Video-assisted thoracoscopic surgery is a promising treatment for solitary fibrous tumor of the pleura

STUDY OBJECTIVES: Solitary fibrous tumors of the pleura (SFTPs) are slow-growing neoplasms. Approximately 800 cases have been reported in the literature to date. The aim of this study was to address our experience with the management of SFTPs and to evaluate the advantage of video-assisted thoracoscopic surgery (VATS) in SFTP treatment. DESIGN: Retrospective analysis of our experience. SETTING: Department of Thoracic and Cardiovascular Surgery, Nara Medical University. PATIENTS: From January 1992 to August 2002, 13 patients with a SFTP were referred to us for surgical resection after VATS was adopted in our hospital. The study group consisted of seven men and six women with a mean age of 49.8 years (age range, 37 to 72 years). RESULTS: Surgical excision was performed with VATS only in nine patients, with VATS plus a small thoracotomy in three patients, and by a posterolateral thoracotomy without VATS in one patient. The mean chest-drain duration was 1.3 days (range, 1 to 3 days), and the mean duration of hospital stay was 8.6 days (range, 3 to 30 days). Eleven tumors, originating from the visceral pleura, were pedunculate, and 2 tumors from the parietal pleura were not pedunculate. Two cases were focally characterized by a mitotic count in excess of four mitoses per 10 high-power fields and by cellular pleomorphism. Follow-up periods ranged from 6 to 120 months, with a mean of 49.7 months and a median of 42 months. All patients have remained well with no recurrence or metastasis. CONCLUSIONS: Complete surgical resection is the treatment of choice for SFTPs. For the pedunculate tumors, therefore, VATS is a powerful and useful approach. Even when it is necessary to perform a small thoracotomy in addition to VATS for the removal of a large tumor, VATS may play an important role in reducing the size of the thoracotomy incision, which results in less invasive surgery. To minimize postoperative morbidity, VATS may be the most promising surgical approach for the resection of SFTPs.     

Possible reduced penetrance of expansion of 44 to 47 CAG/CAA repeats in the TATA-binding protein gene in spinocerebellar ataxia type 17

BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by expansion of CAG/CAA trinucleotide repeats in the TATA-binding protein (TBP) gene. Because the number of triplets in patients with SCA17 in previous studies ranged from 43 to 63, the normal number of trinucleotide units has been considered to be 42 or less. However, some healthy subjects in SCA17 pedigrees carry alleles with the same number of expanded repeats as patients with SCA17. OBJECTIVE: To investigate the minimum number of CAG/CAA repeats in the TBP gene that causes SCA17. DESIGN: We amplified the region of the TBP gene containing the CAG/CAA repeat by means of polymerase chain reaction and performed fragment and sequence analyses. PATIENTS: The subjects included 734 patients with SCA (480 patients with sporadic SCA and 254 patients with familial SCA) without CAG repeat expansions at the SCA1, SCA2, Machado-Joseph disease, SCA6, SCA7, or dentatorubral-pallidolluysian atrophy loci, with 162 healthy subjects, 216 patients with Parkinson disease, and 195 with Alzheimer disease as control subjects. RESULTS: Eight patients with SCA possessed an allele with more than 43 CAG/CAA repeats. Among the non-SCA groups, alleles with 43 to 45 repeats were seen in 3 healthy subjects and 2 with Parkinson disease. In 1 SCA pedigree, a patient with possible SCA17 and her healthy sister had alleles with 45 repeats. A 34-year-old man carrying alleles with 47 and 44 repeats (47/44) had developed progressive cerebellar ataxia and myoclonus at 25 years of age, and he exhibited dementia and pyramidal signs. He was the only affected person in his pedigree, although his father and mother carried alleles with mildly expanded repeats (44/36 and 47/36, respectively). In another pedigree, 1 patient carried a 43-repeat allele, whereas another patient had 2 normal alleles, indicating that the 43-repeat allele may not be pathologic in this family. CONCLUSIONS: We estimate that 44 CAG/CAA repeats is the minimum number required to cause SCA17. However, the existence of unaffected subjects with mildly expanded triplets suggests that the TBP gene mutation may not penetrate fully. Homozygosity of alleles with mildly expanded triplet repeats in the TBP gene might contribute to the pathologic phenotype.     

Non-operative treated spontaneous spinal epidural hematoma in a 12-year-old boy

Spontaneous spinal epidural hematoma (SSEH) has been reported as a rare condition especially in childhood. Because its symptoms are atypical, it is not easy to diagnose the onset of SSEH. However, with wider use of magnetic resonance imaging (MRI), several SSEH cases, especially not requiring surgical intervention, have been reported. We report on a 12-year-old boy who presented with a 5-day history of progressive pain in his back and extremities and numbness of his lower legs. An MRI of the spine demonstrated a dorsal epidural hematoma extending from C4 to T4, and the axial scan of the MRI revealed a posterior hematoma. Neurological deficit was estimated as not severe and not progressive, therefore surgery was postponed, and the patient was discharged without surgical intervention. Seven months later, MRI and myelography were performed, and we confirmed that the spinal epidural hematoma was absorbed. There have been some cases showing spontaneous regression of SSEH, and in younger than 18 years old, most of those cases that were treated with hematopathy such as hemophilia and spontaneous regression after SSEH correlated to larger size of hematoma. Because of bleeding tendencies in these cases the spinal cord was not pressed by the hematoma; this contributed conclusively to the prognosis. On the contrary, the 12-year-old boy, not having bleeding tendency, had the larger lesion of SSEH and recovered spontaneously without surgical intervention. Evaluation of MRI findings and neurological deficits in SSEH cases is important for deciding the indication of surgical intervention.     

Pharmacological modulation of histone demethylase activity by a small molecule isolated from subcritical water extracts of Sasa senanensis leaves prolongs the lifespan of Drosophila melanogaster

ABSTRACT: Backgroud Extracts of Sasa senanensis Rehder are used in traditional medicine;however, little is known about the underlying mechanisms of their potential health benefits. RESULTS: S. senanensis leaves were extracted with subcritical water. An active small-molecule was isolated using reversed-phase high-performance liquid chromatography (HPLC), and identified as 3,4-dihydroxybenzaldehyde (protocatechuic aldehyde or PA). The effects of PA on the activity of histone demethylase, the Drosophila melanogaster lifespan and gene expression in Drosophila S2 cells were investigated. PA inhibited the activity of Jumonji domain-containing protein 2A (JMJD2A) histone demethylase in a dose-dependent manner with a half-maximal inhibitory concentration (IC50) of 11.6 uM. However, there was no effect on lysine-specific demethylase 1 (LSD1), histone deacetylase 1(HDAC1) or HDAC8. PA significantly extended the lifespan of female, but not male, Drosophila. In Drosophila S2 cells, the eukaryotic translation initiation factor 4E binding protein (4E-BP) was up-regulated by PA exposure. CONCLUSIONS: Our findings provide insight into the possible relationship between the pharmacological modulation of histone demethylation and lifespan extension by PA; they might also be important in the development of alternative therapies for age-related disorders.     

Unique biological activity of botulinum D/C mosaic neurotoxin in murine species

Clostridium botulinum types C and D cause animal botulism by the production of serotype-specific or mosaic botulinum neurotoxin (BoNT). The D/C mosaic BoNT (BoNT/DC), which is produced by the isolate from bovine botulism in Japan, exhibits the highest toxicity to mice among all BoNTs. In contrast, rats appeared to be very resistant to BoNT/DC in type C and D BoNTs and their mosaic BoNTs. We attempted to characterize the enzymatic and receptor-binding activities of BoNT/DC by comparison with those of type C and D BoNTs (BoNT/C and BoNT/D). BoNT/DC and D showed similar toxic effects on cerebellar granule cells (CGCs) derived from the mouse, but the former showed less toxicity to rat CGCs. In recombinant murine-derived vesicle-associated membrane protein (VAMP), the enzymatic activities of both BoNTs to rat isoform 1 VAMP (VAMP1) were lower than those to the other VAMP homologues. We then examined the physiological significance of gangliosides as the binding components for types C and D, and mosaic BoNTs. BoNT/DC and C were found to cleave an intracellular substrate of PC12 cells upon the exogenous addition of GM1a and GT1b gangliosides, respectively, suggesting that each BoNT recognizes a different ganglioside moiety. The effect of BoNT/DC on glutamate release from CGCs was prevented by cholera toxin B-subunit (CTB) but not by a site-directed mutant of CTB that did not bind to GM1a. Bovine adrenal chromaffin cells appeared to be more sensitive to BoNT/DC than to BoNT/C and D. These results suggest that a unique mechanism of receptor binding of BoNT/DC may differentially regulate its biological activities in animals.     

Novel monoclonal antibodies for identification of multicentric Castleman's disease; Kaposi's sarcoma-associated herpesvirus-encoded vMIP-I and vMIP-II

Recent studies have indicated that vMIP-I and vMIP-II play important roles in the pathogenesis of Kaposi's sarcoma-associated herpesvirus (KSHV)-related diseases due to the effects of these proteins on vascularization. We developed monoclonal antibodies against KSHV-encoded viral macrophage inflammatory protein-I (vMIP-I) and vMIP-II to study these expression profiles and reveal the pathogenesis of KSHV-related diseases. The MAbs against vMIP-I and vMIP-II reacted to KSHV-infected cell lines after lytic induction. Both vMIP-I and the vMIP-II gene products were detected 24 h post-induction with 12-O-tetradecanoylphorbol-13-acetate until 60 h in the cytoplasm of primary effusion lymphoma cell lines. In clinical specimens, both vMIP-I and vMIP-II gene products were detected in the tissues of patients with multicentric Castleman's disease. On the other hand, only vMIP-II was detected in a subset of Kaposi's sarcoma. We concluded that these antibodies might be powerful tools to elucidate the pathogenesis of KSHV-related diseases.     

Homo-catiomer integration into PEGylated polyplex micelle from block-catiomer for systemic anti-angiogenic gene therapy for fibrotic pancreatic tumors

Homo-poly{N'-[N-(2-aminoethyl)-2-aminoehtyl]aspartamide} [PAsp(DET), H] was attempted to integrate into poly (ethylene glycol) (PEG)-b-PAsp(DET)] (B) formulated polyplex micelle with the aim of enhancing cell transfection efficiency for PEGylated polyplex micelle via H integration. In vitro evaluations verified H integration of potent stimulation in enhancing cell-transfecting activity of PEGylated polyplex micelles via promoted cellular uptake and facilitated endosome escape. In vivo anti-angiogenic tumor suppression evaluations validated the feasibility of H integration in promoting gene transfection to the affected cells via systemic administration, where loaded anti-angiogenic gene remarkably expressed in the tumor site, thereby imparting significant inhibitory effect on the growth of vascular endothelial cells, ultimately leading to potent tumor growth suppression. These results demonstrated potency of H integration for enhanced transfection activity and potential usage in systemic applications, which could have important implications on the strategic use of H integration in the non-viral gene carrier design.