Biomedical subjects

A Kon

Publications and source records attributed to A Kon.

36 records · Page 2Linked to original sources

PubMed1997

Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa.

BACKGROUND: Kindler syndrome is a rare, inherited skin disease characterized by acral bullae formation, fusion of fingers and toes, and generalized progressive poikiloderma. The purpose of this study was to clarify the nature of the bullous component of Kindler syndrome and to determine whether this inherited skin disorder represents a variant of dystrophic epidermolysis bullosa or a unique independent clinical entity. OBSERVATIONS: Two unrelated patients with Kindler syndrome were studied. Electron microscopy demonstrated marked duplication of the lamina densa, and clefts were observed in areas where the lamina densa was destroyed or obscured. Hemidesmosomes and anchoring fibrils showed normal features. Indirect immunofluorescence revealed normal linear labeling with antibodies against hemidesmosomal components (alpha 6 and beta 4 integrins, BPAG1, and BPAG2) and against anchoring filament components such as uncein, as detected by the 19-DEJ-1 monoclonal antibody. However, antibodies against the 3 respective laminin 5 chains, type IV collagen, and various type VII collagen epitopes (the aminoterminal NC1 domain, the central triple helical collagenous domain, and the carboxyterminal end of the triple helical collagenous domain) revealed a broad reticular staining pattern. Molecular screening of the type VII collagen gene (COL7A1) in the patients and their parents by heteroduplex analysis failed to detect any band shifts indicative of pathologic mutations. CONCLUSIONS: These results suggest that the bullous component of Kindler syndrome is distinct from dystrophic epidermolysis bullosa caused by mutations in the type VII collagen gene. Additionally, the differential distribution patterns of uncein and laminin 5 in the patients' skin samples support the hypothesis that uncein and laminin 5 are different molecules.

Adult↗

PubMed1995

A study of the steroid sulfatase gene in families with X-linked ichthyosis using polymerase chain reaction.

We have studied the steroid sulfatase (STS) gene in three Japanese families with X-linked ichthyosis (XLI), using polymerase chain reaction (PCR). PCR was performed using three sets of intraexonic primers covering exons 1, 5 and 10. In affected individuals from two of the families, DNA was not amplified in any of the three exons, suggesting that XLI in these families was due to the complete deletion of the STS gene. In affected individuals in the remaining family, DNA was amplified in predicted sizes in exons 1 and 5, but not in exon 10, suggesting that XLI in this family was due to partial deletion of the STS gene including exon 10. These results suggested that STS gene deficiency is heterogeneous in Japanese families with XLI. PCR is useful for the rapid diagnosis of XLI, the differentiation of XLI from ichthyosis vulgaris, and genetic counseling of XLI families. The PCR method was not applicable for carrier detection.

Adolescent↗

PubMed1995

A visual telemedicine system: the integration of ordinary TV and HDTV still image transmission.

This paper describes a project to develop and test a new telemedicine system using image transmission. The system was implemented at Aomori prefecture, the northernmost prefecture of Japan, to provide medical consultation to remote hospitals from a medical center located in Aomori city, capital of the prefecture. The characteristics of the system are the combination of an HDTV still image transmission system and an ordinary tele-conference system using 65 kilobit telephone line i.e., an ordinary telephone line available in almost any part of Japan. We also developed a disk storage system that stores transmitted images automatically without human intervention. The system was assessed in real clinical settings and has proved to be effective in various areas of medical consultation, including radiology, pathology, dermatology, etc. We hope that this system becomes a standard telemedicine system in the future.

Computer Peripherals↗

PubMed1994

Type VII collagen DNA linkage analysis in a Japanese family with dominant dystrophic epidermolysis bullosa.

Type VII collagen, a major component of anchoring fibrils in the basement membrane zone, is now considered to be a primary genetic factor in the pathogenesis of dominant dystrophic epidermolysis bullosa (DDEB). In this study, we performed genetic linkage analysis in a Japanese family with DDEB using a PvuII polymorphism in the type VII collagen gene. The pedigree consisted of 10 affected and 13 unaffected living individuals and was diagnosed as having Cockayne-Touraine type of DDEB. Electron microscopic examination of the skin demonstrated a diminished number and rudimentary structure of anchoring fibrils. PCR-based detection of PvuII polymorphism resulted in 3 genotypes and co-segregated with DDEB phenotype in this pedigree. The maximum lod score was 2.10 at recombination fraction (theta) of 0. The absence of recombination between DDEB and type VII collagen gene locus, as well as the observation of altered anchoring fibrils, suggested that type VII collagen is a candidate gene for the Japanese family with DDEB, although the lod score was statistically not significant.

Base Sequence↗

PubMed1994

Mouse 230-kDa bullous pemphigoid antigen gene: structural and functional characterization of the 5'-flanking region and interspecies conservation of the deduced amino-terminal peptide sequence of the protein.

The 230-kDa bullous pemphigoid antigen is a hemidesmosomal protein of the cutaneous basement membrane zone. The primary sequences deduced from full-length human cDNAs predict that this molecule consists of a central rod region and flanking globular domains. To get insight into regulation of the 230-kDa bullous pemphigoid antigen gene (BPAG1), and to evaluate evolutionary conservation of the amino-terminus of the protein, we screened a mouse genomic DNA library with a 0.3-kb cDNA corresponding to the 5' end of the human 230-kDa bullous pemphigoid antigen cDNA. A positive clone was isolated, and Southern analysis of the clone with the 0.3-kb cDNA allowed isolation of a 3.0-kb Hind III fragment containing the 5' end of the coding sequence. Alignment of the sequences of this subclone and human BPAG1 sequences revealed that this fragment contained 2466 bp of 5'-flanking DNA, upstream from the ATG translation initiation site, and 258 bp of translatable sequences that encode a putative polypeptide of 86 amino acids at the amino-terminus of the protein. This deduced polypeptide showed 91% homology with the corresponding human sequence. The TATAAA and CCAAT consensus sequences, as well as several putative cis-regulatory elements, were identified in the 5'-flanking region of the mouse DNA. To test the functional promoter activity of the 5'-flanking DNA, three mouse BPAG1 promoter/CAT reporter gene constructs, with the promoter segments spanning from -1133, -525, and -213 to -1, were developed. Transient transfections of mouse transformed keratinocytes (Pam 212 cells) with these constructs revealed clearly detectable CAT activities, indicating that the 5'-flanking region contains a functional promoter. Furthermore, these experiments suggested that the upstream sequences contain upregulatory elements, as well as elements that confer, at least in part, tissue specificity to the expression of the mouse 230-kDa BPA gene.

Amino Acid Sequence↗

PubMed1991

Characterization of beta-D-xyloside-induced glycosaminoglycans and oligosaccharides in cultured human skin fibroblasts.

Human skin fibroblasts were incubated in the presence of a fluorogenic xyloside, 4-methylumbelliferyl beta-D-xyloside. Three fluorogenic components were isolated and purified from the culture medium by gel permeation high-performance liquid chromatography. Their structures were then characterized by enzymatic digestion, fast-atom-bombardment mass spectrometry, gas-liquid chromatography, and electrophoresis on cellulose acetate membrane. The results showed that one of the components was a mixture of dermatan sulfate (70%) and chondroitin sulfate (30%), bearing the 4-methylumbelliferone at the reducing termini, and having an average molecular weight of 9,200. The others had the structures galactosyl-galactosyl-xylosyl-4-methylumbelliferone and galactosyl-xylosyl-4-methylumbelliferone, respectively, representing the linkage region between the glycosaminoglycan chains and core protein, except that 4-methylumbelliferone replaced the amino acid. Moreover, it was demonstrated that these oligosaccharides were intermediates of glycosaminoglycan synthesis, not depolymerized products.

Adult↗

PubMed1991

Application of 2-aminopyridine fluorescence labeling to glycosaminoglycans.

A pyridylamination method was applied to glycosaminoglycans and the characteristics of the resulting pyridylamino glycosaminoglycans were examined. First, glycosaminoglycan chains, which uniformly possess a xylose residue at their reducing termini, were liberated from proteoglycan by successive digestion with protease and endo-beta-xylosidase. Then the glycosaminoglycan chains were coupled with 2-aminopyridine by reductive amination with sodium cyanoborohydride for 15 h according to the method of Hase, S. et al. [J. Biochem. 95, 197-203 (1984)]. The pyridylamination reaction caused neither depolymerization, de-N-acetylation, nor de-N- or de-O-sulfation. The pyridylamino glycosaminoglycan chains had an intact linkage region (GlcA-Gal-Gal-Xyl) between the carbohydrate chain and the peptide core of the proteoglycan. These pyridylamino glycosaminoglycans should be useful as substrates for endo-type glycosidases that act on glycosaminoglycan chains and as markers for studies of glycosaminoglycan metabolism.

Aminopyridines↗

PubMed1991

Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity.

Multiple lines of evidence indicate that PrPSc, found only in scrapie, is a necessary component of the infectious scrapie agent. Equally compelling is the evidence that its accumulation in the brain causes the neuropathology characteristic of scrapie. We measured the regional concentration of PrPSc in nine brain regions throughout the course of scrapie in the Syrian hamster following intrathalamic inoculation of prions. PrPSc was compared to the regional concentration of glial fibrillary acidic protein, a measure of reactive astrocytic gliosis. PrPSc was detected first in the thalamus 14 to 21 days postinoculation and next in the septum at 28 days. Initiation of PrPSc synthesis and accumulation in the thalamus was attributable to the inoculum and in the septum to ventricular spread of de novo synthesized PrPSc. The timing and pattern of PrPSc accumulation in all other brain regions suggested transmission along neuroanatomic pathways. Reactive astrocytic gliosis followed PrPSc accumulation in each region by 1 to 2 weeks. Brain PrPSc, determined by summing the concentrations in each brain region, correlated well with scrapie infectivity titers throughout the course of infection (correlation coefficient = 0.975; slope of linear regression line = 1.136). Our results support the hypothesis that PrPSc participates in both the etiology and pathogenesis of prion diseases.

Animals↗

PubMed1990

Presence of an endo-beta-galactosidase degrading the linkage region between the chondroitin sulfate chain and core peptide of proteoglycan.

Pyridylamino chondroitin sulfate, of which the reducing terminal xylose was coupled with a fluorescent 2-aminopyridine, was incubated at pH 4.0 with an extract from the mid-gut gland of Patnopecten. The high- and low-molecular-weight products were separated by ethanol precipitation, and identified by high-performance liquid chromatography analysis. The enzyme was found to expose a galactose residue at the reducing terminus of chondroitin sulfate, and also released the pyridylamino disaccharide, galactosylxylose, from the reducing terminal site of pyridylamino chondroitin sulfate. These results suggest that endo-beta-galactosidase activity, which hydrolyzes the galactosylgalactose linkage of peptidochondroitin sulfate, is present in the mid-gut gland of Patnopecten.

Aminopyridines↗

PubMed1990

Isolation and characterization of Patnopecten mid-gut gland endo-beta-xylosidase active on peptidochondroitin sulfate.

An endo-beta-xylosidase acting on the linkage region of peptidochondroitin sulfate was isolated from the mid-gut gland of the mollusc Patnopecten and purified about 375-fold, using a combination of ammonium sulfate fractionation, gel filtration on Sephacryl S-200, and DEAE-Sephacel chromatography. The pH optimum and the isoelectric point of this enzyme were 4.0 and 7.0, respectively. The molecular weight, estimated by gel filtration through Sephacryl S-200, was 78,000. The purified enzyme was completely free from protease, exoglycosidases, sulfatase, and phosphatase. This enzyme hydrolyzed the xylosyl serine linkage of the linkage region of various glycosaminoglycans, that is chondroitin sulfate, dermatan sulfate and heparan sulfate, all possessing a very small peptide segment, but not proteoglycans. It was concluded that this endo-beta-xylosidase was involved in the catabolism of proteoglycans.

Animals↗

PubMed1978