Allelic loss of chromosome 6q in gastric carcinoma.

Loss of the long arm of chromosome 6 (6q) has frequently been reported in gastric carcinoma, and most gastric cancer patients have evidence of intestinal metaplasia in the stomach. However, the relationship between loss of chromosome 6q and intestinal metaplasia has not been studied. In the first part of the study, we define the critical deletion region of chromosome 6q using loss of heterozygosity technique (LOH). Seventeen microsatellite markers were used to detect loss of heterozygosity (LOH) in 37 microdissected gastric tumors. We also examined intestinal metaplasia (IM) foci of the stomach in the same cancer patient (17 cases). Losses on chromosome 6q were detected in high frequency (51%) by LOH. Two distinct regions of common allelic loss were identified: one centered on the marker D6S300 (at 6q16.1) and the second on D6S446 (at 6q27), with LOH frequency of 36% and 31.3%, respectively. The deletions fall into 2 discrete regions, suggesting the existence of at least 2 tumor suppressor genes in 6q. The losses at 6q27 were confirmed by fluorescence in situ hybridization study (FISH). In the cases with LOH in the tumor, no LOH were detected in the autologous IM areas, but losses were detected by FISH. In some cases, these genetic changes may be acquired in the transition from normal gastric mucosa to intestinal metaplasia.     

Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development

FOXL2 mutations cause gonadal dysgenesis or premature ovarian failure (POF) in women, as well as eyelid/forehead dysmorphology in both sexes (the 'blepharophimosis-ptosis-epicanthus inversus syndrome', BPES). Here we report that mice lacking Foxl2 recapitulate relevant features of human BPES: males and females are small and show distinctive craniofacial morphology with upper eyelids absent. Furthermore, in mice as in humans, sterility is confined to females. Features of Foxl2 null animals point toward a new mechanism of POF, with all major somatic cell lineages failing to develop around growing oocytes from the time of primordial follicle formation. Foxl2 disruption thus provides a model for histogenesis and reproductive competence of the ovary.     

Interobserver variability in determining MIB-1 labeling indices in oligodendrogliomas

Several studies have shown that MIB-1 labeling indices correlate well with tumor grade and prognosis in a variety of tumor types. Several factors are responsible for some degree of variability in the determination of labeling indices. Interobserver variability is one of the factors often cited as responsible for this variability. A slide from each of 30 oligodendrogliomas, stained with MIB-1 antibody, was distributed to six pathologists. The same set of slides was reviewed by each individual. Each pathologist was instructed to determine a MIB-1 labeling index by evaluating 1,000 tumor cell nuclei from the area of the slide with the most staining. The labeling index record reflected a percentage of positive-staining tumor cells. Interobserver agreement was compared. MIB-1 labeling indices ranged from 0 to 45.7. Overall agreement was good (> or =0.75) with a concordance coefficient of 0.832 (confidence interval, 0.700 to 0.909). Variability was greater among tumors with higher labeling indices as compared with tumors with labeling indices closer to 0. The overall agreement of MIB-1 labeling indices, while not perfect, was good. The generally minor variability among observers may be related to differences in the area of the slide evaluated and in differing lower thresholds for interpreting positivity. Further improvement of concordance may theoretically be attainable by further training and discussion among observers.     

Follow-up study of acute hepatitis C

Summary An extended follow-up study of hepatitis C virus (HVC) infection was conducted in Guangzhou and its nearby regions on patients hospitalized with acute hepatitis. Routine screening of blood donors for HCV was not yet instituted at the time of this study. HCV was found to be a common cause of the disease, and the infection had a close association with recent histories of blood transfusion. Sequential sera obtained from patients during hospitalization and after discharge were tested for the presence of HCV antibodies by the first and the second generation of commercial test kits, for levels of alanine aminotransferase (ALT), and for the presence of HCV-RNA. The development of HCV antibodies in some of the patients may be delayed for protracted period following clinical onset. HCV-RNA was only intermittently detectable both before and after seroconversion. Six of 33 patients studied showed seroreversion and 5 of them were accompanied by loss of HCV-RNA and serum ALT returned to normal levels. The disease persisted in 24 of 27 patients without seroreversion, accompanied by intermittent detection of HCV-RNA throughout the protracted course of the infection. Our results indicate that both EIA for detection of HCV antibodies and PCR for serum HCV-RNA should be used in combination for reliable diagnosis of HCV infection and screening of blood for transfusion.     

Direct sequencing of SSP-PCR-amplified cDNA to identify new alleles in the DR52-associated DRB1 group: identification of DRB1*1115, DRB1*1117 and DRB1*1319

Abstract: Low and high resolution sequence specific oligonucleotide probe hybridization patterns were used to design an approach to direct sequencing of allele specific amplified cDNA. Several PCR amplifications were used to derive overlapping sequence fragments to define complete first domain sequences for a single allele. This method has been used to characterize three new DRB1 alleles in the DR52 family, DRB1*1115, DRB1* 1117, and DRB1*1319. All three alleles carry polymorphisms previously observed in other DRB alleles and underscore the importance of utilizing a directed sequencing approach for obtaining unambiguous typing results in matching for bone marrow transplantation between unrelated donor and recipient.     

A study on Epstein Barr Virus receptor activity in cell free extracts of human lymphoblastoid cells

Summary Epstein Barr Virus (EBV) receptor activity in cell free extracts is operationally defined as one which causes a reduction in the effective concentration of the early antigen inducing particles of an EBV preparation when the latter is preincubated with the extract before infection. Such activity was detected in the surface extract of Raji cells and to a lesser extent in that of BJAB cells, both of which are B lymphoblastoid cells that are susceptible to infection with EBV. Receptor activity was not detected in similar extracts of P₃HR-1 cells and human diploid fibroblasts neither of which are known to be susceptible to EBV infection.Receptor activity in the Raji cell extract was found to be associated with membranous structures. This may have rendered the activity resistant to treatment with trypsin and sonication. The activity was however abrogated if the extract was exposed to neutral detergent.Binding of receptor activity was observed when Raji cell extract was chromatographed on a column of immobilized EBV. Subsequent electrophoretic analysis showed however that this procedure did not result in an appreciable purification of the receptor activity. Neutral detergent treated extract was similarly chromatographed. The resulting eluates did not contain detectable receptor activity but were less heterogeneous in protein content as compared with that of the original extract. It is not certain at present if these EBV binding proteins are involved in the receptor activity of the extract.With 3 Figures     

Case report: human herpesvirus 7 associated fatal encephalitis in a peripheral blood stem cell transplant recipient

Previous studies have suggested a neuroinvasive and neuropersistent potential of human herpesvirus 7 (HHV-7). In this report, a case of fatal encephalitis is described and its association with HHV-7 infection is discussed. An 8-year-old girl received a peripheral blood stem cell transplant for relapsed acute lymphoblastic leukaemia. The post-transplant period was uneventful and a course of intrathecal chemotherapy was given on Day-30. On Day-41, she developed acute encephalopathy with diplopia and nystagmus. She ran a rapid downhill course and succumbed despite antiviral treatment. The only positive pathological finding was the multiple microscopic foci of haemorrhage associated with neuronal degeneration detected in the brain stem. All microbiological investigations were negative, except for the presence of HHV-7 DNA in cerebrospinal fluid and brain stem tissue samples.     

Collision tumour of the oesophagus: a challenge for histological diagnosis.

An unusual case of mantle cell lymphoma metastasising to squamous cell carcinoma of the oesophagus, in a 62 year old Chinese man, is reported. A histological diagnosis based on examination of a small endoscopic biopsy specimen, in the absence of detailed clinical information, may be difficult, as the lymphoma component can be mistaken for reactive lymphoid infiltrate which is sometimes present adjacent to squamous cell carcinoma. Correlation with the clinical history, careful assessment of the subtle histological changes, and use of ancillary methods such as immunohistochemistry are most helpful in making the correct diagnosis. This case also illustrates further the possible occurrence of lymphomatous infiltrates surrounding other lesions in patients with a previous or concurrent history of lymphoma.