A case of aspergilloma detected after surgery for pneumothorax.

We report a case of aspergilloma in an 80-year-old male patient who had no identifiable underlying disease before surgery for pneumothorax. He was hospitalized for left pneumothorax. A chest CT revealed a large bulla in the left lung apex with a nodule (diameter; 1.5 cm) at the edge of the bulla. After thoracodocesis, air leakage persisted and a large bulla and nodule were resected. Aspergillus was detected histopathologically in the nodule. Treatment with itraconazole 200 mg a day followed, and 4 months later he had no recurrent pneumothorax or Aspergillus infection.     

INTRAOPERATIVE BLEEDING IN ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE STOMACH AND STRATEGY FOR PREVENTION AND TREATMENT

To control intraoperative bleeding is an important key to successful endoscopic submucosal dissection. The distribution of submucosal vessels encountered during the procedure differ in places in the stomach and are roughly categorized into three groups: those located in the antrum, those in the lesser curvature, and those on the anteroposterior corpus wall which consists of oblique muscle layers. Therefore, knowledge of a suitable setting of diathermy and adjusted depth of dissection in the submucosal layer for each site is imperative. The combination of utilizing the distal attachment forced or swift coagulation (trimming with coagulation mode) have enable the treatment with an insulation tipped knife safer.     

Usefulness of skin prick test using bifurcated needle for the diagnosis of food allergy among infantile atopic dermatitis--1st report. In the case of egg allergy

OBJECTIVE: We investigated the usefulness of skin prick test (SPT) for the diagnosis of egg white (EW) allergy in infants with atopic dermatitis who showed negative to EW CAPRAST, and followed up the EW-CAPRAST in this study. SUBJECTS AND METHODS: Data of negative SPT using Bifurcated needle (BN) were analyzed from the data of 202 atopic dermatitis infants, who had received SPT from January in 2001 to April in 2005. From the negative SPT value (average and standard deviation) positive SPT value was obtained. Among 202 cases, 89 suspected-egg allergy infants with negative IgE CAPRAST against EW at the time of first visit were recruited to examine the usefulness of SPT. Positive conversion of EW-CAPRAST was checked in 78 cases (65: egg allergy+, 13: egg allergy(-)) who had been followed up in our outpatient clinic. RESULTS: Range of negative SPT control value (mean+2SD) using BF among infants could be set as less than 2 mm for wheal and/or 5 mm for erythema. Among 89 suspected-egg allergy infants with negative EW-CAPRAST, 72 infants (80.9%) were diagnosed as egg allergy by the combination of elimination and provocation test, interestingly 39 infants (54.2%) showed positive SPT results. In the follow up study of 78 negative EW-CAPRAST cases, 47 EW-CAPRAST out of 65 egg-allergy cases turned positive later infantile period (mean EW-CAPRAST: 9.6+/-16.7 Ua/ml at 9.9+/-5.6 months old). EW-CAPRAST of 7 cases in 13 non-egg allergies also turned positive in the follow up, however EW-CAPRAST titer was relatively lower compared to that of egg allergies (1.1+/-1.5 Ua/ml at 13.3+/-2.6 months old). CONCLUSIONS: We experienced fairly number of atopic infants with negative EW-CAPRAST at the first outpatient visit, who were later diagnosed as egg allergy. In about half of these cases, SPT egg-allergy infants, three quarter of EW-CAPRAST turned positive around 10 months old. EW-CAPRAST of atopic infants without egg allergy also turned transiently and slightly positive. In the conclusions, SPT seemed to be more useful than EW-CAPRAST for the diagnosis of egg allergy in early infantile period, however provocation test should be required for the definitive diagnosis in suspected-egg allergy infants without any proof of egg-sensitization.     

Measurement of plasma von Willebrand factor cleaving protease in patients with varied thrombotic microangiopathy

Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorders characterized by thrombocytopenia, microangiopathic hemolytic anemia associated with red cell fragmentation, and neurological and renal symptoms. Plasma of patients with TTP has been shown to contain unusually large von Willebrand factor(vWF) multimers that may cause platelet agglutination in vivo. Recently, a metalloprotease responsible for cleavage of vWF multimers has been isolated from normal human plasma and was found to be deficient in some patients with TTP. We examined the activity of the vWF-cleaving protease(vWF-CP), by modified Furlan's method, in plasma from patients with a familial TTP, 3 acquired TTP, 4 thrombotic microangiopathy(TMA) and 2 veno-occlusive disease(VOD) associated after allo-BMT. Diluted plasma samples of patients were incubated with protease-free vWF purified from normal human plasma, in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in SDS-agarose gels and immunoblotting. Activity of vWF-CP from 12 normal plasma have been shown as 77-180%(average 115%), whereas, no vWF-CP(below 5%) was observed in plasma from familial TTP, before and after plasma exchange, although FFP infusion therapy has been effective for this patient to recover thrombocytopenia. In 3 acquired TTP, 2 patients showed lack of vWF-CP activity in plasma, and inhibitors against vWF-CP have been elucidated by plasma cross-mixing test. After extensive plasma exchange and FFP infusion followed by corticosteroid therapy, normal vWF-CP was recovered in plasma from 2 acquired TTP patients. Among BMT patients, plasma from 4 BMT-TMA showed normal vWF-CP activities as 55-111%, whereas plasma from 2 BMT-VOD revealed low vWF-CP activity, as 24% and 37%, respectively. Thus, measurement of vWF-CP is crucial to predict differentiation of primary forms of TMA to establish the pathogenesis in varied endothelial dysfunction.     

Correlation between mutated genes and forearm deformity in patients with multiple osteochondroma

BackgroundsExostosin-1 (EXT1) and exostosin-2 (EXT2) cause multiple osteochondromas (MO). In this study, we investigated the correlation between forearm deformity and mutant EXTs in Japanese families with MO.MethodsWe evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. Of these, 28 patients were selected and underwent radiography for their forearms since they had gross forearm deformities. We measured the radial articular angle (RAA), ulna variance (UV), carpal slip (CS), and percentage of radial bowing (%RB) to compare between patients with mutant EXT1 or EXT2 and those with missense or other mutations using Student's t-test.ResultsTwenty-two (78.6%) and 6 (11.4%) out of 28 patients had mutations in EXT1 and EXT2, respectively. Nine (32.1%) and 19 (67.9%) of the 28 patients had missense and other mutations, respectively. The mean age of patients with EXT1 and EXT2 were 25.9 ± 20.3 and 33.5 ± 25.4 years, respectively and those with missense mutation and other mutations were 28.7 ± 27.0 and 24.6 ± 17.0 years, respectively. There were no significant differences in RAA, UV, and RB between patients harbouring mutant EXT1 or EXT2 (RAA, 40.1 ± 8.7 and 31.5 ± 13.9°; UV, ?2.7 ± 5.7 and ?3.1 ± 3.7 mm; %RB, 8.6 ± 1.5 and 8.3 ± 2.0%). CS was significantly greater in patients with mutant EXT1 than that in those with mutant EXT2 (EXT1, 44.1 ± 16.8%; EXT2, 18.6 ± 14.0%). There were no significant differences in RAA, UV, CS and %RB between patients with missense and other mutations.ConclusionsPatients with mutant EXT1 displayed greater CS than patients with mutant EXT2, indicating that patients with MO harbouring EXT1 mutations sustain more severe ulnar drift deformities than those with EXT2 mutations.     

Cytolytic Recombinant Vesicular Stomatitis Viruses Expressing STLV-1 Receptor Specifically Eliminate STLV-1 Env-Expressing Cells in an HTLV-1 Surrogate Model In Vitro

Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed “virotherapy”, a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo.     

A genome-wide view of Caenorhabditis elegans base-substitution mutation processes

Knowledge of mutation processes is central to understanding virtually all evolutionary phenomena and the underlying nature of genetic disorders and cancers. However, the limitations of standard molecular mutation detection methods have historically precluded a genome-wide understanding of mutation rates and spectra in the nuclear genomes of multicellular organisms. We applied two high-throughput DNA sequencing technologies to identify and characterize hundreds of spontaneously arising base-substitution mutations in 10 Caenorhabditis elegans mutation-accumulation (MA)-line nuclear genomes. C. elegans mutation rate estimates were similar to previous calculations based on smaller numbers of mutations. Mutations were distributed uniformly within and among chromosomes and were not associated with recombination rate variation in the MA lines, suggesting that intragenomic variation in genetic hitchhiking and/or background selection are primarily responsible for the chromosomal distribution patterns of polymorphic nucleotides in C. elegans natural populations. A strong mutational bias from G/C to A/T nucleotides was detected in the MA lines, implicating oxidative DNA damage as a major endogenous mutagenic force in C. elegans. The observed mutational bias also suggests that the C. elegans nuclear genome cannot be at equilibrium because of mutation alone. Transversions dominate the spectrum of spontaneous mutations observed here, whereas transitions dominate patterns of allegedly neutral polymorphism in natural populations of C. elegans and many other animal species; this observation challenges the assumption that natural patterns of molecular variation in noncoding regions of the nuclear genome accurately reflect underlying mutation processes.     

A selective plasmin inhibitor, trans-aminomethylcyclohexanecarbonyl-L-(O-picolyl)tyrosine-octylamide (YO-2), induces thymocyte apoptosis

The treatment of rat thymocytes with YO-2, a novel inhibitor of plasmin, resulted in an increase in DNA fragmentation. DNA fragmentation was also induced by another YO compounds such as YO-0, -3, -4 and -5. These YO compounds are the inhibitor of plasmin activity. On the other hand, YO-1, -6 and -8 that hardly inhibit plasmin activity had no effect on DNA fragmentation. Analysis of fragmented DNA from thymocytes treated with YO-2 by agarose gel electrophoresis revealed that the compound caused internucleosomal DNA fragmentation. In addition, judging from a laser scanning microscopy, annexin V-positive and propidium iodide-negative cells were increased by the treatment of the cells with the compound. Moreover, chromatin condensation was observed in thymocytes treated with the compound. These results demonstrated that YO-2 induces thymocyte apoptosis. There seemed to be some correlation between the apoptosis induced by YO compounds and their plasmin inhibitory effect. However, because the other protease inhibitors including pepstatin A, leupeptin, AEBSF, DFP and E-64-d did not affect DNA fragmentation, YO compounds are likely to have unique mechanism on plasmin or to show the effect on the other plasmin-like proteases. The plasmin inhibitory activity may have an important role in YO-2-induced apoptosis. Furthermore, the stimulations of caspase-8, -9 and -3-like activities were observed in thymocytes treated with YO-2. These results suggest that YO-2 induces thymocyte apoptosis via activation of caspase cascade.