Enhancing effect of bile and bile acid on stomach tumorigenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The carcinogenic or cocarcinogenic effects of bile or bile acid on stomach carcinogenesis were investigated in inbred W rats. Bile or bile acid was introduced into the stomach by choledochogastrostomy or with food after the administration of N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7; 1-methyl-3-nitro-1-nitrosoguanidine] in drinking water. The animals that received MNNG and bile or sodium taurocholate (CAS: 145-42-6; N-choloyltaurine sodium salt) had a significantly higher incidence of hyperplastic and neoplastic lesions in the stomach mucosa than did the relevant MNNG-treated controls. The result suggested an enhancing effect of bile and sodium taurocholate in stomach tumorigenesis.

Determination of high mobility group I(Y) expression level in colorectal neoplasias: a potential diagnostic marker.

High mobility group I(Y) [HMGI(Y)] proteins are architectural factors abundantly expressed during embryogenesis, and their overexpression is known to be closely associated with neoplastic transformation of cells. This study was performed to investigate whether determination of HMGI(Y) expression level could assist in (a) differential diagnosis between colorectal carcinoma, adenoma, and normal tissue and (b) determination of the prognosis of patients with colorectal cancer. To this end, HMGI(Y) expression was determined at both the protein and mRNA levels in 30 colorectal carcinomas, 26 adenomas, and 23 normal mucosa samples, and further correlations between the protein expression levels and various clinicopathological parameters, such as depth of tumor invasion, lymphatic and/or venous involvement, regional lymph node metastasis, and Dukes' stage, were determined in 30 carcinoma cases. The expression of HMGI(Y) proteins was significantly increased in carcinoma and adenoma with severe atypia compared with that in adenoma with less atypia and normal colorectal mucosa. This increase in HMGI(Y) protein expression was found to be because of an increase in its mRNA expression by RNA in situ hybridization analysis. Clinicopathological analysis revealed that the level of HMGI(Y) protein expression was significantly correlated with parameters known to be indicative of a poor prognosis in colorectal cancer patients. These findings indicate that the determination of the HMGI(Y) protein expression level could be a potential marker for the diagnosis of colorectal neoplasias and can be of great value in predicting the prognosis of patients with colorectal cancer.

Pancreatic duct cell carcinomas express high levels of high mobility group I(Y) proteins.

The high mobility group I (HMGI) family of proteins in mammals belongs to a group of nonhistone nuclear proteins known as architectural transcriptional factors. They function in vivo as both structural components of chromatin and auxiliary gene transcription factors. In an earlier study (N. Abe et al, Cancer Res., 59: 1169-1174, 1999), we demonstrated that the expression level of the HMGI(Y) gene/proteins was significantly increased in colorectal adenocarcinoma and colorectal adenoma with severe cellular atypia. In the current study, we analyzed HMGI(Y) expression in several human pancreatic lesions to investigate (a) whether HMGI(Y) overexpression is also observed in pancreatic carcinoma, and (b) the role of HMGI(Y) in the diagnosis of pancreatic neoplasms. To this end, HMGI(Y) expression was determined at the protein level by immunohistochemistry using a HMGI(Y)-specific antibody in 6 surgically resected specimens of nonneoplastic tissue (4 specimens of normal pancreatic tissue and 2 specimens of chronic pancreatitis tissue), 8 pancreatic cystic neoplasms (5 intraductal papillary mucinous adenomas, 1 serous cystadenoma, and 2 solid pseudopapillary tumors), and 15 duct cell carcinomas of the pancreas. Immunohistochemical analysis revealed intense nuclear staining in the pancreatic carcinoma cells, whereas only very faint nuclear staining was seen in the nonneoplastic cells. There was a strong correlation between HMGI(Y) protein overexpression and a diagnosis of carcinoma (P = 0.000018). Thus, an increased expression level of the HMGI(Y) proteins was clearly associated with the malignant phenotype in pancreatic tissue. In addition, a low level of protein expression was also apparent in two of the cystic neoplasms that exhibited cellular atypia, but not in those that did not exhibit cellular atypia. Based on these findings, we propose that the HMGI(Y) proteins could be closely associated with tumorigenesis in the pancreas and that HMGI(Y) could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignancies unambiguously from normal tissue or benign lesions.

Alpha B-crystallin in skeletal muscle: purification and localization.

Atrophy of rat soleus muscles by hindlimb suspension is characterized by an early dramatic decrease in a soluble 22-kDa protein. The 22-kDa protein was purified from rat red skeletal muscle and rat lens by three different methods of chromatography. The partial amino acid sequence (65% of total amino acids) determined for muscle 22-kDa protein was identical with that of rat lens crystallin. The HPLC elution patterns of lysylendopeptidase fragments of 22-kDa protein from the two sources were identical. Polyclonal antibodies to rat muscle and bovine lens alpha B-crystallin with the two proteins on immunoblotting. alpha B-Crystallin protein was expressed and synthesized efficiently in slow skeletal muscle and poorly in fast muscle. Thus, the decreased 22-kDa protein of slow muscle in the suspension treatment was confirmed to be alpha B-crystallin. Immunoblotting confirmed that most of the alpha B-crystallin was solubilized, though some was tightly bound to myofibrils. This bound portion was localized in Z-bands of isolated myofibrils by immunocytochemical light and electron microscopy. Muscle alpha B-crystallin is tentatively proposed to be a myofibril-stabilizing protein, based upon its extraction characteristics, localization, and amino acid sequence.

Acute biliary pancreatitis: the roles of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography.

BACKGROUND: Acute biliary pancreatitis, particularly severe pancreatitis, necessitates urgent diagnosis and treatment of common bile duct (CBD) stones. The roles of urgent endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in the management of biliary pancreatitis were prospectively studied. METHODS: Thirty-five consecutive patients with suspected acute biliary pancreatitis underwent urgent ultrasonography, computed tomography (CT), EUS, and ERCP. Endoscopic sphincterotomy (ES) was performed for CBD stones. We investigated (1) imaging diagnostic results of CBD stones and intrapancreatic and extrapancreatic pathology and (2) the outcome of ERCP. RESULTS: Imaging studies established a biliary origin in 24 patients, 15 with and 9 without CBD stones. According to Acute Physiology and Chronic Health Evaluation II scores, 6 had severe and 18 had mild pancreatitis. EUS (100%) and ERCP (100%) were significantly more sensitive for CBD stones than were ultrasonography (47%) and CT (47%). EUS detected pancreatic necrosis (100%), as well as inflammation in the lesser sac (100%) and retroperitoneum (81%), which CT confirmed. No complications related to ERCP occurred. After ES, rates of morbidity and mortality related to pancreatitis were 8% and 0%, respectively. CONCLUSIONS: EUS, an accurate and minimally invasive modality, may limit ERCP to therapeutic use in biliary pancreatitis. EUS is recommended if ultrasonography and CT have failed to detect CBD stones. CBD stones should be treated with urgent ES.

Two types of mucin-producing cystic tumors of the pancreas: diagnosis and treatment.

BACKGROUND: This study focuses on clinicopathologic, imaging, and prognostic differences between two types of mucin-producing cystic tumors of the pancreas, with the aim of appropriate management of these tumors. METHODS: Forty-six patients with mucin-producing cystic tumors underwent operation. The types of tumors were as follows: mucinous cystic neoplasm, adenoma (6) and adenocarcinoma (12); intraductal papillary tumor, adenoma (10) and adenocarcinoma (18). RESULTS: Gender, age, symptoms, signs, tumor location and size, and the presence or absence of communication with the pancreatic duct differed between the two types. Mucinous cystadenocarcinomas showed deep invasion more often than intraductal papillary adenocarcinomas. Lymph node involvement was seen in 58% of mucinous cystadenocarcinomas but in only 22% of intraductal papillary adenocarcinomas. Tumors with mural nodules tended to show deep invasion and nodal metastasis. All four intraductal papillary tumors smaller than 3 cm without mural nodules were adenomas. Imaging studies allowed accurate differentiation between the two types but not between adenomas and adenocarcinomas. Five-year survival rates for patients with adenomas, mucinous cystadenocarcinomas, and intraductal papillary adenocarcinomas were 100%, 33%, and 81%, respectively. CONCLUSIONS: Mucinous cystic neoplasm necessitates complete tumor excision with wide dissection of lymph nodes including paraaortic nodes. Intraductal papillary tumor requires only peripancreatic node dissection; for tumors smaller than 3 cm without mural nodules, node dissection may be unnecessary.

Pancreatic disorders associated with anomalous pancreaticobiliary junction.

BACKGROUND: The aim of this study was to establish an optimal management strategy for pancreatic disorders associated with anomalous pancreaticobiliary junction (APBJ). METHODS: In 64 adult surgical cases of APBJ (common channel 15 mm or longer) (43 with and 21 without choledochal cyst), associated pancreatic disorders, pancreatographic results, and treatment outcomes were analyzed. RESULTS: Of 64 patients, 56 had pancreatobiliary symptoms. Twenty-four patients (38%) had pancreatic disorders: acute pancreatitis (n = 20), chronic calcifying pancreatitis (n = 2), and pancreatic carcinoma (n = 2). Twenty patients (31%) had abnormal pancreatograms. The incidence of acute pancreatitis was significantly higher in patients with an abnormal pancreatogram, particularly dilatation, protein plugs or stones of the common channel or main pancreatic duct, and coexisting pancreatic ductal anomaly. All patients with choledochal cyst underwent cyst excision and hepaticojejunostomy. Eleven patients without choledochal cyst or pancreatobiliary carcinoma underwent cholecystectomy alone. Protein plugs and pancreatic stones were extracted through the bile duct stump or by sphincterotomy. No patients experienced pancreatitis during a mean postoperative follow-up of 6.7 years. CONCLUSIONS: In managing APBJ, attention should be paid to the possibility of associated pancreatic disorders and an abnormal pancreatogram. APBJ with choledochal cyst requires cyst excision. Cholecystectomy alone may be adequate for APBJ without cyst.

Reappraisal of intraoperative ultrasonography for pancreatobiliary carcinomas: assessment of malignant portal venous invasion.

BACKGROUND: Conventional preoperative imaging modalities are unreliable for assessing portal venous invasion by pancreatobiliary carcinoma. We evaluated the usefulness of intraoperative ultrasonography for detecting pancreatobiliary carcinoma and assessing portal venous invasion, compared with other imaging modalities. METHODS: Ninety-one patients with pancreatic carcinoma (n = 66) or bile duct carcinoma (n = 25) underwent ultrasonography, computed tomography, angiography, and endoscopic ultrasonography preoperatively. All these patients underwent tumor resection, with (n = 23) or without (n = 68) portal vein resection, after intraoperative ultrasonography. Portal venous invasion was histologically examined in all patients. RESULTS: Intraoperative ultrasonography was significantly more sensitive (100%) than ultrasonography (79%), computed tomography (81%), and angiography (54%) for detecting carcinomas, especially bile duct carcinomas and small (< or = 2.0 cm) tumors. Portal venous invasion was confirmed histopathologically in 25 patients. For diagnosing portal venous invasion, intraoperative ultrasonography was more sensitive (92%) and specific (92%) than ultrasonography (56% and 73%), computed tomography (64% and 79%), and angiography (76% and 83%), respectively. Endoscopic ultrasonography showed a 95% detectability for carcinomas and a 92% accuracy for assessing portal venous invasion. CONCLUSIONS: Intraoperative ultrasonography is a simple and accurate procedure for detection of pancreatobiliary carcinomas and assessment of portal venous invasion.

Diagnosis of anomalous pancreaticobiliary junction: value of magnetic resonance cholangiopancreatography.

BACKGROUND: Anomalous pancreaticobiliary junction (a long common channel), with or without congenital choledochal cyst, is frequently associated with biliary tract carcinoma. We assessed the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) for patients with anomalous pancreaticobiliary junction (PBJ). METHODS: In 159 adult patients with pancreatobiliary disease, breath-hold (1 to 18 seconds) MRCP was performed according to a half-Fourier acquisition single-shot turbo spin-echo sequence. In all patients the length of the common channel demonstrated by MRCP was compared with that demonstrated by endoscopic retrograde cholangiopancreatography. In 11 patients with anomalous PBJ (the common channel > or = 15 mm on endoscopic retrograde cholangiopancreatography), the diagnostic accuracy of MRCP for associated biliary diseases was evaluated. RESULTS: No complications were encountered in performing MRCP. On MRCP, the length of the common channel was calculated to be 15 mm or longer in nine (82%) of 11 patients with anomalous PBJ. In patients with normal PBJ, MRCP identified PBJ with the channel measuring 0 mm in length. MRCP allowed detailed visualization of congenital choledochal cyst (all seven patients) but failed to depict carcinoma (one patient) and mucosal hyperplasia (five patients) of the gallbladder. CONCLUSIONS: MRCP is a noninvasive and accurate imaging method for diagnosing anomalous PBJ and congenital choledochal cyst.

Relationship between lactate threshold during running and relative gastrocnemius area.

This study examined the relationship between the work rate at which blood lactate accumulation begins (lactate threshold) during running and relative gastrocnemius area in four different groups. Twenty nonathletic and 11 athletic boys (age 9-12 yr), 15 female adult runners, and 11 male nonathletic students participated in this study. The muscle composition of the leg and thigh were measured by ultrasound. The lactate threshold was assessed in terms of both the absolute work rate (ml.kg-1.min-1) and relative work rate. The relative cross-sectional area of the gastrocnemius to the plantar flexor (relative gastrocnemius area) was significantly negatively related to the absolute and relative lactate threshold in all groups. These results suggest that the relative gastrocnemius area may play an important role in determining the relative and absolute lactate threshold during running.

Fiber-type-specific alphaB-crystallin distribution and its shifts with T(3) and PTU treatments in rat hindlimb muscles.

Changes in alphaB-crystallin content in adult rat soleus and extensor digitorum longus (EDL) were examined after 8 wk of 3,5, 3'-triiodothyronine (T(3)) and propylthiouracil (PTU) treatments. Cellular distributions of alphaB-crystallin expression related to fiber type, and distribution shifts with these treatments were also examined in detail from the gray level of reactivity to specific anti-alphaB-crystallin antibody. alphaB-crystallin content in both soleus and EDL muscles was significantly decreased after T(3), and that in EDL was significantly increased over twofold after PTU treatment. In both control soleus and EDL muscles, the gray level of type I fibers was higher than that of type II fibers. alphaB-crystallin expression among type II subtypes was muscle specific; the order was type I > IIa > IIx > IIb in control EDL muscle and type IIx > or = IIa in soleus muscle. The relation was basically unchanged in both muscles after T(3) treatment and was, in particular, well maintained in EDL muscle. Under hypothyroidism conditions with PTU, the mean alphaB-crystallin levels of type IIa and IIx fibers were significantly lower than levels under control conditions. Thus the relation between fiber type and the expression manner of stress protein alphaB-crystallin is muscle specific and also is well regulated under thyroid hormone, especially in fast EDL muscle.

Treatment of acute cholangitis due to choledocholithiasis in elderly and younger patients.

OBJECTIVE: To evaluate management strategies for acute cholangitis in elderly patients (age, > or = 80 years). DESIGN: Nonrandomized control trial. SETTING: A university hospital. PATIENTS: Patients (n = 191) who underwent urgent biliary drainage for acute cholangitis due to choledocholithiasis. Thirty-seven patients were elderly, and 154 were younger (age, < 80 years). INTERVENTIONS: Surgical (8 elderly and 48 younger patients), percutaneous transhepatic (11 elderly and 47 younger patients), or endoscopic drainage (18 elderly and 59 younger patients). MAIN OUTCOME MEASURES: Clinical features of acute cholangitis and outcomes of biliary drainage. RESULTS: The elderly patients had higher incidences of septic shock or mental confusion (acute severe cholangitis)(43.2%) and concomitant diseases (81.1%) than the younger patients (25.3% and 42.9%, respectively). The elderly patients had significantly greater morbidity (37.8%) and mortality (10.8%), compared with the younger patients (16.9% and 3.2%, respectively). Mortality was 18.8% in elderly patients with severe cholangitis and 4.8% in those with nonsevere cholangitis. In the elderly patients, endoscopic drainage yielded lower morbidity (16.7%) and mortality (5.6%) than surgical (87.5% and 25.0%, respectively) and percutaneous drainage (36.4% and 9.1%, respectively). No complications occurred after endoscopic nasobiliary drainage without sphincterotomy. CONCLUSIONS: Elderly patients with acute cholangitis have high incidence of severe disease and concomitant medical problems. They should undergo endoscopic biliary drainage, especially nasobiliary drainage without sphincterotomy, because of its safety and effectiveness.

Opsonin receptor expression on peritoneal exudative and circulatory neutrophils in murine acute pancreatitis.

Acute severe (necrotizing) pancreatitis is often associated with pancreatic or peripancreatic infection. Decreased bacterial clearance due to impaired immune defense may cause local infection. We investigated expressions of surface opsonin receptors (CD11b, complement receptor 3; CD32/CD16, immunoglobulin G Fc receptor) on local and circulatory neutrophils, in murine acute pancreatitis. The mild and severe forms of acute pancreatitis were induced by seven and 13 subcutaneous injections of caerulein, respectively. Peritoneal exudative and circulatory neutrophils were counted and assayed for receptor expressions by flow cytometry, serially at 1-72 hours after pancreatitis induction. Histologically, mild and severe forms showed edematous and necrotizing pancreatitis, respectively. The peritoneal exudative neutrophil count was greater in mild than in severe pancreatitis. Expressions of CD11b and CD32/CD16 on local neutrophils were upregulated early in mild pancreatitis. This upregulation was attenuated in severe pancreatitis. The circulatory neutrophil count was elevated in severe pancreatitis but was unchanged in mild pancreatitis. Opsonin receptor expression on circulatory neutrophils showed a transient, modest upregulation in the early phase of mild pancreatitis. Receptor-positive circulatory neutrophils showed a marked elevation that persisted throughout the course of severe pancreatitis. In conclusion, severe (necrotizing) pancreatitis is associated with reduced opsonin receptor expression on local neutrophils and enhanced expression on circulatory neutrophils, as compared with mild (edematous) pancreatitis. These changes may contribute to local infectious complications and multiple organ failure, in severe pancreatitis.

Immunohistochemical localization of beta-1,4-galactosyltransferase in human pancreatic tissues.

beta-1,4-Galactosyltransferase (GalTase) is the glycosyltransferase in the Golgi apparatus that transfers galactose from UDP-galactose to terminal N-acetylglucosamine residues in glycoconjugates with formation of a beta-1,4 linkage. Neoplasms undergo various changes in the carbohydrate moieties of their glycoconjugates. This process also indicates the possibility of changes in glycosyltransferases themselves. Therefore, we compared the binding pattern of a monoclonal antibody (MAb8628) against GalTase in both normal and neoplastic exocrine pancreatic tissues. Ten normal and 11 neoplastic human exocrine pancreatic tissues obtained from surgery were used. Frozen sections were incubated with this antibody. Supranuclear regions and terminal bars of normal duct cells and acinar cells revealed positive staining for GalTase at the light microscopic level. Centroacinar cells revealed positive staining in their perinuclear region. Neoplastic cells were also stained in their supranuclear regions and terminal bars. Supranuclear regions were well developed in neoplastic cells and intensely stained compared with those in normal cells. The supranuclear regions and the terminal bars corresponded to the trans cisternae of the Golgi apparatus and the junctional complex (i.e., tight junction and adherens junction), respectively, seen at the electron microscopic level. Pancreatic neoplastic changes thus led to an increase in the expression of GalTase in the Golgi apparatus, the increase of which may have an important effect on the intercellular adhesion and communication among pancreatic epithelial cells. Measurement of this enzyme is useful for diagnosis of exocrine pancreatic neoplastic changes from normal tissues.

Effect of oral administration of protease inhibitor on pancreatic exocrine function in WBN/Kob rats with chronic pancreatitis.

The effect of oral administration of protease inhibitor (camostat) on pancreatic morphology and exocrine function (conscious rat model) was investigated using WBN/Kob rats with spontaneous chronic pancreatitis. In nontreated WBN/Kob rats (2-12 months of age), pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis appeared at 3 months and advanced with each month. Pancreatic secretion was markedly impaired at all ages. In WBN/Kob rats fed diets containing camostat (from 2-3 or 4-5 months of age), the pancreas was hypertrophic and did not show any histological appearances compatible with chronic pancreatitis, and moreover, exocrine function was thoroughly restored with increased plasma cholecystokinin concentrations. Oral administration of protease inhibitor has both preventive and therapeutic effects on pancreatic lesions and dysfunction in an animal model of chronic pancreatitis, probably via endogenous cholecystokinin release.

Distribution of a synthetic protease inhibitor in rat pancreatic acini after supramaximal secretagogue stimulation.

Protease inhibitors may have a beneficial effect in acute pancreatitis. The effects of E3123, a new low molecular weight protease inhibitor, on the ultrastructure of isolated pancreatic acini were examined using transmission electron microscopy. Acini supramaximally stimulated with cerulein (10(-8) M) formed large cytoplasmic vacuoles similar to those generated in the cerulein-induced in vivo model of pancreatitis. Pretreatment of isolated acini with E3123 significantly reduced the size and number of vacuoles associated with cerulein treatment. The distribution of 3H-E3123 in acinar cells was examined using a pulse-chase protocol and electron microscopic autoradiography. Cellular levels of 3H-E3123 increased about 30-fold in acinar cells treated with cerulein (10(-8) M) compared to unstimulated controls. In cerulein-treated acini examined after a 5-min chase, 47.4% of the autoradiographic grains were associated with the rough endoplasmic reticulum and 13.2% were associated with zymogen granules. After 30 min of incubation, the grains associated with the endoplasmic reticulum decreased to 18.5% but increased to 26.3% over zymogen granules. Thus, E3123 is taken up by the acinar cell and follows a cellular itinerary similar to that of newly synthesized secretory proteins. One potential conclusion from these studies is that the ability of E3123 to reduce the formation of vacuoles in supra-maximally stimulated acini may be due to its inhibition of proteases within the secretory pathway.

Effect of oral protease inhibitor administration on gallbladder motility in patients with mild chronic pancreatitis.

Oral administration of a protease inhibitor (camostat) induces pancreatic hypersecretion via hormonal and neural systems in humans. Camostat may also affect gallbladder motility via these systems. The aim of this study was to evaluate the effect of camostat on gallbladder function. Gallbladder emptying in response to caerulein administration and to egg yolk ingestion was examined ultrasonographically in 15 patients with mild chronic pancreatitis before and after 6 months of camostat treatment, and in 10 control subjects. The plasma cholecystokinin concentration after yolk ingestion was measured by radioimmunoassay. Fasting gallbladder volume and contractile function, whether stimulated by caerulein or yolk, did not differ between pancreatitis patients before camostat treatment and controls. Plasma cholecystokinin levels, basal and yolk-stimulated, did not differ between nontreated pancreatitis patients and control subjects. Fasting volume had decreased significantly by 1, 3, and 6 months of camostat treatment, while contractile function was not affected. Camostat did not influence plasma cholecystokinin levels. Oral administration of a protease inhibitor appears to decrease fasting gallbladder volume via a mechanism other than cholecystokinin release.

Pancreatic carcinoma accompanied by pseudocyst: report of two cases.

Two cases of pancreatic cancer accompanied by pseudocyst are reported. Case 1 was a 60-year-old man who was admitted to our hospital complaining of left lower abdominal discomfort. A cystic lesion, about 3 cm in diameter, was found in the pancreatic tail by ultrasonography (US) and computed tomography (CT). No signs of chronic pancreatitis were found. At operation, an elastic, hard, white tumor, about 1 cm in diameter, was felt adjacent to the cystic lesion on the duodenal side. Histologically, this tumor was a duct cell carcinoma with an adjacent pseudocyst upstream of the pancreas. Case 2 was a 57-year-old man who complained of back pain and loss of body weight. US and CT examination revealed a cystic lesion, 11 x 7 cm in size, in the tail of the pancreas. Histological examination of the resected specimen revealed both a duct cell carcinoma, 3 cm in size, in the body of the pancreas and a pseudocyst, 9 cm in size. Pseudocysts accompanying carcinoma are thought to develop from obstruction of the pancreatic duct by the carcinoma, followed by intraductal high pressure and disruption of ductules upstream of the pancreas. Thus, we should pay careful attention to pseudocyst of the pancreas, especially when signs of diffuse chronic inflammation cannot be found, to help identify duct cell carcinoma in the early stage. Further detailed examinations of the cyst fluid or pancreatic juice, such as cytology, tumor marker determinations, or establishment of K-ras codon 12 mutation, are needed.

Decreased physical performance of congenic mice with mismatch between the nuclear and the mitochondrial genome.

Maternal transmission of mitochondrial DNA (mtDNA) allows us to generate mtDNA congenic strain by repeating backcrosses of female mice to male mice of an inbred strain, which carries different mtDNA haplotype from that of the female progenitor. Since genetic backgrounds of inbred strains commonly used (e.g., C57BL/6J [B6] and BALB/c) are mainly derived from an European subspecies of Mus musculus domesticus, congenic strains, in which mtDNA originated from an Asian subspecies M. musculus musculus or an European species M. spretus, give in vivo condition that mismatch occurs between the mitochondrial and the nuclear genome. So far, little has been known how the mismatch condition affects the physiological phenotype of the mice. To address this question, we established two mtDNA congenic strains, C57BL/6J(B6)-mtSPR and BALB/c-mtSHH, which carry M. spretus- and M. m. musculus-derived mtDNAs, representing the conditions of interspecific and intersubspecific mitochondrial-nuclear genome mismatch, respectively. Using these congenic strains, we examined their physical performance by measuring their running time on a treadmill belt until exhaustion. The result clearly showed that the mtDNA congenic strains manifested a significant decrease in the level of physical performance, when compared with their progenitor strains. It also appeared that the congenic mice manifested growth rate. Thus, all results indicated that mismatch between the mitochondrial and the nuclear genome causes phenotypic changes in individuals of mice.