Statistische Untersuchungen zur intra- und interfamiliären Variabilität des Monilethrix-Gens

Zusammenfassung Die monileformen Kopfhaare von 33 an Monilethrix erkrankten Patienten aus fünf Familien wurden mikroskopisch vermessen und mit Hilfe statistischer Berechnungen auf ihre intra- und interfamiliäre Variabilität hin untersucht.Bei der Berechnung der intrafamiliären Variabilität ergaben sich signifikante Unterschiede bei den Meßwerten der untersuchten Strukturelemente: Nodi, Internodi und Längeneinheiten. Faktoren, die diese Unterschiede bewirken könnten, werden erörtert.Die Berechnung der Variabilitäten zwischen unseren fünf Familien zeigte Hinweise auf signifikante Unterschiede bei den Meßwerten der Nodi und denen der Längeneinheiten. Somit scheinen die einflußnehmenden Faktoren nur wahrscheinlich (nicht sicher) ein familienspezifisches Niveau zu besitzen.Bei den Meßwerten der Internodi hingegen konnte kein signifikanter Unterschied zwischen den Familien festgestellt werden. Deshalb nehmen wir an, daß nur am Internodus die Wirkung des Monilethrix-Gens frei von familienspezifischen Einflüssen zum Ausdruck kommt.

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Summary The pathological hairs of 33 patients with monilethrix (Aplasia pilorum intermittens) we have measured with a microscopic measuring-instrument. Furthermore we have examined the differences within and between our five families with statistical methods.The variability within the families shows significant differences for the results of nodi, internodi and lengths. The factors which may cause these differences are discussed.Analysis of variance and co-variance between our five families shows only small differences at the border line of statistical significance for nodi and lengths. There is only a small probability that these differences between our families reflect the influence of other genetic factors.The measurements of internodi show no significant differences between the families. It is concluded that the gene for monilethrix is expressed in the internoduswidth without influences of other family-specific factors.

     

Functional polymorphism 57Val>Ile of aurora kinase A associated with increased risk of gastric cancer progression

Overexpression or amplification of the aurora kinase A (AURKA) gene induces chromosomal instability and transformation. AURKA SNPs are associated with several human cancers but their association with gastric cancer has yet to be investigated. In this study, 501 gastric cancer patients and 427 controls were genotyped for two coding SNPs in AURKA, 91A>T (31Ile>Phe) and 169G>A (57Val>Ile). Allele or genotype association with gastric cancer susceptibility was not observed in comparisons between the patient and control samples. However, 169G/G genotype was significantly more frequent in advanced gastric cancers than in early gastric cancers (age/sex-adjusted OR=2.2, 95% CI=1.3-3.8, P=0.0042). Moreover, the elevated risk of gastric cancer progression was associated with 91T-169G (age/sex-adjusted OR=1.9, 95% CI=1.1-3.4, P=0.025) and 91A-169G (age/sex-adjusted OR=1.6, 95% CI=1.0-2.6, P=0.048) haplotypes, having approximately 2.5-fold higher kinase activity than 91T-169A haplotype. The results suggest that 169G>A in AURKA is associated with progression of gastric cancer by affecting relative kinase activities of AURKA variants.     

Effects of mixed leukocyte reaction,hydrocortisone and cyclosporine on expression of leukocyte adhesion molecules by endothelial and mesangial cells.

We investigated the effects of mixed leukocyte reaction (MLR), hydrocortisone (HC) and cyclosporine A (CsA) on the expression of leukocyte adhesion molecules on the mesangial (MC) and endothelial cells (EnC). Cell surface enzyme immunoassay showed that INFnu, IL-1beta, or TNF alpha stimulated expression of ICAM-1, or VCAM-1 on MC after 24 hours. Flow cytometric analysis demonstrated that MLR supernatant induced a marked increase in mean fluorescence of or % of cells highly expressing intercellular adhesion molecule(ICAM)-1 or vascular cell adhesion molecule (VCAM)-1 on both cells after 24 hours (p<0.001). HC treatment(300 ng/ml) during MLR effectively inhibited MLR-induced upregulation of ICAM-1 and VCAM-1 on both cells (p<0.005). When MLR supernatant with HC was added to adhesion molecule assay, there was no inhibitory effect of HC on VCAM-1. CsA treatment (500 ng/ml) during MLR caused a modest decrease in upregulation of VCAM-1 on EnC (p<0.05), but had no effects on ICAM-1 on both cells. CsA directly decreased expression of VCAM-1 on MC. In conclusion, alloreactive lymphocytes and monocytes upregulate the expression of VCAM-1 and ICAM-1 on target cells probably by the mediation of cytokines. HC effectively prevents MLR-induced upregulation of VCAM-1 and ICAM-1. CsA does not increase the expression of VCAM-1 and ICAM-1.     

Impact of Reduced Vancomycin MIC on Clinical Outcomes of Methicillin-Resistant Staphylococcus aureus Bacteremia

Vancomycin has been a key antibiotic agent for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. However, little is known about the relationship between vancomycin MIC values at the higher end of the susceptibility range and clinical outcomes. The aim of this study was to determine the impact of MRSA bacteremia on clinical outcomes in patients with a vancomycin MIC near the upper limit of the susceptible range. Patients with MRSA bacteremia were divided into a high-vancomycin-MIC group (2 μg/ml) and a low-vancomycin-MIC group (≤1.0 μg/ml). We examined the relationship between MIC, genotype, primary source of bacteremia, and mortality. Ninety-four patients with MRSA bacteremia, including 31 with a high vancomycin MIC and 63 with a low MIC were analyzed. There was no significant difference between the presence of agr dysfunction and SCCmec type between the two groups. A higher vancomycin MIC was not found to be associated with mortality. In contrast, high-risk bloodstream infection sources (hazard ratio [HR], 4.63; 95% confidence interval [CI] = 1.24 to 17.33) and bacterial eradication after treatment (HR, 0.06; 95% CI = 0.02 to 0.17), irrespective of vancomycin MIC, were predictors of all-cause 30-day mortality. Our study suggests that a high-risk source of bacteremia is likely to be associated with unfavorable clinical outcomes, but a high vancomycin MIC in a susceptible range, as well as genotype characteristics, are not associated with mortality.     

Results of a cemented titanium alloy straight femoral shaft prosthesis after 10 years of follow-up

Two-hundred fifty implantations of a cemented femoral stem made of titanium alloy in 239 patients were followed for 9.7 years (range 8.7-10.3 years). Eighty-nine patients with 93 hips have died and two could not be located. Five hips have been revised, two for infection, one for aseptic loosening and two during revision of the cup. Three stems showed radiological loosening but have not been revised. The average hip score was 85. The results are encouraging and comparable to other cemented femoral stems.     

The relationship between circulating fibroblast growth factor 23 and bone metabolism factors in Korean hemodialysis patients

Background  

Fibroblast growth factor 23 (FGF-23) is a circulating factor that acts as a phosphaturic factor in the kidneys. It is also involved in several disorders of phosphate regulation and bone metabolism. We hypothesized that increased FGF-23 levels in patients with endstage renal disease (ESRD) on maintenance hemodialysis would be associated with increased bone demineralization, and we analyzed the relationship between FGF-23 levels and bone mineral density (BMD).     

High fat diet downregulates regulatory T cells in the myocardium of spontaneous hypertensive rats

Background and aimRegulatory T cells (Tregs) play an important role in cardiovascular complications with the immune response. However, the role of Tregs in high fat diet (HFD)-induced myocardial fibrosis has not been fully elucidated to date. Therefore, we investigated whether HFD suppresses Tregs activation in the myocardium of spontaneously hypertensive rats (SHRs), which aggregates myocardial fibrosis.Methods and resultsEight-week-old male SHRs were fed to either HFD or control diet (CHO) groups for 12 weeks. We measured Tregs (CD4+FoxP3+) in the heart and mediastinal lymph nodes (LNs). The flow cytometry analysis confirmed that SHR-HFD exhibited a decreased Tregs compared to that of SHR-CHO in the heart and mediastinal LNs. Furthermore, the CD4 and FoxP3 antigens were used in the immunofluorescence microscopy of Tregs in the heart tissues. In the heart, dual staining for the Treg population was increased more in SHR-CHO than it was in SHR-HFD rats. In line with these findings, SHR-HFD significantly exacerbated myocardial fibrosis.ConclusionWe found that diet-induced obesity typically showed an exacerbated myocardial fibrosis and down-regulation of Tregs pathway in the heart and mediastinal LNs. Therefore, we suggest that the up-regulation of Tregs may be a promising therapeutic approach to preventing obesity induced heart failure.     

The usefulness of multiplex PCR for the identification of bacteria in joint infection

Background: The diagnosis of septic arthritis (SA) relies on synovial analysis and conventional culture. But, these methods lack of sensitivity and culture is time consuming to establish a definite diagnosis. This study evaluated a new multiplex PCR assay which entailed screening PCR for Gram typing and identification PCR for species identification using two primer mixes. Methods: A total of 80 synovial fluid samples from patients with suspected SA were collected. Culture, multiplex PCR, and 16S rRNA gene PCR were performed. Results: The analytical sensitivity of multiplex PCR assay was 10¹ CFU/ml for each type of bacteria. There was no cross‐reactivity with common bacterial pathogens. Bacteria were detected in 20, 25, and 26 of 80 samples for culture, multiplex PCR, and 16S rRNA gene PCR, respectively. Nineteen (95%) of 20 culture‐positivesamples and 6 (10%) of 60 culture‐negative samples were positive for the multiplex PCR. Five of six samples which were positive only from multiplex PCR were also positive in 16S rRNA gene PCR. The multiplex PCR showed 2 false‐negative in 27 true‐positive samples but no false‐positive. The sensitivity and specificity of the multiplex PCR were 92.6 and 100%, and the agreement with culture and 16S rRNA gene PCR were 91.3 and 96.3%, respectively. The time to detection for multiplex PCR was a maximum of 6 hr. Conclusion: This multiplex PCR assay offers high sensitivity and improved detection speed relative to culture. The appropriate combination of this new multiplex PCR assay with culture may contribute to the accurate and rapid diagnosis of SA. J. Clin. Lab. Anal. 24:175–181, 2010. © 2010 Wiley‐Liss, Inc.