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Biomedical subjects

T Okada

Publications and source records attributed to T Okada.

At least 55 records · Page 3Linked to original sources
PubMed2004

Differential roles of interleukin-1beta and interleukin-8 in neutrophil transendothelial migration in patients with Helicobacter pylori infection.

BACKGROUND: Little information is currently available on the contribution of locally generated inflammatory and chemotactic cytokines to endothelial cell activation and subsequent neutrophil transendothelial migration in patients with Helicobacter pylori (H. pylori)-associated gastritis. METHODS: The contents of interleukin (IL)-1beta and IL-8 in the organ culture supernatants of antral mucosal tissues were measured with an enzyme-linked immunosorbent assay. The effects of the endogenous IL-1beta and IL-8 in mucosal tissues on neutrophil adherence and transendothelial migration were investigated using an experimental model of human umbilical vein endothelial cells (HUVEC). RESULTS: The contents of IL-1beta and IL-8 in organ cultures of antral mucosal tissues were significantly higher in patients with H. pylori infection than in those without infection. The organ culture supernatants from H. pylori-positive patients induced the expression of intercellular adhesion molecule-1 mRNA in HUVEC with increased binding of neutrophils, and these stimulatory effects were inhibited when HUVEC were pretreated with a nuclear factor-kappaB inhibitor, MG-132. Moreover, neutrophil adherence to HUVEC induced by the supernatants decreased after preincubation with neutralizing anti-IL-1beta antibody. As compared with the supernatants from H. pylori-negative patients, the samples from H. pylori-positive patients exhibited a significantly higher chemotactic activity for neutrophils, which was inhibited almost completely by preincubation of the supernatants with anti-IL-8 antibody. CONCLUSIONS: Locally generated IL-1beta and IL-8 could coordinate with each other during the process of neutrophil infiltration into the gastric mucosa in patients with H. pylori infection.

Adolescent↗
PubMed2004

Long-term efficacy of immunoadsorbent plasmapheresis in a patient with Budd-Chiari syndrome due to antiphospholipid syndrome: case report with nine-year follow-up.

We describe the safety and efficacy of long-term immunoadsorbent plasmapheresis (IAPP) with dextran sulfate-cellulose bead columns in antiphospholipid syndrome (APS). IAPP was administered to a 38-year old male Japanese patient with APS with Budd-Chiari syndrome (BCS), who had presented with refractory lower leg skin ulcers and arterial and venous thromboses including BCS. After hepatic vein transluminal angioplasty was performed, the combination of corticosteroid, aspirin and IAPP was administered because of an underlying bleeding tendency related to liver dysfunction. From February 1994 to February 2003, a total of 228 procedures were performed. No further thrombosis-related symptoms or bleeding have occurred for more than nine years, suggesting that IAPP with dextran sulfate cellulose columns is safe and effective for APS in preventing additional thrombotic events. This IAPP supplements anticoagulation, antiplatelet, corticosteroid and immunosuppressant therapies.

Adult↗
PubMed2003

Vestibular perception in patients with acquired ophthalmoplegia.

Using a perceptual technique it is shown that patients with chronic external ophthalmoplegia have shortened vestibular responses. It is postulated that this is secondary to the retinal image slip experienced by these patients during head movements and a useful compensatory mechanism to suppress motion-induced sickness and spatial disorientation.

Adult↗
PubMed2003

Extirpation of mass-screened adrenal neuroblastomas by retroperitoneoscopy.

BACKGROUND: A mass-screened neuroblastoma (MSN) shows low-grade malignancy. Although the tumor is small, open laparotomy requires a large incision. PURPOSE: Extirpation by retroperitoneoscopy (ER) was performed in children with MSN to reduce the surgical stress. METHODS: The indications for ER were (1) MSN originating from the adrenal gland and (2) a tumor size of less than 4 cm. Between January 2000 and June 2002, 6 children (mean age: 8.5 +/- 0.6 months) underwent ER. RESULTS: All children successfully underwent ER and no conversion of laparoscopy to open surgery was required. The only complication in one patient was a peritoneal tear. Oral intake was possible in all children the day after the operation. No port site metastasis or local recurrence was observed during follow-up (15 to 29 months). CONCLUSIONS: Adrenal MSN less than 4 cm were successfully extirpated by ER. This method has the advantage of allowing patients an early return to eating and has no risk of postoperative ileus. ER is an available surgical technique for children with MSN less than 4 cm.

Adrenal Gland Neoplasms↗
PubMed2003

Facial affect recognition in pre-lingually deaf people with schizophrenia.

The present study examined facial affect recognition in pre-lingually deaf individuals with schizophrenia. Affective facial-labeling task and the control task of face feature processing (the Benton facial recognition test) were performed by deaf subjects with schizophrenia using French sign language (FSL), hearing subjects with schizophrenia, and hearing healthy controls. Deaf subjects with schizophrenia performed more poorly than hearing clinical controls with schizophrenia or healthy controls on the affective facial-labeling task. No differences were found on the control task between deaf subjects with schizophrenia and hearing clinical or healthy controls. The results showed that facial affect recognition and face feature processing were differently impaired in pre-lingually deaf individuals with schizophrenia, suggesting that neurocognitive backgrounds of impaired affective facial processing may be distinct from those of general impairment in face processing.

Adult↗
PubMed2003

Multicystic dysplastic kidney detected by prenatal ultrasonography: natural history and conservative management.

Conservative management of multicystic dysplastic kidney (MCDK) without nephrectomy has recently been advocated. The purpose of this study was to determine the clinical course of conservatively managed unilateral MCDK detected prenatally. Between 1991 and 2001, ten children (three boys and seven girls) with unilateral MCDK detected by prenatal ultrasonography (US) were prospectively followed at our institution. At birth, US confirmed the prenatal findings in all cases. All patients underwent voiding cystourethrography, intravenous pyelography, and radionuclide scans. Postnatal follow-up US examinations were performed every 3 months until patients were 5 years old and annually from then forward. The mean age at diagnosis during the prenatal period was 29 weeks of gestation (range 21-38 weeks). Median follow-up time was 42 months (range 17-125 months). Follow-up US was performed in eight children; three (38%) showed partial resolution, three (38%) complete resolution, and two (24%) no change in cyst size. The mean age at complete resolution of the lesion was 23 months (range 9-33 months). No children developed hypertension or tumors, and all maintained normal growth. In the present study, the natural history of MCDK was benign, and serial US monitoring showed that the affected kidneys frequently showed resolution with time. The results of this study support the conclusion that a nonsurgical approach for patients with MCDK is advisable.

Child, Preschool↗
PubMed2003

Neural substrates participating in acquisition of facial familiarity: an fMRI study.

The amygdala is related to recognition of faces and emotions, and functional magnetic resonance imaging (fMRI) studies have reported that the amygdala is habituated over time with repetition of facial stimuli. When subjects are presented repeatedly with unfamiliar faces, they come to gradually recognize the unfamiliar faces as familiar. To investigate the brain areas participating in the acquisition of familiarity to repeatedly presented unfamiliar faces, we conducted an fMRI study in 16 healthy subjects. During the task periods, the subjects were instructed to see presented unfamiliar faces repeatedly and to judge whether the face was male or female or whether the face had emotional valences. The experiment consisted of nine sessions. To clarify the brain areas that showed increasing or decreasing activation as the experimental session proceeded, we analyzed the fMRI data using specified linear covariates in the face recognition task from the first session to the ninth session. Imaging data were investigated on a voxel-by-voxel basis for single-group analysis according to the random effect model using Statistical Parametric Mapping. The bilateral posterior cingulate cortices showed significant increases in activity as the experimental sessions proceeded, while the activation in the right amygdala and the left medial fusiform gyrus decreased. Thus, the posterior cingulate cortex may play an important role in the acquisition of facial familiarity.

Adult↗
PubMed2003

Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers.

The regenerating potential of human bone is limited. The repair of large bone defects often associated with bone tumor resections is not observed, and nonunion or delayed union of bone is a serious problem for fracture treatment. In these cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require invasive surgical procedures. An alternative approach described in this paper involves the injection of bone morphogenetic proteins (BMPs) in a polymeric delivery system. We demonstrate that synthetic biodegradable polymers, poly-D,L-lactic acid-polyethylene glycol (PLA-PEG) block copolymers, which exhibit an exquisite temperature-dependent liquid-semisolid transition, work well as an injectable delivery system for recombinant human (rh) BMP-2. The thermosensitive property of the PLA-PEG/rhBMP-2 composite is permissive to percutaneous injection when heated. The fluidity of this composite decreases as it cools down to body temperature and the resultant semisolid form provides a scaffold for bone formation through the gradual local release of the rhBMP-2. This new type of injectable osteoinductive material will enable a less invasive approach to surgeries involving the restoration or repair of bone tissues.

Animals↗
PubMed2003

Suicide gene therapy using AAV-HSVtk/ganciclovir in combination with irradiation results in regression of human head and neck cancer xenografts in nude mice.

The application of adeno-associated virus (AAV) vectors to cancers is limited by their low transduction efficiency. Previously, we reported that gamma-ray enhanced the second-strand synthesis, leading to the improvement of the transgene expression, and cytocidal effect of the herpes simplex virus type-1 thymidine kinase (HSVtk) and ganciclovir (GCV) system. In this study, we extended this in vitro findings to in vivo. First, the laryngeal cancer cell line (HEp-2) and HeLa were treated with AAVtk/GCV, the number of surviving cells was reduced as the concentration of GCV increased. Furthermore, the 4 Gy irradiation enhanced the killing effects of AAVtk/GCV by four-fold on HeLa cells and 15-fold on HEp-2 cells. Following the in vitro experiments, we evaluated the transgene expression and the antitumor activity of the AAV vectors in combination with gamma-ray in nude mice inoculated with HEp-2 subcutaneously. The LacZ expression was observed in the xenografted tumors and significantly increased by gamma-ray. The AAVtk/GCV system suppressed the tumors growth, and gamma-ray augmented the antitumor activity by five-fold. These findings suggest that the combination of AAVtk/GCV system with radiotherapy is significantly effective in the treatment of cancers and may lead to reduction of the potential toxicity of both AAVtk/GCV and gamma-ray.

Animals↗
PubMed2003

Enhancement of thymidine kinase-mediated killing of malignant glioma by BimS, a BH3-only cell death activator.

Herpes simplex virus thymidine kinase (HSV-tk)/gancyclovir (GCV) therapy has the ability to inhibit tumor formation in animal models but the results of clinical trials have been disappointing. To improve the performance of tk/GCV therapy, we tried combination therapy designed to enhance its cytotoxic effects by introducing genes that induce apoptosis of the tumor cells through different pathways. We concentrated our efforts on the use of Bim, a BH3-only member of death activators in the Bcl-2 superfamily, because Bim is not involved in the pathways through which HSV-tk/GCV therapy induces apoptosis in malignant glioma cells. Among three alternative splicing variants, BimEL, BimL, and BimS, BimS lacks the binding domain for the dynein light chain LC8, which negatively regulates the proapoptotic function of BimEL and BimL. All four malignant glioma cell lines, U251, A172, T-430, and U373 underwent cell death after transfer of BimS using an adenovirus vector (AVC2). Intriguingly, combination of AVC2-BimS with AVC2-tk markedly increased the sensitivity of U251 cells to GCV both in vitro and in vivo. In contrast, AVC2-BimL did not induce significant cell death. These results indicated that BimS had the ability to improve the efficiency of HSV-tk/GCV therapy in the treatment of malignant glioma and suggested that the targeting of different proapoptotic pathways may be a useful strategy for the development of an effective gene therapy approach to treatment.

Adenoviridae↗
PubMed2003

Significance of extensive Mongolian spots in Hunter's syndrome.

BACKGROUND: The importance of early diagnosis in infants with a mild form of Hunter's syndrome should be emphasized. If applied sufficiently early, haematopoietic stem cell transplantation (HSCT) or recombinant enzyme therapy may improve the prognosis. At present, however, diagnosis of the mild form of Hunter's syndrome tends to be delayed, especially in infants with relatively normal intelligence. OBJECTIVES: To investigate the occurrence of Mongolian spots in infants with Hunter's syndrome, and to clarify the relationship between the Mongolian spots and Hunter's syndrome clinically and histopathologically. METHODS: Seven Japanese boys with Hunter's syndrome who had received HSCT at ages 4-11 years were observed. The cutaneous manifestations of Mongolian spots before HSCT were evaluated, and compared with those after HSCT. In two patients, the hyperpigmentation from the Mongolian spots was examined by light and electron microscopy. RESULTS: Pre-HSCT observation revealed that all the patients had an extensive Mongolian spot. These were present at birth and have shown no signs of resolution during the post-HSCT period. Electron microscopic findings showed that pigment-bearing dermal melanocytes contained many free melanosomes in stage IV. These were surrounded by extracellular sheaths and encircled by elastic fibres. CONCLUSIONS: Our results indicate a strong clinical correlation between the extensive Mongolian spots and Hunter's syndrome. Ultrastructural findings also clearly suggest that the hyperpigmentation is a long-lasting symptom. The recognition of the extensive Mongolian spots is essential as it may lead to early diagnosis in patients with a mild form of Hunter's syndrome.

Child↗
PubMed2003

Sunburn reaction in the dorsal skin of hypotrichotic WBN/ILA-Ht rats.

The dorsal skin responses to a single irradiation with a high-dose of UVB (10kJ/m2) were examined histologically and immunohistochemically in UVB-sensitive Wistar-derived hypotrichotic WBN/ILA-Ht rats (HtRs). Sunburn cells (SBCs) which were characterized by pyknotic nuclei and eosinophilic cytoplasm and had ultrastructual characteristics of apoptotic cells were first observed in the epidermis at 3 hours (h) after irradiation. The number peaked at 6 h, and then decreased rapidly. The expressions of p53 protein, which is known to be closely related to the formation of SBCs, and of p21 protein, which is one of the transcriptional target genes of p53, were immunohistochemically detected, and their labeling index (LI) in the epidermis peaked at 12 to 24 h (p53) or at 24h (p21) after irradiation. On the other hand, proliferating cell nuclear antigen (PCNA)-LI in keratinocytes was significantly lower than the control group at 6 h after irradiation and thereafter it increased and became significantly higher than the control group from 24 to 48 h. At 48 h, moderate hyperplasia with moderate numbers of mitotic keratinocytes was first observed in the epidermis. In the dermis, mild edema developed from 12 to 36 h and it accompanied mild lymphocyte infiltration at 36 h. Judging from the present results, it was suggested that some factors other than p53 might be involved in SBC formation, and that p53 might induce p21 protein and play an important role in cell growth arrest in keratinocytes after UVB irradiation.

Animals↗
PubMed2002

Management of blunt hepatic injury in children: usefulness of emergency transcatheter arterial embolization.

We reviewed our experience to determine the usefulness of emergency transcatheter arterial embolization (TAE) for severe blunt hepatic injury (BHI) in children. Between 1978 and 2000, 21 children with BHI (14 boys and 7 girls, ranging in age from 2 to 14 years) were managed according to our protocol. The patients who were hemodynamically stable, and had no other associated injury requiring laparotomy, regardless of the hepatic injury grade, were managed nonsurgically. Emergency angiography and TAE performed after a CT scan revealed extravasation of the contrast medium. Of the 21 patients, 3 underwent emergency laparotomy; 2 due to hemodynamic instability despite fluid resuscitation (1 died), and the 3rd patient because of associated injury. The other 18 patients (86%) were initially managed nonsurgically; however, 2 underwent delayed laparotomy because of complications (1 each of suspected delayed hepatic hemorrhage and liver abscess). Nonsurgical management was completed in the remaining 16 (89%) with no morbidity and mortality. Two of the 16 returned to a hemodynamically stable condition with fluid resuscitation, but were compromised with persistent hepatic hemorrhage, and were successfully treated with emergency TAE. We propose that emergency TAE should be considered as an initial treatment for severe BHI in children.

Adolescent↗
PubMed2002

Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study.

Human lesion or neuroimaging studies suggest that amygdala is involved in facial emotion recognition. Although impairments in recognition of facial and/or emotional expression have been reported in schizophrenia, there are few neuroimaging studies that have examined differential brain activation during facial recognition between patients with schizophrenia and normal controls. To investigate amygdala responses during facial recognition in schizophrenia, we conducted a functional magnetic resonance imaging (fMRI) study with 12 right-handed medicated patients with schizophrenia and 12 age- and sex-matched healthy controls. The experiment task was a type of emotional intensity judgment task. During the task period, subjects were asked to view happy (or angry/disgusting/sad) and neutral faces simultaneously presented every 3 s and to judge which face was more emotional (positive or negative face discrimination). Imaging data were investigated in voxel-by-voxel basis for single-group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM). No significant difference in task accuracy was found between the schizophrenic and control groups. Positive face discrimination activated the bilateral amygdalae of both controls and schizophrenics, with more prominent activation of the right amygdala shown in the schizophrenic group. Negative face discrimination activated the bilateral amygdalae in the schizophrenic group whereas the right amygdala alone in the control group, although no significant group difference was found. Exaggerated amygdala activation during emotional intensity judgment found in the schizophrenic patients may reflect impaired gating of sensory input containing emotion.

Adolescent↗
PubMed2002

A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes.

AIMS/HYPOTHESIS: Peroxisome proliferator activated receptor gamma coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARgamma, plays a role in adaptive thermogenesis and insulin sensitivity. Plasma fasting insulin has been linked to the chromosomal region where the PGC-1 gene is located. Thus, PGC-1 can be viewed as a functional and positional candidate for the susceptibility gene for Type II (non-insulin-dependent) diabetes mellitus. METHODS: After screening the PGC-1 gene for single nucleotide polymorphisms (SNPs), we performed an association study using the newly detected SNPs in 537 Type II diabetic patients and 417 non-diabetic subjects. RESULTS: We found three relatively frequent SNPs in the PGC-1 gene (IVS4-11T > C, Thr394Thr and Gly482Ser). There were significant differences in fasting insulin (Gly/Gly; 37.7 +/- 1.43, Gly/Ser; 40.2 +/- 1.21, Ser/Ser; 44.3 +/- 1.82 pmol/l, p = 0.018) and insulin resistance index (Gly/Gly; 1.48 +/- 0.06, Gly/Ser; 1.56 +/- 0.05, Ser/Ser; 1.75 +/- 0.08, p = 0.027) according to the genotype of the Gly482Ser polymorphism. The Thr394Thr - Gly482Ser haplotype was associated with Type II diabetes (p = 0.00003). CONCLUSION/INTERPRETATION. The results of this study suggested that the PGC-1 gene might be implicated in the pathogenesis of Type II diabetes.

Base Sequence↗
PubMed2002

Functional magnetic resonance imaging evidence for a representation of the ear in human primary somatosensory cortex: comparison with magnetoencephalography study.

Our previous study (T. Nihashi et al., 2001, Neuro- Image 13: 295-304), using magnetoencephalography (MEG), revealed somatotopy of the ear in the human primary somatosensory cortex (SI); that is, the signals following stimulation of the ear reach both the neck and face areas of the SI. However, since this was the first report on somatotopy of the ear in humans, we performed an fMRI activation study to confirm the somatotopic representation, and compared the electrical activity by MEG and the cerebral blood flow change by fMRI. We studied eight healthy subjects using 3-T MRI. We stimulated three parts of the left ear: the helix, the lobulus, and the tragus. First, we identified the location of the ear area in the SI based on our previous MEG study, in which equivalent current dipoles (ECDs) were located in the neck and/or face areas of the SI. Then, we determined the search volume as a sphere with a 15-mm radius, which was placed in the neck and/or face area. We analyzed whether or not fMRI activation occurred inside such spheres. Stimulation of the helix activated the neck area of the SI in four of eight subjects, and both the neck and face areas in two. No activation was observed in two subjects. Stimulation of the lobulus activated the neck area in one subject, the face area in two, both in four, and neither in one. Stimulation of the tragus activated the face in four, both in three, and neither in one. These fMRI findings confirm the result of MEG that the representation of the ear in the SI is separated into neck and face areas.

Adult↗