Frequent premature ventricular contractions induced by itraconazole.

Itraconazole is widely used to treat onychomycosis because of its significant therapeutic effects. An otherwise healthy 30-year-old man treated with itraconazole developed frequent premature ventricular contractions (PVC). He presented with a dry cough and palpitation. The results of 12-lead electrocardiography (ECG) were essentially normal, but Holter ECG revealed 17,484 (18%) uniform PVC, including 4 short runs among 96,930 beats/day. Another Holter ECG after withdrawing itraconazole revealed 1,032 premature atrial contractions but no PVC. The corrected QT interval was 0.39 s without itraconazole, 0.41 s with itraconazole, and 0.43 s when multiple PVC were documented. Itraconazole inhibits the fungal cytochrome P450 that is involved in fungal cell membrane formation, interrupts human cytochrome P450A4 in the liver and causes adverse interactions with various drugs such as antiarrythmics, but its cardiac side-effects are obscure. Both patients and physicians should be aware that itraconazole can cause PVC as a side-effect.     

The UDP-galactose translocator gene is mapped to band Xp11.23-p11.22 containing the Wiskott-Aldrich syndrome locus

We have cloned a segment of the human gene encoding UDP-galactose translocator by genetic complementation of its defective mutant in mouse FM3A cells. Chromosome mapping using fluorescentin situ hybridization revealed that the cloned gene hybridized to the Xp11.23-11.23 region of the X chromosome. This region is shared by the locus of Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency disorder, characterized by defective sugar chains on cell surface components. Genetic and phenotypic similarities suggest a possible link between UDP-galactose translocator and the Wiskott-Aldrich syndrome (WAS).     

Rapid preparation of diagnostic probes for the fragile X syndrome by direct PCR amplification of human chromosomal DNA

Summary The fragile X syndrome is a common familial form of mental retardation and is associated with a rare fragile site at Xq27.3 (FRAXA). This disorder has recently been reported to correlate with length variations of restriction genomic DNA fragments which may due to the amplification of (CCG)_n trinucleotide repeats located at the FRAXA locus. We described here a rapid preparation method of diagnostic DNA probes for the fragile X syndrome by direct enzymatic amplification of human chromosomal DNA. ThePstI-assay, which is Southern blot analysis of DNA samples probed by PCR products, was shown to be sensitive method for diagnostic purposes to detect the size variations specific in the fragile X syndrome.     

Myopathy phenotype in transgenic mice expressing mutated PABPN1 as a model of oculopharyngeal muscular dystrophy

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD)is a late-onset disorder characterized clinically by progressiveptosis, dysphagia and limb weakness, and by unique intranuclearinclusions in the skeletal muscle fibers. The disease is causedby the expansion of a 10-alanine stretch to 12–17 alanineresidues in the poly(A)-binding protein, nuclear 1 (PABPN1;PABP2). While PABPN1 is a major component of the inclusionsin OPMD, the exact cause of the disease is unknown. To elucidatethe molecular mechanism and to construct a useful model fortherapeutic trials, we have generated transgenic mice expressingthe hPABPN1. Transgenic mice lines expressing a normal hPABPN1with 10-alanine stretch did not reveal myopathic changes, whereaslines expressing high levels of expanded hPABPN1 with a 13-alaninestretch showed an apparent myopathy phenotype, especially inold age. Pathological studies in the latter mice disclosed intranuclearinclusions consisting of aggregated mutant hPABPN1 product.Furthermore, some TUNEL positive nuclei were shown around degeneratingfibers and a cluster of it in the lesion in necrotic musclefibers. Interestingly, the degree of myopathic changes was moreprominent in the eyelid and pharyngeal muscles. Further, muscleweakness in the limbs was apparent as shown by the fatigabilitytest. Nuclear inclusions seemed to develop gradually with aging,at least after 1 week of age, in model mouse muscles. We establishedthe first transgenic mouse model of OPMD by expressing mutatedPABPN1, and our model mice appear to have more dramatic alternationsin myofiber viability. ^* To whom correspondence should be addressed. Tel: +81 963736083; Fax: +81 963736599; Email: yamamura{at}gpo.kumamoto-u.ac.jp     

蘡Ao中分离的多酚化合物

目的分离鉴定蘡Ao地上部分的化学成分。方法通过硅胶柱色谱，Sephadex LH-20及制备HPLC方法分离，对其进行理化常数和光谱分析确定结构。结果自蘡Ao地上部分分离得到11个多酚化合物，均属首次分离。结论化合物1为新化合物，经鉴定其结构为3，5-二甲氧基-4-羟基苯丙醇-9-氧-β-D-吡喃葡萄糖苷。     

(+)-cis-ε-Viniferin的结构确证

用光化学沟通方法确证了从葡萄科植物蘡薁Vitis thunbergii(Vitaceae)中分离得到的( )-cis-ε-viniferin的结构；并纠正了文献核磁共振氢谱(^1H-NMR)数据。     

The inotropic consequences of cooling: Studies in the isolated rat heart

Summary To investigate the controversial effects of hypothermia on cardiac contractile performance, we have carried out ventricular volume-loading experiments in 23 perfused, paced (2 Hz), isolated rat hearts, contracting isovolumically at various temperatures. A water-filled, unstressed latex balloon was inserted into the left ventricle and its volume was controlled with a microsyringe. Left ventricular pressure (LVP), its first derivative (dP/dt) and coronary flow were recorded. One group of hearts (n=7) were perfused at 37°C over 2 h. Another group of hearts (n=16) were cooled in a stepwise manner from 37°C to 21°C, with 10-min perfusion at each of seven different temperatures, and then rewarmed to 37°C. E_max, an index of contractility, calculated as the slope of the regression line of the end-systolic pressure-volume relationship, was found toincrease as temperature fell (3.9, 4.6, 4.9, 5.5, 5.5, 6.2, and 6.3 cm H₂O/µl at 37°, 34°, 31°, 29°, 27°, 24° and 21°C, respectively) while it remained constant over the 2-h perfusion in the normothermic perfusion group. By contrast, peak positive dP/dt/ peak-developed pressure (+dP/dt/DP) progressivelydecreased during cooling without any change in the normothermic perfusion group. The results indicate that hypothermia can be designated as a positive inotropic intervention in terms of forcegeneration (E_max) but as a negative inotropic intervention in terms of shortening velocity of contractile element in Hill's model (+dP/dt/DP).     

Metachronous solitary mediastinal lymph node metastases of hepatocellular carcinoma treated by video‐assisted thoracic surgery twice: Report of a case

Solitary mediastinal lymph node metastasis of hepatocellular carcinoma (HCC) is rare. We report a case of metachronically solitary mediastinal metastases of HCC treated by video‐assisted thoracic surgery (VATS) twice. A 66‐year‐old man underwent repeated laparoscopic radiofrequency ablation or trans‐arterial catheter chemo‐embolization against HCC for more than 10 years. The level of alpha fetoprotein protein was elevated, and radiological modalities including FDG‐PET revealed solitary mediastinal tumor metachronically. VATS was performed bilaterally twice. The postoperative course was uneventful and there had no recurrence of extra‐hepatic metastases and tumor markers are within normal limits at 18 months after second VATS. VATS is a minimally invasive and useful procedure for solitary mediastinal lymph node metastasis of HCC. If primary HCC was controlled and lymph node metastasis was solitary, mediastinum lymphadenectomy using VATS might give good short and long term results.