The structuring of an allergy index based on IgE-mediated skin sensitivity to common environmental allergens

We computed skin-test sensitivity levels in 485 adults puncture-tested with eight standardized, high-quality inhalant allergens tested at single concentrations. In order to quantitate the "average" IgE-mediated skin sensitivity of each subject, we used both nonparametric and parametric statistical methods to generate two "allergy indices" (Allergy Index I and Allergy Index II) based on sensitivity end-point data from the subpopulations of individuals positive to six of the eight allergens. For the 192 skin test-positive subjects, Allergy Index I and Allergy Index II were significantly correlated with each other (rs = 0.98, p less than 0.001) and with the number of positive skin-test reactions (rs congruent to 0.9, p less than 0.001) as well as with log[total serum IgE] (r congruent to 0.4, p less than 0.01). In 102 ragweed-positive subjects, log[specific IgE to ragweed] was significantly correlated with ragweed-specific "ragweed indices I and II" (r congruent to 0.6, p less than 0.01). Furthermore, the average daily symptom scores reported by 14 ragweed-positive subjects during the ragweed pollination season were significantly correlated with ragweed indices I and II (p less than 0.05). We propose the use of Allergy Index II in epidemiologic and genetic studies of allergic phenotypes as well as in clinical decisions for diagnosis and immunotherapeutic intervention.     

Surface markers of human natural killer cells as analyzed in a modified single cell cytotoxicity assay on poly-L-lysine coated cover slips

A modified single cell cytotoxicity assay using poly-L-lysine coated cover slips (PLL-SCCA) was employed to study the frequency and surface marker profile of human peripheral blood lymphocytes (PBL) with NK reactivity against K 562 target cells. When compared with the previously described agarose single cell cytotoxicity assay (A-SCCA) identical results were obtained. For 13 donors tested 18.1 +/- 4.4% of the PBL formed conjugates with K 562 and 2.7 +/- 1.6% displayed NK reactivity. In contrast to the A-SCCA, the PLL-modified assay permits direct identification of both conjugate forming (TBC) and cytolytic PBL (NK) by means of surface markers. Indirect immunofluorescence studies with monoclonal anti-PBL antibodies revealed that neither the plating procedures nor the incubation conditions employed affected the expression of the antigens recognized by these reagents. This method of directly identifying NK cells showed that OKM1+ cells were enriched among the NK cells as compared to PBL and TBC (55% vs. 23% and 43%, respectively). In contrast, the OKT3+ or Leu1+ fraction of the NK cells was reduced as compared to PBL and TBC. However, using this method of identification at the effector cell level, a substantial proportion of the NK cells were OKT3+ or Leu1+ (57% or 58% respectively, 7 donors). Approximately 25% of the NK cells were Leu2a+ and 30% were Leu3a+, respectively. However, the size of the Leu3a+ fraction varied considerably with individual donors and the size of this fraction appeared to be inversely related to that of the donors NK pool.     

Will the new cytogenetics replace the old cytogenetics?

With the advent of array-based comparative genomic hybridization technology, the analog cytogenetic analysis that has been used for the past 100 years could be replaced by the quantitative, microarray-based molecular analysis. Major advantages of the new array-based cytogenetic technologies are the high resolution and the high throughput. This technology is the first to offer an autonomous whole-chromosome analysis in one hybridization reaction for the detection of submicroscopic gains/losses. However, as with any new technology, it needs to be validated with regard to its performance in various applications (e.g. clinical genetic testing and cancer applications), comparative cost, and the data interpretation.     

Radial artery running beneath the biceps tendon and its interrelation between the radial recurrent arteries

A radial artery running beneath the biceps tendon was found in the cadaver of a Japanese woman during a student dissection course at Kumamoto University School of Medicine in 2006. The brachial artery bifurcated into the radial artery and the ulnar artery in the cubital fossa, and the radial artery twisted laterally running beneath the biceps tendon, and when it was situated laterally to the tendon, twisted distally at the level of the radial tuberosity, and then twisted medially again. After the radial artery passed over the biceps tendon, it turned distally and continued as a normal radial artery. The superficial brachial artery, which coexisted with the brachial artery, was given off from the axillary artery and it continued to the final twist of the radial artery. The course of this radial artery is similar to the arterial rings surrounding the biceps tendon, found during the same dissection course. The arterial rings were formed between the brachial artery and the radial artery, and their proximal origins ran beneath the biceps tendon, while the distal origins were superficial. The present arterial variation is thought to have occurred when the normal part of the radial artery in the cubital fossa was substituted by the arterial ring, coexisting with the superficial brachial artery, which usually disappears during normal development. Furthermore, it is suggested that a part of the arterial ring always remains as a radial recurrent artery.     

Heritability and Expression of C-Reactive Protein in Type 2 Diabetes in the Diabetes Heart Study

Elevated C-reactive protein (CRP) levels are associated with both prevalent and incident cardiovascular disease. In this study, familial aggregation was estimated, and we tested for association between serum CRP levels and polymorphisms within the CRP and APOE genes in sib-ships with type 2 diabetes mellitus, a population at increased risk for cardiovascular disease. CRP levels were determined in 461 diabetes-affected subjects from 224 sibships from the Diabetes Heart Study (DHS). Heritability estimates of CRP levels were obtained using variance component models. Genetic influence on serum CRP levels by single nucleotide polymorphisms (SNPs) in the CRP and APOE genes was evaluated by association analysis using mixed models. Subjects were Caucasian American (84%) and African-American (16%), 53% female, and had an average age of 62.2 ± 9.2 years. The median CRP level was 3.3 mg/L (range 0 to 59.3 mg/L), and estimated heritability for CRP was approximately 40%. Estimates of heritability were significantly greater than zero (P < 0.0001) and relatively constant, despite adjustments for important modifiers (age, sex, ethnicity, diabetes duration, statin-use and anti-inflammatory use) of CRP. There was no significant evidence for association of CRP levels with CRP gene SNPs; however, consistent with previous reports, there was significant evidence of association of CRP levels with polymorphisms within the APOE gene. These data indicate CRP levels are significantly influenced by genetic (and/or environmental) factors that are shared within DHS families. While the APOE locus shows evidence of contributing to CRP levels, no evidence of CRP gene polymorphism association with CRP levels was observed.     

Methodologic problems in establishing normal values for IgG subclass concentrations in a pediatric population; comparison of radial immunodiffusion and ELISA methods

The aim of this study was to establish an enzyme-linked immunosorbent assay (ELISA) to measure IgG subclasses by means of monoclonal antibodies. The distribution of IgG subclass protein concentrations in sera from 227 healthy Danish children and 90 adults was measured. Furthermore, this newly established ELISA was compared with different assay systems for determination of IgG subclasses: two radial immunodiffusion methods (RID), one using polyclonal and one using monoclonal antibodies, as well as a commercially available ELISA kit. There was good agreement of results obtained by the different methods of measuring IgG3 and IgG4 concentrations. There was good correlation between results obtained by both RID methods. Despite good correlation between the assays, the ELISA kit showed higher levels of IgG1 in all investigated sera, and the ELISA kit showed no correlation with the other methods, when IgG2 was measured. Analysis of the normal ranges measured by ELISA developed in our laboratory and by RID with polyclonal antibodies showed that the levels obtained by RID were higher than those obtained by our ELISA in sera with low levels of both IgG1 and IgG2, and lower in sera with high concentrations of these two immunoglobulins. Our results emphasize the importance of establishing age-related normal limits for any novel assay measuring IgG subclass concentrations.     

The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy

Cardiomyopathy is a heart muscle disease with impaired stretch response that can result in severe heart failure and sudden death. A small proportion of hepatitis C virus (HCV)-infected patients may be predisposed to develop dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The molecular mechanisms involved in the predisposition remain unknown due in part to the lack of information on their genetic background. Because the human leukocyte antigen (HLA) region has a pivotal role in controlling the susceptibility to HCV-induced liver disease, we hypothesized that particular HLA alleles and/or non-HLA gene alleles within the human major histocompatibility complex (MHC) genomic region might control the predisposition to HCV-associated DCM (HCV-DCM) and/or HCV-associated HCM (HCV-HCM). Here, we present mapping results of the MHC-related susceptibility gene locus for HCV-associated cardiomyopathy by analyzing microsatellite and single nucleotide polymorphism markers. To delineate the susceptibility locus, we genotyped 44 polymorphic markers scattered across the entire MHC region in a total of 59 patients (21 HCV-DCM and 38 HCV-HCM) and 120 controls. We mapped HCV-DCM susceptibility to a non-HLA gene locus spanning from NFKBIL1 to MICA gene loci within the MHC class III-class I boundary region. Our results showed that HCV-DCM was more strongly associated with alleles of the non-HLA genes rather than the HLA genes themselves. In addition, no significant association was found between the MHC markers and HCV-HCM. This marked difference in the MHC-related disease susceptibility for HCV- associated cardiomyopathy strongly suggests that the development of HCV- DCM and HCV-HCM is under the control of different pathogenic mechanisms.     

Modulation of human cutaneous reflexes during rhythmic cyclical arm movement

The organization and pattern of cutaneous reflex modulation is unknown during rhythmic cyclical movements of the human upper limbs. On the assumption that these cyclic arm movements are central pattern generator (CPG) driven as has been suggested for leg movements such as walking, we hypothesized that cutaneous reflex amplitude would be independent of electromyographic (EMG) muscle activation level during rhythmic arm movement (phase-dependent modulation, as is often the case in the lower limb during locomotion). EMG was recorded from eight muscles crossing the human shoulder, elbow, and wrist joints while whole arm rhythmic cyclical movements were performed. Cutaneous reflexes were evoked with trains of electrical stimulation delivered at non-noxious intensities (approximately 2 x threshold for radiating paresthesia) to the superficial radial nerve innervating the lateral portion of the back of the hand. Phasic bursts of rhythmic muscle activity occurred throughout the movement cycle. Rhythmic EMG and kinematic patterns were similar to what has been seen in the human lower limb during locomotor activities such as cycling or walking: there were extensive periods of reciprocal activation of antagonist muscles. For most muscles, cutaneous reflexes were modulated with the movement cycle and were strongly correlated with the movement-related background EMG amplitude. It is concluded that cutaneous reflexes are primarily modulated by the background muscle activity during rhythmic human upper limb movements, with only some muscles showing phase-dependent modulation.     

Propene Polymerisation with rac‐[Me2Si(2‐Me‐4‐(α‐naphthyl)‐1‐Ind)2]ZrCl2 as a Highly Active Catalyst: Influence of Monomer Concentration,Polymerisation Temperature and a Heterogenising Support

Propene was polymerised at high temperatures (up to 90 °C) using rac‐[Me₂Si(2‐Me‐4‐(α‐naphthyl)‐1‐Ind)₂]ZrCl₂/MAO as the catalytic system. The increasing deactivation reaction rate of the catalyst for polymerisations above 60 °C was less for a silica supported catalyst compared with the homogeneous one. The isotacticity of polypropene decreases from 99 to 96%. Also the morphology changes with different temperatures.

Increasing of the thermal stability for the rac‐[Me₂Si(2‐Me‐4‐(α‐naphthyl)‐1‐Ind)₂]ZrCl₂/MAO/SiO₂ with respect of the rac‐[Me₂Si(2‐Me‐4‐(α‐naphthyl)‐1‐Ind)₂]ZrCl₂/MAO system.     

Aberrant expression of beta-catenin and mutation of exon 3 of the beta-catenin gene in renal and urothelial carcinomas

The present study attempted to clarify the significance of aberrant expression of beta-catenin protein and mutation of exon 3 of the beta-catenin gene in renal and urothelial carcinogenesis. beta-Catenin expression was examined immunohistochemically and mutation of the beta-catenin gene was analyzed by polymerase chain reaction-single strand conformation polymorphism (SSCP) and direct sequencing. beta-Catenin immunoreactivity was observed at the cell membrane in all 30 renal cell carcinomas (RCC) examined, and no RCC showed a mobility-shifted SSCP band. Of 46 transitional cell carcinomas (TCC) examined, there was reduced expression of beta-catenin, as compared with its expression in non-cancerous transitional epithelium, in 22 cases (48%) and beta-catenin accumulation in the nucleus in five cases (11%). Of four renal pelvis TCC examined, point mutation of exon 3 of the beta-catenin gene at codon 45 resulting in amino acid substitution (Ser to Phe) was detected in one (25%). The incidence of reduced expression of beta-catenin correlated significantly with the growth pattern (superficial type vs invasive type) of TCC (P < 0.05). These data indicate that: (1) aberrant beta-catenin expression may be at least partly involved in urothelial carcinogenesis, but less significantly so in renal carcinogenesis, and (2) it may be associated with the progression of TCC showing invasive growth.