Identical allelic losses in mature teratoma and other histologic components of malignant mixed germ cell tumors of the testis

Teratomas of the testis in post-pubertal patients are histologically diverse tumors that often coexist with other types of germ cell tumors. Using laser capture microdissection and loss of heterozygosity analysis, we investigated the clonality of mature teratoma and its relationship to other components of malignant mixed germ cell tumors to gain potential insight into the histogenetic relationship of teratoma with other germ cell tumor components. All 16 patients had mature teratoma as one component of their mixed germ cell tumors. The other histological subtypes included immature teratoma, seminoma, embryonal carcinoma, yolk sac tumor, and choriocarcinoma. Laser-assisted microdissection was performed on the formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 1p36.2 (D1S508), 2q22-32 (D2S156), 9p21-22 (D9S162), 11p13 (D11S903), 12q22-23 (D12S1051), and 18q21 (D18S46). Fourteen of 16 (88%) cases showed allelic loss in one or more components of the mixed germ cell tumors. Fourteen of 16 mature teratomas showed allelic loss in at least one of six microsatellite polymorphic markers analyzed. The frequency of allelic loss in mature teratoma was 50% (7 of 14) with D1S508, 33% (5 of 15) with D2S156, 58% (7 of 12) with D9S162, 43% (6 of 14) with D11S903, 20% (3 of 15) with D12S1051, and 33% (5 of 15) with D18S46. Completely concordant allelic loss patterns between mature teratoma and all of the other germ cell tumor components were seen in 10 of 14 tumors in which mature teratoma showed loss of heterozygosity. Our data support the common clonal origin of mature teratoma with other components of malignant mixed germ cell tumors of the testis.     

Behavior in chimeric mice combining differently behaving strains

A/J and C57BL/6J mice behave differently in tests for alcohol preference, open-field activity, defecation in the open field, cricket attacking, and rope climbing. Chimeric mice, i.e., mice containing both A/J cells and C57BL/6J cells, were constructed and tested for these behaviors. Patterns of behavior among A/JC57BL/6J chimeras are such as to suggest that none of these behavior differences is controlled by a single cell or clone and that the same cell population that gives rise to the strain difference in alcohol preference also gives rise to the differences in open-field activity and defecation, while separate cell populations control cricket killing and rope climbing.This research was supported by Research Grants AA 00388 and HD 03015 to M. N. N. and MH 18996 to K. B. Computing assistance was obtained from the Health Sciences Computing Facility, UCLA, supported by NIH Special Research Resources Grant RR-3.     

Mitogenic response of mouse spleen cells and gelation of limulus lysate by lipopolysaccharide of Yersinia pestis and evidence for neutralization of lipopolysaccharide by polymyxin B.

Lipopolysaccharide (LPS) extracted with phenol and water from Yersinia pestis was compared with LPS of Escherichia coli for stimulation of deoxyribonucleic acid synthesis in mouse spleen cells (lymphocyte mitogenesis), gelation of limulus lysate, pyrogenicity in the rabbit, and susceptibility to inhibition of these activities by polymyxin B sulfate (PBS). LPS of Y. pestis stimulated deoxyribonucleic acid synthesis in mouse spleen cell cultures over the same quantitative range as LPS of E. coli. In the limulus tests and rabbit pyrogenicity studies, the LPS of Y. pestis was active but about 10 times less potent than E. coli LPS on a weight basis. PBS in concentrations from 1 to 10 microgram/ml diminished the rate of deoxyribonucleic acid synthesis in spleen cell cultures stimulated by LPS of both Y. pestis and E. coli. Addition of PBS to LPS of both Y. pestis and E. coli in a ratio of 100 parts of PBS to 1 part of LPS by weight increased by 10-fold the concentration of LPS required to produce gelation of limulus lysate and inhibited significantly pyrogenic responses in rabbits. These results demonstrating similarities of LPS of Y. pestis and E. coli may suggest that the pathogenesis of plague is similar to that of other gram-negative bacterial infections.     

Lymphopenia in acute nitrofurantoin pleuropulmonary reactions

Each of 5 patients with acute nitrofurantoin pleuropulmonary reactions had profound lymphopenia and 4 had eosinophilia developing early in the clinical course after the drug was withdrawn. The 2 patients tested had only one third of the normal numbers of E rosettes (T lymphocytes) in the peripheral blood during recovery. Lymphoblastic transformation tests with purified nitrofurantoin were done in 3 patients and all of them were negative; responses to phytohemagglutinin, concanavalin A, and pokeweed were decreased but still normal. The diagnosis of various nitrofurantoin hypersensitivity reactions relies on clinical data. The mechanisms of these reactions presently remain unclear.     

B cell chronic lymphocytic leukaemia cells have reduced capacity to upregulate expression of MHC class I in response to interferon-gamma

AIMS: An important consideration in the design of a tumour vaccine is the ability of tumour-specific cytotoxic T lymphocytes (CTL) to recognise unmanipulated tumour cells in vivo. To determine whether B-CLL might use an escape strategy, the current studies compared B-CLL and normal B cell MHC class I expression. METHODS: Flow cytometry, TAP allele PCR and MHC class I PCR were used. RESULTS: While baseline expression of MHC class I did not differ, upregulation of MHC class I expression by B-CLL cells in response to IFN-gamma was reduced. No deletions or mutations of TAP 1 or 2 genes were detected. B-CLL cells upregulated TAP protein expression in response to IFN-gamma. Responsiveness of B-CLL MHC class I mRNA to IFN-gamma was not impaired. CONCLUSIONS: The data suggest that MHC class I molecules might be less stable at the cell surface in B-CLL than normal B cells, as a result of the described release of beta(2)m and beta(2)m-free class I heavy chains from the membrane. This relative MHC class I expression defect of B-CLL cells may reduce their susceptibility to CTL lysis in response to immunotherapeutic approaches.     

Spatial summation in lateral geniculate nucleus and visual cortex

We have compared the spatial summation characteristics of cells in the primary visual cortex with those of cells in the dorsal lateral geniculate nucleus (LGN) that provide the input to the cortex. We explored the influence of varying the diameter of a patch of grating centred over the receptive field and quantitatively determined the optimal summation diameter and the degree of surround suppression for cells at both levels of the visual system using the same stimulus parameters. The mean optimal summation size for LGN cells (0.90 degrees) was much smaller than that of cortical cells (3.58 degrees). Virtually all LGN cells exhibited strong surround suppression with a mean value of 74%+/-1.61% SEM for the population as a whole. This potent surround suppression in the cells providing the input to the cortex suggests that cortical cells must integrate their much larger summation fields from the low firing rates associated with the suppression plateau of the LGN cell responses. Our data suggest that the strongest input to cortical cells will arise from geniculate cells representing areas of visual space located at the borders of a visual stimulus. We suggest that analysis of response properties by patterns centred over the receptive fields of cells may give a misleading impression of the process of the representation. Analysis of pattern terminations or salient borders over the receptive field may provide much more insight into the processing algorithms involved in stimulus representation.     

Tubal metaplasia: A cytologic study with comparison to other neoplastic and non-neoplastic conditions of the endocervix

Tubal metaplasia of the endocervix (TME), a condition that may be con/used morphologically with glandular neoplasia, is frequently found in cone or hysterectomy specimens. To determine the frequency of detecting TME in cytologic smears, we retrospectively reviewed 28 Papanicolaou (Pap) smears from 22 women (mean age 39.1 yr; range 25-60 yr) with histologically proven TME. Our criteria for TME were the presence of two cell types in addition to endocervical secretory cells, i.e., peg cells (cells with dark and granular cytoplasm and elongate nuclei) and ciliated cells. All women had cervical cytology specimens obtained with an endocervical brush shortly before the procedures in which TME was diagnosed, and five also had at least one post-procedure smear. Of 20 smears with an adequate, non-neoplastic endocervical component, TME was found in 2 (10%). In these two, TME cells constituted 10% and < 5% of all the glandular cells, respectively, and the percentage of ciliated cells in the TME was approximately 25% and 75%. In conclusion, TME was noted infrequently (10%) on the cervical cytosmears of women with histologically-proven TME. This result corresponds to the histologic finding that TME typically involves the upper endocervix and glandular epithelium, with only 13% of the women having TME on the surface of the lower endocervix. Atypical glandular cells on cervical cytology are a problem for clinicians and pathologists alike. The differential diagnosis of such atypia, including TME, cells of the lower uterine segment, squamous intraepithelial lesion in glands and glandular neoplasia, is discussed.     

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation

Background  

Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process.