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Biomedical subjects

A Inoue

Publications and source records attributed to A Inoue.

At least 73 records · Page 4Linked to original sources

Repeated haloperidol treatment decreases sigma(1) receptor binding but does not affect its mRNA levels in the guinea pig or rat brain.

The effects of chronic treatment with haloperidol on sigma (sigma) receptors were investigated across brain regions and species. The regional distribution of [3H](+)-pentazocine binding to sigma(1) receptor was similar between the guinea pig and rat brains. The highest level of binding was detected in the brain stem and lowest in the striatum and hippocampus. The regional distribution of [3H]1, 3-di (2-tolyl) guanidine ([3H]DTG) binding in the presence of 100 nM (+)-pentazocine to sigma(2) receptor was similar to that of the [3H](+)-pentazocine binding in the guinea pig brain, while in the rat brain high levels of [3H]DTG binding were detected in the cortex, frontal cortex and cerebellum. The intraperitoneal administration of 2 mg/kg of haloperidol to guinea pig and rats once a day for 21 days produced inhibition of [3H](+)-pentazocine binding but did not affect [3H]DTG binding to sigma(2) receptors in any brain region examined. The effects of haloperidol on [3H](+)-penazocine binding in the rat were much weaker than those in the guinea pig. The regional distribution of the level of sigma(1) receptor mRNA determined by the ribonuclease protection assay was similar to that of the [3H](+)-pentazocine binding activity, except in the cortex and cerebellum where the levels of sigma(1) receptor mRNA were low in guinea pig and rat. Treatment with haloperidol did not affect the levels of sigma(1) receptor mRNA in any brain region in either species. These findings suggested that the sigma receptors differentially distributed in brain regions are down regulated by treatment with haloperidol across sigma receptor subtypes and animal species without changing the transcriptional activity of the sigma(1) receptor. The mechanisms by which sigma receptors could be differently regulated in vivo by chronic treatment with haloperidol in different species may contribute to the therapeutic efficacy of haloperidol.

Animals↗

High-dose mouse immunoglobulin G administration suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease.

We studied the effect of high-dose mouse IgG on TMEV-induced demyelinating disease (TMEV-IDD). We injected TMEV intracerebrally into susceptible SJL/J mice and induced TMEV-IDD. Mouse IgG were injected intraperitonealy, and clinical course and various immunological indicators were studied. The results show that TMEV-IDD was significantly suppressed both clinically and histologically (P<0.01) when IgG were administered in the effector phase. The delayed type hypersensitivity and T cell proliferative response specific for TMEV were decreased by this treatment. In an ELISPOT assay, the number of TNF-alpha producing lymphocytes in the spinal cords was low in high-dose IgG treated mice compared with PBS treated control mice. These data suggest that administration of IgG suppresses TMEV-IDD and may be promising treatment to prevent exacerbation of human multiple sclerosis.

Animals↗

The transcript for a novel protein with a zinc finger motif is expressed at specific stages of mouse spermatogenesis.

The cDNA for an RNA that is expressed predominantly in mouse spermatogenic cells was cloned and characterized. It was found to encode novel zinc finger protein. We first generated a cDNA fragment from mouse osteoblastic cells by the differential display method. To our surprise, Northern blot analysis revealed that the corresponding transcript was expressed at high levels in the testis rather than in osteoblastic cells. Therefore, using this fragment as a probe, we isolated the full-length cDNA (3340 bp) from a mouse testis cDNA library. Analysis of the open reading frame of the cDNA indicated that the encoded protein was a polypeptide of 942 amino acids residues that included three distinct domains, namely, a zinc finger domain of the Cys(2)-His(2) type, four basic amino acid-rich domains, and a myosin II-homology domain. In situ hybridization indicated that the transcript was present in seminiferous tubules of adult mice. Elevated expression of the transcript during testicular development in mice was restricted to spermatocytes at the pachytene stage of meiotic prophase and to round and elongated spermatids, as indicated by Northern blot analysis and RT-PCR. Our results suggest that this novel zinc finger protein might act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division.

Amino Acid Sequence↗

Nitric oxide accelerates the ascorbic acid-induced osteoblastic differentiation of mouse stromal ST2 cells by stimulating the production of prostaglandin E(2).

Nitric oxide (NO) promoted the differentiation of clonal stromal cells (ST2 cells) derived from mouse bone marrow to osteoblast-like cells. The level of expression of mRNA for osteocalcin, a marker of osteoblastic differentiation, and the formation of mineralized nodules, increased in ST2 cells treated with a donor of NO. We used the reverse transcriptase-polymerase chain reaction (RT-PCR) to identify the subtypes of NO synthase that were expressed in the ST2 cells and we detected the expression of an inducible NO synthase gene in response to tumor necrosis factor-alpha (TNF-alpha). In various types of cell, NO induces the synthesis of prostaglandin E(2) and cGMP, which are known as regulators of osteoblastic differentiation, by activating cyclooxygenases and soluble guanylate cyclase, respectively. Prostaglandin E(2) was generated in response to NO in ST2 cells, however, no synthesis of cGMP in response to NO was detected. Two inhibitors of cyclooxygenase-2, N-[4-nitro-2-phenoxyphenyl]-methanesulfonamide (nimesulide) and 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid (indomethacin), inhibited the formation of mineralized nodules by ST2 cells. Our observations suggest that NO might promote osteoblastic differentiation of ST2 cells by stimulating the production of prostaglandin E(2).

Animals↗

Quantification of telomerase activity in sporadic colorectal carcinoma: association with tumor growth and venous invasion.

BACKGROUND: Activation of telomerase, a ribonucleoprotein enzyme complex that synthesizes telomere repeats, is associated with acquisition of unlimited cellular proliferation and is commonly detected in human cancer. Measurement of telomerase activity (TA) may provide important information as a diagnostic marker or a prognostic indicator. The authors studied the quantification of TA and assessed its utility as a prognostic marker in sporadic colorectal carcinoma. METHODS: Sixty surgical specimens, including 30 specimens of cancer tissue and 30 specimens of corresponding normal colorectal mucosa, were examined. TA was measured by a fluorescence-based telomeric repeat amplification protocol assay. The authors determined the telomerase index (TI = log (A-B), where A represented TA of cancer tissues and B represented TA of normal mucosa) and examined the relation between TI and clinicopathologic factors using the Student t test, analysis of variance, the Chi-square test, and the Fisher PLSD as a post hoc test. RESULTS: TA of cancer and corresponding normal mucosa was 51.87+/-27.38 and 7.14+/-9.85, respectively (P<0.0001). The cutoff value was determined to be 26 in a receiver operating characteristic study, with 90% sensitivity, 96.7% specificity, and 96.4% positive predictive value. TI was closely correlated with depth of invasion (P = 0.0129) but not with age, gender, histologic type, location, lymph node metastasis, lymphatic infiltration, or Dukes stage. There was a significant difference in TI between tumors with and without venous invasion (P = 0.0003). Four of five tumors with synchronous liver metastasis showed high TI (1.555 <TI). CONCLUSIONS: High TI may be a risk factor for metastasis of colorectal carcinoma to the liver.

Adenocarcinoma↗

A solitary bone cyst in the spinous process of the cervical spine: a case report.

STUDY DESIGN: A case report. OBJECTIVES: To illustrate a rare case of histologically confirmed solitary bone cyst involving the spinous process of C7. SUMMARY OF BACKGROUND DATA: A solitary bone cyst involving the spine is very unusual. Although four cases of a solitary bone cyst in the spine have been reported in the literature, the current authors have been able to find only one case of solitary bone cyst in the spinous process. All four patients reported in the literature were over 30 years of age. The patient in the current case was a 13-year-old girl with no history of trauma. METHODS: Radiographs and a computed tomography scan of the cervical spine were performed before the operation, as was a histologic examination to make a diagnosis of the lesion. RESULTS: The intraoperative findings from examination of the stagnant fluid within the lesion and the histologic examination indicated the diagnosis of a solitary bone cyst. CONCLUSIONS: A solitary bone cyst in the spine is rare, especially in the young. An osteolytic lesion in the spinous process of the spine tends to be diagnosed as an osteoblastoma or as a giant cell tumor of the bone. A solitary bone cyst of the spine, although rare, must be considered as a differential diagnosis.

Adolescent↗

Anti-IL-12 antibody prevents the development and progression of multiple sclerosis-like relapsing--remitting demyelinating disease in NOD mice induced with myelin oligodendrocyte glycoprotein peptide.

Treatment with monoclonal anti-IL-12 antibody injected on day 0, 7 and 10 after immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 in NOD mice resulted in significant suppression of the development and the severity of the chronic relapsing-remitting experimental autoimmune encephalomyelitis (EAE) both clinically and histologically. The spleen cells from anti-IL-12 antibody treated mice displayed markedly inhibited MOG35-55 specific proliferation and IFN-gamma production. MOG35-55 specific antibody production was enhanced by anti-IL-12 antibody treatment. These results suggest that IL-12 is critically involved in the pathogenesis of MOG-induced EAE and that antibody to IL-12 could be an effective therapeutic agent in the clinical treatment of autoimmune demyelinating diseases such as multiple sclerosis (MS).

Animals↗

Increased concentrations of nitrate and nitrite in the cyst fluid suggesting increased nitric oxide synthesis in solitary bone cysts.

The etiology and treatment of a solitary bone cyst have remained undefined. Surgical treatments have not been encouraging, because a less invasive corticosteroid-injection treatment has afforded good results. However, there has been little scientific rationale supporting corticosteroid treatment. In recent reports, bone-resorbing factors, including matrix metalloproteinases, prostaglandins, interleukin-1, and oxygen free radicals, have been demonstrated in the cyst fluid. To better elucidate the pathophysiology of the solitary bone cyst, we examined the activities of nitric oxide and cytokines in the cyst fluid as well as in the cyst membrane. The levels of nitrate and nitrite were significantly higher in the cyst fluid than in serum. Immunostaining of cells in the stroma and lining cells of the cyst wall was strongly positive for inducible nitric synthase. The levels of interleukin-6 and interleukin-1beta in the cyst fluid were elevated, and cells in the cyst membrane were positive for tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. Cultured cells from the cyst membrane were induced in the production of nitrate and nitrite in response to cytokine treatment. These findings suggest that the solitary bone cyst was in a state favorable for the production of nitric oxide.

Adolescent↗

p21 and parathyroid hormone-related peptide in the growth plate.

It is essential for terminal chondrocytes to die before the conversion of calcified cartilage to bone. We have previously demonstrated that apoptosis occurred in the terminal hypertrophic chondrocyte of the growth plate. However, the essential mechanism by which the differentiation of chondrocytes is regulated has not yet been characterized. The purpose of this study was to investigate the mechanism for regulating chondrocyte differentiation. We focused on PTHrP and p21 which regulated the differentiation of chondrocytes and investigated how these factors interacted with each other in chondrocyte differentiation in the growth plate. PTHrP was strongly positive on immunostaining at the interface between the proliferating and the upper zone of the hypertrophic chondrocytes, whereas p21 was negative. On the other hand, p21 was positive in the lower zone of hypertrophic chondrocytes. Furthermore, PTHrP up-regulated the cell proliferation and down-regulated the expression of the p21 messengers in SW-1353 chondrosarcoma cells. These findings indicated that PTHrP might be a negative regulator for p21 in the differentiation of chondrocytes.

Animals↗

Development of a solitary bone cyst--a report of a case suggesting its pathogenesis.

The origin and natural course of solitary bone cysts (SBC) still remain controversial. Knowledge of the process of cyst formation and enlargement would be helpful for investigating its pathogenesis. Only two papers have described a radiodense nidus of the diaphysis as a precursor. Their cases were unique in that the initial lesions were in the diaphysis and that the cysts did not abut onto the epiphyseal line. This study reports a case in a patient with a tiny erosive lesion in the endosteal surface of the humeral metaphysis, which developed expansively into a typical large cyst over 6 years. Serial roentgenograms taken every year demonstrated the process of cyst enlargement. This is the first longitudinal study of a case with SBC documented from its onset.

Bone Cysts↗

Intradiscal pressure after intradiscal injection of hypertonic saline: an experimental study.

Although chemonucleolysis with chymopapain is a long-established treatment for lumbar intervertebral disc herniation, serious complications have been reported. Accordingly, alternative substances for chemonucleolysis have been sought. The main beneficial effect of chemonucleolysis derives from the decrease in intradiscal pressure. Several previous studies have investigated the relationship between physiological saline injection and disc mechanics in cadaveric specimens [2, 5, 16]. However, no previous study has assessed the intradiscal pressure after intradiscal injection of "hypertonic saline" in living animals. The present study compared the changes in intradiscal pressure after intradiscal injection of hypertonic saline with those after chymopapain injection. The lumbar intervertebral discs of 26 living rabbits were examined: 10% hypertonic saline was injected in ten rabbits, and chymopapain (10 pikokatal units) was injected intradiscally in another ten, with the remaining six being used as controls. The intradiscal pressure was measured at 1, 4, and 12 weeks after injection. The intradiscal pressure of the hypertonic saline-injected group at 4 weeks was significantly lower than that of the control group, but by 12 weeks it had recovered. On the other hand, that of the chymopapain-injected group remained significantly lower than that of the control group at 12 weeks. The results of this study found that hypertonic saline injected into the intervertebral discs temporarily decreased the intradiscal pressure.

Animals↗

Radiographic studies of the wrist and elbow in cerebral palsy.

We retrospectively studied and evaluated radiographs of the bilateral wrists and elbows in 96 patients with cerebral palsy. There were 55 patients (57.3%) with athetospastic quadriplegia, 30 (31.3%) with spastic diplegia, and 11 (11.4%) with spastic hemiplegia. Plain antero-posterior and lateral roentgenograms were taken of both wrists and both elbows. Overall negative ulnar variance was seen in 18.2% of wrists, and, the variance was highest in athetospastic quadriplegia. We could not find any case of Kienböck's disease. The radiolunate angle was negative in the wrists of those with athetospastic quadriplegia. Scapholunate dissociation was found in 2 wrists (1%). Four dislocations of the radial head were found in 2 patients (2%). The humero-radial distance and humero-ulnar distance were both narrowed. The formation of osteophytes was mainly found in the humero-ulnar joint, especially in those with athetospastic quadriplegia.

Adolescent↗

Syntactic features in reanalysis: positive and negative symptoms.

Meng and Bader have presented evidence that a Case conflict is a more effective cue for garden-path reanalysis than a number conflict is, for German wh-sentences with subject-object ambiguities. The preferred first-pass analysis has the wh-trace in subject position, although object position is correct. In a speeded grammaticality judgment task, perceivers accepted Case-disambiguated examples more often and more rapidly than number-disambiguated examples, although comprehension questions indicated that both were eventually understood correctly. For ungrammatical sentences, a Case mismatch error resulted in more false positive grammaticality judgments than a number mismatch error. We offer an explanation for why Case and number features differ in these two ways in their effects on sentence processing. We propose, within the Diagnosis Model of garden-path processing, that reanalysis triggered by a Case mismatch guides the parser more effectively toward the correct structure. Case is a positive symptom, which carries information about the new structure that must be built. By contrast, a number mismatch is a negative symptom; it invalidates the incorrect structure without showing how to rebuild it. This difference in the transparency of garden-path repair can also account for the greater overacceptance of Case-disambiguated ungrammatical sentences. The speeded grammaticality judgment task is designed to encourage hasty responses. Usually, these are hasty rejections of garden path sentences that, on calmer reflection, the parser would find acceptable. Conversely, over-hasty acceptance could occur if some initial progress is made in resolving a grammatical problem. Thus, a higher rate of false positives on ungrammaticals is to be expected where reanalysis proceeds successfully for a while before blocking.

Affect↗

Joint-preserving operation for osteoarthrosis of the hip in adult cerebral palsy.

BACKGROUND: A joint-preserving operation was performed on 15 hips with osteoarthrosis, involving 12 patients who had adult cerebral palsy. METHODS: Eleven hips underwent Chiari pelvic osteotomy only; three hips underwent Chiari pelvic osteotomy with femoral osteotomy and the other one hip underwent femoral varus osteotomy only. The mean follow-up period after surgery was 6 years and 2 months (with follow-up range of 2 years and 3 months to 10 years and 6 months). RESULTS: Good results were achieved in 13 of the 15 hips (86.6%). Two patients with athetotic tetraplegia treated with Chiari pelvic osteotomy had pelvic obliquity. Progressive osteoarthrotic change continued in bilateral hips in one case treated with Chiari pelvic osteotomy. CONCLUSION: We confirm that usual treatment for osteoarthrosis of the hip was also applicable for osteoarthrosis of the hip in cases of adult cerebral palsy, provided sufficient attention is given to the complications accompanying spastic paralysis.

Adult↗

Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia.

Brain microglia are a major source of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), which have been implicated in the progression of neurodegenerative diseases. Recently, microglia were revealed to be highly responsive to ATP, which is released from nerve terminals, activated immune cells, or damaged cells. It is not clear, however, whether released ATP can regulate TNF-alpha secretion from microglia. Here we demonstrate that ATP potently stimulates TNF-alpha release, resulting from TNF-alpha mRNA expression in rat cultured brain microglia. The TNF-alpha release was maximally elicited by 1 mM ATP and also induced by a P2X(7) receptor-selective agonist, 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, suggesting the involvement of P2X(7) receptor. ATP-induced TNF-alpha release was Ca(2+)-dependent, and a sustained Ca(2+) influx correlated with the TNF-alpha release in ATP-stimulated microglia. ATP-induced TNF-alpha release was inhibited by PD 098059, an inhibitor of extracellular signal-regulated protein kinase (ERK) kinase 1 (MEK1), which activates ERK, and also by SB 203580, an inhibitor of p38 mitogen-activated protein kinase. ATP rapidly activated both ERK and p38 even in the absence of extracellular Ca(2+). These results indicate that extracellular ATP triggers TNF-alpha release in rat microglia via a P2 receptor, likely to be the P2X(7) subtype, by a mechanism that is dependent on both the sustained Ca(2+) influx and ERK/p38 cascade, regulated independently of Ca(2+) influx.

Adenosine Triphosphate↗