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Introduction Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%–95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS.Methods and analysis ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%–95% of the target SpO2) or the control (98%–100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1–2 at 90 days after ROSC, to be compared using an intention-to-treat analysis.Ethics and dissemination This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations.Trial registration number UMIN Clinical Trials Registry (UMIN000046914).

Osteogenesis imperfecta (OI) is a hereditary skeletal disease characterized by bone fragility. Areal bone mineral density (BMD), evaluated by dual-energy X-ray absorptiometry (DXA), is used to assess bone brittleness. The height-adjusted BMD Z-score (BMDHAZ) is calculated in children and adolescents with OI to reduce the confounding factor of short stature. However, even with the BMDHAZ, severity evaluation in children and adolescents with OI is challenging because certain abnormalities in bone quality cannot be accurately assessed by BMD analysis. The trabecular bone scores (TBS) and bone mineral apparent density (BMAD), which represent the structural integrity of bone and bone-size-associated BMD, respectively, are associated with fracture risk. Recently, age- and sex-specific reference ranges have been reported, enabling the calculation of Z-scores for children. To evaluate which density measurements show the highest correlation with fracture risk, we analyzed the associations between the Z-scores of TBS, BMAD, and BMDHAZ, fracture rate, and genetic variants. We retrospectively reviewed 42 participants with OI aged 5 to 20 years who underwent DXA. COL1A1/2 pathogenic variants were detected in 41 of the 42 participants. In participants with nonsense and frameshift variants (n = 17) resulting in haploinsufficiency and mild phenotype, the TBS Z-score was negatively correlated with fracture rate (FR) (r = -0.50, p = 0.042). In participants with glycine substitution (n = 9) causing the severe phenotype, the BMAD Z-scores were negatively correlated with FR (r = -0.74, p = 0.022). No correlation between the BMDHAZ and FR was observed in both groups. These findings suggest that the TBS and BMAD are useful in assessing children and adolescents with OI with specific genetic variants.

Background: There are a few reports on antibody responses after a two-dose BNT162b2 vaccination in non-epidemic areas. We evaluated this phenomenon. Methods: A total of 344 healthcare workers were vaccinated, and the serum anti-receptor-binding domain (RBD) antibody concentrations before and after two weeks following the two-dose BNT162b2 vaccination were measured using electro chemiluminescence immunoassay system. Results: Before vaccination, the antibody titers of all participants were less than 0.6 U/mL. After two doses of the BNT162b2 vaccine injection in 342 participants (2 excluded), a high seroconversion rate (99.7%) was observed. The average (±standard deviation) serum anti-RBD antibody titers were 2324 ± 1739 U/mL. Antibody levels in females and males were 2443 ± 1833 U/mL and 1908 ± 1287 U/mL, respectively (p = 0.037). Conclusion: In a non-epidemic area, two BNT162b2 doses induced a satisfactory antibody response, and the antibody concentrations in females were higher than in males.

Treatment with a combination of norepinephrine and doxazosin was effective in a patient with pheochromocytoma who had blood pressure fluctuation, hypotension, and recurrent syncope. After adrenalectomy, his blood pressure, heart rate, and plasma levels of catecholamines remained normal and stable without any medication. (Level of Difficulty: Beginner.)

Abstract Aims/Objectives Glycemic control varies according to stress level and the efficacy of control measures, affecting the outcomes of diabetes. Although detailed coping styles have not been well studied in patients with type 2 diabetes mellitus, problem‐focused coping strategies are believed to be related to better control of blood glucose. Associations between coping profiles/dimensions and blood glucose control were examined in individuals with type 2 diabetes. Materials and Methods The participants included 503 Japanese patients (mean age 63.9 ± 12.6 years) with type 2 diabetes. The average glycated hemoglobin A1c (HbA1c) levels were calculated from HbA1c levels measured more than four times within the 12 months before the assessment. Coping profiles were assessed using the Brief Scale for Coping Profile. Lifestyle factors were also included in the analyses. Results Factors other than age were not associated with HbA1c levels in patients who used insulin. Conversely, habitual alcohol consumption, single status, the adaptive emotion‐focused coping dimension, and changing mood and changing one’s point of view profiles were associated with HbA1c levels. Conclusions These findings suggest that adaptive emotion‐focused coping supports glycemic control in type 2 diabetes patients who do not use insulin. Additional studies using a longitudinal design are required to further examine the relationships between psychological factors and glycemic control.

Abstract Objective Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of depression, which is influenced by personality traits and coping style. However, these psychological factors have not been well studied in individuals with T2DM. The association between coping behaviors and the reported levels of depressive symptoms was examined in individuals with T2DM. Methods The subjects were 435 T2DM patients (mean age 63.1 ± 12.6 years). Depressive status, personality traits and coping behaviors were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Brief Scale for Coping Profile (BSCP). Lifestyle factors and glycated hemoglobin A1c (HbA1c) levels in the patients were also included in the analyses. Results Among the 435 subjects with T2DM, 130 (29.9%) exhibited possible depression, and 68 (15.6%) displayed probable depression. After adjustment for confounders, logistic and multiple regression analyses revealed that certain coping profile scores, such as Changing one’s point of view, Emotional expression involving others and Avoidance and suppression, were consistently and significantly associated with the presence and severity of depression. No relationship was found between depression and HbA1c. Conclusion These findings indicate that Maladaptive emotion-focused coping strategies, such as Emotional expression involving others and Avoidance and suppression, are protective factors and that Adaptive emotion-focused coping, such as Changing one’s point of view, is a risk factor for depression in T2DM patients. Psychological intervention focusing on the coping profile may reduce depressive symptoms. Additional studies are needed to examine the relationships between psychological factors and depressive symptoms using a longitudinal study design.

Abstract Aims/Introduction Insomnia is associated with type 2 diabetes mellitus, and results in a low quality of life. There are several known relationships between insomnia and personality. Thus, we clarified the association between some personality traits and insomnia among Japanese type 2 diabetes mellitus patients. Materials and Methods The participants were 504 type 2 diabetes mellitus patients (mean age 63.9 ± 12.5 years). Sleep disturbance and personality traits were evaluated using the Pittsburgh Sleep Quality Index‐Japanese version and the Ten‐Item Personality Inventory Japanese version, respectively. Lifestyle factors, glycated hemoglobin levels and depressive status of the patients were also included in the analyses. Results Among the 504 participants with type 2 diabetes mellitus, 154 (30.6%) showed probable insomnia. After adjustment for confounders, being female, living alone, high body mass index and “high neuroticism” were found to be significantly correlated with current insomnia. No other relationships between insomnia and glycated hemoglobin or lifestyle factors, such as smoking, drinking alcohol or exercise frequency, were found. Conclusions The prevalence of insomnia in individuals with type 2 diabetes mellitus was high, and the risk factors included some personality factors. Future prospective studies are required to confirm the therapeutic effects of behavioral interventions for insomnia in patients with type 2 diabetes mellitus.

Endosalpingiosis is a benign condition characterized by the presence of tubal epithelium outside the fallopian tube and the absence of endometrial stroma. Florid cystic endosalpingiosis is a very rare form of endosalpingiosis that presents as a tumor-like lesion. We report the case of a 67-year-old woman who presented with a cystic lesion of the uterus. Macroscopically, a cut section revealed a multicystic, whitish mass in the myometrium of the fundus. Histologically, the lesion consisted of numerous variably sized glands that were lined with a single or stratified layer of ciliated columnar cells similar to tubal epithelium.

Abstract Background Renal cell carcinoma is well-known for its propensity to metastasize to unusual sites. However, metastasis to the gallbladder has been rarely reported in the literature. Case presentation A 75-year-old Japanese (Asian) woman presented for further evaluation of a gallbladder polyp, 15 years after right radical nephrectomy for renal cell carcinoma. Computed tomography revealed a 12 mm enhancing pedunculated tumor in the gallbladder fundus. Open simple cholecystectomy was performed and the tumor was histologically confirmed as a metastasis of renal cell carcinoma to the gallbladder. Our patient is alive and has been disease-free for 3 years after cholecystectomy. Conclusions Although metastasis of renal cell carcinoma is a rare differential diagnosis of gallbladder tumors, simple cholecystectomy is likely to offer a chance of long-term survival for patients with gallbladder metastases of renal cell carcinoma.

Abstract This paper sheds light on the increase in generation of non-metallic mineral wastes and the decrease in demand for construction by investigating the material flow resulting from and the economic influence of changes in the supply and demand for wastes, focusing on the period from the near future to 2030. We predict the amount of final disposal of non-metallic mineral wastes and its influence on industries in the future under the assumption of two scenarios—zero emission and business-as-usual—using linear programming and input–output techniques developed for non-metallic mineral materials. We conclude that zero emission can be achieved at the cost of a 3.76% decrease in the value added of industries related to non-metallic mineral wastes. Otherwise, the final disposal might increase 13 times the size of 2005’s disposal. Considering the empirical results, we discuss an effective policy for non-metallic mineral waste management from the viewpoints of material flow and economic influence.

We report a case of multiple benign metastasizing leiomyoma (BML) lung nodules showing faint or non-avid uptake of F-18 fluorodeoxyglucose (FDG) (respective 1-hour early and 2-hour delayed maximum standardized uptake values; 1.3 or less and 1.2 or less) in a 50-year-old woman with a history of hysterectomy for uterine leiomyoma at the age of 38 years. When multiple lung nodules show faint or non-avid FDG uptake in a patient with a history of hysterectomy for uterine leiomyoma, BML should be included in the differential diagnosi.

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is very rare and aggressive. The prognosis is very poor despite multimodal treatment. We report a virgin woman with FIGO stage 4b LCNEC of uterine cervix coexisting with squamous cell carcinoma. An early thirties virgin woman presented with 2-month history of abdominal pain. A chest X-ray showed multiple lung metastatic tumors. A vaginal smear showed malignant cells, and a biopsy specimen had features of LCNEC. The tumor showed trabecular patterns. Tumor cells possessed a moderate amount of cytoplasm, prominent nucleoli, and large nuclei. The tumor cells are stained positive for synaptophysin, chromogranin A, and neuron specific enolase (NSE). The invasive tumor cells in connection with cervical squamous epithelium were focally positive for 34bE12. We made a diagnosis of composite LCNEC and nonkeratinizing squamous cell carcinoma. High-risk HPV test was negative with hybridized captured method 2.

Hollow spheres of poly (1,4-phenylene-5-hydroxyisophthalamide) (PPHIA) which was an intractable aromatic polyamide were prepared by the reaction-induced phase separation during polymerization, and they are hopeful candidates as high-performance hollow spheres. In this study, porosity control of PPHIA hollow spheres was examined by optimizing polymerization conditions, focusing on polymerization temperature and time. Porosity became lower with smaller sphere size, and this tendency was more conspicuous at lower polymerization temperature. Skin layer gradually became thicker with polymerization owing to the accumulation of oligomers on both the outer surface and the inner surface of hollow spheres, resulting in the decrease in the porosity. The porosity of PPHIA hollow sphere could be controlled in the range from 4% to 16% by tuning polymerization temperature and time. [ABSTRACT FROM AUTHOR]

Congenital generalized lipodystrophy type 4 (CGL4) is a rare disease caused by mutations in the gene polymerase I and transcript release factor (PTRF), the main symptoms of which are systemic reductions in adipose tissue and muscular dystrophy. The strategy of treating CGL4 is to improve the insulin resistance and hypertriglyceridemia that result from systemic reductions in adipose tissue. Metreleptin, a synthetic analog of human leptin, is effective against generalized lipodystrophies; however, there are no reports of the use of metreleptin in the treatment of CGL4. Herein, we discuss the treatment of a six-year-old boy diagnosed with CGL4 due to a homozygous mutation in PTRF with metreleptin. His serum triglyceride level and homeostasis model assessment of insulin resistance (HOMA-IR) value decreased after two months of metreleptin treatment. However, the efficacy of metreleptin gradually decreased, and the treatment was suspended because anaphylaxis occurred after the dosage administered was increased. Subsequently, his serum triglyceride level and HOMA-IR value significantly increased. Anti-metreleptin-neutralizing antibodies were detected in his serum, which suggested th a t these antibodies reduced the efficacy of metreleptin and caused increased hypersensitivity. Thus, metreleptin appeared to be efficacious in the treatment of CGL4 in the short term, although an adverse immune response resulted in treatment suspension. Further studies are needed to evaluate metreleptin treatments for CGL4. [ABSTRACT FROM AUTHOR]

Behavioral flexibility and impulse control are necessary for successful execution of adaptive behavior. They are impaired in patients with damage to the prefrontal cortex (PFC) and in some clinically important conditions, such as obsessive-compulsive disorder. Although the medial prefrontal cortex (mPFC) has been investigated as a critical structure for behavioral flexibility and impulse control, the contribution of the underlying pyramidal neuron cell types in the mPFC remained to be understood. Here we show that interneuron-mediated local inactivation of pyramidal neurons in the mPFC of male and female mice induces both premature responses and choice bias, and establish that these impulsive and compulsive responses are modulated independently. Cell-type-specific photoinhibition of pyramidal deep layer corticostriatal or corticothalamic neurons reduces behavioral flexibility without inducing premature responses. Together, our data confirm the role of corticostriatal neurons in behavioral flexibility and demonstrate that flexible behaviors are also modulated by direct projections from deep layer corticothalamic neurons in the mPFC to midline thalamic nuclei. [ABSTRACT FROM AUTHOR]

Methane from landfills contributes to global warming and can pose an explosion hazard. To minimize these effects emissions must be monitored. This study proposed application of portable gas detector (PGD) in point and scanning measurements to estimate spatial distribution of methane emissions in landfills. The aims of this study were to discover the advantages and disadvantages of point and scanning methods in measuring methane concentrations, discover spatial distribution of methane emissions, cognize the correlation between ambient methane concentration and methane flux, and estimate methane flux and emissions in landfills. This study was carried out in Tamangapa landfill, Makassar city- Indonesia. Measurement areas were divided into basic and expanded area. In the point method, PGD was held one meter above the landfill surface, whereas scanning method used a PGD with a data logger mounted on a wire drawn between two poles. Point method was efficient in time, only needed one person and eight minutes in measuring 400 m² areas, whereas scanning method could capture a lot of hot spots location and needed 20 min. The results from basic area showed that ambient methane concentration and flux had a significant (p < 0.01) positive correlation with R² = 0.7109 and y = 0.1544 x. This correlation equation was used to describe spatial distribution of methane emissions in the expanded area by using Kriging method. The average of estimated flux from scanning method was 71.2 g m-2 d-1 higher than 38.3 g m-2 d-1 from point method. Further, scanning method could capture the lower and higher value, which could be useful to evaluate and estimate the possible effects of the uncontrolled emissions in landfill. [ABSTRACT FROM AUTHOR]

Anaerobic landfills are the type most commonly adopted in the majority of developing countries. However, environmental problems generated from anaerobic-type landfills such as high concentrations of organic carbon (TOC) and nitrogen (TN) in leachate, a long stabilization period, and a heavy generation of greenhouse gases (GHG) are attracting more and more attentions. The aerobic-anaerobic method was initially touted as a new landfill method that incorporated the advantages of aerobic-type landfill, while at the same time lowering operational costs. Air is injected into the solid waste layer of an anaerobic-type landfill at the appropriate stabilization phase and depth to create an aerobic atmosphere in the solid waste layer, which enhances the decomposition of TOC and TN. During the decomposition of TOC, it can be expected that aerobic decomposition will restrain the emission of methane gas, as well as achieve an earlier stabilization of landfilled solid waste. The objective of this study is to clarify the air injection conditions that are optimal to improve leachate quality, restrain GHG emission, and enhance landfilled solid waste stabilization. Three large lysimeters, measuring 3 m in height, were constructed for the execution of experiments under different air injection conditions, and the resultant leachate quality and gas composition in the lysimeters were examined. In addition, a one-dimensional landfill model was developed and the influences of air injection conditions on leachate quality, landfill gas generation and stabilization of landfilled solid waste were estimated by numerical simulation. As a result, it was clarified that air injection at the deepest depth, which is 2.5 m depth in this study, is best for decreasing TOC discharge and GHG emission. [ABSTRACT FROM AUTHOR]

Claudins are involved in the formation of tight junctions in epithelial and endothelial cells. Claudins form a family of 24 members displaying organ- and tissue-specific patterns of expression. In the present study, we evaluated the specificity of the claudin-2 expression in various normal human tissues and gastrointestinal cancers by quantitative reverse transcriptase–polymerase chain reaction and immunohistochemistry. In 14 various normal tissues, claudin-2 mRNA was expressed in the kidney, liver, pancreas, stomach, and small intestine; the highest level of which was detected in the kidney. Colorectal cancers (CRCs) expressed claudin-2 mRNA at high levels. Immunohistochemical analysis of claudin-2 in 146 gastric cancers (GCs) and 99 CRCs demonstrated claudin-2 expression in 2.1% of GCs and 25.3% of CRCs, respectively. There was no obvious correlation between claudin-2 expression and clinicopathological parameters of CRCs. These results suggest that the expression of claudin-2 may involve organ specificity, and increased expression of claudin-2 may participate in colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]

Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis. [ABSTRACT FROM AUTHOR]

Cbl proteins play important roles in downregulation of growth factor receptors by acting as ubiquitin ligases and multi-adapter proteins. Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) has been shown to be controlled by Cbl. In the present study, we examined the expression of Cbl in gastric carcinomas and studied the correlation of Cbl expression with clinicopathological characteristics as well as EGFR expression. Cbl protein was expressed in 67% (82/122) of gastric carcinomas, and diffuse expression of Cbl was detected in 29% (35/122) of the cases. The incidence of cases with diffuse expression of Cbl was significantly higher in advanced cases (28/70, 40%) than in early cases (7/52, 14%) ( P=0.0010). Diffuse expression of Cbl was significantly associated with metastasis of tumor cells in lymph nodes ( P=0.0318). Diffuse expression of EGFR was significantly associated with depth of invasion ( P=0.0057), lymph-node metastasis ( P=0.0371) and tumor stages ( P=0.0278). As the grades of Cbl expression became stronger, the cases with diffuse EGFR expression increased, the positive correlation being significant ( P=0.049). All the cases with diffuse expression of Cbl and EGFR were found to show nodal metastasis and to be at an advanced stage. Moreover, the prognosis of the patients with synchronous diffuse expression of Cbl and EGFR was significantly poorer than that of the patients negative for Cbl and focal or negative for EGFR ( P=0.0086). The expression of Cbl protein was clearly induced in gastric carcinoma cell lines by transforming growth factor-a treatment. These results suggest that Cbl in connection with the EGFR system may be associated with stomach carcinogenesis, invasion and metastasis. Cbl may serve as a novel molecular marker for aggressive gastric carcinoma. [ABSTRACT FROM AUTHOR]

Patients with long-standing and extensive ulcerative colitis (UC) have an increased incidence of colorectal cancer (CRC). It has been reported that a DNA repair gene, O 6-methylguanine-DNA methyltransferase ( MGMT) is inactivated by promoter hypermethylation in sporadic CRCs. Hence, we investigated the promoter methylation status of MGMT by methylation specific polymerase chain reaction (PCR) in a total of 67 tissue samples (61 non-cancerous tissues and 6 cancer tissues) from 24 patients with UC. Promoter hypermethylation of MGMT was detected in one well-differentiated adenocarcinoma (16.7%) of 6 cancer samples and not detected in any of adenomas and dysplasias. In non-dysplastic tissues, promoter hypermethylation of MGMT was detected in 2 (3.7%, mucosa with mild inflammation) of 54 samples. The frequency of MGMT promoter hypermethylation in UC-associated CRCs found in this study (16.7%) is obviously lower than previously reported in sporadic CRCs (39.0?42.0%). We also confirmed that 42.9% (6/14) of sporadic CRCs showed the promoter methylation. These findings indicated that promoter hypermethylation of the MGMT gene is infrequent in patients with UC, and may not closely contribute to UC-associated colorectal tumorigenesis. A different genetic pathway for tumor progression may exist between sporadic CRC and UC-associated CRC. [ABSTRACT FROM AUTHOR]

Osteoprotegerin (OPG), identical with osteoclastogenesis inhibitory factor, is a member of a subgroup of the tumor necrosis factor (TNF)-receptor superfamily, which functions as a soluble decoy receptor. It has been reported that OPG expression is associated with bone metastasis of cancer of the breast and prostate. In the present study, we examined the expression of OPG in gastric carcinomas using immunohistochemistry and reverse-transcription polymerase chain reaction methods, and compared with clinicopathological parameters. The expression of OPG mRNA was confirmed in a gastric carcinoma cell line (MKN-7) and gastric carcinoma tissues. Immunohistochemically, strongly positive staining of OPG was found in 65% (67/103) of gastric carcinomas, whereas OPG protein was not detected in non-neoplastic mucosal epithelia. The expression of OPG protein in gastric carcinoma tissues correlates significantly with depth of tumor invasion, nodal metastases and advanced tumor stage. Furthermore, the prognosis of the cases with strong OPG expression was significantly worse than those with weak or no expression of OPG. These results suggest that OPG may participate in stomach carcinogenesis, invasion and metastasis, and may serve as a novel molecular marker for aggressive gastric cancer. [ABSTRACT FROM AUTHOR]

In liver injuries, the quiescent hepatic stellate cells (HSCs) promptly change to activated HSCs, which are easily identified by the intense immunoreactivity for a-smooth muscle actin. However, reproducible markers for quiescent HSCs in formalin-fixed, paraffin-embedded liver tissue sections have not yet been reported. We immunohistochemically examined the expression of vinculin, one major protein of dense plaques, on cultured LI90 cells and on HSCs in normal and diseased human and rat livers. In cultured LI90 cells, vinculin appeared as small linear patches. Although vinculin was consistently negative in the routine liver tissue sections, an antigen retrieval technique using microwave oven heating yielded excellent effects. Using this technique, the formalin-fixed, paraffin-embedded human and rat normal liver tissue sections showed the vinculin immunoreactivity along the sinusoidal wall. Immunoelectron microscopic observation of hepatic parenchyma demonstrated that the vinculin was exclusively expressed in quiescent HSCs. In fetal rat livers, vinculin-positive quiescent HSCs gradually increased in number with gestation. In diseased livers the activated HSCs showed more intense immunoreaction for vinculin. These results indicate that, using microwave pretreatment, vinculin is expressed in quiescent and activated HSCs in routinely processed liver tissue sections. It could allow us to evaluate the development and distribution of quiescent HSCs and to examine the relationship between quiescent and activated HSCs. [ABSTRACT FROM AUTHOR]

abstract thrombospondin-1 (tsp-1) has been shown to play a role in angiogenesis in a variety of cancers, but some studies indicated a difference in the mechanism of tsp-1 on neovascularization according to organ or histological type. wild-type p53 protein has been shown to induce tsp-1 expression. we examined the expression of tsp-1 protein in 80 gastric carcinomas using immunohistochemistry and studied the relationship with microvessel counts, p53 expression and clinicopathological factors. we also performed reverse-transcriptase polymerase chain reaction analysis for the tsp-1 mrna expression in gastric carcinoma cell lines and gastric cancer tissue after laser capture microdissection. strong expression of tsp-1 protein was detected in 30 (38%) of the 80 cases. positive staining for tsp-1 was seen in the cytoplasm of the cancer cells. tsp-1 mrna expression was confirmed in a majority of gastric carcinoma cell lines and carcinoma tissues. microvessel counts were significantly higher in tumors with strong tsp-1 protein expression than in those without expression or weak expression of tsp-1 (p=0.011). no significant correlation was found between tsp-1 expression and p53 staining and clinicopathological factors. our results support an idea that increased tsp-1 expression may be associated with an angiogenic phenotype in gastric carcinoma and suggest that tsp-1 may play diverse roles in each organ. [ABSTRACT FROM AUTHOR]

Abstract. Integrin-linked kinase (ILK), a serine/threonine protein kinase, implicates in cellular control of cell-matrix interactions and cell proliferation that is associated with a highly invasive phenotype of certain tumors. To study whether ILK is involved in the development and progression of gastric carcinoma, we examined the expression of ILK in gastric carcinoma cell lines, primary gastric carcinomas and corresponding non-neoplastic mucosa using reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry and analyzed the relationship with clinicopathological parameters. The expression of ILK mRNA was detected in 4 of 5 gastric carcinoma cell lines and 22 of 35 (63%) microdissected tumor samples of primary gastric carcinoma using RT-PCR. The incidence of cases with ILK mRNA expression was significantly higher in scirrhous and intermediate type (82%) than in medullary type (44%) (P=0.0204). Significant association was detected between ILK mRNA expression and presence of nodal metastasis (P=0.0388). Immunohistochemically, strong expression of ILK protein (over 50% of tumor cells were positive) was detected in 69% (84/122) of primary gastric carcinomas, whereas no ILK expression was found in non-neoplastic gastric epithelia. Strong expression of ILK protein was significantly associated with scirrhous and intermediate type (P=0.0217), deep invasion of tumor cells in gastric wall (P=0.0006), and presence of nodal metastasis (P=0.0176). These results strongly suggest that ILK may participate not only in stomach carcinogenesis especially of scirrhous and intermediate types but also in invasion and metastasis of gastric carcinoma. ILK might be a novel molecular marker for aggressive gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract. We examined regeneration and fibrosis in the necrotic areas of hepatic stellate cells (HSCs). Acute hepatic injury was induced in rats by administration of an intraperitoneal injection of high-dose dimethylnitrosamine (50 mg/kg body weight). Liver samples were obtained from rats 6, 12, 24, 36 h and 2, 3, 5, 7, 10, and 14 days after the injection. They were examined by light and electron microscopy and by immunohistochemical methods. Hemorrhagic necrosis became most prominent 36 h after treatment and extended into zones 3 and 2. In the submassive necrotic areas the sinusoidal structure was destroyed. No HSCs positive for α-smooth muscle actin or desmin were present. On day 5, when necrotic tissues were almost removed by infiltrating macrophages, HSCs strongly positive for α-smooth muscle actin and desmin appeared along the surface of the preserved parenchyma and migrated into the necrotic areas along the residual reticulin fibers. By day 14 most of the necrotic areas were almost completely replaced by the regeneration of hepatocytes and central to central (C-C) bridging fibrosis. Our results indicate that following submassive complete necrosis, HSCs in the preserved liver parenchyma have roles in the formation of sinusoidal wall for remodeling in necrotic areas via their activation, proliferation, and migration into the necrotic areas. [ABSTRACT FROM AUTHOR]