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Biomedical subjects

N Onoda

Publications and source records attributed to N Onoda.

At least 73 records · Page 4Linked to original sources

Increased concentration of vascular endothelial growth factor/vascular permeability factor in cyst fluid of enlarging and recurrent thyroid nodules.

Human thyrocytes produce vascular endothelial growth factor (VEGF), a potent angiogenic factor, also known as vascular permeability factor (VPF), which increases vascular permeability. Based on the assumption that VEGF/VPF is involved in fluid accumulation in thyroid cysts, we determined the VEGF/VPF concentration in cyst fluids of thyroid nodules from 79 patients. VEGF/VPF was found to be abundantly present in the cyst fluids (0.02-183 ng/mL). There was no significant difference of VEGF/VPF concentration in the cyst fluid obtained from thyroid adenoma or from adenomotous goiter with cystic degeneration. Immunoreactive VEGF/VPF in cyst fluid was eluted mainly at 45 kDa, and stimulated endothelial cell proliferation, which was partially blocked by anti-VEGF/VPF antibody. The VEGF/ VPF concentration in the cyst fluid obtained from patients who required repeated aspiration or underwent surgical resection because of recurrent accumulation (84.8 +/- 58.3 ng/mL, mean +/- SD, n = 18) was significantly higher than that in the cysts that regressed or disappeared after a single aspiration (4.3 +/- 4.4 ng/mL, n = 12, P < 0.001). These in vitro and clinical findings suggest that VEGF/VPF is at least partly involved in the accumulation of cyst fluid in thyroid nodules, and that a high VEGF/VPF concentration predicts rapid accumulation of the cyst fluid, possibly necessitating interventional treatment.

Adenoma↗

[Malignancy of colorectal cancer analyzed by expression of cyclin D1].

We evaluated the clinical significance of cyclin D1 expression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal cancers were investigated by staining with a monoclonal antibody against cyclin D1. The possible correlations among cyclin D1 expression, clinicopathologic factors and prognosis were studied. There was no significant association between cyclin D1 expression and various clinicopathological factors. However, disease-free survival was significantly worse in the patients with cyclin D1 strongly positive tumors than in those with cyclin D1 negative tumors. Cyclin D1 overexpression may be useful as a predictor of disease recurrence in patients with colorectal adenocarcinoma.

Adenocarcinoma↗

[Immunohistochemical study of p21 expression in gastric carcinoma].

In this study, the expression of p21 protein was investigated immunohistochemically in 152 patients with gastric cancer. Expression of p21 was detected in 64 tumors (42.1%). There were significant differences among the expression of p21, histologic type, depth of invasion, lymph node metastasis, liver metastasis, and peritoneal metastasis. The deeper the tumor invaded, the more frequent p21 expression increased. Of the 152 patients, lymph node, liver and peritoneal metastasis were found in 86, 13 and 23 patients, respectively. p21 expression was more frequently lost in tumors from patients with metastasis. In relation to prognosis, patients with p21-positive tumors had a significantly better prognosis than those with p21-negative tumors. In conclusion, this study suggested that expression of p21 has a prognostic value in gastric cancer.

Cyclin-Dependent Kinase Inhibitor p21↗

[Eumycotic mycetoma of the lower leg].

Eumycotic mycetomas are extremely rare diseases in Japan. Only four cases have been reported. In the present report, eumycotic mycetoma of right lower leg of a 44-year-old male of Thai origin, resident in Japan for more than five years, was presented. An induration was noticed on the antero-medial side beneath the knee. Computed tomography showed slightly high dense subcutaneous mass-like lesion at the medial side of the right tibia. Though no draining sinus was formed, histologic examination disclosed grains composed of septated hyphae with Splendore-Hoeppli material. Since more people from foreign countries tend to reside in Japan, physicians and pathologists should be aware of various infections which are not commonly found in Japan.

Adult↗

Immunolocalizations of human gelatinase (type IV collagenase, MMP-9) and TIMP (tissue inhibitor of metalloproteinases) in normal epidermis and some epidermal tumors.

The matrix metalloproteinases (MMPs) MMP-2 and MMP-9 (gelatinases) have been suggested as serving an important role in cleaving the basement membrane structure. Tissue inhibitors of metalloproteinases TIMPs (particularly TIMP-1) are known to inhibit MMPs. Based on this background, we raised monoclonal antibodies against human gelatinase (MMP-9) and human recombinant TIMP (TIMP-1), and immunostained these two components in skin from patients with squamous cell carcinoma (SCC), Bowen's disease (BD) and keratoacanthoma (KA). MMP-9 showed positive staining mainly in the granular layer of normal epidermis. In some cases of SCC and BD, MMP-9 showed positive staining in the dysplastic lesions even in the basal layer. TIMP showed a thorough positivity in normal epidermis. Unstained regions with this antibody were observed in SCC and BD. These results suggest that an altered staining pattern for MMP-9 and TIMP may be closely related to the malignant transformation of SCC and BD.

Animals↗

Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma.

It is known that angiogenesis plays an important role in the growth and metastasis of solid tumours. Several angiogenic factors have been identified and platelet-derived endothelial cell growth factor (PD-ECGF) is thought to be one such factor. Recently, it was reported that thymidine phosphorylase (dThdPase) is identical to PD-ECGF. Using immunohistochemical staining with an anti-dThdPase antibody, we investigated the correlation between dThdPase expression and the microvessel density in 120 gastric carcinomas. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in dThdPase-positive tumours than in dThdPase-negative tumors. There was a significant correlation between dThdPase expression and the increment of microvessel density. Moreover, regarding distant organ metastasis, the frequency of hepatic metastasis was significantly higher (P < 0.01) in patients with dThdPase-positive tumours than in those with dThdPase-negative tumors. In summary, it was suggested that dThdPase expression is closely associated with the promotion of angiogenesis and hepatic metastasis in gastric carcinoma.

Adult↗

'Seronegative' Sjögren's syndrome manifested as a subset of chronic fatigue syndrome.

We determined the extent to which chronic fatigue syndrome (CFS) patients with sicca symptoms fulfil the diagnostic criteria for Sjögren's syndrome (SS). Three sets of diagnostic criteria for SS, formulated by the Japanese, Europeans and Fox, were used. One-third of the CFS patients with sicca symptoms fulfilled the diagnostic criteria for SS. However, they were 'seronegative', differing from the ordinary primary SS.

Adult↗

Overexpression of c-myc messenger RNA in primary and metastatic lesions of carcinoma of the stomach.

BACKGROUND: Although c-myc expression in carcinoma of the stomach has been reported to be involved in progression of the disease, little is known about the mechanism or significance of its expression. STUDY DESIGN: We measured c-myc messenger RNA (mRNA) levels by Northern blot hybridization in 51 primary gastric carcinoma lesions and 15 metastatic lesions accompanied by normal mucosal tissues from the same patients. The extent of c-myc mRNA expression in malignant lesions was determined and compared with that in normal mucosal tissues. The clinical and pathologic significance of c-myc mRNA expression was investigated. RESULTS: In 35 (68.6 percent) of 51 primary gastric carcinomas c-myc mRNA was overexpressed. Expression was found to be more frequent and stronger in early lesions than in advanced lesions (90 percent, 6.15-fold compared with 54.8 percent, 2.42-fold, p < 0.05). However, c-myc mRNA expression in the primary lesions showed little influence on either the histologic features or the disease progression. C-myc mRNA levels were higher in every metastatic lesion than in the primary lesions (9.89-fold compared with 3.04-fold, p < 0.05). CONCLUSIONS: These observations suggest that c-myc mRNA overexpression may play a role in the early development of primary lesions as well as in the formation of metastatic lesions of carcinomas of the stomach.

Blotting, Northern↗

[Correlation between expression of RB protein and prognosis of gastric cancer].

In this study, the expression of retinoblastoma (RB) protein was investigated immunohistochemically in 94 patients with gastric cancer. Overexpression of RB was detected in 48 tumors (51.1%). There was no significant association among the expression of RB, histologic type, lymph node metastasis, and liver metastasis. However, a significant difference was noted with respect to depth of invasion and peritoneal metastases. Among 94 patients, peritoneal metastases were observed in 11 patients. RB expression was detected in only two of these cases with peritoneal metastases, which was significantly less than those without peritoneal metastases. In relation to prognosis, patients with RB-positive tumors had a significantly better prognosis than those with RB-negative tumors. In conclusion, this study suggested that expression of RB has a prognostic value in gastric cancer.

Adenocarcinoma↗

Damped oscillatory activity in the guinea pig accessory olfactory bulb slice.

Extracellular field potentials were recorded from guinea pig accessory olfactory bulb (AOB) slices following electrical stimulation of the vomeronasal nerve layer (VNL). A single shock of the VNL provoked a characteristic damped oscillatory field potential, which consisted of a compound action potential followed by 6-7 periodic negative peaks (n1, n2, n3, n4, n5, n6 or n7). The average frequency of the oscillation was 32 Hz. The existence of oscillation in the AOB suggests the possibility that the oscillatory activity not only may reflect 'quantal' sampling periods, but also may be dynamically altering the AOB conditions under which incoming pheromone-like information is processed.

Action Potentials↗

Gonadotropin-releasing hormone overcomes follicle-stimulating hormone's inhibition of insulin-like growth factor-5 synthesis and promotion of its degradation in rat granulosa cells.

The effect of a gonadotropin-releasing hormone-agonist (GnRH-a) on the synthesis of insulin-like growth factor-binding protein-5 (IGFBP-5), a physiological marker for atresia, was investigated. Granulosa cells obtained from diethylstilbestrol (DES)-treated immature female rats were cultured in serum-free medium for 72 h with GnRH-a and the conditioned media were subjected to immunoblot analysis using rat IGFBP-5 specific antibody. GnRH-a caused a dose-dependent (ED50 = 8.6 x 10(-11) M) accumulation of IGFBP-5, which migrated as 35 (non-glycosylated) and 36 kDa (glycosylated) bands under reducing conditions. A maximally effective dose of GnRH-a (10(-9) M) caused a 4-fold increase in IGFBP-5 accumulation. In contrast, increasing doses of porcine follicle-stimulating hormone (pFSH) caused a biphasic effect on IGFBP-5 accumulation. A low dose of pFSH (0.25 ng/ml) increased and higher doses of pFSH (22.5 ng/ml) decreased the 35 and 36 kDa IGFBP-5 bands. In the presence of high doses of pFSH (20.75 ng/ml), a 22 kDa band corresponding to a cleaved IGFBP-5 fragment appeared in the media. When the granulosa cells were cultured with a saturating dose of pFSH, co-addition of GnRH-a dose dependently inhibited the FSH effects (ED50 = (2.3-3.7) x 10(-10) M). The GnRH-a effects were completely blocked by co-incubation with GnRH-antagonist. IGFBP-5 mRNA accumulation levels were increased by GnRH-a in a dose dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mucoepidermoid carcinoma of the pancreas: report of a case.

We present herein the case of a 64-year-old man diagnosed as having a mucoepidermoid carcinoma of the pancreas. The tumor originated in the tail of the pancreas and invaded the spleen, left adrenal gland, left kidney, and transverse colon. Liver and peritoneal metastases were also noted. Despite surgical treatment and adjuvant chemotherapy, the disease progressed rapidly and the patient died of cachexia 4 months after his initial diagnosis. Mucoepidermoid carcinoma of the pancreas is a rare entity, and is believed to be a form of adenosquamous carcinoma known as adenoacanthoma. However, in this patient, no differentiated squamous cell component could be detected. In fact, the tumor was composed of mucin-producing cells, epidermoid cells, and intermediate cells. Immunohistochemical staining for the carcinoembryonic antigen, CA19-9, and SPan-1 demonstrated a production of cancerous mucin in the epidermoid cells, suggesting that mucoepidermoid carcinoma may arise from the squamoid metaplasia of an adenocarcinoma.

Biomarkers, Tumor↗

Tumour angiogenesis and tumour cell proliferation as prognostic indicators in gastric carcinoma.

Tumour growth depends on neovascularisation and tumour cell proliferation. Factor VIII-related antigen (F-VIII RA) localises to vascular endothelium. Expression of proliferating cell nuclear antigen (PCNA) is correlated with cell proliferation. We investigated the correlation between the expression of these antigens and prognosis in gastric carcinoma. A total of 108 specimens resected from patients with gastric carcinoma were investigated by staining with monoclonal antibodies against F-VIII RA and PCNA. Microvessel count (MVC; the mean number of microvessels in the five areas of highest vascular density at 200 x magnification) and PCNA labelling index (PCNA LI; percentage of positive cells in more than 500 tumour cells) were determined. The results showed that prognosis was significantly worse in patients who had a tumour with a high MVC (16 or greater) or a high PCNA LI (42% or greater) than in those patients who had a tumour with a low MVC (less than 16) or a low PCNA LI (less than 42%). Furthermore, MVC was significantly associated with the risk of hepatic recurrence. In conclusion, both MVC and PCNA LI may be good prognostic indicators in patients with gastric carcinoma.

Adult↗

Extensive lichen amyloidosus refractory to DMSO.

While lichen amyloidosus reportedly may respond to dimethyl sulfoxide (DMSO) application, we present a patient whose lesions were refractory to this agent. This Japanese woman had chronic extensive lichen amyloidosus, mainly on her trunk. Her 10-year history of using nylon towels was the suspected cause. The application of DMSO ointment had no clinical effect, and the amyloid deposits persisted in the histological specimens despite the treatment. The administration of a topical corticosteroid led to gradual clinical improvement.

Administration, Topical↗

Tumor angiogenesis as a predictor of recurrence in gastric carcinoma.

PURPOSE: We investigated the correlation between tumor angiogenic activity and progression of gastric carcinoma using immunohistochemical staining with antifactor VIII-related antigen (F-VIII RAg) antibody. MATERIALS AND METHODS: One hundred twenty-four specimens resected from patients with gastric carcinoma were investigated by staining with a monoclonal antibody against F-VIII RAg. Correlations between the microvessel count (the mean number of microvessels in the five areas of highest vascular density at 200 times magnification), various clinicopathologic factors, and prognosis were studied. RESULTS: The microvessel count increased with histologic stage. The microvessel count was significantly higher in patients with lymph node metastases than in those without such metastases. Moreover, in patients with a high microvessel count (> or = 16), prognosis was significantly poorer than in those with low count (< 16). Multivariate analysis indicated that the microvessel count is an independent prognostic factor in patients with gastric cancer. According to the mode of recurrence, the frequency of hepatic metastases was significantly increased in patients with a high count. CONCLUSION: Microvessel count may be a good prognostic indicator and may be useful as a predictor for the mode of recurrence in patients with gastric carcinoma.

Adenocarcinoma↗

[Correlation between malignancy of gastric cancer and c-myc DNA amplification or overexpression of c-myc protein].

The amplification of c-myc DNA for fresh frozen tissue of 31 gastric adenocarcinomas was examined with dot blot hybridization method. Using the avidin-biotin peroxidase complex method, the expression of c-myc protein was examined immunohistochemically for formalin-fixed paraffin embedded tissue of 51 gastric adenocarcinomas including the same cases for c-myc DNA analysis. c-myc DNA amplification was detected in only 4 cases (12.9%). However, c-myc protein overexpression was recognized in 21 cases (41.2%). Only one of 4 cases showing c-myc DNA amplification indicated overexpression of c-myc protein. There was no statistically significant relation of c-myc protein overexpression with clinicopathological factors (histology, depth of invasion, invasion of the vessels, metastasis, intraabdominal dissemination and histological staging). These results suggest overexpression of c-myc protein could be recognized even in early gastric cancer indicating the relation of this gene product with proliferation of gastric cancer cells, although its role in the progression and metastasis of gastric adenocarcinoma might be minimal.

Adenocarcinoma↗