A novel isoform of the smooth muscle cell differentiation marker smoothelin

Studies on smooth muscle cell differentiation and those on vascular development in mouse and humans have long been hampered by the lack of suitable markers. Here we describe a novel, large isoform of smoothelin, a structural protein of differentiated, contractile smooth muscle cells. The protein, which is highly conserved in mouse and humans, shows homology with other cytoskeleton-associated smooth muscle cell proteins and contains an actinin-type actin-binding domain. Northern blot analysis from various mouse organs identified short and long smoothelin mRNA forms, which exhibit distinct tissue expression patterns. The short form is highly expressed in visceral muscle tissues such as intestine and stomach and is not detectable in brain, while the long mRNA form is expressed in all vascularized organs. These results may provide new tools and approaches to study both smooth muscle cell differentiation and proliferative vascular disease. Received: 25 August 1998 / Accepted: 19 October 1998     

Clonal chromosome abnormalities in human breast carcinomas I. Twenty-eight cases with primary disease

Cytogenetic analysis was performed on a selected series of short-term cultures of primary breast carcinomas from 28 patients. All patients had histopathologically confirmed malignancies, with the majority (25/28 cases) demonstrating infiltrating ductal carcinoma. All 28 cases evidenced clonal chromosome abnormalities, with 10/28 displaying only numeric aberrations, whereas 18/28 displayed clonal structural alterations. In near-diploid tumors the most common numeric changes were — 17 and — 19. However, trisomy 7 was the only numeric change in two near-diploid tumors. Structural chromosome alterations were primarily isochromosomes, apparent terminal deletions, and unbalanced non-reciprocal translocations. Chromosomes 1 (10/18–56%) and 6 (8/18–44%) were most frequently altered in this series. Breakpoints of clonal structural abnormalities were shown to cluster to several chromosome segments, including 1p22-q11, 3p11, 6p11–13, 7p11-q11, 8p11-q11, and 19q13. Analysis of the gain or loss of specific chromosome segments revealed that the most consistent tendency was over-representation of 1q, 3q, and 6p. © 1993 Wiley-Liss, Inc.     

Transgenic rat model of Huntington's disease

Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation.     

From rafts to crafts: membrane asymmetry in moving cells

Many important biological events, including the leukocyte-mediated immune response, wound repair, axon guidance and developmental patterning, involve persistent cell movement towards a directional signal, a process termed chemotaxis. Establishment of functional and spatial cell polarity is an absolute requirement for this response. We propose that redistribution of specific membrane microdomains, termed rafts, during cell migration is a pivotal step in achieving polarity. On the one hand, partitioning of molecules into rafts might help to localize proteins at the front or the rear of moving cells, and on the other hand, rafts might function as platforms for local activation and coordination of the signaling pathways involved in cell migration.     

Testing human sera for antibodies against avian influenza viruses: Horse RBC hemagglutination inhibition vs. microneutralization assays

BACKGROUND: The hemagglutination inhibition (HI) assay is a frequently used method to screen human sera for antibodies against influenza A viruses. Because HI has relatively poor sensitivity in detecting antibodies against avian influenza A strains, a more complicated microneutralization (MN) assay is often preferred. Recent research suggests that the sensitivity of the HI assay can be improved by switching from the traditionally used turkey, guinea pig, human, or chicken RBCs to horse RBCs. OBJECTIVE: To evaluate the performance of the horse RBC HI when screening for human antibodies against avian influenza types H3, H4, H5, H6, H7, H9, H11, and H12. STUDY DESIGN: We evaluated the reproducibility of horse RBC HI and its agreement with MN results using sera from people exposed or not exposed to wild and domestic birds. RESULTS: The horse RBC HI assay had high reliability (90%-100%) and good agreement with MN assay results (52%-100%). CONCLUSION: The horse RBC HI assay is reliable, less expensive, less complex, and faster than the MN assay. While MN will likely remain the gold standard serologic assay for avian viruses, the horse RBC HI assay may be very useful as a screening assay in large-scale epidemiologic studies.     

Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

Effect of Hypolaetin-8-Glucoside on Human Platelet Aggregation induced by ADP

Hypolaetin-8-glucoside, a flavonoid isolated from SIDERITIS MUGRONENSIS possessing anti-inflammatory activity inhibited dose-dependently the human PRP aggregation induced by ADP with a IC (50) = 2.4 x 10 (-4) M. This action does not seem to be related to cyclo-oxygenase, as this flavonoid is not an inhibitor and even is able to act as a cofactor for this enzyme.     

An approach to the antiinflammatory activity of borjatriol

The antiinflammatory activity of borjatriol (a diterpenoid isolated from SIDERITIS MUGRONENSIS Borja) was tested using the cotton pellet-granuloma assay. The compound inhibited the granuloma weight and the serum lysozyme activity in a dose-dependently way. The determination of this enzyme has allowed us to distinguish between an irritant (carrageenan) which reduces the granuloma weight and antiinflammatory substances (phenylbutazone and borjatriol).     

Association Between Maternal Work and Exclusive Breastfeeding in Countries of Latin America and Caribbean

Maternal and Child Health Journal - The aim of this study was to estimate the association between individual and contextual characteristics related to maternal work and exclusive breastfeeding...