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Biomedical subjects

Y Horikawa

Publications and source records attributed to Y Horikawa.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Surgical treatment of multiple inflammatory aortic aneurysms of the aortic arch and thoracoabdominal aorta.

A 67-year-old woman hospitalized with pleuritis was treated with antibiotics. Although the inflammation was resolved, saccular aneurysms in the aortic arch and thoracoabdominal aorta enlarged rapidly. We conducted graft replacement of the aortic arch, but despite careful blood pressure control, the thoracoabdominal aneurysm rapidly enlarged even further. We conducted graft replacement of the thoracoabdominal aorta on day 25 after the first operation. The postoperative course was uneventful and no exacerbation was found 18 months after the second operation. These multiple aortic aneurysms were diagnosed as inflammatory because bacterial tests of blood and aneurysmal walls were all negative and cells infiltrating aneurysmal walls were pathologically plasma cells.

Aged↗
PubMed2000

Juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease) with diffuse neurofibrillary and lewy body pathology.

We describe an unusual case of Hallervorden-Spatz disease (HSD). After presenting with limb rigidospasticity at the age of 9 years, our patient developed progressive dementia, spastic tetraparesis and myoclonic movements, leading to akinetic mutism. He died of pneumonia at the age of 39 years. Autopsy revealed a severely atrophic brain, weighing 510 g. Histologically, there were iron deposits in the globus pallidus and substantia nigra pars reticulata, and numerous axonal spheroids throughout the brain and spinal cord. Neurofibrillary tangles were abundant in the hippocampus, cerebral neocortex, basal ganglia and brain stem. Neuritic plaques and amyloid deposits were absent. Lewy bodies and Lewy neurites, which were immunolabeled by anti-alpha-synuclein, were found in the brain stem, cerebral cortex and spinal gray matter. Sarkosyl-insoluble tau extracted from the temporal cortex resolved on immunoblots into three major bands of 60, 64 and 68 kDa and a minor band of 72 kDa, as reported for Alzheimer's disease. The present case, together with a few similar cases reported previously, may represent a particular subset of neuroaxonal dystrophy, i.e., HSD associated with extensive accumulation of both tau and alpha-synuclein.

Adolescent↗
PubMed2000

Measurement of urinary annexin V by ELISA and its significance as a new urinary-marker of kidney disease.

To confirm the significance of excretion of annexin V into the urine and the change of urinary annexin V concentration in kidney disease, a sandwich enzyme-linked immunosorbent assay (ELISA) was developed using two monoclonal antibodies. Urinary annexin V concentration was measured in healthy individuals and patients with kidney and other diseases. Urinary annexin V did not change over a range of pH between 5.0 and 8.0, and was stable during the course of the study for 24 h at room temperature and for 8 days at 4 degrees C. The mean urinary annexin V concentration in 105 normal healthy individuals was 1.5+/-1.5 ng/ml, while that in patients with nephrotic syndrome and systemic lupus erythematosis (SLE) nephritis was 9.3+/-9.1 and 6.6+/-6.7 ng/ml, respectively, and that in IgA nephropathy and chronic renal failure was 2.6+/-2.1 and 1.3+/-0.7 ng/ml, respectively. Annexin level correlated with urinary protein concentration (r=0. 717), but not the serum creatinine concentration, blood urea nitrogen (BUN) and 24-h creatinine clearance. Mean urinary annexin V concentration in patients with ischemic heart disease, hypertension, and diabetes mellitus was 1.4+/-1.0, 1.4+/-1.1, and 1.7+/-1.3 ng/ml, respectively. In one case of relapsing nephrotic syndrome, the urinary annexin V concentration was markedly increased in the early phase after admission and then decreased. This patient later required hemodialysis. These results suggest that a high urinary annexin V concentration may be an indicator of acute renal injury related to the urinary protein level.

Adult↗
PubMed2000

Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.

Adult↗
PubMed2000

Sternal tuberculosis in a 9-month-old infant after BCG vaccination.

UNLABELLED: Tuberculosis osteitis is mainly observed as a late complication of the pulmonary infection. We describe a 9-mo-old Japanese infant who became infected with Mycobacterium tuberculosis even after receiving Bacillus Calmette-Guerin (BCG) vaccination at 3 mo of age. This is the first report that the sternum is the localization for tuberculous osteitis in infants. He developed a localized tumor in the sternum without any respiratory symptom. Mycobacterium tuberculosis complex was detected by means of nucleic acid amplification test. Gastric aspirates also yielded Mycobacterium tuberculosis. The source of the infection was unclear. CONCLUSION: Tuberculous osteitis should be excluded in infants with undiagnosed bone lesions, even if they have been vaccinated with BCG.

Antitubercular Agents↗
PubMed2000

A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance.

Previous linkage studies in Mexican-Americans localized a major susceptibility locus for type 2 diabetes, NIDDM1, to chromosome 2q. This evidence for linkage to type 2 diabetes was recently found to be associated with a common G-->A polymorphism (UCSNP-43) within the CAPN10 gene. The at-risk genotype was homozygous for the UCSNP-43 G allele. In the present study among Pima Indians, the UCSNP-43 G/G genotype was not associated with an increased prevalence of type 2 diabetes. However, Pima Indians with normal glucose tolerance, who have a G/G genotype at UCSNP-43, were found to have decreased rates of postabsorptive and insulin-stimulated glucose turnover that appear to result from decreased rates of glucose oxidation. In addition, G/G homozygotes were found to have reduced CAPN10 mRNA expression in their skeletal muscle. A decreased rate of insulin-mediated glucose turnover, or insulin resistance, is one mechanism by which the polymorphism in CAPN10 may increase susceptibility to type 2 diabetes mellitus in older persons.

Adolescent↗