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Biomedical subjects

R Tanaka

Publications and source records attributed to R Tanaka.

At least 37 records · Page 2Linked to original sources

Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial.

In this Phase I/II trial, the patient's peripheral blood dendritic cells were pulsed with an autologous tumour lysate of the glioma. Seven patients with glioblastoma and three patients with anaplastic glioma, ranging in age from 20 to 69 years, participated in this study. The mean numbers of vaccinations of tumour lysate-pulsed dendritic cells were 3.7 times intradermally close to a cervical lymph node, and 3.2 times intratumorally via an Ommaya reservoir. The percentage of CD56-positive cells in the peripheral blood lymphocytes increased after immunisation. There were two minor responses and four no-change cases evaluated by radiological findings. Dendritic cell vaccination elicited T-cell-mediated antitumour activity, as evaluated by the ELISPOT assay after vaccination in two of five tested patients. Three patients showed delayed-type hypersensitivity reactivity to the autologous tumour lysate, two of these had a minor clinical response, and two had an increased ELISPOT result. Intratumoral CD4+ and CD8+ T-cell infiltration was detected in two patients who underwent reoperation after vaccination. This study demonstrated the safety and antitumour effects of autologous tumour lysate-pulsed dendritic cell therapy for patients with malignant glioma.

Adult↗

Mesenchymal chondrosarcoma of the sellar region.

BACKGROUND: It is known that, although rare, mesenchymal chondrosarcoma can originate intracranially. However, no such malignant tumour has been described in the sellar region. CLINICAL PRESENTATION: We report a case of mesenchymal chondrosarcoma in a 21-year-old man who presented with double vision, right blepharoptosis and facial pain. Upon initial admission, no endocrinological abnormalities were found, and computed tomography and magnetic resonance imaging revealed a mass with calcification in the sella and right cavernous sinus. INTERVENTION: For this malignant tumour, three surgical resections, two sessions of gamma-knife radiosurgery, one session of fractional irradiation, and one cycle of chemotherapy were performed, resulting in only brief arrest of the tumour growth. Pathologically, the tumour consisted of undifferentiated small cells of high cellularity, and islands of hyaline cartilage. The undifferentiated small cells showed immunoreactivity for vimentin and ultrastructural features suggesting a mesenchymal origin. Lacunar cells in the islands were immunopositive for S-100 protein and vimentin. CONCLUSION: Although malignant tumours in the sellar region are rare, they should be considered in the differential diagnosis of various sellar tumours typified by non-functioning pituitary adenoma, and mesenchymal chondrosarcoma is one possible candidate.

Adult↗

Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia.

Brain ischemia induces a marked response of resident microglia and hematopoietic cells including monocytes/macrophages. The present study was designed to assess the distribution of microglia/macrophages in cerebral ischemia using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). At 24 h after middle cerebral artery occlusion (MCAO), many round-shaped EGFP-positive cells migrated to the ischemic core and peri-infarct area. At 48-72 h after MCAO, irregular round- or oval-shaped EGFP/ionized calcium-binding adapter molecule 1 (Iba 1)-positive cells increased in the transition zone, while many amoeboid-shaped or large-cell-body EGFP/Iba 1-positive cells were increased in number in the innermost area of ischemia. At 7 days after MCAO, many process-bearing ramified shaped EGFP/Iba 1-positive cells were detected in the transition to the peri-infarct area, while phagocytic cells were distributed in the transition to the core area of the infarction. The distribution of these morphologically variable EGFP/Iba 1-positive cells was similar up to 14 days from MCAO. The present study directly showed the migration and distribution of bone marrow-derived monocytes/macrophages and the relationship between resident microglia and infiltrated hematogenous element in ischemic mouse brain. It is important to study the distribution of intrinsic and extrinsic microglia/macrophage in ischemic brain, since such findings may allow the design of appropriate gene-delivery system using exogenous microglia/macrophages to the ischemic brain area.

Animals↗

Successful treatment of natural killer (NK) cell leukemia following a long-standing chronic active Epstein-Barr virus (CAEBV) infection with allogeneic bone marrow transplantation.

The optimal treatment for natural killer (NK) cell leukemia after chronic active Epstein-Barr virus (CAEBV) infection has not been determined. A 15-year-old boy presented with NK cell leukemia following CAEBV infection for 5 years. The peripheral blood and BM had an increased number of CD3(-)CD56(+) large granular lymphocytes and a monoclonal integration of the EBV genome was detected. Chemotherapy was not sufficiently effective to control the disease. Allogeneic BMT from an HLA-identical sister was performed using a conditioning regimen consisting of total body irradiation, cyclophosphamide and thiotepa. The patient is disease-free with a perfect performance status 24 months after BMT. This is the first report to show that allogeneic BMT is potentially able to cure NK cell leukemia after CAEBV infection.

Adolescent↗

MxA expression in patients with viral infection after allogeneic stem cell transplantation.

Many patients suffer febrile diseases soon after allogeneic stem cell transplantation (SCT). Some of the symptoms of viral infections and acute GVHD are often difficult to distinguish. However, an accurate diagnosis is important since the treatments for these conditions are different. It is known that MxA protein is specifically induced in patients with several viral infections. We investigated the cytoplasmic expression of MxA in the peripheral blood mononuclear cells (PBMCs) of patients with fever after allogeneic SCT using a newly generated monoclonal antibody (KM1135) and flow cytometry. The level of MxA expression was significantly higher in patients diagnosed with viral infections (n=6, cytomegalovirus in three, Epstein-Barr virus in one, human herpesvirus-6 in one, adenovirus in one) than control individuals (n=9) (P<0.05, Mann-Whitney test). The level of MxA in patients with aGVHD (n=7) was identical to that in controls. The level of MxA correlated well with the amount of the cytomegalovirus antigen-positive cells in the presence of acute GVHD in two patients. The measurement of MxA is simple and useful in distinguishing viral disease from acute GVHD after allogeneic SCT.

Adolescent↗

Seven-hour fluorescence in situ hybridization technique for enumeration of Enterobacteriaceae in food and environmental water sample.

AIMS: A fluorescent in situ hybridization (FISH) technique using an Enterobacteriaceae-specific probe (probe D) to target 16S rRNA was improved in order to enumerate, within a single working day, Enterobacteriaceae present in food and environmental water samples. METHODS AND RESULTS: In order to minimize the time required for the FISH procedure, each step of FISH with probe D was re-evaluated using cultured Escherichia coli. Five minutes of ethanol treatment for cell fixation and hybridization were sufficient to visualize cultured E. coli, and FISH could be performed within 1 h. Because of the difficulties in detecting low levels of bacterial cells by FISH without cultivation, a FISH technique for detecting microcolonies on membrane filters was investigated to improve the bacterial detection limit. FISH with probe D following 6 h of cultivation to grow microcolonies on a 13 mm diameter membrane filter was performed, and whole Enterobacteriaceae microcolonies on the filter were then detected and enumerated by manual epifluorescence microscopic scanning at magnification of x100 in ca 5 min. The total time for FISH with probe D following cultivation (FISHFC) was reduced to within 7 h. FISHFC can be applied to enumerate cultivable Enterobacteriaceae in food (above 100 cells g-1) and environmental water samples (above 1 cell ml-1). CONCLUSIONS: Cultivable Enterobacteriaceae in food and water samples were enumerated accurately within 7 h using the FISHFC method. SIGNIFICANCE AND IMPACT OF THE STUDY: A FISHFC method capable of evaluating Enterobacteriaceae contamination in food and environmental water within a single working day was developed.

Colony Count, Microbial↗

Primary malignant mixed mesenchymal tumour of the heart in a dog.

A case of primary malignant mixed mesenchymal tumour of the heart in an 8-year-old golden retriever is described. The cardiac tumour, measuring 2.5 x 3 x 5 cm, was located in the posterior part of the atrial septum, extending into the surrounding region. Histologically, the tumour was composed of multiple mesenchymal elements of fibrosarcoma, rhabdomyosarcoma, liposarcoma and chondrosarcoma. No previous reports of such a tumour occurring in the heart of the dog were found in the literature.

Animals↗

Surgical correction of cor triatriatum dexter in a dog under extracorporeal circulation.

A shiba inu dog with marked abdominal distension was diagnosed with cor triatriatum dexter and surgical correction was performed under extracorporeal circulation. The total duration of cardiac arrest was 11 minutes and total perfusion time was 34 minutes. The dog had an uneventful postoperative recovery. Postoperative contrast radiography of the caudal vena cava revealed normal flow into the right heart. Abdominal distension was no longer observed. Although several methods have been used to treat cor triatriatum dexter in dogs, the authors consider surgical correction under extracorporeal circulation to be a reliable approach.

Animals↗

Pharmacology of novel heteroaromatic polycycle antibacterials.

Heteroaromatic polycycle (HARP) compounds are a novel class of small (M(w), 600 to 650) DNA-binding antibacterials. HARP compounds exhibit a novel mechanism of action by preferentially binding to AT-rich sites commonly found in bacterial promoters and replication origins. Noncovalent binding in the minor groove of DNA results in inhibition of DNA replication and DNA-dependent RNA transcription and subsequent bacterial growth. HARP compounds have previously been shown to have potent in vitro activities against a broad spectrum of gram-positive organisms. The present report describes the extensive profiling of the in vitro and in vivo pharmacology of HARP antibacterials. The efficacies of representative compounds (GSQ-2287, GSQ-10547, and GSQ-11203), which exhibited good MIC activity, were tested in murine lethal peritonitis and neutropenic thigh infection models following intravenous (i.v.) administration. All compounds were efficacious in vivo, with potencies generally correlating with MICs. GSQ-10547 was the most potent compound in vitro and in vivo, with a 50% effective dose in the murine lethal peritonitis model of 7 mg/kg of body weight against methicillin-sensitive Staphylococcus aureus (MSSA) and 13 mg/kg against methicillin-resistant S. aureus (MRSA). In the neutropenic mouse thigh infection model, GSQ-11203 reduced the bacterial load (MRSA and MSSA) 2 log units following administration of a 25-mg/kg i.v. dose. In a murine lung infection model, treatment with GSQ-10547 at a dose of 50 mg/kg resulted in 100% survival. In addition to determination of efficacy in animals, the pharmacokinetic and tissue disposition profiles in animals following administration of an i.v. dose were determined. The compounds were advanced into broad safety screening studies, including screening for safety pharmacology, genotoxicity, and rodent toxicity. The results support further development of this novel class of antibiotics.

Acetamides↗

Magnetoencephalographic representation of the sensorimotor hand area in cases of intracerebral tumour.

OBJECTIVE: To assess the clinical value of magnetoencephalography (MEG) in localising the primary hand motor area and evaluating cortical distortion of the sensorimotor cortices in patients with intracerebral tumour. METHODS: 10 normal volunteers (controls) and 14 patients with an intracerebral tumour located around the central region were studied. Somatosensory evoked magnetic fields (SEFs) following median nerve stimulation, and movement related cerebral magnetic fields (MRCFs) following index finger extension, were measured in all subjects and analysed by the equivalent current dipole (ECD) method to ascertain the neuronal sources of the primary sensory and motor components (N20m and MF, respectively). These ECD locations were defined as the primary hand sensory and motor areas and the positional relations between these two functional areas in controls and patients were investigated. RESULTS: The standard range of ECD locations of MF to N20m was determined in controls. In 11 of the 14 patients, MRCFs could identify the primary motor hand area. ECD locations of MF were significantly closer to the N20m in the medial-lateral direction in patients than in controls. In patients with a tumour located below the sensorimotor hand area, relative ECD locations of MF to N20m moved anteriorly over the standard range determined in the control subjects. These MEG findings correlated well with radiological tumour locations. The mean estimated ECD strength of MF was significantly lower in patients than in controls. CONCLUSIONS: MRCF was useful in localising the primary motor hand area in patients with intracerebral tumour. The relative ECD locations of MF to N20m describe the anatomical distortion of the sensorimotor cortex.

Adult↗

Ictal magnetoencephalographic discharges from elementary visual hallucinations of status epilepticus.

PURPOSE: To report the rare opportunity to study ictal magnetoencephalography (MEG) in a 26 year old man with simple partial status epilepticus that presented as elementary visual hallucinations (EVHs) in the right upper visual field. METHODS: The patient described his EVHs as "snowing on TV," "flickering lights," and "rotating coloured balls" that continued for several days. MEG and simultaneous EEG were recorded twice: during an episode of EVHs (ictal recordings) and after EVHs were controlled by medications (interictal recordings). RESULTS: During EVHs, MEG showed continuous periodic epileptiform discharges over the left posterior superior temporal region, while simultaneous EEG showed rhythmic theta waves and sporadic spikes over the left temporal region. The MEG discharge consisted of a three phase spike complex. Equivalent current dipoles (ECDs), modelled from spike complexes, localised in the left superior temporal area. After drug treatment controlled the EVHs, interictal MEG and EEG showed rare spikes over the same left temporal region. The average ictal ECD moment (mean (SD)) (128.7 (32.8 nAm)) was significantly weaker than the average interictal ECD moment (233.0 (63.9) nAm) (p<0.05). CONCLUSIONS: The continuous, periodic, and clustered discharges seen on ictal MEG were the sources of EVH. The weaker ictal ECD sources were frequently not detected by scalp EEG, while the stronger interictal sources, presumably originating from an extensive interictal zone, were sufficiently large to be seen as EEG spikes.

Adult↗

Thickness of the roof of the glenoid fossa and condylar bone change: a CT study.

OBJECTIVES: The aim of this study is to investigate the relationship between the thickness of the roof of the glenoid fossa in the temporomandibular joint (TMJ) and the existence and types of condylar bone change. MATERIALS AND METHODS: Helical CT was used to measure the thickness of the roof of the glenoid fossa at its thinnest part in 37 orthodontic patients with temporomandibular disorders. Condylar bone changes were classified into four types: no bone change (24 joints); flattening (19 joints); osteophyte formation (13 joints); and erosion (18 joints). RESULTS: The roof of the glenoid fossa was significantly thicker in joints with bone change than in joints with no bone change (Mann-Whitney U-test, P<0.05). There was also a significant difference in relation to the type of condylar bone change: the thickness of the roof of the glenoid fossa in the erosion group was significantly greater than in the no bone change (P<0.01), flattening (P<0.05) and osteophyte formation (P<0.05) groups (Kruskal-Wallis and Games-Howell tests). CONCLUSION: Compensative bone formation in the roof of the glenoid fossa might help to withstand the increased stress in the TMJ accompanying condylar bone change, especially erosion.

Adolescent↗

Successful treatment of relapsed blastic natural killer cell lymphoma with unrelated cord blood transplantation.

The prognosis for blastic natural killer (NK) cell lymphoma is generally dismal. We report a patient who was successfully treated with unrelated cord blood transplantation (UCBT). A 15-year-old boy was diagnosed as having blastic NK cell lymphoma in the cervical lymph nodes. Autologous peripheral blood stem cell transplantation was performed on achieving a complete remission. However, the disease recurred in the bone marrow 6 months later. Chemotherapy induced a second remission and the patient received UCBT with a conditioning regimen consisting of total body irradiation, thiotepa and cyclophosphamide. Chronic GVHD of the lung occurred, but it was well controlled with steroids. At the time of writing, he remains in remission 18 months after UCBT with an excellent performance status. UCBT may be an option for patients with blastic NK cell lymphoma.

Adolescent↗

Oligonucleotide probe for detecting Enterobacteriaceae by in situ hybridization.

AIMS: To develop oligonucleotide probes for visualizing bacteria belonging to Enterobacteriaceae. METHODS AND RESULTS: 24-mer oligonucleotide probe (probe D) was designed by comparison of 16S rDNA sequences of 35 species of Enterobacteriaceae, eight species of Vibrionaceae and six species of Pasteurellaceae. The sequence of the probe corresponding to the complementary sequence of a position 1251-1274 of Escherichia coli 16S rRNA was found to be a highly conserved region of 16S rDNA sequence in Enterobacteriaceae different from that of Vibrionaceae and Pasteurellaceae. The fluorescent dye-labelled probe was tested for the specificity by in situ hybridization and epifluorescence microscopy. Seventy-six out of 78 strains belonging to Enterobacteriaceae were visualized in an optimal hybridization condition. No bacterial strains belonging to Vibrionaceae (31 strains) and Gram-positive bacteria (three strains) were visualized. CONCLUSIONS: In situ hybridization using probe D allows the detection of bacterial cells belonging to Enterobacteriaceae without false positive reaction. SIGNIFICANCE AND IMPACT OF THE STUDY: In situ hybridization techniques using the probe D are potential tools for detecting Enterobacteriaceae in food and water samples.

DNA, Bacterial↗

A novel synbiotic therapy dramatically improved the intestinal function of a pediatric patient with laryngotracheo-esophageal cleft (LTEC) in the intensive care unit.

To demonstrate the beneficial effects of synbiotic therapy (combined use of probiotics and prebiotics) in critically ill patients, we designed a new protocol for such therapy. Three agents were used as synbiotics: Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides. More than 1 x 10(9) of probiotic bacteria were contained in each 1.0 g pack. We administered 3.0 g per day of each agent to the patient.A critically ill 9-month-old girl with laryngotracho-esophageal cleft (type IV) was treated by our new synbiotic therapy. Abundant amounts of synbiotic bacteria were detected in the feces which suggests that these administered bacteria affected intestinal function in situ. Bowel movements resumed soon after the commencement of synbiotic therapy and considerable amounts of short chain fatty acids were detected in the feces. Growth of the patient was satisfactory under this treatment. Our new synbiotic therapy had a beneficial effect to improve intestinal function. We recommend synbiotic therapy for critically ill patients in intensive care units as an important immunonutritional therapy.

Abnormalities, Multiple↗

Pathogenicity and virulence of Candida dubliniensis: comparison with C. albicans.

Candida dubliniensis is a newly described fungus that is frequently isolated from the oral cavities of HIV-positive patients. Although extensive studies have been performed on the phylogeny of C. dubliniensis, little is known about the pathogenic ecology of this yeast. Here we examined aspects related to C. dubliniensis in comparison with those of C. albicans. When injected intravenously into mice, C. dubliniensis had a higher survival rate than C. albicans. Histopathological analysis disclosed that C. dubliniensis remained mostly in the yeast form in the infected organs, whereas C. albicans changed into the mycelial form. The host inflammatory reaction was aggressive with C. dubliniensis infection and mild with C. albicans infection. Co-culture of the yeasts with human polymorphonuclear leukocytes disclosed that C. dubliniensis is more vulnerable to the fungicidal activity of leukocytes than C. albicans. C. dubliniensis was also more susceptible to the toxic effect of hydrogen peroxide. When cultured in vitro, C. dubliniensis grew more slowly than C. albicans, but the formation of germ tubes was faster. When the fungi were cultured in RPMI 1640, a fetal bovine serum supplement suppressed the growth of C. dubliniensis but enhanced that of C. albicans. These results clearly indicated that C. dubliniensis is less virulence than C. albicans.

Animals↗