Complex translocations derived stepwise from standard t(15;17) in a patient with variant acute promyelocytic leukemia

We report the case of an elderly man with an acute promyelocytic leukemia variant carrying complex variant translocations. The Q-banded karyotype and spectral karyotyping method revealed a typical t(15;17), and two complex rearrangements caused by stepwise translocation derived from a typical t(15;17). Chromosomes 8 and 14 were related to these rearrangements. The patient received induction chemotherapy using all-trans retinoic acid and achieved complete remission. To our knowledge, a case with complex rearrangements, caused by apparent stepwise translocation, at diagnosis, has not been reported previously.     

Generation of a novel CD30+ B cell subset producing GM-CSF and its possible link to the pathogenesis of systemic sclerosis

Systemic sclerosis (SSc) is a T helper type 2 (Th2)-associated autoimmune disease characterized by vasculopathy and fibrosis. Efficacy of B cell depletion therapy underscores antibody-independent functions of B cells in SSc. A recent study showed that the Th2 cytokine interleukin (IL)-4 induces granulocyte–macrophage colony-stimulating factor (GM-CSF)-producing effector B cells (GM-B_effs) in humans. In this study, we sought to elucidate the generation mechanism of GM-B_effs and also determine a role of this subset in SSc. Among Th-associated cytokines, IL-4 most significantly facilitated the generation of GM-B_effs within memory B cells in healthy controls (HCs). In addition, the profibrotic cytokine transforming growth factor (TGF)-β further potentiated IL-4- and IL-13-induced GM-B_effs. Of note, tofacitinib, a Janus kinase (JAK) inhibitor, inhibited the expression of GM-CSF mRNA and protein in memory B cells induced by IL-4, but not by TGF-β. GM-B_effs were enriched within CD20⁺CD30⁺CD38^−/low cells, a distinct population from plasmablasts, suggesting that GM-B_effs exert antibody-independent functions. GM-B_effs were also enriched in a CD30⁺ fraction of freshly isolated B cells. GM-B_effs generated under Th2 conditions facilitated the differentiation from CD14⁺ monocytes to DC-SIGN⁺CD1a⁺CD14⁻CD86⁺ cells, which significantly promoted the proliferation of naive T cells. CD30⁺ GM-B_effs were more pronounced in patients with SSc than in HCs. A subpopulation of SSc patients with the diffuse type and concomitant interstitial lung disease exhibited high numbers of GM-B_effs. Together, these findings suggest that human GM-B_effs are enriched in a CD30⁺ B cell subset and play a role in the pathogenesis of SSc.     

Synthesis of cyanooxovanadate and cyanosilylation of ketones

The cyanosilylation was performed by using metavanadate catalysts, and in situ measurements revealed the formation of [VO₂(CN)₃]²⁻ and [VO₄TMS₂]⁻ under reaction conditions. The reaction of [VO₂(CN)₃]²⁻, trimethylsilyl cyanide (TMSCN), and water afforded [VO₄TMS₂]⁻ and CN⁻, which reacted with ketones to yield the corresponding cyanohydrin trimethylsilyl ethers over [VO₂(CN)₃]²⁻. Compound [VO₂(CN)₃]²⁻ showed high catalytic performance for cyanosilylation of various carbonyl compounds. In the case of n-hexanal, turnover frequency reached up to 250 s⁻¹.

Two key catalytic vanadium species involved in cyanosilylation of ketones were observed by in situ measurement.     

Development of culture-sensitive clinical teacher evaluation sheet in the Japanese context

Aim: Many instruments for evaluating clinical teaching have been developed, albeit most in Western countries. This study aims to develop a validated cultural and local context sensitive instrument for clinical teachers in an East Asian setting (Japan), Japanese Clinical Teacher Evaluation Sheet (JaCTES).

Methods: A multicenter, cross-sectional evaluation study was conducted. We collected a total of 1368 questionnaires on 304 clinical teachers, completed by residents in 16 teaching hospitals. The construct validity was examined by conducting a factor analysis and using structural equation modeling (SEM). We also assessed the reliability using generalizability analysis and decision study.

Results: Exploratory factor analysis resulted in three-factor (role model, teaching activities, and accessibility) model including 18 items. Confirmatory factor analysis was performed, using SEM. The comparative fit index was 0.931 and the root mean square error of approximation was 0.087, meaning an acceptable goodness of fit for this model. To obtain a reliable dependability-coefficient of at least 0.70 or higher, 5–8 resident responses are necessary.

Discussion and conclusion: JaCTES is the first reported instrument with validity evidence of content and internal structure and high feasibility in Japan, an East Asian setting. Medical educators should be aware of the local context and cultural aspects in evaluating clinical teachers.     

Cerebral oxygenation monitor during head-up and -down tilt using near-infrared spatially resolved spectroscopy

Reflectance near-infrared spectroscopy (NIRS) has become a suitable and easily manageable method to monitor cerebral oxygenation changes in presyncopal and syncopal symptoms caused by postural changing or standing. A new clinical tissue oxygenation monitor has been recently developed which measures absolute tissue haemoglobin saturation (Tissue Oxygenation Index, TOI) utilizing spatially resolved spectroscopy (SRS). The present study examined the effects of postural changes on cerebral oxygenation as reflected in SRS-NIRS findings. Cerebral oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), and the TOI were recorded from both sides of the forehead in five healthy male subjects (age range, 28-40 years) during 90 degrees head-up tilt (HUT) and -6 degrees head-down tilt (HDT). Three series of measurements were carried out on separate days. O2Hb was decreased during HUT. TOI was significantly lower in HUT than in the supine position (SUP). There was no significant change in TOI during HDT. A significant session effect was observed in the left forehead TOI during SUP, but not in the right. SRS-NIRS measurements confirmed sub-clinical alterations of cortical oxygenation during HUT. NIRS data from the left side of the forehead, which may vary with cognitive or emotional activation, were more variable than those from the right side.     

Increased formaldehyde in jet engine exhaust with changes to JP-8, lower temperature, and lower humidity irritates eyes and respiratory tract

BACKGROUND: Formaldehyde (FA) in exhaust from F-4 aircraft with low smoke combustor(LSC) J79 engines has been reported to be of sufficient concentration to cause irritation. It has also been noted that eye and respiratory irritation became more frequent and severe after the fuel was changed from JP-4 to JP-8. The present sturdy investigated the effect of jet fuel and power setting on formaldehyde concentrations in the exhaust. We also investigated the exposure to formaldehyde among pilots and flight line personnel. METHODS: The exhaust from LSC J79 engines using different types of fuel (JP-8 and JP-4) was sampled 50 m behind the engine at different power settings in July (summer season in Japan) and February (winter season ). It was also sampled at 75% power settings using JP-8 in July. RESULTS: At an idle power setting, the FA concentration was higher in the exhaust of engines using JP-8 (1.31 ppm in July and 2.78 ppm in February) than in engines using JP-4 (0.95 ppm in July and 1.84 ppm in February). The FA concentration increased as both ambient temperature and relative humility decreased in the sampling atmosphere. The FA concentration of JP-8 fuel at an idle power setting (65%) was higher than that at a 71.5% power setting (1.32 ppm and 0.86 ppm, respectively). CONCLUSIONS: The FA concentrations in LSCJ79 engine exhaust varies depending on the type of fuel, engine power settings, and ambient air conditions. A high FA concentration at ground level due to a change in the fuel type, low temperature, and humidity, causes frequent severe eye respiratory irritation.     

Gastric gastrointestinal stromal tumor smaller than 20 mm with liver metastasis

There have been no reports of gastric gastrointestinal stromal tumors (GISTs) <20 mm with distant metastasis. We report a case of a 15-mm gastric GIST with liver metastasis 1 year after surgical resection of the primary lesion. A 35-year-old man underwent routine esophagogastroduodenoscopy in July 2009. A submucosal tumor (SMT) <20 mm was incidentally detected at the posterior wall of the gastric body. Endoscopic ultrasound (EUS) indicated that it was a gastrointestinal mesenchymal tumor, including GIST, leiomyoma or schwannoma. He did not accept regular follow-up for this gastric SMT, therefore local laparoscopic excision was carried out in October 2009. The final pathological diagnosis after surgery was GIST, 15 mm in size, and a mitotic rate of 7/50 high-power fields, which did not indicate a high metastatic risk. The patient was followed up regularly without adjuvant chemotherapy. At 1 year after surgery, a space-occupying lesion ~15 mm was detected in the left lobe of the liver by abdominal ultrasound, where no mass lesion had been observed before surgery. To make a definite diagnosis of the hepatic mass lesion, EUS-guided fine-needle aspiration was performed, which demonstrated a metastatic liver tumor from a gastric GIST. Although this was a rare case, we should keep in mind that gastric GISTs do have a chance of malignant behavior, even if <20 mm.     

Transient cyclophosphamide treatment before intraportal readministration of an adenoviral vector can induce re-expression of the original gene construct in rat liver.

Although adenovirus is an attractive vehicle for transferring therapeutic genes in vivo, animal studies have indicated that the clinical usefulness of adenoviruses may be limited by their immunogenicity. Although immunosuppressive strategies around the time of initial exposure of adenoviruses have been shown to prevent the formation of neutralizing antibodies and permit the successful readministration of adenoviruses in animals, the practicality of the approaches remains questionable. Because the majority of prospective gene therapy patients have already been infected with wild-type adenoviruses, initial treatment with adenoviruses in humans may correspond to readministration of adenoviruses into animals. It is shown here that although intraportal infusion of adenoviruses carrying a reporter lacZ gene resulted in transient high levels of transgene expression in the rat liver, intraportal readministration of adenoviruses failed to induce detectable levels of transgene expression. Conversely, when animals were treated transiently with cyclophosphamide before the intraportal readministration of adenoviruses, development of neutralizing antibodies and antigen-specific T cell proliferation in response to adenoviral readministration was significantly suppressed and successful re-expression of the transgene was achievable. These results may have important implications for efficacy considerations when adenoviral vectors are employed in clinical settings.     

Association between ApoE phenotypes and telomere erosion in Alzheimer's disease

Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.