Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer.

BACKGROUND: Mesothelin is expressed in various types of malignant tumour, and we recently reported that expression of mesothelin was related to an unfavourable patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined the clinicopathological significance of the mesothelin expression in gastric cancer, especially in terms of its association with the staining pattern. METHODS: Tissue specimens from 110 gastric cancer patients were immunohistochemically examined. The staining proportion and intensity of mesothelin expression in tumour cells were analysed, and the localisation of mesothelin was classified into luminal membrane and/or cytoplasmic expression. RESULTS: Mesothelin was positive in 49 cases, and the incidence of mesothelin expression was correlated with lymph-node metastasis. Furthermore, luminal membrane staining of mesothelin was identified in 16 cases, and the incidence of luminal membrane expression was also correlated with pT factor, pStage, lymphatic permeation, blood vessel permeation, recurrence, and poor patient outcome. Multivariate analysis showed that luminal membrane expression of mesothelin was an independent predictor of overall patient survival. CONCLUSION: We described that the luminal membrane expression of mesothelin was a reliable prognostic factor in gastric cancer, suggesting the functional significance of membrane-localised mesothelin in the aggressive behaviour of gastric cancer cells.

[Development of retrieval system about clinical laboratory handbook "Kensa Koujien"].

Medical knowledge has been increasing and diversifying on a worldwide scale, while specialization of physicians has been extended vigorously. The knowledge has extended beyond the memory of human beings, there by causing the deterioration of service, called "Knowledge crisis". To tackle this problem, the electronic medical textbook(EMT) has been conceived and set up as a medical knowledge base for physician to optimize their specialties and activities in clinical practice. The doctors' diagnostic process is to be mentioned as the solution of backward problem, to speculate problem such as disease by the information observed from symptoms and findings. The EMT is more powerful tool for diagnosis than experiences or textbook that will aid for specifying the name of disease by arranging and combining information. Meanwhile, laboratory information systems are widely introduced. However, there are few systems which allow interpretation of the findings obtained. With this in mind, we have improved the utility of the EMT by enhancing its function with laboratory information follow-up, thesaurus back-up, Japanese language support, and on-line access. It made use of these experiences, we compiled an clinical laboratory handbook "Kensa Koujien", and developed retrieval system.

MERIT-9: a patient information exchange guideline using MML, HL7 and DICOM.

To realize clinical data exchange between healthcare providers, there must be many standards in many layers. Terms and codes should be standardized, syntax to wrap the data must be mutually parsable, then transfer protocol or exchange media should be agreed. Among many standards for the syntax, HL7 and DICOM are most successful. However, everything could not be handled by HL7 solely. DICOM is good for radiology images, but, other clinical images are already handled by other 'lighter' data formats like JPEG, TIFF. So, it is not realistic to use only one standard for every area of clinical information. For description of medical records, especially for narrative information, an standard generalized mark-up language, document type definition (SGML DTD) for medical information, called MML (medical markup language) had been created in Japan. It is already implemented in more than ten healthcare providers. However, it is again not realistic to use MML solely for clinical information in various level of detail. Therefore, we proposed a guideline for use of available medical standards to facilitate clinical information exchange between healthcare providers. It is called MERIT-9 (Medical Records, Images, Texts, -Information Exchange). A typical use is HL7 messages, DICOM files, referred from an MML file in a patient record, as external entities. Both MML and MERIT-9 have been research projects of Japanese Ministry of Health and Welfare and the purpose is to facilitate clinical data exchanges. They are becoming to be used in technical specifications for new hospital information systems in Japan.

Patient information exchange guideline MERIT-9 using medical markup language MML.

To realize clinical data exchange between healthcare providers, there must be many standards in many layers. Terms and codes should be standardized, syntax to wrap the data must be mutually parsable, then transfer protocol or exchange media should be agreed. Among many standards for the syntax, HL7 and DICOM are most successful. However, everything could not be handled by HL7 solely. DICOM is good for radiology images, but, other clinical images are already handled by other "lighter" data formats like JPEG, TIFF. So, it is not realistic to use only one standard for every area of clinical information. For description of medical records, especially for narrative information, we created SGML DTD for medical information, called MML (Medical Markup Language). It is already implemented in more than 10 healthcare providers in Japan. As it is a hierarchical description of information, it is easily used as a basis of object request brokering. It is again not realistic to use MML solely for clinical information in various level of detail. Therefore, we proposed a guide-line for use of available medical standards to facilitate clinical information exchange between healthcare providers. It is called MERIT-9 (MEdical Records, Images, Texts,--Information eXchange). A typical use is HL7 files, DICOM files, referred from an MML file in a patient record, as external entities. Both MML and MERIT-9 are research projects of Japanese Ministry of Health and Welfare, and the purpose is to facilitate clinical data exchanges. They are becoming to be used in technical specifications for new hospital information systems in Japan.

Computer-aided clinical laboratory diagnosis in conjunction with the electronic medical textbook.

1. INTRODUCTION. Medical knowledge has been increasing and diversifying on a worldwide scale, while the specialization of physicians has been extended vigorously. Under this environment, it may be natural that mistakes are made in a comprehensive diagnosis, as the physician cannot master all of this dramatically increasing volume of knowledge. The knowledge has extended beyond the memory of human beings, thereby causing the deterioration of service; this is called the "Knowledge crisis." To tackle this problem, the Electronic Medical Textbook (EMT) has been conceived and set up as a medical knowledge base for physicians to optimize both their specialties and activities in clinical practice. Meanwhile, laboratory information systems were widely introduced. However, there are few systems which allow interpretation of the findings obtained. With this in mind, we have improved the utility of the EMT by enhancing its function with laboratory information follow-up, thesaurus back-up, Japanese language support, and online access. 2. SYSTEM DESCRIPTION. The knowledge database for medical decision-making consists of three categories: 1) Medical domain knowledge (including approximately 3500 diseases) from the AMA's "The Current Medical Information & Terminology (CMIT)"; 2) Knowledge on relationship between laboratory testing results and diseases from "The Effects of Disease on Clinical Laboratory," compiled by the AACC; and 3) Clinical testing knowledge from Otsuka's laboratory test handbook "Kensa-Kojien." These categories are connected by links in the process of cross-reference. In actual use, the first is to select the supporting system bringing up clinical signs and findings on CRT from which users can then choose any representations corresponding to the patient's clinical state. Once the relevant objects have been selected, the system presents the correlated investigative tests to be performed, along with a scope of laboratory tests ordering for its initial investigative task. The required tests against the data objects denoted by "High," "Low," or "Abnormal" are linked to possible diagnoses, which appear on CRT in order of likelihood. Similarly, the possible diagnoses can be obtained directly by consulting the patient's laboratory test results in linkage, by way of automated data transformation into the corresponding data object using the reference interval. If necessary, additional information relative to clinical signs can be added. With the repetition of this procedure, clinically useful tests can be located, thus increasing the likelihood of an appropriate diagnosis. The proposed diseases can be confirmed through cross-reference to the patient's clinical signs from the description in the Textbook on CRT. In order to bolster the efficiency of cross-checking on CRT, the sentences including hit-words are highlighted in red. Moreover, with regard to specific keywords for disease, those sentences are highlighted in green to emphasize differences in between. In parallel, the description points out an active behavior of laboratory test results in the progression of the disease and is also able to display applicable laboratory test listings. Furthermore, this knowledge-based interpretation system is directly accessible via online network services in referring to laboratory test results. 3. CONCLUSION. A combination of the CMIT and laboratory diagnostic information in the knowledge database allows the narrowing down of proposed diagnoses due to its flexible approach, which depends not only on clinical signs and findings, but also on applicable test-ordering support and suggestions. This enhances the potential usefulness of the EMT. The system contributes to the support of the diagnostic procedures and assists in educational setting, because the process can be operated in reverse based on clinical signs and laboratory findings in a dialogue style on CRT. The related disease description highlighted in color has won a good reputation dur

Discrepancy of xenon concentrations between end-tidal and blood collection methods in xenon-enhanced computed tomographic measurements of cerebral blood flow.

Using xenon-enhanced computed tomography for the study of cerebral blood flow, simultaneous measurements of end-tidal and arterial blood xenon concentrations using the blood collection method were performed to investigate the validity of substituting the end-tidal for the arterial blood xenon concentration. Simultaneous measurement by both methods was performed 68 times in 27 patients. There was no statistical correlation between the arterial blood accumulation rate constant obtained by arterial blood and end-tidal samples, nor between the arterial blood saturation value obtained by the two methods, even when correction was made for age. In brain tissue, all parameters calculated using the end-tidal concentration were lower than those using arterial blood. We therefore suggest that cerebral blood flow values calculated using end-tidal xenon concentration are useful only for qualitative cerebral blood flow mapping, and not applicable to absolute values of cerebral blood flow.

Functional imaging of cerebral blood volume using simultaneous measurements of dynamic and xenon computerized tomography (CT).

This report describes a method for measuring regional cerebral blood volume (r-CBV), by simultaneously using dynamic computerized tomography (DCT) and stable Xenon-enhanced CT (Xe CT). Local cerebral blood flow (CBF) was measured using a Xe CT blood sampling method, and mean transit time (MTT) was calculated using DCT after a rapid injection of iodinated contrast material. A functional image of r-CBV was obtained from multiplication of CBF and MTT on each pixel using the formula: CBF x MTT = CBV. This calculated value is not suitable to indicate a r-CBV which directly reflects cerebral microcirculation. Accordingly, only a comparative estimation of relative r-CBV images is applicable. However, laterality of image and comparison of serial studies are useful in hemodynamic evaluations, especially in ischemic cerebrovascular diseases, because they indicate hemodynamic reserve within the hypoperfused region.

[Study on the radiation effects toward function and vessels of parotid gland in rat].

The effect of irradiation on the parotid gland was determined from 99mTc-pertechnetate (99mTcO4-) uptake and the course of vessels in the parotid gland, by investigating the uptake and excretion of 99mTcO4- in 60Co-gamma ray-irradiated rat parotid gland and ovserving the course of blood vessels and the histological changes. 1. In the uptake test, radiation activity of 99mTcO4- taken into the parotid gland per unit weight was the highest three days after irradiation for both 10 Gy (1.68 x 10(5)cpm/g) and 50 Gy (2.05 x 10(5)cpm/g); however, it began to decrease gradually at 7 days after irradiation. 2. In the clearance test, as in the uptake test, the radiation activity of 99mTcO4- per unit weight remaining in the parotid gland after stimulation of secretion, was high at 3 days after irradiation for both 10 Gy and 50 Gy (0.86 x 10(5), 1.28 x 10(5)cpm/g, respectively) and 7 days (0.88 x 10(5), 1.29 x 10(5)cpm/g) after irradiation, and gradually decreasing thereafter. 3. Stimulation-secretion coefficients determined from the ratio of uptake and clearance of 99mTcO4- were lower in all groups with irradiation than in the group without irradiation, with especially low values at 7 and 14 days after radiation. Thus, parotid function declined after irradiation. 4. With respect to the effect of irradiation on blood vessels, mild dilation was observed at 10 Gy at 3 and 7 days after irradiation, then constriction and meandering were noticed. Such changes were greater at 50 Gy than at 10 Gy. 5. Histological changes appeared 6h after irradiation in the 10 Gy- and 50 Gy-irradiation groups. Derangement of cells in the terminal parts, dilation of conduits, and proliferation of connective tissue were observed from 3 days after irradiation. 6. The periodic aid-Schiff (PAS) reaction was decreased in the 10 Gy- and 50 Gy-irradiation groups, with few PAS-positive cells at 28 days after irradiation. In conclusion, the decline in parotid function after 10 Gy- and 50 Gy-irradiation was related to histological changes in the vascular system and glandular tissues.

A study of two kinds of thermoluminescent dosimeters; CaF2:Tm and CaSO4:Dy in LiF.

We studied two kinds of thermoluminescent dosimeters using 60Co gamma rays. In CaF2:Tm, the intensity of the glow curve integral as a function of dose increased linearly; the dose response curve of the main peak (at 165 degrees C) was sublinear and that of the high temperature peak (at 220 degrees C) was supralinear. In CaSO4:DY in LiF, the main peak (at 215 degrees C) and the glow curve integral as a function of dose were linear; the low temperature peak (at 170 degrees C) was sublinear. The relative responses of CaF2:Tm and CaSO4:Dy in LiF were greater than that of LiF (TLD-100) by a factor of about 11 and 4, respectively. In CaF2:Tm, the high temperature peak was very stable, but the main peak faded away with post-irradiation storage time. For CaSO4:Dy in LiF, the main peak was very stable and the low temperature peak was relatively stable. Based on the glow curve integral, we determined that the fading of CaF2:Tm and CaSO4:DY in LiF was 36 and 38%, respectively, for a month.

Biosynthesis of rat kidney catalase. Double-labeling by [14C]leucine and delta-amino[3H]levulinic acid.

Kidney catalase [EC 1.11.1.6] was doubly labeled by injecting a mixture of [14C]-leucine and delta-amino[3H]levulinic acid (ALA) into normal and allyliso-(2-isopropyl-4-pentenoyl)urea (Sedormid)-treated rats. Shortly after the injection of a tracer dose or the precursors, catalase in microsomes showed the highest specific radioactivities among catalases from various cell fractions. On the other hand, peroxisomal catalase was labeled gradually, reaching a plateau at about 90 min. The patterns of incorporation of both isotopes were similar to those obtained previously with rat live catalase, except that the 3H-radioactivities were much higher. From the results obtained it could be postulated that kidney catalase is synthesized on polysomes and then transferred to peroxisomes, directly or via the soluble phase. The ratio of 3H/14C incorporated was lowest in microsomal catalase, highest in microsomal catalase, highest in peroxisomal enzyme and intermediate in catalase of the soluble fraction. The increment with time was large in the latter two catalases, while the former showed a rather small change. The evidence suggests that nascent catalase contains less heme than the completed molecule; further addition of heme to this intermediate seems to occur in the cytosol, and possibly also in peroxisomes. Administration of a porphyrinogenic drug, (2-isopropyl-4-pentenoyl)urea, produced a remarkable decrease in the incorporation of [3H]ALA into kidney catalase, with no significant effect on that of [14C]leucine.

Biosynthesis of liver catalase in rats treated with allylisopropylacetylcarbamide. I. Immunochemical assay of catalase in liver cell fractions.

Rats were injected twice intraperitoneally with 20 mg of allylisopropylacetylcarbamide (Sedormid) per 100 g of body weight at an interval of 12 hr. The level of catalase [EC 1.11.1.6] in various liver cell fractions was determined both enzymatically and immunochemically 12 hr after the second injection. 1. The decrease in catalase protein assayed by the immunochemical method directly confirmed the inhibition of biosynthesis of the enzyme by this porphyrinogenic drug. 2. The occurrence of a considerable amount of catalase protein with no enzymatic activity was demonstrated both in the peroxisomes and in the supernatant fraction. 3. The amount of catalase-synthesizing polysomes in hepatic cell was reduced in Sedormid-treated rats by the extent comparable to the decrease in the concentration of liver catalase.

Biosynthesis of liver catalase in rats treated with allylisopropylacetylcarbamide. II. Double-labeling of catalase with (14C)leucine and delta-(3H)aminolevulinic acid.

Double-labeling of liver catalase [EC 1.11.1.6] with [14-c]leucine and delta-[3H]aminolevulinic acid was carried out both in vivo and in vitro using rats treated with allylisopropylacetylcarbamide (Sedormid). These radioactive precursors were incorporated into catalase at a lower rate than in normal rats. In particular, the incorporation of 3H was remarkably inhibited. The results suggest that the administration of Sedormid can inhibit synthesis of the protein moiety of catalase, and possibly interfere with the binding of heme to the catalase protein.