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Biomedical subjects

M Kanai

Publications and source records attributed to M Kanai.

At least 109 records · Page 6Linked to original sources

Exposure of hepatic sinusoidal mononuclear cells to UW solution in situ but not ex vivo induces apoptosis.

BACKGROUND/AIMS: We have previously reported that human hepatic sinusoidal mononuclear cells may have a higher sensitivity to induction of apoptosis than peripheral blood mononuclear cells. In this study, the effects of two different preservation solutions on the functions of those hepatic mononuclear cells were evaluated in living-related liver transplantation. METHODS: Ten and 11 liver grafts were perfused via the portal vein with University of Wisconsin solutions (UW group) and Bretschneider's Histidine-Tryptophan-Ketoglutarate solutions (HTK group), respectively. Hepatic mononuclear cells were isolated from the effluent preservation solution passing through the graft livers. Cytofluorometry, cytotoxic assay, and DNA analysis were performed. RESULTS: There were no significant differences in surface antigens and natural killer activity of hepatic sinusoidal mononuclear cells between the UW and HTK groups. At the time of isolation, the viability of hepatic sinusoidal mononuclear cells in both groups was more than 99%. In the UW group, the viability of hepatic sinusoidal mononuclear cells decreased to 30% through apoptosis in in vitro culture at 48 h after isolation. In the HTK group, however, their viability was maintained at more than 90% at 48 h in the same culture conditions, and additional exposure to UW solution ex vivo for 30 min did not induce apoptosis. CONCLUSION: Hepatic sinusoidal mononuclear cells isolated from the UW solution, not from the HTK solution, passing through the liver died through apoptosis, which was not induced by each component of the UW solution, but by exposure in situ.

Adenosine↗

Primary lymphoma of the liver with bile duct invasion and tumoral occlusion of the portal vein: report of a case.

A 55-year-old woman presented to hospital with epigastric pain and jaundice. Diagnostic imaging studies revealed a biliary stricture of the hepatic confluence and a hepatic tumour of the left and caudate lobes with a portal tumour thrombus, which occupied the main portal trunk, the umbilical portion of the left portal vein, and the right anterior and posterior portal branches. Left hepatic trisegmentectomy, caudate lobectomy, portal tumour thrombectomy, bile duct resection and bilioenteric anastomosis were performed. There were no other lesions, and so it was diagnosed as a primary lymphoma of the liver (B-cell, diffuse, large cell type). The patient underwent postoperative chemotherapy and has remained well for 4.5 years after surgery. Primary lymphoma of the liver is very rare, and this is the first case report with bile duct invasion and tumoral occlusion of the portal vein.

Bile Duct Neoplasms↗

Different gastric emptying of solid and liquid meals after pylorus-preserving pancreatoduodenectomy.

BACKGROUND: Transient gastric stasis immediately after pylorus-preserving pancreatoduodenectomy (PPPD) is a common complication, but the cause remains unknown. Changes in gastric emptying were investigated in patients undergoing PPPD for periampullary malignancy. METHODS: In 14 patients undergoing PPPD, liquid- and solid-phase gastric emptying were evaluated before and after operation (mean 38 (range 27-53) days after operation). Two pharmacological gastric-emptying tests were used: the acetaminophen test for liquid-phase emptying and the sulphamethizole capsule food test for solid-phase gastric emptying. RESULTS: All patients exhibited delayed solid emptying but fairly good liquid emptying. CONCLUSION: Gastric function in the early postoperative period after PPPD is characterized by delayed solid-phase but good liquid-phase emptying.

Acetaminophen↗

Presence of conserved domains in the C-terminus of MARCKS, a major in vivo substrate of protein kinase C: application of ion trap mass spectrometry to the elucidation of protein structures.

MARCKS, the major protein kinase C substrate in various cells and tissues, binds to calmodulin, acidic membrane phospholipids, and actin filaments, and these interactions are regulated by protein phosphorylation. We have previously analyzed MARCKS purified from bovine brain using capillary liquid chromatography/electrospray mass spectrometry and found that the protein structure differed significantly from that deduced from cDNA sequences [Taniguchi, H., Manenti, S., Suzuki, M., and Titani, K. (1994) J. Biol. Chem. 269, 18299-18302]. Moreover, the alignment of the protein from various species showed a lack of any conserved sequences in the C-terminal half of the molecule. This prompted us to reexamine the C-terminal amino-acid sequence of bovine MARCKS. The purified protein was digested with lysyl endoprotease, and the obtained C-terminal peptide was further digested with either Staphylococcus V8 protease or NTCB. The small peptides thus obtained were analyzed by liquid chromatography/electrospray/tandem mass spectrometry. This combined with gas-phase Edman sequencing allowed us to determine the C-terminal primary structure. The sequence obtained differed significantly from that reported previously, and the comparison with other species revealed the presence of a novel conserved domain in the C-terminal region of MARCKS.

Amino Acid Sequence↗

The pattern of infiltration at the proximal border of hilar bile duct carcinoma: a histologic analysis of 62 resected cases.

OBJECTIVE: To clarify the importance of different patterns of infiltration at the proximal border of hilar bile duct carcinomas. SUMMARY BACKGROUND DATA: There are few detailed pathologic studies on the proximal resection margins in patients with hilar bile duct carcinoma. METHODS: Serial sections of 62 specimens of resected hilar bile duct carcinoma were examined histologically to determine the involved layers and routes of invasion at the proximal border. The degree of cancer extension was determined, and the relation between the length of the tumor-free resection margin and postoperative anastomotic recurrences was analyzed. RESULTS: Mucosal extension was predominant in papillary and nodular tumors, but submucosal extension was predominant in diffusely infiltrating and nodular-infiltrating tumors. Submucosal extension usually consisted of direct or lymphatic invasion. The mean length of submucosal extension was 6.0 mm. Superficial spread of cancer, defined as mucosal extension of more than 20 mm from the main lesion, was seen in 8 specimens. No patient had an anastomotic recurrence when the tumor-free resection margin was greater than 5 mm. CONCLUSIONS: The pattern of infiltration at the proximal border of resected hilar bile duct carcinomas is closely related to the gross tumor type. The length of submucosal extension is usually less than 10 mm. Superficial spread of cancer is seen in more than 10% of cases. A tumor-free proximal resection margin of 5 mm appears to be adequate in hilar bile duct carcinoma.

Adult↗

Intestinal fibroblasts regulate intestinal epithelial cell proliferation via hepatocyte growth factor.

Although the presence of subepithelial intestinal fibroblasts has been well recognized, the effects of fibroblasts on intestinal epithelial cell (IEC) growth are incompletely understood. In vitro studies were undertaken to evaluate the effects of fibroblasts on the proliferation of model IEC lines. IECs (Caco-2, T84, and IEC-6) were grown alone or in the presence of human intestinal (CCD-18), lung (CCD-37), or skin explant-derived fibroblasts. Cocultures were carried out directly on irradiated fibroblasts or by Transwell coculture technique with fibroblasts and epithelial cells separated by a porous filter. Cell proliferation was assessed by [3H]thymidine incorporation and cell counts. Hepatocyte growth factor (HGF) and c-met transcript expression in IECs and fibroblasts was examined by RT-PCR and Northern blotting; protein expression was evaluated by immunoblotting. Intestinal as well as lung and skin fibroblasts substantially stimulated proliferation of Caco-2, T84, and IEC-6 cells in both direct and Transwell cocultures. In addition, fibroblast-conditioned medium stimulated IEC proliferation, suggesting a paracrine mechanism. Anti-human HGF-neutralizing antibodies blocked the growth-promoting effects in both fibroblasts and fibroblast-conditioned medium. Recombinant human HGF dose dependently promoted IEC proliferation. HGF mRNA and protein expression was restricted to fibroblasts. High levels of c-met expression were found in Caco-2 and T84 cells; in contrast, expression in fibroblasts was weak. In summary, fibroblasts stimulate IEC proliferation through a paracrine mechanism mediated predominantly by HGF.

Cell Division↗

Determination of urinary and serum pentosidine and its application to elder patients.

Pentosidine, a fluorescent cross-linking compound, accumulates in extracellular matrix, especially in the collagen, and is formed by the nonenzymatic process of advanced Maillard reaction. We developed a method of determination of pentosidine and tried to examine its level in urine and serum of elder patients. The method, which involves the hydrolysis of samples, pretreatment using a CF-11 cellulose column and HPLC quantification, resulted in a high recovery (94.3%) of pentosidine with low coefficient of variation (8-10%) of total analysis. Serum and urinary levels of pentosidine in control subjects gradually increased with age. Elder patients with cerebral infarction showed higher levels of serum and urinary pentosidine as compared with those with senile dementia and other geriatric disorders. These results suggest that serious damage to systemic vascular tissues has already occurred in these patients due to glycation.

Adult↗

Immediate increase in arterial blood flow in embolized hepatic segments after portal vein embolization: CT demonstration.

OBJECTIVE: This study was conducted to determine whether an immediate change occurs in the blood flow distribution in hepatic segments after segmental portal vein embolization. CONCLUSION: We found an immediate change in the distribution of blood flow in the liver after embolization; with portal vein embolization, we found an immediate increase in the hepatic artery blood flow in the affected segments.

Bile Duct Neoplasms↗

A new nonamyloid transthyretin variant, G101S, detected by electrospray ionization/mass spectrometry. Mutations in brief no. 201. Online.

Familial amyloidotic polyneuropathy is caused by transthyretin (TTR) variants. The identification of new variants with and without amyloidosis may help to clarify the mechanism of amyloid fibril formation. We detected several variant TTRs from patients with and without symptoms of amyloidosis using mass spectrometry (MS). TTR was isolated by mixing test serum with anti-transthyretin antiserum, and the generated immunoprecipitate was analyzed by high performanced liquid chromatography/electrospray ionization (HPLC/ESI) MS. Variant TTRs showed extra peaks in addition to normal TTR peaks. A variant found in nonamyloid group was sequenced by HPLC/ESI tandem MS using peptides obtained by protelytic digestion of TTR and by DNA analysis. The structure was new, [G101S], and was found in a 74 years old Japanese male. This mutation results from substitution in a CpG hot spot. The substitution in the surface loop, 98-102, between F and G b-strands may not cause amyloid formation.

Aged↗

[Differences in strategies for carcinoma of the pancreas between Japan and western countries].

Differences in surgical strategies for carcinoma of the pancreas, especially the head of the pancreas, between Japan and western countries are described. In Japan, pancreatoduodenectomy (PD) or pylorus-preserving PD, accompanied by extensive lymph node and extra-pancreatic nerve plexus dissection, is performed for this difficult disease. Combined resection of the portal vein is also done when needed (radical resection). In western countries, a standard PD does not include extensive lymph node dissection and portal vein resection (standard resection). Although some Japanese surgeons reported about 30% postoperative 5-year survival rates after radical resection and some American surgeons achieved about 20% 5-year survival rates after standard resection, there are some problems with comparison of these results. Surgeons in Japan and western countries use different staging systems, namely, the classifications of the Japanese Pancreas Society and the Union of Internationale Contre le Cancer (UICC). It is essential to establish a more accurate international staging system to scientifically evaluate the difference in surgical results between Japan and western countries.

Europe↗

Protection against dynorphin-(1-8) hydrolysis in membrane preparations by the combination of amastatin, captopril and phosphoramidon.

The amounts of dynorphin-(1-8) [dyn-(1-8)] and its seven hydrolysis products, Y, YG, YGG, YGGF, YGGFL, YGGFLR and YGGFLRR, were estimated after incubating dyn-(1-8) with a membrane fraction from either guinea-pig ileum or striatum for various times at 37 degrees C. The major hydrolysis products during the initial 5-min incubation were YGGFLR and Y, which indicates that dipeptidyl carboxypeptidase and aminopeptidase activities were mainly involved in the hydrolysis. After 60 min of incubation, dyn-(1-8) was completely hydrolyzed in both membrane preparations. When the ileal and the striatal preparations were incubated for 60 min in the presence of both captopril, a dipeptidyl carboxypeptidase inhibitor, and amastatin, an aminopeptidase inhibitor, 63.8 and 49.3% of dyn-(1-8), respectively, were hydrolyzed. The YGG fragment was the major hydrolysis product in both preparations. When the ileal and the striatal membrane fractions were incubated with dyn-(1-8) in the presence of three peptidase inhibitors, captopril, amastatin and phosphoramidon (an inhibitor of endopeptidase-24.11), approximately 95% of the opioid octapeptide remained intact in both cases. This shows that dyn-(1-8) was almost exclusively hydrolyzed by three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive dipeptidyl carboxypeptidase I and phosphoramidon-sensitive endopeptidase-24.11, in both ileal and striatal membranes. Additionally, the Ke (equilibrium dissociation constant) values of selective antagonists against dyn-(1-8) and its initial main hydrolysis product YGGFLR in two isolated preparations pretreated with the three peptidase inhibitors indicate that the latter acts on mu receptors in guinea pig ileum but delta receptors in mouse vas deferens and the former acts on kappa receptors in both preparations. It is indicated, therefore, that in the absence of peptidase inhibitors endogenously released dyn-(1-8) acts either through dyn-(1-8) itself on kappa receptors or through YGGFLR on mu or delta receptors depending on both the three peptidase activities and the three receptor type densities at the target synaptic membrane.

Animals↗

[Value of paraaortic lymphadenectomy for gallbladder carcinoma].

Seven reports of paraaortic lymphadenectomy for advanced carcinoma of the gallbladder were reviewed and positive paraaortic nodes were found in 20-40% of the resected patients and 10-15% of those with subserosal cancer invasion. The rate of patients with positive paraaortic nodes/all patients with positive nodes was 30-50%. Paraaortic lymphadenectomy did not improve the surgical outcome, and most of the patients with positive paraaortic nodes died within 1 year even after aggressive surgery with extensive lymph node dissection. Therefore it is important to clarify the value of paraaortic lymph node dissection for patients with possibly positive paraaortic node metastasis and those with histologically positive nodes excluding the paraaortic area. Although pancreatoduodenectomy for prophylactic lymphadenectomy around the head of the pancreas has been carried out in some institutions, the procedure does not seem to be effective because the main lymphatic route from the gallbladder has a direct connection with the paraaortic nodes via the pericholedochal, periportal, and/or the posterior nodes along the common hepatic artery. The present authors recommend a D2 plus paraaortic lymph node dissection (ext D2) as a standard surgical strategy for carcinoma of the gallbladder.

Aorta↗

Biogenesis and function of lipolysosomes in developing chick hepatocytes.

Proliferation of lipolysosomes is one of the characteristic aspects of embryonic chick hepatocytes. Formation of lipolysosomes is observed in the well-developed trans-Golgi network, with the highest frequency occurring from 11 to 14 days of incubation. The lipolysosomes usually contain a small and electron-dense lipid inclusion; however, during development, they gradually enlarge with an accompanying reduction in the electron density of the inclusion. Lipolysosomes isolated from neonatal chick liver homogenates were mainly composed of esterified cholesterol and showed considerably high activity of lysosomal enzymes. Moreover, the lipolysosome fraction is clearly shown to be a function of intralysosomal lipolysis via acid lipase. This accumulation of esterified cholesterol within lipolysosomes might be attributed to an excessive uptake and conversion of plasma lipoproteins to lipolysosomes. This concept is supported by the appearance of an abundance of coated pits and both "early" and "late" endosomes. The major components of plasma lipoprotein are low density lipoprotein (LDL) and high density lipoprotein (HDL), the cholesterol-rich lipoproteins, whose cholesterol content increases during the last week of incubation when the lipolysosomes quickly enlarge. Plasma lipoprotein particles are produced in the yolk sac epithelium from yolk very low density lipoprotein (VLDL) and transferred via the vitelline circulation to the chick liver. After hatching, when the supply of nutrients from the yolk sac is terminated, lipolysosomes immediately decrease in size and number. The cholesterol and fatty acids released are useful as an energy source and lipid metabolism in general, especially after hatching. Food intake induces the use of and accelerates the disappearance of lipolysosomes. Instead of lipolysosomes, lipid droplets appear and increase in number and size with concomitant increases of triglyceride concentrations in the liver homogenates, suggesting that lipogenesis has begun in the chick hepatocyte.

Animals↗

Lysosomal generation of amyloid beta protein species in transgenic mice.

Soluble amyloid beta protein (A beta)1-40 and highly amyloidogenic A beta 1-42/43 were immunocytochemically labeled in lysosomes of acinar cells and macrophages in the pancreas of transgenic mice systemically expressing a C-terminal fragment of the A beta precursor. A beta 1-42/43 and long A beta species extending their C-termini were detected in the detergent-insoluble fraction. Immunoreactivity of cathepsin D was markedly increased in lysosomes filled with A beta fibrils. These findings indicated that A beta 1-40, A beta 1-42, A beta 1-43 and longer A beta species were generated in the lysosomes of the transgenic pancreas, and suggested that the activation of cathepsin D, a candidate gamma-secretase, leads to acceleration of A beta amyloid formation.

Amyloid beta-Protein Precursor↗

Signal transduction pathway of human fibroblast growth factor receptor 3. Identification of a novel 66-kDa phosphoprotein.

Stimulation of fibroblast growth factor receptor 3 (FGFR3) results in a variety of functional effects, including regulation of epithelial cell growth and differentiation. In order to characterize the signaling pathway through which FGFR3 regulates cell growth, L6 cells lacking any endogenous FGFR were stably transfected with the two different human isoforms, FGFR3 IIIb and FGFR3 IIIc, that result from alternative splicing of exon III of the FGFR3 gene encoding the ligand binding domain. Expression of FGFR3 IIIc in stably transfected L6 cells conferred growth responses to several members of the FGF family including FGF-1, -2, -4, and -6, while FGFR3 IIIb-expressing cells responded only to FGF-1. Activation of FGFR3 upon ligand binding resulted in activation of mitogen-activated protein kinase pathway. FGFR3 utilizes two different pools of adapter protein GRB2 to link to Ras. Activated FGFR3 predominantly interacts with GRB2.Sos in complex with a previously identified 90-kDa protein and designated protein 80K-H. In addition, 80K-H.GRB2. Sos complex was found to contain a novel 66-kDa protein. Tyrosine phophorylation of the 66-kDa protein was dependent on ligand activation of FGFR3, suggesting that the 66-kDa protein may play an important role in FGFR3-specific signaling. In addition to this unique pathway, FGFR3 also links to GRB2.Sos complex via the adapter protein Shc. Furthermore, activated FGFR3 was not able to induce dissociation of GRB2.Sos complex following Sos phosphorylation. In summary, FGFR3 signaling pathway utilizes two GRB2-containing complexes; Shc.GRB2.Sos and 80K-H.pp66.GRB2.Sos; these two complexes may alternatively link FGFG3 to mitogen-activated protein kinase. Finally, activated FGFR3 was also found to result in phosphorylation of phospholipase C-gamma but reduced phosphorylation of c-Src.

Adaptor Proteins, Signal Transducing↗

Clinicopathologic study on pancreatic cancer associated with pancreatic stones.

Four cases of pancreatic cancer associated with pancreatic stones were investigated clinicopathologically. In Case 1, pancreatic cancer was diagnosed 2 yr 9 mo after the diagnosis of pancreatolithiasis. Numerous large stones were present throughout the pancreas, and stones in the resected specimen were embedded in the tumor. Chronic inflammation, including inflammatory infiltration and fibrosis, were found around the pancreatic duct where the stones were present, both within and adjacent to the tumor, suggesting that chronic pancreatitis had been present for a protracted period. In Cases 2-4, a few small free stones were found in the dilated pancreatic ducts and a cyst upstream from the tumor, but there were no stones noted within the tumor. Microscopically, mild atrophy of the pancreatic parenchyma and fibrosis were seen. In each of these three cases, it was considered that the pancreatic cancer was the primary event, with the pancreatic stones arising as a secondary process. The pancreatic cancers associated with pancreatic stones were classified into two groups, one with pancreatic stones preceding the pancreatic cancer and the other three cases in which the reverse occurred.

Aged↗

Distal pancreatectomy with en bloc resection of the celiac artery for carcinoma of the body and tail of the pancreas.

CONCLUSION: Combined resection of the celiac artery with a distal pancreatectomy (DP) increases the resectability and improves the overall prognosis of patients with locally advanced ductal cancer of the body and tail of the pancreas. BACKGROUND: Carcinoma of the body and tail of the pancreas is often unresectable because of invasion to adjacent organs. We evaluated a DP including an en bloc resection of the celiac artery ("extended"), for pancreatic cancer that had invaded the common hepatic and/or celiac arteries. METHODS: Six cases of an "extended" DP were compared with 19 cases of a "standard" DP for pancreatic ductal carcinoma in terms of clinical and pathologic findings, perioperative course, and long-term outcome. We also compared the survival rate of these two groups with a third group consisting of 22 patients with unresectable pancreatic ductal carcinoma. RESULTS: The mean operative time, postoperative serum aspartate aminotransferase concentration, and length of hospital stay did not significantly differ between the "extended" and "standard" DP groups. The cumulative 1- and 3-yr accumulated survival rates for the "extended," "standard," and unresectable groups were 40.0, 33.3, and 5.4, and 20.0, 16.6, and 0%, respectively. Statistically significant differences (p < 0.01) existed between the "extended" and unresected groups.

Adult↗