Churg-Strauss Syndrome with Necrosis of Toe Tips

Churg-Strauss syndrome (CSS) is a granulomatous necrotizing vasculitis of unknown etiology associated with bronchial asthma. Despite affecting small to medium-sized vessels, necrosis of the digits due to vasculitis is extremely rare. We report a case of CSS with necrosis of the toe tips. A 37-year-old woman with asthma, who had been diagnosed with CSS 2 years ago, was admitted to our hospital with an exacerbation of CSS. The patient had a high grade fever and complained of abdominal pain and numbness of the lower extremities. Blood examination revealed marked eosinophilia. The fever pattern, abdominal pain and blood eosinophilia showed improvement by combination treatment with prednisolone and cyclophosphamide. However, the color of her right toe tips changed, and necrosis finally resulted despite antithrombotic therapy. Arteriography showed narrowing of the dorsalis pedis artery and of the more peripheral arteries of her right leg. Stump plasty with negative pressure dressing therapy for the toe tips, but not amputation, was done to preserve the leg function. While numbness of the extremities remained, no recurrence of necrosis was seen. Clinicians need to be aware that rare complications of CSS, including necrosis of the digits, can occur

Synergistic defect in 60S ribosomal subunit assembly caused by a mutation of Rrs1p, a ribosomal protein L11-binding protein, and 3′-extension of 5S rRNA in Saccharomyces cerevisiae

Rrs1p, a ribosomal protein L11-binding protein, has an essential role in biogenesis of 60S ribosomal subunits. We obtained conditionally synthetic lethal allele with the rrs1-5 mutation and determined that the mutation is in REX1, which encodes an exonuclease. The highly conserved leucine at 305 was substituted with tryptophan in rex1-1. The rex1-1 allele resulted in 3′-extended 5S rRNA. Polysome analysis revealed that rex1-1 and rrs1-5 caused a synergistic defect in the assembly of 60S ribosomal subunits. In vivo and in vitro binding assays indicate that Rrs1p interacts with the ribosomal protein L5–5S rRNA complex. The rrs1-5 mutation weakens the interaction between Rrs1p with both L5 and L11. These data suggest that the assembly of L5–5S rRNA on 60S ribosomal subunits coordinates with assembly of L11 via Rrs1p

Effects of swimming training in the hot spring pool on ventilatory function in bronchial asthma

Effect of free swimming training in the hot spring pool (30℃) on ventilatory function were observed in nine patients with intractable asthma by measuring FVC, FEV(1.0), PEFR, MMF, V(50), V(25). 1. Swimming in the hot spring pool for three months allowed the reduction of glucocorticoid used for their asthma attack. 2. Although FVC was not affected by swimming training, EEV(1.0), PEFR, MMF, V(50), V(25) which represent obstructive ventilatory function were gradually improved by swimming training. The results show that free swimming training in the hot springpool is clinically available in intractable asthma

DNA markers based on retrotransposon insertion polymorphisms can detect short DNA fragments for strawberry cultivar identification

In this study, DNA markers were developed for discrimination of strawberry (Fragaria × ananassa L.) cultivars based on retrotransposon insertion polymorphisms. We performed a comprehensive genomic search to identify retrotransposon insertion sites and subsequently selected one retrotransposon family, designated CL3, which provided reliable discrimination among strawberry cultivars. Through analyses of 75 strawberry cultivars, we developed eight cultivar-specific markers based on CL3 retrotransposon insertion sites. Used in combination with 10 additional polymorphic markers, we differentiated 35 strawberry cultivars commonly cultivated in Japan. In addition, we demonstrated that the retrotransposon-based markers were effective for PCR detection of DNA extracted from processed food materials, whereas a SSR marker was ineffective. These results indicated that the retrotransposon-based markers are useful for cultivar discrimination for processed food products, such as jams, in which DNA may be fragmented or degraded

Coordinately Co-opted Multiple Transposable Elements Constitute an Enhancer for wnt5a Expression in the Mammalian Secondary Palate

Acquisition of cis-regulatory elements is a major driving force of evolution, and there are several examples of developmental enhancers derived from transposable elements (TEs). However, it remains unclear whether one enhancer element could have been produced via cooperation among multiple, yet distinct, TEs during evolution. Here we show that an evolutionarily conserved genomic region named AS3_9 comprises three TEs (AmnSINE1, X6b_DNA and MER117), inserted side-by-side, and functions as a distal enhancer for wnt5a expression during morphogenesis of the mammalian secondary palate. Functional analysis of each TE revealed step-by-step retroposition/transposition and co-option together with acquisition of a binding site for Msx1 for its full enhancer function during mammalian evolution. The present study provides a new perspective suggesting that a huge variety of TEs, in combination, could have accelerated the diversity of cis-regulatory elements involved in morphological evolution

Clinical effects of swimming training in a hot spring pool on bronchial asthma

Five severe bronchial asthma patients with glucocorticoid therapy have had free swimming training in the hot spring pool at Misasa Medical Branch. The clinical effect of the swimming training was evaluated after 3 months' training. 1. A slight increase in pulse rate and blood pressure was observed immediately after 30 minutes, swimming, although no significant increase in the two parameters was shown 30 min. after the training. 2. No significant fall in ventilatory function tests such as % FVC, FEV(1.0)%, V(50) and V(25) was demonstrated following the swimming training in a hot spring pool. The results suggest that the free swimming training in a hot spring pool does not induce bronchoconstriction. 3. Clinical efficacy of the swimming training on bronchial asthma was evaluated according to a treatment score, an attack score and an asthmatic score. These scores were decreased during the swimming training. The results obtained in this study showed that free swimming training in a hot spring pool is one of the most suitable therapies for severe bronchial asthma patients

Clinical problems of long-term steroid regimen for bronchial asthma, with reference to steroid-dependent cases

Adverse side effects of steroid therapy were investigated in 32 asthmatic patients. Thirty-two patients were classified into three groups according to steroid therapy for the past five years; group 1 has been treated with continuous steroid therapy, group 2 with occasional steroid therapy and group 3 without steroid therapy. The results were as follows. 1. Group 1 showed a low level of serum cortisol at 8-9 a. m. The serum concentration of cortisol in patients with daily steroid regimen was lower as compared to that in patients with alternateday steroid therapy. 2. The daily profile of serum cortisol was low in the steroid dependent asthmatic patients, and little increase of serum cortisol level after the administration of prednisolone was shown in group 1. 3. Serum IgG and IgM levels were significantly low in steroid dependent asthmatic patients. 4. The level of serum potassium was low in group 1

An Order of Magnitude Faster AIP1-Associated Actin Disruption than Nucleation by the Arp2/3 Complex in Lamellipodia

The mechanism of lamellipod actin turnover is still under debate. To clarify the intracellular behavior of the recently-identified actin disruption mechanism, we examined kinetics of AIP1 using fluorescent single-molecule speckle microscopy. AIP1 is thought to cap cofilin-generated actin barbed ends. Here we demonstrate a reduction in actin-associated AIP1 in lamellipodia of cells overexpressing LIM-kinase. Moreover, actin-associated AIP1 was rapidly abolished by jasplakinolide, which concurrently blocked the F-actin-cofilin interaction. Jasplakinolide also slowed dissociation of AIP1, which is analogous to the effect of this drug on capping protein. These findings provide in vivo evidence of the association of AIP1 with barbed ends generated by cofilin-catalyzed filament disruption. Single-molecule observation found distribution of F-actin-associated AIP1 throughout lamellipodia, and revealed even faster dissociation of AIP1 than capping protein. The estimated overall AIP1-associated actin disruption rate, 1.8 µM/s, was one order of magnitude faster than Arp2/3 complex-catalyzed actin nucleation in lamellipodia. This rate does not suffice the filament severing rate predicted in our previous high frequency filament severing-annealing hypothesis. Our data together with recent biochemical studies imply barbed end-preferred frequent filament disruption. Frequent generation of AIP1-associated barbed ends and subsequent release of AIP1 may be the mechanism that facilitates previously observed ubiquitous actin polymerization throughout lamellipodia