A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study.

Few biomarkers have been known that can easily measure clinical conditions in mental illnesses such as schizophrenia. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) is a new method that can measure ionized and low-molecular-weight metabolites. To explore global metabolomic alterations that characterize the onset of schizophrenia and identify biomarkers, we profiled the relative and absolute concentrations of the plasma metabolites from 30 patients with first-episode schizophrenia (FESZ, four drug-naïve samples), 38 healthy controls and 15 individuals with autism spectrum disorders using CE-TOFMS. Five metabolites had robust changes (increased creatine and decreased betaine, nonanoic acid, benzoic acid and perillic acid) in two independent sample sets. Altered levels of these metabolites are consistent with well-known hypotheses regarding abnormalities of the homocysteine metabolism, creatine kinase-emia and oxidative stress. Although it should be considered that most patients with FESZ received medication, these metabolites are candidate biomarkers to improve the determination of diagnosis, severity and clinical stages, especially for FESZ.

Velocity pulse advances pressure pulse by close to 45 degrees in the rat pial arterioles.

In order to clarify the phase relationship between velocity pulse and pressure pulse propagating along microvessels, the red cell velocity and intravascular pressure were simultaneously measured in the rat pial arterioles of 41-53 microm in diameter with a high temporal resolution by a laser-Doppler anemometer and a servo-null micropressure system. It was found that the velocity pulse preceded the pressure pulse in all the measured arterioles by 18.7-35.6 ms. The corresponding phase difference was 43.6+/-6.9 degrees (mean +/- SD), which is not statistically different from 45 degrees. The value is consistent with the phase difference predicted for the blood flow in microvessels with a small reflection coefficient at frequencies as low as the heart rate of the rats. The present results suggest that the upstream changes in blood flow are transmitted by the velocity pulse faster than by the pressure pulse in the microvasculature.

Building a controlled health vocabulary in Japanese.

OBJECTIVES: This study is aimed at developing a controlled clinical vocabulary for use in electronic patient record (EPR) systems. METHODS: In this paper, we propose a model for building the vocabulary. The model is composed of a Canonical Term Dictionary, an Atom Dictionary, a Composite Atom Dictionary, and an Index. Parsing and composing functions are included in this model. Canonical terms were extracted from reference terminologies. Atoms were extracted from the Canonical Term Dictionary and reduced to a set from which the Composite Atom Dictionary can be built. The index was built to link these two dictionaries. For testing the model, we compiled a sample vocabulary and applied the model to a SNOMED translation system (English to Japanese) and a term similarity estimation system. RESULTS: The sample vocabulary consisted of 15,600 atomic terms and 4,450 composite terms. 33,441 SNOMED terms were translated by the SNOMED translation system. The system gave adequate Japanese candidates in 56.3% of cases. The similarity estimation system found an average of 5.4 candidates when the equality ratio was over 50%. CONCLUSIONS: The trial applications produced good results. The model seems promising for building a standard clinical vocabulary system. This system can be applied in certain other Asian countries, such as China and Korea.

Clinical management of intraductal papillary mucinous tumors of the pancreas based on imaging findings.

The aim of this study was to assess the imaging findings of pathologically proven intraductal papillary-mucinous tumors of the pancreas and the natural history of follow-up cases, and to optimize the therapeutic management of patients with these tumors according to their imaging findings. All nine patients with main duct type tumors were histologically diagnosed as having adenocarcinoma or adenoma, with no hyperplastic lesion. The images failed to discriminate between the two histologic types. In 26 patients with branch duct type tumors, all but one with intraductal mural nodules or tumors of > or = 30 mm had adenocarcinoma or adenoma, regardless of the caliber of the main duct. Of the nine patients with tumors < 30 mm and no mural nodules. three had adenoma, and six had hyperplasia. All of four patients had hyperplasia, with the additional caliber of the main duct being < 6 mm. In a series of 23 cases in which the patient was followed-up, no apparent progression was found in 17 patients who had no mural nodules and tumors of < 30 mm. Given these results, patients with main duct type tumors, and those with branch duct type tumors showing mural nodules or a tumor diameter of > or = 30 mm, are at high risk of developing neoplasms, including adenocarcinoma, for which surgical resection should be considered, whereas those patients with tumors < 30 mm and no mural nodules can be followed.

Apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative administration of 5-fluorouracil.

The purpose of this study was to examine the correlations among enhancement of apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative oral administration of 5-fluorouracil (5-FU). The occurrence of spontaneous apoptotic cell death in 42 patients with gastric carcinoma was analyzed in the biopsy specimens preoperatively. p53 status was examined by polymerase chain reaction-single strand confirmation polymorphism and sequencing. Fourteen patients received oral administration of 5-FU at 300 mg/body/day for 7 days preoperatively. For detection of apoptotic cells, apoptotic incidences (AIs) were examined by the terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate biotin nick end labeling method, on gastric carcinoma lesions based on the endoscopic findings before administration in the biopsy and resected tissues. Expressions of p53, Bcl-2, Bax gene and proliferating cell nuclear antigen (PCNA) were also examined by immunohistochemical staining. On preoperative biopsy, p53 point mutation was observed in 14 of the 42 tumors. The immunohistochemical staining status and point mutation of p53 gene (positive or negative) were identical in 32 of the 42 tumors (76.2%). The average AIs of the biopsy specimens were 1.58+/-1.26% on p53-negative staining (n=19) and 1.14+/-1.02% on p53-positive staining (n=23), a significant association was not recognized between p53 expression and AI. In the preoperative administration group, the PCNA labeling index was significantly higher in the biopsy specimens than in the resected tissues (43. 6+/-12.8% vs. 35.3+/-8.8%, p<0.01). In addition, postoperatively, the rate of AI was significantly more accelerated in p53-negative staining (n=6) than in p53-positive staining (n=8) (0.89+/-0. 65%right curved arrow 4.18+/-3.26%, p<0.05 vs. 1.20+/-0.60%right curved arrow 2.60+/-2.60%, NS). There was no significant correlation between AI and Bcl-2 or Bax staining. Immunohistochemical analysis of p53 and PCNA stainings in biopsy specimens appears to be a well-characterized indicator of sensitivity of chemotherapy in gastric carcinomas.

Standard method for describing an electronic patient record template: application of XML to share domain knowledge.

A Template Definition Language (TDL) was developed to share knowledge of how to construct an electronic patient record (EPR) template. Based on the extensible markup language XML, TDL has been designed to be independent of EPR platforms or databases. Our research of TDL was conducted through evaluation of the description of various templates in the currently available EPRs and through comparisons with some electronic clinical guidelines. We conclude that TDL is sufficient for the objective but still needs improvement of the algorithm for describing dynamic changes.

Serum levels of pancreatitis-associated protein in digestive diseases with special reference to gastrointestinal cancers.

The serum levels of pancreatitis-associated protein (PAP) were measured in 196 patients with digestive diseases and 15 healthy subjects by an enzyme-linked immunosorbent assay. The serum PAP levels were significantly elevated in the patients with gastric, colorectal, biliary tract, hepatocellular, or pancreatic cancers compared with the healthy subjects. After curative resection of the tumor, serum PAP levels were significantly decreased. The serum PAP levels were not related to clinicopathological factors except for the tumor size of pancreatic cancer. There were some cases of PAP-positive and carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9 -negative gastric and colorectal cancers. The serum PAP levels were also significantly elevated in the patients with acute pancreatitis compared with those in not only the healthy subjects but also the patients with chronic pancreatitis. The peak PAP levels were significantly correlated with the severity of acute pancreatitis and reflected the clinical healing of the disease. The peak of serum PAP was significantly delayed compared with those of other pancreatic enzymes. These results suggest that the increase of serum PAP levels in patients with gastrointestinal cancers reflects an ectopic expression of PAP in cancer cells and that increased serum levels of PAP in acute pancreatitis are correlated with the disease severity and are prolonged than those of other pancreatic markers.

Computer-assisted instructions for patients with bronchial asthma.

We produced computer-assisted instruction (CAI) software for bronchial asthma patients (asthma educational system with computer-assisted instruction; ASTCAI) to assist in self-management and avoid asthmatic attacks and death. ASTCAI is a question-and-answer program operating in a multimedia environment, and was evaluated from questionnaires which 33 patients were asked. Thirty-two patients could perform ASTCAI without any assistance. The responses of 31 patients (94%) indicated that they had no difficulty with manipulation, and 29 patients (88%) stated that the program was beneficial to control of their asthma. Elderly patients (over 65) required more time than younger adults. Emergency visits or admissions of at least 1 year after the first CAI trial decreased in eight out of 26 patients, while only two patients deteriorated compared to the previous year. Our results show that CAI is feasible for most patients, and through active self-learning CAI can improve motivation for self-management as well as supplement the physician's instructions.

Standardizations of clinical laboratory examinations in Japan.

In this paper we introduce Japanese activities concerning laboratory examinations by illustrating three major categories. The first is the contribution of JCCLS to ISO/TC212 clinical laboratory testing and in vitro diagnostic test systems, with NCCLS and CEN TC140. The second is the establishment and promotion of JLAC Classification and Coding for Clinical Laboratory Tests by The Japan Society of Clinical Pathology. The third is a clinical data exchange format between healthcare facilities using MML/MERIT-9 standard, started as a Ministry research project.

Urinary gonadotropin peptide in patients with cancer of digestive organs.

Urinary gonadotropin peptide (UGP) has been measured in gynecological and urological cancers, but its usefulness in the diagnosis of cancers of digestive organs has not been investigated. In this report, UGP was measured by sandwich enzyme immunoassay in 311 patients, including 166 patients with cancers of digestive organs and 43 healthy controls. Positive rates of UGP in various cancers of digestive organs were as follows: biliary tract 61.5%, pancreas 61.5%, esophagus 50.0%, liver 38.7%, colon and rectum 24.2%, and stomach 23.9%. The positive rate of UGP in benign diseases was 8.1%, and most false-positive patients were postmenopausal females. Positive rates of UGP were increased at advanced stages of gastric cancers, and UGP was decreased after tumor resection. From these results, it is suggested that UGP can be used as a tumor marker for the cancers of digestive organs.

Detection of K-ras point mutations at codon 12 in pancreatic juice for the diagnosis of pancreatic cancer by hybridization protection assay: a simple method for the determination of the types of point mutation.

The present study was undertaken to detect K-ras oncogene point mutations at codon 12 in pure pancreatic juice (PPJ) by the hybridization protection assay (HPA) method for the diagnosis of pancreatic cancer (PC). This assay can be carried out within 30 min and can determine not only the presence of a mutation, but also the mutational type of K-ras at codon 12. The minimal ratio of mutant DNA detectable by the HPA was 5-10% of the total DNA. PPJ was collected through a cannula under duodenal fiberscope control from 20 patients with PC and 20 patients with chronic pancreatitis (CP). Analysis of PPJ by the HPA revealed that the incidence of K-ras point mutations at codon 12 was 55% (11/20) in patients with PC and 0% (0/20) in those with CP. Mutational types of K-ras at codon 12 in PC were aspartic acid (Asp) in nine cases, both Asp and cysteine in one case, and arginine in one case. Analysis of K-ras point mutations at codon 12 in PPJ using the HPA method seems promising as a new genetic test for the diagnosis of PC, because the HPA method is simple, and can easily determine the mutational type.

Prospective assessment of donor blood screening for antibody to hepatitis C virus by first- and second-generation assays as a means of preventing posttransfusion hepatitis.

In November 1989, the Japanese Red Cross began screening blood donors for the hepatitis C virus antibody (anti-HCV) by first-generation assay and high-titer hepatitis B virus core antigen antibody. A significant reduction in the incidence of acute posttransfusion hepatitis was reported; however, the incidence still ranged from 2 percent to 4 percent. The Red Cross changed to the second-generation assay in February 1992, the objective being the complete elimination of potential posttransfusion hepatitis. The aim was to elucidate the advantage of second-generation assay as a blood-donor screening test. The incidence of posttransfusion hepatitis after the introduction of second-generation assay was compared with that before the introduction of the first-generation assay and with that during its use. The incidence of posttransfusion hepatitis was 9.6 percent (216/2,240) before anti-HCV-s donor screening. It was 3.7 percent (24/655) and 0.9 percent (3/326) after the introductions of the first- and second-generation hepatitis C virus (HCV) assays, respectively (chi (2) = 50.0, P < .01). Blood-donor screening by second-generation anti-HCV provided a significant benefit compared with the first-generation assay.

Detection of K-ras point mutations at codon 12 in pure pancreatic juice for the diagnosis of pancreatic cancer by PCR-RFLP analysis.

The present study was undertaken to detect K-ras point mutations at codon 12 in pure pancreatic juice (PPJ) for the diagnosis of pancreatic cancer (PC) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. PPJ was collected through a cannula under a duodenal fiberscope from 26 patients with PC and 32 patients with chronic pancreatitis (CP). DNA was extracted from PPJ and was used as the template for PCR. Analysis of PPJ by PCR-RFLP with BstNI revealed that the incidence of K-ras point mutations at codon 12 was 81% (21/26) in patients with PC and 6% (2/32) in those with CP. With reference to the location of PC, the incidence of K-ras mutations was 79% (11/14) in the head, 86% (6/7) in the body, and 80% (4/5) in the tail of the pancreas. The incidence of K-ras mutants was 50% (1/2) in tumor size 1 (TS1; < or = 2.0 cm in size), 71% (5/7) in TS2 (2.1 to < or = 4.0 cm), 89% (8/9) in TS3 (4.1 to < or = 6.0 cm), and 88% (7/8) in TS4 (> 6.1 cm). These results suggested that analysis of K-ras point mutations at codon 12 in PPJ using the PCR-RFLP method is a promising new genetic test for the diagnosis of PC.

Measurement of serum PSP/reg-protein concentration in various diseases with a newly developed enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay, based on two monoclonal antibodies (Hreg1-1 and Hreg101-1) specific for pancreatic stone protein (PSP)/reg-protein, was developed to determine the concentration of this protein in serum from individuals with various diseases. The serum concentration of PSP/reg-protein was significantly higher in patients with various pancreatic diseases than in normal controls, and was also significantly higher in patients with acute pancreatitis or chronic relapsing pancreatitis than in patients with chronic pancreatitis. Furthermore, the serum PSP/reg-protein concentration was also significantly increased in liver cirrhosis, choledocholithiasis, and various cancers of the digestive system, and was extremely high in all patients tested with chronic renal failure. A significant correlation was apparent between the serum concentration of PSP/reg-protein and elastase-I in 68 patients with chronic pancreatitis or pancreatic cancer. Whereas only 7 of these patients showed a normal serum PSP/reg-protein concentration and a significantly increased elastase-I concentration, 15 of these patients showed a significantly increased serum PSP/reg-protein concentration and a normal serum elastase-I concentration. These results indicate that the serum PSP/reg-protein concentration may reflect pancreatic damage, especially in acute pancreatitis, and may be a sensitive a marker for such damage as elastase-1, although false positivity was apparent in renal failure and in some patients with hepatic dysfunction or digestive system malignancies.