Biomedical subjects

N Onoda

Publications and source records attributed to N Onoda.

At least 37 records · Page 2Linked to original sources

PubMed2001

A combination analysis of p53 and p21 in gastric carcinoma as a strong indicator for prognosis.

We studied p53 and p21 expression simultaneously in gastric carcinoma tissues to investigate the clinical significance of p53-p21 pathway in this disease. One hundred sixty-four primary gastric carcinoma specimens were immunohistochemically stained for p53 and p21 protein, and clinicopathological features of the cases were examined. P53 was stained negatively, while p21 was stained positively in each normal stomach epithelium. P53, and p21 positive staining was observed in 82 (50%) and 61 (37.2%) tumors, respectively. Unexpectingly, no correlation was found between p53 and p21 staining status. Tumors demonstrating preserved p53-p21 pathway [p53(-)/p21(+)], observed in 20.1% of the tumors, displayed less aggressive characteristics, and no recurrent disease after curative resection. While tumors demonstrating disrupted p53-p21 pathway [p53(+)/p21(-)], observed in 32.9% of the tumors, displayed significantly more aggressive characteristics, poorer survival and higher recurrence rate than the tumors demonstrating other staining patterns. P53-p21 pathway was widely altered in gastric carcinomas. The combined evaluation of p53 and p21 expression in gastric carcinoma tissues is suggested to have clinical importance by indicating not only the malignant potential of each tumor, but also the prognosis of this disease.

Adenocarcinoma↗

PubMed2001

Proliferating cell nuclear antigen labeling index and p53 expression predict outcome for breast cancer patients with four or more lymph node metastases.

In general, extensive lymph node metastasis indicates poor prognosis in breast cancer. Nevertheless, some patients with this condition survive for a long time without recurrent disease. This study involved 112 breast cancer patients with four or more lymph node metastases and without distant metastasis who underwent surgery. p53 expression was associated with shorter overall and disease-free survival. High PCNA labeling index was associated with shorter overall disease-free survival. p53-negative and low-PCNA patients survived much longer than p53-positive and high-PCNA patients. This study showed that p53-negative or low-PCNA index patients have relatively good prognoses despite extensive lymph node metastasis.

Adult↗

PubMed2001

Interleukin 10 expression is correlated with thrombospondin expression and decreased vascular involvement in colon cancer.

Interleukin 10 (IL-10) is an immuno-suppressive cytokine produced by T-lymphocytes, and a regulatory molecule for angiogenesis in various cancers. We examined IL-10 gene expression in 53 colon cancer patients who underwent surgical resection. IL-10 gene expression was correlated with TSP1 and TSP2 gene expression (P=0.0049, P=0.0285). Colon cancer with IL-10 gene expression (19/53) showed significantly decreased venous involvement (P=0.0433). The mean vessel counts in the colon cancers with IL-10 gene expression were significantly lower than those without IL-10 gene expression (P<0.001). These results suggested that IL-10 stimulates angiostatic factor gene expression, and results in suppression of venous involvement.

Adenocarcinoma↗

PubMed2001

[A case of amphetamine-induced down-regulation of beta-adrenoceptor].

A 29-year-old man with severe pyloric stenosis confessed that he had been a chronic amphetamine abuser just after awakening from anesthesia for partial gastrectomy. Anesthesia was maintained with thoracic epidural bupivacaine combined with continuous i.v. infusion of propofol. Decreased arterial blood pressure was observed 10 min after starting epidural anesthesia, and remained stable at 80-90 mmHg of systolic blood pressure in spite of massive fluid resuscitation in addition to repeated i.v. administration of ephedrine/methoxamine and continuous i.v. infusion of dopamine at a rate of 8 micrograms.kg-1.min-1. Finally, arterial blood pressure rose gradually after i.v. administration of methylpredonisolone 500 mg. We speculate that the down-regulation of beta-adrenoceptor induced by the sympathomimetic action of amphetamine, might be a major cause of refractory hypotension.

Adult↗

PubMed2000

Synchronous multiple primary gastrointestinal cancer exhibits frequent microsatellite instability.

Colorectal (CRC) and gastric cancers (GC), the most common gastrointestinal malignancies, have been known to develop occasionally in a same patient. Previous studies have focused on the etiology of patients with multiple primary gastric and colorectal cancer (MPGCC); however, the carcinogenic process of MPGCC remains unclear. In this study, we have examined the genetic alterations in MPGCC in order to clarify the carcinogenic pathway. Twenty patients with sporadic MPGCC were examined for microsatellite instability (MSI) and frameshift mutations of target genes such as TGFbetaRII, BAX and IGFIIR. In 10 (50%) of 20 patients with MPGCC, MSI was present at least at 1 lesion of GC or CRC. Four (50%) of 8 cases with synchronous MPGCC displayed MSI in both GC and CRC, while only 1 (8%) of 12 cases of metachronous MPGCC exhibited MSI in both organs. Carcinogenic process of MPGCC was fairly associated with the MSI pathway, particularly in cases of synchronous MPGCC. MSI was found in 5 (25%) of 20 GCs and in 10 (50%) of 20 CRCs. MSI was involved more closely in CRC than in GC among MPGCC. Although most frameshift mutations at target genes were found in the MSI-positive MPGCC, infrequent mutations were observed in the genes. Frameshift mutation was found in only 1 of 5 cases of MSI-positive GC at TGFbetaRII. Only 2 of 10 cases of CRC with MSI showed mutation at TGFbetaRII, and 1 case also showed mutation at BAX and IGFIIR. Our findings suggest that TGFbetaRII, BAX and IGFIIR are not the main target genes for carcinogenesis in MSI-positive MPGCC.

Aged↗

PubMed2000

Novel subdivisions of the rat accessory olfactory bulb revealed by the combined method with lectin histochemistry, electrophysiological and optical recordings.

Wistaria floribunda agglutinin and peanut agglutinin were found to bind histochemically to the anterior and posterior regions, respectively, of the vomeronasal nerve and glomerular layers in the rat accessory olfactory bulb. Furthermore, Ricinus communis agglutinin showed strong binding to the anterior region of the vomeronasal nerve and glomerular layers, whereas it bound weakly and/or moderately to the rostral two-thirds of the posterior glomerular layer but not at all to the caudal one-third. This suggests that the posterior region is further divided into two subregions. An electrophysiological mapping study in sagittal slice preparations demonstrated that stimulation given within the anterior vomeronasal nerve layer elicited field potentials within the anterior region of the external plexiform layer, whereas shocks to the rostral two-thirds and the caudal one-third of the posterior vomeronasal nerve layer provoked field responses within the rostral two-thirds and within the caudal one-third of the posterior external plexiform layer, respectively, indicating that the posterior external plexiform layer is also divided into two subregions. Real-time optical imaging showed similar results as above, except that neural activity also spread into mitral cell layers. Furthermore, the most anterior and posterior ends of the neural activity evoked in the rostral two-thirds of the posterior region immediately adjoined the posterior border of that evoked in the anterior region and the anterior border of that evoked in the caudal one-third of the posterior region, respectively. Moreover, the granule cell layer was also found to have similar boundaries. Thus, optical imaging studies demonstrated individual precise boundaries of these subdivisions, which were positioned right beneath those defined by Ricinus communis agglutinin histochemistry. The presence of functional segregation in each layer leads us to conclude that there are at least three different input-output pathways in the rat vomeronasal system.

Animals↗

PubMed2000

Laparoscopic adrenalectomy for benign adrenal tumors.

Laparoscopic adrenalectomy has been rapidly accepted for treatment of benign adrenal tumors. To evaluate the advantages of laparoscopic adrenalectomy, we examined 55 patients who underwent laparoscopic adrenalectomy. In all patients, adrenal tumors were successfully removed. The mean operating time was 143 minutes, and the estimated mean blood loss was 49 mL in all patients. The postoperative course was uneventful in all cases. The mean frequency of administration of analgesics was only 2.9 times, and the time elapsed to first walking after surgery was 17 hours. The peak white blood cell count and C-reactive protein values after surgery were 8,266 +/- 1,963/mm3 and 2.5 +/- 1.2 mg/dL, respectively. Of the 55 patients, 44 underwent total adrenalectomy and another 11 underwent partial adrenalectomy, which was introduced in the expectation of preserving normal adrenal cortex; it is therefore indicated in solitary and peripherally located benign tumors. The mean operating time was 154 minutes for the total adrenalectomy, which was longer than that of partial adrenalectomy (92 minutes). The estimated blood loss was 50 mL for the total and 46 mL for the partial adrenalectomy. The postoperative course was uneventful and surgical outcome was excellent in each group. In conclusion, our results are encouraging enough to suggest that laparoscopic adrenalectomy should be a preferential therapeutic option for benign adrenal tumors; also, partial adrenalectomy could be a safe, effective, and less invasive procedure in selected cases.

Adrenal Gland Neoplasms↗

PubMed2000

Selective suppression of horizontal propagation in rat visual cortex by norepinephrine.

The release of norepinephrine in the cerebral cortex from axon terminals of locus coeruleus neurons was suggested to be involved in the control of attention. Accumulating data indicate that the responses of cortical neurons are varied when norepinephrine is applied iontophoretically in the vicinity of the cells being recorded. However, it is not known how the pattern of excitatory propagation is modified when norepinephrine is applied over a wide area in the visual cortex. By applying optical imaging to rat visuocortical slices, we found a new mode of norepinephrine action; a prominent suppression of the horizontal propagation in layers II/III. This action of norepinephrine was confirmed by the simultaneous recording of field potentials from multiple sites by use of a multi-electrode dish. Furthermore, our electrophysiological recordings showed that this norepinephrine action is exerted through suppression of excitatory neural transmission and enhancement of inhibitory transmission to the pyramidal neurons in these layers. Because the release of norepinephrine in the visual cortex is regulated by the level of attention, the neural basis of visual attention may relate partially to the suppression of the integration of visual information by norepinephrine resulting in a state-dependent restructuring of the receptive field.

2-Amino-5-phosphonovalerate↗

PubMed2000

Genetic structure of the five-factor model of personality in a Japanese twin population.

Dimensional approaches have been used to describe the fundamental dimensions that underlie the entire domain of normal and pathological personality. We tested the five factor model of personality structure in a sample of Japanese twins, to clarify the contributions of genetic and environment. The revised NEO personality inventory (NEO-PI-R) was administered to 251 twin pairs, ranging in age from 15 to 27 years of age. The NEO-PI-R is a 240-item questionnaire which was developed to assess the dimensions of personality. Univariate genetic analysis showed that the AE model in which phenotypic covariances are explained only by additive genetic (A) and nonshared environment (E) is still a plausible model, and that the relative proportion of genetic influence was comparable to that reported by Loehlin (1992). Multivariate genetic analysis of the Japanese data suggested/revealed that the five factors are genetically dependent on each other and one common genetic factor mediates their interdependence. Previous studies have assumed that they are phenotypically independent and robust. Although there are sampling biases in the present study, it is noteworthy that the results for all five factors depicted by the NEO-PI-R were comparable to those reported by Western researchers, and the genetic structure of the five-factor model is complex.

Adolescent↗

PubMed2000

Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma.

Solid tumors require neovascularization for growth and metastasis. Vascular endothelial growth factor (VEGF) is a well-characterized inducer of angiogenesis, while, thrombospondin-1 (TSP-1) is thought to be an antiangiogenic factor. In this study, we examined the expressions of these antigens and their relationship with microvessel density, and determined their prognostic significance. One hundred specimens resected from patients with colorectal adenocarcinoma were examined using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumors that were VEGF-positive and TSP-1-negative than in other tumors. Patients with VEGF-positive tumors had a significantly worse prognosis than did those with VEGF-negative tumors, and TSP-1 expression was inversely correlated with prognosis. The frequency of hepatic recurrence was significantly higher in patients with tumors that were VEGF-positive and TSP-1-negative than in all other patients. In conclusion, VEGF and TSP-1 are important regulators of tumor angiogenesis, and combined analysis of VEGF and TSP-1 may be useful for predicting recurrence in patients with colorectal adenocarcinoma.

Adenocarcinoma↗

PubMed2000

Caspase-1 activity as a possible predictor of apoptosis induced by cisplatin in gastric cancer cells.

Recent studies have shown that caspases, which are cystein proteases, elevate endonuclease activity and induce apoptosis. Caspase-1, an interleukin-1beta converting enzyme, has been reported to be related with anti-cancer drug induced apoptosis as well as with caspase-3. To elucidate the caspase-1 activity, which might be a predictor for the effect of chemotherapy, we examined the changes of caspase-1 activity induced after exposure to cisplatin (CDDP) in six gastric cancer cell lines. A high correlation between the 50% inhibitory concentration (IC50) and caspase-1 activity ratio was shown (r=0.83, p=0.041) (caspase-1 activity ratio: the caspase-1 activity of cells at 4 h after CDDP treatment/the caspase-1 activity of untreated cells). Further, we examined the correlation between caspase-1 activity and apoptosis induced by CDDP in two cell lines that have very different CDDP sensitivities; OCUM-2M and OCUM-2M/DDP (IC50; 0. 85+/-0.4 microg/ml and 9.0+/-1.2 microg/ml, respectively). The apoptotic index of OCUM-2M was significantly higher than that of OCUM-2M/DDP (19.8+/-3.8% vs. 4.5+/-1.2%, respectively; p=0.0005). In both cell lines, caspase-1 activity began to increase immediately after exposure to CDDP and peaked at approximately 4 h after cessation of exposure to CDDP, and gradually decreased thereafter. The caspase-1 activity of OCUM-2M was approximately 1.8-times higher than that of OCUM-2M/DDP at 4 h after exposure to CDDP. Taken together, our results indicate that evaluating the changes of caspase-1 activity after exposure to CDDP may be useful to predict apoptosis following CDDP treatment in gastric cancer cells.

Antineoplastic Agents↗

PubMed2000

Effects of "isolating hemodialysis" on prevention of methicillin-resistant Staphylococcus aureus cross-infection in a hemodialysis unit.

AIM: To evaluate the effects of a contact isolation program against methicillin-resistant Staphylococcus aureus (MRSA) cross-infection among patients in a hemodialysis unit. CLINICAL SETTING AND METHODS: In all patients maintaining hemodialysis therapy were tested for MRSA infection and who had MRSA infection, not only inpatients but also outpatients were separated into a designated area (isolating hemodialysis). Clinically isolated MRSA strains were clonotyped with coagulase typing, staphylococcal enterotoxin typing and restriction enzyme analysis of plasmid DNA. RESULTS: The frequency of patients with MRSA infection was 4.5% before starting this protocol and was reduced to 2.9% two and a half years later. At this time, MRSA was isolated from the 8 patients. These 8 clinical strains were differentiated into 6 clonotypes and 3 strains showed the same patterns. Two of 3 were isolated from inpatients and the other was from a patient with community onset MRSA colitis. In this case, most MRSA infections were independent under prophylaxis control and cross-infection was observed only once between hospitalized patients who stayed in a same ward. CONCLUSION: This "isolating hemodialysis" should be useful to prevent cross-infection among patients in end-stage renal disease in a dialysis unit.

Adult↗

PubMed2000

[Three cases of metastatic breast cancer, resistant to pre-chemo and/or endocrine therapy, markedly improved with UFT and cyclophosphamide oral combination therapy].

The cases of 3 female patients with metastatic breast cancer treated with oral UFT and cyclophosphamide (CPA) are reported. Patient 1 had lymph node and bone metastases. Patient 2 had bone metastasis. Patient 3 had skin, lymph node, and peritoneal metastases. All had a history of mastectomy and chemo- and/or endocrine therapy for metastatic lesions. Patients 2 and 3 had also undergone CAF combination chemotherapy. However, the lesions did not change. UFT 400 mg and CPA 100 mg, everyday, were administered to patient 1. UFT 400 mg and CPA 100 mg, 2 weeks, and UFT 400 mg, 2 weeks, were given every 4 weeks to patient 2. UFT 300 mg and CPA 150 mg, 6 weeks per 8 weeks were given to patient 3. Improvements in the metastatic lesions were seen 4 weeks after the beginning of UFT and CPA therapy. Therapy is now continuing, and no patients had a progression of the disease. All had leukopenia 2 or 4 weeks after the beginning of this therapy, and two temporarily stopped the therapy. No other side-effect was observed. Oral UFT and CPA combination therapy was considered useful for metastatic breast cancer. To prevent leukopenia and prolong the term of treatment efficacy, a treatment regimen will need to be established.

Administration, Oral↗

PubMed1999

Vascular endothelial growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric carcinoma.

BACKGROUND: Recently many studies have demonstrated that the degree of tumor angiogenesis is related to the aggressiveness of the tumor and clinical outcome. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. In this study, the authors investigated the prognostic significance of VEGF expression in patients with early gastric carcinoma together with p53 gene abnormality and tumor cell proliferation. METHODS: One hundred ninety-five endoscopically biopsied specimens obtained preoperatively from patients with early gastric carcinoma were studied immunohistochemically. RESULTS: According to conventional clinicopathologic factors, submucosal invasion, lymph node metastases, and tumor size were associated significantly with the incidence of disease recurrence. According to conventional biologic factors, VEGF expression was observed more frequently in patients with disease recurrence compared with those without disease recurrence whereas neither p53 abnormality nor tumor cell proliferation were correlated with prognosis. Moreover, multivariate analysis indicated that VEGF expression (as well as submucosal invasion and lymph node metastases) is an independent predictor of disease recurrence. CONCLUSIONS: The results of the current study show that VEGF expression may be a useful prognostic factor for patients with early gastric carcinoma.

Adult↗

PubMed1999

Neuroendocrine carcinoma of the sigmoid colon: report of a case.

Neuroendocrine carcinoma of the colon is a rare entity; however, this type of tumor is known for its aggressive progression and poor prognosis. A case of a 56-year-old Japanese male is presented in this report. A huge, child's head-sized tumor was found to have grown extraluminally on the sigmoid colon with multiple liver metastases. The tumor measured 16.5 x 15 x 8.2 cm in size and weighed 1 300 g. The patient died of hepatic failure due to massive liver metastases 6 months after operation. The pathological findings including an electron microscopic analysis were correlated with those of neuroendocrine carcinoma. We reviewed the English literature, and analyzed 94 cases of neuroendocrine carcinoma which had been reported previously. The nomenclature and definition of this disease still remains somewhat unclear, and not a small population of this disease may thus have been misdiagnosed and treated as other less aggressive entities. The necessity to make an accurate differential diagnosis in such cases is thus emphasized.

Carcinoma, Neuroendocrine↗

PubMed1999

Effects of GABAergic agonists and antagonists on oscillatory signal propagation in the guinea-pig accessory olfactory bulb slice revealed by optical recording.

To investigate the action of GABAergic agents on oscillatory signal propagation induced by electrical stimulation of the vomeronasal nerve layer, optical and electrophysiological recordings were carried out in slice preparations of the guinea-pig accessory olfactory bulb. In response to electrical stimuli, characteristic optical signals appeared in each layer: in the vomeronasal nerve layer, a transient presynaptic response; in the glomerular layer, pre- and postsynaptic responses; in the external plexiform, mitral cell and granule cell layers, a damped oscillatory response. Application of the GABAergic agonists, that is, GABA, muscimol (a GABAA receptor agonist) and baclofen (a GABAB receptor agonist), suggested that the GABAB action existed mainly in the glomeruli, whereas the GABAA action was present in both the glomeruli and the external plexiform layer. Bicuculline (a GABAA receptor antagonist) produced long-lasting but nonoscillating excitation in the external plexiform and mitral cell layers, indicating that the GABAA action contributes to the formation of oscillatory responses. When double-pulse stimulation was applied to the vomeronasal nerve layer, the test responses in the glomerular layer and external plexiform and mitral cell layers were depressed, but those in the vomeronasal nerve layer were not. Application of 2-hydroxysaclofen (a GABAB receptor antagonist) mostly blocked paired-pulse depression occurring in the glomerular layer and restored the reduced transmission to mitral cells, but had only a small effect on the depressed oscillatory response in the external plexiform and mitral cell layers. These observations suggest that GABAB action in the glomerular layer might, at least, regulate information flow from vomeronasal afferents to apical dendrites of mitral cells, like a gate inhibition. However, actions other than GABAB could also be involved in the depression of the oscillation in the external plexiform and mitral cell layers.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

[A case of interstitial nephritis induced by a super antigen produced by methicillin-resistant Staphylococcus aureus (MRSA) presenting as acute renal failure].

We report the case of a 21-year-old man who had been developing acute renal failure with Methicillin-resistant Staphylococcus aureus (MRSA) colitis and sepsis. He was admitted for consciousness disturbance, nausea, vomiting, and diarrhea. Oliguria was also observed and his serum creatinine level was elevated to 10 mg/dl. Urinary protein was positive and an abundance of hyaline cast were seen in urinary sedimentation. Diarrhea and pyrexia were prolonged and serum C-reactive proteins were elevated, but lymphocyte and leukocyte counts temporarily decreased from the 3rd to the 6th hospital day and remained low until normalizing after the 14th day. His clinical symptoms improved with hemodialysis (HD) and effective antibiotic therapies. An MRSA strain producing toxic shock syndrome toxin-1 (TSST-1), a super antigen which specifically stimulates human V beta 2-positive T cells, was separated from his feces and blood. To ascertain the cause of his renal dysfunction, a renal biopsy was performed on the 8th day. His renal histology revealed acute interstitial nephritis with severe inflammatory cell infiltration around the medullary areas without glomerular changes. Most of the infiltrated cells were small monocytes, and lymphoid cells were rich in the interstitium. With immunohistochemical staining, over 70% of T-cells were V beta 2-positive. TSST-1-producing MRSA was detected in his blood specimen. Furthermore, V beta 2-positive T cells were accumulated in the renal intersititium, and transient lymphocytopenia was observed. These data suggested the following possible pathogenesis for interstitial nephritis: TSST-1 acts as a super antigen in the renal interstitium where major histocompatibility complex (MHC) is class-2-positive, thereby resulting in interstitial nephritis with T cell migration.

Acute Kidney Injury↗

PubMed1998

Serum CA 125 level as a predictor of peritoneal dissemination in patients with gastric carcinoma.

BACKGROUND: Prediction of peritoneal dissemination is very difficult using current diagnostic tools such as computed tomography, ultrasonography, or various tumor markers. The predictive value of serum CA 125 levels for peritoneal metastasis from gastric carcinoma was studied. METHODS: The sera from 384 patients with gastric carcinoma were measured for CA 125 titer using an immunoradiometric assay. Carcinoembryonic antigen, carbohydrate antigen 19-9, and sialyl-Tn antigen were measured in the same samples. RESULTS: The serum CA 125 level was elevated according to the degree of peritoneal dissemination. The reference value for peritoneal dissemination was determined to be 35 U/mL, resulting in a sensitivity of 39.4%, specificity of 95.7%, and diagnostic accuracy of 90.8%. The diagnostic ability was more reliable than the other imaging modalities including computed tomography and ultrasonography and the other useful tumor markers for gastric carcinoma. The serum CA 125 level was elevated after gastrectomy for approximately 2 months, most likely due to the continuous inflammation of the peritoneum and lost predictive significance for peritoneal dissemination during this period. CONCLUSIONS: Measurement of the serum CA 125 titer may be a powerful predictor of peritoneal metastases in patients with gastric carcinoma.

Adult↗