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Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 91 records · Page 5Linked to original sources

Ligation of the Fas antigen stimulates chemokine secretion in pancreatic cancer cell line PANC-1.

BACKGROUND AND AIM: The role of chemokines in the process of immune cell infiltration into pancreatic cancer tissue has been reported. In this study, we investigated the induction of chemokines (interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) by Fas antigen (Ag)-stimulation in a human pancreatic cancer cell line, PANC-1. METHODS: The chemokine secretion was evaluated by using an ELISA and a northern blot, and the activation of nuclear factor-kappa B (NF-kappa B) was assessed by using an electrophoretic gel mobility shift assay (EMSA). RESULTS: The Fas antigen (Ag) stimulation clearly induced an increase in IL-8 and MCP-1 secretion in PANC-1 cells. This effect was also observed at the mRNA level. The induction of chemokine secretion by Fas Ag stimulation required de novo gene expression and protein synthesis. The pretreatment with interferon (IFN)-gamma markedly enhanced the effects of Fas Ag stimulation; IFN-gamma pretreatment and Fas Ag stimulation synergistically induced not only apoptosis but also IL-8 and MCP-1 secretion. Flow cytometric analysis demonstrated that IFN-gamma significantly enhanced Fas Ag expression. In addition, Fas Ag stimulation actually evoked NF-kappa B activation in this cell line. CONCLUSION: Our results indicate that Fas Ag stimulation can induce chemokine secretion in PANC-1 cells, suggesting the contribution of Fas stimulation to the accumulation of immune cells in pancreatic cancer tissue.

Adenocarcinoma↗

Global intellectual deterioration in Alzheimer's disease and a reverse model of intellectual development: an applicability of the Binet scale.

Since intellectual deterioration in Alzheimer's disease (AD) might be considered to demonstrate a reverse of the intellectual development of children, we herein investigated the applicability of the Tanaka-Binet Intelligence scale (TB scale). This scale can assess the mental age (MA) and the lower-limit age (LLAge) values, and was reported to be correlated with the tasks determining Piaget's developmental stages of intelligence. Thirty AD patients and 30 age-matched normal control subjects were examined with the scale. We found that the mean MA values of the AD patients and controls were 97.4 and 150.3 months, respectively. In the control group, there were significant correlations between the MA and chronological age, and between the MA and years of education. In the AD patients, there was a significant correlation between the MA and the MMSE score. Regarding the LLAge for the AD patients, similar to the theory of Piaget, there was a tendency that they could be classified into three LLAge groups. We consider that the TB scale is useful in assessing the intellectual function in AD patients.

Aged↗

Cognitive function and frontal lobe atrophy in normal elderly adults: Implications for dementia not as aging-related disorders and the reserve hypothesis.

We examined the relations between cognitive function and age and education in the normal elderly population. As per the community-based stroke, dementia, and bed confinement prevention in the town of Tajiri, neuropsychological assessments, including the Cognitive Ability Screening Instrument (CASI), were performed for 99 randomly selected normal elderly subjects. We assessed the frontal function (working memory, word fluency, Trail-Making Tests, CASI subitems of list-generating fluency, attention, and concentration/mental manipulation), language function (proverbs, CASI subitem language), non-language function (the digit symbol test of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), CASI subitem visual construction), memory (Alzheimer's Disease Assessment Scale recall/recognition, story recall, CASI subitems short and long-term memory, the Rey-Osterrieth Complex Figure Test), and the global function (CASI subitems orientation and abstraction and judgment). We found that the only test affected by age was the digit symbol test of the WAIS-R. The effects of education were distributed among various tests. There was a significant correlation between age and the frontal lobe atrophy in the lower educated group. The present findings suggest that cognitive function is spared by the aging process itself and dementia should be considered as age-related, not aging-related disorders, and that education might have a protective effect on cognitive change, supporting the reserve hypothesis.

Age Factors↗

Discrepancies between Gleason scores of needle biopsy and radical prostatectomy specimens.

The purpose of this study was to determine the accuracy of Gleason scores in prostate needle biopsy diagnosis and to investigate factors affecting the accuracy of the tumor grade. A single pathologist reviewed 116 sets of prostate cancer biopsies and radical prostatectomy specimens. The following factors were examined to determine their effect on the accuracy of the biopsy Gleason scores: (i) relative tumor differentiation; (ii) pathological stage; (iii) amount of tissue in the biopsy specimen; (iv) amount of cancer tissue in the biopsy specimen; (v) tumor heterogeneity; (vi) clinical findings (prostate specific antigen value and digital rectal examination); and (vii) interobserver variability. In 53 cases the Gleason score of biopsy specimens was identical to the score of prostatectomy specimens (45.7%). Fifty-four cases (46.6%) of biopsy specimens were undergraded. The most common discrepancy was diagnosis of well-differentiated carcinoma in the biopsy but diagnosis of moderately differentiated tumor in the corresponding prostatectomy specimen. This discrepancy occurred when the amount of tumor in the biopsy was 3 mm or less. Biopsy and prostatectomy results showed less agreement when the original biopsy tumor grade rendered by nine different pathologists was used, suggesting that interobserver variability can adversely affect the accuracy of tumor grade. Clarifying the histologic criteria for distinguishing each grade, especially between Gleason grades 2 and 3, is important for accurate grading.

Adenocarcinoma↗

Comparison of Japanese general rules of prostatic cancer and Gleason grading system.

BACKGROUND: We compared the prognostic efficacy between the Japanese General Rules of Prostatic Cancer (JGRPC) and the Gleason grading system (GGS) by applying them to a single set of patients and assessing the survival outcome. METHODS: One hundred and seventy-six patients with previously untreated prostate cancer were studied. One experienced Japanese pathologist graded the slides with JGRPC. Another experienced American pathologist graded the same slides with the Gleason grading system. The JGRPC grades were correlated with the Gleason scores (GS) grouped into three (GS 2-4, 5-7 and 8-10) or four (GS 2-4, 5-6, 7 and 8-10) tiers. RESULTS: The highest cancer death rates were seen in the higher grade groups in both systems. Comparison of JGRPC grade and three-tiered grouping of the GS showed identical grades in 81 of 176 cases (46.0%). The overall kappa value of agreement was only 0.151. The 96 cases of JGRPC moderately differentiated carcinoma group contained two nearly equal-sized groups by the Gleason grading system, those with GS 5-7 (47cases) and GS 8-10 (49 cases). There was a significant difference in survival rate between the GS 5-7 and GS 8-10 groups. No significant differences were noted in the reverse analysis of survival by JGRPC groups within patients with the same GS three-tiered groups. Similar trends were seen when JGRPC was compared with the four-tiered grouping of the GS. CONCLUSION: Both JGRPC and the Gleason grading system are useful in estimating the prognosis of prostate cancer, but only a mild correlation was found between the two systems. The Gleason grading system may provide more prognostic information than JGRPC in the moderately differentiated group.

Adenocarcinoma↗

Hybrid artificial liver using hepatocyte organoid culture.

We developed 2 types of hybrid artificial liver modules using hepatocyte organoid culture. One was a polyurethane foam (PUF)/hepatocyte spheroid packed-bed module. Hepatocytes spontaneously formed spheroids in the PUF pores, and they maintained liver-specific functions well for at least 2 weeks in vitro. As a preclinical experiment, a hybrid artificial liver with 200 g porcine hepatocytes was applied to a pig (25 kg) with liver failure and showed that the hybrid artificial liver was effective in support of liver functions and stabilization of general conditions. We established a new technique of hepatocyte organoid formation using centrifugal force. A hepatocyte organoid formed by centrifugation in hollow fibers maintained functions for more than 4 months in vitro. We developed a new sinusoid-like structure module having hollow fibers arranged by spacers in a micro-regular arrangement. Inoculated hepatocytes in the extra-fiber space of the module formed the organoid by centrifugation, and they maintained the functions for at least 1 month in vitro. The results indicated that this module seems to be promising as a hybrid artificial liver.

Animals↗

Application of indirect flow rate measurement using motor driving signals to a centrifugal blood pump with an integrated motor.

The method of measuring the flow rate of a centrifugal blood pump from the input electric power, which will be indispensable for the long-term use of such devices, was developed and was applied to the direct-driven centrifugal blood pump that has been developed by our research group. The accuracy was evaluated in a chronic animal experiment using an adult goat. The results demonstrated that this method carries the sufficient potential of the instantaneous monitoring method, but errors due to electromagnetic and mechanical losses were not determined always precisely. The detection of adverse phenomena such as the obstruction of the inlet cannula was also possible from the estimated value of the flow rate and its waveform pattern.

Animals↗

The role of p27kip1 protein expression on the biological behavior of intrahepatic cholangiocarcinoma.

Recent studies have reported that a decreased p27kip1 protein (p27) expression is associated with aggressive tumor behavior in several human malignancies. In this study, we examined the role of p27 expression in intrahepatic cholangiocarcinoma (ICC) and the noncancerous intrahepatic bile duct epithelium and assessed its association with clinicopathologic features, especially the influence of decreased p27 expression by the tumor on its prognosis as determined by immunohistochemistry. Almost all noncancerous bile duct epithelia show positive nuclear staining and reveal a faintly positive reaction in the cytoplasm. In 62 surgically resected ICCs, a variable degree of positive p27 nuclear staining is recognized. A subset (13 of 62 cases; 21.0%) of the carcinomas displayed cytoplasmic staining. We classified 62 cases into 2 groups, a low expression group (< 50% of p27 nuclear positive cells) and a high expression group (> or = 50% of p27 nuclear positive cells), and tested for the association between positive expression and clinicopathologic features. We found that a low expression of nuclear p27 was correlated with positive vascular invasion (P < .05). The survival curve of the group with low p27 nuclear expression was significantly lower than that of the group with high p27 nuclear expression (P < .005). According to the multivariate analyses, low p27 expression can be considered an independent prognostic factor whose occurrence indicates a worse prognosis. We conclude that a decreased p27 expression adds an independent parameter that can be used when determining the prognosis of patients with ICC.

Bile Duct Neoplasms↗

Disease recurrence after living liver transplantation for primary biliary cirrhosis: a clinical and histological follow-up study.

We describe the recurrence of primary biliary cirrhosis (PBC) in recipients of living liver transplants. We are not aware of similar previous reports. Because most donors for living liver transplantation (LLT) are blood relatives with close HLA matches, the recurrence of PBC in transplant recipients might offer additional insights in the pathogenesis of the condition. We studied 6 women (age, 29 to 61 years) with PBC who survived LLT for at least 1 year. Tests for antimitochondrial autoantibody (AMA), antipyruvate dehydrogenase complex-E2, immunoglobulin G (IgG) anti-M2, and IgM anti-M2 had confirmed the diagnosis. Donors were blood relatives in 5 instances, and one donor who was not a blood relative still had multiple HLA matches with the recipient. After LLT, we observed a decrease in AMA titers, but within 1 year, these titers increased again in 5 of the 6 patients to pre-LLT levels or greater. Immunoblotting analysis of the anti-M2 protein profile failed to show loss of bands and showed new bands in 3 of 6 patients. Histologically, strong evidence of recurrent PBC was found in 2 patients, and findings compatible with PBC were present in 1 additional patient. All 6 patients are doing well, without symptoms of recurrent PBC (median time post-LLT, 35.5 months; range, 12 to 50 months).

Adult↗

Influence of natural and synthetic compounds on cell surface expression of cell adhesion molecules, ICAM-1 and VCAM-1.

Various natural and synthetic compounds including alkaloids, terpenoids and phenolics were tested for inhibition of the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), both of which are crucial in the regulation of immune response and inflammation. Of 40 compounds tested, two compounds significantly downregulated the expression of VCAM-1 on murine endothelial cells (F-2) and ten compounds that of ICAM-1 on mouse myeloid leukemia cells (M1). Sanguinarine chloride (5) and isoliquiritigenin (13) were capable of lowering the levels of both ICAM-1 and VCAM-1. The structure-activity relationships study on chalcone and flavone derivatives related to 13 suggested that the inhibitory activity of the chalcone derivatives is attributable to the 4-hydroxy group as well as the possible coplanarity between the phenyl ring and the adjacent conjugated ketone.

Alkaloids↗

Endoscopic ablation with cyanoacrylate glue for isolated gastric variceal bleeding.

BACKGROUND: Endoscopic ablation with cyanoacrylate glue may achieve gastric variceal obliteration. A prospective evaluation of its therapeutic effects on bleeding gastric varices was conducted, focusing on endoscopic features. METHODS: Thirty-seven patients with bleeding gastric varices underwent endoscopic ablation with cyanoacrylate. RESULTS: Patients with localized-type gastric varices (n = 14) had a better clinical course in terms of recurrent bleeding, variceal eradication, and survival than those with diffuse-type gastric varices (n = 23) after endoscopic ablation with cyanoacrylate. These clinical effects were related to the vascular anatomy of the gastric varices as determined by varicography and 3-dimensional CT. Type 1 vascular anatomy (one varicose vessel without noticeable ramifications) was much more common (86%) in localized-type gastric varices, whereas type 2 vascular anatomy (multiple varicose vessels with complex connecting ramifications) was found almost exclusively (91%) in diffuse-type gastric varices. CONCLUSIONS: Endoscopic ablation with cyanoacrylate is an effective and safe procedure for patients with bleeding gastric varices. Determination of variceal anatomy may be useful for improving treatment strategies for such patients.

Adhesives↗

Treating chronic diffuse sclerosing osteomyelitis of the mandible with saucerization and autogenous bone grafting.

OBJECTIVE: Chronic diffuse sclerosing osteomyelitis of the mandible is a difficult-to-treat disease characterized by recurrent symptoms. The purpose of this study was to determine the results of particulate cancellous bone and marrow grafting after saucerization in the surgical treatment of diffuse sclerosing osteomyelitis of the mandible. STUDY DESIGN: Six patients with chronic diffuse sclerosing osteomyelitis of the mandible were treated by particulate cancellous bone and marrow grafting after saucerization and were retrospectively evaluated. Treatment results were evaluated with repeated comprehensive clinical investigation and radiologic/scintigraphic analysis. RESULTS: After the surgical procedure, all patients indicated maintenance of mandible continuity, contour, and function. Furthermore, 3 patients were symptom-free and the remaining 3 patients exhibited improvement. CONCLUSIONS: The partial resection of the mandible is associated with disadvantages, including loss of mandibular support, dysfunction, and problems related to mandibular reconstruction. Therefore, it would be reasonable to choose saucerization combined with particulate cancellous bone and marrow grafting, which is a relatively conservative surgical treatment for chronic diffuse sclerosing osteomyelitis of the mandible.

Adolescent↗

Changes in the caudate lobe that is transplanted with extended left lobe liver graft from living donors.

BACKGROUND: Caudate lobe transplantation with an extended left lobe graft is an innovative and promising method for increasing the graft volume in living donor liver transplantation. However, little is known about the fate of the caudate lobe after transplantation. METHODS: Eight extended left lobe grafts with the caudate lobe were included in this study. No attempt was made to reconstruct the short hepatic veins. On the basis of the computed tomography scans that were obtained before the operation and 1 month after the transplantation, the increase in the graft volume by the addition of the caudate lobe and the changes in the transplanted caudate lobe were evaluated. RESULTS: The addition of the caudate lobe increased the graft volume by 25 +/- 2 g, corresponding to a 2% increase in graft volume/standard liver volume ratio. One month after the transplantation, the caudate lobe volume increased in all patients but 1. The regeneration rate of the caudate lobe and other segments (segments II-IV) 1 month after transplantation was 62% +/- 24% (24 +/- 4 mL- 37 +/- 4 mL) and 152% +/- 35% (374 +/- 45 mL-930 +/- 65 mL), respectively (P <.01). CONCLUSIONS: This technique affords a modest increase in liver volume with living donor left liver procurement.

Humans↗

Microautoradiographic studies of glucose uptake in skeletal muscle fibers at rest.

In the present study, differences in glucose uptake by muscle fibers in deep, middle, and superficial regions of the gastrocnemius were studied at rest by 2-deoxyglucose (2-DG) microautoradiography. Expression of the glucose transporter 4 (GLUT-4) protein, an isoform of the glucose transporter family, was analyzed as well. These data were compared with the activity of succinate dehydrogenase, a marker of oxidative metabolism, a-glycerophosphate dehydrogenase, an indicator of the glycolytic capacity, and myofibrillar ATPase. In the deep regions of the muscle, most fibers (86.9%) showed high 2-DG uptake and large amounts of GLUT-4 protein, whereas in the superficial regions, all fibers showed low 2-DG uptake and GLUT-4 expression. In the middle regions, fibers dominated (80.4%) showed low 2-DG uptake and small amounts of GLUT-4 protein. Analysis of metabolic properties revealed that most fibers in the deep region were oxidative and showed the highest 2-DG uptake; in the superficial region, the fibers were anaerobic and showed the lowest 2-DG uptake. In the middle region, most fibers were of the anaerobic and fast twitch type. It is concluded that 2-DG uptake correlates with GLUT-4 expression in the plasma membrane of type I and IIx fibers rather than with oxidative enzyme activity.

Animals↗

Hydrophilic and hydrophobic bile acids exhibit different cytotoxicities through cytolysis, interleukin-8 synthesis and apoptosis in the intestinal epithelial cell lines. IEC-6 and Caco-2 cells.

BACKGROUND: Bile acids have been shown to exhibit varying degrees of cytotoxicity, depending on their hydrophobic-hydrophilic balance. We have recently reported the strong cytotoxicity of hyodeoxycholic acid (HDCA), and the aim of the present study is to investigate the mechanisms underlying the cytotoxicity of HDCA. METHODS: The intestinal cell lines IEC-6 and Caco-2 cells were used. The cytotoxicities of various bile acids were evaluated using the MTS assay; their cytolytic effects were measured using the LDH release assay. The induction of apoptosis was determined by the specific figure changes in the cellular cytoplasm and nucleus, including DNA ladder formations. IL-8 synthesis induced by the bile acids was measured using an ELISA assay. RESULTS: The bile acids induced cytotoxic effects, LDH release, IL-8 synthesis and apoptosis, depending on their hydrophobic properties. On the other hand, HDCA induced strong cytotoxicity, apoptosis and IL-8 synthesis but not cytolysis, although HDCA has a hydrophilic nature. In addition, HDCA exerted the strongest effects on dispersing monolayer cells. CONCLUSIONS: These results strongly suggest that HDCA induces cytotoxicity through its ability to induce apoptosis rather than its detergent effect.

Apoptosis↗

Coordinate upregulation of interleukin-8 and growth-related gene product-alpha is present in the colonic mucosa of inflammatory bowel.

BACKGROUND: Although ãlpha-chemokines, such as interleukin (IL)-8 and epithelial neutrophil-activating peptide 78, are implicated in the pathogenesis of inflammatory bowel disease (IBD), little information is currently available on the expression and cellular source of growth-related gene product-alpha (GROalpha) and its functional relationship to other ãlpha-chemokines in the intestinal mucosa of patients with IBD. METHODS: The contents of IL-8 and GROalpha in organ cultures, the expression of IL-8 and GROalpha mRNA, and the modulatory effects of inflammatory mediators on IL-8 and GROalpha-producing cells were examined using colonic mucosal tissues. In vitro stimulatory effects of IL-8 and GROalpha on neutrophils were investigated in terms of chemotactic migration and superoxide anion generation. RESULTS: The contents of IL-8 and GROalpha in organ cultures were elevated in patients with IBD, especially in those with active ulcerative colitis (UC). Both IL-8 and GROalpha contents increased according to an increase in histological disease activity in patients with UC, but not in those with Crohn disease. In contrast, no significant correlation was found between the contents of these alpha-chemokines and clinical disease activity. In situ hybridization detected increased expression of IL-8 and GROalpha mRNA in macrophages, pericrypt myofibroblasts, and the epithelium of tissue specimens with active lesions of IBD. The secretion of IL-8 and GROalpha from macrophages and myofibroblasts obtained from control patients was upregulated by inflammatory cytokines and bacterial products. The concentrations of recombinant (r)-IL-8, which covered the levels of activity detected in individual organ cultures or cell cultures of fractionated mucosal cells, could induce chemotactic migration and superoxide anion generation in neutrophils in vitro, and r-GROalpha had synergistic effects on r-IL-8-induced neutrophil activation. CONCLUSIONS: A coordinate upregulation of IL-8 and GROalpha may be involved in the tissue injury in patients with IBD through their stimulatory effects on neutrophils.

Adult↗

A trigeminal neuralgia-like paroxysmal pain condition presumably due to buccal nerve compression in the temporalis muscle.

We encountered three patients with trigeminal neuralgia-like paroxysmal pain in the buccal nerve region. In all cases, paroxysmal pain was felt spreading to the receptive field of the ipsilateral buccal nerve, and clear tenderness was observed during intraoral palpation at the inner side of the mandibular ramus where the temporalis muscle runs and attaches. It was assumed that the paroxysmal pain might be caused by nerve compression related to temporalis muscle hyperactivity. To lend support to this hypothesis, we also studied the anatomical relationship between the buccal nerve and the masticatory muscles. In this autopsy study, the buccal nerve pierced the temporalis muscle in six (12%) of 52 specimens from 26 cadavers. These findings support the hypothesis that peripheral buccal nerve compression could be an etiology of paroxysmal neuropathic pain in the unilateral orofacial region.

Aged↗