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Biomedical subjects

K Sudo

Publications and source records attributed to K Sudo.

At least 73 records · Page 4Linked to original sources
PubMed1998

Butyrylcholinesterase genes in individuals with abnormal inhibition numbers and with trace activity: one common mutation and two novel silent genes.

A random population was screened for abnormal dibucaine and fluoride numbers (DN & FN) to find some common mutations in butyrylcholinesterase (BCHE) gene. Of 2375 unrelated individuals, 10 were found to have low DN and FN and were selected for further studies. DNA analysis of these hypocholinesterasemics revealed that seven patients were heterozygous for missense mutation at codon 330 (TTA to ATA; BCHE*330I). The frequency of BCHE*330I mutation was calculated to be at least 0.29% among the Japanese. On the other hand, two novel mutations were found in three families and two individuals including probands whose enzyme activity was very low (silent gene). Polymerase chain reaction and single stranded conformation polymorphism (PCR-SSCP) and restriction fragment length polymorphism (PCR-RFLP) were used for identification of the common and known mutation types such as BCHE*250P (ACT to CCT), BCHE*365R (GGA to CGA), and BCHE*539T (GCA to ACA; K-polymorphism), whereas PCR-SSCP was used in combination with direct DNA sequencing for new mutations like BCHE*446V (TTT to GTT) and BCHE*451X (GAA to TAA).

Butyrylcholinesterase↗
PubMed1998

Inhibitory effects of podophyllotoxin derivatives on herpes simplex virus replication.

Podophyllotoxin and its derivatives were examined for inhibitory effects on the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), including acyclovir-resistant virus and clinical isolates. Deoxypodophyllotoxin (RD4-6266) proved to be a highly potent and selective inhibitor of all HSV strains in MRC-5 cells. EC50 values of RD4-6283 (in which the methylenedioxy ring A is modified) for HSV-1 and -2 were inferior to those of deoxypodophyllotoxin. However, podorhizol (RD4-6277) and 5'-methoxy-podorhizol (RD4-6276), in which ring C is absent, did not inhibit HSV replication. Moreover, RD4-6266 also inhibited the production of infectious virus particles of HSV-1 KOS strain and HSV-2 G strain. In contrast, none of the podophyllotoxin derivatives were found to have an antiviral effect against influenza A virus, respiratory syncytial virus or human cytomegalovirus in doses not toxic to the cells.

Antiviral Agents↗
PubMed1998

[The recent progress and future prospects of diagnostic DNA testing--experience in DNA analysis of serum enzymes].

Rapid progress in the molecular technology has stimulated attempts to establish DNA diagnosis of human diseases. However, advances in technology have led to improvements at the research level but not in routine laboratory work because only few laboratory tests are covered by medical insurance; the methodologies cannot be easily applied to routine work; and the equipment and reagents are relatively expensive. This paper provides an overview of recent progress in DNA diagnosis and my experience in the DNA diagnostic field. I started working in the DNA diagnostic field in January 1988 with research on mutation analysis of lactate dehydrogenase subunit deficiency. I worked in Dr. Steven Li's laboratory at the National Institutes of Health in North Carolina and discussed with him about screening the patient's genomic library instead of using PCR because PCR was not adequate for mutation analysis. We successfully completed the mutation analysis and I returned to Japan. Thereafter, PCR has been increasingly improved and is now applicable to mutation analysis. Currently, amplification is essential for many DNA diagnostic technologies. The Human Genome Project has progressed and will be finished around 2002. In this process, DNA diagnosis will play an important role in the clinical laboratory. Common diseases, such as atherosclerosis, diabetes mellitus, hypertension and so on, have also been analyzed and the responsible genes will have been identified. Each laboratory should have a specialty and characteristic, and should be ready to help and assist each other via a network. Network communication is clearly needed by laboratories in the future.

Arteriosclerosis↗
PubMed1998

Features of spontaneous improvement in syringomyelia with low-situated cerebellar tonsils.

We analysed six patients who showed spontaneous improvement among the 19 nonsurgically treated cases of syringomyelia with low-situated cerebellar tonsils who visited our outpatient clinic. MR images both before and after improvement were available for two of these patients; CT-myelography before improvement and MR images after improvement were used for two patients; and in the remaining two patients, MR images after improvement only were used. Consequently, we were able to abstract several features from detailed and precise neurological and radiological evaluations of these patients. These features consisted of mild (rather than severe) disability, as well as four radiological features--a rounded shape of the lower edge of the cerebellar tonsils, a low tightness of the foramen magnum, an elevation of the tonsils during the course of the disease. Results of our radiological analyses were consistent with the theories proposed for the pathogenesis of syringomyelia in the light of the CSF flow around the foramen magnum. We propose that the features we have isolated are useful in determining treatment policies and prognoses of patients with syringomyelia accompanied by low-situated cerebellar tonsils.

Adult↗
PubMed1998

Features of spontaneous improvement in syringomyelia with low-situated cerebellar tonsils.

We analysed four patients who showed spontaneous improvement among the 19 nonsurgically treated cases of syringomyelia with low-situated cerebellar tonsils who visited our outpatient clinic. MR images both before and after improvement were available for two of these patients; CT-myelography before improvement and MR images after improvement were used for two patients. Consequently, we were able to abstract several features from detailed and precise neurological and radiological evaluations of these patients. These features consisted of mild (rather than severe) disability, as well as three radiological features--a rounded shape of the lower edge of the cerebellar tonsils, a low tightness of the foramen magnum, an elevation of the tonsils during the course of the disease. Results of our radiological analyses were consistent with the theories proposed for the pathogenesis of syringomyelia in the light of the CSF flow around the foramen magnum. We propose that the features we have isolated are useful in determining treatment policies and prognoses of patients with syringomyelia, accompanied by low-situated cerebellar tonsils.

Adult↗
PubMed1997

Human butyrylcholinesterase L330I mutation belongs to a fluoride-resistant gene, by expression in human fetal kidney cells.

We noticed a Japanese male showed low serum butyrylcholinesterase (BCHE) activity on health examination. The phenotyping analysis revealed a reduced dibucaine number (DN) and an especially low fluoride number (FN), similar to an FS phenotype. A homozygous missense mutation, a T to A transversion at nucleotide 988, was identified in his BCHE gene. This mutation resulted in the replacement of leucine by isoleucine at codon 330 (L330I). DN and FN of recombinant BCHE(L330I) secreted by human fetal kidney cells were compared to recombinant wild-type(usual gene) BCHE and normal serum BCHE. These results showed this amino acid substitution of BCHE, Leu330 to Ile, really caused the abnormal DN and FN. We conclude that the BCHE L330I mutation is a fluoride-resistant gene, a Japanese type fluoride-resistant gene.

Amino Acid Substitution↗
PubMed1997

Novel hepatitis C virus protease inhibitors: thiazolidine derivatives.

This study evaluated the inhibitory effects of thiazolidine derivatives on hepatitis C virus (HCV) protease and other human serine proteases. The inhibition efficacy was tested with a reversed-phase high-performance liquid chromatography (HPLC) assay system using a NS3-NS4A fusion protein as the HCV protease and a synthetic peptide substrate that mimics the NS5A-5B junction. Nine thiazolidine derivatives showed more than 50% inhibition at 50 microg/ml. The most potent derivative was RD4-6250, with 50% inhibition at a concentration of 2.3 microg/ml; this concentration was lower than those of other protease inhibitors reported previously. The most selective derivative was RD4-6205, with 50% inhibition at a concentration of 6.4 microg/ml, a lower concentration than those on other serine proteases (chymotrypsin, trypsin, plasmin, and elastase). These results suggest that the RD4-6205 skeleton is an important structure for inhibitory activity on the HCV protease NS3-NS4A.

Enzyme Inhibitors↗
PubMed1997

High-performance liquid chromatographic method for determination of DX-9065a, a novel anticoagulant, in human urine and feces using cation-exchange solid-phase extraction.

A simple HPLC method for determination of DX-9065a in human urine and feces was developed. The drug was extracted by Bond Elut CBA, a cation-exchange solid-phase extraction cartridge. The extracted drug was analyzed by HPLC with UV detection at 242 nm. With this extraction procedure, no interfering peaks were observed. The method developed was validated and showed adequate precision and accuracy. This method was applied to human clinical samples obtained from healthy Japanese volunteers who had orally received the drug. Using this method, the excretion profile of the drug in human after oral administration was revealed for the first time.

Anticoagulants↗
PubMed1997

Involvement of neutrophil elastase in crescentic glomerulonephritis.

To elucidate the role of neutrophils in the tissue damage of crescentic glomerulonephritis (GN), we examined neutrophils infiltrated in renal tissues and the localization of neutrophil elastase (NE), as a neutrophil-derived tissue destructive mediator, using an immunohistochemical technique with antibodies specific for neutrophils and neutrophil elastase; the enzyme histochemical technique (chloroesterase staining) also was used to detect neutrophils. In normal controls, neutrophil infiltration was scarce, and NE was localized in neutrophil cytoplasm. Neutrophils were abundant in crescentic GN and infiltrated in the glomerulus and interstitium; the infiltrating neutrophils were often aggregated. NE was localized in the cytoplasm of neutrophils and also appeared extracellularly (in granular or diffuse patterns) in glomerular necrotizing lesions, crescents, ruptured portions of Bowman's capsules, and in periglomerular and perivascular sites of the interstitium. Moreover, urinary concentration of NE measured by enzyme-linked immunosorbent assay (ELISA) in crescentic GN patients was significantly higher than in normals (93.6 +/- 13.3 v 1.4 +/- 0.5 microg/g x Cr, respectively; P < .001). These data suggest that NE plays a significant role in renal tissue damage, especially in the formation of glomerular necrotizing and crescentic lesions and in periglomerular interstitial lesions of crescentic GN.

Antigens, CD↗
PubMed1997

Antidiabetic effect of seishin-kanro-to in KK-Ay mice.

The hypoglycemic effect of Seishin-kanro-to (SK) was investigated in KK-Ay mice, one of the non-insulin dependent diabetic mellitus types. SK (1700 mg/kg) reduced the blood glucose of KK-Ay mice from 557 +/- 17 to 383 +/- 36 mg/100 ml 7 hours after single oral administration (P < 0.001). SK also decreased the blood glucose and improved glucose tolerance 5 weeks after repeated administration in KK-Ay mice. These results support, therefore, the use of SK in patients with diabetes and confirm its role as a traditional medicine. In addition, the active plants of SK were identified as the rhizome of Anemarrhena asphodeloides Bunge and the radix of Rehmannia glutinosa Liboschitz.

Animals↗
PubMed1997

A monoclonal antibody modulates neutrophil adherence while enhancing cell motility.

A monoclonal antibody (MoAb) to human neutrophils, designated 3H9, was established by screening for the inhibition of neutrophil adherence to plastic plates containing a medium supplemented with fetal calf serum (FCS medium). The antigen recognized by 3H9 was shown to be present on human leukocytes and found at the highest levels on granulocytes. On Western blotting, 3H9 reacted with a molecule having a molecular weight of 80 kDa. When this MoAb was added at the same time as a neutrophil stimulant (fMLP), the inhibition of neutrophil adherence to plastic plates in the presence of FCS medium was observed after 60 min incubation. Furthermore, this MoAb enhanced not only fMLP-induced chemotaxis but random migration of neutrophils as well. The mechanisms of these phenomena are discussed.

Animals↗
PubMed1997

[Simple method for typing human immunodeficiency virus type I (B, E) by PCR and chronological change of distribution of subtype (B to E) in Japan].

We analyzed the clade distribution of B and E in HIV-1 isolates in Japan by a nested PCR method using 5'-CCCACAAGATTTAAATATG-3' of the gag gene as clade B primer and 5'-CCCACAAGATTTAAACTCC-3' of the gag gene as clade E primer. Seventy-two anti-HIV-1 confirmatory positive serum samples were collected during a period of 1991-1996 in two hospitals in Yokohama City. Peripheral blood mononuclear cells were obtained from the buffy coat of these samples and extracted DNA were used for nested PCR. The 72 cases comprised of 11 Japanese hemophiliacs, 14 Japanese male homosexuals, 19 Japanese male heterosexuals, 5 Japanese female heterosexuals and 23 Thai female heterosexuals. Of these 36 were clade B and 35 were clade E and one case showed positive PCR results for both B and E primers. Almost all male Japanese hemophiliacs and homosexuals in our sample have clade B, while the female Thai heterosexuals have clade E, irrespective of the year of isolation. As for Japanese male heterosexuals, through 1993, clade B was predominant but since 1994, the predominate clade switched to clade E. Although the number of Japanese female heterosexuals in our sample is small, clade B was isolated in 2 cases even after 1994.

Female↗
PubMed1997

Genetic mutations of butyrylcholine esterase identified from phenotypic abnormalities in Japan.

We have identified 12 kinds of genetic mutations of butyrylcholine esterase (BCHE) from phenotypic abnormalities, showing that BCHE activities were deficient or diminished in sera. These genetic mutations, detected by PCR-single-strand conformation polymorphism analysis and direct sequencing, consisted of one deletion (BCHE*FS4), nine missense (BCHE*24 M, *1005, *250P, *267R, *330I, *365R, *418S, *515C, *539T), and two nonsense mutations (BCHE*119STOP, *465STOP). All of the individuals deficient in serum BCHE activity were homozygous for silent genes (6 of 6). Fifty-eight percent of the individuals (31 of 53) with slightly reduced serum BCHE activity were heterozygous for silent genes. They also showed a higher frequency (47% as allele frequency) of the K-variant than the general population (17.5%). Finally, we confirmed low serum BCHE activity in 10 of 23 individuals heterozygous for silent genes.

Butyrylcholinesterase↗
PubMed1997

[A case of Sjögren syndrome associated with multiple mononeuritis and dysautonomia including bilateral tonic pupils].

Sjögren syndrome (SjS) is a glandular disease characterized by dry eyes and dry mouth. Extraglandular manifestations in SjS are also common, and peripheral nerve involvement has been reported in 10-20% of cases. We report a case of Sjögren syndrome with bilateral tonic pupils, dysautonomia, and multiple mononeuritis. The fact that sural nerve sections, in addition to marked loss of myelinated and unmyelinated fibers, showed an increased number of infiltrating macrophages without lymphocytes and aberrant expression of HLA-DR (class II) antigen in Schwann cells was an especially interesting finding. No evidence of active vasculitis was detected. The patient was treated with corticosteroids and her condition gradually improved, as confirmed by thermography. Our findings suggested the presence of specific immunological abnormalities simultaneously involving the ciliary ganglia, autonomic ganglia, and dorsal root ganglia in this peculiar form of SjS.

Autonomic Nervous System Diseases↗
PubMed1997

[A report of two cases of Carpentier-Edwards pericardial mitral valve malfunction due to neointimal overgrowth expanding to valve cusps].

Two cases of Carpentier-Edwards pericardial mitral valve malfunction due to neointimal overgrowth were reported. Case one was a 51-year-old female undergone redo mitral valve replacement at nine years after first operation. Removed valve showed remarkable overgrowth of neointima expanding to the valve cusps. Case two was a 67-year-old male. A valve removed at nine years after first operation and at 1.5 years after recovery of prosthetic valve endocarditis. Removed valve also showed neointimal overgrowth expanding to the valve cusps. Although we experienced only two cases of neointimal overgrowth, these findings were considered being important in durability of Carpentier-Edwards pericardial valve.

Aged↗