Secular trends in the incidence,mortality, and survival rate of gastric cancer in a general Japanese population: the Hisayama study

To examine secular trends in the incidence and mortality of gastric cancer in a Japanese community, Hisayama, we established three study-cohorts of Hisayama residents aged ≥40 years in 1961 (1637 subjects), 1974 (2054), and 1988 (2602). Each cohort was followed up for ten years. The age-standardized mortality from gastric cancer significantly decreased from 2.4 per 1000 person-years in the first cohort to 0.8 in the third cohort for men, and from 1.0 to 0.2, respectively, for women (p < 0.01 for trend in both sexes). The five-year survival rate after gastric cancer significantly improved from the first (32.6%) to the third cohort (73.0%, p < 0.01) for men and from 43.2% to 72.3% (p < 0.05), respectively, for women. The age-standardized incidence of cancer in men was not different among the cohorts (4.3 per 1000 person-years in the first, 5.0 in the second, and 4.9 in the third cohort), while it decreased significantly in women (2.0, 1.8, and 1.2, respectively, p < 0.01 for trend). In conclusion, our findings suggest that in a Japanese population, the mortality from gastric cancer declined during the past 40 years, due mainly to the improvement of survival in both sexes and a decrease in the incidence for women.     

Induction of apoptosis in human salivary gland tumor cells by anti-NCAM antibody

Neural cell adhesion molecule (NCAM) is a type of cell surface glycoprotein and a member of the immunoglobulin superfamily. It has been reported that NCAM may be associated with perineural invasion by malignant salivary gland tumors such as adenoid cystic carcinoma. We have previously demonstrated that NCAM is constitutively expressed in the human salivary gland tumor cell line HSG, in vitro. In the present study, we have aimed to clarify the hypothesis that NCAM-mediated inhibition of salivary gland tumor proliferation is caused by homophilic binding and involves the prevention of signal transduction for perineural invasion using HSG cells. NCAM mRNA and protein expression was found to decrease in a dose-dependent manner upon treatment with the anti-NCAM antibody (MAb NCAM) for 24 h. The MTT assay showed a significant reduction in the number of viable HSG cells. Confocal laser microscopy showed that HSG cells underwent apoptosis after treatment with MAb NCAM. The activation of caspases 3, 7 and 9 was observed in HSG cells after treatment with MAb NCAM, thus confirming that apoptosis was induced by the activated caspases. Apaf-1 activity was also detected in HSG cells in a dose-dependent manner after treatment with MAb NCAM. The up-regulation of TGF-beta1-mediated NCAM expression appeared to lead to the activation of homophilic NCAM binding, further accelerating HSG cell proliferation. In addition, the localization of NCAM in adenoid cystic carcinomas (ACCs) was examined using an immunohistochemical method. NCAM was slightly to moderately positive in 9 of 13 cases (69.2%) of ACC. These findings suggest that NCAM is associated not only with a cell-to-cell adhesion mechanism, but also with tumorigenesis, including growth, development and perineural invasion in human salivary gland tumors.     

Black sheep effect and ingroup favoritism in social identity perspective

Black sheep effect (Marques, Yzerbyt, & Leyens, 1988) and ingroup favoritism (Tajfel, Billig, Bundy, & Flament, 1971) appear to contradict each other with respect to the evaluation of inferior ingroup members. In addition to examining the relationship between the two phenomena, this study also examined the effect of ingroup identification on them. Sixty-one female student-nurses participated in the study. To measure black sheep effect, superior and inferior ingroup and outgroup members were rated on 20 adjectives. Distribution matrices (Tajfel et al., 1971) were used to measure ingroup favoritism. The participants were median split according to their level of group identification. Black sheep effect was found only among high-identification participants, who also showed ingroup favoritism. Ingroup identification had a positive correlation with both ingroup favoritism and black sheep effect. Overall, ingroup favoritism had a positive correlation with the evaluation of superior members, while it had a negative correlation with that of inferior ingroup members.     

In vivo evidence for a lack of central effect of ebastine,an antihistaminic agent,in rats: a microdialysis study

The effects of ebastine and its active metabolite carebastine on brain dopamine uptake and the accessibility to brain were compared with those for a classical antihistaminic agent chlorpheniramine by using the microdialysis technique. Both carebastine and chlorpheniramine potently inhibited brain [(3)H]dopamine uptake and increased the extracellular concentration of dopamine in the striatum after local perfusion via microdialysis probes, although systemic injection of ebastine but not chlorpheniramine did not change the dopamine level. These findings suggest that neither ebastine nor carebastine affects central dopamine metabolism because of a limited access to brain, in spite of having a potent inhibitory action on neuronal dopamine uptake.     

Non-invasive lobular carcinoma within a fibroadenoma, a preoperatively diagnosed case

Breast cancer within a fibroadenoma is rare and usually diagnosed postoperatively from pathological specimens. This paper reports a 54-year-old female with non-invasive carcinoma within a fibroadenoma, diagnosed preoperatively. She underwent a medical examination and mastopathy was suspected. On physical examination a mass 2 cm in diameter was palpated in the left breast. Ultrasonography showed a mass with smooth margins and uniform internal echoes, but cytology showed malignancy. Mammography showed a round mass with distinct margins and no calcification. As fibroadenoma, diagnosed by ultrasonography and mammography, and breast cancer, diagnosed by cytology, were not consistent results several core biopsies were performed. Needle biopsy showed proliferation of atypical epithelial cells; breast cancer within a fibroadenoma was diagnosed. MRI showed a circular mass with distinct, smooth margins and in a dynamic study, the mass showed irregular staining and the presence of early staining. Left lumpectomy and dissection of the left axillary lymph nodes was performed. Histological examination showed non-invasive lobular carcinoma occurring within a fibroadenoma.     

Statistics on the operations at the Department of Urology, Fuji City General Hospital during a 10-year period (January 1989-December 1998)

A 10-year statistic survey was carried out on the operations performed at the Department of Urology, Fuji City General Hospital. The total number of operations was 1,862 cases during 10 years. The number of operations for malignant tumors has increased since 1994 year after year. Transurethral resection of prostate for benign prostatic hyperplasia has decreased since 1992, with the advent of the alpha 1-blocker. The patients with urolithiasis are being cured by extracorporeal shock wave lithotripsy on an outpatient basis, at our hospital, except in special cases. It was suggested to be safe, so the complications needing admission appeared in only 1.2% of the cases.     

A case of renal cell carcinoma diagnosed by MAG3 scintigraphy because of moderate renal dysfunction

An 84-year-old man presented at our hospital with complaints of severe gross hematuria and lower right abdominal pain. A right renal mass was detected by ultrasound sonography and plain computerized tomography (CT) scan, but an exact diagnosis was not obtained. Because the patient presented with moderate renal dysfunction and severe gross hematuria, we were unable to perform imaging studies using contrast material or ureteroscopic instruments. Finally, mercaptoacetylglycyl-glycylglycine (MAG3) scintigraphy and magnetic resonance imaging (MRI) demonstrated renal cell carcinoma, and we performed transarterial embolization (TAE) therapy using ethanol and gel foam. Based on their efficacy and noninvasiveness, we conclude that MAG3 scintigraphy and MRI are the optimal modalities for imaging in patients with renal dysfunction.     

Angiotensin-converting enzyme inhibitors and probucol suppress the time-dependent increase in urinary Type IV collagen excretion of Type II diabetes mellitus patients with early diabetic nephropathy

BACKGROUND: A multicenter prospective clinical trial was carried out in 9 National Hospitals in Japan to elucidate the time-dependent change in urinary Type IV collagen excretion rate of Type II diabetes mellitus (DM) patients, and to investigate whether an angiotensin-converting enzyme inhibitor (ACE-I) or probucol is effective in preventing progression of renal involvement of diabetics by evaluating urinary Type IV collagen excretion. METHODS: Normo- and microalbuminuric patients with Type II DM were recruited. Patients were assigned to either the control (n = 88), ACE-I (n = 43) or probucol (n = 37) group and treated for 24 months. Besides albumin excretion rate (AER), urinary Type IV collagen excretion rate was also measured. RESULTS: Although, AER, urinary N-acetyl-beta-D-glucosaminidase and beta2-microglobulin excretion rates in the control group did not vary over 24 months, urinary Type IV collagen excretion rate in the control group increased time-dependently (p < 0.01 vs baseline at 18 months and p < 0.005 vs baseline at 24 months). In the ACE-I and probucol groups, time-dependent increases in urinary Type IV collagen excretion rates were not observed. In the ACE-I group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 24 months (p < 0.05). In the probucol group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 6 months (p < 0.05). In the ACE-I group, AER decreased significantly compared with baseline at 18 months (p < 0.05) and at 24 months (p < 0.005). CONCLUSIONS: ACE-I has a beneficial effect and probucol may have a beneficial effect in preventing the progression of early diabetic nephropathy. Measurement of the urinary Type IV collagen excretion rate in combination with AER would be useful for the management of early renal involvement in Type II DM.     

Expression of heat shock protein 72 in atrophied rat skeletal muscles.

Changes in the expression of heat shock protein 72 (HSP72) in response to atrophic-inducing perturbations of muscle involving chronic mechanical unloading and denervation were determined. Adult male Wistar rats were assigned randomly to a sedentary cage control (CON), hind limb unloading (HU, via tail suspension), HU plus tenotomy (HU + TEN), HU plus denervation (HU + DEN), or HU + TEN + DEN group. Tenotomy and DEN involved cutting the Achilles tendon and removing a segment of the sciatic nerve, respectively. After 5 days, HSP72 levels in the soleus of the HU + DEN and HU + TEN + DEN groups were 42 (P < 0.05) and 53% (P < 0.01) less than CON, respectively. Soleus weight decreased in both groups. Heat shock protein 72 levels in the plantaris of the HU + TEN, HU + DEN, and HU + TEN + DEN groups were 31, 25, and 30% lower than CON, respectively (P < 0.05). Plantaris weight decreased in the HU + DEN and HU + TEN + DEN, but not in the HU + TEN group. Hind limb unloading alone had little effect on the HSP72 level in either muscle. Reduced levels of HSP72 were associated with a decreased soleus (r=0.62, P < 0.01) and plantaris (r=0.78, P < 0.001) weight. These results indicate that the levels of HSP72 in both a slow and a fast rat plantarflexor are responsive to a chronic decrease in the levels of loading and/or activation and suggest that the neuromuscular activity level and the presence of innervation of a muscle are important factors that induce HSP72 expression.     

Functional promoter polymorphisms of the macrophage migration inhibitory factor gene in gastric carcinogenesis

The macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. Two functional polymorphisms have been identified in the promoter region of the MIF gene. We attempted to clarify the associations of these polymorphisms with the development of gastric cancer. The study was performed in 229 patients with gastric cancer and 428 subjects with no evidence of gastric malignancies on the upper gastro-duodenal endoscopy. The severity of histological chronic gastritis was classified according to the updated Sydney system. Overall, the 5-CATT carriers had a reduced risk of developing gastric cancer (OR, 0.67; 96% CI, 0.48-0.93; p=0.015), especially the diffuse type cancer. In subjects >60 years, the adjusted risk for gastric cancer among individuals who were -173C carriers was 1.71 (range, 1.03-2.84; p=0.038) compared to the G/G homozygous genotype. The number of 7-CATT alleles was also positively correlated with the development of intestinal type gastric cancer (adjusted OR, 1.70; 95% CI, 1.02-2.58; p=0.043). In subjects <60 years, the 7/7-CATT homozygous genotype was linked with a risk for the progression of atrophic gastritis (adjusted OR, 8.74; 95% CI, 1.31-58.6; p=0.026). In addition, the number of 7-CATT alleles was significantly correlated with the activity and inflammation scores (p=0.010 and 0.030, respectively). Our results suggested that functional promoter polymorphisms of the MIF gene are associated with the progression of gastric mucosal inflammation and the development of mucosal atrophy at an early stage in life and these genotypes may increase the risk for the subsequent development of gastric cancer, especially the intestinal type, in older subjects.