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N Arita

Publications and source records attributed to N Arita.

At least 19 recordsLinked to original sources
PubMed2005

Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early rheumatoid arthritis in association with production of Mig/CXCL9 by synovial fibroblasts.

Accumulation of plasma cells in the synovium is one of the diagnostic hallmarks in the histopathological manifestations of rheumatoid arthritis (RA). This seems to be prominent even prior to significant B cell infiltration and/or formation of lymphoid follicles in the synovium. To clarify the mechanism of early plasma cell accumulation, we examined in situ expression of chemokines and their receptors using synovial targeting biopsy specimens, which were obtained under arthroscopy from early RA patients. By immunohistochemical staining, plasma cells were found to express a chemokine receptor CXCR3, while synovial fibroblasts in the synovial sublining regions expressed its ligand, Mig/CXCL9. By reverse transcription-polymerase chain reaction (RT-PCR), using targeted lesions of synovial tissues obtained by laser capture microdissection, expression levels of Mig/CXCL9 in the synovial sublining regions were remarkably high and were likely to be associated with interferon (IFN)-gamma expression. Furthermore, cultured synovial fibroblasts were confirmed to produce Mig/CXCL9 upon stimulation with IFN-gamma. Our results indicate that in the early stage of RA, plasma cells expressing CXCR3 may be recruited directly from the circulation into the synovial sublining regions by its ligand, Mig/CXCL9, produced by synovial fibroblasts.

Adult↗
PubMed2002

Unexpected delayed rupture of the vertebral-posterior inferior cerebellar artery aneurysms following closed head injury.

Subarachnoid haemorrhage secondary to closed head injury is rarely associated with traumatic aneurysms of the posterior circulation. We report two cases of ruptured vertebral-posterior inferior cerebellar artery (VA-PICA) pseudoaneurysms following closed head injuries. In each case, there was no associated penetrating injury or skull fracture. The first patient was kicked followed by disturbed consciousness. The computerized tomography (CT) scan on admission and cerebral angiography on the 11th day after the trauma revealed a massive subarachnoid haemorrhage (SAH) with pan-ventricular haemorrhage and an aneurysm of the right PICA near its origin. Further ruptures occurred on the 12th, 15th, and 66th day, and he died on the 69th day. The second patient complained of persistent headache and nausea following a fight on the previous day. A CT scan and angiography on the 1st day after the trauma showed posterior fossa SAH with fourth ventricular blood and a tiny protrusion of the left VA-PICA. On the 14th day, repeated angiography revealed a remarkable growth of the aneurysm, followed by the second rupture. The repair of the VA-PICA junction was urgently performed with successful exclusion of the aneurysm. To our knowledge, only eight cases of traumatic aneurysms located at the VA or the PICA near its origin have been reported. When intraventricular blood is found with massive subarachnoid blood or with posterior fossa SAH, this ominous complication should be considered. Traumatic VA-PICA pseudoaneurysms are curable by refined microsurgical techniques, if diagnosed in time.

Adult↗
PubMed2001

PTEN mutations in malignant gliomas and their relation with meningeal gliomatosis.

A putative tumor suppressor, the PTEN gene at chromosome 10q23. was identified and found to be mutated in many different human tumors. PTEN was recently found to be also involved in focal cell adhesion and cell migration. To identify the role of PTEN gene in malignant gliomas. we used PCR-SSCP and direct sequencing methods to examine 44 malignant gliomas comprising 29 cases without and 15 cases with meningeal gliomatosis. In malignant gliomas without meningeal gliomatosis, 2/29 (7%) of the cases showed alteration of the PTEN gene. In contrast, 5/15 (33%) of malignant gliomas with meningeal gliomatosis cases showed this alteration. These findings indicate that PTEN gene mutation contributes not only to the neoplastic evolution in gliomas but also to the meningeal dissemination of glioma cells.

Adolescent↗
PubMed2001

Characterization of premature atherosclerosis of carotid arteries in acromegalic patients.

OBJECTIVE: Acromegalic patients have increased mortality from vascular diseases. Although atherosclerotic risk factors such as hypertension, diabetes mellitus and dyslipoproteinaemia are highly associated with acromegaly, the prevalence of premature atherosclerosis in acromegalic patients and its relationship to these risk factors have not been reported. DESIGN: We measured mean intima-media thickness (IMT) of the carotid arteries in 21 acromegalic patients without symptomatic atherosclerotic vascular disease, by ultrasound high-resolution B-mode imaging. In analysis 1, it was compared with the predicted mean IMT based on data from existing risk factors (age, male sex, dyslipoproteinaemia, hypertension, diabetes mellitus, smoking status) in 282 non-acromegalic subjects. In analysis 2, the mean IMT in the 21 acromegalic patients was compared with that in 42 non-acromegalic subjects matched for age, sex and the other atherosclerotic risk factors. We also analysed clinical characteristics between the acromegalic patients with and without the atherosclerosis. RESULTS: Mean IMT in 21 acromegalic patients was 0.92 +/- 0.21 (mean +/- SD) mm. It was significantly (P < 0.05) lower than the mean IMT (1.03 +/- 0.12 mm) predicted from their existing risk factors (analysis 1). It was also less than that in 42 non-acromegalic subjects matched for atherosclerotic risk factors (1.07 +/- 0.37 mm; P < 0.05) (analysis 2). Among the acromegalic patients, 10 patients (48%) had increased mean IMT (> or = 1.1 mm) and/or plaque lesions whereas the other 11 had no such atherosclerotic changes. In the patients without the atherosclerotic changes, plasma insulin-like growth factor-I (IGF-I) concentration was significantly (P < 0.01) higher, and the prevalence of hypertension was significantly (P < 0.05) lower than in those with the atherosclerotic changes. CONCLUSIONS: The extent of carotid atherosclerosis in the acromegalic patients was not higher than that in non-acromegalic subjects, considering their atherosclerotic risk factors. Increased concentration of IGF-I might be involved in the lack of susceptibility to atherosclerosis in some acromegalic patients.

Acromegaly↗
PubMed2001

Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity.

Tumor cells often express phenotypic markers that are specific to the cells from which they originated. A neural RNA-binding protein, Musashil, is an evolutionarily well-conserved marker for neural stem cells/ progenitor cells. To examine the origin of gliomas, we examined the expression of the human Musashil homolog, MSI1, in human glioma tissues and in normal human adult and fetal brains. As we had seen previously in rodents, in the normal human brain, MSI1 was expressed in cells located in the ventricular and subventricular zones, in GFAP-negative glial cells, and in GFAP-positive astrocytes. In glioblastomas, MSI1 was expressed in GFAP-negative tumor cells forming foci that were clearly demarcated and surrounded by GFAP-positive cells. Tumor cells arranged in pseudopalisades were also strongly immunoreactive with MSI1 antibodies. The percentage of MSI1-labeled tumor cells increased in higher-grade astrocytomas and correlated with proliferative activity, as estimated by an MIB-1 staining index. Our results indicate that MSI1 is an excellent marker for neural progenitor cells including neural stem cells in normal human brains. Furthermore, the expression of MSI1 correlates well with the immature nature as well as the malignancy of tumor cells in human gliomas. Thus, we expect the analysis of MSI1 expression to contribute to the understanding of the cellular origin and biology of human gliomas.

Adult↗
PubMed2000

Estrogen deficiency is a potential cause for osteopenia in adult male patients with Noonan's syndrome.

Osteopenia is frequently observed in patients with Turner's syndrome. By contrast, there is no report concerning bone metabolism in patients with Noonan's syndrome which comprises Turner's phenotypic characteristics without any sex chromosome abnormalities. In the present investigation, we determined bone mineral density (BMD) as well as serum and urine indices of bone turnover in two male patients with Noonan's syndrome. Both patients showed remarkably decreased BMD, measured at two sites on the lumbar spine (L2-L4) and the distal end of the radius using dual energy X-ray absorptiometry (DXA). Urinary pyridinoline (PYD) and deoxypyridinoline (DPD) concentrations were significantly elevated in both patients, and serum osteocalcin and carboxyterminal propeptide of type I procollagen (PICP) concentrations were elevated in one patient. Surprisingly, both patients had a low level of serum 17beta-estradiol compared with control males, whereas they had normal levels of serum testosterone and dihydrotestosterone. Conjugated estrogens (Premarin 0.625 mg/day) were continued to be administered to these patients, followed up for 12 months. Urinary PYD and DPD concentrations gradually decreased, followed by an increase in their BMD. This is the first report that male patients with Noonan's syndrome showed osteopenia associated with increased bone resorption. Our data indicate that hypoestrogenism plays a potentially significant role in the abnormal bone metabolism in these patients.

Adolescent↗
PubMed2000

Intracavernous sinus ectopic adrenocorticotropin-secreting tumours causing therapeutic failure in transsphenoidal surgery for Cushing's disease.

BACKGROUND: The major cause of surgical failure in the treatment of Cushing's disease lies in unsuccessful identification of adenomas. In the present study, we investigated the pathogenesis of negative exploration in transsphenoidal surgery for Cushing's disease by analyzing neuro-imaging studies, endocrinological examination and selective venous sampling. METHODS: Thirty patients with ACTH-dependent Cushing's syndrome that met the endocrinological criteria for Cushing's disease were treated by transsphenoidal microsurgery. Depending on positive or negative identification of adenomas during the surgery, selective adenomectomy, partial hypophysectomy or subtotal hypophysectomy was performed. FINDINGS: All nine patients who underwent selective adenomectomy showed endocrinological remission and did not need any hormone replacement therapy. Of the 12 patients who underwent partial hypophysectomy, 11 showed normalization of hypercortisolism but seven needed permanent replacement of hydrocortisone. Four patients underwent subtotal hypophysectomy because no adenoma could be identified in spite of detailed exploration, and three of them showed remission but with permanent requirements of hydrocortisone and other pituitary hormones. Five patients, whose hypercortisolism persisted after initial surgery, underwent total hypophysectomy as secondary transsphenoidal surgery, and only one of them showed endocrinological remission. Of the six patients with surgical failure, four were thought to be rare cases in whom the ACTH-secreting tumours may have occurred ectopically in the cavernous sinus without direct contact with the pituitary gland. Endocrinologically, these four patients showed a low or no response to corticotropin releasing hormone (CRH) stimulation, and for three of them, radiation therapy to the sellar region including the cavernous sinus was effective for persistent hypercortisolemia. INTERPRETATION: Recognition of an ectopic intracavernous sinus ACTH-secreting tumour as a pathological entity for Cushing's disease may not only enhance the diagnostic accuracy but also be important for determining the optimal surgical mode for persistent Cushing's disease.

Adenoma↗
PubMed2000

Phase II trial of pre-irradiation KRN8602 (MX2) in malignant glioma patients.

KRN8602 (MX2) is a newly developed morpholino anthracycline that crosses the blood-brain barrier where it becomes distributed in brain tissue after intravenous administration. This morpholino anthracycline has been found to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo, We performed a phase II trial using KRN8602 as a single agent in malignant glioma patients who had not received prior adjuvant therapy. The 13 patients (5 glioblastomas, 7 anaplastic astrocytomas and 1 malignant oligodendroglioma) enrolled received at least 1 cycle of KRN8602 at 35 mg/m2/day in 3-4 week intervals by intravenous bolus. Ten of these patients could be evaluated for response, and 13 for toxicity. Three patients (1 glioblastoma and 2 anaplastic astrocytomas) demonstrated a complete response (3/10, 30%). Concerning side effects, myelosuppression was moderately severe, with 30.7% of patients developing grade 3 leukopenia. Severe nausea/vomiting was observed in 69% of the patients, however, cardiotoxicity was not observed. The results indicate that KRN8602 demonstrated modest activity against malignant glioma with relatively severe, but manageable toxicity. Further assessment of the efficacy and toxicity of KRN8602 against malignant glioma may be worthwhile.

Adult↗
PubMed2000

Calphostin C-mediated translocation and integration of Bax into mitochondria induces cytochrome c release before mitochondrial dysfunction.

Calphostin C-mediated apoptosis in glioma cells was reported previously to be associated with down-regulation of Bcl-2 and Bcl-xL. In this study, we report that 100 nM calphostin C also induces translocation and integration of monomeric Bax into mitochondrial membrane, followed by cytochrome c release into cytosol and subsequent decrease of mitochondrial inner membrane potential (DeltaPsim) before activation of caspase-3. The integration of monomeric Bax was associated with acquirement of alkali-resistance. The translocated monomeric Bax was partly homodimerized after cytochrome c release and decrease of DeltaPsim. The translocation and homodimerization of Bax, cytochrome c release, and decrease of DeltaPsim were not blocked by 100 microM z-VAD.fmk, a pan-caspase inhibitor, but the homodimerization of Bax and decrease of DeltaPsim were inhibited by 10 microM oligomycin, a mitochondrial F0F1-ATPase inhibitor. Therefore, it would be assumed that mitochondrial release of cytochrome c results from translocation and integration of Bax and is independent of permeability transition of mitochondria and caspase activation, representing a critical step in calphostin C-induced cell death.

Apoptosis↗
PubMed2000

Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients.

OBJECTIVE: Abnormal glucose tolerance is often demonstrated in acromegalic patients. Although insulin resistance is a common feature of acromegaly, it remains unclear whether the extent of insulin resistance per se determines the abnormal glucose tolerance. In order to elucidate this issue, we investigated insulin sensitivity and beta-cell function in acromegalic patients. DESIGN: Twenty-four acromegalic patients were studied in comparison with 24 healthy control subjects. To estimate insulin sensitivity and beta-cell function, we used correct homeostasis model assessment (HOMA) model, a computer-solved model. We also investigated the effects of surgical success on both parameters. RESULTS: HOMA insulin sensitivity (HOMA-%S) in the acromegalic patients was 74 +/- 51 (SD)%, significantly lower than that in 24 healthy controls (144 +/- 49%). HOMA-%S in 12 normal glucose tolerance (NGT) patients was 54 +/- 31%, not significantly different from that in impaired glucose tolerance (IGT; n = 11) or diabetes mellitus (DM; n = 1) patients (93 +/- 60%). By contrast, HOMA beta-cell function (HOMA-%beta) in the NGT acromegalic patients was 163 +/- 67%, significantly higher than the IGT/DM acromegalic patients (89 +/- 34%) and the healthy controls (72 +/- 19%). In 11 patients who achieved complete normalization of GH excess after surgery, HOMA-%S significantly increased to control ranges (from 76 +/- 26 to 159 +/- 61%) within 2 weeks after the surgical success. CONCLUSIONS: We conclude that insulin sensitivity is reduced to a similar extent in acromegalic patients with normal glucose tolerance and those with impaired glucose tolerance or diabetes. Compensatory hyperfunction of beta-cells appears to counterbalance the reduced insulin sensitivity in the acromegalic patients with normal glucose tolerance but not in those with impaired glucose tolerance or diabetes.

Acromegaly↗
PubMed2000

Atypical hyperplasia of choledocho-pancreatic duct epithelium in an Otsuka Long Evans Tokushima Fatty strain of rats.

Epithelial papillary hyperplasia of choledocho-pancreatic duct, associated with cellular atypism, was observed in Otsuka Long Evans Tokushima Fatty (OLETF) rats, a strain originally established as an animal model for non-insulin-dependent diabetes mellitus (NIDDM). To investigate the potential feasibility of OLETF rats as an animal model for pancreatic ductal carcinoma, we examined the pathological characteristics of ductal lesions in OLETF rats aged from 5 to 50 weeks. Hyperplastic lesions in OLETF rats became apparent after 10 weeks of age and increased in severity and frequency of atypical changes in hyperplastic epithelium appearing after 20 weeks. We compared ductal lesions from OLETF rats with those from age-matched Long Evans Tokushima Otsuka (LETO) rats, which share a similar genetic background with OLETF rats but do not develop NIDDM. While LETO rats also display a tendency toward ductal hyperplasia, lesions from OLETF rats were more numerous and larger in size than those from age-matched LETO rats. In addition, lesions from OLETF rats contained a significantly higher number of proliferating cell nuclear antigen-positive cells than those from LETO rats. Finally, lesions in OLETF rats were accompanied by inflammation, and the observed morphological alteration of lesions correlated well with the grade of inflammation.

Aging↗
PubMed2000

Sclerosing encapsulating peritonitis and non-occlusive mesenteric infarction found at autopsy in a man who had undergone continuous ambulatory peritoneal dialysis: a histochemical and immunohistochemical study.

This is a report of a post-mortem histological, histochemical, and immunohistochemical examination of a rare case of sclerosing encapsulating peritonitis (SEP) and non-occlusive mesenteric infarction (NOMI), two serious complications of continuous ambulatory peritoneal dialysis (CAPD), with which a man suffering hepatitis C virus (HCV)-induced liver cirrhosis for 7 years and trauma-induced paraplegia for 50 years had been treated for 1 year. The direct cause of death was encephalopathy caused by extreme hyperammonemia (11 250 microg/dL in serum). The autopsy revealed that the SEP had drastically reduced the length of the small intestine to 210 cm, 180 cm of which presented acute ischemic enteritis with Gram-negative bacterial infection. Histological examination of the SEP revealed that the exterior was composed of normal serosal elastic lamina, but with a cocoon-like appearance remarkably thickened by fibrosis to 3-8 times that of the normal subserosal layer and consisting of spindle cells and blood vessels, with some infiltration of mast cells and lymphocytes. The immunohistochemical examination of the spindle cells revealed few AE1/AE3(+) cells, HHF35(+) cells, and CD34(+) cells, many CD117(+) cells with slight proliferative activity based on MIB-1 positivity (proliferation index <1%), but no CD44(+) cells. It was concluded that either the few CD34(+) and/or the many CD117(+) cells were mesenteric stem cells that had originated from the serosa, proliferated, then differentiated into myofibroblasts or fibroblasts, producing collagen and hyaluronic acid in the matrix, leading to the gradual formation of the SEP, which was induced by the continual irritation of CAPD.

Aged↗
PubMed1999

Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene.

A novel human homologue (GCMB) of the Drosophila glial cells missing gene (dGCM) was isolated using RACE. GCMB contained a gcm motif sequence and a nuclear targeting sequence similar to that of dGCM and mouse GCMb. Homology searches indicated that GCMB was located within chromosome 6p24.2. Transcripts of GCMB were detected by means of RT-PCR in fetal brain, normal adult kidney, 3/3 medulloblastomas, 1/3 gliomas and 4/8 non-neuroepithelial tumor cell lines. Our data suggest that humans have two homologues of gcm like mice and that human gcm genes form a novel family which may function not only during fetal development but also in the postnatal or pathological stage.

Amino Acid Sequence↗
PubMed1999

A phase II study of KRN8602(MX2), a novel morpholino anthracycline derivative, in patients with recurrent malignant glioma.

KRN8602(MX2) is a newly developed morpholino-anthracycline that has been found to cross the blood-brain barrier and be distributed in brain tissue after intravenous administration and to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo. In order to confirm these promising preclinical observations clinically, we performed a phase II trial of KRN8602 in patients with recurrent malignant glioma. The 44 patients enrolled received at least 2 cycles of KRN8602 35 mg/m2/day at 3-4 week intervals by intravenous bolus. Of the 44 patients, 37 could be evaluated for response, and 39 for toxicity. One patient with anaplastic astrocytoma had a complete response (1/37, 3%), and 2 patients with anaplastic astrocytoma and 1 with brain stem glioma had a partial response (3/37, 8%). The overall response rate was 11% (4/37). All patients who responded had received prior chemotherapy that included nitrosoureas. No response was observed in the patients with glioblastoma. Myelosuppression was moderately severe, with 72% of patients developing grade 3 or 4 leukopenia. Severe nausea/vomiting was observed in 31% of the patients. No severe cardiotoxicity was observed. The results indicate that KRN8602 has modest activity against recurrent malignant glioma with relatively severe, but manageable toxicity. It seems to be worthwhile to further assess the efficacy and toxicity of KRN8602 against malignant glioma, which is generally less sensitive to chemotherapy.

Adult↗
PubMed1999

ACNU, MTX and 5-FU penetration of rat brain tissue and tumors.

The distribution of radio-labeled ACNU, MTX and 5-FU in brain and tumor tissue was studied in female Wistar rats by macroautoradiography after intrathecal administration. In normal rats, ACNU and 5-FU, administered intracisternally, distributed rapidly in the subarachnoid space, ventricular system and cerebrospinal fluid (CSF). 5-FU and MTX penetrated the brain deeply; the diffusional transport of ACNU was limited to a depth of 1 or 2 mm from the CSF surface of the brain. MTX and 5-FU clearance into the blood circulation was rather slow while ACNU cleared relatively quickly. The half time of ACNU, 5-FU and MTX radioactivity at the ventricular surface was 10, 21, and 110 min, respectively, at their maximal concentration after intracisternal administration. In rats with leptomeningeal tumor induced by intracisternal inoculation of Walker 256 cells, the distribution patterns of ACNU, 5-FU, and MTX were essentially the same as in normal rats despite 10-20 cell layers of tumor growing in the subarachnoid space. 5-FU and MTX were able to penetrate tumor masses in the subarachnoid space; MTX penetration was slower than that of 5-FU and ACNU failed to penetrate to more than a depth of 1 or 2 mm from the tumor surface.

Animals↗