Detection and characterization of gastric carcinoma associated with epstein-barr herpes virus

The present investigation was carried out to estimate the incidence of Epstein-Barr virus (EBV)-associated cases among gastric carcinoma (GC) patients in Russia. Carcinoma specimens from 184 patients with GC treated at the Cancer Research Center were investigated by EBV encoded RNA-1 (EBER-1) in situ hybridization. Seventeen (9.24%) cases showed uniform EBER-1 expression restricted to the carcinoma cells. Hybridized signals were not detected in the non-neoplastic gastric epithelium. EBV involvement was significantly more frequent among males, especially in the tumors belonging to less differentiated types (moderately differentiated tubular adenocarcinomas and poorly differentiated solid adenocarcinomas) and located in the upper stomach (cardia and middle part). Most EBV-positive GCs were characterized by great lymphoid compartment involvement. The findings of the distribution of EBV-positive. GCs by sex, site, and histology are similar to those in Japan; however, the detection rate of EBV-positive cases in Russia is higher than that in Japan (6.7%) and lower than that in the USA (16%).     

Cleavage of integrin by mu-calpain during hypoxia in human endometrial cells

PROBLEM: The distribution and activation of mu-calpain and possible cleavage of integrin in human endometrial cells under hypoxic condition were investigated. METHOD OF STUDY: Human endometrial epithelial and stromal cells were subjected to hypoxia, and subsequently used for immunostaining and western blot analysis. RESULTS: The proform of mu-calpain was detected in the cytoplasm of normal cells, and displayed a substantial decrease after hypoxia. Conversely, the active form of mu-calpain was not detected in normal cells, but was abundant after hypoxia. The cytoplasmic domain of integrin beta3 was also detected in the cytoplasm of endometrial cells. Western blot analysis confirmed that both the proform of mu-calpain and the integrin beta3 cytoplasmic domain decreased during hypoxia. CONCLUSIONS: Mu-calpain is activated in human endometrial cells during hypoxia and that subsequent cleavage of the integrin beta3 cytoplasmic domain may give some adverse effects to the function of human endometrium.     

Lung adenocarcinoma with bronchioloalveolar carcinoma component is frequently associated with foci of high-grade atypical adenomatous hyperplasia

We assessed the occurrence of atypical adenomatous hyperplasia (AAH) in whole lung lobes with primary cancer lesions. Following surgical resection, tissue specimens were sliced to a thickness of 4 mm (3,641 specimens from 61 cases; mean = 59.7 specimens per case). A total of 119 AAH foci were found and an association was evident in 25 (57%) of 44 adenocarcinomas, 3 (30%) of 10 squamous cell carcinomas, and 2 (29%) of 7 other lung cancers. Histologic evaluation showed that 108 AAH foci were categorized as low-grade and the other 11 as high-grade AAH. These 11 foci of high-grade AAH were present in 7 patients with adenocarcinoma, and in 1 patient there was a synchronous double primary lung adenocarcinoma. High-grade AAH was closely associated with bronchioloalveolar carcinoma (BAC) type adenocarcinoma, and low-grade AAH with non-BAC adenocarcinoma. The mean +/- SD Ki-67 labeling index in high-grade AAH (3.5%+/-2.9%) was significantly higher than for the low-grade index (1.4%+/-1.6%). We propose that foci of high- but not low-grade AAH may be potential precursor lesions of lung adenocarcinoma, especially with the BAC component.     

HLA class I distribution in Japanese patients with schizophrenia

Several Caucasian studies and one Japanese study have observed associations between human leukocyte antigen (HLA) class I specificities, including A24 (9) and A26 (10) and schizophrenia. Most of those studies were conducted in 1970s and early 1980s, when the typing technique of HLA was not adequately reliable. Also, an operational diagnostic system was not employed in many of the studies. The present study investigated frequencies of HLA-A specificities in schizophrenia patients (ICD-10 and DSM-III-R, n=98) and sex-matched healthy controls (n=392) from population in the southwestern part of Japan. HLA-B and -C specificities were studied in addition. Frequencies of subjects possessing A24 and A26 were not different between the patients and controls (54% and 24% in the patients and 62% and 24% in the controls, respectively). No significant difference was found in frequencies of other class I (A, B, and C) specificities between the patients and the controls. Thus, the present study provided no evidence for an association between the HLA class I specificities, including A24, A26, and others, and schizophrenia in the Japanese population.     

Differential effect of brain-derived neurotrophic factor on high-threshold mechanosensitivity in a rat neuropathic pain model

We investigated the effect of the systemic infusion of brain derived neurotrophic factor (BDNF) on the behavioral response in a rat neuropathic pain model. One microgram per hour infusion of BDNF significantly attenuated mechanical hyperalgesia tested by the pin-prick test, however, 20 microg/h-BDNF infusion, on the contrary, enhanced the response. Neither 0.5 nor 10 microg/h-BDNF infusion influenced the mechanical hyperalgesia. Mechanical allodynia and thermal hyperalgesia, tested using a von Frey filament (23.0 mN) and the plantar test, were not influenced by BDNF treatment. These data suggest that systemic BDNF treatment can specifically alter high-threshold mechanosensitivity.     

HLA-B40, B18, B27, and B37 allele discrimination using group-specific amplification and SSCP method

We developed a system for discriminating HLA-B40, B18, B27, and B37 alleles using a two-step PCR method followed by SSCP analysis. Fragments (0.8 kb) including exon 2, intron 2, and exon 3 were amplified in the first PCR. We used two sets of primers, one specific for HLA-B60-related alleles and the other specific for HLA-B6l-related, B18, B27, and B37 alleles. No amplifications of other class I genes or pseudogenes were observed. In the second PCR, exon 2 and exon 3 were amplified separately, using diluents of the first PCR products as templates. HLA-B6l-related, B18, B27, B37, and B60-related alleles were clearly discriminated in the SSCP analysis of the second PCR products. In a population study in which B6l alleles were analyzed, B^*4003 was detected in two Japanese individuals in addition to two B6l alleles previously reported to occur in Japanese, B^*4002 and B^*4006. The relative frequencies of B^*4002, B^*4006, and B^*4003 in Japanese were 58, 35, and 6%, respectively. The individuals having B^*4003 are the first non-South Americans in whom this allele has been detected. The SSCP banding patterns of 18 HLA-B60-positive Japanese population samples were identical to those of a B^*40012 sample for both exon 2 and exon 3. We also demonstrated that the B37 allele occurring in some Japanese is B^*3701.     

Role of apoptosis controlled by cytochrome c released from mitochondria for luteal function in human granulosa cells

PROBLEM: The aim of this study was to investigate the relationship between apoptosis by the mitochondrial pathway and luteal function in human granulosa cells. METHOD OF STUDY: Granulosa cells were obtained by ultrasound-guided follicular aspiration from patients undergoing in vitro fertilization and embryo transfer. After the addition of RU486, cells were stained with a mitochondria-specific fluorescent dye, MitoTracker Red CM x Ros. Using flow cytometry and National Institute of Health image, the mitochondrial fluorescent area was measured. After staining with Hoechst 33258 dye, the number of apoptotic bodies per 1000 cells were counted at random on photomicrographs. Homogenates were used for sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blot analysis using antibodies against cytochrome c or caspase-3. RESULTS: The incidence of apoptotic bodies increased and the mitochondrial membrane potential decreased time dependently. The opposite effect was observed dose dependently with RU486 treatment. Western blot analysis showed increased cytochrome c expression, after treatment with 1-2 microg/mL of RU486 which then decreased with 5-10 microg/mL of RU486. Caspase-3 expression increased dose dependently with RU486. CONCLUSIONS: These results suggest that the activation of caspase-3 caused by cytochrome c released from mitochondria plays an important role in apoptosis-related luteal function in human granulosa cells.     

C7*N is a hypomorphic allele of the human complement c7 M/N protein polymorphism.

Two complement C7 protein polymorphisms exist. One is determined by isoelectric focussing whereas the other is determined by the reaction pattern of a monoclonal C7-allospecific antibody in an ELISA assay. C7 concentrations quantitated by an ELISA based on polyclonal C7-specific IgG and data from functional haemolytic assays were compared with the allotypes of both C7 protein polymorphisms. Testing a randomly selected Japanese population revealed that not only C7*3 but also C7*N is a hypomorphic allele. However, no significant disease association of C7*N or C7*M was found in studies of hospitalized patients.     

Eosinophilic neuronal inclusion bodies in the temporal lobe.

Intracytoplasmic neuronal inclusion bodies were found in the temporal lobe of an elderly woman. The oval or rod-shaped inclusion bodies were eosinophilic, showed bright red staining with azan, and were about half the size of the nucleus of a large neuron. They were non-argyrophilic and non-congophilic. Ultrastructurally, the inclusion bodies consisted of aggregates of filamentous materials showing partial periodicity. Among inclusion bodies reported up to now, the present ones resembled some described previously as "thalamic inclusions", but were different with regard to their partial filament periodicity, and unusual in that they were located in the deep layer of the temporal lobe and not in the thalamic nuclei.     

POLYMORPHISM OF THE COMPLEMENT COMPONENT C6 IN JAPANESE

Genetic polymorphism of human C6 was investigated in Japanese using isoelectric focusing and a specific haemolytic overlay method. Three common and six rare allotypes were identified. Five of these nine allotypes were reference-typed by the International Reference Laboratory. Five of the six rare allotypes were considered to be new. The allele frequencies were estimated in the population study as follows: C6 A 0.427, C6 B 0.483 C6 B2 0.076, and the rere alleles (A3, A21, M1, M2, B3, and B4) 0.041.Inheritance of the three common and the two rare (A3 and M1) allotypes was demonstrated in the family study. The patterns obtained by the pretreatment with neuraminidase are presented.