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K Sugimoto

Publications and source records attributed to K Sugimoto.

At least 721 records · Page 40Linked to original sources

Insulin receptor in rat peripheral nerve: its localization and alternatively spliced isoforms.

BACKGROUND: Diabetic neuropathy accompanies both Type 1 and Type 2 diabetes, although it shows in both humans and animal models distinct differences between the two types of diabetes. Progressive paranodal degenerations occurring in Type 1, but not in Type 2, diabetes is believed to account for the more severe functional deficits in Type 1 diabetic rats. This suggests that factors other than hyperglycemia, such as insulin deficiency, may play a pathogenetic role. In this study, we investigated the immunolocalization of the insulin receptor (IR) and the expression of its two alternatively spliced isoforms in adult rat peripheral nerve. METHODS: Adult male Wistar rats 6-8 months of age were examined. Both light and ultrastructural immunohistochemistry was employed for localization of IR. The antibody was a mouse monoclonal antibody raised against the beta-subunit of human IR. Reverse transcription polymerase chain reaction (RT-PCR) was used to identify the two IR isoforms in peripheral nerve and seven other organs. Localization of the mRNA message was assessed by in situ hybridization. RESULTS: IR was localized to paranodal terminal Schwann cell loops and microvilli and to the paranodal axolemma. Furthermore, IR immunoreactivity was also present in Schmidt-Lantermann incisures. Endoneurial vessels showed IR localization on plasma membranes and in endocytotic vesicles of endothelial cells and pericytes. A high intensity of immunostained IR was found in close proximity to interendothelial tight junctions. Peripheral nerve showed, like the brain, predominantly the high affinity IR lacking exon 11. The mRNA message was localized to Schwann cells, endothelial cells and pericytes. CONCLUSION: Peripheral nerve expresses predominantly the high affinity IR, which is localized to strategic structures associated with the blood-nerve barrier and the paranodal ion-channel barrier.

Alternative Splicing↗

Diabetic neuropathy--a continuing enigma.

In this article we will review the clinical signs and symptoms of diabetic somatic polyneuropathy (DPN), its prevalence and clinical management. Staging and classification of DPN will be exemplified by various staging paradigms of varied sophistication. The results of therapeutic clinical trials will be summarized. The pathogenesis of diabetic neuropathy reviews an extremely complex issue that is still not fully understood. Various recent advances in the understanding of the disease will be discussed, particularly with respect to the differences between neuropathy in the two major types of diabetes. The neuropathology and natural history of diabetic neuropathy will be discussed pointing out the heterogeneities of the disease. Finally, the various prospective therapeutic avenues will be dealt with and discussed.

Animals↗

Effect of D-glucose on nitric oxide release from glomerular endothelial cells.

BACKGROUND: Altered glomerular production of nitric oxide (NO) may be involved in hyperfiltration in early diabetic nephropathy. However little is known as to the role of glomerular endothelial cells (GECs) in diabetic hyperfiltration and their ability to release NO in response to hyperglycemia. METHODS: Using an established cell line, we directly monitored NO release from GECs in response to various concentrations of D-glucose, D-mannitol, and L-arginine, an NO synthase (NOS) agonist. L-Arginine-induced NO release was examined in the cells pretreated for different periods up to 24 h with 10 or 30 mM D-glucose. We also measured serially the accumulation of nitrite, the stable metabolite of NO, produced by the cells incubated for up to 24 h under 10 or 30 mM D-glucose conditions in the presence or absence of the NOS inhibitor, L-NAME. RESULTS: Direct measurement of NO demonstrated that D-glucose, but not D-mannitol, stimulation resulted in a rapid and dose-dependent increase in NO release by the cells. However, L-arginine-induced NO release was attenuated significantly in the cells preincubated for more than 12 h with 30 mM D-glucose compared to 10 mM D-glucose. The L-NAME-inhibitable production of nitrite in the media was significantly increased 1.5--2.0-fold until 6 h after incubation with 30 mM D-glucose compared to 10 mM D-glucose. CONCLUSIONS: We conclude that D-glucose, but not D-mannitol, produces a rapid and dose-dependent increase in NO release, whereas exposure to high D-glucose for more than 12 h may blunt NOS activity and/or NO stability in the GECs. These observations may therefore be important for glomerular endothelial dysfunction induced by hyperglycemia that is still tentative and may have a role in diabetic nephropathy.

Analysis of Variance↗

Complications following balloon-occluded arterial infusion chemotherapy for pelvic malignancies.

PURPOSE: To evaluate the incidence and causes of complications associated with balloon-occluded arterial infusion chemotherapy (BOAI) for pelvic malignancies. METHODS: In 34 courses of BOAI in 22 patients with pelvic malignancies, we analyzed the incidence of complications as well as the effect of the dose of the anticancer drugs, the infusion site, and the number of BOAI administrations on these complications. Complications were divided into two categories: cystitis-like symptoms and neurological complications such as pain, numbness, and paresthesia of the lower extremities and the hip. RESULTS: Eleven patients (50%) suffered from complications, seven (31.8%) from neurological complications and four (18.2%) from cystitis-like symptoms. The complications appeared in 14 courses (42. 4%) of BOAI, neurological complications in 10 (30.3%) and cystitis-like symptoms in four (12.1%). A high dose of anti-cancer drugs and infusion from the anterior division tended to induce neurological complications more frequently; however, the cystitis-like symptoms were not related to any factors. CONCLUSION: Our results indicate that a smaller dose of anti-cancer drugs should be infused from the bilateral internal iliac arteries for safer pelvic BOAI.

Aged↗

Contingent negative variation enhancement in tinnitus patients.

Contingent negative variations recorded in 20 tinnitus patients with an average hearing level within 40 dB were compared with those from age-matched healthy controls. In addition, negative and positive potentials (N100 and P300), which are presumed to reflect stimulus information processing, were examined. Contingent negative variation amplitude was significantly greater in patients than in controls (P less than .05, ANOVA), but no significant differences were observed in the N100 and P300 latencies and amplitudes for the two groups. We interpret these results as evidence of abnormalities in the central information processing mechanism of tinnitus patients.

Adult↗

An in vitro method generating base substitutions in preselected regions of plasmid DNA: application to structural analysis of the replication origin of the Escherichia coli K-12 chromosome.

A method for introducing base substitutions in defined regions of plasmid DNA has been developed. In principle, a circular heteroduplex DNA containing a gap is constructed by annealing of two kinds of linear molecules derived from the same plasmid: One is the molecule shortened either by exonucleolytic digestion from the termini generated at a restriction site or by removal of a region flanked by two restriction sites, and the other the full-length molecule linearized at a different site. The deleted region in the shorter linear molecule becomes a single-stranded gap in the circular heteroduplex DNA. The heteroduplex is then treated with sodium bisulfite that converts specifically cytosine residues to uracil residues in single-stranded regions. After filling in the gap by repair synthesis, transformation is carried out to isolate mutant plasmids. Since two kinds of circular heteroduplexes are formed by annealing in which the sequences in the gaps are complementary to each other, mutagenesis of both strands can be accomplished in one experiment. This method was applied to construction of mutants with base substitutions in the replication origin region (oriC) of the Escherichia coli K-12 chromosome which had previously been cloned in colicin E1 plasmid vectors, and various mutants in defined regions of oriC were successfully isolated at high efficiencies. Analysis of these mutants provided evidence that oriC contains special regions, designated spacers, which separate neighboring important sequences specifying interactions with initiation factors for DNA replication at precise distances.

Base Sequence↗

Emulsification tendency of silicone-phenylsilicone copolymer.

PURPOSE: We compared the emulsification tendency of silicone-phenylsilicone copolymer (DPC; 5%-phenylated, specific gravity 0.984) with that of silicone oil (SO; specific gravity 0.966) and fluorosilicone oil (FSO; specific gravity 1.256), all of which are used clinically as intraocular tamponades. METHODS: We investigated the tendencies of emulsification in SO, FSO, and DPC. Each was placed in a separate glass container with equal amounts of albumin solution (1 mg/mL) or 1 gamma-globulin solution (1 mg/mL) and shaken. We also investigated the toxicity of DPC in the rabbit eye. Following vitrectomy, we injected DPC into the vitreous cavity and assessed the retinal damage histologically. RESULTS: The SO and DPC, because their specific gravities, are closer to water, tended to become less emulsified than did FSO. We found that DPC did not cause any severe histological damage in the rabbit retina. CONCLUSION: Highly phenylated DPC is slightly heavier than water and may be used instead of FSO to treat inferior retinal detachment.

Animals↗

Effects of cilostazol on the peripheral nerve function and structure in STZ-induced diabetic rats.

We examined the effect of cilostazol (CZ), antiplatelet agent and potent vasoactive compound, which has an inhibitory effect on tissue phosphodiesterase, on peripheral nerve in streptozotocin-induced diabetic rats. Diabetic rats were fed for 12 weeks with a chow containing 0.01% or 0.03% CZ (w/w) and the results were compared with untreated diabetic rats. The 0.03% CZ treatment significantly improved motor nerve-conduction velocity and restored nerve Na+, K(+)-ATPase activity in diabetic rats without affecting body weight and glycated hemoglobin levels, but the effects of 0.01% CZ treatment did not reach statistical difference. Elevated sorbitol and reduced myo-inositol levels in diabetic nerve tissues were not influenced by CZ treatment. Structural analysis of the sural nerve demonstrated a partial but significant effect on decreased mean myelinated fiber area and atrophic changes of the axon in diabetic rats treated with 0.01% CZ. CZ treatment inhibited reduction of pericyte area of endoneurial microvessels in diabetic rats. Expansion of endoneurial microvessels and luminal area in relation to vascular area also tended to be inhibited by CZ treatment. Thus CZ treatment ameliorated, although not completely, functional and structural abnormalities in peripheral nerve of diabetic rats without effecting the polyol pathway. These results support the contention that vascular factors may play an important role in the etiology of experimental diabetic neuropathy and suggest that CZ may have a beneficial therapeutic effect on diabetic neuropathy.

Animals↗

Primary structure of the alpha-subunit of transducin and its relationship to ras proteins.

A group of membrane-associated guanine nucleotide binding proteins (G-proteins) are essential for transducing signals generated at cell-surface receptors into changes in cellular function and metabolism. These proteins are a complex of three subunits designated alpha, beta and gamma. The alpha-subunit is responsible for binding guanine nucleotides and seems to be characteristic of each protein. Transducin, a member of this protein family, mediates visual transduction by coupling the signal of photolysed rhodopsin with activation of a cyclic GMP phosphodiesterase. We have now cloned and sequenced the complementary DNA encoding the alpha-subunit of bovine retinal transducin and from this we have deduced the complete amino-acid sequence. The transducin alpha-subunit shares several homologous amino-acid sequences with ras gene products. The homologous segments correspond mostly to the regions thought to be involved in the guanine nucleotide binding and GTPase activity of ras proteins and to the ADP-ribosylation sites of the transducin alpha-subunit.

Adenosine Diphosphate Ribose↗

Intracerebral hematoma developing during MR examination.

We report a case of a 78-year-old woman with cerebellar infarction who developed intracerebral bleeding during the magnetic resonance (MR) examination. The intensity of the hematoma was heterogeneous corresponding to the heterogeneous density shown on CT study that immediately followed the MR examination.

Aged↗

High potassium diets reduce macrophage adherence to the vascular wall in stroke-prone spontaneously hypertensive rats.

Our previous study demonstrated that high potassium (K) diets reduce stroke mortality in stroke-prone spontaneously hypertensive rats (SHRsp) even when the blood pressure is not lowered. On the other hand, macrophage infiltration into the vascular wall is known to play an important role in the development of arterial lesions. In this study, in vivo and in vitro experiments were performed to examine the effect of high K diets on macrophage adherence to the vascular wall in SHRsp rats. In the in vivo study, 51Cr-labelled macrophages, collected from the peritoneal cavity, were injected intravenously to SHRsp rats fed 6% high NaCl diets containing either normal 0.5% K or high 2.1% K, and, 45 min later, the rats were perfused with buffered saline to remove blood. Radioactivity from macrophages in the aorta was 40% lower in the high K SHRsp than in the normal K SHRsp (p < 0.002), and the brain of high K SHRsp also showed a 52% lower macrophage radioactivity than that of normal K SHRsp (p < 0.007). Although the mean blood pressure was slightly lower in the high K diet group than in the normal K diet group (167 vs. 184 mm Hg), these differences remained still prominent even when we compared groups with matching blood pressures; -33% for the aorta (p < 0.02) and -55% for the brain (p < 0.02). In the in vitro study, the aortas of SHRsp rats similarly fed on normal or high K diet were excised and mounted in a perfusion chamber. They were perfused with labelled macrophages at normotensive or hypertensive pressure. In normal K SHRsp, macrophage radioactivity remained in the washed aorta was 158% higher in high perfusion pressure group than in normal pressure (p < 0.002). However, they did not significantly differ between two perfusion pressures in high K SHRsp. These results indicate that high K diets reduce endothelial injuries which allow adherence and infiltration of macrophages into the vascular wall of hypertensive animals, and thereby contribute to the reduction of vascular lesions and stroke mortality.

Animals↗

Intraabdominal lymphangiosarcoma in a Fischer-344 rat.

A Sarcoma arising in the abdominal cavity in an aged Fischer-344 rat was studied by immunohistochemistry and electron microscopy. The white-yellow soft mass was located on the lumbosacral vertebrae, compressing adjacent parenchymal organs. The tumor was made up of spindle shaped cells situated in a background of myxoid substance and a small amount of reticulin and collagen fibers. The tumor cells grew in a loose storiform pattern and often adhered to each other by their cell processes to form ovoid or slitlike spaces. Immunohistochemically, the tumor cells were strongly positive for vimentin but negative for keratin, macrophage ED1 antigen, alpha-smooth muscle actin, Factor VIII-related antigen, and S100 protein. Electron microscopy demonstrated the endothelial differentiation of the tumor cells, such as occasional luminal spaces, a small number of micropinocytotic vesicles, and interdigitating junctions with desmosomes between cell processes of adjacent cells. Furthermore, its endothelial origin was suggested by the presence of electron-dense rods resembling Weibel-Palade bodies. Instead of a definitive basement lamina surrounding the tumor cells, there were extracellular thin "anchoring filaments" that were attached to the cell surface at areas of increased electron density. These findings indicate that the tumor is of lymphatic vessel type rather than blood vessel type.

Abdominal Neoplasms↗

A clinical study on SSP (silver spike point) electro-therapy combined with splint therapy for temporo-mandibular joint dysfunction.

When the functional limits of the muscles related to the temporo-mandibular joint and adjacent tissue exceed their anatomical capability, pain, crepitation, and functional abnormality appear as the main complaints. Although the precise nature of the condition is unknown, pain at the temporo-mandibular joint sometimes in combination with muscular tension is assumed to be due to compression of the myoneural mechanism. It is reported that occlusal lifting using a splint enables the alleviation of this muscular tension. On the other hand, there are only a few reports on the usefulness of SSP therapy for Temporo-Mandibular Joint Dysfunction. We studied the efficacy of SSP therapy combined with splint therapy in 33 patients diagnosed as having Temporo-Mandibular Joint Dysfunction who consulted our department primarily due to pain, and report our findings below. Evaluation of the results was conducted 2 weeks later. Very beneficial results were seen in 6 cases. Beneficial results were seen in 7 cases. Slightly beneficial results were seen in 18 cases, while there were no changes found in 2 cases. When combined SSP and splint therapies were conducted for Temporo-Mandibular Joint Dysfunction, favorable results were seen in about 90% of the cases.

Acupuncture Analgesia↗