Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 127 records · Page 7Linked to original sources

PubMed2000

Temperature-sensitive mutation of PEX6 in peroxisome biogenesis disorders in complementation group C (CG-C): comparative study of PEX6 and PEX1.

Peroxisome biogenesis disorders (PBD), including Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease, are a group of genetically heterogeneous autosomal-recessive diseases caused by mutations in PEX genes that encode peroxins, proteins required for peroxisome biogenesis. Zellweger syndrome patients present the most severe phenotype, whereas neonatal adrenoleukodystrophy patients are intermediate and infantile Refsum disease patients have the mildest features. PEX6 is a causative gene for PBD of complementation group C (CG-C) and encodes the peroxin Pex6p, one of the ATPases associated with diverse cellular activities and a member of the same family of proteins as Pex1p, a causative protein for PBD of CG-E (CG1). Here, we identified the temperature sensitivity of peroxisomes in the fibroblasts of a patient with neonatal adrenoleukodystrophy in CG-C. Peroxisomes were morphologically and biochemically formed at 30 degrees C but not at 37 degrees C. This patient was homozygous for a missense mutation, T-->C at nucleotide 170 resulting in a change from leucine to proline at amino acid 57 (L57P) in Pex6p. CG-C cell mutants (ZP92) in the Chinese hamster ovary transfected with L57P in HsPEX6 revealed the same temperature-sensitive phenotype. However, PEX1-deficient Chinese hamster ovary cell mutants (ZP101) transfected with L111P in PEX1, the counterpart to L57P in PEX6, showed no temperature sensitivity. In addition, ZP92 transfected with G708D in PEX6, the counterpart to the temperature-sensitive mutation G843D in PEX1, revealed no temperature-sensitive phenotype. These results indicate that L57P in Pex6p is a temperature-sensitive mutation causing the milder phenotype in a patient with PBD in CG-C. They also indicate that the amino acid residues responsible for temperature sensitivity do not seem to be conserved between Pex6p and Pex1p.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2000

[Pharmacological properties of nateglinide, rapid-onset/short-duration insulinotropic agent, in the treatment of type 2 diabetes].

An early defect in Type 2 diabetes is the loss of acute insulin release after food intake, which causes prolonged elevation of postprandial glucose levels. Suppressing postprandial hyperglycemia is considered to be very important for preventing diabetic complications. Sulfonylureas are well-known insulin secretagogues and have been widely used in the treatment of Type 2 diabetes. These agents, however, do not appear to be able to ameliorate impairment of the first phase of insulin secretion and postprandial hyperglycemia. Nateglinide, which is a derivative of D-phenylalanine, is a non-sulfonylurea insulin secretagogue. Although the in vitro insulin-releasing effect of nateglinide is similar to that of sulfonylureas, its hypoglycemic effect is more rapid and short lasting. The in vivo unique pharmacodynamic profile of nateglinide is likely to result from its rapid absorption and elimination. This novel antidiabetic agent has made it possible to compensate for the impaired first phase insulin response and thus suppresses postprandial hyperglycemia. In clinical trials, nateglinide reduced prandial glucose excursion and improved early phase of insulin release dose-dependently after 12 weeks treatment. Nateglinide is a highly physiologic mealtime glucose regulator, which rapidly increases insulin secretion when taken before meals, mimicking early-phase insulin release lost in patients with Type 2 diabetes.

Animals↗

PubMed2000

Molecular cloning of the gene encoding an outer-membrane-associated beta-N-acetylglucosaminidase involved in chitin degradation system of Alteromonas sp. strain O-7.

The gene encoding beta-N-acetylglucosaminidase (GlcNAcaseA) was cloned using PCR with degenerate oligonucleotide primers from the partial amino acid sequence of the enzyme. The gene encoded a polypeptide of 863 amino acids with a predicted molecular mass of 97kDa. A characteristic signal peptide, which was present at the amino-terminus of the precursor protein, contained four amino acids (Ala-Gly-Cys-Ser) identical in sequence and location to the processing and modification sites of the outer membrane lipoprotein of Escherichia coli, indicating that the mature GlcNAcaseA is a lipoprotein the N-terminal cysteine residue of which would be modified by the fatty acid that anchors the protein in the membrane. The predicted amino acid sequence of GlcNAcaseA showed similarity to bacterial beta-N-acetylglucosaminidases belonging to the family 20 glycosyl hydrolases.

Acetylglucosaminidase↗

PubMed2000

Temperature sensitivity in peroxisome assembly processes characterizes milder forms of peroxisome biogenesis disorders.

Peroxisome biogenesis disorders (PBDs) contain various clinical phenotypes; Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), decreasing in the clinical severity in this order. We found that all IRD cell lines and some NALD lines belonging to several different complementation groups are temperature-sensitive in peroxisome assembly; that is, they lacked catalase-positive peroxisomes at 37 degrees C, but do gain the peroxisomes at 30 degrees C. We identified heterozygous mutations E55K/R119Stop in the PEX2 gene of an IRD patient of complementation group F. The E55K mutation was the direct cause of the temperature-sensitivity because similar phenotypes could be transferred to PEX2-defective CHO cells by transfecting the mutant gene. Thus, temperature-sensitive peroxisome assembly is representative of milder forms of PBDs.

Humans↗

PubMed2000

Acute glomerulonephritis superimposed on focal segmental glomerulosclerosis: a case report.

A 9-year-old boy was referred to our hospital because of significant hematuria and proteinuria associated with hypocomplementemia. Although he had had a 3-year history of asymptomatic persistent proteinuria detected by urine screening of school children, he did not visit a physician. Finally, he visited a regional hospital, and hypocomplementemia was noted there. A percutaneous renal biopsy performed hospital day 4 revealed diffuse endocapillary proliferative glomerulonephritis with severe tubulointerstitial changes. Although his hematuria and hypocomplementemia spontaneously subsided within a month, proteinuria remained. A renal biopsy performed 4 months after the first renal biopsy revealed the lesion suggesting advanced focal segmental glomerulosclerosis (FSGS). Despite corticosteroid treatment, his proteinuria persisted, and he developed end stage renal failure. These clinical observation indicated that he had acute glomerulonephritis (AGN) superimposed on non-nephrotic FSGS, and that the episode of AGN might cause exacerbation of the FSGS.

Child↗

PubMed2000

Long-term follow-up of periodontitis in a patient with Chédiak-Higashi syndrome. A case report.

Chediak-Higashi syndrome (CHS) is an extremely rare hereditary disease characterized by leukocyte dysfunction. We report on a 21-year-old woman who presented at the age 9 years with CHS and serious periodontal tissue destruction around erupted teeth. The patient had received systemic, radiographic, immunological, microbial, and clinical periodontal examinations since childhood. The chemotactic activity of neutrophils in the Boyden chamber assay was 22% of the control, and leukocyte bactericidal activity was one-third of the control. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia were isolated from periodontal pockets. Periodontal treatment including oral hygiene was provided, followed by professional tooth cleaning from the age of 12 to 21 years. However, the mobility of teeth and the inflammation of periodontal tissue progressed. This CHS patient presented with periodontal disease of extremely early onset, which was resistant to periodontal treatment.

Actinobacillus Infections↗

PubMed2000

Characterization of the nuclear localization signal in the DNA helicase responsible for Bloom syndrome.

Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, photosensitivity, immunodeficiency and a high predisposition to various types of cancer. BLM was identified as the causative gene for BS. The BLM protein is homologous to DNA helicase and has two basic amino acid clusters in its C-terminal region. Previously, we reported that the distal arm of these basic amino acids clusters in the BLM protein functioned as the nuclear localization signal (NLS) of the protein. In this study, we generated plasmid constructs for expression of enhanced green fluorescent protein (EGFP) fused with various BLM protein variants having a mutation with deletions or substitutions in the basic amino acid and analyzed the subcellular localization of the expressed proteins. The EGFP-fused protein containing the basic amino acid cluster region proximal to the C-terminus of BLM helicase was localized exclusively in the nucleus. However, the EGFP-BLM proteins that lacked either Arg1344 or Lys1346 distributed in both the cytoplasm and the nucleus equally. Deletion of Arg1347 also resulted in localization in both the nucleus and cytoplasm, and substitution of Arg1344, Lys1346, Arg1347 or Arg1348 with non-basic amino acids reduced the nuclear localization of BLM protein. Mouse BLM protein which also migrate to the nucleus has two basic amino acid clusters in the C-terminus and the basic amino acids (Lys1346-Pro1347-Lys1348-Arg1349-Arg1350) proximal to the C-terminus are conserved between mouse and human. These findings suggest that the Arg1344-Ser1345-Lys1346-Arg1347 sequence at the C-terminus of the human BLM protein is essential for nuclear localization of this protein.

Adenosine Triphosphatases↗

PubMed2000

[Bloom syndrome].

Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, sunsensitivity, immunodeficiency and a high predisposition to various types of cancer. BLM was identified as the causative gene for BS, and BLM protein is homologous to DNA helicase. In 1995 the causative gene for BS was identified using somatic crossover point mapping and termed BLM. BLM is a 4437 bp cDNA that encodes a 1417 amino acid peptide which is homologous to ATP-dependent DNA helicases. DNA helicases are the enzymes which catalyze the unwinding of double-stranded DNA to provide single- stranded templates for the processes of replication, repair, recombination and transcription. BLM is a member of the RecQ helicase family, consisting of human WRN, RECQL and yeast Sgs1. The BLM protein translocates into the nucleus and the distal arm of the bipartite basic residues in the C-terminus of the BLM protein is essential for targeting the nucleus. Here, we also describe relationship between the BLM gene and the cancer.

Adenosine Triphosphatases↗

PubMed2000