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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 37 records · Page 2Linked to original sources

Mediastinal emphysema and bilateral pneumothoraces with chronic GVHD in patients after allogeneic stem cell transplantation.

It is difficult to treat lung complications caused by chronic graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). We retrospectively analyzed the characteristics of five patients with mediastinal emphysema (ME) and bilateral pneumothoraces (BP) caused by chronic lung GVHD after allo-SCT. Four of these patients had undergone unrelated SCT, and three had had HLA-identical unrelated donors. All patients received total body irradiation (TBI) during conditioning. Immunosuppressive agents were administered as GHVD prophylaxis, but two patients developed acute GVHD and all the five developed chronic GVHD. The onset of lung complications was 99-1915 days (median, 202 days) after SCT. The onset of ME and BP was 6-48 days (median, 23 days) after the onset of lung complications. Immunosuppressive agents were initially beneficial on the lung complications, but the patients later showed no response to therapy, and all died from respiratory failure 7-195 days (median, 28 days) after the development of ME and BP. The results suggest that these complications progress rapidly, are resistant to treatment, and have a poor prognosis. It is therefore important to start prophylaxis and treatment as early as possible.

Adolescent↗

Successful non-T-cell-depleted nonmyeloablative hematopoietic stem cell transplantation (NST) from an HLA-haploidentical 2-loci-mismatched sibling in a heavily transfused patient with severe aplastic anemia based on the fetomaternal microchimerism.

A 37-year-old Japanese man with systemic hemochromatosis due to multiple transfusions was referred to us for the treatment of severe aplastic anemia (SAA), from which he had been suffering for 24 years. The patient had diabetes arising from the hemochromatosis, chronic anal fissures, and a kidney abscess due to neutropenia. He was treated with a nonmyeloablative preconditioning regimen followed by non-T-cell-depleted (non-TCD) allogeneic peripheral blood stem cell transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical 2-loci-mismatched sibling. Prompt engraftment of granulocytes and platelets was observed, and graft-versus-host disease was easy to control. Noninherited maternal antigens in the donor were confirmed prior to PBSCT, and they were also detected in small quantities in the recipient. This report describes the first successful nonmyeloablative hematopoietic stem cell transplant in a heavily transfused SAA patient from an HLA-haploidentical 2-loci-mismatched sibling donor. The result suggests that a long-term fetomaternal microchimerism-positive sibling can be a second-line donor if an alternative HLA-identical donor is not available.

Adult↗

Cerebral cortex activity during supramaximal exhaustive exercise.

AIM: The purpose of this study was to examine the effect of fatigue resulting from supramaximal dynamic exercise on cerebral cortex activity. METHODS: Five healthy male subjects (age 24.6+/-0.4 years, body weight 62.9+/-1.1 kg, height 175.3+/-1.2 cm, and maximal O2 uptake per body mass 48.4+/-1.3 ml/kg/min) participated in this study. All subjects performed at 120% of maximal oxygen uptake (VO2peak) on a cycle ergometer until reaching a state of volitional fatigue. Cerebral oxygenation was measured by near-infrared spectroscopy (NIRS) throughout the supramaximal constant exhaustive exercise. RESULTS: The mean exercise duration of the subjects was 147.2+/-3.4 s. The peak value of blood lactate concentration within 3-10 min after the exercise test was 14.4+/-0.1 mmol/l. Cerebral oxygenation (8.8+/-1.8 micromol/l) was increased significantly during the first minutes of exercise compared with the pre-exercise value (p<0.05) and cerebral oxygenation decreased with the passage of time during exercise. Cerebral oxygenation at the end of exercise decreased significantly compared with the resting value (-29.9+/-3.4 micromol/l, p<0.05). CONCLUSION: These findings suggest that the exhaustive exercise induces the decrease of cerebral function and that the fatigue resulting from dynamic exercise decreases the cerebral cortex activity.

Adult↗

Possible efficacy of lamivudine treatment to prevent hepatitis B virus reactivation due to rituximab therapy in a patient with non-Hodgkin's lymphoma.

We used regimens containing rituximab in the treatment of five hepatitis B virus surface antibody (HBsAb)-positive patients with non-Hodgkin's lymphoma (NHL). Serum levels of HBsAb were obtained and analyzed in four of these patients. Two patients were HBs antigen (HBsAg) positive. One of these HBsAg-positive patients was treated with lamivudine because the patient developed fulminant hepatitis from hepatitis B virus (HBV) infection prior to chemotherapy. However, none of the other patients were administered lamivudine. An HBsAg-positive patient who did not receive lamivudine treatment later developed fulminant hepatitis. Another HBsAg-positive patient receiving lamivudine prophylaxis did not develop severe hepatitis arising from HBV. In the three patients not receiving lamivudine treatment, serum HBsAb titers decreased soon after the administration of rituximab. These results suggest that rituximab reduced the antibody titer for HBV, thus inducing an immunological environment leading to easy reactivation of HBV. Lamivudine prophylaxis was effective, at least when rituximab was given to an HBsAg-positive patient with non-Hodgkin's lymphoma.

Aged↗

Phase I/II study of daily carboplatin, 5-fluorouracil and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities and the response rate of carboplatin and 5-fluorouracil administered daily with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, unresectable stage IIIA or IIIB non-small-cell lung cancer (NSCLC) were enrolled. Carboplatin (20-40 mg m(-2) 2-h infusion, daily) and 5-fluorouracil (200 mg m(-2) 24-h continuous infusion, daily) were administered concurrently with radiotherapy on days 1-33. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions on days 1-40. In the phase I portion, the daily dose of carboplatin was escalated from 20 to 40 mg m(-2). Once the maximum tolerated dose (MTD) and recommended dose (RD) of carboplatin was determined, the study entered the phase II portion. In the phase I portion, the daily MTD and RD of carboplatin were 40 and 35 mg m(-2), respectively. The dose-limiting toxicity was neutropenia. In the following phase II study, 30 patients were entered and the objective response rate was 76.7% (95% CI, 62-92%) and the local control rate was 85.7%. The median survival time was 19.8 months, with a survival rate of 70% at 1 year, 36.7% at 2 years. The major toxicities of treatment were neutropenia (>or=grade 3, 87.9%) and thrombocytopenia (>or=grade 3, 23.3%). This combined therapy for locally advanced non-small-cell lung cancer is promising and shows acceptable toxicity.

Adult↗

The risk of persistent carriage of methicillin-resistant Staphylococcus aureus in hematopoietic stem cell transplantation.

The clinical course of hematopoietic stem cell transplantation (HSCT) recipients was retrospectively analyzed to determine whether carriage of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for MRSA infection during the neutropenic period. We studied four patients in whom MRSA colonies developed before HSCT. Two patients were previously diagnosed as having MRSA infection and two were carriers of MRSA. We tried to eliminate MRSA before HSCT and succeeded in eradication in two patients. MRSA infection did not develop in one patient who received prophylactic administration of vancomycin (VCM), but MRSA-induced phlegmon developed during neutropenia in one patient who did not receive prophylaxis. Of the other two patients who had been persistently positive for MRSA, MRSA did not develop in one patient who received prophylaxis, but the another patient who did not receive prophylaxis died from MRSA-induced sepsis in the early post-transplant period. We therefore recommend that MRSA be eliminated by prophylactic administration of anti-MRSA drugs such as VCM before HSCT when patients have persistent MRSA.

Adolescent↗

Latent HIV-1 reactivation in transgenic mice requires cell cycle -dependent demethylation of CREB/ATF sites in the LTR.

OBJECTIVE: We previously produced a line of transgenic mice that carried the HIV-1 genome deficient in the gene. Although the HIV-1 genome in the lymphocytes was dormant under normal physiological conditions, it could be reactivated by lipopolysaccharide (LPS) administration via induction of interleukin-1alpha/beta and tumour necrosis factor-alpha. In this report, we analysed further the reactivation mechanism of the latent HIV-1 using this transgenic mouse model. DESIGN: and methods: Possible involvement of CpG methylation in HIV-1 latency was examined by treating transgenic lymphocytes with a demethylating agent, 5'-azacytidine. CpG methylation in the HIV-1 long terminal repeat (LTR) was analysed using the bisulfite genomic sequencing method. As previous studies suggested that CpG demethylation depended on the cell cycle progression, we analysed the relation between cell cycle progression and LPS-induced reactivation of HIV-1 by labelling lymphocytes with an intracellular fluorescein, carboxyfluorescein diacetate succinimidyl ester. RESULTS: We found that 5'-azacytidine enhanced HIV-1 expression ninefold compared to treatment with LPS alone. Furthermore, HIV-1 p24 induction by LPS was observed only in cells that had undergone cell division, while induction was prevented in cells in which cell cycle progression was blocked either by mimosine, aphidicolin, or nocodazole. LPS-induced HIV-1 reactivation was associated with demethylation of two CpG sites located in the CREB/ATF binding sites in the HIV-1 LTR in a cell cycle-dependent manner. CONCLUSIONS: These observations indicate that cell cycle progression-dependent demethylation of the CREB/ATF sites in the LTR is crucial for the reactivation of latent HIV-1 genome in transgenic mice.

Activating Transcription Factors↗

Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori.

The relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been investigated in several studies. We investigated the prevalence of H. pylori infection and the clinical effects of eradication in 22 Japanese patients with chronic ITP. H. pylori infection was found in 14 (63.6%) of the patients by histologic and culture examinations of biopsy samples obtained by gastrointestinal endoscopy. H. pylori was eradicated by proton pump inhibitors and 2 kinds of antibiotics in 13 (92.9%) of the 14 patients in whom the results of treatment could be evaluated. Five (38.4%) of those 13 patients had platelet recovery (platelet count of more than 100 x 10(9)/L and an increase of more than 30 x 10(9)/L with respect to the baseline value) after eradication. The median follow-up period was 15 months. One patient who had a complete response had a partial relapse after cessation of prednisolone treatment without any evidence of H. pylori reinfection. Another patient, in whom H. pylori was not eradicated even after 2 treatment sessions, had a partial response after treatment. A screening examination for H. pylori infection may be necessary for Japanese patients with newly diagnosed ITP. Although the exact mechanism underlying platelet recovery after H. pylori eradication is not clear, the results of this study indicated that H. pylori eradication treatment is a good option for some patients with chronic ITP.

Adult↗

Microstructure analysis of calcium phosphate formed in tendon.

The surface of soft tendon tissue has been modified using calcium phosphate in order for the tendon to directly connect with hard bone and reconstruct an injured ligament. Calcium phosphate was coated onto the tendon in a soaking process using alternating a CaCl(2) (200 mM) and a Na(2)HPO(4) (120 mM) solution. According to SEM/EDX observations, calcium phosphate was formed, not only on the tendon surface, but also inside the tendon tissue. When the tendon was treated with seven soaking cycles, calcium phosphate was detected between 0-500 microm from the tendon surface. According to TEM observations, the crystal morphology of calcium phosphate depends on the distance from the surface. Hydroxyapatite crystals were observed near the surface, while octa-calcium phosphate crystals could be observed further from the surface, thus at initial soaking. The crystals were formed on collagen fibrils in spaces between the collagen fibrils with the c-axes of the crystals aligned parallel with the collagen fibrils. This finding suggests Ca(2+) ions to interact with the tendon surface, most probably with the carboxyl functional groups of collagen, and subsequently forming nucleation centers for the crystals.

Journal Article↗

Adenovirus-mediated overexpression of a gene prevents hearing loss and progressive inner hair cell loss after transient cochlear ischemia in gerbils.

The use of adenoviral vectors has recently provided a novel strategy for direct gene transfer into the cochlea. In this study, we assessed the utility of an adenoviral vector expressing glial-cell-derived neurotrophic factor (GDNF) in ischemia-reperfusion injury of the gerbil cochlea. The vector was injected through the round window 4 days before ischemic insult. The distribution of a reporter transgene was confirmed throughout the cochlea from the basal to the apical turn and Western blot analysis indicated significant upregulation of GDNF protein 11 days following virus inoculation. Hearing ability was assessed by sequentially recording compound action potentials (CAP), and the degree of hair cell loss in the organ of Corti was evaluated in specimens stained with rhodamine-phalloidin and Hoechst 33342. On the seventh day of ischemia, the CAP threshold shift and inner hair cell loss were remarkably suppressed in the Ad-GDNF group compared with the control group. These results suggest that adenovirus-mediated overexpression of GDNF is useful for protection against hair cell damage, which otherwise eventually occurs after transient ischemia of the cochlea.

Adenoviridae↗

Newly developed 3D endoscopic system: preliminary experience.

Although there have been earlier reports on the use of three-dimensional endoscopic systems in the gastrointestinal tract, real-time three-dimensional imaging has not previously been described. This paper presents experience in three cases with a novel endoscopic system for three-dimensional observation in clinical situations. Case 1 was a hyperplastic gastric polyp, the shape of which was considerably enhanced in comparison with two-dimensional endoscopic viewing. Case 2 was an advanced esophageal cancer, in which the sense of depth was improved in the esophagus. Case 3 was a depressed early gastric cancer, the shape of which was also enhanced. Between July 2001 and March 2002, three experienced endoscopists also used this new system in a further 34 patients. A three-dimensional endoscopic environment was visible with the system in all patients, and all of the endoscopists were able to obtain visual information regarding spatial depth. This experience suggests that the three-dimensional video-endoscopic system used here can be of value in gastrointestinal endoscopy.

Endoscopy, Gastrointestinal↗

Virtual histology of colorectal lesions using laser-scanning confocal microscopy.

BACKGROUND AND STUDY AIMS: Histological examination of gastrointestinal lesions is currently based on light-microscopic examination of thin-slice specimens, with hematoxylin and eosin staining. A study of the use of laser-scanning confocal microscopy (LCM) to obtain immediate microscopic images of untreated specimens for examining colorectal lesions was carried out. A probe-type LCM prototype endomicroscope that can be passed through the working channel of an endoscope has also been developed. MATERIALS AND METHODS: The study materials consisted of colorectal lesions resected either endoscopically or surgically at Showa University Northern Yokohama Hospital. One hundred untreated specimens were examined using LCM. The histopathological findings in the lesions were seven cases of normal colonic mucosa, five hyperplastic polyps, 68 adenomas with low-grade dysplasia, 10 adenomas with high-grade dysplasia, and 10 adenocarcinomas. An argon laser beam with a wavelength of 488 nm was used for the LCM study. Observation of the resected normal colonic mucosa (in vitro) and the rectal mucosa of a healthy volunteer (in vivo) was possible using the endomicroscope. The LCM images for each specimen were compared with the hematoxylin-eosin-stained histopathological cross-sections. RESULTS: The LCM images corresponded well with the conventional hematoxylin-eosin light-microscopic images. The nuclei were not visualized in normal mucosa or hyperplastic polyps. In adenomas with high-grade dysplasia and carcinomas, nuclei were more often visible than in adenomas with low-grade dysplasia. The rate of visualization of nuclei was significantly different ( P < 0.01) between these two groups (60.0 % vs. 10.3 %). In LCM images using endomicroscope, it was possible to recognize the orifices of the colonic glands and goblet cells both in vitro and in vivo. CONCLUSIONS: Laser-scanning confocal microscopy provides immediate images that correspond well with those of hematoxylin-eosin staining. An improved probe-type LCM endomicroscope is being developed which should provide better histological images of colorectal lesions in vivo.

Adenocarcinoma↗

[Ventricular pseudo-false aneurysm after myocardial infarction; report of a case].

A 72-year-old man was admitted to our hospital with chest discomfort and syncope. The echocardiography showed the left ventricular aneurysm. The coronary arteriography revealed a complete occlusion at distal portion of the right coronary artery and anterior aneurysm of the left ventricle was demonstrated. We diagnosed that it was false aneurysm because of communicating with the left ventricle through a small orifice. Surgical repair was carried out after resection of the aneurysm of the left ventricle. The postoperative course was uneventful and discharged on the 33rd day after surgery. Pseudo-false ventricular aneurysm of the left ventricle was diagnosed by histological examination.

Aneurysm, False↗