The biosynthetic gene cluster of antifungal agent jawsamycin (FR-900848) has been identified by heterologous expression. A series of gene inactivations and in vitro and in vivo analysis of key enzymes in the biosynthetic pathway established their functions. A novel mechanism involving a radical S-adenosyl methionine (SAM) cyclopropanase collaborating with an iterative polyketide synthase is proposed for the construction of the unique polycyclopropanated backbone. Our reconstitution system sets the stage for studying the catalytic mechanism of this intriguing contiguous cyclopropanation.

We were able to show the predominant incorporation of a single enantiomer and intact incorporation of multiply labelled synthetic diketide precursors (and), which established the intermediacy of cyclopropanated diketide and led to our proposal for the unprecedented biological cyclopropation, via PKS (polyketide synthase) having a novel cyclopropanase domain, in the biosynthesis of FR-900848 (1).

A 62-year-old man had a right renal mass incidentally diagnosed by ultrasonography. Magnetic resonance imaging revealed a well-defined right renal mass with homogenous low-signal intensity on the T 1 -weighted pulse sequence and heterogeneous high-signal intensity on the T 2 -weighted pulse sequence. A right nephrectomy was performed. The histological examination showed a myxoma, which is a very uncommon neoplasm in the kidney. Eight cases have been reported previously.

Abstract. This study investigated the expression of hypoxiainducible protein 2 (HIG2), a novel renal cell carcinoma (RCC)-associated molecule and an essential growth factor for RCC, in kidneys to elucidate its clinical significance in RCC. An immunohistochemical study of HIG2 was conducted in 93 surgical samples of RCC tissues and 10 samples of normal kidney tissues obtained after nephrectomies for localized RCC. HIG2 expression was also correlated with clinicopathological characteristics and survival. Only faint or weak immunostaining for HIG2 was observed in normal kidney samples. HIG2 expression was found in 86% of RCC tissues (80/93). When analyzed by histological type, positive staining for HIG2 was detected in all papillary (7/7), chromophobe (1/1) and cyst-associated (3/3) RCC. In contrast, the HIG2 expression was observed in 85% of clear cell (68/80) and 50% of spindle cell (1/2) RCC. Labeling indices were 74.1, 45.4, 39, 24.8 and 12.1% in papillary, spindle, clear cell, cyst-associated and chromophobe RCC, respectively. A significant increase in HIG2 expression was noted in RCC tissues obtained from patients with high stage RCC, lymph node metastasis and high nuclear grade (p<0.001, p<0.02 and p<0.006, respectively). RCC patients with a negative HIG2 staining had prolonged 5-year cancer-specific survival. In conclusion, HIG2 expression was extensively observed in RCC tissues and was higher in advanced RCC, suggesting that HIG2 is a candidate for the development of molecular targeting therapy.

Using Luria's motor sequence test, we studied the learning ability of 34 right-handed patients with unilateral hemisphere lesions. Patients with ideomotor apraxia needed 4 to 6 trials in the test, while the remainder needed only 1 or 2. Ideomotor apraxics also required more time to complete the test. The lesions of patients who failed to master this test were not always found in the frontal lobes. These results suggest that the ability to learn motor sequences is impaired in apraxic patients and that the left hemisphere of the brain plays the major role in learning a new motor sequence. Patients with ideomotor apraxia are impaired not only when performing previously learned motor tasks but also when learning a new motor task.