Expression of TGF-ß Signaling Regulator RBPMS (RNA-Binding Protein With Multiple Splicing) Is Regulated by IL-1ß and TGF-ß Superfamily Members, and Decreased in Aged and Osteoarthritic Cartilage.

OBJECTIVE: RNA-binding protein with multiple splicing (RBPMS) has been shown to physically interact with Smads and enhance transforming growth factor-ß (TGF-ß)-mediated Smad2/3 transcriptional activity in mammalian cells. Objective of this study was to examine whether expression of RBPMS is regulated by interleukin-1ß (IL)-1ß and TGF-ß superfamily growth factors and whether expression of RBPMS is altered during aging and experimental osteoarthritis. METHODS: Expression of RBPMS protein was investigated in chondrocyte cell lines of murine (H4) and human (G6) origin using Western blot analysis. Regulation of RBPMS expression in H4 chondrocytes at mRNA level was done by reverse transcriptase-quantitative polymerase chain reaction. Furthermore, characterization of Smad signaling pathways regulating RBPMS expression was performed by blocking studies using small molecule inhibitors or by transfection studies with adenoviral vector constructs (constitutive-active ALK1 and constitutive-active ALK5). Expression of RBPMS in cartilage of different age groups of C57BL/6N mice (6 months and 20 months) and in a surgically induced osteoarthritis (OA) mouse model was analyzed using immunohistochemistry. RESULTS: RBPMS was shown to be expressed in chondrocytes and cartilage of murine, human, and bovine origin. TGF-ß inhibited RBPMS expression while BMP2 and IL-1ß increased its expression. TGF-ß-induced inhibition was blocked by ALK5 inhibitor. Overexpression of ca-ALK1 stimulated RBPMS expression. Moreover, RBPMS expression was found to be reduced with ageing and in OA pathogenesis. CONCLUSIONS: Expression of RBPMS in chondrocytes is regulated by TGF-ß superfamily members and IL-1ß, indicating a counter-regulatory mechanism. Expression of RBPMS, in cartilage and its reduction during ageing and OA might suggest its potential role in the maintenance of normal articular cartilage.

Current health status of patients who have survived for more than 15 years after liver transplantation.

BACKGROUND: Liver transplantation was started in our centre as early as 1979. We have studied the clinical outcome of patients surviving longer than 15 years, with special interest for the broad range of comorbidity and the self-perceived quality of life. METHODS: All patients who underwent a liver transplantation at an adult age, between March 1979 and February 1991, and who had survived at least 15 years were eligible for the study. Data were collected from the medical records. Health-related quality of life was assessed using the Six-Dimensional EuroQol test. RESULTS: The five-year survival of patients alive 15 years after transplantation was 78%. Thirty-seven patients are currently alive with a median follow-up of 18.8 years (range 15.0 to 26.8) after transplantation. Comorbidity consists predominantly of overweight (57%), osteoporosis (49%), de novo cancer (38%, mainly skin cancer), hypertension (38%), cardiovascular events (19%), diabetes mellitus (22%), cataract (24%), and renal clearance<50 ml/min (11%). The pattern of comorbidity seems to relate to the type of immunosuppression which consisted mainly of prednisolone and azathioprine. Quality of life was perceived as satisfactory (7 on a scale of 0 to 10). However, about half of the patients reported limitations in the domains mobility, usual activities and pain/discomfort. In addition a minority reported some anxiety or depression. CONCLUSION: The outcome of liver transplantation in this early cohort of patients is fairly good. Improvements may be achieved by adaptations in the immunosuppressive regimen.

Phylogenetic analysis of Phytophthora species based on mitochondrial and nuclear DNA sequences.

A molecular phylogenetic analysis of the genus Phytophthora was performed, 113 isolates from 48 Phytophthora species were included in this analysis. Phylogenetic analyses were performed on regions of mitochondrial (cytochrome c oxidase subunit 1; NADH dehydrogenase subunit 1) and nuclear gene sequences (translation elongation factor 1alpha; beta-tubulin) and comparisons made to test for incongruence between the mitochondrial and nuclear data sets. The genus Phytophthora was confirmed to be monophyletic. In addition, results confirm that the classical taxonomic grouping as described by [Waterhouse (1963)] does not reflect true phylogenetic relations. Phytophthora species were redistributed into 8 clades, providing a more accurate representation of phylogenetic relationships within the genus Phytophthora. The evolution and transition of morphological, pathogenic, and reproductive traits was inferred from the cladogram generated in this study. Mating system was inferred to be a homoplasious trait, with at least eight independent transitions from homothallism to heterothallism observed.

Genetic Diversity of Phytophthora infestans sensu lato in Ecuador Provides New Insight Into the Origin of This Important Plant Pathogen.

ABSTRACT The metapopulation structure of Phytophthora infestans sensu lato is genetically diverse in the highlands of Ecuador. Previous reports documented the diversity associated with four putative clonal lineages of the pathogen collected from various hosts in the genus Solanum. This paper simultaneously analyzes diversity of the complete collection of isolates, including a large number that had not yet been reported. This analysis confirmed the existence of three pathogen populations, which all appear to be clonal lineages, and that correspond to those previously reported as US-1, EC-1, and EC-3. No evidence was found from the analyses of recently collected isolates that would contradict earlier reports about these three lineages. In contrast, new data from a group of isolates from several similar hosts caused us to modify the previous description of clonal lineage EC-2 and its previously proposed hosts, S. brevifolium and S. tetrapetalum. Given the uncertainty associated with the identification of these hosts, which all belong to the section Anarrhichomenum, we refer to them as the Anarrhichomenum complex, pending further taxonomic clarification. New pathogen genotypes associated with the Anarrhichomenum complex were isolated recently that are A1 mating type and Ia mitochondrial DNA (mtDNA) haplotype, and therefore differ from the previously described EC-2 lineage, which is A2 and Ic, respectively. Because of uncertainty on host identification, we do not know if the new genotypes are limited to one host species and therefore represent yet another host-adapted clonal lineage. For now, we refer to the new genotypes and previously described EC-2 genotypes, together, as the pathogen group attacking the Anarrhichomenum complex. Two A2 isolates identical to the previously described EC-2 archetype were collected from severely infected plants of pear melon (S. muricatum). Pear melon is generally attacked by US-1, and this is the first clear case we have documented in which two distinct pathogen genotypes have caused severe epidemics on the same host. Based on presence of unique marker alleles (restriction fragment length polymorphism [RFLP] and mtDNA) and genetic similarity analysis using RFLP and amplified fragment length polymorphism data, EC-3 and isolates from the Anarrhichomenum complex are genetically distinct from all genotypes of P. infestans that have been reported previously. No current theory of historical migrations for this pathogen can adequately support a Mexican origin for EC-3 and genotypes of the Anarrhichomenum complex and they may, therefore, be palaeoendemic to the Andean highlands. To date, we have identified 15 hosts in the genus Solanum, in addition to the Anarrhichomenum complex, and some unidentified species of P. infestans sensu lato in Ecuador. Five of the Solanum hosts are cultivated. One isolate was collected from Brugmansia sanguinea, which represents the first report from Ecuador of a host of this pathogen that is not in the genus Solanum. However, P. infestans sensu lato was only found on flower petals of B. sanguinea. This study provides new insights into the population structure of highly specialized genotypes of P. infestans sensu lato in the Andean highlands. The results are discussed in light of previous hypotheses regarding the geographic origin of the pathogen.

Influence of individual differences in craving and obsessive cocaine thoughts on attentional processes in cocaine abuse patients.

In the present pilot-study, the relation between craving, obsessive thoughts about cocaine, experienced control, and attentional bias for cocaine related words is investigated. Sixteen cocaine abuse patients participated in a reaction time (RT) experiment which was employed to measure the ability of subjects to shift their attention away from cocaine related words. Postexperiment craving was found to be positively correlated with reaction times on drug related cues, in contrast to RT on neutral cues. Furthermore, obsessive thoughts about cocaine use and the experienced cocaine use control, in the week before the experiment, were correlated in a higher degree with RTs on drug cues than postexperiment craving. Attentional bias for drug cues was evidenced in patients with higher scores on obsessive cocaine thoughts and higher craving scores. This study shows that individual differences on information processing, within a cocaine abuse patient population, are present.

Selective cognitive processing of drug cues in heroin dependence.

Previous studies provide evidence for the selective processing of disorder related stimuli on anxiety, depression, and eating disorders. There exist some preliminary indications that selective processing of drug cues may be involved in drug craving and relapse that deserve further investigation. In order to investigate the role of processing bias in an abnormal motivational system, the attentional bias for drug related stimuli was studied in a heroin dependent population. Heroin dependent participants (n = 21) and control participants (n = 30) performed a supra- and subliminal heroin Stroop task and heroin craving was assessed. Heroin dependent participants showed a considerable attentional bias for supraliminally presented heroin cues. However, there was no evidence for a preattentive bias on the subliminal presented cues. Reaction time on heroin cues was significantly predicted by heroin craving-levels. Results indicate that selective processing may be related to motivational induced states in general. The finding are discussed in the context of selective information processing in general psychopathology and in motivational processes as addiction specifically.

Gene Genealogies and AFLP Analyses in the Fusarium oxysporum Complex Identify Monophyletic and Nonmonophyletic Formae Speciales Causing Wilt and Rot Disease.

ABSTRACT The monophyletic origin of host-specific taxa in the plant-pathogenic Fusarium oxysporum complex was tested by constructing nuclear and mitochondrial gene genealogies and amplified fragment length polymorphism (AFLP)-based phylogenies for 89 strains representing the known genetic and pathogenic diversity in 8 formae speciales associated with wilt diseases and root and bulb rot. We included strains from clonal lineages of F. oxysporum f. spp. asparagi, dianthi, gladioli, lilii, lini, opuntiarum, spinaciae, and tulipae. Putatively nonpathogenic strains from carnation and lily were included and a reference strain from each of the three main clades identified previously in the F. oxysporum complex; sequences from related species were used as outgroups. DNA sequences from the nuclear translation elongation factor 1alpha and the mitochondrial small subunit (mtSSU) ribosomal RNA genes were combined for phylogenetic analysis. Strains in vegetative compatibility groups (VCGs) shared identical sequences and AFLP profiles, supporting the monophyly of the two single-VCG formae speciales, lilii and tulipae. Identical genotypes were also found for the three VCGs in F. oxysporum f. sp. spinaciae. In contrast, multiple evolutionary origins were apparent for F. oxysporum f. spp. asparagi, dianthi, gladioli, lini, and opuntiarum, although different VCGs within each of these formae speciales often clustered close together or shared identical EF-1alpha and mtSSU rDNA haplotypes. Kishino-Hasegawa analyses of constraints forcing the monophyly of these formae speciales supported the exclusive origin of F. oxysporum f. sp. opuntiarum but not the monophyly of F. oxysporum f. spp. asparagi, dianthi, gladioli, and lini. Most of the putatively nonpathogenic strains from carnation and lily, representing unique VCGs, were unrelated to F. oxysporum f. spp. dianthi and lilii, respectively. Putatively nonpathogenic or rot-inducing strains did not form exclusive groups within the molecular phylogeny. Parsimony analyses of AFLP fingerprint data supported the gene genealogy-based phylogram; however, AFLP-based phylogenies were considerably more homoplasious than the gene genealogies. The predictive value of the forma specialis naming system within the F. oxysporum complex is questioned.

Advances in conventional and innovative therapies for respiratory distress syndrome in children.

Adult respiratory distress syndrome is a phenomenon encountered by many pediatric critical care nurses. Care of these complex patients is multifaceted and requires an in-depth understanding of pathophysiology and therapeutic intervention. Several innovative treatments are now available as biomedical and technical advances have evolved. Outcomes will improve as clinicians improve patient selection, identify therapeutic endpoints, and risk/benefits. This article addresses the current understanding of pathophysiology, innovative treatments, and nursing care issues.

Hospital mouth-cleaning aids may cause dental erosion.

Maintaining satisfactory oral health in bed-ridden patients often calls for special aids, such as moistened cotton swabs. The purpose of this in vitro study was to investigate three commercially available swabsticks meant for hospital use (Dentiswab, Lemon-Glycerin Swabsticks, and Lemon Glycerine Swabs), and one saliva-stimulant chewing tablet (Cassisal), regarding their possible erosive effects on dental enamel. A bovine enamel model system was used. Specimens were incubated for 4 hours in the test solutions made of the products. The results showed statistically significant enamel softening caused by two of the cotton swabs (Lemon-Glycerin Swabsticks and Lemon Glycerine Swabs). Incubation in the solutions made of Dentiswab cotton swabs and Cassisal tablets caused only minimal changes in microhardness. Profilometric measurements supported these results. Stereomicroscopy and SEM showed distinct erosion in specimens treated with the lemon swab solution, while the other two did not cause erosion. Thus, attention should be focused on choosing the less erosive products if special mouth-cleaning aids are used.

Prescription of antibiotics to out-patients in hospital clinics, community health centres and private practice.

Prescription of antibiotics in Sweden varies between countries within a range of 13-20 DDD/1000 inhabitants/day. In Malmöhus county, which accounts for the highest prescription rate, the amounts and proportions of erythromycin and tetracyclin prescribed are particularly large. All prescriptions for antibiotics dispensed in half of the pharmacies in the county during a one-week period were examined with respect to type of antibiotic and category of physician responsible for the prescription. Among 5,165 antibiotic prescriptions examined, broad spectrum antibiotics were more frequent in urban than in rural areas, and were more often prescribed by hospital physicians and private practitioners than by district physicians. Erythromycin was particularly often prescribed by paediatricians, the frequency being comparable to that of phenoxymethylpenicillin. Retrospective analysis of consultations at the ENT and paediatric clinics for respiratory tract infections showed that phenoxymethylpenicillin was not always the drug of choice by hospital physicians, despite a recommendation to that effect by the Board of Health and Welfare. The findings suggest that the choice of antibiotics is determined not only by medically relevant factors and Board recommendations but also by the habits of the consulting physicians.

Delivery circumstances in relation to adult septum deviation.

The present study elucidates whether factors correlated to septum dislocation in newborns have quantitative significance for septum deviation demanding surgery in adults. The delivery circumstances of 95 patients operated upon for septum deviation were compared to those of 79 control subjects with straight septa. Patients and control subjects were born in the same area and at the same period of time. Eleven possible nose traumatizing factors were analyzed. No difference was found. There was, however, a male overrepresentation by 3:1 amongst the operated patients which may be explained by postnatal nose trauma. It is concluded that delivery circumstances have only minor influence on the number of adults demanding septum surgery.

The effect of divalent cations on the amidolytic activity of bovine plasma activated protein C and des-1-41-light chain activated protein C.

The effect of the divalent cations Ca2+ and Mn2+ on the amidolytic activity of bovine plasma activated protein C and a limited chymotryptic digestion product, des-1-41-light chain activated protein C, which lacks all of the gamma-carboxyglutamic acid present in activated protein C, has been examined at 30 degrees C. In each case, the enzymic activities were dependent upon the presence of these cations, which exerted their effects primarily through influence on the kcat of the reaction. For both enzymes (E), the mechanism of the reaction was most consistent with a rapid equilibrium, random addition of substrate (S), and a single cation (A), with substrate hydrolysis occurring only with the ternary complex of S.E.A. The divalent cation site of importance was not associated with gamma-carboxyglutamic acid residues and was found to be independent of the monovalent cation sites, which also function to activate the amidolytic and esterolytic activities of these enzymes.

Urinary tract infection after vaginal surgery. Effect of prophylactic treatment with methenamine hippurate.

One hundred and nine consecutive patients undergoing surgery for uterovaginal prolapse followed by indwelling urinary catheter for 3 days were randomized for prophylactic treatment with methenamine hippurate (MH) or no MH prophylaxis. Significantly less bacteriuria occurred in the MH-treated patient group. In particular, the opportunistic hospital flora appeared to be suppressed by MH treatment. It is suggested that MH prophylaxis, 1 g three times daily, be used in gynecological surgery followed by short-term urinary catheterization.

Pharmacokinetics of dixyrazine: low bioavailability, improved by food intake.

The single-dose kinetics of the psychotropic phenothiazine dixyrazine was assessed in eight young healthy volunteers given the drug at three occasions: 10 mg intravenously, 25 mg orally in the fasting state, and 25 mg orally together with a standardized breakfast of 1,840 kJ. The plasma concentrations of dixyrazine were measured by high-pressure liquid chromatography. Like some other lipophilic weakly basic drugs, dixyrazine showed a rapid disappearance from plasma, having an elimination half-life of 3.4 h, a clearance of about 1,200 ml/min, and an apparent volume of distribution of 5.9 l/kg. Dixyrazine was found to have a very low and interindividually varying bioavailability; in the fasting state, dixyrazine bioavailability was only 1% in one subject, 3-6% in five others, and 11 and 24% in the remaining two subjects. The mean fasting bioavailability was 7.4%. After intake with breakfast, the mean bioavailability was increased to 12.4% (p less than 0.01), with a range of 2-29%. Probably, the low oral bioavailability is due to extensive presystemic (hepatic) degradation, and the food effect to a reduction of this process.