Characterization of the specific meningeal T cell response to intracerebral inoculation of Theiler's murine encephalomyelitis virus

The presence of a resident T lymphocyte population in the meninges of normal SJL/J mice has been detected by the use of the T cell-specific mitogen concanavalin A. Optimal conditions for [3H]thymidine incorporation were studied. An antigen-specific meningeal T cell proliferative response in SJL/J mice, primed by intracerebral inoculation of Theiler's murine encephalomyelitis virus, was also detected. This response indicated that leptomeningeal mononuclear cell infiltrations are involved in the immune response that triggers the demyelinating disease.     

Musculo-fibrous anomaly in Barrett's mucosa with dysplasia

We investigated the histological alterations occurring in the muscularis mucosae, the lamina propria mucosae, and the submucosa in areas adjacent to invasive adenocarcinoma in 32 resected esophagi with Barrett's mucosa. In 26 of the 32 specimens, we observed a thickening of the muscularis mucosae, with overgrowth of the muscle fibers into the lamina propria mucosae. In other areas, collagen-rich fibrotic tissue replaced the muscularis mucosae, the lamina propria mucosae, and even the submucosa. In 31 of the 32 specimens, we noted cystic dilatations of the esophageal glands. Normal esophageal glands and cystically dilated glands with dysplastic lining were often surrounded, compressed, and deformed by the fibrotic tissue. The compression of the glandular outlets by the collagen-rich tissue or by proliferating dysplastic cells appeared to be the two main factors in the histogenesis of these cysts. This may result in difficulty in differentiating, in biopsy specimens, between normal and dysplastic esophageal glands "trapped" in the collagen-rich fibrotic tissue and true invasive adenocarcinoma in the Barrett's mucosa.     

A model to evaluate acute and chronic stress in the colonic mucosa of rats

The effect of acute and chronic stress on the colonic mucosa of the rat was investigated at various time intervals, ranging from one day to eight weeks. The amount of DNA synthesized by the mucosa was used as a marker of time-related events. A total of 75 Sprague-Dawley rats were investigated. Acute stress was considered for rats briefly plunged (psychic stimulus) or swimming for two hours (physical stimulus). Chronic stress was determined when rats were briefly plunged or swam for two hours for periods ranging from one to eight weeks. "Sham-transported" rats were used as controls. DNA in the descending colon decreased significantly in rats swimming for two weeks, but increased (even for plunged rats) at four and eight weeks. In the ascending colon, a substantial increase in DNA content was found in rats plunged or swimming for eight weeks. The descending colon appears to be quantitatively more affected by various stressors than the ascending colon. It is apparent that, in control rats, the mucosa of the descending colon differs from the ascending colon. Fluctuations in the colonic DNA synthesis throughout the experiment suggest that this phenomenon may be connected to compensatory mechanisms toward cell adaptation to stress conditions. The model may prove of value in studies of the therapeutic abrogation of the fluctuations of the DNA replication of the colonic mucosa during the acute and chronic phases of a given stress.     

Further studies on the musculo-fibrous anomaly of the Barrett's mucosa in esophageal carcinomas.

A total of 50 esophagi with carcinoma were reviewed for the presence of histological changes in the subepithelial tissues of the Barrett's mucosa. Those changes consisted in the thickening of the muscularis mucosae, the presence of muscle fibres in the lamina propria mucosae, fibrosis of the submucosa and sometimes total obliteration of the subepithelial tissues by collagen-rich sclerosis. Those changes have been connoted as "musculo-fibrous anomaly". Barrett's mucosa was present in all 18 specimens with adenocarcinoma and in 13 of the remaining 32 specimens with squamous cell carcinoma. Musculo-fibrous anomaly of the Barrett's mucosa occurred in all 18 specimens with adenocarcinoma and in 10 of the 13 specimens with a concomitantly growing squamous cell carcinoma. Esophageal and metaplastic glands were surrounded, compressed and deformed by the fibrotic tissue. The histological changes described explain the difficulties in the differential diagnosis--in biopsy specimens--between normal glands or glands with dysplastic changes "trapped" in the collagen-rich fibrotic tissue and true invasive adenocarcinoma of the Barrett's esophagus.     

The Turner syndrome research registry: Creating equipoise between investigators and participants

To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources.     

Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells

The biological basis for the pleiotropic activity of extracellular human immunodeficiency virus (HIV)-1 Tat protein on lymphoid T cell survival is not well understood. We have here demonstrated that the addition in culture of 0.1–10 nM Tat protein to 36-h serum-starved lymphoblastoid Jurkat T cells rapidly stimulates the catalytic activity of phosphatidylinositol 3-kinase (PI 3-K). The peak of activation was observed 30 min after Tat addition. Extracellular Tat also stimulated the catalytic activity of the Akt/PKB kinase, a major target of PI 3-K lipid products. Pretreatment of serum-starved Jurkat cells with 100 nM wortmannin (WT) or 10 μM LY294002, two unrelated pharmacological inhibitors of PI 3-K, markedly suppressed the catalytic activity of both PI 3-K and Akt/PKB in Jurkat cells. Moreover, at low concentrations (0.1–1 nM), extracellular Tat showed a small but reproducible protection of Jurkat cells from apoptosis induced by serum deprivation (p < 0.05), while the combination of Tat plus 100 nM WT significantly (p < 0.05) increased the percentage of apoptosis with respect to cells left untreated or treated with Tat alone. Taken together, these data suggest that the anti-apoptotic activity of low concentrations of Tat protein on Jurkat cells is mediated by a PI 3-kinase/Akt pathway.     

Atypical mitoses in colorectal adenomas

The frequency of spontaneously occurring mitotic figures, the proportion atypical mitoses and spatial position (vertical, oblique or horizontal) of metaphasial plates were studied in 62 specimens: 47 with colorectal adenomas, and 15 with chronic ulcerative colitis (control cases). The characteristics of the atypical mitoses at pro-phase, pro-metaphase, metaphase, anaphase and telophase were defined and illustrated. The results indicated that atypical mitoses occurred in 8.9% in control patients, in 37.2% of the specimens tubular adenomas having low-grade dysplasia, in 80.8% in tubular adenomas with high-grade dysplasia, in 68.5% of villous adenomas with low-grade dysplasia and in 65.5% of villous adenomas with high-grade dysplasia. For villous adenomas with high-grade dysplasia having invasive growth, 81.3% of atypical mitoses was recorded. Oblique or horizontal metaphasial plates were present in 8% of the metaphases in control cases but in as much as 25% in tubular adenomas with low-grade dysplasia, in 37% of those with high-grade dysplasia, in 42% for villous adenomas with low-grade dysplasia, in 56% for those with high-grade dysplasia and in 53% for villous adenomas with invasive growth. The classification of the various degrees of dysplasia is at present done by the characteristic of the dysplastic cells at interphase. This paper demonstrates that qualitative and quantitative morphological alterations of the mitotic apparatus takes place in the various histological types of colorectal adenomas. Perhaps both the number of atypical mitoses and the spatial position of the mitoses should be registered in attempts to shed more light on the biological behaviour of adenomatous lesions of the colorectal mucosa.