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Articles by K Nakashima
Total Records ( 5 ) for K Nakashima
  Y Kanda , M Shimoda , S Hamamoto , K Tawaramoto , F Kawasaki , M Hashiramoto , K Nakashima , M Matsuki and K. Kaku

Pioglitazone preserves pancreatic β-cell morphology and function in diabetic animal models. In this study, we investigated the molecular mechanisms by which pioglitazone protects β-cells in diabetic db/db mice. In addition to the morphological analysis of the islets, gene expression profiles of the pancreatic islet were analyzed using laser capture microdissection and were compared with real-time RT-PCR of db/db and nondiabetic m/m mice treated with or without pioglitazone for 2 wk or 2 days. Pioglitazone treatment (2 wk) ameliorated dysmetabolism, increased islet insulin content, restored glucose-stimulated insulin secretion, and preserved β-cell mass in db/db mice but had no significant effects in m/m mice. Pioglitazone upregulated genes that promote cell differentiation/proliferation in diabetic and nondiabetic mice. In db/db mice, pioglitazone downregulated the apoptosis-promoting caspase-activated DNase gene and upregulated anti-apoptosis-related genes. The above-mentioned effects of pioglitazone treatment were also observed after 2 days of treatment. By contrast, the oxidative stress-promoting NADPH oxidase gene was downregulated, and antioxidative stress-related genes were upregulated, in db/db mice treated with pioglitazone for 2 wk, rather than 2 days. Morphometric results for proliferative cell number antigen and 4-hydroxy-2-noneal modified protein were consistent with the results of gene expression analysis. The present results strongly suggest that pioglitazone preserves β-cell mass in diabetic mice mostly by two ways; directly, by acceleration of cell differentiation/proliferation and suppression of apoptosis (acute effect); and indirectly, by deceleration of oxidative stress because of amelioration of the underlying metabolic disorder (chronic effect).

  H Koike , N Atsuta , H Adachi , M Iijima , M Katsuno , T Yasuda , Y Fukada , K Yasui , K Nakashima , M Horiuchi , K Shiomi , K Fukui , S Takashima , Y Morita , K Kuniyoshi , Y Hasegawa , Y Toribe , M Kajiura , S Takeshita , E Mukai and G. Sobue

Acute autonomic and sensory neuropathy is a rare disorder that has been only anecdotally reported. We characterized the clinical, electrophysiological, pathological and prognostic features of 21 patients with acute autonomic and sensory neuropathy. An antecedent event, mostly an upper respiratory tract or gastrointestinal tract infection, was reported in two-thirds of patients. Profound autonomic failure with various degrees of sensory impairment characterized the neuropathic features in all patients. The initial symptoms were those related to autonomic disturbance or superficial sensory impairment in all patients, while deep sensory impairment accompanied by sensory ataxia subsequently appeared in 12 patients. The severity of sensory ataxia tended to become worse as the duration from the onset to the peak phase of neuropathy became longer (P < 0.001). The distribution of sensory manifestations included the proximal regions of the limbs, face, scalp and trunk in most patients. It tended to be asymmetrical and segmental, rather than presenting as a symmetric polyneuropathy. Pain of the involved region was a common and serious symptom. In addition to autonomic and sensory symptoms, coughing episodes, psychiatric symptoms, sleep apnoea and aspiration, pneumonia made it difficult to manage the clinical condition. Nerve conduction studies revealed the reduction of sensory nerve action potentials in patients with sensory ataxia, while it was relatively preserved in patients without sensory ataxia. Magnetic resonance imaging of the spinal cord revealed a high-intensity area in the posterior column on T2*-weighted gradient echo image in patients with sensory ataxia but not in those without it. Sural nerve biopsy revealed small-fibre predominant axonal loss without evidence of nerve regeneration. In an autopsy case with impairment of both superficial and deep sensations, we observed severe neuronal cell loss in the thoracic sympathetic and dorsal root ganglia, and Auerbach’s plexus with well preserved anterior hone cells. Myelinated fibres in the anterior spinal root were preserved, while those in the posterior spinal root and the posterior column of the spinal cord were depleted. Although recovery of sensory impairment was poor, autonomic dysfunction was ameliorated to some degree within several months in most patients. In conclusion, an immune-mediated mechanism may be associated with acute autonomic and sensory neuropathy. Small neuronal cells in the autonomic and sensory ganglia may be affected in the initial phase, and subsequently, large neuronal cells in the sensory ganglia are damaged.

  K Zannis , J. F Deux , B Tzvetkov , K Nakashima , D Loisance , A Rahmouni and M. E.W. Kirsch

The present study was undertaken to evaluate clinical, hemodynamic, and morphologic results of composite stentless xenograft with polyethylene terephthalate fiber (Dacron; DuPont, Wilmington, DE) graft extension for combined replacement of the aortic valve, root, and ascending aorta.


Between 1997 and 2008, 55 consecutive patients (33 men, 71 ± 11 years) underwent ascending aortic replacement using Medtronic Freestyle with Dacron graft extension (DuPont). Indications included aneurysm (n = 31, 56%), dissection (n = 16, 29%), and endocarditis (n = 8, 15%). Associated procedures were performed in 25 patients (46%). Preoperative logistic EuroSCORE averaged 34% ± 28%. Mean cardiopulmonary bypass and aortic cross-clamp times were 244 ± 134 minutes and 162 ± 69 minutes, respectively.


Clinical follow-up was 100% complete and averaged 2 ± 3 years. Early mortality was 0% (n = 0) in patients with a preoperative EuroSCORE of less than 20 (n = 26, mean expected mortality, 13% ± 5%) and 31% (n = 9) in those with preoperative logistic EuroSCORE of at least 20 (n = 29, mean expected mortality, 52% ± 28%). One- and 3-year survival rates were 83% ± 5% and 78% ± 7%, respectively. No major thromboembolic or spontaneous bleeding events were recorded. One patient (2%) required late reoperation for prosthetic valve endocarditis. Echocardiographic follow-up showed no valve dysfunction and low mean transvalvular gradients (7 ± 5 mm Hg). A 64-channel computed tomographic scan was performed in 33 patients at 32.4 ± 34 months and revealed two small pseudoaneurysms in a single patient.


Composite Freestyle with Dacron graft extension appears to be a safe option for bioprosthetic replacement of the aortic root and tubular ascending aorta. However, long-term results using this composite graft will have to be determined.

  I Hojo Nakashima , R Sato , K Nakashima , T Hagiwara and M. Yamada

Peptidylarginine deiminases (PADs) consist of five enzymes which are widely distributed in human and rodent tissues. The two types of enzymes are found in human peripheral blood cells; PAD4 mainly in granulocytes and monocytes and PAD2 in lymphocytes and macrophages. Little is known about the regulation of PAD expression in macrophages. Here, we report that PAD2 is expressed in human monocytic leukaemia THP-1 cells during differentiation into macrophages by 12-O-tetradecanoylphorbol-13-acetate. During this differentiation, the levels of PAD2 mRNA and protein increased concomitantly, indicating the transcriptional regulation of PAD2 gene expression in the cells. The treatment of THP-1-derived macrophages with calcium ionophore A23187 generated vimentin deimination and resulted in the disruption of vimentin filament organization. We discuss the possible role of vimentin deimination in cell physiology.

  R Gohara , D Liu , K Nakashima , Y Takasaki and S. Ando

Organic compounds are used as templates to regulate the morphology of inorganic nanostructures. In the present study, we used intermediate filaments (IFs), the major cytoskeleton component of most eukaryotic cells, as a template for hollow silica nanotube preparation. Sol–gel polymerization of tetraethoxysilane proceeded preferentially on the surface of IFs assembled from vimentin protein in vitro, resulting in silica-coated fibres. After removing IFs by calcination, electron microscopy revealed hollow silica nanotubes several micrometers long, with outer diameters of 35–55 nm and an average inner diameter of 10 nm (comparable to that of IFs). Furthermore, the silica nanotubes exhibited a gnarled surface structure with an 18–26 nm repeating pattern (comparable to the 21-nm beading pattern along IFs). Thus, the characteristic morphology of IFs were well replicated into hollow silica nanotubes, suggesting that IFs maybe useful as an organic template.

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