Identification of a SACS gene missense mutation in ARSACS

The authors describe two patients in a Japanese family with autosomal recessive spastic ataxia of Charlevoix-Saguenay. They presented early onset spastic ataxia, sensorimotor neuropathy, nystagmus, slurred speech, and hypermyelinated retinal nerve fibers. The authors identified a homozygous missense mutation (T7492C) in the SACS gene, which resulted in the substitution of arginine for tryptophan at amino acid residue 2498 (W2498R).     

Riboflavin-radical formation by mechanochemical solid-state reaction using stainless steel vessel

The mechanochemical reaction of free riboflavin (FR) due to vibratory ball milling was carried out in a stainless steel vessel at room temperature under anaerobic conditions. The ESR of the fractured sample showed a broad single-line spectrum. It is suggested that the solid-state single-electron transfer (SSET) reaction from the surface of the stainless steel vessel to FR proceeded during the vibratory milling, resulting in the formation of the corresponding anion radicals. When the mechanochemical reaction of FR in the presence of calcium pantothenate (PC) was carried out, the radical concentration increased with the increasing PC content. It was shown that the anion radical in the metal complex was stable for a lengthy period of time even in highly humid air.     

Differential gene expressions during immortalization of normal human fibroblasts and endothelial cells transfected with human telomerase reverse transcriptase gene

It is widely accepted that telomerase, which compensates for telomere shortening, is finally activated in almost all kinds of human malignant neoplasms, and ectopic expression of telomerase may endow some kinds of human somatic cells with indefinite proliferation capacity, i.e., immortality. To clarify the intrinsic responses required in acquiring immortality, we investigated the chronological changes in the expression levels of the cell cycle and apoptosis-related genes by real-time RT-PCR in human normal fibroblasts and endothelial cells after hTERT transfection. We found that fibroblast MJ90 required intrinsic responses including reversible upregulation of cell-cycle promoting genes and down-regulation of apoptosis-inducing genes in early phase after transfection, whereas the endothelial cell HUE142-2 did not. In addition, the microarray analysis of the fibroblast strains revealed that the dysregulated genes during cellular immortalization were different from those reported in fibroblasts probably having acquired telomere maintenance mechanism concomitant with hTERT induction. These findings indicate that cell-type specific differential gene expression after telomerase activation may be important to acquire telomere-maintenance capacity and immortality in some non-cancerous human cells. Investigation of these molecules may elucidate the differences in the capacity of acquiring immortality in cancer and normal somatic cells in future.     

Fracture mechanisms of retrieved titanium screw thread in dental implant

Titanium and its alloy are increasingly attracting attention for use as biomaterials. However, delayed fracture of titanium dental implants has been reported, and factors affecting the acceleration of corrosion and fatigue have to be determined. The fractured surface of a retrieved titanium screw and metallurgical structures of a dental implant system were analyzed. The outer surface of the retrieved screw had a structure different from that of the as-received screw. It was confirmed that a shear crack initiated at the root of the thread and propagated into the inner section of the screw. Gas chromatography revealed that the retrieved screw had absorbed a higher amount of hydrogen than the as-received sample. The grain structure of a titanium screw, immersed in a solution known to induce hydrogen absorption, showed features similar to those of the retrieved screw. It was concluded that titanium in a biological environment absorbs hydrogen and this may be the reason for delayed fracture of a titanium implant.     

Delayed radiation necrosis with extensive brain edema after gamma knife radiosurgery for multiple cerebral cavernous malformations--case report

A 39-year-old man presented with multiple intracranial cavernous malformations manifesting as intractable seizures persisting for more than 20 years. He underwent gamma knife radiosurgery (GKRS) for right frontal and left temporal cavernous malformations. He began to suffer from progressive left hemiparesis and inattention 2 years 5 months after the GKRS. Magnetic resonance imaging showed abnormal ring enhancement and extensive brain edema around the right frontal lesion. Conservative therapies such as external decompression, low-dose barbiturates, and mild hypothermia had no effect on his clinical status. Stereotactic biopsy of the ring-enhanced area demonstrated gliosis. Signs of cerebral herniation appeared, so we performed partial resection of the right frontal lobe. His symptoms recovered immediately. Subsequent hyperbaric oxygen (HBO) therapy significantly improved the extensive brain edema. Delayed radiation necrosis associated with potentially fatal brain edema may occur after GKRS for cavernous malformations. Internal decompression and subsequent HBO therapy were very effective for the treatment of these lesions.     

Successful total arch replacement for a 92-year-old woman with acute Stanford A aortic dissection: report of a case

We reported a successful case of emergent total arch replacement for a nonagenarian with acute Stanford A aortic dissection. A 92-year-old woman complained of general fatigue, with hypotension. Echocardiography showed moderate pericardial effusion and aortic regurgitation. Computed tomography (CT) scan showed widely extended aortic dissection from the ascending aorta to descending thoracic aorta, and cardiac tamponade. An emergent total arch replacement was performed under hypothermic selective cerebral perfusion with bladder temperature of 22.5 degrees C. Although she suffered from pneumothorax, renal insufficiency and gastrointestinal (GI) bleeding postoperatively, she tolerated the operation and complications, well. She is now leading a good life with the same level of activities of daily living (ADL) as preoperative one.     

Loss of von Hippel-Lindau protein causes cell density dependent deregulation of CyclinD1 expression through hypoxia-inducible factor

Loss of the von Hippel-Lindau gene (VHL) expression ca-uses deregulation of contact inhibition of cell growth, which might be one of the bases of the tumor suppressor function of VHL. Here we show that this function of the VHL gene product (pVHL) depends on cell autonomous events. To identify the target gene of pVHL, which is directly involved in the contact inhibition, we compared the gene expression profile between VHL-deficient renal carcinoma 786-O cells and those infected with an adenovirus vector encoding VHL. In addition to known pVHL-regulated genes, such as vascular endothelial growth factor and carbonic anhydrase, we found cyclinD1 as a new target of pVHL at a high cell density. In VHL-expressing cells (VHL (+) cells), the cyclinD1 mRNA expression level diminishes at a high cell density, while it remains at a relatively high level in VHL-deficient cells (VHL (-) cells). The cyclinD1 expression level was also abnormally high in VHL (-) cells at a high cell density. Consequently, the phosporylation level of the retinoblastoma (Rb) protein remained high in these cells, whereas there was no phosporylated Rb in VHL (+) cells under the contact inhibition. The abnormal expression of cyclinD1 at a high cell density was observed even in VHL (+) cells under the hypoxic state. Moreover, ectopic expression of a HIF mutant resistant to pVHL-mediated proteolysis causes the abnormal cyclinD1 expression in VHL (+) cells. Taken together, these observations indicate that VHL is required for the downregulation of cyclinD1 at a high cell density through HIF.     

Disseminated infection due to Scedosporium apiospermum in a patient with acute myelogenous leukemia

A 62-year-old man diagnosed with acute myelogenous leukemia which had developed from myelodysplastic syndrome received cytarabine and idarubicine as an induction therapy. The patient developed pneumonia and bacterial sepsis during profound neutropenia. Fever and sepsis improved by using many anti-bacterials and anti-fungals but he became febrile again and complained of severe lumbar pain. 67Ga scintigram showed abnormal uptake in the lumbar vertebra and left sternoclavicular joint, suggesting a diagnosis of discitis and osteomyelitis in the lumbar vertebra and sternoclavicular arthritis. We biopsied the site several times but culture of the biopsy specimen could not isolate any pathogens, and high fever persisted for about 10 months despite administration of various anti-bacterials and anti-fungals. Finally we inserted a catheter into the abscess at the iliopsoas muscle and Scedosporium apiospermum was isolated in the bloody pus obtained from the catheter. Itraconazole and amphotericin B were restarted, and the high fever and lumbar pain improved rapidly. The findings of S. apiospermum infection in this patient emphasizes the importance of being aware of this pathogen in patients with hematologic malignancy during the neutropenic phase.