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Biomedical subjects

Y Horikawa

Publications and source records attributed to Y Horikawa.

At least 19 recordsLinked to original sources
PubMed2001

Coherence resonance with multiple peaks in a coupled FitzHugh-Nagumo model.

Coherence resonance in a coupled excitable system is studied, through both a computer simulation and a circuit experiment, using a piecewise linear version of the FitzHugh-Nagumo model. White noise is added to the first element and spikes are accordingly generated and transmitted to the second element. The mean, standard deviation, and coefficient of variation of the interspike intervals in the second element have multiple peaks as the noise strengthens, when the coupling strength is small. This results from the phase locking to the spikes that the noise generates.

Animals↗
PubMed2001

Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom.

Variation in CAPN10, the gene encoding the ubiquitously expressed cysteine protease calpain-10, has been associated with type 2 diabetes in Mexican Americans and in two northern-European populations, from Finland and Germany. We have studied CAPN10 in white subjects of British/Irish ancestry, using both family-based and case-control studies. In 743 sib pairs, there was no evidence of linkage at the CAPN10 locus, which thereby excluded it as a diabetes-susceptibility gene, with an overall sib recurrence risk, lambda(S), of 1.25. We examined four single-nucleotide polymorphisms (SNP-44, -43, -19, and -63) previously either associated with type 2 diabetes or implicated in transcriptional regulation of calpain-10 expression. We did not find any association between SNP-43, -19, and -63, either individually or as part of the previously described risk haplotypes. We did, however, observe significantly increased (P=.033) transmission of the less common C allele at SNP-44, to affected offspring in parents-offspring trios (odds ratio 1.6). An independent U.K. case-control study and a small discordant-sib study did not show significant association individually. In a combined analysis of all U.K. studies (P=.015) and in combination with a Mexican American study (P=.004), the C allele at SNP-44 is associated with type 2 diabetes. Sequencing of the coding region of CAPN10 in a group of U.K. subjects revealed four coding polymorphisms-L34V, T504A, R555C, and V666I. The T504A polymorphism was in perfect linkage disequilibrium with the diabetes-associated C allele at SNP-44, suggesting that the synthesis of a mutant protein and/or altered transcriptional regulation could contribute to diabetes risk. In conclusion, we were not able to replicate the association of the specific calpain-10 alleles identified by Horikawa et al. but suggest that other alleles at this locus may increase type 2 diabetes risk in the U.K. population.

Alleles↗
PubMed2001

Reduced skeletal muscle calpain-10 transcript level is due to a cumulative decrease in major isoforms.

The DNA polymorphism SNP-43 in the calpain-10 gene is associated with insulin resistance and reduced skeletal muscle transcript in Pima Indians. Alternative splicing generates transcript isoforms calpain-10a to -10h. We determined the contribution of calpain-10 mRNA isoforms to the decreased total skeletal muscle calpain-10 mRNA levels observed in the G/G homozygotes. The expression levels of the major isoforms, calpain-10a and -10f, were positively correlated with the total calpain-10 mRNA levels, indicating a cumulative effect.

Calpain↗
PubMed2001

Gut transit time after ileal pouch-anal anastomosis using a radiopaque marker.

PURPOSE: The aim of this study was to determine the contribution of gastrointestinal motility to bowel function and the pathogenesis of pouchitis after ileal pouch-anal anastomosis. METHODS: Gastrointestinal transit time was assessed by a radiopaque marker technique in 32 patients with ulcerative colitis. RESULTS: Small intestinal transit time and pouch emptying time were 4.1 +/- 2 hours and 4.1 +/- 2.5 hours, respectively. There was no significant difference in pouch emptying time between patients with and without pouchitis. When only patients with acute pouchitis that responded to metronidazole were analyzed, there was a trend toward a prolonged pouch emptying time compared with those without pouchitis (P = 0.095). Whole gut transit time was inversely correlated with 24-hour stool frequency in patients without pouchitis (r = -0.63, P < 0.005). In the analysis of regional transit time, only small intestinal transit time was inversely correlated with 24-hour stool frequency (r = -0.472, P < 0.05). Significant prolongation of small intestinal transit time was demonstrated in patients over a period of 41 months (the median time) after ileostomy closure compared with those whose pouches had been functioning for 6 to 41 months (5.4 +/- 1.7 hours vs. 3.1 +/- 1.3 hours, P < 0.005). CONCLUSIONS: There was an association between small intestinal motility and bowel frequency. Further investigation is necessary in the pathogenesis of acute pouchitis regarding the relationship between delayed pouch emptying and subsequent development of mucosal inflammation.

Adolescent↗
PubMed2001

Acute aortic dissection associated with Sheehan's syndrome.

A 69-year-old woman with Sheehan's syndrome who suffered acute Stanford type A aortic dissection had received corticosteroids and thyroid hormones for over 20 years. The entire ascending aorta was replaced in emergency graft replacement. We administered twice the usual dose of methylprednisolone during cardiopulmonary bypass and twice the patient's usual dose of prednisolone from postoperative day 1 to 6. The usual 100 micrograms of levothyroxine sodium was given orally from postoperative day 1. The patient's postoperative course was uneventful. This case emphasizes the importance of early active supplementary treatment with steroids and thyroid hormones for major surgery in patients with Sheehan's syndrome.

Acute Disease↗
PubMed2001

Localization of annexin V in rat normal kidney and experimental glomerulonephritis.

The localization of annexin V, a calcium binding protein, was immunochemically and immunohistologically studied in experimental rat glomerulonephritis using annexin V polyclonal antibody. Plasma and urinary annexin V levels were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). Urinary annexin V level, which was correlated with urinary L-lactate dehydrogenase activity, N-acetyl-beta-D-glucosaminidase activity and protein level, increased time-dependently after the injection of nephritogenic antigen (bovine glomerular basement membrane), progressively increasing to attain a peak level at 4 weeks of 51.5 +/- 11.3 ng/h. However, plasma annexin V level showed no increase during the study period. Normal kidneys showed strong staining for annexin V in distal tubules, being particularly strong in tubules of the inner stripe of the outer medulla, but could not be detected in proximal tubules. Annexin V was seen in visceral epithelial cells. Bowman's capsule of the glomerulus, the vascular endothelium of arterioles and interlobular arteries, and vascular smooth muscle. In nephritis, the lumen of distal tubules and the luminal cell membrane were deeply stained, with leakage of annexin V being observed from tubular cells. In the present study, renal annexin V was markedly excreted into urine, and its urinary level reflected the severity of damage of renal tissue and the progression of nephritis. These changes of annexin V in the distal tubule and visceral epithelial cells may be of significance in cell injury of the kidney.

Animals↗
PubMed2001

Inhibitory effect of losartan on laser-induced choroidal neovascularization in rats.

PURPOSE: To investigate the inhibitory effects of losartan, an angiotensin receptor antagonist, on angiogenesis in a rat model of laser-induced choroidal neovascularization. METHODS: Experimental study. Fifteen Brown-Norway male rats received losartan (approximately 5 mg/kg/d) in drinking water, and 15 Brown-Norway male rats received unsupplemented drinking water 1 week before photocoagulation, and it was continued to the end of the study. Two weeks after intense laser photocoagulation, choroidal neovascularization was evaluated by fluorescein angiography and histopathologic evaluation. RESULTS: The incidence of choroidal neovascularization formation was 99.5 +/-.2% (mean +/- standard deviation) in controls and 72.5 +/- 8.8% in losartan-treated rats (P <.01). Quantitative morphometric assessment revealed mean choroidal neovascularization lesion thickness of 54 and 44.8 microm, respectively, in controls and losartan-treated rats (P <.01). CONCLUSION: Losartan seems to inhibit development of laser-induced choroidal neovascularization. Angiotensin receptor antagonists may be useful as prophylaxis against choroidal neovascularization associated with age-related macular degeneration.

Angiotensin Receptor Antagonists↗
PubMed2001

Dynamic observation of selective accumulation of a photosensitizer and its photodynamic effects in rat experimental choroidal neovascularization.

PURPOSE: The authors investigated the selective accumulation of a photosensitizer, ATX-S10(Na), in experimental choroidal neovascularization (CNV) in rats using a highly sensitive colorchromatic charge coupled device (CCD) camera. METHODS: To detect the development of experimental CNV in 30 rats, the animals were followed weekly with simultaneous fluorescein and indocyanine green angiography. After injecting ATX-S10(Na), the authors detected fluorescence from the photosensitizer using a highly sensitive color CCD camera. The camera was connected to a surgical microscope, under which rat fundi were observed through a coverglass in contact with the cornea. The retinas were excited with 405-435 nm light, and the light emitted from the photosensitizer passed through a 680-nm bandpass filter before being detected by the CCD camera. RESULTS: Immediately after injection, fluorescence appeared in the retinal vessels and then the entire retina. Thirty minutes postinjection, the intensity of the fluorescence was still strong from the whole retina, and the CNV was not detected. One hour after injection, retinal fluorescence was weak but still observable; 1.5 hours postinjection, retinal fluorescence was undetectable but fluorescence was strong from the CNV. Under the optimum therapeutic conditions, CNV was effectively occluded. CONCLUSION: ATX-S10(Na) selectively accumulates in the CNV in rats. The optimum therapeutic timing is approximately 1.5 hours postinjection of the dye in this CNV model.

Animals↗
PubMed2001

Mutations in the coding region of the neurogenin 3 gene (NEUROG3) are not a common cause of maturity-onset diabetes of the young in Japanese subjects.

Mutations in transcription factors that play a role in the development of the endocrine pancreas, such as insulin promoter factor-1 and NeuroD1/BETA2, have been associated with diabetes. Cell type-specific members of the basic helix-loop-helix (bHLH) family of transcription factors play essential roles in the development and maintenance of many differentiated cell types, including pancreatic beta-cells. Neurogenin 3 is a bHLH transcription factor that is expressed in the developing central nervous system and the embryonic pancreas. Mice lacking this transcription factor fail to develop any islet endocrine cells and die postnatally from diabetes. Because neurogenin 3 is required for the development of beta-cells and other pancreatic islet cell types, we considered it a candidate diabetes gene. We screened the coding region of the human neurogenin 3 gene (NEUROG3) for mutations in a group of unrelated Japanese subjects with maturity-onset diabetes of the young (MODY). We found three sequence variants: a deletion of 2-bp in the 5'-untranslated region (NEUROG3-g.-44-45delCA), a G-to-A substitution in codon 167 (g.499G/ A), resulting in a Gly-to-Arg replacement (G/R167), and a T-to-C substitution in codon 199 (g.596T/C), resulting in a Phe/Ser polymorphism F/S199. These polymorphisms were not associated with MODY, thereby suggesting that mutations in NEUROG3 are not a common cause of MODY in Japanese patients.

Amino Acid Substitution↗
PubMed2001

Calpains play a role in insulin secretion and action.

Studies of the genetic basis of type 2 diabetes suggest that variation in the calpain-10 gene affects susceptibility to this common disorder, raising the possibility that calpain-sensitive pathways may play a role in regulating insulin secretion and/or action. Calpains are ubiquitously expressed cysteine proteases that are thought to regulate a variety of normal cellular functions. Here, we report that short-term (4-h) exposure to the cell-permeable calpain inhibitors calpain inhibitor II and E-64-d increases the insulin secretory response to glucose in mouse pancreatic islets. This dose-dependent effect is observed at glucose concentrations above 8 mmol/l. This effect was also seen with other calpain inhibitors with different mechanisms of action but not with cathepsin inhibitors or other protease inhibitors. Enhancement of insulin secretion with short-term exposure to calpain inhibitors is not mediated by increased responses in intracellular Ca2+ or increased glucose metabolism in islets but by accelerated exocytosis of insulin granules. In muscle strips and adipocytes, exposure to both calpain inhibitor II and E-64-d reduced insulin-mediated glucose transport. Incorporation of glucose into glycogen in muscle also was reduced. These results are consistent with a role for calpains in the regulation of insulin secretion and insulin action.

Adipocytes↗
PubMed2001

Expression and properties of human liver beta-ureidopropionase.

A cDNA encoding beta-ureidopropionase (BUP) was isolated from a human liver cDNA library, expressed in E. coli, and purified from the culture extract. The 2,006 bp cDNA contained a 1,152 bp open reading frame encoding a protein of 384 amino acids with a molecular weight of 43,165 Da. The subunit molecular weight of the enzyme expressed was about 43,000 Da. The enzyme was inhibited by 1 mM propionate, but not by 10 mM beta-alanine. Chemical analysis of the purified human BUP showed 0.54 zinc atoms per subunit, and the sequence of BUP cDNA contained one putative zinc-binding site motif. The purified enzyme had a pI of 5.65, and exhibited positive cooperativity with N-carbamoyl-beta-alanine as the substrate with a Hill coefficient 2.0. These properties of human BUP, except the inhibition by beta-alanine, were similar to the rat liver purified enzyme. Beta-alanine inhibits rats BUP activity. The complex regulatory function and the negative cooperative mechanism of BUP by beta-alanine have been observed in rats. This kind of mechanism may not exist in humans, because beta-alanine did not inhibit human BUP.

Amidohydrolases↗
PubMed2001

[A case of retroperitoneal fibrosis responding to steroid therapy].

A 73-year-old man presented with acute renal failure due to bilateral hydronephroses. Urography and CT scan revealed stenosis and medial deviation of the bilateral ureters surrounded by a soft tissue mass at the level of the 4-5th lumber vertebrae. Under a diagnosis of retroperitoneal fibrosis, bilateral nephrostomies were temporarily placed and prednisolone administration was initiated at a dose of 20 mg/day. Ureteral passage markedly improved within 2 weeks in association with a decrease in size of the retroperitoneal soft tissue mass. The steroid therapy was continued for 4 months with decreasing dosing schedule. The patient has been doing well without any signs of recurrence for 3 months after the cessation of the steroid therapy.

Aged↗
PubMed2001

[Anesthetic management of a morbidly obese patient undergoing laparoscopic gastric bypass surgery].

We describe a successful anesthetic management of a morbidly obese patient, weighing 170 kg, height of 170 cm and body mass index of 58.8 kg.m-2, who received gastric bypass surgery performed using laparoscopic assist. After arriving in the operating room, an epidural catheter was inserted into the epidural space at the T 7-8 intervertebral space. The trachea was intubated nasally under bronchofiberscopic assist, after which anesthesia was induced with propofol and maintained with nitrous oxide and oxygen (FIO2 = 0.5), i.v. propofol, fentanyl, and epidural anesthesia. Propofol infusion rate was determined using the corrected body weight drawn by Servin et al. Anesthetic management and recovering from anesthesia were uneventful. For propofol anesthesia, infusion rates determined using the corrected body weigh, was preferable for morbidly obese patients.

Adult↗
PubMed2001

[Three cases of pituitary abscess].

We report three cases of pituitary abscess. Three patients, all females, had suffered headache and complained of general fatigue. In each case magnetic resonance imaging (MRI) revealed a sellar mass with suprasellar extension. T1-weighted images revealed an isointense or slightly hypointense lesion with thin ring-enhancement following gadolinium injection. No inflammatory signs were found in two cases. In one case, a gradual change in clinical symptoms and MRI findings was noted: the hypophyseal hemorrhagic lesion detected on MRI changed into a cystic lesion with thin ring-enhancement. Transsphenoidal surgery was performed in all three cases. In each case, however, no organism was cultured and no tumor component was found. It is difficult to diagnose pituitary abscess prior to surgery if no inflammatory signs are present. Diagnosis of this condition requires careful radiological evaluation. Findings of a suprasellar round cystic mass with thin ring-enhancement on MRI associated with thickened stalk, hyperprolactinemia, and diabetes insipidus may be suggestive of a pituitary abscess.

Adult↗
PubMed2001

[The effect of obesity on spinal anesthesia for cesarean section].

To evaluate the effect of obesity on spinal anesthesia for cesarean section, we retrospectively studied 90 parturients who had undergone cesarean section, dividing the patients into 2 groups: obesity group (body mass index > 30, n = 41); control group (body mass index < 30, n = 49). Total surgical time and anesthetic time were longer in the obesity group than in the control group. The amount of ephedrine administered was also greater in the obesity group than in the control group. However, there were no significant differences in time for spinal tap and the incidence of hypotension between the two groups. Spinal anesthesia for cesarean section in obese patients may be an acceptable method.

Adult↗
PubMed2001

[Epiduroscopy in patients with chronic low back pain without remarkable findings on magnetic resonance imaging].

Two patients with chronic low back pain and sciatica failed to respond to conservative treatments. In these patients, magnetic resonance imaging (MRI) showed no remarkable findings corresponding to their symptoms. We treated these patients using epiduroscopy. Epiduroscopic visualization of the spinal canal permits efficient adhesiolysis and irrigation. One patient got better after two epiduroscopic procedures, and the other did not. Epiduroscopy may be an effective, minimally invasive treatment as well as examination for patients with chronic low back pain without remarkable findings on MRI.

Adult↗
PubMed2000

MODY associated with two novel hepatocyte nuclear factor-1alpha loss-of-function mutations (P112L and Q466X).

Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of diabetes characterized by early onset of pancreatic dysfunction. MODY type 3 is caused by mutations in the hepatocyte nuclear factor (HNF)-1alpha. During a screening of Norwegian patients with suspected MODY we identified two novel HNF-1alpha mutations, P112L and Q466X. The molecular mechanisms underlying the disease were studied by analyzing the DNA binding properties, transcriptional activation, and subcellular localization of HNF-1alpha P112L and Q466X compared to wild type HNF-1alpha. P112L had reduced ability to bind an HNF1 consensus sequence and to activate transcription. Q466X did not differ from wild type HNF-1alpha in DNA binding activity. Transactivation, however, was markedly reduced. When both mutants were coexpressed with wild type HNF-1alpha in HeLa cells, transcriptional activity appeared unaffected, suggesting that a dominant-negative mechanism was not present. Immunolocalization experiments showed that P112L HNF-1alpha was correctly targeted to nuclei in HeLa cells. In contrast, some Q466X HNF-1alpha protein was retained in the cytoplasm, which indicated that the mechanism for nuclear localization was disturbed. Thus, the HNF-1alpha mutations P112L and Q466X both seem to impair pancreatic beta-cell function by loss-of-function mechanisms; P112L by reduced DNA binding and reduced ability to transactivate, and Q466X by reduced transactivation and incomplete nuclear targeting.

DNA↗