolinium compounds may be beneficial for enhancing the radiation dose to the tumor. Chinese hamster fibroblast V79 cells were used. For the neutron targeting compounds, 10B (BSH) at 0, 5, 10, and 15 ppm, and 157Gd (Gd-BOPTA) at 0, 800, 1600, 2400, 3200, and 4800 ppm, were combined. The neutron irradiation was performed with thermal neutrons for 30 min. (neutron flux: 0.84 x 10(8) n/cm2/s in free air). The combination of the boron and gadolinium compounds showed an additive effect when the gadolinium concentration was lower than 1600 ppm. This additive effect decreased as a function of gadolinium concentration at 2400 ppm and resulted in no additive effect at more than 3200 ppm of gadolinium. In conclusion, the combination of the boron and gadolinium compounds can enhance the therapeutic effect with an optimum concentration ratio. When the gadolinium concentration is too high, it may weaken the boron neutron capture reaction due to the high cross-section of gadolinium compound against neutrons.

Animals↗

Magnetic noise rejection in the MCG using independent component analysis.

In magnetocardiogram (MCG) measurements, the magnetic noise from any magnetic wire, used to suture the sternum after heart surgery, becomes a problem. As one method of noise rejection, independent component analysis is seen here to be effective. In this study, MCG measurements were carried out under conditions where a wire was attached to a normal subject, also where no wire was attached. Signal processing by independent component analysis was carried out in order to reduce the effect of magnetic noise from the wire. From the comparison of the waveforms after this signal processing and the waveforms where the wire was not attached, it was apparent that the magnetic noise from the wire was reduced. Thus, we have shown that independent component analysis is effective for the reduction of magnetic noise from a magnetic wire, in MCG measurements.

Electricity↗

Verification of the computational dosimetry system in JAERI (JCDS) for boron neutron capture therapy.

Clinical trials for boron neutron capture therapy (BNCT) by using the medical irradiation facility installed in Japan Research Reactor No. 4 (JRR-4) at Japan Atomic Energy Research Institute (JAERI) have been performed since 1999. To carry out the BNCT procedure based on proper treatment planning and its precise implementation, the JAERI computational dosimetry system (JCDS) which is applicable to dose planning has been developed in JAERI. The aim of this study was to verify the performance of JCDS. The experimental data with a cylindrical water phantom were compared with the calculation results using JCDS. Data of measurements obtained from IOBNCT cases at JRR-4 were also compared with retrospective evaluation data with JCDS. In comparison with phantom experiments, the calculations and the measurements for thermal neutron flux and gamma-ray dose were in a good agreement, except at the surface of the phantom. Against the measurements of clinical cases, the discrepancy of JCDS's calculations was approximately 10%. These basic and clinical verifications demonstrated that JCDS has enough performance for the BNCT dosimetry. Further investigations are recommended for precise dose distribution and faster calculation environment.

Algorithms↗

Predicting gene regulation by sigma factors in Bacillus subtilis from genome-wide data.

MOTIVATION: Sigma factors regulate the expression of genes in Bacillus subtilis at the transcriptional level. We assess the accuracy of a fold-change analysis, Bayesian networks, dynamic models and supervised learning based on coregulation in predicting gene regulation by sigma factors from gene expression data. To improve the prediction accuracy, we combine sequence information with expression data by adding their log-likelihood scores and by using a logistic regression model. We use the resulting score function to discover currently unknown gene regulations by sigma factors. RESULTS: The coregulation-based supervised learning method gave the most accurate prediction of sigma factors from expression data. We found that the logistic regression model effectively combines expression data with sequence information. In a genome-wide search, highly significant logistic regression scores were found for several genes whose transcriptional regulation is currently unknown. We provide the corresponding RNA polymerase binding sites to enable a straightforward experimental verification of these predictions.

Algorithms↗

Current clinical results of the Tsukuba BNCT trial.

Nine high grade gliomas (5 glioblastomas and 4 anaplastic astrocytomas) were treated with BSH-based intaoperative boron neutron capture therapy (IOBNCT). BSH (100 mg/kg body weight) was intravenously injected, followed by single fraction irradiation using the mixed thermal/epithermal beam of Japan Research Reactor 4. The blood boron level at the time of irradiation averaged 29.9 (18.8-39.5)microg/g. The peak thermal neutron flux as determined by post-irradiation measurements varied from 1.99 to 2.77x10(9) n cm(-2)s(-1). No serious BSH-related toxicity was observed in this series. The interim survival data in this study showed median survival times of 23.2 months for glioblastoma and 25.9 months for anaplastic astrocytoma, results which are consistent with the current conventional radiotherapy with/without boost radiation. Of the 4 residual tumors, 2 showed complete response (CR) and 2 showed partial response (PR) within 6 months following BNCT. No linear correlation was proved between the dose and the occurrence of early neurological events. The maximum boron dose of 11.7-12.2 Gy in the brain related to the occurrence of radiation necrosis. The clinical application of a mixed thermal/epithermal beam and JRR-4 facilities on BSH-based IOBNCT proved to be safe and effective in this series.

Adult↗

Improvement of dose calculation accuracy for BNCT dosimetry by the multi-voxel method in JCDS.

To carry out boron neutron capture therapy (BNCT) clinical trials based on accurate dosimetry of several dose components given to a patient, we had developed the JAERI computational dosimetry system (JCDS), which can determine the absorbed doses by numerical simulation. The verification results of initial version of JCDS indicated that JCDS causes characteristic discrepancy, when JCDS estimates a sharp change arising such as near the surface. The aim of this study is to improve the accuracy of the BNCT dosimetry efficiently. The multi-voxel calculation method that reconstructs the original voxel model by combining several voxel cell sizes such as 0.125, 1 and 8 cm(3) has been developed. To verify the accuracy of the method, the calculation results were compared with the phantom experimental data. Furthermore, to verify its practicality to BNCT, retrospective evaluation of an actual BNCT in JRR-4 was performed by the multi-voxel method. The results of the comparison with the phantom experiments demonstrated that the calculation accuracy for the distributions of the thermal neutron flux was improved by employing the multi-voxel method. The computing time using the multi-voxel method increased only approximately 33% compared to the conventional uniform 1cm(3) voxel method. These results proved that the multi-voxel calculation enables JCDS to more accurately estimate the absorbed doses to a patient by efficient calculations.

Boron Neutron Capture Therapy↗

Kernohan's phenomenon associated with left ruptured occipital arteriovenous malformation.

A 23-year-old woman presented with ipsilateral hemiparesia due to rupture of a left occipital arteriovenous malformation (AVM). Emergency decompression (the onset-operation interval was 46 minutes,) was carried out and the patient could leave the hospital upon recovery without neurological deficits. In general, Kernohan's phenomenon is caused by the gradual displacement of the cerebral peduncle against the tentorial edge caused by compression by the contralateral mass. This phenomenon is very rare among the cases with spontaneous intracranial hemorrhage and only three cases including the present one have been reported in the literature. In all cases the onset-operation intervals of were very short. Kernohan's phenomenon associated with a ruptured AVM is a rare condition and emergency decompression is required.

Adult↗

Intra-arterial steroid-injection therapy for steroid-refractory acute graft-versus-host disease with the evaluation of angiography.

We treated three patients with steroid-refractory acute graft-versus-host disease (aGVHD) with intra-arterial steroid-injection therapy (IAST). Two patients with gut aGVHD received IAST into both superior and inferior mesenteric arteries, while one patient with liver aGVHD received IAST into the proper hepatic artery. The volume of stools and the bilirubin level improved soon after IAST. Angiography of the superior and inferior mesenteric arteries was performed in the two patients with steroid-refractory gut aGVHD, and identical abnormal findings were obtained. IAST might be an earlier option for steroid-refractory aGVHD.

Acute Disease↗

Inhibition of nuclear factor kappa B activation and inducible nitric oxide synthase transcription by prolonged exposure to high glucose in the human keratinocyte cell line HaCaT.

BACKGROUND: In human skin, inducible nitric oxide synthase (iNOS) appears to be a key enzyme during wound healing and has roles in protection from infection. We speculated that diabetic skin complications such as delayed wound healing and skin infection were due to iNOS activity altered by high glucose in skin keratinocytes. OBJECTIVES: The purpose of this study was to see how high levels of glucose affect iNOS activity in the human keratinocyte cell line (HaCaT). METHODS: HaCaT cells were exposed to high glucose for 1 day or 10 days. We measured nitric oxide (NO) end product nitrite in the culture medium using the Griess reagent, and intracellular tetrahydrobiopterin (BH(4), a cofactor of NOS) content by using high-performance liquid chromatography, analysed the expression level of iNOS mRNA by the reverse transcriptase-polymerase chain reaction method and evaluated the DNA binding activity of nuclear factor kappa B (NF-kappaB) by enzyme-immunoassay. RESULTS: Short-term exposure (1 day) to a high level of glucose increased BH(4) and iNOS activity at the post-translational level. However, long-term exposure (10 days) to high glucose downregulates NF-kappaB binding activity and inhibits iNOS transcription and its activity. CONCLUSIONS: Pretreatment with high glucose for 10 days down-regulated NF-kappaB activity and inhibited iNOS transcription and NO production, implying the involvement of a deficiency in NO synthesis in both skin infection and impaired wound healing in diabetic patients.

Antioxidants↗

Atrophic dermatofibroma.

Atrophic dermatofibroma, a newly proposed entity in recent times, is thought to be a specific variant of dermatofibroma. We report a typical case of atrophic dermatofibroma on the thigh of a 69-year-old female. The lesion consisted clinically of a light brown, intracutaneous nodule with a central crateriform depression, and histologically of fibrohistiocytic components in the thinning dermis. On elastica van Gieson stain, loss of elastic fibres and dense accumulation of elastic fibres around medium-sized vessels were observed in the lesion.

Aged↗