U1 snRNP inhibits pre-mRNA polyadenylation through a direct interaction between U1 70K and poly(A) polymerase

The brain damage produced by unilateral cerebral hypoxia-ischemia in the immature rat results from major alterations in cerebral energy metabolism and glucose utilization which begin during the course of the insult and proceed into the recovery period. Consistent with a lack of pathology, the alterations in the hemisphere contralateral to the carotid artery ligation are transient and return to normal within 24 h of recovery, whereas the hemisphere ipsilateral to the ligation exhibits both early and late responses, and infarction. The facilitative glucose transporter proteins mediate glucose transport across the blood-brain barrier (55 kDa GLUT1), and into neurons and glia (GLUT3 and 45 kDa GLUT1), and demonstrate both early and late responses to perinatal hypoxia-ischemia. This study employed in situ hybridization histochemistry to investigate the temporal and regional patterns of GLUT1 and GLUT3 gene expression following a severe (2.5 h) hypoxic-ischemic insult in the 7-day old rat brain. Enhanced GLUT1 mRNA expression was apparent in cerebral microvessels of both hemispheres and remained elevated in the ipsilateral hemisphere through 24 h of recovery, consistent with our previous observation of increased microvascular 55 kDa GLUT1 protein. The expression of the neuronal isoform, GLUT3, was enhanced in penumbral regions, such as piriform cortex and amygdala, but was rapidly reduced in the affected areas of cortex, hippocampus and thalamus, reflecting necrosis. The late response, observed at 72 h of recovery, was characterized by extensive necrosis in the ipsilateral hemisphere, loss of GLUT3 expression, and a gliotic reaction including increased GLUT1 in GFAP-positive astrocytes. This study demonstrates that cerebral hypoxia-ischemia in the immature rat produces both immediate-early and long-term effects on the glucose transporter proteins at the level of gene expression.     

Involvement of the Saccharomyces cerevisiae UTH1 gene in the oxidative-stress response

Despite lack of empirical support, facilitated communication was rapidly adopted and used with individuals who have severe communication disorders. An overview of the psychological literature was provided here to support theoretical explanations for this rapid adoption. The literature suggests that cognitive biases, ambiguous stimuli, and biases in data may be associated with a tendency to adopt interventions such as facilitated communication. Psychosocial influences associated with autism, the helping relationship, and the professional career cycle may enhance a readiness to adopt alternative treatments. Social influences may create an environment in which fads arise. Suggestions were provided for students and professionals in the broad fields of rehabilitation and education on how to improve their participation in developing and monitoring innovative treatment methods.     

Usefulness of biochemical tumor markers (CEA, Ca 19-9, ferritin and sialic acid) in diagnosis and prognosis of colonic neoplasms

The aim of the study was: to determine the value of CEA, Ca 19-9, ferritin and sialic acid in diagnostics, to assess the prognostic role of serum CEA and Ca 19-9 levels before surgery and to evaluate their usefulness in diagnostics of recurrences. The study included 352 patients with colorectal carcinoma (adenocarcinoma). The preoperative level of CEA was elevated in 286 patients, Ca 19-9 in 108, ferritin in 60 and sialic acid in 58 patients. All of them are poor markers in diagnostics because of the low sensitivity, respectively 47.6%, 37.0%, 16.7% and 55.2%. Preoperative high, CEA and Ca 19-9 values are associated with a significantly poorer prognosis and with frequency of recurrences.     

Importance of structural differences between complementary RNA molecules to control of replication of an IncB plasmid

Replication of the IncB miniplasmid pMU720 is dependent on the expression of repA, the gene encoding replication initiator protein RepA. Binding of a small antisense RNA (RNAI) to its complementary target (stem-loop I [SLI]) in the RepA mRNA prevents the participation of SLI in the formation of a pseudoknot that is an enhancer of translation of this mRNA. Thus, RNAI regulates the frequency of replication of pMU720 by controlling the efficiency of translation of the RepA mRNA. Mutational analysis of the two seven-base complementary sequences involved in formation of the pseudoknot showed that only the five central bases of each were critical for the formation of the pseudoknot. Physical analysis of SLI showed that despite the complete complementarity of its sequence to that of RNAI, the structures of the two molecules are different. The most prominent difference between the two structures is the presence of a 4-base internal loop immediately below the hairpin loop of SLI but not that of RNAI. Closure of this internal loop in SLI resulted in a 40-fold reduction in repA expression and loss of sensitivity of the residual expression to inhibition by RNAI. By contrast, repA expression was largely unaffected by the closure of a lower internal loop whose presence in SLI and RNAI is essential for effective interaction between these two molecules. These results suggest that the interaction of SLI with the distal pseudoknot bases is fundamentally different from the RNAI-SLI binding interaction and that the differences in structure between RNAI and SLI are necessary to allow SLI to be able to efficiently bind RNAI and to participate in pseudoknot formation.     

Uniparental disomy 7 in Silver-Russell syndrome and primordial growth retardation

Maternal uniparental disomy for the entire chromosome 7 has so far been reported in three patients with intrauterine and postnatal growth retardation. Two were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous, and one because he was homozygous for a rare COL1A2 mutation. We investigated 35 patients with either the Silver-Russell syndrome or primordial growth retardation and their parents with PCR markers to search for uniparental disomy 7. Four of 35 patients were found to have maternal disomy, including three with isodisomy and one with heterodisomy. The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7. It is suggested to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardation.     

Compound muscle action potential amplitude and area changes in normal subjects and patients with carpal tunnel syndrome

Miyoshi-type distal muscular dystrophy (MMD) is an autosomal recessively inherited progressive disorder. The putative locus of MMD is linked to the limb-girdle muscular dystrophy 2B locus on chromosome 2p12-14. In this study three of four MMD pedigrees show non-linkage to the region spanned by D2S134-D2S358-D2S145 on chromosome 2p, indicating genetic heterogeneity. A genome wide screen was performed to identify loci linked to MMD. In two non-chromosome 2-linked families, a 23 cM region on chromosome 10 segregated with MMD.     

The clinical value of solid marker transit studies in childhood constipation and soiling

Assessment of constipation in childhood is difficult, particularly when the presenting symptom is spurious diarrhoea or faecal incontinence. We have therefore assessed the clinical usefulness, reliability and acceptability of a solid marker transit technique in 52 patients with constipation (median age 8.0 years; range 2-13.5 years) at two referral centres. Median duration of symptoms was 60 months. Soiling was a prominent feature in 43 children (83%). Ten, 3 mm pieces of 6FG radio-opaque Silastic tubing were given orally at 9am on days 1, 2 and 3 and a plain abdominal film taken on day 5. Laxative treatment was not interrupted. Each film was divided into right colon, left colon and rectosigmoid areas, using bony landmarks, and the marker content of each area counted. The coefficient of variation of intra and inter-observer errors was 3.1% and 2.1% respectively. By day 5, 7% (group median) of markers were still in the right colon, 17% in the left colon and 42% in the rectosigmoid. Twenty-one patients (40%) had normal transit, 4 (8%) mild delay, 9 (17%) moderate and 18 (35%) severe transit delay. Marker distribution indicated slow pan-colonic transit in 29% and slow segmental transit in 10%. In 21%, clustering of markers in the rectosigmoid suggested outlet obstruction. A significant correlation was found between both transit delay and marker distribution and the severity of clinical symptoms of constipation and soiling. Repeat studies in six children following colonic evacuation revealed significant improvement (P < 0.05) in marker transit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Polysaccharide lyases

Polysaccharide lyases are the products of various microorganisms, bacteriophage and some eukaryotes. All such enzymes cleave a hexose-1,4-alpha- or beta-uronic acid sequence by beta-elimination. They are in some examples, the only known type of enzymes degrading their polyanionic substrates. Although only a small number of these enzymes have been exhaustively studied, the pectin lyases of bacterial origin have proved to be of interesting crystal structure containing a parallel beta-helix domain. Alginate and heparin lyases may yield products with biotechnological potential.     

Effect of bilayer curvature on vibrational Raman spectroscopic behavior of phospholipid-water assemblies

In order to clarify the effect of bilayer curvature upon phospholipid conformation, vibrational Raman spectra were recorded for dipalmitoyl and dimyristroyl phosphatidylcholine in the gel state for both multilayer and single-wall vesicle assemblies. An intensity comparison, based upon a nonperturbing internal standard, between the two classes of bilayrer systems reflected a decrease in peak height intensity for the observed hydrocarbon chain transitions in the single shell vesicle form. No intensity change between bilayer form was detected, however, for the two observed head group modes. Trends in the peak height intensity rations for the 1100 cm-1 carbon-carbon stretching vibrations indicated an increase in hydrocarbon chain transgauche isomerization for the vesicle in comparison to the multilayer arrangements. The sensitivity of the methylene carbon-hydrogen stretching modes to interchain interactions was demonstrated by comparisons of the intensity patterns in the 2900 cm-1 region to the intensity characteristics of the carbon-carbon stretching region for polycrystalline, multilayer and vesicle materials. Examination of various carbon-carbon stretching mode intensity ratios for cholesterol doped dipalmitoyl phosphatidylcholine bilayers indicated that while 25 mol% cholesterol increased the transgauche acyl chain isomerization in multilayers, no comparable effect was observed for the vesicle forms. In contrast, the methylene twisting/methylene deformation intensity ratios for the cholesterol containing systems suggested that some further type of interchain perturbation occurs in the vesicle aggregations.