Paraneoplastic encephalomyelitis and seminoma: importance of testicular ultrasonography

We report two patients with paraneoplastic limbic and brainstem encephalitis associated with occult nonmetastatic testicular seminoma. In each patient, the neoplasm was detectable only by testicular ultrasonography. Male patients with this syndrome in whom lung cancer is not found should undergo testicular ultrasonography as part of the search for an extrapulmonary neoplasm. A normal clinical testicular examination is insufficient to exclude an occult seminoma.     

Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function

Coat colors in the chestnut horse, the yellow Labrador retriever, the red fox, and one type of yellow mouse are due to recessive alleles at the extension locus. Similarly, dominant alleles at this locus are often responsible for dark coat colors in mammals, such as the melanic form of the leopard, Panthera pardus. We show here that the murine extension locus encodes the melanocyte-stimulating hormone (MSH) receptor. In mice, the recessive yellow allele (e) results from a frameshift that produces a prematurely terminated, nonfunctioning receptor. The sombre (Eso and Eso-3J) and tobacco darkening (Etob) alleles, which both have dominant melanizing effects, results from point mutations that produce hyperactive MSH receptors. The Eso-3J receptor is constitutively activated, while the Etob receptor remains hormone responsive and produces a greater activation of its effector, adenylyl cyclase, than does the wild-type allele.     

Biology and pathology of Schistosoma mansoni and Schistosoma japonicum infections in several strains of nude mice

Schistosoma mansoni and S. japonicum infections in nude mice (nu/nu) were compared with infections in nu/+ heterozygotes or intact mice. Seven to 12 weeks after exposure to S. mansoni, the responses of Swiss NCR, C3H, BALB/c and C57B1/6 nude mice did not differ substantially. Nude mice of all these strains showed minute granulomas around eggs in the liver and minimal hepatic fibrosis. Microvesicular and necrotizing changes in hepatocytes were similar in all mouse strains, and S. mansoni infections were frequently lethal to nude, but not to intact mice between the seventh and ninth weeks of infection. Nude mice that survived the ninth week of infection generally lived until the 12th week. The number of eggs per mature worm pair in the tissues of S. mansoni-infected nude mice was similar to the number in intact mice, but nude mice passed fewer eggs in the feces. Nude mice that received serum from infected intact mice excreted eggs in the stool in numbers equivalent to intact mice, but continued to form minute granulomas around S. mansoni eggs. Reconstitution with fetal thymus or with splenocytes from normal or S. mansoni-infected mice partially or completely restored hepatic granuloma size, granuloma eosinophils, hepatic fibrosis, and excretion of eggs in the feces. In contrast to S. mansoni infection, S. japonicum infections in nude mice did not cause necrosis of hepatocytes or excessive mortality, and S. japonicum eggs were passed in the feces in numbers equivalent to those passed by infected intact mice.     

Effects of Helicobacter pylori vacuolating cytotoxin on primary cultures of human gastric epithelial cells

BACKGROUND: Many Helicobacter pylori strains produce a cytotoxin that induces cytoplasmic vacuolation in various types of eukaryotic cells. In contrast with the marked cell vacuolation that occurs in vitro in response to this cytotoxin, comparatively little epithelial vacuolation has been observed in the gastric mucosa of H pylori infected persons. AIMS: Experiments were performed to determine the susceptibility of human gastric epithelial cells in vitro to H pylori vacuolating cytotoxin activity. METHODS: Human gastric epithelial cells, harvested from upper gastrointestinal endoscopic biopsy specimens, were incubated overnight with broth culture supernatants from either a wild type cytotoxin producing (tox+) H pylori strain or an isogenic mutant strain that lacks cytotoxin activity. RESULTS: Prominent cytoplasmic vacuolation occurred in response to tox+ supernatant, but not supernatant from the isogenic mutant strain. Primary human gastric epithelial cells were significantly more sensitive to H pylori vacuolating cytotoxin activity than were either HeLa or AGS cells. Exposure of human gastric epithelial cells to high concentrations of tox+ supernatant for 48 hours caused lethal cell injury. CONCLUSIONS: These studies indicate that primary human gastric epithelial cells are highly sensitive to H pylori vacuolating cytotoxin activity.     

A model for the assessment of medical workstations for health care support

The development of medical workstations for the support of patient care, the assessment of care, management support, and education is just at its beginning. During the Working Conference on the Health care Professional Workstation held in Washington DC, June 1993, several aspects of such workstations were discussed, but it was also recognized that prototyping or learning by experience could be a rich source to further promote the progress in this field. Eight such prototypes or already operational medical workstations were demonstrated and a preliminary user assessment was done to obtain a first insight in the advantages and the type of criteria of such evaluations. It was concluded that such assessments were of great value to (i) give feedback to the designers of medical workstations, (ii) indicate areas of strength and for further research, and (iii) to offer criteria to potential users of such workstations for making decisions on using such systems. The assessment criteria deal with functionality, architecture, user interfaces, communications and integration, and data and knowledge management.     

Informing consumer decisions in health care: implications from decision-making research

Despite the wider dissemination of health plan report cards, little is known about whether consumers will use this information in making plan and provider choices. Studies of human judgment and decision making are reviewed, as are their implications for devising strategies to inform consumers. The limitations of human information processing suggest that many consumers will not use performance information in making choices. Strategies are needed to support consumers who prefer to rely on intermediaries as well as those who wish to apply the information for their own use. Many current strategies are based on assumptions not supported by existing decision-making research. Although there is much to learn about assisting consumers in making informed choices, a great deal is known from decision-making research. Our approaches and our research agenda must be based on this existing foundation of knowledge.     

Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface

Recognition by integrin proteins on the cell surface regulates the adhesive interactions between cells and their surroundings. The structure of the 'I' domain that is found in some but not all integrins, has been determined. However, the only integrin ligands for which structures are known, namely fibronectin and VCAM-1, are recognized by integrins that lack I domains. The intercellular adhesion molecules ICAM-1, 2 and 3 are, like VCAM-1, members of the immunoglobulin superfamily (IgSF), but they are recognized by an I domain-containing integrin, lymphocyte-function-associated antigen 1 (LFA-1, or CD11a/CD18). Here we present the crystal structure of the extracellular region of ICAM-2. The glutamic acid residue at position 37 is critical for LFA-1 binding and is proposed to coordinate the Mg2+ ion in the I domain; this Glu 37 is surrounded by a relatively flat recognition surface and lies in a beta-strand, whereas the critical aspartic acid residue in VCAM-1 and fibronectin lie in protruding loops. This finding suggests that there are differences in the architecture of recognition sites between integrins that contain or lack I domains. A bend between domains 1 and 2 of ICAM-2 and a tripod-like arrangement of N-linked glycans in the membrane-proximal region of domain 2 may be important for presenting the recognition surface to LFA-1. A model of ICAM-1 based on the ICAM-2 structure provides a framework for understanding its recognition by pathogens.     

An expert decision support system for network routing: a case study

The paper presents a case study of the development of an expert decision support system which uses simple heuristic methods for fast determination of routes for simultaneous signals in a transmission network of limited capacity. It illustrates how heuristic solutions can be embodied in a model-based DSS and how the standard decision support literature, although intuitively appealing, provides little practical assistance in system construction or classification