Morphometric analysis, ploidy and response to chemotherapy in squamous carcinomas of the head and neck

The histopathology of 54 squamous carcinomas of the head and neck was evaluated by qualitative grading and morphometry in order to identify those features which predicted a good response to cisplatinum chemotherapy. The histopathology of 66 cases was correlated with tumour ploidy, determined by flow cytometry of paraffin-embedded material, since a separate study has shown that aneuploid carcinomas respond better to chemotherapy. The degree of differentiation was a poor predictor of ploidy, although diploid carcinomas did show more keratin and less nuclear pleomorphism than aneuploid carcinomas. The prominence of nucleoli in tumour cells and the surface area to volume (s/v) ratio of the tumour islands were the variables most strongly correlated with ploidy, with diploid carcinomas having prominent nucleoli and a low s/v ratio. A good response to chemotherapy was related partly to the architecture of the carcinoma (pushing border and low s/v ratio), and partly to the tumour cells (well differentiated) and the percentage of necrotic tumour. A lack of inflammatory reaction or desmoplasia was associated with a poor response. The results indicate that both subjective and objective histopathological criteria may be used to predict ploidy and the response to cisplatinum chemotherapy of squamous carcinoma of the head and neck. A combination of s/v ratio and the percentage of necrotic tumour can be used to identify a group of patients with a relatively good survival.     

Cancer mortality in a cohort of United Kingdom steel foundry workers: 1946-85

The mortality experienced by a cohort of 10,491 United Kingdom steel foundry workers during the period 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 10 participating foundries in 1946-65; all had worked in the industry for a minimum period of one year. Compared with the general population of England and Wales, statistically significant excesses relating to cancer mortality were found for cancer of the stomach (E = 77.4, O = 106, SMR = 137) and cancer of the lung (E = 229.2, O = 441, SMR = 147). A statistically significant deficit was found for cancer of the brain (E = 19.4, O = 10, SMR = 51). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, in "dust exposed" jobs, in "fume exposed" jobs, in foundry area jobs, in fettling shop jobs, and in foundry area or fettling shop jobs, of those dying from cancers of the stomach and lung with those of all matching survivors. The RMLT analyses provided evidence of an occupational involvement in the risk of death from lung cancer from work in the foundry area or fettling shop, and weaker evidence of an occupational involvement in the risk of death from stomach cancer from work in the foundry area.     

Analysis of Scottish Duchenne and Becker muscular dystrophy families with dystrophin cDNA probes.

One hundred and thirty-two Scottish families, representing the majority of currently known cases in this country with at least one living subject affected by DMD (110) or BMD (22), were studied with a series of cDNA probes excluding the 3' region of the gene (probes 10-14). Using mainly HindIII digested DNA from affected males, 89 patients showed deletions which ranged from 1 to 32 HindIII fragments in size. Two patients were also detected with exon duplications. Abnormalities were found to be particularly concentrated in the area of probe cDNA 8, with 56 patients being deleted for at least one of the fragments detected by this probe. A second smaller concentration of deletions was found with probe 1-2a which showed 16 deletions and two duplications. The endpoints of cDNA deletions or duplications were determined with a maximum variability of one HindIII fragment in 83 patients, while the remaining eight patients had a single deletion endpoint defined. The deletions found in two of our patients appear to conflict with the previously stated exon order at the 5' end of the gene. Although no specific deletion patterns were apparent for DMD, the deletions found in 13 of the BMD patients all included the most proximal (10 kb) fragment detected by probe 8.     

In vitro regulation of thyroglobulin (Tg) autoantibody production by Tg-specific T-cell lines and hybridomas.

To define the interactions between self thyroglobulin (Tg)-reactive T and B we co-cultured enriched B cells taken from rat or mouse Tg-primed mice with major histocompatibility complex (MHC) class II-restricted T-cell lines specific for iodinated determinants on self-Tg, or hybridomas derived from those lines. Using two clonally distinct T-cell hybridomas, ADA2 and CH9, in vitro help for Tg autoantibody responses was observed using mouse (M)Tg-primed B cells and a 100 ng/ml MTg challenge. Using rat Tg-primed B cells and the same conditions, only CH9 provided help, indicating that the fine specificity of B cells influences their ability to interact with specific anti-Tg T-cell clones. In contrast to T-cell hybridomas, their parent T-cell lines MTg9B3 and MTg12B suppressed Tg autoantibody responses in vitro, although they augmented bystander proliferation of unprimed B cells. The MTg12B cells also (i) diminished the survival of Tg-primed B cells, and (ii) inhibited the proliferation of an antigen-presenting B-cell hybridoma (LK35.2) in a cytostasis assay. These findings together support the view that their suppressive activity is mediated through cytotoxicity. While the role of class II-restricted cytotoxic cells in thyroid autoimmunity is unknown, the results suggest that such cells may act to suppress autoantibody responses as well as to mediate tissue damage to class II-expressing thyroid cells.     

Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic stem cell transplantation.

Pulmonary dysfunction is a significant complication following allogeneic hematopoietic stem cell transplantation (HSCT), and is associated with significant morbidity and mortality. Effective antimicrobial prophylaxis and treatment strategies have increased the incidence of noninfectious lung injury, which can occur in the early posttransplant period or in the months and years that follow. Late-onset noninfectious pulmonary complications are frequently encountered, but diagnostic criteria and terminology for these disorders can be confusing and therapeutic approaches are suboptimal. As a consequence, inaccurate diagnosis of these conditions may hamper the appropriate data collection, enrollment into clinical trials, and appropriate patient care. The purpose of this review is to clarify the pathogenesis and diagnostic criteria of representative conditions, such as bronchiolitis obliterans syndrome and bronchiolitis obliterans organizing pneumonia, and to discuss the appropriate diagnostic strategies and treatment options.     

High efficiency antigen presentation by thyroglobulin-primed murine splenic B cells

B cells primed in vivo with mouse or rat thyroglobulin present these antigens at very low concentrations to CH9, an Ly 1+2- T cell hybridoma specific for mouse and rat thyroglobulin. Presentation measured by interleukin 2 release from CH9 is sensitive to treatment with a monoclonal antibody eliminating splenic B cells but is unaffected by anti-Thy-1.2 or 33D1 (which destroy T cells and dendritic cells, respectively). Presentation is specific for the priming antigen and is blocked by preincubation of the B cells with sheep anti-mouse F(ab')2. We suggest that in this system, primed B cells present thyroglobulin and that this may represent a means by which an initial triggering event priming both B and T cells could allow maintenance of autoreactive responses in vivo in the presence of low concentrations of circulating antigen.     

Partial rescue of the Dazl knockout mouse by the human DAZL gene

Y-chromosomal DAZ (deleted in azoospermia) and autosomal DAZ-like (DAZL) comprise a gene family involved in gametogenesis. Y-chromosomal and autosomal genes only co-exist in humans and old world monkeys, indicating that DAZ genes are a recent acquisition of the Y chromosome. In most mammals, the ancestral Dazl alone is sufficient to complete gametogenesis. It is not yet understood why humans and old world monkeys have a second set of genes that are apparently necessary for spermatogenesis, since deletions removing the Y-chromosomal DAZ are often associated with azoo- or oligospermia. We used transgenic mice carrying either human DAZL or human DAZ on a mouse Dazl null background to investigate the functions of the human homologues. Both transgenes enabled prophase spermatocytes to be produced, mainly of the leptonema/zygonema stage, but failed to promote differentiation into mid- to late pachytenes. The presence of human DAZL resulted in a larger amount of early germ cells compared with that observed in DAZ. The degree of rescue was independent of copy number, integration site or presence of the DAZ repeat region for the DAZ transgenes. These findings confirm that DAZL and DAZ can only substitute for early functions of the murine homologue resulting in the establishment of the germ cell population and partial progression into meiosis.     

Thyroid autoimmunity

Antigenic structure remains a major focus in thyroid immunology. The genes for three major thyroid antigens--thyroglobulin, thyroid peroxidase and the thyrotropin receptor--were sequenced in the late 1980's, and epitopes for antibody and T cells have been reported within the last year. In addition, new evidence for selective use of T-cell receptor V gene segments in human thyroid infiltrates may point the way to specific immunotherapy.