Differential expression of beta 1 integrins in nonneoplastic smooth and striated muscle cells and in tumors derived from these cells.

Integrins are a superfamily of transmembrane alpha beta heterodimers that play an important role in cell-matrix and cell-cell interactions by acting as receptors for extracellular matrix proteins and for cell adhesion molecules. Using monoclonal antibodies against beta 1, alpha 1 to alpha 6, and alpha v subunits, the in situ distribution pattern of beta 1 integrins was examined immunohistochemically in nonneoplastic smooth and striated muscle cells and in their tumors. Nonneoplastic smooth muscle cells were beta 1+, alpha 1+, alpha 3+, alpha v+ and, in diverse localizations, also alpha 5+ or even alpha 6+. The expression of the beta 1 chain was conserved in all leiomyomas and leiomyosarcomas. The distribution pattern of the alpha subunits by contrast underwent several changes during malignant transformation of smooth muscle cells. These alterations consisted in a neoexpression of alpha 2, alpha 4, and alpha 6 as well as in an abnormal abrogation of alpha 1 and alpha 3 in some leiomyosarcomas. Except for the absence of alpha 5 in the majority of epithelioid leiomyosarcomas, expression of the alpha 5 and alpha v subunits was mainly conserved. In addition, tumors with epithelioid differentiation differed from typical cases by the absence of alpha 1 and the simultaneous presence of alpha 4. Adult striated muscle cells were beta 1+ but alpha 1- to alpha 6- and alpha v-, whereas fetal striated muscle cells were not only beta 1+ but also alpha 3+/-, alpha 4+/-, alpha 5+ and alpha 6+. In all rhabdomyosarcomas the expression of beta 1 was retained. Furthermore, the majority of cases showed the expression of one or more alpha subunits most of which, ie, alpha 4, alpha 5, and alpha 6, were also found in fetal striated muscle cells. In conclusion, beta 1 integrins exhibited a differential expression pattern along the two lines of myogenic differentiation. This integrin profile underwent characteristic changes during malignant transformation. Nevertheless, the compiled distribution patterns of the alpha 1, alpha 3, and alpha v subunits allowed in most instances the discrimination between tumors of smooth (alpha 1+/alpha 3+/alpha v+) and striated muscle (alpha 1-/alpha 3-/alpha v-) differentiation.     

Primary gastric apoptosis-rich T-cell lymphoma co-expressing CD4, CD8, and cytotoxic molecules

In contrast to primary gastric lymphomas of B-cell type, little is known about primary gastric T-cell lymphomas. We describe three cases with remarkably similar features: diffuse growth, epitheliotropism, medium too large cell size, high apoptotic rates, and a CD3+, CD4+, CD8+, CD45RO+ immunophenotype. Clonal TCRγ gene rearrangement was shown in two cases. Epstein-Barr virus infection was excluded in two cases. Taking advantage of fresh-frozen material, we analyzed two cases further, revealing CD5–, CD16+, CD56–, CD57–, CD25+, CD30+, CD103 (αEβ7)+, bcl-2 protein+, CD95+, CD95 ligand(L)–. CD95L, however, was detected in histiocytic and fibroblastoid by stander cells. The lymphomas expressed granzyme B, perforin, and the TIA-1 antigen in various combinations. All three cases had a very unfavorable clinical course characterized by local recurrence and/or dissemination to other epithelial sites, leading to death within 6–12 months after the initial diagnosis despite surgery and aggressive antineoplastic treatment. These data suggest a novel variant of peripheral T-cell lymphoma operationally characterized as primary gastric, apoptosis-rich, CD103+, EBV-, T-cell lymphoma co-expressing CD4, CD8, CD16 and cytotoxic molecules. Received: 20 August 1999 / Accepted: 2 November 1999     

Blutdruck,relatives Körpergewicht,Alkoholkonsum und Elektrolytausscheidung in der BRD und der DDR: Die Intersalt-Studie

Summary The relationships between body mass index (BMI) and age, alcohol consumption, 24-hr urinary electrolyte excretion, and BP were studied in 588 subjects from three German centers participating inIntersalt, a highly standardized, previously reported protocol. Men and women aged 20–59 were sampled in Bernried, FRG; Cottbus, GDR; and Heidelberg, FRG. The subjects from the three centers did not differ in BMI, level of education, physical activity, cigarette- or alcohol-consumption patterns, or urinary Cl excretion. Mean Na excretion was 167, 147, and 172 mmol/24 hr in Bernried, Cottbus, and Heidelberg, while mean K excretion was 72, 55, and 73 mmol/24 hr, respectively. The excretion of these electrolytes was significantly lower in Cottbus than in Bernried or Heidelberg. BMI increased progressively in men with age; in women BMI plateaued until the 5th decade, after which it increased to equal that of men. In individual centers, the excretion of electrolytes was correlated with BML Sodium and chloride excretion were highly correlated. The data from each individual center were fitted to a multiple regression model. Age, BMI, sex, and alcohol consumption entered the model.

     

Capsaicin-sensitive non-cholinergic excitatory innervation of the guinea-pig tracheobronchial smooth muscle

Field stimulation of the isolated main bronchi of the guinea-pig results in a rapid contraction followed by a sustained contractile response. Tetrodotoxin abolished these effects. The first phase was strongly inhibited by hyoscine, indicating that it was mediated mainly by excitation of cholinergic nerves. The lasting contraction was abolished by capsaicin tachyphylaxis but it was resistant to the effects of hyoscine, hexamethonium or physostigmine. It is suggested that capsaicin-sensitive non-cholinergic nerves have major excitatory effect on the guinea-pig bronchial smooth muscle and there is also evidence for their influence on the trachea.     

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD)

A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha- synuclein gene were amplified by PCR from index cases of 30 European and American Caucasian kindreds affected with autosomal dominant PD. Each product was sequenced directly and examined for mutations in the open reading frame. No mutations were found in any of the samples examined. We conclude that the A53T change described in the alpha- synuclein gene is a rare cause of PD or may even be a rare variant. Mutations in the regulatory or intronic regions of the gene were not excluded by this study.