Extracellular and Intracellular Regulation of Biliary Lecithin Hydrophobicity

Bromosulfophthalein and papaverine have beendemonstrated to inhibit biliary lipid secretion withoutaffecting secretion of bile salts in normal rats,so-called uncoupling. Bromosulfophthalein inhibits the capacity of intracanalicular bile saltmicelles to induce biliary lipid secretion, andpapaverine inhibits vesicular transport within thehepatocyte. We compared the effects ofbromosulfophthalein and papaverine on biliary lipid secretion in normalSprague-Dawley rats and Eizai hyperbilirubinuria rats.The fatty acyl chain saturation in biliary lecithinincreased during bromosulfophthalein infusion and decreased during papaverine infusion inSprague-Dawley rats. Bromosulfophthalein had no effecton biliary lipid secretion in Eizai rats, whilepapaverine induced uncoupling. The degree of fatty acylchain saturation in biliary lecithin was unchangedduring bromosulfophthalein infusion, but decreased withpapaverine in Eizai rats. We deduce that selection ofbiliary lecithin species occurs at various points in the lipid transport pathway at intracellularand intracanalicular sites.     

Angiotensin-converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism

BACKGROUND: The D allele of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and coagulation activity play important roles in cardiovascular events, however, the precise association between these two risk factors remains unclear. METHODS: We identified the ACE I/D genotype and measured the plasma coagulation factor VII and X (FVII and FX) activities and serum lipids in 172 patients (110 men and 62 women, mean age 56.7+/-13.3 years) undergoing coronary angiography. RESULTS: The frequency of the D allele was significantly higher in those with a history of myocardial infarction (MI) than in those with normal coronary arteries, but there was no significant association between FVII and FX activities and the stage of coronary disease. Plasma coagulation factor VII and FX activities were significantly lower in the DD genotype (n=42) than in the II genotype (n=67, P<0.001 and P<0.001, respectively) or the ID genotype (n=63, P<0.01 and P<0.05, respectively). The association of the ACE D allele with lower activities of FVII and FX was also seen in patients with coronary artery disease (CAD). There was a significant association between serum triglyceride levels with FVII and FX, but not with the ACE I/D genotype. CONCLUSION: We concluded that the ACE I/D polymorphism may contribute more to the onset of MI than the activities of FVII and FX and that the ACE D allele might be associated with lower plasma activities of FVII and FX. The potential link between ACE I/D polymorphism and the plasma activities of FVII and FX is probably independent of triglyceride metabolism.     

Randomized controlled trial of two forms of self-management group education in Japanese people with impaired glucose tolerance

The aim of this study was to determine the effectiveness of education on diabetes prevention in subjects with impaired glucose tolerance. A total of 100 subjects of impaired glucose tolerance with hemoglobin A1c (HbA1c) levels >/=5.5 to <6.1% were assigned randomly to either support or control groups. All subjects received education in 8 sessions over a 6-month period. The support group consisted of 10 members collaborating with a dietitian or a nurse who learned coping skills by employing a participant-centered approach. Participants in the support group were required to keep a diary that monitored weight, food intake and blood glucose levels, while the control group attended several lectures. Subjects assigned to the support group had a reduction in mean HbA1c levels from 5.77 +/- 0.36% at baseline to 5.39 +/- 0.24% at the endpoint (p<0.01). Weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels also decreased (p<0.01) in the support group, whereas subjects in the control group had no observable reduction in these indices. After intervention, participants of the support group had improvements in their 2-h post-meal blood glucose levels. Support group education can be effective for improving glycemic control in participants when carried out in collaboration with educators and other team members.     

Lymphatic invasion according to D2-40 immunostaining is a strong predictor of nodal metastasis in superficial squamous cell carcinoma of the esophagus: algorithm for risk of nodal metastasis based on lymphatic invasion

In squamous cell carcinoma (SCC) of the esophagus, D2-40 immunostaining has recently been used to detect lymphatic invasion, but invasion detected using D2-40 immunostaining for a predictor of nodal metastasis was controversial. Therefore, the usefulness of detecting lymphatic invasion by D2-40 immunostaining as a predictor of nodal metastasis was examined in superficial (mucosal and submucosal) SCC of the esophagus. A total of 115 superficial SCC of the esophagus were examined on immunohistochemistry using D2-40. It was found that lymphatic invasion demonstrated on D2-40 immunostaining was mainly detected in the lamina propria mucosa. Lymphatic invasion was found in 37 cases and the invasion detected in the entire tumor tissue was statistically correlated with nodal metastasis. Based on the lymphatic invasion according to D2-40 immunostaining, an algorithm was devised for the risk (low, intermediate and high) of nodal metastases in superficial SCC in the esophagus. In conclusion, the detection of lymphatic invasion on D2-40 immunostaining in tumor tissue is a strong predictor for nodal metastasis in superficial SCC of the esophagus. Lymphatic invasion was found mainly in the lamia propria mucosa, thus the devised algorithm is useful for determining the optimal treatment strategy after endoscopic mucosal resection for esophageal SCC.     

Expression of cell cycle regulators and growth factor/receptor systems in gastric carcinoma in young adults: association with Helicobacter pylori infection

We studied the expression of cell cycle regulators and growth factor-receptor systems in gastric carcinoma in young adults and tried to clarify the specific alterations associated with H. pylori. We studied 33 young patients (18-29 years old, mean age 26.4) with gastric carcinoma. The patients were classified into two groups according to the degree of atrophic gastritis. Then we examined the expression of p53, cripto, cyclin-E, c-met, c-erbB2 and TGF-alpha immunohistochemically and compared the results between the two groups. The results were compared with 66 sex-, tumor histology-, and depth-matched elder controls (36-86 years old, mean age 64.0). H. pylori was judged by Giemsa staining. Seventeen patients had atrophic changes in the corpus (Group A), while 16 showed superficial gastritis or normal mucosa (Group S). All 17 patients of Group A showed H. pylori infection, while the 3 of the 16 members of Group S did not have H. pylori. p53 overexpression was observed more frequently in Group S (88%) than in Group A (41%, p<0.05). In the 3 patients without H. pylori infection, all carcinoma specimens showed p53 overexpression. Overexpression of cyclin-E was detected in 4 patients from Group S. On the other hand, cripto was observed more frequently in Group A than in Group S. No obvious differences were observed in c-erbB2, TGF-alpha and c-met expression. Overall, p53 overexpression was detected more frequently in younger than in older patients, whereas cripto expression was less detected. These results suggest that p53 and cyclin-E may act in an H. pylori-independent or -adjunctive manner for gastric carcinogenesis. Cripto expression might be correlated tightly with H. pylori infection.     

Vitamin D receptor gene polymorphism is associated with serum total and ionized calcium concentration

Restriction fragment length polymorphisms of the vitamin D receptor gene have recently been reported to be associated with changes in bone mineral density. Alterations in systemic calcium balance and Ca-regulating hormones such as 1,25(OH)2 vitamin D3 and parathyroid hormone have been demonstrated in essential hypertension. We investigated the relationship between polymorphisms of the vitamin D receptor gene and systemic Ca metabolism in patients with essential hypertension and in normotensives. We compared 147 subjects with essential hypertension and 100 normotensive control subjects. The genotype distribution and derived allele frequencies for the vitamin D receptor gene were similar in the two groups (genotype bb/Bb/BB and allele B/b: 60.1/32.6/7.2 and 0.24/0.76 in hypertensives vs. 56.0/36.0/8.0 and 0.26/0.74 in normotensive subjects). Serum concentrations of total Ca in the bb, Bb, and BB groups were, respectively, 4.5+/-0.3 vs. 4.5+/-0.4 vs. 4.4+/-0.5 mmol/l in normotensives and 4.6+/-0.3 vs. 4.6+/-0.4 vs. 4.4+/-0.5 mmol/l in hypertensives. Ionized Ca levels were 1.17+/-0.04 vs. 1.16+/-0.04 vs. 1.15+/-0.04 mmol/l in normotensives and 1.16+/-0.04 vs. 1.16+/-0.04 vs. 1.14+/-0.05 mmol/l in hypertensives, respectively. These results indicate that the BB genotype of the vitamin D receptor gene is associated with lower serum Ca levels but is not a useful predictive marker for the development of essential hypertension in Japanese subjects.     

Survival impact of capsule rupture in stage I clear cell carcinoma of the ovary in comparison with other histological types

Objective

We analyzed a large number of stage I clear cell carcinoma of the ovary (CCC) patients to estimate the survival impact of the capsule status in stage I CCC patients, particularly in comparison with non-CCC patients.

Methods

Clinicopathologic data on 564 patients with stage I epithelial ovarian cancer (EOC) collected under the central pathological review system were subjected to uni- and multivariable analyses to evaluate the disease-free survival (DFS) and overall survival (OS).

Results

There was no significant difference in both the OS and DFS of CCC patients between IA and IC(ir) (intraoperative capsule rupture) {IA vs. IC(ir); OS: P = 0.1402, DFS: P = 0.2701}. In contrast, CCC patients at IC(non-ir) {IC excluding for IC(ir), such as preoperative capsule rupture, positive ascites/washing, and surface involvement} showed a poorer OS and DFS than those at IC(ir), or those at the corresponding stage in non-CCC. In multivariable analysis, the capsule status was an independent prognostic factor of a poor OS and DFS {OS: HR, 2.832; 95% CI 1.156-6.938; P = 0.023; DFS: HR, 4.327; 95% CI, 1.937-9.667; P = 0.0004)} {In contrast, non-CCC: N.S. (OS/DFS)}. Furthermore, in CCC patients, intraperitoneal recurrences were more frequently observed in IC(non-ir) CCC than IA or IC(ir) CCC (P = 0.0083) {In contrast, non-CCC: N.S.}.

Conclusion

This study suggests that CCC patients other than those with intraoperative capsule rupture show a considerable risk for mortality despite adjuvant chemotherapy.     

Gemcitabine in elderly patients with unresectable pancreas cancer

The efficacy and safety of gemcitabine at a starting dose of 1,000 mg/m2 administrated once a week for 3 weeks with 1 week's rest was investigated in elderly 11 patients with unresectable pancreatic cancer. Objective response was not documented. However, pain intensity, analgesic consumption and Karnofsky Performance Status (KPS) were frequently improved. In total, a clinical benefit was observed in 8 out of 11 (73%) patients. Toxicity was mild and well tolerated. These results suggest that gemcitabine had a superior clinical benefit and a mild toxicity profile. Gemcitabine should be the standard treatment in elderly patients with unresectable pancreatic cancer.