Response of isolated guinea pig myocardium to insulin therapy during normothermia and graded hypothermia

The discovery of insulin in 1922 aroused immediate clinical interest in its use in heart disease. In severe heart failure, insulin release is suppressed by the combined effect of poor pancreatic perfusion and by increased sympathetic activity. In these circumstances, myocardial metabolism of glucose may break down through the deficiency of insulin. Because of this, glucose, insulin and potassium solution (GIK solution) has been used in cardiopulmonary resuscitation. However, its mechanism is not yet fully known. This study was designed to determine the effect of insulin on cardiac muscle at various temperatures. The mechanical response of papillary muscle isolated from guinea pig ventricle was observed under various thermal conditions (23-37 degrees C). Twitch tension was increased by the administration of 0.2 I.U./ml insulin under each thermal condition. In all circumstances, the increase in contractile force was noted about 2 min after the administration of insulin. The effect of insulin on 20 preparations demonstrated the mean maximum contractile force was 226% ( +/- 34 S.D., n = 5) in 37 degrees C, 194% ( +/- 36 S.D., n = 5) in 30 degrees C, 190% ( +/- 30 S.D., n = 5) in 27 degrees C and 200% ( +/- 36 S.D., n = 5) in in 23 degrees C. The differences between different temperatures was not significant. The effect of insulin during depression Na-K pump by high concentration of ouabain (g-strophanthin, 10(-5) M) was also observed. Insulin (0.2 I.U./ml) was administered when the papillary muscle showed no response to electrical stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of surgical insults for colorectal cancers on neuroendocrine and immune parameters

In surgery for colorectal cancer, a tendency of immune suppression was noted as seen in surgery for other types of gastro-intestinal cancer. This tendency was also found in the biological response, and it was related to the operative procedures and insults for rectal cancer. The degree of immunosuppression was milder in patients who underwent procedures that preserve the natural sphincter than in those who underwent colostomy. It is important for surgeons to avoid postoperative immunosuppression in order to prevent recurrence and improve prognosis. Given similar degrees of operative insult and stage of cancer, an operative procedure which causes as little immunosuppression as possible should be selected.     

E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer

To identify germline E-cadherin mutations responsible for the predisposition to diffuse gastric cancer (DGC) among the Japanese, we screened 17 patients with familial aggregation of gastric cancer by sequencing analysis. All the patients were diagnosed with DGC and had at least 1 sibling with gastric cancer. Two novel E-cadherin gene variants were detected. One was detected in 1 patient only and associated with an amino acid substitution (Val/Met) at codon 832 in the region essential for binding to beta-catenin. The M832 variant was detected not only in the proband but also in 2 other gastric cancer patients in the family. Immunohistochemical analysis of gastric cancer tissue from the proband revealed that E-cadherin expression was markedly reduced and beta-catenin expression was also reduced in cancer cells. However, no significant difference in the activity of beta-catenin binding was detected between the M832 variant and V832 wild-type E-cadherin in immunofluorescence and immunoprecipitation/Western blot analyses. The other was detected in 5 patients and was located in the splice donor site (IVS1+6T/C); however, RT-PCR analysis indicated that the IVS+6C variant did not cause an aberrant splicing. Thus, the M832 variant could be a germline mutation causative of familial aggregation of DGC, although further functional studies are needed to understand the pathogenic significance of this variant.     

Mutation analysis of the Smad3 gene in human ovarian cancers.

The Smad3 gene is a member of the Smad family, vertebrate homologues of Drosophila Mad, and its gene product is a cytoplasmic element in the transforming growth factor-beta (TGF-beta) signaling pathway. Mutations in TGF-beta receptors and their cytoplasmic elements of transduction signals commonly accompany various cancers. Using PCR-SSCP analysis we searched for the presence of Smad3 gene mutations in 36 human ovarian cancers, and found that 15 cases (41. 7%) had a polymorphism at codon 103. Because this mutation was not accompanied by amino acid replacement, the present results show that the mutations in the Smad3 gene are unlikely to be involved in human ovarian cancers.     

Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a prognostic factor in human endometrial carcinoma

OBJECTIVE: Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed in endometrial carcinoma. Our goal was to investigate if ATP7B is expressed in endometrial carcinoma and whether its expression correlates with prognosis. METHODS: We performed immunohistochemical analysis of ATP7B using a monoclonal antibody against ATP7B in 51 endometrial endometrioid adenocarcinomas. 27 of 51 patients were treated with cisplatin-based chemotherapy after surgery. RESULTS: Cytoplasmic staining of tumor cells was observed in 37.3% (19/51 cases) of the analyzed carcinomas and no staining was observed in adjacent non-neoplastic cells. ATP7B positivity in the degree of differentiation of G2 and G3 carcinoma was significantly higher than that of G1 carcinoma (P = 0.019). The patients with ATP7B-positive tumors had a worse prognosis than that with ATP7B-negative tumors in overall survival and disease-free survival, respectively (P < 0.01). CONCLUSIONS: These findings suggest that overexpression of ATP7B expression in endometrial carcinoma is correlated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. ATP7B expression could be considered as a prognostic factor in patients with endometrial carcinoma.     

Levandoski panographic analysis in the diagnosis of hyperplasia of the coronoid process

The Levandoski panographic analysis of routine panoramic radiographs was developed to improve the diagnosis of hyperplasia of the coronoid process. The ratio of the length of the coronoid process to the condylar process in the Levandoski panographic analysis has a linear relationship with that in the cephalometric analysis (r = 0.75, n = 59). The ratio in patients with hyperplasia of the bilateral coronoid process was significantly greater than that of the control on both sides (P < 0.01). Although the minimum value of ratio in the patients was 1.15, the maximum value of the controls was 1.07. These results show that the Levandoski panographic analysis is useful in the evaluation of hyperplasia of the coronoid process in adults. When a patient complains of limited mouth-opening and the ratio is more than 1.1, further investigations should be made to verify the diagnosis of hyperplasia of the coronoid process.     

Expression of phospholipase D2 in human colorectal carcinoma

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline. PA acts as a second messenger in cell proliferation; therefore PLD is believed to play an important role in carcinogenesis. PLD activity has been reported to be elevated in human breast, gastric, renal cell and colorectal carcinomas, compared with adjacent non-neoplastic tissues. The activity of PLD was also correlated with nuclear grade in breast cancer, tumor size in gastric carcinoma, and nodal involvement and deeper invasion in colorectal carcinoma. However, the number of cases in each study was small. The aim of this study was to investigate the expression level of PLD2 and its association with clinicopathological features in human colorectal carcinoma. Ninety-seven colorectal carcinomas were obtained from surgery. Expression level of PLD2 was assessed by real-time PCR. The prognostic relevance of PLD2 expression level in patients with colorectal carcinoma was also analyzed by the survival analysis of mortality follow-up data covering the period 2000-2004. PLD expression level was varied from tumor to tumor. Expression level of PLD was significantly correlated with tumor size (P<0.05); it was independent of lymph node metastasis, extent of invasion, pathological classification, distant metastasis and Dukes' stage. PLD expression level was also significantly correlated with survival of patients with colorectal carcinoma (P<0.05). These findings suggested that PLD2 plays an important role in progression of colorectal carcinoma and that PLD2 could be a target for therapy in colorectal carcinoma.