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Biomedical subjects

H Nakase

Publications and source records attributed to H Nakase.

At least 19 recordsLinked to original sources

Genetic analysis to complement histopathological diagnosis of brain tumors.

Gliomas, the most frequent tumors originating in the human nervous system, are divided into various subtypes. Currently, microscopic examination alone is insufficient for classification and grading so that genetic profiles are increasingly being emphasized in recognition of the emerging role of molecular diagnostic approaches to glioma classification. Glioblastomas (WHO grade IV) may develop de novo (primary glioblastomas) or through progression from lower-grade astrocytomas (secondary glioblastomas), while both glioblastomas show similar histological features. In contrast, they do constitute distinct disease entities that evolve through different genetic pathways, and are likely to differ in prognosis and response to therapy. Oligodendrogliomas (WHO grade II) account for 2.7% of brain tumors and 5-18% of all gliomas. Since this tumor is recognized as a particular subtype of glioma that shows remarkable responses to chemotherapy, a correct diagnosis is of prime importance. The difficulty is that histological differentiation of oligodendrogliomas from diffuse astrocytomas is highly subjective in cases without typical morphological features and there is a lack of reliable immunohistochemical markers. While histological distinction of low-grade gliomas from reactive astrocytes is also often difficult, reactive astrocytes usually lack genetic alterations. More biological and molecular approaches to glioma classification thus appear warranted to provide improved means to achieve correct diagnoses.

Astrocytoma↗

Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice.

BACKGROUND AND AIMS: Major histocompatibility complex class II deficient (Aalpha0/0) mice have decreased CD4+ T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aalpha0/0 mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aalpha0/0 mice. METHODS: Stomachs from 1-6 month old Aalpha0/0 mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll-like receptors (TLRs), cyclooxygenase (COX)-2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. RESULTS: Aalpha0/0 mice had a diffusely thick corpus mucosa with infiltration of CD11b+ granulocytes and macrophages. Anti-Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1beta, interferon gamma, TLR-2, TLR-4, and COX-2 were upregulated, and MPO activity was increased. Only a small amount of non-pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg-Ialpha positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. CONCLUSION: Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aalpha0/0 mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

The use of ultrasonic bone curettes in spinal surgery.

OBJECT: The author describes a clinical applications, procedure, and efficacy of ultrasonic bone curette (UBC) (bone-removal bar) in spinal surgery. METHODS: From July 2003 to March 2005, we operated on 98 consecutive spinal disorders by using UBC, Sonopet UST-2001; Chiari type-1 malformation (6 cases), cervical disorders (64 cases), thoracic disorders (5 cases), and lumbar disorders (23 cases). The instrument was devoid of any spinning parts, and the risk of grabbing cotton pledgets and damaging normal tissue was thereby avoided. Support from assistants for irrigation and suction was not required. FINDINGS: In this series, there were no iatrogenically induced injuries for example, direct or heat damage to surrounding soft tissues, including nerves, vessels, spinal cord, and dura matter. Considering potential complications of mechanical injuries by ultrasonic technique, intermittent usage and cotton protection during use under an operating microscope are recommended. We found that the ultrasonic device is easy to handle; however, it is time consuming for removing a large amount of bone and ossified lesions. Therefore, we recommend the combined use of this method with standard drilling. CONCLUSIONS: This system appears to be versatile, safe, and efficient in spinal surgery and could be improved by the development of a better handpiece.

Aged↗

Possible role of REG Ialpha protein in ulcerative colitis and colitic cancer.

BACKGROUND AND AIMS: Although regenerating gene (REG) Ialpha protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the REG Ialpha gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for REG Ialpha gene expression and whether REG Ialpha protein has a trophic and/or an antiapoptotic effect on colon cancer cells. METHODS: Expression of REG Ialpha mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on REG Ialpha promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG Ialpha protein on growth and H(2)O(2) induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. RESULTS: REG Ialpha protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG Ialpha mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. REG Ialpha promoter activity was enhanced by stimulation with interferon gamma or interleukin 6. REG Ialpha protein promoted cell growth and conferred resistance to H(2)O(2) induced apoptosis in LoVo cells. REG Ialpha protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. CONCLUSIONS: The REG Ialpha gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.

Adenoma↗

Vascular endothelial growth factor antagonist reduces brain edema formation and venous infarction.

BACKGROUND AND PURPOSE: Cerebral venous ischemia often induces severe brain edema. Vascular endothelial growth factor (VEGF), which induces angiogenesis, is also known as vascular permeability (VP) factor. The present study was undertaken to investigate whether the inhibition of VEGF could reduce brain edema formation and cerebral venous infarction (CVI) in a rat 2-vein occlusion (2-VO) model. METHODS: We used 2-VO model in which 2 adjacent cortical veins were photochemically occluded. Male Wistar rats (n=25) were divided into 2 groups: one group was treated with a VEGF antagonist (antagonist group, n=10) and the second group was treated with phosphate-buffered solution (PBS) (PBS group, n=15). VEGF antagonist or PBS was injected intraperitoneally immediately after 2-VO. The developing ischemic infarct was evaluated by magnetic resonance imaging (MRI) and histology 24 hours after occlusion. RESULTS: VEGF expression was observed in the cytoplasm of neurons exclusively in the area of vasogenic edema that was shown as a high-intensity area in the apparent diffusion coefficient of water map. Ischemic volumes calculated from each MR images, which are related to infarction and/or vasogenic edema, respectively, were significantly smaller in the antagonist group as compared with the PBS group (P<0.05) CONCLUSIONS: Our study is the first to provide evidence that the inhibition of VEGF attenuates VP and reduces CVI in the acute stage. Although VEGF is a significant angiogenesis factor, we concluded that the inhibition of VEGF might be a new therapy for both brain edema formation and CVI.

Animals↗

Clinical features of postoperative cerebral venous infarction.

There is a potential risk of sacrificing the cortical vein during neurosurgical operations, particularly in the interhemispheric or subtemporal approach. An impaired cortical vein might cause cerebral venous circulatory disturbances (CVCDs) resulting in venous infarction. In this article, we have reviewed the management and results of eight cases with symptomatic postoperative venous infarction. We have encountered eight cases with symptomatic postoperative venous infarction (0.3%) during the past 5 years. The series is composed of 3 males and 5 females, with ages that ranged from 43 to 76 years (mean age of 58.1 years), and consisted of five brain tumors, one cavernoma, one dural AVF, and one trigeminal neuralgia. Initial symptoms occurred intra-operatively in two, on 0 day after the operation in one, 1 day in three, 3 days in one, and 4 days in one case. The symptoms were intra-operative brain edema in two cases, disorientation in one, cerebellar signs in one, hemiparesis in one, aphasia in two, and headache in one case. Two cases required surgical intervention. The results were a good outcome in 6 and a fair outcome in 2 cases. In conclusion, there are two types of postoperative venous infarction; severe onset (severe type) and gradual onset (mild type). The former needs immediate treatment from the intra-operative period onward, and the prevention of the ongoing venous thrombosis is essential in the latter.

Adult↗

Usefulness of famotidine in functional dyspepsia patient treatment: comparison among prokinetic, acid suppression and antianxiety therapies.

BACKGROUND: The treatment of functional dyspepsia is controversial. AIM: The purpose of this paper is to clarify the initial effect of prokinetic, acid suppression and antianxiety treatment for functional dyspepsia patients. PATIENTS AND METHODS: Sixty-four functional dyspepsia patients without Helicobacter pylori infection were randomly assigned to 15 mg/day of mosapride, 40 mg/day of famotidine, or 30 mg/day of tandospirone during an 8-week treatment. Individual functional dyspepsia symptoms were evaluated with 4 cm visual analogue scale before and at 2, 4 and 8 weeks after treatment. RESULTS: Among 64 enrolled patients, 62 completed the study. Within 2 weeks, visual analogue scale score in the mosapride-treated group decreased from 2.29 +/-0.14 to 1.57 +/- 0.20; in the famotidine from 2.04 +/- 0.16 to 1.09 +/- 0.12 (mean +/- S.E.). Therefore, there were significant improvements of functional dyspepsia symptoms in mosapride- and famotidine-treated patients (P <0.01). Furthermore, famotidine was significantly more effective than mosapride (P < 0.05). On the contrary, visual analogue scale score in the tandospirone therapy was 2.23 +/- 0.20 and 2.13 +/- 0.22 before and at 2 weeks, respectively, without any significant improvement. CONCLUSIONS: A treatment regimen of famotidine at 40 mg/day had a significant favourable effect on the clinical outcome in functional dyspepsia patients.

Anti-Anxiety Agents↗

Syringomyelia caused by cervical spondylosis.

Syringomyelia is generally associated with Chiari type malformations, spinal tumors, or spinal trauma. Cervical spondylosis is only rarely involved. We here present a case of a 64-year-old woman with severe radicular pain in the right arm and the syringomyelic syndrome. Lateral radiographs of the cervical spine demonstrated spondylotic change at the C4/5 and C6/7 levels, and instability at C4/5. Dynamic magnetic resonance (MR) imaging revealed the spinal cord to be compressed at C5 and C6 with the body in extension, and the syrinx extended from C2 to the Th3 level on sagittal images. It was reduced remarkably after anterior decompression and stabilization at C4/5 and C6/7, and her symptoms also improved after surgery. We concluded that the syrinx in this case might have developed due to craniospinal pressure dissociation caused by intermittent spinal cord compression.

Cervical Vertebrae↗

Observation of arterial and venous thrombus formation by scanning and transmission electron microscopy.

BACKGROUND: In order to examine the process of thrombosis formation in artery and vein, the reactions of the arterial and venous endothelial surfaces were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in the photothrombosis model. MATERIALS AND METHODS: Thirty-nine rats were divided into the following 4 groups: 1) Sham group (n = 5) without illumination, 2) group A (n = 10) irradiated for 1 min, 3) group B (n = 10) irradiated for 5 min, 4) group C (n = 14) irradiated for 10 min at the level of the left common carotid artery and internal jugular vein. RESULTS: SEM provided no evidence of damage or adhesion of blood platelets to the endothelium of either the artery or vein in shams or group A animals. In group B, evidence of damage to endothelial cell membrane (e.g., plasmalemmal pits, crater-like structures associated with tears between endothelial cells, and decreased number of microvilli) was obtained in the arterial wall but not in the vein. In group C, there was extensive or widespread adhesion of blood platelets and other cells, tears between arterial endothelial cells, and a decrease in the number of microvilli in the artery but not in the vein (p < 0.05). CONCLUSIONS: Cell membrane injuries, tears between the endothelial cells, and endothelial detachment occur before adhesion of blood platelets and thrombus formation in the blood vessel occlusion model by photochemical reaction. These changes occur significantly earlier in the artery than in the vein.

Animals↗

Vasogenic edema and VEGF expression in a rat two-vein occlusion model.

Vasogenic edema plays an important etiologic role in the pathogenesis of cerebral venous circulation disturbances (CVCDs). Since vascular endothelial growth factor (VEGF) is a major mediator in angiogenesis and vascular permeability, including induction of vasogenic edema, the present study was undertaken to investigate whether it has any relevance to CVCDs. Male Wistar rats (n = 15) were used. Two adjacent cortical veins were occluded photochemically using rose bengal dye and fiberoptic illumination, with evaluation 24 hours thereafter by magnetic resonance imaging (MRI). Each brain was removed from the skull immediately after MRI and processed for hematoxylin-eosin staining (H&E staining) of sections for histopathology and comparison with MRI data. VEGF expression as demonstrated immunohistochemically appeared to coincide with vasogenic edema, diagnosed as high intensity areas on apparent diffusion coefficient of water (ADCw) maps. On the basis of these data, we conclude that VEGF is related to formation of vasogenic edema in the acute stage of CVCD.

Animals↗

Inhibitory effects of Helicobacter pylori infection on murine autoimmune gastritis.

BACKGROUND AND AIM: Long term Helicobacter pylori infection leads to atrophic gastritis but the relation between H pylori infection and autoimmune related atrophic gastritis (AIG) remains unclear. We studied the effects of H pylori infection on the pathophysiology of AIG in mice. MATERIALS AND METHODS: BALB/c nu/nu mice (n=40) with or without H pylori infection received splenocytes from neonatally thymectomised mice to induce AIG. Half of the mice were orally infected with H pylori prior to AIG induction. Histological findings, and local and systemic immune responses were serially evaluated. RESULTS: Two and six months after transfer, parietal cells in uninfected mice were depleted while those in infected mice were well preserved. The degree of gland atrophy (p<0.01), hyperplasia (p<0.01), gastric pH (p<0.05), and serum gastrin levels of infected mice were significantly lower than those of uninfected mice. Serum antiparietal cell antibody levels gradually decreased in infected mice, and were significantly lower than those of uninfected mice at six months (p<0.05). Real time polymerase chain reaction studies revealed significantly higher interleukin 4 (p<0.05) and transforming growth factor beta (p<0.05) gene expression in the gastric mucosa in infected mice than in uninfected mice at both two and six months after AIG induction. CONCLUSIONS: H pylori infection inhibited the development of AIG in mice. Th2-type immune responses and transforming growth factor beta in the gastric microenvironment might be involved in the inhibitory effects of H pylori infection on the development of AIG, in which Th1-type responses have an important role.

Animals↗

The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients.

It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.

Adult↗

Rectal immunization with antigen-containing microspheres induces stronger Th2 responses than oral immunization: a new method for vaccination.

The rectum as an effective site for induction of systemic and local immunity has received little attention. Rectal immunization with microspheres-containing ovalbumin (MS-OVA) was tested for its ability to elicit systemic and mucosal immune responses. Rectal immunization with MS-OVA enhanced both Th2 dominant OVA-specific IgG levels in the serum and OVA-specific IgA levels in fecal extracts more prominently than did oral immunization. Cytokine analysis of CD4(+) T cells indicated a predominant induction of Th2-type responses compared to Th1-type responses following rectal immunization compared to oral immunization. These results demonstrate that rectal immunization with microspheres could be an effective new vaccination method.

Administration, Oral↗

Frequent alterations of the p14(ARF) and p16(INK4a) genes in primary central nervous system lymphomas.

To elucidate the role of p53/p16(INK4a)/RB1 pathways in the tumorigenesis of primary central nervous system lymphomas (PCNSLs), we have analyzed p14(ARF), p16(INK4a), RB1, p21(Waf1), and p27(Kip1) status in a series of their 18 sporadic cases of diffuse large B-cell lymphoma, using methylation-specific PCR, differential PCR, and immunohistochemistry. Homozygous deletion or methylation of p14(ARF) was detected in 10 (56%) PCNSLs, and they were almost entirely deletions (except 1 case). A total of 11 (61%) PCNSLs demonstrated homozygous deletion (6 cases) or methylation (5 cases) of p16(INK4a). Six tumors showed both p14(ARF) and p16(INK4a) homozygous deletions. Hypermethylation of the RB1 and the p27(Kip1) promoter region was detected in 2 (11%) cases, whereas p21(Waf1) methylation was not detected in any. Immunohistochemistry revealed loss of p14(ARF) and p16(INK4a) expression in 10 (56%) samples, correlating with the gene status. Four cases showed independent negative immunoreactivity for pRB and p27(Kip1), and nearly one-half of cases (8 of 18; 44%) were characterized by lack of p21(Waf1) expression. These results indicate that inactivation of p14(ARF) and p16(INK4a) by either homozygous deletion or promoter hypermethylation represents an important molecular pathogenesis in PCNSLs. Hypermethylation of RB1, p21(Waf1), and p27(Kip1) appears to be of minor significance, these genes being independently methylated in PCNSLs.

Cell Cycle Proteins↗

Budd-Chiari syndrome and extrahepatic portal obstruction associated with congenital antithrombin III deficiency.

We report a patient with Budd-Chiari syndrome (BCS) and extrahepatic portal obstruction (EHO) associated with congenital antithrombin (AT) III deficiency. A 35-year-old man was admitted to Nishi Kobe Medical Center for evaluation of abnormal intrahepatic veins. By various imaging modalities, BCS and EHO were diagnosed. Laboratory data revealed parallel decreases in activity and antigen concentration of AT III despite normal liver function. Taken together, the etiology of both BCS and EHO was considered to be thrombosis, associated with congenital AT III deficiency. Two years after beginning warfarin therapy, the patient has no symptoms and his liver function remains normal. Anticoagulant therapy is considered useful for preventing progression of the disease.

Adult↗

Therapeutic effects on intestinal Behçet's disease of an intravenous drug delivery system using dexamethasone incorporated in lipid emulsion.

Recurrent intestinal ulcer is a frequent problem in the management of Behçet's disease. However, no standard therapy for intestinal Beheçt's disease has been established. We report two patients with intestinal Behçet disease and recurrent ileal ulcers who were treated successfuly with a lipid emulsion of dexamethasone. In one patient, the cecal ulcer did not relapse after the intravenous administration initiation of a lipid emulsion of dexamethasone once a week, despite the discontinuation of prednisolone. In the other patient, the cecal ulcer showed a healing tendency, and oral administration of prednisolone was reduced from 40 to 15 mg/day after intravenous administration of a lipid emulsion of dexamethasone. Both patients experienced no complications associated with the administration of the emulsion. These results suggest that an intravenous drug delivery system using a lipid emulsion of dexamethasone is useful for treatment of intestinal Behçet's disease.

Anti-Inflammatory Agents↗