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.     

Pregnancies after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa

In 25 patients (14 suffering from obstructive azoospermia, sixfrom non-obstructive azoospermia, three from astheno-azoospermiaand two from absence of ejaculation) spermatozoa were extractedfrom testicular biopsies. Intracytoplasmic sperm injection (ICSI)with fresh testicular spermatozoa was performed in 18 cases;spermatozoa in excess were cryopreserved in pills. No pregnancieswere achieved. In the remaining seven patients, testicular spermatozoawere retrieved and cryopreserved during a diagnostic testicularbiopsy. After thawing, sperm motility was assessed in 17 cases(68%), and 18 ICSI with cryopreserved testicular spermatozoawere performed. The mean two-pronuclear (2PN) fertilizationrate was 59%, the mean cleavage rate was 92%, and six clinicalpregnancies were achieved, all of them still ongoing (pregnancyrate 33%). A comparison of the results of ICSI carried out withfresh or cryopreserved testicular spermatozoa showed that themean 2PN fertilization rates per cycle (53 compared with 55%),mean cleavage rates per cycle (99 compared with 96%) and embryoquality were not significantly different In conclusion, cryopreservationof testicular spermatozoa is feasible, even in patients withnon-obstructive azoospermia, and the results of ICSI with frozen-thawedtesticular spermatozoa are similar to those obtained using freshtesticular spermatozoa. Cryopreservation of testicular spermatozoamay avoid repetition of testicular biopsies to retrieve spermatozoafor successive ICSI cycles in patients in whom the only sourceof motile spermatozoa is the testicle.     

Clear cell adenocarcinoma of the colon.

A case of clear cell adenocarcinoma of the colon is reported. The histological examination of both the surgical specimen and of the metastases at necropsy showed columnar or polygonal cells with vesicular nuclei. The cytoplasm was usually clear with multiple, often empty looking vacuoles. From a panel of histochemical and immunohistochemical reactions, carcinoembryonic antigen and tissue polypeptide antigen showed strong positivity. The histochemical and immunohistochemical differential diagnosis with another common clear cell tumour, namely clear cell renal adenocarcinoma, is discussed.     

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.     

SKALP/elafin gene polymorphisms are not associated with pustular forms of psoriasis

Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear leukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known as elafin, is a potent inhibitor of human leukocyte elastase and proteinase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein level, SKALP is significantly decreased in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis. This finding raised the possibility that SKALP could be one of the candidate genes for pustular forms of psoriasis. We therefore performed single strand conformation polymorphism (SSCP) analysis on the SKALP gene to screen for mutations/polymorphisms in the exons of 30 patients with plaque-type psoriasis, 15 patients with pustular psoriasis and 48 healthy controls. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threonine for alanine in the signal peptide. In the promoter region a dinucleotide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that there is no allelic association between pustular psoriasis and SKALP gene polymorphisms.     

Functional Analysis of B-L (Ia-Like) Antigen-Bearing Chicken Peripheral Blood Cells

The functional of B-L (Ia-equivalent)-positive (B-L+) adn -negative (B-L-) chicken peripheral blood lymphocytes (PBL) was studied in vitro and in vivo. The PBL were first stained in direct immunofluorescence tests with a fluorescein isothiocyanate-labelled anti-B-L alloantiserum and then separated by means of a fluorescence-activated cell sorter. In agreement with our previous findings, B-L- cells showed functional properties of T lymphocytes, responding to concanavalin A and phytohaemagglutinin-P in vitro and inducing a graft-versus-host (GVH) reaction when injected into allogeneic embryos. Sorted B-L+ gave no responses in any of these assays. Neither B-L+ nor B-L- cells, when tested alone, responded significantly to pokeweed mitogen, but mixtures of the two restored the responsiveness to that of the original unsorted suspension. Of the B-L+ PBL, 10% were T cells, which may account for the low GVH reactivity given by this population.     

bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors

Proliferative expansion and apoptotic cell death play prominent roles in T cell development. The molecular control of cell cycle progression and apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit apoptosis and slow cell cycle progression in cortical thymocytes and mature T cells, particularly during the transition from the quiescent state into the cell cycle. Here the impact of bcl-2 transgene expression on CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival of these progenitors at all of the four major differentiation stages, CD25- CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene we conclude that Bcl-2 inhibits proliferation only of T cell progenitors that are activated via the pre- TCR, not those stimulated via c-Kit and the IL-7 receptor.