Harumasa Ohyanagi

Increased levels of soluble triggering receptor expressed on myeloid cells-1 in patients with acute pancreatitis.

Objective:To determine the contribution of triggering receptor expressed on myeloid cells (TREM)-1 in acute pancreatitis (AP). Design:Prospective study. Setting:General intensive care unit at Kobe University Hospital. Patients:Forty-eight patients with AP and seven patients as control. Interventions:None. Measurements and Main Results:We measured serum concentrations of soluble TREM-1 (sTREM-1) at the time of admission by enzyme-linked immunoadsorbent assay. Serum sTREM-1 levels increased significantly in AP (63 ± 11 pg/mL) and correlated with Ranson score (R = .628, p < .001) and Acute Physiology and Chronic Health Evaluation II score (R = .504, p < .001). Serum TREM-1 levels were higher in patients with early organ dysfunction (which occurred within 7 days after onset) than those without early organ dysfunction (101 ± 19 vs. 25 ± 4 pg/mL, p < .001). Incidences of early organ dysfunction in patients whose serum sTREM-1 levels were ≤40 and >40 pg/mL were 17% and 83%, respectively (p < .001). The usefulness of serum sTREM-1 in detecting early organ dysfunction was superior to that of C-reactive protein, interleukin-6, interleukin-8, Ranson score, and Acute Physiology and Chronic Health Evaluation II score. Serum sTREM-1 levels decreased with resolution of early organ dysfunction. Conclusions:Serum sTREM-1 levels were significantly increased and correlated with disease severity and early organ dysfunction in patients with AP. Serum sTREM-1 level may be a useful marker for early organ dysfunction in AP.

Protective effect of a microtubule stabilizer taxol on caerulein-induced acute pancreatitis in rat.

The effect of taxol, which is a microtubule stabilizer, was examined in a model of acute edematous pancreatitis induced in rat by the administration of caerulein. Prophylactic administration of taxol ameliorated inhibition of pancreatic secretion, increased level of serum amylase, pancreatic edema, and histological alterations in this model. Immunofluorescence studies revealed that taxol stabilized the arrangement of microtubules by the action of promoting tubulin polymerization and prevented inhibition of pancreatic digestive enzyme secretion. In isolated rat pancreatic acini, taxol reversed the inhibition of amylase secretion induced by supramaximal concentrations of cholecystokinin octapeptide and did not affect the binding of cholecystokinin octapeptide to its receptor. The results obtained in this study suggest that microtubule disorganization is the initiating event in caerulein-induced pancreatitis and that the inhibition of pancreatic digestive enzyme secretion by interfering with intracellular vesicular transport due to microtubule disorganization causes caerulein-induced pancreatitis.

Molecular cloning and characterization of a ras p21-like GTP-binding protein (24KG) from rat liver

We have isolated cDNA clones from a rat liver cDNA library that encode a ras p21-like small GTP-binding protein (24KG) which was purified from the microsomes-Golgi complex fraction of the rat liver. The cloning was accomplished using polymerase chain reaction amplified with a set of oligonucleotide primers which were designed from the partial amino acid sequences for 24KG. The cDNA contained an open reading frame encoding a 216 amino acid protein with a calculated Mr weight of 24,397. This Mr weight was similar to that of the purified 24KG estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The sequence analysis of 24KG revealed that a 24KG cDNA is the rat counterpart of a rab11 cDNA cloned from a Madin-Darby canine kidney cell cDNA library. The 1.0-kilobase 24KG mRNA corresponding to the isolated cDNA was also detected in various rat tissues, such as brain, testis, spleen, and heart.

Present status of clinical studies of Fluosol-DA (20%) in Japan.

Fluosol-DA (20%) is a fine-particle stable emulsion with low toxicity and rapid elimination from the body. Based on comprehensive animal experiments and phase one human studies, Fluosol-DA (20%) has been given clinically to 401 patients in Japan. In 270 of these patients, it was given to treat severe hemorrhage, and in 131, it was given to improve impaired cerebral circulation or for other nonhemorrhagic indications. In these studies, Fluosol-DA (20%) was effective as a blood gas carrier as well as a plasma expander. After infusion of 20 ml of Fluosol-DA (20%) per kilogram of body weight, while maintaining the FIO2 at or near 0.5 or 0.6, PFCs transport an amount of oxygen equivalent to approximately 6.3 +/- 1.4% of the oxygen transported by the hemoglobin phase and approximately 100% of the oxygen transported by plasma. The arteriovenous oxygen difference in the PFC phase was approximately 25 to 30% of that in the hemoglobin phase. Of the oxygen consumed by the tissues, approximately 17% was provided by the PFC phase after treatment with Fluosol-DA (20%). Hemodynamic parameters of patients with hemorrhage were either maintained or recovered to normal levels after Fluosol-DA (20%) infusion. No acute or chronic untoward reactions were observed either early or late after infusion of Fluosol-DA (20%), except for a transient decrease in neutrophils and platelets after the initial administration of a test dose of 1 ml, and these parameters recovered spontaneously in 30 minutes. No abnormal findings that could be attributed to Fluosol-DA (20%) were found in the heart, lungs, liver, spleen, kidneys, bone marrow, endocrine system, or other organs. Organ retention of PFC particles was evaluated in 6 autopsy cases in Japan. Although PFCs were detected in many organs several months after a single Fluosol-DA (20%) injection of 20 ml per kilogram of body weight, PFCs were not found in body tissues of those who were autopsied more than 7 months after its infusion. RES function was slightly depressed for a few days in patients receiving 20 ml of Fluosol-DA (20%) per kilogram of body weight. It was also depressed for several days in rats given 40 ml per kilogram of body weight. Compared with that of control patients, recovery to preoperative levels was slightly delayed in patients receiving Fluosol-DA (20%). Despite this, administration of up to 20 ml of Fluosol-DA (20%) per kilogram of body weight should be safe with respect to the RES function.(ABSTRACT TRUNCATED AT 400 WORDS)

Papillary hyperplasia of the pancreas.

We report the first case of surgically resected pure papillary hyperplasia of the pancreas. Interestingly, it was not associated with chronic pancreatitis or pancreatic cancer. Histologic and immunohistochemical features are described, with a review of the literature on papillary hyperplasia of the pancreas.

Overexpression of c-Ki-ras and c-fos in human pancreatic carcinomas

SummaryThe mRNA expression of protooncogenesc-Ki-ras, c-myc, andc-fos was studied in five pancreatic carcinomas and five normal pancreatic tissues using RNase protection assay and Northern blot analysis. The expression of those protooncogenes was detected in total mRNA from all specimens. However, the amounts in carcinomas and in normal tissues differed.C-Ki-ras mRNA in all the tumors was expressed up to sixfold more than in normal tissues.C-fos mRNA was also overexpressed up to tenfold in four of five tumors. In contrast,c-myc mRNA levels were varied and did not differ significantly between tumors and normal tissues. The results suggest that the overexpression ofc-Ki-ras andc-fos mRNA are implicated in the development of pancreatic adenocarcinoma.

Enhancement of fibroblast growth factor-induced diacylglycerol formation and protein kinase C activation by colon tumor-promoting bile acid in Swiss 3T3 cells: Different modes of action between bile acid and phorbol ester

A small amount (50–200 μM) of deoxycholate (DOC), a colon tumor‐promoting bile acid, did not show a direct effect on protein kinase C activity in a cell‐free system, but enhanced fibroblast growth factor (FGF)‐induced diacylglycerol formation and protein kinase C activation in Swiss 3T3 cells. DOC potentiated both reactions induced by submaximal doses of FGF but showed little effect on the maximal levels of the reactions. DOC alone was inactive in eliciting both reactions in the absence of FGF. DOC did not affect the binding of FGF to the cells. Since it has been described that diacylglycerol serves as a messenger for the activation of protein kinase C in the action of FGF in Swiss 3T3 cells [(1985) FEBS Lett. 191, 205‐210], these results suggest that a small amount of DOC increases the sensitivity to FGF of diacylglycerol formation and thereby potentiates protein kinase C activation in this cell line. This action of DOC was in marked contrast to that of 12‐O‐tetradecanoylphorbol‐13‐acetate, a potent tumor‐promoting phorbol ester, which directly activated protein kinase C in cell‐free and intact cell systems.

Enhancement of secretagogue-induced phosphoinositide turnover and amylase secretion by bile acids in isolated rat pancreatic acini.

Small amounts (0.1-0.5 mM) of deoxycholate enhanced amylase secretion, which had been induced by submaximal doses of carbachol or cholecystokinin octapeptide, without affecting the maximal levels of these reactions from isolated rat pancreatic acini. Deoxycholate alone did not induce these reactions. The other bile acids such as cholate, chenodeoxycholate, ursodeoxycholate, and taurocholate were also active. Under the similar conditions, deoxycholate enhanced the secretagogue-induced diacylglycerol formation that was derived mainly from the phospholipase C-mediated hydrolysis of phosphatidylinositol and phosphatidylinositol-4-monophosphate. Deoxycholate did not enhance the secretagogue-induced hydrolysis of phosphatidylinositol-4,5-bisphosphate or Ca2+ mobilization. Deoxycholate did not affect amylase secretion, which was induced by the simultaneous addition of protein kinase C-activating 12-O-tetradecanoylphorbol-13-acetate and Ca2+ ionophore ionomycin. Since diacylglycerol and Ca2+ may be responsible for the secretagogue-induced amylase secretion, our results indicate that small amounts of bile acids increase the sensitivity to the secretagogue of diacylglycerol formation and subsequent activation of protein kinase C, and thereby enhance amylase secretion from pancreatic acini.

Discussion and Considerations for the Excretion Mechanism of Perfluorochemical Emulsion

It has been assumed that a mononuclear phagocyte system is related to the excretion of PFC emulsions: PFC particles are phagocytized by blood monocytes to be expelled through the lung alveoli. This monocyte-related mechanism may well explain excretion at an early stage when PFC particles are abundant in the blood stream. It does not, however, fully explain the manner by which PFC cells are released from the RES cells into the blood stream and into the adipose tissue. To explain this, the following mechanism has been proposed and discussed based on some experimental results. PFC emulsion particles taken up by the RES organs, are stripped at their surfactant layers in the cells and move across the cell membranes to the blood vessels and into other tissues such as adipose, at a rate that depends on the lipophilicity of the PFCs. In the blood stream, PFCs are delivered by lipoproteins to the lung and excreted into the expired air. Pharmacokinetical analysis with a compartmental model for the excretion also supported this proposed mechanism.

Laparoscopic splenopexy for adult wandering spleen: sandwich method with two sheets of absorbable knitted mesh.

Wandering spleen is a rare entity with a constant danger of splenic torsion leading to splenomegaly and infarction, which requires surgery. The authors describe a 30-year-old woman with intermittent left hypochondralgia and back pain with wandering spleen, who was successfully treated with a new method of laparoscopic splenopexy. In this procedure, two sheets of absorbable knitted mesh were used to sandwich the detorsed spleen. The procedure is feasible and less invasive, without impaired splenic function, and is applicable even for adult splenomegalic wandering spleen.