Kounis syndrome caused by protamine shock after coronary intervention: A case report.

We report a case of Kounis syndrome that led to shock after protamine administration during percutaneous coronary intervention (PCI). A man in his 50s was admitted to the nearest hospital following the onset of acute myocardial infarction. Coronary angiography showed a single-vessel lesion in the left anterior descending artery (LAD). He was admitted for PCI. After heparin administration, the procedure was completed by implantation of a coronary stent with the usual procedure. For hemostasis, following protamine administration, the patient went into shock. Subsequently, electrocardiography showed bradycardia with ST-segment elevation at leads II, III, aVF, and V3-6. Cardiopulmonary resuscitation was started immediately. As pulseless electrical activity continued, extracorporeal membrane oxygenation (ECMO) was introduced. Coronary angiography demonstrated coronary spasm in the LAD. He was withdrawn from the ECMO on day 7. His intradermal tests were positive for protamine in the convalescent phase. The patient was diagnosed with protamine shock and type I Kounis syndrome. Protamine shock is not uncommon, but Kounis syndrome may be hidden in it. Thus, similar cases should not be treated as a simple protamine shock. .

Predictive ability and efficacy for shortening door-to-balloon time of a new prehospital electrocardiogram-transmission flow chart in patients with ST-elevation myocardial infarction - Results of the CASSIOPEIA study.

BACKGROUND: The purposes of this study were to create a new flow-chart of prehospital electrocardiography (ECG)-transmission, evaluate its predictive ability for ST-elevation myocardial infarction (STEMI) and shorten door-to-balloon time (DTBT). METHOD AND RESULTS: The new transmission flow-chart was created using symptoms from previous medical records of STEMI patients. A total of 4090 consecutive patients transferred emergently to our hospital were divided into two groups: those in ambulances with an ECG-transmission device with the new flow-chart (ECGT-FC) and those transferred without an ECG-transmission device (non-ECGT) groups. A STEMI group comprising walk-in patients during the same period was used as a control group. The predictive ability of STEMI and the effectiveness of shortening the DTBT by the new flow-chart of ECG-transmission was evaluated. In the ECGT-FC group, the prevalence of STEMI in the ECG-transmission by the new flow-chart were significantly higher than in the non-ECG-transmission patients (6.71% vs. 0.19%; p<0.001). The sensitivity and specificity of the new ECG-transmission flow-chart were 83.3% and 88.1%, respectively. The median DTBT was significantly shortened (p=0.045) and the prevalence of DTBT<90min was significantly higher in the ECGT-FC group (p=0.018) than the other groups. CONCLUSION: The sensitivity and specificity of the new flow-chart for ECG-transmission were high. The new flow-chart combined with an ECG-transmission device could detect STEMI efficiently and shorten DTBT.

Sustained Increase in the Incidence of Acute Decompensated Heart Failure After the 2011 Japan Earthquake and Tsunami.

This study investigated the long-term impact of the 2011 Japan earthquake and tsunami on the incidence of acute decompensated heart failure (HF) in the disaster area. This was a population-based study using comprehensive registration for all hospitals within the study area. The standardized incidence ratio (SIR) and 95% confidence interval (CI) for new onset of HF during the disaster year (2011) and postdisaster years (2012 to 2014) were determined. When SIR were compared between the low- and high-impact areas, as defined by the extent of tsunami inundation in residential areas, SIR showed a significant increase in high-impact areas in 2011 (1.67, 95% CI 1.45 to 1.88) and tended to return to baseline in 2012, the first postdisaster year (1.25, 95% CI 1.06 to 1.43). The rate again increased in 2013 (1.38, 95% CI 1.18 to 1.57) and 2014 (1.55, 95% CI 1.35 to 1.75). In low-impact areas, no such increase was apparent during either the disaster year or the postdisaster years. Mean postdisaster period SIR for municipalities significantly correlated with the percentage of tsunami flooding in residential areas (r = 0.52, p <0.05) and with the percentage of refugees within the population (r = 0.74, p <0.01). There was no significant relation between maximum seismic intensity and mean SIR in these municipalities. In conclusion, these results suggest that the catastrophic tsunami but not the earthquake per se resulted in a prolonged increase in the incidence of HF among the general population living in tsunami-stricken areas.

A case of gastric cancer with heterogeneous components of EB virus (+)/TP53 (+) and EB virus (-)/TP53 (-).

Epstein-Barr virus (EBV)-associated gastric adenocarcinoma is a histological subtype of gastric adenocarcinoma, in which all of the carcinoma cells are basically positive for EBV-encoded small RNA (EBER) by in situ hybridization. Although its typical histology has some overlap with gastric carcinoma with lymphoid stroma, absence of massive lymphoid infiltrate is sometimes observed either in whole or in part. EBV-associated adenocarcinoma is one of the four representative molecular pathological subtypes recently identified by comprehensive genomic analysis of gastric adenocarcinomas. According to the analysis, typical EBV-associated gastric adenocarcinoma constitutes an independent molecular pathological subgroup, which is mutually exclusive to TP53-mutated adenocarcinoma with chromosomal instability, another molecular pathological subtype in gastric adenocarcinomas. Here, we report a rare case of gastric cancer heterogeneously composed of EBER (+)/TP53 (+) and EBER (-)/TP53 (-) portions. The EBER (+)/TP53 (+) component with massive lymphoid infiltrate surrounded the EBER (-)/TP53 (-) component showing well to moderately differentiated tubular adenocarcinoma. Although collision of two independent gastric cancers could be the simplest and most possible explanation for this situation, we discussed another possibility. In the case of gastric collision tumors, concurrent development of EBER (+) gastric adenocarcinomas and EBER (-) gastric adenocarcinomas in a single stomach is a rare incident. Since presence of the EBER (+)/TP53 (+) tumor component is atypical in itself, we also discussed the mechanism of development of the clone.

Sex-specific temporal trends in the incidence and prevalence of hospitalized patients with preserved versus reduced left ventricular ejection fraction heart failure: A Japanese community-wide study.

BACKGROUND: Sex specific temporal trends in the incidence and prevalence of hospitalization for heart failure (HF), particularly in conjunction with reduced and preserved left ventricular ejection fraction (EF) remain unclear, especially in Asian general populations. METHODS: We conducted a community based HF registration study over a 10 year period in an aging cohort of the Japanese general population. RESULTS: A total of 2598 cases of hospitalized HF were registered during the survey period. Of these 1413 cases (55%) were initial admissions for HF (incident case). The study period was divided into five 2-year terms (T1, 2003-2004; T2, 2005-2006; T3, 2007-2008; T4, 2009-2010; T5, 2011-2012), and data were compared among the terms. Age adjusted incidence of HF (per 105 person-year) remained stable in men, but decreased significantly by 25% in women (from 104 at T1 to 79 at T5; p for trend < 0.05). Among incident cases who underwent echocardiography (≈ 90%), the proportion of HF with preserved EF increased in men (from 32% at T1 to 43% at T5; p for trend < 0.05), and was relatively high and remained stable throughout the study period in women (from 52% at T1 to 58% at T5; p for trend; NS). CONCLUSION: Although the incidence of HF has declined especially in women between 2003 and 2012 in the study population, the proportion of HF with preserved EF has increased over time. These trends suggest a future prevalence of HF with preserved EF rather than HF with reduced EF in aging Asian populations.

The first genetically confirmed case of Dioctophyme renale (Nematoda: Dioctophymatida) in a patient with a subcutaneous nodule.

We describe a nematode larva in a subcutaneous nodule excised from a 44-year-old Chinese male who had been living in Japan for 15 years. Morphological features suggested that the worm was a dioctophimatid nematode. PCR amplification and sequencing of small subunit ribosomal DNA and mitochondrial cytochrome subunit c oxidase genes allowed us to identify the larva as the giant kidney worm, Dioctophyme renale (Goeze, 1972). This is the first molecularly confirmed human case of a dermal D. renale infection.

Comparison of the incidence of acute decompensated heart failure before and after the major tsunami in Northeast Japan.

On March 11, 2011, a huge tsunami attacked the northeastern coast of Japan after a magnitude 9 earthquake. No reports have investigated the impact of tsunamis on the incidence of cardiovascular disease, especially heart failure (HF). We investigated the number and clinical characteristics of hospitalized patients with acute decompensated HF (ADHF) in the east coast of Iwate hit by the tsunami (tsunami area) for a 12-week period around the disaster. For comparison with previous years, numbers of ADHF were surveyed in the corresponding area in 2009 and 2010. In addition, to elucidate the impact of the tsunami, a similar study was performed in a remote area where the tsunami had minimal effect (control area). After the disaster, the number of patients with ADHF in the tsunami area was significantly increased compared to the predisaster period (relative risk 1.97, 95% confidence interval 1.50 to 2.59). The peak was found 3 to 4 weeks after the disaster. In contrast, in the control area, no significant change in ADHF events was observed (relative risk 1.29, 95% confidence interval 0.94 to 1.78). There was a significant correlation between changes in the number of ADHF admissions and percent tsunami flood area (r = 0.73, p <0.001) or the number of shelter evacuees (r = 0.83, p <0.001). In conclusion, these findings suggest that large and sudden changes in daily life and the trauma associated with a devastating tsunami have a significant impact on the incidence of ADHF.

Plasma B-type natriuretic peptide is useful for cardiovascular risk assessment in community-based diabetes subjects: comparison with albuminuria.

Diabetes mellitus (DM) is a strong risk factor for cardiovascular (CV) disease. Plasma B-type natriuretic peptide (BNP) levels are elevated in various types of cardiac diseases. Increased plasma BNP levels have been reported to be associated with CV risk in apparently healthy individuals. However, no studies have yet examined the specific value of plasma BNP for predicting CV incidence in unselected DM subjects in a community-based population.In a community-based DM cohort (n = 1,059, mean = 66 years), baseline BNP levels were determined, and CV events were followed and captured prospectively. The cohort was divided by plasma BNP quintiles. The Cox proportional hazard model was used to determine the relative hazard ratios (HR) among the quintiles. In addition, the effects of adding the plasma BNP or urine albumin-to-creatinine ratio (UACR) to an established CV risk scoring model was examined by calculating the area under the receiver operating characteristic (ROC) curve (AUC).During the 5.7 year follow-up period, CV events were identified in 65 of the DM cohort. There was a significant association between plasma BNP levels and CV event rate (P < 0.001). HR was significantly increased in the highest quintile compared to the lowest (HR = 4.38; 95%CI 1.69 -11.84). The AUC generated from ROC analysis of the Framingham risk score for predicting general CV events was improved by adding BNP testing (from 0.66 to 0.74; P = 0.05), but not by adding UACR (from 0.66 to 0.67; P = 0.49).In a community sample of people with DM, plasma BNP levels above the 80 percentile are directly associated with CV risk, and measurement of plasma BNP alone or in conjunction with an established CV risk score is of value in predicting CV events in these subjects.

Sex-specific threshold levels of plasma B-type natriuretic peptide for prediction of cardiovascular event risk in a Japanese population initially free of cardiovascular disease.

Elevated plasma B-type natriuretic peptide (BNP) levels have been reported to be related to a high risk for cardiovascular (CV) disease in the general population. However, there has been no accurate determination of the threshold levels of plasma BNP that indicate an increased potential for the development of general CV events (i.e., heart failure, stroke, and myocardial infarction) and the validity of these levels for predicting CV events compared to classic risk markers. To establish gender-specific thresholds of plasma BNP levels associated with increased risk for CV disease in the general population, baseline BNP levels were determined in community-dwelling adults (n = 13,209, mean age 62 ± 10 years,) and CV events in the cohort were captured prospectively. The cohort was divided by deciles of plasma BNP level in each gender. A Cox proportional-hazards model was used to determine the relative hazard ratios among the deciles. In addition, to compare the utility of plasma BNP to the Framingham 10-year risk score for predicting general CV events, receiver-operating characteristic analysis was performed. During follow-up, CV events were identified in 429 patients in the cohort. Compared to the reference decile level (first to fourth), the hazard ratio was significantly increased from the ninth decile in men (greater than approximately 37 pg/ml) and the highest decile in women (greater than approximately 55 pg/ml). The area under the curve generated on receiver-operating characteristic analysis of plasma BNP testing was comparable to that for the Framingham risk scoring system (0.67 vs 0.68 in men, 0.63 vs 0.68 in women; p = NS for both). In conclusion, within a community-based general population with no CV history, plasma BNP levels higher than defined thresholds show increased risk for general CV events, and the predictive ability for CV events occurring within several years may be comparable to that of an established long-standing risk score.

Platelet high-density lipoprotein activates transferrin-derived phagocytosis activators, MAPPs, following thrombin digestion.

Macromolecular activators of phagocytosis from platelets (MAPPs), transferrin-derived phagocytosis activators released from platelets, activate leukocytic phagocytosis via Fcγ receptors. It has been found that MAPPs can be prepared using stored platelets or their lysate. Using this artificial MAPP production system, it has been found that they can be produced from precursors (tetrameric and dimeric transferrins) following reaction with a low-molecular-weight (LMW) activator of MAPPs, which is liberated from a high-molecular-weight activator of MAPP (HMW activator) by reaction with thrombin. In this study, the HMW activator in platelet lysate was characterized by assaying phagocytosis of washed neutrophils. In an ultracentrifugation study of the platelet lysate, HMW activator activity was observed in the fraction corresponding to the density of high-density lipoprotein (HDL). The activity was observed in the apolipoproteins obtained from the HDL fraction. Among the apolipoproteins tested only apolipoprotein CIII showed the activity to produce MAPP in vitro. Affinity chromatography of the apolipoproteins from the HDL fraction of the platelet lysate using an anti-apolipoprotein CIII column revealed that the substance that binds with the antibody showed MAPP-forming activity. In a gel filtration study of thrombin-treated apolipoprotein CIII, a peak of LMW activator activity was observed for fractions with a molecular size smaller than that of apolipoprotein CIII. Finally, MAPP-forming activity of HDL obtained from the plasma was examined. MAPP was formed only when delipidized HDL was used. In conclusion, it is suggested that platelet HDL is the HMW activator and that this activation is achieved via apolipoprotein CIII after thrombin reaction in platelets.

Prehypertension subtype with elevated C-reactive protein: risk of ischemic stroke in a general Japanese population.

BACKGROUND: Prehypertension (PreHT) and low-grade inflammation are both known to be related to the incidence of cardiovascular events. This cohort study investigated whether the high-risk group for future ischemic stroke among PreHT subjects can be predicted by stratification of high-sensitivity C-reactive protein (hsCRP). METHODS: A total of 22,676 subjects aged 40-80 years from the general population who had no cardiovascular history underwent baseline measurement of serum hsCRP, and were followed for the incidence of ischemic stroke. RESULTS: During the mean follow-up period of 2.7 years, 143 subjects had a first ischemic stroke. In a Cox multivariable model after adjustment for cardiovascular risk factors, there was no significant difference in hazard ratio (HR) for incidence of ischemic stroke between the normotension (NT) and PreHT subjects (HR = 1.72, 95% confidence interval (CI): 0.93-3.18, vs. NT subjects). In contrast, the HR for incidence of ischemic stroke in PreHT subjects with higher hsCRP levels (≥0.5 mg/l in men, ≥0.4 mg/l in women, more than median levels according to sex) was increased compared to NT subjects with lower hsCRP levels (HR = 2.63, 95% CI: 1.11-6.24). Moreover, the HR for incidence of ischemic stroke in PreHT subjects with lower CRP levels (HR = 0.91, 95% CI: 0.31-2.73) did not differ from that in NT subjects with lower hsCRP levels. CONCLUSIONS: This study showed that, in a Japanese general population, hsCRP was a marker for relatively short-term risk of ischemic stroke in PreHT subjects.

The expression of LDL receptor in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model.

We previously reported that the blood-brain barrier (BBB) function was deteriorated in vessels located in the hippocampus in stroke-prone spontaneously hypertensive rats (SHRSP). In order to assess whether substances with oxidative stress such as amyloid-beta (Abeta) can be scavenged in the BBB-damaged vessels, we examined the gene expression of representative efflux and influx transporters of Abeta, such as low-density lipoprotein receptor (LDLR), LDL-related protein 1 (LRP1), and the receptor for advanced glycation end product (RAGE) in the hippocampus of SHRSP with the BBB impairment and Wistar Kyoto rats (WKY) without the impairment. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis revealed that LDLR gene expression was increased in the samples of SHRSP compared with those of WKY, while there was no significant difference in LRP1 or RAGE gene expression between SHRSP and WKY. Western blot analysis revealed that the protein expression of LDLR was increased in the samples of SHRSP compared with those of WKY. Immunoelectron microscopic examination revealed that the LDLR expression was seen in the luminal and abluminal cytoplasmic membranes and vesicular structures of the endothelial cells and the cytoplasm of perivascular cells, especially in vessels with immunoreactivity of albumin showing increased vascular permeability. These findings suggest that the expression of LDLR was increased in the hippocampus of SHRSP compared with that of WKY and was seen in the luminal and abluminal cytoplasmic membranes and vesicular structures of endothelial cells, suggesting a role of LDLR in the vessels with BBB impairment.

Age-related changes in P-glycoprotein expression in senescence-accelerated mouse.

P-glycoprotein, the gene product of ATP-binding cassette, sub-family B (Abcb1), is a representative efflux transporter of cerebral vessels. It was recently reported that the expressions of P-glycoprotein and Abcb1 gene were increased in hippocampal vessels with blood-brain barrier (BBB) damage in stroke-prone hypertensive rats. SAMP8, senescence-accelerated mice with age-related deficits in memory and learning, are known to show age-related damage of BBB. Accordingly, in this study, we examined the P-glycoprotein expression and the gene expression (Abcb1a/b) by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical techniques. SAMR1, which has a spontaneous retroviral insertional mutation in Abcb1a gene, was used to assess the effects of Abcb1a gene mutation. The brain samples of SAMR1 showed decreased expressions of P-glycoprotein and Abcb1a genes and increased expression of Abcb1b gene, compared with those of SAMP8 mice. The P-glycoprotein expression increased with aging in the brain samples of SAMP8, but not in those of SAMR1. The gene expressions of Abcb1a and Abcb1b increased with aging in the brain samples of SAMP8. Immunosignals of P-glycoprotein were seen in vessel walls, mainly in the cytoplasm of CD34-positive endothelial cells and partially in astrocytes, in all mice. These findings indicate that the expressions of Abcb1a and Abcb1b genes and their gene products, P-glycoprotein, were increased with aging in SAMP8, suggesting age-related response to prevent toxic substance from accumulating in the brains of SAMP8.

RAGE, LDL receptor, and LRP1 expression in the brains of SAMP8.

SAMP8, senescence-accelerated mice with age-related deficits in memory and learning, are known to show age-related increases of amyloid precursor protein (APP) expression and to be under elevated oxidative stress. The receptor for advanced glycation end product (RAGE) is a representative influx transporter of APP or amyloid-beta (A beta) protein in cerebral vessels, while low-density lipoprotein receptor (LDLR) and LDL-related protein 1 (LRP1) are efflux transporters. These receptors play roles not only in clearance of A beta protein but also in control of oxidative stress. In this study, we examined the gene and protein expressions of these receptors, by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical techniques. SAMR1 mice with lower expression of APP were as controls. The gene and protein expressions of RAGE were lower in SAMP8 brains than in SAMR1. Those of LDLR were higher in SAMP8 brains than those of SAMR1. There were no differences in the expressions of LRP1 between SAMP8 and SAMR1. Immunosignals of RAGE and LDLR were seen in the cytoplasm of CD34-positive endothelial cells and also in astrocytes, in both strains of mice. These findings suggest that the lower expression of RAGE and the higher expression of LDLR may contribute to clearance of toxic substances and, in addition, be related to elevated oxidative stress in SAMP8 brains.

Abcb1a and Abcb1b expression in senescence-accelerated mouse (SAM).

It was recently reported that some strains of senescence-accelerated mouse (SAM) including SAMR1 had a spontaneous retroviral insertional mutation in the ATP-binding cassette, sub-family B, member 1A (Abcb1a) gene, while other strains including SAMP8 had not. The Abcb1 gene product, P-glycoprotein, is a representative efflux transporter of cerebral vessels. In this study, using brain samples of SAMR1, Abcb1a gene-mutant mice, and of SAMP8 without that mutation, we examined the gene expression of some representative ATP-binding cassettes, such as Abcb1a, Abcb1b, Abcc, and Abcg2, and the protein expression of P-glycoprotein by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical techniques. The gene expression of Abcb1a was decreased in the brain samples of SAMR1 compared with those of SAMP8, while that of Abcb1b was increased in the samples of SAMR1 compared with those of SAMP8. There were no differences in the gene expression of Abcc and Abcg2 between the samples of SAMR1 and SAMP8. The protein expression of P-glycoprotein was decreased in the brain samples of SAMR1 compared with those of SAMP8. Immunosignals of P-glycoprotein were seen in vessels walls, mainly CD34-positive endothelial cells and partially astrocytic cells, in both mice. These findings indicate that SAMR1, Abcb1a-mutant mice, showed decreased expression of Abcb1a gene and P-glycoprotein and increased gene expression of Abcb1b, compared with those of SAMP8 without that mutation, suggesting no clear effect of increased gene expression of Abcb1b on decreased expression of P-glycoprotein. The combination of SAMR1 and SAMP8 may be a good tool to investigate which transporter, Abcb1a or Abcb1b, can be used in drug delivery into the brain.

Medulloblastoma with myogenic differentiation showing double immunopositivity for synaptophysin and myoglobin.

Reported herein is a case of medulloblastoma with myogenic differentiation in a 3-year-old girl who died 1 year after appearance of clinical signs. Magnetic resonance imaging indicated a mass lesion in the cerebellar vermis. She underwent total resection of the tumor, followed by chemotherapy and radiotherapy in the brain and spinal cord. The resected specimen mainly consisted of densely packed cells with round-to-oval highly chromatic nuclei surrounded by scanty cytoplasm and focally of long spindle-shaped cells with elongated nuclei and eosinophilic cytoplasm showing discernible cross-striations. Immunohistochemistry indicated partial expression of synaptophysin in the former area and focal expression of desmin in the latter area. The diagnosis was medulloblastoma with myogenic differentiation, also known as medullomyoblastoma. Autopsy indicated disseminated proliferation of immature neuroglial cells with highly chromatic nuclei and scanty cytoplasm showing partial expression of synaptophysin, neurofilaments, and GFAP, and focal proliferation of round-to-oval immature cells showing immunoreactivity of myoglobin. The tumor cells had large nuclei, frequent mitoses, apoptoses, nuclear molding, and cell wrapping, indicating moderate anaplasia. Their Ki-67 labeling index was 54%. In addition, some tumor cells had double immunopositivity for synaptophysin or neurofilament and myoglobin, suggesting that the neuroectodermal cells may undergo differentiation into rhabdomyoblasts.

Comparison between mucinous cystic neoplasm and intraductal papillary mucinous neoplasm of the branch duct type of the pancreas with respect to expression of CD10 and cytokeratin 20.

OBJECTIVE: Mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm of the branch duct type (IPMN-BD) differ in biological and clinical behaviors, but MCN is often misdiagnosed as IPMN-BD. The purpose of this study was to find useful markers for the differential diagnosis of MCN and IPMN-BD. METHODS: Immunohistochemically, the expression of the 2 types of mucin (MUC) 1 (MUC1/DF3 and MUC1/CORE), MUC2, MUC5AC, MUC6, human gastric mucin (HGM), caudal-related homeobox transcription factor 2 (CDX2), CD10, cytokeratin (CK) 7, and CK20 was examined in 7 cases of MCN and 16 cases of IPMN-BD. RESULTS: Expression frequencies in MCN and IPMN-BD were 100% versus 44% for MUC1/DF3, 86% versus 31% for MUC1/CORE, 57% versus 19% for MUC2, 86% versus 100% for MUC5AC, 57% versus 88% for MUC6, 86% versus 100% for HGM, 57% versus 0% for CDX2, 71% versus 0% for CD10, 100% versus 69% for CK7, and 86% versus 6% for CK20. CONCLUSIONS: Mucin 1/DF3, MUC1/CORE, CDX2, CD10, and CK20 were expressed significantly more frequently in MCN than in IPMN-BD. In particular, CD10 and CK20 showed marked differences in immunohistochemical sensitivity and specificity between MCN and IPMN-BD. It is therefore proposed that CD10 and CK20 may be used for the differential diagnosis of MCN and IPMN-BD.

The expression of matrix metalloproteinase-13 is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model.

We previously reported that the blood-brain barrier (BBB) function was deteriorated in vessels located in the hippocampus, but not the cerebral cortex, in 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP). Recently published data suggest that matrix metalloproteinase (MMP)-2 and MMP-9 play a critical role in the BBB disruption in stroke or cerebral ischemia. In this study, we examined gene and protein expressions of MMPs in the BBB-damaged hippocampal vessels of 3-month-old SHRSP, in the cerebral cortical vessels without BBB damage of SHRSP, and in the hippocampal and cerebral cortical ones without BBB damage of 3-month-old Wistar Kyoto (WKY) rats. The expressions of MMPs were examined by real-time quantitative reverse transcriptase-PCR (RT-PCR), western blotting and immunohistochemical techniques. The gene and protein expressions of MMP-13 were significantly increased in the hippocampal samples of SHRSP compared with samples without BBB damage, such as cerebral cortical samples of SHRSP or hippocampal samples of WKY. Immunostaining of MMP-13 was seen in the cytoplasm of ED-1-positive perivascular cells in both rats and was colocalized with those of type IV collagen or osteopontin. The type IV collagen was also localized in the basement membrane. These findings indicate that the expression of MMP-13 is increased in BBB-damaged hippocampal vessels in hypertensive SHRSP compared with vessels without BBB impairment in normotensive WKY rats and may be involved in vascular remodeling.

Comparison between colorectal low- and high-grade mucinous adenocarcinoma with MUC1 and MUC5AC.

AIM: To explore useful prognostic factors for mucinous adenocarcinoma (MAC) in the colon and rectum. METHODS: MAC was divided into low- and high-grade types based on the degree of structural differentiation; low-grade MAC arisen from well to moderately differentiated adenocarcinoma and papillary carcinoma, and high-grade MAC from poorly differentiated adenocarcinoma and signet ring cell carcinoma. Immunohistochemically, the expression of 2 types of MUC1 (MUC1/DF and MUC1/CORE), MUC2, 2 types of MUC5AC (MUC5AC/CHL2 and HGM), MUC6, CDX2, and CD10 was examined in 16 cases of MAC consisting of 6 low- and 10 high-grade types. RESULTS: MUC1/DF3 was expressed in 3 of 6 low-grade MAC (50%) and 10 of 10 high-grade MAC (100%). MUC1/CORE was expressed in 1 of 6 low-grade MAC (16.7%) and 7 of 10 high-grade MAC (70%). MUC2 was expressed in all MAC regardless of the grade. MUC5AC was expressed in 6 of 6 low-grade MAC (100%) and 4 of 10 high-grade MAC (40%). HGM was expressed in 5 of 6 low-grade MAC (83.3%) and 6 of 10 high-grade MAC (60%). Expression of MUC6 and CD10 was undetected in all MAC regardless of the grade. CDX2 was expressed in 5 of 6 low-grade MAC (83.3%) and 7 of 10 high-grade MAC (70%). Taken together, MUC1/DF3 was expressed significantly more frequently in high-grade MAC than in low-grade, and MUC5AC/CHL2 was expressed significantly more frequently in low-grade MAC than in high-grade. CONCLUSION: It is proposed that MUC1/DF3 and MUC5AC/CHL2 immunostaining is useful to discriminate high-grade MAC from low-grade MAC.