Hiromichi Mitsuyasu

Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma.

Atopy is an immune disorder characterized by heightened immunoglobulin E (IgE) production and leads to the clinical disorders of asthma, eczema and rhinitis1. Interleukin 4 (IL4) is a pleiotropic cytokine which plays a crucial role in IgEdependent atopic disorders2; it is central to B cells switching to IgE antibody production and to the maturation of T-helper cells to the Th2 phenotype (type-2 Thelper lymphocyte). Human IL4 operates through the IL4 receptor (IL4R) and thereby Stat6 (signal transducer and activator of transcription 6) activation3. Mice deficient in Stat6 (refs 4,5) or the IL4Rα chain6 lack IgE production and Th2 inflammatory reactions. IL4Rα is therefore a crucial component required for IL4 binding and signal transduction. A cytoplasmic variant of IL4Rα, an Arg576Gln substitution (numbering from the first ATG), has been recently identified and is found in excess in a study of a group of individuals with hyper-IgE syndrome and severe eczema7; functional assays showed impaired binding of the negative regulatory molecule, protein tyrosine phosphatase, SHP-1, and increased expression of CD23 was found on peripheral blood mononuclear cells after being challenged with IL4. Stat6 activation, however, was not upregulated and no information was provided on cellular IgE synthesis. An extracellular variant, Thr49Ile, in IL4Rα of BALB/c mice alters the ligandbinding affinity of IL4Rα (ref. 8). An Ile50Val (numbering for mature peptide) variant of human IL4Rα has also been identified9,10 and it is, to date, the only known extracellular variant of human IL4Rα (ref. 11). To test whether the Ile50Val variant promotes dysregulation of IgE synthesis, we first conducted a genetic association study for serum IgE levels in a Japanese population. There was a significant difference in Ile/Val 50 genotype frequencies between control and atopic subjects (Table 1); Ile50 associated with atopic asthma but not with non-atopic asthma; Ile50 specifically and significantly associated with raised total serum IgE levels and mite-specific IgE. The association with atopy was especially strong in children. The high frequency of Ile50 homozygotes (approximately 60%) in the childhood atopic asthma group described here, and the significant skewing from Hardy-Weinberg equilibrium (P<0.0001), suggest a largely recessive genetic effect for Ile50 on atopy; the previously reported

Clinical features of multiple epiphyseal dysplasia expressed in the knee

The purpose of this study is to clarify the clinical features of the knee affected by multiple epiphyseal dysplasia. Thirty-one cases of multiple epiphyseal dysplasia were reviewed. Of the patients, 11 were male and 20 were female. The average age at onset of symptoms was 22.5 years. The average age at initial visit to the authors’ hospital was 28.9 years. Radiographic findings showed epiphyseal abnormality of the knee in all but two (93%) cases. Irregularity, segmentation of the epiphysis, widening of the joint space, and genu valgum deformity were the dominant findings before epiphyseal closure. After epiphyseal closure, the most characteristic finding was a shallow femoral trochlear groove, which was observed in 56.5% of the cases. Other findings in adult patients included early onset osteoarthritic change, genu valgum, depression of the lateral tibial plateau, and multiple free bodies. However, there still is a possibility that multiple epiphyseal dysplasia exists, even if the patient lacks a shallow femoral trochlear groove. If genu valgum or varum, free bodies, and premature osteoarthritis are observed, one should evaluate other joints, keeping a diagnosis of multiple epiphyseal dysplasia in mind. Patients with knees that have a femoral trochlear groove of normal or near normal shape do exist, and premature osteoarthritic changes may develop in such patients.

Structure of the human transcription factor TFIIF revealed by limited proteolysis with trypsin

In this study, the human general transcription factor IIF (TFIIF), a heteromeric complex of RAP74 and RAP30 subunits, was subjected to limited proteolysis with trypsin. The central region of RAP74 was demonstrated to be highly sensitive to trypsin while both the N‐ and C‐terminal regions contained trypsin‐resistant structures. In contrast, RAP30 digestion occurred after proteolysis of RAP74. The digestion pattern of RAP74 recruited into the preinitiation complex showed no marked difference from that of IIF, while RAP30 in the complex was protected from trypsin. These results indicate that RAP74 apparently contains three structural domains, the central one of which is externally surfaced and unstructured, but RAP30 is internally wrapped by RAP74. Furthermore, the accessibility of the central region of RAP74 is unaltered in the minimal preinitiation complex, while RAP30 is involved in promoter recognition through its DNA binding activity.

Strength enhancement of the interlocking mechanism in cross-stitch peripheral sutures for flexor tendon repair: Biomechanical comparisons by cyclic loading

The fatigue strength of three peripheral suture techniques for flexor tendon repair was compared by cyclic loading of repairs in a cotton dental roll tendon model. Thirty pairs of dental roll were sutured using only peripheral sutures with 6-0 polypropylene. An initial cyclic load of 5 N for 500 cycles was applied and increased by 5 N for an additional 500 cycles at each new load until rupture. The fatigue strength of an interlocking cross-stitch suture was 113% greater than a running suture and 36% greater than a standard cross-stitch suture. Interlocking the cross-stitch prevented shortening of the transverse portions under load and appears to be a useful technique for increasing the strength of the peripheral suture.

The biomechanical assessment of gap formation after flexor tendon repair using partial interlocking cross-stitch peripheral sutures

The gap formation of five core plus peripheral suture techniques for flexor tendon repair was evaluated by cyclic load testing. Fifty pairs of dental roll tendon models were sutured using six-strand Pennington modified Kessler core suture with 4-0 Polypropylene. One-half or three-fourths circumferential interlocking cross-stitch, or three complete circumferential peripheral suture techniques were performed using 6-0 Polypropylene. An initial cyclic load of 10 N for 500 cycles was applied and increased by 5 N for an additional 500 cycles at each new load until rupture. The complete circumferential interlocking cross-stitch had the greatest fatigue strength. The partial circumferential cross-stitches resulted in significantly larger gap formations at both the repaired and unrepaired sides than the complete circumferential sutures, and were also associated with early rupture. The full circumference of the cut tendon must be sutured using an interlocking cross-stitch peripheral suture to improve strength and avoid gap formation.

Right thoracic curvature in the normal spine

BackgroundTrunk asymmetry and vertebral rotation, at times observed in the normal spine, resemble the characteristics of adolescent idiopathic scoliosis (AIS). Right thoracic curvature has also been reported in the normal spine. If it is determined that the features of right thoracic side curvature in the normal spine are the same as those observed in AIS, these findings might provide a basis for elucidating the etiology of this condition. For this reason, we investigated right thoracic curvature in the normal spine.MethodsFor normal spinal measurements, 1,200 patients who underwent a posteroanterior chest radiographs were evaluated. These consisted of 400 children (ages 4-9), 400 adolescents (ages 10-19) and 400 adults (ages 20-29), with each group comprised of both genders. The exclusion criteria were obvious chest and spinal diseases. As side curvature is minimal in normal spines and the range at which curvature is measured is difficult to ascertain, first the typical curvature range in scoliosis patients was determined and then the Cobb angle in normal spines was measured using the same range as the scoliosis curve, from T5 to T12. Right thoracic curvature was given a positive value. The curve pattern was organized in each collective three groups: neutral (from -1 degree to 1 degree), right (> +1 degree), and left (< -1 degree).ResultsIn child group, Cobb angle in left was 120, in neutral was 125 and in right was 155. In adolescent group, Cobb angle in left was 70, in neutral was 114 and in right was 216. In adult group, Cobb angle in left was 46, in neutral was 102 and in right was 252. The curvature pattern shifts to the right side in the adolescent group (p < 0.01) and in adult group (p < 0.001) compared to the child group. There was no significant difference in curvature pattern between adolescent and adult group.ConclusionsBased on standing chest radiographic measurements, a right thoracic curvature was observed in normal spines after adolescence.

Lipoma causing posterior interosseous nerve palsy or superficial radial nerve paraesthesia

Dear Sir, A lipoma is a benign slow-growing tumour that is usually subcutaneous. A deep lipoma at the elbow may cause compression of the posterior interosseous nerve, leading to weakness of extension of digits, and/or compression of the superficial division of the radial nerve, leading to paraesthesia (Bieber et al., 1986; Fitzgerald et al., 2002; Lidor et al., 1992). We report eight patients who had a lipoma at the elbow, two male and six female, with a mean age of 54.6 years (range, 26 to 75 years). Three patients had palsy, one of which was accompanied by paraesthesia in the radial half of the dorsum of the hand. Four patients had paraesthesia without palsy. The mean duration of symptoms to surgery was 12.7 (range, 1 to 24) months. One case had no neurological symptoms. All had surgery through an anterior approach. The compression of the posterior interosseous nerve and the superficial division of the radial nerve were recorded. Two of three cases with palsy recovered. Muscle strength was measured as described by the Medical Research Council (MRC) using the numeral grades 0–5 (Medical Research Council, 1976). One showed recovery from grade 3 (fair) to grade 5 (normal), and the other from grade 2 (poor) to 4 (good). The patient with complete paralysis showed no recovery after surgery. In all three patients with paralysis, the posterior interosseous nerve was compressed toward the flexor side (Fig 1). In the other five cases without palsy, the posterior interosseous nerve was compressed toward the flexor side in one and toward the extensor side in four. In the five patients with paraesthesia, the superficial division of the radial nerve was compressed toward the flexor side in four and toward the extensor side in one. In the other three patients without paraesthesia, the superficial division of the radial nerve was compressed toward the flexor side in one but was not compressed in two. The posterior interosseous nerve passes through the supinator muscle under the arcade of Frohse. When a tumour is located on the extensor side of the posterior interosseous nerve, it would compress it against the edge of the arcade. The superficial division of the radial nerve passes above the supinator muscle and the arcade of Frohse and is compressed by the mass itself.

Degenerative Lumbosacral Kyphosis in Elderly Patients

A flexed posture is seen to develop in association with increasing age. Patients with such a flexed posture have several problems, and it is difficult to treat these favorably. To treat this type of deformity, we must understand the alignment of the patients spine.We classified lumbosacral kyphosis into three types depending on sacral inclination and disc degeneration in the lower lumbar spine. Patients with a deformity due to loss of sacral inclination and malalignment in lower lumbar spine showed marked disability in daily life and had severe lumbago.Sacral inclination seemed to be an important factor in the treatment of patients with deformity both surgically and non-surgically. We may operate on them using lumbosacral fusion and correction using Galveston technique with ISOLA instrumentation.