To evaluate the efficacy of preoperative chemotherapy in the treatment of gastric carcinoma, 48 previously untreated patients with locoregional advanced gastric carcinoma were consecutively enrolled in this study and received preoperative 5-fluorouracil (5-FU) or 5'-deoxy-5- fluorouridine (5'-DFUR). Histopathologically, 17 patients showed no response, 27 responded slightly, 3 moderately, and 1 had an excellent response to the chemotherapy. Based on clinical cancer staging, the overall 5-year survival rate was 79% in patients with stages IB and II cancer, 44% in patients with stage III cancer, and 14% in those with stage IV cancer. In patients with stages IB, II, and IIIA disease, the 5-year survival rate for those with a positive histopathologic response to the chemotherapy was 74%, whereas that for the nonresponders was 45%. No relationship was seen between the grade of the histopathologic response and the 5-year survival rate of patients with stage IIIB and IV carcinoma. In a second group of 27 patients who received preoperative chemotherapy with 5-FU, the effect of 5-FU was evaluated using thymidylate synthetase (TS) inhibition. Free TS and total TS were measured in the tumor samples, and the thymidylate synthetase inhibition rate (TSIR) was calculated. TSIR ranged from 0% to 90.7%. The mean TSIR was 66.2% in patients with a positive histopathologic response to chemotherapy and 30.3% in those with a negative response. Mild chemotherapy as orally administered 5-FU or 5'-DFUR was found to be useful in patients with resectable gastric cancer. Furthermore, a correlation was found in chemosensitivity, histopathologic response, and TSIR.

Adenocarcinoma↗

PubMedDate not supplied

Anaphylatoxin C3a induces rapid protein phosphorylation in guinea pig platelets.

We investigated C3a signal transduction using guinea pig platelets. Anaphylatoxin C3a induced cytosolic calcium influx and turnover of inositol phospholipids and caused protein phosphorylation via specific C3a receptors on guinea pig platelets. Phosphorylation of 40 kDa and 20 kDa proteins was detected within 30 s after C3a stimulation. From phosphoamino acid analysis of both proteins, it was found that about 80% was serine and 20% was threonine. Phosphorylation was decreased by pretreatment of platelets with calcium blockers, diltiazem and TMB-8. A protein kinase C inhibitor, staurosporine, effectively blocked phosphorylation of both proteins, but H-7 did not. The effects of these inhibitors on platelet aggregation were correlated with their effects on protein phosphorylation. These results suggest that protein-serine/threonine phosphorylation is important for C3a signal transduction in guinea pig platelets and that the isoenzyme of protein kinase C or another kinase probably participates in such protein phosphorylation. C3a also caused protein-tyrosine phosphorylation of 56 kDa and 33-36 kDa proteins within 30 s. Staurosporine effectively blocked phosphorylation of these bands. It is suggested that tyrosine kinase also may be involved in C3a signalling in guinea pig platelets.

Animals↗

PubMedDate not supplied

Mouse soluble CD14 truncated at amino acid 71 in transgenic mice: preventive effect on endotoxin-mediated toxic shock.

Mouse soluble CD14 truncated at amino acid 71 (N71) contains the lipopolysaccharide (LPS)-binding sequence. Transgenic mice carrying alpha1-antitrypsin (AT) promoter-N71 fusion genes, designated AT363-1 and AT363-2, were produced. These mice constitutively produced elevated levels of N71. The concentration of LPS in sera after intraperitoneal LPS injection was lower in AT363-1 mice than in nontransgenic mice. The expression of N71 mRNA was enhanced by subcutaneous turpentine oil injection. The levels of serum LPS and tumor necrosis factor-alpha (TNF-alpha) after intraperitoneal LPS injections were lower in AT363-1 mice than in nontransgenic mice. Cell surface TNF-alpha and CD14 expression in exudate peritoneal macrophages prepared by intraperitoneal injection of proteose peptone and then LPS were higher in AT363-1 mice than in nontransgenic mice. Neutrophil infiltration in the liver after induction of the generalized Shwartzman reaction was lower in AT363-1 mice than in nontransgenic mice. Lethality of the Shwartzman reaction was significantly lower in AT363-1 than in nontransgenic mice. These findings suggest that the endotoxin-binding protein (N71) from CD14 prevents endotoxin-mediated toxic shock.

Animals↗

PubMedDate not supplied

Influence of vagal pyloric branches on gastric acid secretion and gastrointestinal motility in patients following a pylorus preserving pancreatoduodenectomy.

BACKGROUND/AIMS: The authors evaluated the influence of the vagal pyloric branches on the gastrointestinal function in patients who underwent a pylorus preserving pancreatoduodenectomy (PPPD). METHODOLOGY: Twenty-seven patients with pancreatobiliary and duodenal diseases underwent a PPPD between 1991 and 1994. We analyzed several variables including the daily volume of gastric juice, days of gastric suctioning, start of diet, gastric acid, and gastrin levels. In addition, a gastric emptying scintigram and gastrointestinal manometry were measured. These variables were compared between two groups, namely, those with retained superior pyloric branches of the vagus nerve (preserved group: n = 14), and those without these branches (non-preserved group: n = 13). RESULTS: There were no significant differences in basal acid output, maximum acid output, or plasma gastrin levels between the preserved group and the non-preserved group. In addition, a gastric emptying scintigram demonstrated no difference between the two groups. Finally, on gastrointestinal manometry, there was no significant difference between the two groups during gastric and jejunal phase III activity of migrating motor complex. CONCLUSIONS: Preservation of the vagal pyloric branches did not influence gastric exocrine and endocrine secretion, nor did it effect the gastric emptying of patients who underwent a PPPD.

Adult↗

PubMedDate not supplied

Manual verification of computer analysis of 24-hour esophageal motility.

The application of solid-state technology to intraesophageal pressure monitoring over an entire circadian cycle has resulted in large amounts of data that require computer analysis. Recently available commercial software has yet to be validated. The aim of this study was to compare the analysis of ambulatory esophageal manometry by an automated computer program with manual analysis and make the software modifications necessary to validate the automated system for clinical use. Computer-aided analysis of a large number of esophageal contractions recorded during ambulatory esophageal manometry was compared with manual analysis by four experienced physicians. Good correlations were found between manual and computerized measurements of contraction amplitude and duration (r = 0.99 and r = 0.73, respectively). Software modifications resulted in correct identification of 94% of contractions and correct classification of 93.3% of these waves as peristaltic or simultaneous. These results demonstrate that the evaluated program for automated analysis of ambulatory esophageal manometry is accurate and reliable for research and clinical applications.

Circadian Rhythm↗

PubMedDate not supplied

Hepatic blood flow after acute biliary obstruction and drainage in conscious dogs.

BACKGROUND AIMS: Obstructive jaundice is a factor which effects hepatic blood flow and the relative contribution of the hepatic arterial flow and portal venous flow. In this study, and were measured in conscious dogs and the influence of biliary obstruction and drainage was investigated. MATERIAL AND METHODS: Hepatic arterial flow (HAF) and portal venous flow (PVF) after biliary obstruction and subsequent drainage were continuously measured in conscious dogs using implantable transit time ultrasonic flow-meters. RESULTS: After biliary obstruction hepatic arterial flow rapidly increased compared to the pre-obstructed values(p < 0.01), while portal venous flow was significantly decreased (p < 0.01). Total hepatic blood flow was initially increased (p < 0.01) until 2 hours after obstruction. It then decreased gradually. After 2 weeks, it was less than the pre-obstructed values, but this was not significant. Biliary drainage was performed after 2 weeks. Hepatic arterial flow subsequently decreased (p < 0.01) and portal venous flow increased (p < 0.05). Blood flow did not change. CONCLUSION: Biliary obstruction resulted in significant changes in liver circulation. Biliary drainage facilitated recovery from these changes.

Animals↗