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Multiple gastric cancers at the same time (synchronous) or recurrence after 1 year (metachronous) are frequently encountered. Since their genetic profiles were not well elucidated, we molecularly subtyped the genetic events of synchronous and metachronous early-stage gastric cancers. We studied mismatch repair (MMR) genes in 84 tumors from 31 patients (15 synchronous and 16 metachronous) by immunohistochemistry. We performed microsatellite instability analysis and targeted sequencing of 58 significantly mutated genes (SMGs) in 35 tumors from thirteen patients. Genomic data from TCGA were used for comparisons with advanced-stage cancers. Among the 31 patients, at least one deficient-MMR (dMMR) tumor was observed in eight (26%). Of eight patients, seven showed a mixture of proficient-MMR (pMMR) and dMMR tumors. The one case with only dMMR had six recurrent tumors within 2 years. To further subtype, we sequenced 58 SMGs in 35 samples (25 pMMR and 10 dMMR) from thirteen patients. In 35 samples, 163 mutations were identified, but none matched in almost cases, strongly indicating different clonal origins, whether synchronous or metachronous occurrences. Of the 25 pMMR cases, 1 belonged to Epstein–Barr virus (EBV), 24 belonged to chromosomal instability (CIN) subtypes. Of the thirteen cases, repetitive CIN, a mixture of CIN and MSI, a mixture of CIN and EBV, and repetitive MSI were observed in nine (70%), two (15%), one (8%) and one (8%), respectively. Despite multiple tumors occurring in the same patient simultaneously or several years apart, clonal origin was totally different. ‘Switching’ or ‘mixing’ of dMMR and pMMR, EBV or CIN occurred, which had clinical relevance with regard to immunotherapy.

Background: The Tokyo Guidelines (TG; 2013) indicated that emergency cholecystectomy is an important early treatment option for acute cholecystitis; however, surgical intervention is not necessarily indicated in patients with advanced age. We evaluated percutaneous transhepatic gallbladder aspiration (PTGBA), percutaneous transhepatic gallbladder drainage (PTGBD), and the administration of antibiotics alone as treatment options for acute ­cholecystitis. Methods: From January 2010 to December 2017, 159 patients with acute cholecystitis were treated at our institution. The data from these patients were retrospectively analyzed. Results: Of these 159 cases, 109 underwent PTGBA, 28 underwent PTGBD, and 22 were administered antibiotics alone. None of the 159 patients needed urgent (early) cholecystectomy, and all patients were discharged without mortality. PTGBA was unsuccessful in only 6 of 109 patients; PTGBD was performed in these 6 cases. Long-term follow-up was conducted in all cases. Of the 159 patients, 146 had gallbladder stones initially, while 13 had none at the time of presentation. Of these 146 patients with gallbladder stones, 84 underwent elective cholecystectomy, while 62 did not. Of the 84 patients who underwent elective cholecystectomy, 2 developed choledocholithiasis; of the 62 patients who did not undergo elective cholecystectomy, 5 developed choledocholithiasis and 2 developed acute cholecystitis. The incidences of choledocholithiasis and acute cholecystitis did not significantly differ between the 2 groups (p = 0.06). Conclusions: Despite the recommendations in the TG (2013), emergency cholecystectomy was not needed in any of the present patients with acute cholecystitis. Acute cholecystitis can be successfully treated with ­PTGBA or PTGBD, which are simple procedures with good short- and long-term safety. These procedures are highly recommended for patients with acute cholecystitis, especially in the elderly population.

Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines

Hepatitis B virus (HBV) infection is one of the serious health problems in the world as HBV causes severe liver diseases. Moreover, HBV reactivation has occasionally been observed in patients with resolved HBV infection and patients using immunosuppression and anticancer drugs. Large-scale hospital data focused on HBV infection and severe liver function were analyzed at our hospital, located in an urban area adjacent to Tokyo, the capital city of Japan. A total of 99,932 individuals whose blood samples were taken at 7,170,240 opportunities were analyzed. The HBV surface antigen (HBsAg)-positive group had a more frequent prevalence of patients with higher transaminase elevations than the HBsAg-negative group. However, among the HBsAg-negative group, patients who were positive for anti-HBV surface antibody and/or anti-HBV core antibody, had more severe liver conditions and fatal outcomes. More careful attention should be paid to alanine transaminase (ALT) elevations higher than 1000 IU/L in patients who had current and previous HBV infection.

BackgroundStudies indicate that gastric cancer (GC) incidence has decreased, whereas signet ring cell carcinoma (SRC) incidence has increased. However, recent trends in GC incidence are unclear. We used our hospital cancer registry to evaluate the changes in the incidence of GC, SRC, and non-SRC (NSRC) over time in comparison to changes in theH. pyloriinfection rates over time.MethodsWe identified 2532 patients with GC enrolled in our registry between January 2007 and December 2018 and statistically analyzed SRC and NSRC incidence. TheH. pyloriinfection rate in patients with SRC was determined by serum anti-H. pyloriantibody testing, urea breath test, biopsy specimen culture, and immunohistochemical analysis (IHC) of gastric tissue. Additionally, genomic detection ofH. pyloriwas performed in SRCs by extracting DNA from formalin-fixed paraffin-embedded gastric tissue and targeting 16S ribosomal RNA ofH. pylori.ResultsOverall, 211 patients had SRC (8.3%). Compared with patients with NSRC, those with SRC were younger (P P P H. pyloriinfection prevalence between the SRC and NSRC groups. IHC and genomic methods detectedH. pyloriin 30 of 37 (81.1%) SRCs.ConclusionsReduction inH. pyloriinfection prevalence may be associated with the decrease in the incidence of SRC, which was higher than that of NSRC.

Signet ring cell (SRC) gastric cancer at advanced stage has poor prognosis. While a recent study reported nearly one-third of SRC cases contain tumors with deficient mismatch repair (MMR) genes, other studies in SRC have been inconclusive. To re-analyze the results, we performed immunohistochemical staining of MLH1, MSH2, MSH6 and PMS2 proteins in 38 SRC gastric tumors compared with 109 non-SRC (NSRC) tumors from 94 patients. In contrast to the previous study, all SRC gastric tumors normally expressed MMR proteins, whereas 22 of 109 of NSRC (20%) showed deficient MMR proteins. To reinforce our results, we referred to the Cancer Genome Atlas (TCGA) genomic database and found that only 6 (6%) of 99 samples with diffuse gastric tumors showed deficient MMR, whereas 64 (21%) of 304 in intestinal gastric tumors showed deficient MMR. Our results as well as the TCGA database indicated that MMR genes are infrequently inactivated in SRC gastric cancer. These findings indicate that SRC patients may not be the best candidates for immuno-oncology therapy.

Lenvatinib (an inhibitor of vascular endothelial growth factor (GF) receptors 1–3, fibroblast GF receptors 1–4, platelet-derived GF receptor α, rearranged during transfection, and stem cell factor receptor) was non-inferior to sorafenib in a phase 3 (REFLECT) trial of advanced hepatocellular carcinoma. This study examined the efficacy and safety of lenvatinib in a real-world setting. This was a retrospective, multicenter, observational study. Inclusion and exclusion criteria were based on the phase 3 trial, and participants were observed for at least 12 weeks. Therapeutic effect was determined using the modified Response Evaluation Criteria In Solid Tumors (m-RECIST) at the 8th week. Patients received oral lenvatinib 12 mg/day (body weight > 60 kg) or 8 mg/day (body weight

Background The clonality of primary tumors is well elucidated. In contrast, the relation to metastatic foci is not well understood. We examined genomic clonality of primary tumors and metastatic foci. Method We studied 144 foci (34 primaries, 104 lymph nodes, 6 organ mets) from 10 patients with gastrectomy (c-Stage 3). We also searched the expression of MMR proteins. Results In 10 primaries, mutations were found in all (range 3-12, mean 6). Of 104 lymph nodes, 64 lymph nodes carrying mutations identical to corresponding primaries in all. In addition, all the genomic profiles were replicated in corresponding lymph nodes and visceral mets. Among 3 cases with dMMR, all metastatic foci showed identical phenotypes. Conclusion Surprisingly, significantly mutated genes (SMGs) profiles in all lymph nodes and visceral mets were identical to the primaries. In addition, MMR/MSI status was also identical. These results indicated proper selection of chemo-, molecular-, and immune-oncology treatments could be effectively applied to the spreaded mets. Internoduler ""de novo"" heterogeneity was so scarce. Often claimed tumor heterogeneity could be due to inappropriate selection of drugs and due to their pressure.

To estimate the response to hormone replacement therapy (HRT) by bone metabolic markers, 36 patients with postmenopausal osteoporosis or osteopenia were studied to assess the correlation between percent baseline changes in lumbar bone mineral density (BMD) after 12 months and those in various bone metabolic markers after 3, 6, and 12 months of HRT. All the patients were treated with 0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone per day and continued for 12 months. BMD was significantly increased up to 4.19 +/- 0.87% after 6 months and 4.93 +/- 1.27% after 12 months of HRT (p = 0.0001 by analysis of variance). In accordance with this, changes in the levels of osteocalcin (p = 0.041), alkaline phosphatase (p = 0.0001), N-terminal osteocalcin (p = 0.0001), urinary excretion of pyridinoline/Cr (p = 0.0001), and deoxypyridinoline/Cr (p = 0.0001) were significantly decreased, respectively. Among these bone metabolic markers, only the change in the serum N-terminal osteocalcin at 3 months (r = 0.557, p = 0.0022), at 6 months (r = 0.470, p = 0.0184), and at 12 months (r = 0.545, p = 0.0061) significantly correlated with the change in BMD 12 months after HRT. The elution profiles of immunoreactive osteocalcin-related molecules in serum fractionated by reverse-phase high performance liquid chromatography revealed that the N-terminal fragment as well as the intact osteocalcin molecule decreased after 3 months of HRT. These results demonstrate that N-terminal osteocalcin is a suitable predictor for estimating good responders to HRT in postmenopausal women.

Blood flow to the gravid and nongravid uterine horns of four multiparous Holstein cows (mean +/- SD, BW=641.8 +/- 95.4 kg; age=4.8 +/- 1.2 years; parity=3.0 +/- 1.2) was measured on days 225, 248, and 266 of gestation. Surgery was conducted on day 214.5 +/- 4.0 of gestation through the flank of the standing cows. Transit-time ultrasonic flow probes (diameter 12 or 14 mm) were fitted surgically around the uterine arteries of each cow. Surgery was completed within two hours of anesthesia, and the animals recovered rapidly following surgery. Uterine blood flow (UBF, l/min) was recorded at 10 sec intervals for approximately 23.5 hours; these values were averaged to determine UBF. The mean gravid UBF was significantly (P0.05) greater than the nongravid UBF in this study. The range of the gravid and nongravid UBFs varied from 3.61 to 14.05 and 0.72 to 6.54 l/min, respectively. There were no changes (P0.1) in the mean gravid and nongravid UBFs from day 225 to 266 of gestation.

Seven Holstein cows (BW = 639.4 +/- 28.8 kg, age = 62.6 +/- 6.9 mo, parity = 3.1 +/- 0.4 yr) (mean +/- SE) were used to measure uterine blood flow using a transit time ultrasonic flow meter. Ultrasonic flow probes were implanted (d 218 +/- 4 of gestation) around both uterine arteries (n = 3) or the gravid uterine artery (n = 4) to measure variations in uterine blood flow through this vessel in response to postural change (standing and lying). Implantation of the ultrasonic blood flow probe was successful in all 7 cows. Uterine blood flow was measured for 22.9, 23.1, and 21.4 h/d on d 226, 248, and 269 of gestation, respectively. Cows exhibited normal durations of gestation (272.8 +/- 1.6 d), gave birth to normal healthy calves (birth weight = 41.5 +/- 3.0 kg), and did not retain their placenta. Uterine blood flow to the gravid horn during lying was greater than during standing on d 226 (standing vs. lying, 8.04 vs. 8.79 L/min, respectively), d 248 (9.87 vs. 11.06 L/min), and d 269 (8.15 vs. 9.74 L/min) of gestation. Cows spent nearly 50% of their time lying during our observations at all gestational ages. Greater blood supply to the gravid uterus was observed during lying than during standing in this study.

Protein C is one of the most important antithrombotic components. After activation by the thrombin-thrombomodulin complex on endothelial cells, activated protein C (APC) inactivates factors Va and VIIIa, which leads to the inhibition of thrombin formation. We examined the association of plasma levels of APC with the responsiveness to coronary thrombolytic therapy of the infarct-related coronary artery in patients with acute myocardial infarction (AMI). Plasma levels of APC, thrombin-antithrombin III complex (TAT), and plasminogen activator inhibitor (PAI) activity were measured in 32 consecutive AMI patients who underwent coronary angiography followed by thrombolytic therapy, and compared to the measurements in 23 control subjects. On admission, APC levels (ng/mL) were significantly elevated in patients with AMI, as compared with controls (2.5+/-0.4 vs. 1.2+/-0.2, 1.3+/-0.2, respectively, p0.01). At discharge, plasma levels in AMI patients decline to values not significantly different from those in controls. (1.2+/-0.2, 1.3+/-0.2, respectively). TAT levels (ng/mL) were different among the groups in a fashion similar to that of APC (14.1+/-3.1 on admission vs. 3.3+/-0.4 at discharge, 1.8+/-0.1 in the control subjects, respectively, p0.01). PAI activity levels (IU/mL) were higher on admission than at discharge and higher than the control subjects (19.7+/-1.8 vs. 10.5+/-1.0, 5.4 +/- 0.7, respectively, p0.01). Thirty-two patients with AMI were classified into two groups according to the results of thrombolysis: the success group (24 patients) and the failure group (eight patients). APC levels were higher in the failure group than in the success group (5.1+/-0.7 vs. 1.6+/-0.2, p0.01). TAT levels were also higher in the failure group than in the success group (30.8+/-9.6 vs. 8.6+/-1.7, p0.01). PAI activity levels (IU/mL) were lower in the failure group than in the success group (13.5+/-3.1 vs. 21.7+/-2.1, p0.05). There were correlations between APC and TAT levels both on admission (r=0.75, p0.0001) and at discharge (r=0.71, p0.0001). Elevated APC was thought to correlate with increased thrombin generation in patients with AMI. This study demonstrated that there was a significant relation between plasma APC level and the responsiveness to thrombolytic therapy of the infarct artery. This study may also indicate that increased thrombin generation is a cause of the resistance to thrombolytic therapy.

Pulmonary surfactant protein A (SP-A) is known to be a major phospholipid-associated glycoprotein in pulmonary surfactant, which is specific to the lung. In this study, the SP-A concentrations in sera of patients with various lung diseases were determined using an enzyme-linked immunosorbent assay. Patients with idiopathic pulmonary fibrosis (IPF) and pulmonary alveolar proteinosis (PAP) exhibited prominently high concentrations of serum SP-A compared to those of other lung diseases and healthy volunteers, although there were significant increases in serum SP-A concentrations in patients with pulmonary tuberculosis, chronic pulmonary emphysema, diffuse panbronchiolitis and bacterial pneumonia compared to those of healthy volunteers. Successive measurement in 2 patients with IPF showed that serum SP-A levels reflect the disease activity of IPF. In patients with IPF, serum SP-A concentrations were significantly correlated with those of serum lactate dehydrogenase, whereas there were no significant correlations of serum SP-A concentrations with erythrocyte sedimentation rate, arterial oxygen saturation, vital capacity and carbon monoxide diffusing capacity. Determination of serum SP-A will contribute to diagnosing IPF and PAP, and may reflect the disease activity of IPF.

Background/aims In both SHARP and Asia-Pacific Study, sorafenib was proved to improve the overall survival of the patients with hepatocellular carcinoma. However, factors contributing to the improvement of overall survival of the patients treated by sorafenib have not been fully evaluated. In this study, patient-derived, background liver disease-derived and tumor-derived factors before treatment were evaluated whether they have contributed to the improvement of the overall survival. Methodology Forty-seven cases with HCC treated by sorafenib between Sept 2009 and Feb 2011 were included in this analysis. The survival of these cases was analyzed by Kaplan-Meier Method. Factors used for univariate analysis were two patient-derived parameters, two background liver disease-derived, five tumor-derived. Factors related to the over-all survival were analyzed by multivariate analysis using Cox regression model. Results In the multivariate analysis, only background liver disease-derived parameter Child-Pugh class A vs. B, (p=0.007, HR=0.21 (0.07-0.65)) was significant. No other parameters including tumor-derived factors were statistically significant by multivariate analysis. Conclusions We undertook the statistical analysis on the three categories. Surprisingly, no tumor derived parameter contributed to the overall survival. Background liver disease-derived parameter rather than tumor-derived parameter was found to define the prognosis of patients with advanced HCC treated by sorafenib.

The 4-kd amyloid beta protein (A beta) deposited as amyloid in Alzheimer's disease (AD) is produced and released by normal proteolytic processing of the amyloid beta protein precursor (beta APP) and is readily detected in cerebrospinal fluid (CSF). Here, we present the levels of A beta in CSF from a total of 95 subjects, including 38 patients with AD, 14 with early-onset AD and 24 with late-onset AD, 25 normal control subjects, and 32 patients with other neurological diseases. The level of A beta decreased with normal aging, and there was a significant elevation in the level of A beta in the CSF of early-onset AD patients (4.14 +/- 1.37 pmol/ml, p < 0.01). Neither Mini-Mental State nor Functional Assessment Staging were correlated with the amount of A beta in the CSF. The A beta/secreted form of beta APP ratio was elevated, but the level of alpha 1-antichymotrypsin in the CSF did not correlate with the level of CSF A beta in early-onset AD patients. Thus, the level of A beta in the CSF is elevated in early-onset AD patients and is suggested to be correlated with the pathology in the brain that characterizes AD.

Background. Resistance to chemotherapeutic agents is a major problem in non-small cell lung cancer (NSCLC) chemotherapy, and recent studies have indicated that glutathione S-transferase-π (GST-π) may play an important role in the resistance of cancer cells to alkylating agents that include platinum compound. Methods. GST-π in serum of 121 patients with NSCLC was measured by a sandwich enzyme-linked immunosorbent assay, and the serum concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, and neuron-specific enolase (NSE) were also examined. Serum levels of these tumor markers were also evaluated in relation to therapeutic response in 69 patients who received combination chemotherapy with platinum compound. Results. Fifty of 121 patients with NSCLC (41.3%) showed elevated serum GST-π levels above a cutoff value of 34.8 ng/ml (mean + two standard deviations in 30 healthy control subjects). The positive rate of GST-π in patients with NSCLC was higher than those of CEA (37.2%), SCC (15.7%), and NSE (14.9%). The mean pretreatment GST-π level was significantly lower in patients with a partial response to chemotherapy than in those with no response (26.9 ± 11.3 ng/ml versus 38.8 ± 16.7 ng/ml; P < 0.003). Among patients with elevated levels of pretreatment serum GST-π, only 13.8% (four of 29) responded to the combination chemotherapy, whereas partial response was observed in 40.0% of patients (16 of 40) with serum GST-π concentration below the cutoff level (P < 0.02). Neither CEA, SCC, nor NSE showed such a relationship. Conclusions. The serum GST-π level may have limited value as a tumor marker for NSCLC. Interestingly, pretreatment serum GST-π levels may be a useful parameter for predicting therapeutic response to combination chemotherapy regimens that include platinum compound. Cancer 1994; 73:1377–82.

The purpose of the present study was to determine the levels of osteocalcin, a bone specific matrix protein, in gingival crevicular fluid (GCF) from periodontal disease patients and to investigate the relationship between GCF osteocalcin levels and clinical parameters. Nineteen initial visit patients, 5 patients with gingivitis and 14 patients with adult periodontitis, participated in this study. The clinical parameters including probing depth, attachment level, gingival index, and tooth mobility were recorded following careful sampling of GCF with a filter paper strip harvested for 3 minutes. Osteocalcin adsorbed on a strip was extracted in a plastic tube containing 150 microliters of 10 mM sodium phosphate buffer (pH 6.5). GCF osteocalcin was determined by a newly-developed, high sensitive enzyme immunoassay which could recognize the N-terminal 20 residue peptide. In gingivitis patients, no significant amounts of osteocalcin were detected. In periodontitis patients, on the other hand, osteocalcin levels were detected, ranging between 0 and 540 pg/tube and positively correlated with these clinical parameters (P < 0.01). Moreover, in several sites in GI = 3 group, extremely higher levels of GCF osteocalcin were detected. These results strongly suggest that in addition to the presence of GCF osteocalcin the levels of osteocalcin may reflect the degree of the periodontal inflammation at the sampled sites.

In pneumonia in the elderly, one occasionally encounters difficulties in evaluation with respect to both clinical observation and treatment. Thus a simple serum indicator is indicated. We measured secretory leukoprotease inhibitor (SLPI) concentrations in sera to see whether this can provide a useful indicator for pneumonia, especially in the elderly. Serum samples from patients over 65 yr of age, with (n = 54) or without (n = 87) pneumonia, and from healthy, young (n = 16) and aged (n = 188) control subjects were assayed using ELISA for human SLPI. Comparisons were made between groups with clinical diagnoses of either definite or probable pneumonia and among cases with various other respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease, and lung cancer. The mean SLPI concentration in patients with pneumonia was significantly higher than in patients without pneumonia or in healthy controls. The data suggest that the measurement of SLPI can provide a useful indicator for pneumonia to be used in clinical evaluation.

To establish a sensitive marker for bone formation we have developed a sandwich enzyme-linked immunosorbent assay for intact osteocalcin (OC) and its propeptide. Serum levels of these peptides were studied in 185 normal children, aged 4-15 yr, and in 23 GH-deficient children treated with GH. The serum levels of the propeptide in normal prepubescent children were 1.43 +/- 0.23 (mean +/- SE) micrograms/L in boys and 1.53 +/- 0.23 micrograms/L in girls. The peak value occurred at the age of 13 yr in boys (2.91 +/- 0.42 micrograms/L) and 11 yr in girls (2.34 +/- 0.34 micrograms/L). The serum intact OC levels in prepubescent boys and girls were 18.8 +/- 2.1 and 20.7 +/- 2.1 micrograms/L, respectively, and these levels increased to 41.0 +/- 3.7 micrograms/L in boys aged 13 yr and to 27.0 +/- 2.5 micrograms/L in girls aged 11 yr. In the GH-deficient patients, a 2.3-fold increase in the propeptide level and a 1.7-fold increase in the intact OC level was observed after 1 month of GH therapy. Serum propeptide and intact OC levels after 1 month of GH therapy correlated with the growth response after 12 months of GH therapy (r = 0.660 and P0.01, for propeptide; r = 0.537 and P0.01 for intact OC). These results show that since both propeptide and intact OC in serum were increased when the growth rate was elevated, these peptides are sensitive markers of bone formation. Serum levels of these peptides, particularly propeptide, after 1 month of GH therapy might be a helpful predictor of the growth response to long term GH therapy.

Object representation in the inferior temporal cortex (IT), an area of visual cortex critical for object recognition in the primate, exhibits two prominent properties: (1) objects are represented by the combined activity of columnar clusters of neurons, with each cluster representing component features or parts of objects, and (2) closely related features are continuously represented along the tangential direction of individual columnar clusters. Here we propose a learning model that reflects these properties of parts-based representation and topographic organization in a unified framework. This model is based on a nonnegative matrix factorization (NMF) basis decomposition method. NMF alone provides a parts-based representation where nonnegative inputs are approximated by additive combinations of nonnegative basis functions. Our proposed model of topographic NMF (TNMF) incorporates neighborhood connections between NMF basis functions arranged on a topographic map and attains the topographic property without losing the parts-based property of the NMF. The TNMF represents an input by multiple activity peaks to describe diverse information, whereas conventional topographic models, such as the self-organizing map (SOM), represent an input by a single activity peak in a topographic map. We demonstrate the parts-based and topographic properties of the TNMF by constructing a hierarchical model for object recognition where the TNMF is at the top tier for learning high-level object features. The TNMF showed better generalization performance over NMF for a data set of continuous view change of an image and more robustly preserving the continuity of the view change in its object representation. Comparison of the outputs of our model with actual neural responses recorded in the IT indicates that the TNMF reconstructs the neuronal responses better than the SOM, giving plausibility to the parts-based learning of the model.

The present study deals with an analysis of the selection function for mills using balls as grinding media. The grinding mechanism assumes that a particle caught by two colliding balls will be ground only if the ball impact generates or activates at least one single crack within the particle causing the fragmentation. The derived selection function becomes convex in relation to particle size on a log—log chart, which has been observed experimentally. Further, the effects of ball properties and powder and ball fillings on the selection function or the mill capacity are examined theoretically and agree reasonably well with experiment.

Clinical diagnosis for Alzheimer's disease (AD) is provided by the criteria of DSMIV and clinical progress in addition to imaging analysis with MRI after negative screening. The final exclusive diagnosis is confirmed by the neuropathological findings of neurofibrillary tangles and senile plaques in autopsy brains. We developed a new ELISA system to measure the amount of tau in cerebrospinal fluids (CSF) using phosphorylation-independent and sequence-specific antibodies. The present ELISA was sensitive enough to detect tau in CSF of normal subjects. The amount of tau was significantly elevated in CSF of AD subjects compared with those of normal subjects and subjects with dementia of cerebrovascular disease, suggesting that tau in CSF reflects the massive and continuous neuronal cell death in the AD brain. In conclusion, we established an ELISA system which enabled us to detect tau in CSF and demonstrated that tau was significantly and specifically elevated in CSF of AD subjects. This assay system can provide us with a potent diagnostic tool for clinical AD.

The levels of α1-antichymotrypsin (ACT) in cerebrospinal fluid (CSF) from 66 sporadic Alzheimer's disease (AD) patients and 54 normal controls were measured by enzyme immunoassay and compared. There was no correlation (r=0.259, n=54) between the ACT level and normal aging. The levels of ACT were significantly higher in the total AD group (p

A technique for the rapid detection of cytomegalovirus (CMV) antigen-positive blood leucocytes (CMV antigenaemia) was evaluated in 15 marrow transplant patients as a means of diagnosis and for monitoring CMV-associated disease. CMV antigenaemia was determined by direct immunoperoxidase staining of leucocytes with a peroxidase-labelled monoclonal antibody, HRP-C7, which binds an immediate-early antigen of human CMV. CMV antigenaemia occurred in 7/15 marrow transplant patients (47%) and was initially detected between 4 and 6 weeks after transplantation. CMV-associated diseases developed in 3/15 patients (20%). All patients with CMV-associated disease had a relatively large number of CMV antigen-positive leucocytes, exceeding 10 per 50,000 white blood cells (WBCs). In the remaining 12 patients, CMV antigen-positive leucocytes were less than 10 per 50,000 WBCs or were undetectable. CMV-associated disease did not develop in these patients during the period of monitoring. CMV antigen-positive leucocytes were detected more frequently in patients who developed acute graft-versus-host disease (GVHD) or haemorrhagic cystitis than in those without such complications. CMV antigens were detectable from 1 to 4 weeks before the onset of CMV-associated disease which allowed initiation of ganciclovir treatment at an early stage. The degree of CMV antigenaemia paralleled the clinical symptoms and signs, higher degrees of antigenaemia being associated with more significant disease. Thus, the detection of CMV antigen-positive blood leucocytes is useful for the diagnosis and monitoring of CMV-associated disease following bone marrow transplantation.

The human placental form of glutathione S-transferase pi (GST-pi) was measured by a sandwich enzyme-linked immunosorbent assay in lung cancer cell lines established in our laboratories. In classic-type small cell lung cancer (SCLC), variant-type SCLC and non-small cell lung cancer (NSCLC), the respective mean GST-pi values were 0.83 +/- 0.88, 3.27 +/- 2.85 and 2.40 +/- 0.76 micrograms/mg protein. Cell lines with high GST-pi content had low levels of neuron specific enolase, which is known as a representative tumor marker for SCLC. This suggests that GST-pi may also be used as a potential marker for NSCLC. The lines with low GST-pi content were more sensitive to radiation than those with high GST-pi content. Cell lines not subjected to prior therapy also showed a good correlation between GST-pi levels and chemosensitivity to cisplatin. The findings suggest that GST-pi can be used as an adjunctive marker for lung cancer.

Based upon a simplified grinding mechanism, an analysis of the selection function is made for vibration mills. The mechanism considered is that a particle nipped by two colliding balls is to be ground only if the ball impact generates or activates at least one crack within the particle and the crack is big enough for fragmentation. The derived selection function increases with increasing size up to a certain value and then decreases with increasing particle size. This trend has been observed elsewhere by experiment. Also, the present paper examines the effects of the ball on the selection function.

Background Massive gastrointestinal bleeding in children, mostly caused by esophageal varices secondary to chronic liver disease, is uncommon. Dieulafoy lesion in the gastrointestinal tract is a rare but important cause of gastrointestinal bleeding; massive bleeding from this lesion can be fatal unless adequate treatment is promptly initiated. We report a case of gastric Dieulafoy lesion in a 2-year old successfully treated with endoscopic hemoclipping. Case presentation A 2-year-old Japanese boy was admitted to our department with sudden massive hematemesis. He had no significant past medical illness, and he was well just before the episode of hematemesis. A clinical examination revealed anemia (hemoglobin, 8.0 g/dl). The rapidly progressive anemia associated with massive hematemesis indicated the presence of an active bleeding in his upper gastrointestinal tract. We performed emergency gastroscopy under general anesthesia. The gastroscopy revealed the presence of an abnormal visible vessel with an adherent clot on the lower body of his stomach. No mucosal abnormality surrounding the lesion was noted; the lesion was thus diagnosed as Dieulafoy lesion. One hemostatic clip was placed on the Dieulafoy lesion and excellent hemostasis was obtained. He recovered without blood transfusion and was discharged 4 days post-endoscopy. He has recovered well with no recurrence of hematemesis. Conclusions Dieulafoy lesion is rare cause of sudden massive gastrointestinal bleeding in children. Nevertheless, it should be considered a differential diagnosis, even in babies. With advances in gastrointestinal endoscopy, as both a diagnostic and therapeutic modality, laparotomy secondary to gastrointestinal bleeding from Dieulafoy lesion has decreased in pediatric cases. Our case report demonstrates the feasibility of endoscopic hemoclipping for gastric Dieulafoy lesion in a child.