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Biomedical subjects

N Kanda

Publications and source records attributed to N Kanda.

At least 55 records · Page 3Linked to original sources
PubMed1997

Avascular necrosis of bone in systemic lupus erythematosus. The predictive role of precipitating autoantibodies.

The association between the type of precipitating autoantibodies and occurrence of avascular necrosis of bone (AVN) was examined. We prospectively analyzed clinical and laboratory findings of our 113 patients with SLE. Seven of 113 (6%) patients developed AVN. Anti-Ro (SS-A) and anti-RNP antibodies coexisted in 3 of 7 AVN patients. The same combination of these two antibodies were observed in 1 without AVN. Antibodies to topoisomerase I were detected in 2 other patients with AVN but not in any of the patients without AVN. The coexistence of the former two or the presence of the latter one is rare in SLE. However, these (combination of) antibodies can be useful as a local ischemic marker predicting the development of AVN.

Adolescent↗
PubMed1996

Amplification of a DEAD box gene (DDX1) with the MYCN gene in neuroblastomas as a result of cosegregation of sequences flanking the MYCN locus.

A DEAD box gene (DDX1) characterized by a motif with a putative RNA helicase was found at elevated levels, with multiple copies, in a neuroblastoma and in some retinoblastoma cell lines in which the MYCN gene was amplified. The present study was aimed at determining whether amplification of the DDX1 gene is critical for human neuroblastomas exhibiting MYCN gene amplification. Extended DNA panels of tumors and cell lines revealed amplification of the DDX1 gene in approximately half of the specimens exhibiting MYCN gene amplification, which is in good agreement with a finding reported recently. Because its profile was similar to that of the cDNA marker G21 and another flanking DNA marker, clone 8, both of which localize outside the core of the amplicon of the MYCN gene, we noted that we could localize the DDX1 gene in relation to the MYCN gene. Utilizing pulsed-field gel electrophoresis according to a method based on the combinatorial alignment of multiple single digests and a 5.5-megabase map surrounding the MYCN locus, we mapped the DDX1 gene within a 100 kb region about 400 kb upstream from the MYCN gene, where G21 is localized. Further hybridization experiments with both genes, complete sequencing of G21, and its comparison with that of the DDX1 gene eventually confirmed that the DDX1 gene is identical to G21. G21 is a cDNA clone isolated by differential screening of a library from a neuroblastoma cell line, IMR-32, but its function has not yet been identified. Coamplification of the DDX1 gene with the MYCN gene is a consequence of the segregation of continuous DNA stretches spanning both loci during the amplification process.

Amino Acid Sequence↗
PubMed1996

An increased NM23H1 copy number may be a poor prognostic factor independent of LOH on 1p in neuroblastomas.

In a study of 154 neuroblastomas, loss of heterozygosity (LOH) was observed on 1p (13%, 19/143), 11q (19%, 11/59), 14q (15%, 15/97), 17p (5%, 5/105) and 17q (17%, 9/52). We also found an increase in NM23H1 copy number in 14% (13/95) of neuroblastomas. All except one tumour with an increased copy number stained positive with anti-NM23H1 monoclonal antibody. Event-free survival (EFS) was significantly shorter in 19 patients with LOH on 1p than in 128 without (41% vs 77% 4 year EFS, P=0.0093), and in 13 patients with increased NM23H1 copy numbers than in 82 with normal copy numbers of the gene (61% vs 84% 4 year EFS, P=0.0103). LOH on 11q, 14q or 17q did not affect EFS. Most tumours with LOH on 1p, increased NM23H1 copy numbers or MYCN amplification occurred in patients aged 12 months or more, those with advanced stage disease, and those who showed near diploidy or pseudodiploidy. However, LOH on 1p was found in only 1 of the 13 tumours with increased NM23H1 copy numbers, and MYCN amplification of four copies occurred in only one other such tumour. These findings suggest that the increased NM23H1 copy number may be a predictor for poor prognosis, independent of LOH on 1p, and probably also of MYCN amplification.

Alleles↗
PubMed1996

Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells.

We studied the in vitro effect of testosterone on spontaneous immunoglobulin production by human peripheral blood mononuclear cells (PBMC). Testosterone inhibited IgG and IgM production by PBMC both from males and females. The inhibitory effect of testosterone was revealed at doses more than 1 nM, increased dose-dependently, and reached a plateau at 100 nM. At doses < 1000 nM, testosterone did not reduce cell viability. Testosterone treatment reduced IgG production by 59.0% and that of IgM by 61.3% compared with control. Immunoglobulin production by B cells was also suppressed by testosterone, though the magnitude of the suppressive effect on B cells was lower than that on whole PBMC; testosterone-induced decrease of IgG production compared with control was 26.9% and that of IgM was 24.9%. Exogenous IL-6 partially restored the impaired immunoglobulin production of testosterone-treated PBMC; IgG production in testosterone culture was increased by IL-6 from 35.6% to 66.5% of control and that of IgM was also increased from 38.9% to 71.2%, respectively. Testosterone treatment reduced IL-6 production of monocytes by 78.4% compared with control, but neither affected that of T cells or B cells. These results suggest that testosterone may suppress immunoglobulin production of human PBMC directly by inhibiting B cell activity and indirectly by reducing IL-6 production of monocytes. It is thus indicated that this hormone may have protective and therapeutic effects on human autoimmune diseases.

Adult↗
PubMed1996

Genetic clinical markers of human neuroblastoma with special reference to N-myc oncogene: amplified or not amplified?--An overview.

Neuroblastoma is the most common extracranial tumor in children, and cytogenetically, chromosome 1p deletions, extrachromosomal double minutes, and homogeneously staining regions (HSRs) are commonly observed in cell lines and in tumors in advanced stages. It is found that an HSR represents genomic amplification of N-myc, which plays a key role in determining the aggressiveness of neuroblastoma. However, stage IV neuroblastomas or cell lines which lack N-myc amplification are also progressive, and some of them show evidence of N-myc expression in terms of mRNA and/or N-Myc oncoprotein. It was recently shown that a small proximal locus mapped between 1p35-36.1 and 1p36.23 may function as a suppressor gene of N-myc amplification. In neuroblastoma, a pattern of diploidy is associated with rapid tumor growth and poor survival. Expression of bcl-2 proto-oncogene is strongly associated with unfavorable histology, while expressions of Ha-ras and trk-A proto-oncogenes indicate a favorable prognosis. trk-A proto-oncogene encodes a receptor for nerve growth factor. Genetic characteristics of neuroblastomas found by urinary catecholamine mass screening are also discussed.

Biomarkers, Tumor↗
PubMed1996

Competitive polymerase chain reaction for the quantification of N-myc gene copy number in neuroblastoma.

An absolute quantification method for the N-myc gene copy number of neuroblastoma specimens was established by applying the competitive polymerase chain reaction (cPCR). The competitor plasmid (pZH2) lacking an MluI site in the exon 2 was constructed to distinguish two product species amplified from genomic DNA and the competitor plasmid. By using this cPCR system, we could obtain qualitative results within 1 day, i.e. amplified or unamplified, and quantitative results by using radiolabelled nucleotides within 4 days. The copy numbers of N-myc in 47 neuroblastoma specimens by cPCR correlated well with those by Southern hybridization (r = 0.85). We conclude that cPCR is a simple and rapid method, requires only a small amount (200 ng) of sample DNA, and is expected to be used for prognostic evaluation in neuroblastomas.

Base Sequence↗
PubMed1996

Clinical features of systemic lupus erythematosus in men. Characteristics of the cutaneous manifestations.

BACKGROUND: Cutaneous manifestations of systemic lupus erythematosus (SLE) in men have not been precisely investigated. OBJECTIVE: The purpose of this study is to define the clinical features of SLE in men, focusing on skin lesions. METHODS: The clinical and laboratory manifestations of 28 male and 111 female patients were compared. RESULTS: Widespread discoid lupus erythematosus (DLE) and papular and nodular mucinosis (PNM) were significantly more common in men than in women. Serum sex hormone levels were within the normal range in all make patients examined. CONCLUSION: This study suggests that gender differences exist in SLE and that male patients tend to present with atypical cutaneous manifestations.

Adolescent↗
PubMed1995

Identification of the human ERK gene as a putative receptor tyrosine kinase and its chromosomal localization to 1p36.1: a comparative mapping of human, mouse, and rat chromosomes.

From a newly determined cDNA sequence of the human ERK gene, a highly hydrophobic portion was identified upstream of the putative tyrosine kinase domain. This is the first evidence that the ERK protein possesses a receptor-like membrane-spanning structure. Fluorescence in situ hybridization analysis of R-banded metaphase chromosomes revealed that the ERK gene is located in chromosome region 1p36.1. This locus is near the frequent translocation breakpoint or deletion region of neuroblastoma and some other cancers. A comparative mapping study of the mouse and rat homologues indicated that each counterpart maps to the mouse chromosome 4D2.2-D3 and rat chromosome 5q36.13 regions, both of which have conserved linkage homology to human chromosome 1p.

Amino Acid Sequence↗
PubMed1995

Effects of D-phenylalanine-derivative hypoglycemic agent A-4166 on pancreatic alpha- and beta-cells: comparative study with glibenclamide.

We have reported that N-[(trans-4-isopropyl-cyclohexyl)-carbonyl]-D-phenylalanine (A-4166) stimulates insulin secretion in animal studies. To further elucidate the mechanisms underlying the actions of this agent, we investigated the effects of A-4166 on insulin and glucagon secretion with or without diazoxide, an ATP-sensitive potassium channel opener, using isolated perfused rat pancreas preparations, and compared the results with those of glibenclamide. Both 30 mumol/l A-4166 and 3 mumol/l glibenclamide significantly stimulated insulin secretion and reduced glucagon secretion to similar levels at a glucose concentration of 5.6 mmol/l (p < 0.01 for both vs. basal levels). After infusion of A-4166 was stopped, insulin levels promptly returned to the basal values, while insulin levels increased further even after discontinuation of glibenclamide. Furthermore, 100 mumol/l diazoxide significantly inhibited the insulin-stimulatory effects of both 30 mumol/l A-4166 and 3 mumol/l glibenclamide (p < 0.05 and p < 0.01, respectively). However, the effects of diazoxide on glucagon secretion differed between the two groups; 30 mumol/l A-4166 produced a transient increase in glucagon secretion (p < 0.05 vs. basal levels) but 3 mumol/l glibenclamide suppressed glucagon secretion further (p < 0.01 vs. without diazoxide) with concomitant administration of 100 mumol/l diazoxide. These findings suggest that A-4166 directly stimulates insulin secretion, at least in part, through mechanisms resembling those of sulfonylurea, but exerts different effect on glucagon secretion in isolated perfused rat pancreas.

Analysis of Variance↗
PubMed1994

Sequence homology of Chinese hamster metallothionein genes I and II to those of the mouse and rat, and their amplification in Cd-resistant cells.

The metallothionein (MT) I and II genes were isolated from Chinese hamster cells and sequenced. The MT-II gene is located about 6 kb upstream of the MT-I gene and their arrangement is similar to those of the mouse and rat MT genes. The sequence of the Chinese hamster MT-I gene is highly homologous to those of the mouse and rat, particularly in their promoter regions of MT-I. However, the promoter region of MT-II has less homology with those of the mouse and rat due t to insertions and deletions. The MT-I and MT-II genes were equally amplified 4-8-times in the Cd-resistant Chinese hamster cells, suggesting that both genes are included in the same amplification unit. Cytogenetic analysis of Cd-resistant cells by in situ hybridization showed that they are randomly integrated into multiple sites on the chromosomes.

Amino Acid Sequence↗
PubMed1994

Megabase-scale analysis of the origin of N-myc amplicons in human neuroblastomas.

In order to elucidate the initiation of the N-myc gene amplification, we have analyzed the original structures of the N-myc amplicons among 38 human neuroblastomas. Nineteen DNAs isolated from the N-myc amplicons recognized a continuous stretch totally encompassing a 5.5 megabase region spanning the normal N-myc gene. The co-amplification profiles with these DNAs showed that two of them, which mapped into a 300 kb region flanking the N-myc gene, were commonly amplified in most specimens, while others were differentially amplified among various subsets. These profiles enabled us to divide the N-myc amplicons into several groups and outline their original domains as a continuous stretches, pointing to the existence of 'consensus sites' for the ends of the initial domains in the original region. In one cell line, the domain was found to be several times larger than that of the derivative amplicon; and the rearranged sites identified within the amplicons, which showed no site specificity, were consistent with those deduced from the domain structure. These results lead to a model in which N-myc gene amplification is initiated at some consensus sites by a preferential mechanism and followed by a random loss of the domain structures during subsequent stages.

DNA Probes↗
PubMed1994

There may be two tumor suppressor genes on chromosome arm 1p closely associated with biologically distinct subtypes of neuroblastoma.

We studied loss of heterozygosity (LOH) on chromosome arm 1p in 108 neuroblastomas using 14 polymorphic DNA markers. One-hundred and four tumors with one or more informative loci; 21 (20%) of the 104 tumors showed LOH on 1p, and were classified into three groups on the basis of interstitial or terminal allelic loss, and presence or absence of LOH on 1p. Seven of the 21 tumors showed an interstitial deletion which encompassed a small region in 1p36 (group A), and the other 14 showed a terminal deletion which encompassed the region from 1pter to 1p32 (group B). Eighty-three tumors without LOH on 1p were classified as group C. The group A patients were mostly less than 12 months of age (6/7), were frequently found by a mass screening program for infants (5/7), had a tumor of non-adrenal origin, and rarely progressed to stage IV (1/7). Most group B patients were 12 months or older (11/14), were found clinically (11/14), had tumors of adrenal origin, and progressed to stage IV (10/14). Analysis of biologic characteristics in group C tumors suggested that they may comprise group A and B tumors. While all group A tumors were in the triploid range (3n) (4/4), most group B tumors were diploid (2n) or tetraploid (4n) (7/10). MYCN amplification was found in 8 group B tumors, but in none of group A tumors. Event-free survivals of groups A, B, and C patients at 3 years were 86, 49, and 74%, respectively (P = 0.0287). These findings suggest that there may be two tumor suppressor genes on 1p which are closely associated with two biologically distinct subtypes of neuroblastoma.

Alleles↗
PubMed1994

Localization of synaptophysin immunoreactivity in the human liver.

The distribution of synaptophysin, specifically located in nerve terminals, was investigated immunohistochemically in normal and diseased human livers in 4 patients with normal liver, 6 with chronic active hepatitis, 12 with cirrhosis, and 8 with hepatocellular carcinoma. In normal liver and chronic hepatitis synaptophysin immunoreactivity was detected in the lobules and portal areas. In cirrhosis it was found in the fibrous septum but in no pseudolobules. Parenchymal innervation would thus appear to cease with the development of cirrhosis, and denervation from the parenchyma may lead to various functional abnormalities in liver cirrhosis. In hepatocellular carcinoma no synaptophysin immunoreactivity was found along carcinomatous sinusoids. Immunoreactive spots were present in the capsules of hepatocellular carcinoma to a much lesser extent than in the fibrous septum of cirrhosis. Neural functions may thus have little effect on the microcirculation of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1994

[Basic aspects of bone metabolic markers].

Bone formation and bone resorption are altered in most metabolic bone diseases. Recent advances in measurement of bone metabolic markers arrows as the non-invasive investigation of bone metabolic balance. The rate of formation or degradation of the bone matrix can be assessed by the measurement of bone specific proteins and it's degradative products. Among the posturated products, osteocalcin, carboxy-terminal propeptide of type I collagen (PICP) are considered to be more specific indices to know the osteoplastic function. On the other hand, pyridinoline or deoxypyridinoline in urine strongly reflects bone resorption rate. However some criticisms still exist in the evaluation of serum or urinary levels of bone metabolic markers, especially in formation markers. In adults, bone formation marker such as osteocalcin negatively correlated with their bone mineral density. On the other hand, in children, osteocalcin positively correlated with height velocity. Therefore we have to pay special attention to dysfunction of osteoblast, such as retarded calcification in evaluation of serum level of bone formation markers.

Biomarkers↗
PubMed1993

Human smooth muscle myosin heavy chain gene mapped to chromosomal region 16q12.

The partial nucleotide sequence encoding the rod portion of the entire amino acid sequence of human smooth muscle myosin heavy chain (MHC) which corresponds to MYH11, according to Human Gene Mapping nomenclature, has been determined by cloning a complementary DNA (cDNA) and sequencing the cDNA (UMYHSM). Northern blot analysis with the UMYHSM fragment (4.3 Kb) showed that the smooth muscle MHC of the human umbilical artery is expressed in the human umbilical artery, bladder, esophagus and trachea. Southern blot analysis of human genomic DNA from human-mouse or human-Chinese hamster somatic cell hybrids demonstrated that the human smooth muscle MHC was mapped to human chromosome 16. Regional mapping of UMYHSM was performed using human cell lines with partial deletion and trisomy of chromosome 16. As a result, the human smooth muscle MHC gene segregated with 16p11-q12. In situ hybridization of biotin-labeled human smooth muscle MHC probe (UMYHSM fragment) to normal human metaphase chromosome independently showed that the human smooth muscle MHC gene (MYH11) is assigned to chromosome region 16q12. Analysis of early metaphase chromosomes showed that hybridization signals were in 16q12.1. In the human, although skeletal, cardiac, smooth muscle, and nonmuscle MHC genes are mapped to chromosomes 17, 14, 16, and 22, respectively, structural similarities of these MHC genes strongly suggest the common origin of these genes.

Amino Acid Sequence↗
PubMed1993

Structural organization of MYCN amplicons of neuroblastoma tumors, xenografts, and cell lines characterized by the sequences encompassing the MYCN amplicons in a human neuroblastoma cell line.

We characterized differences in the structural organization of the MYCN amplicons of a number of neuroblastomas by analyzing 8 contigs spanning 330 kb cloned from the MYCN amplicon of a neuroblastoma cell line. Some regions were amplified in almost all specimens, the conserved regions (CRs), and others were differentially amplified in some subsets, the non-conserved regions (NCRs). CRs constituted only 20% of the 330 kb region, with the remainder being NCRs. The regions that inevitably co-segregate with the MYCN gene make up the core, whereas flanking regions are retained at random. If a histogram of the frequency with which the amplified NCR sequences from one specimen match those of the cell line MC-NB-I shows a random distribution, the NCRs would co-segregate with MYCN as a result of random events. However, both the tumors and cell lines/xenografts showed a distribution with two distinct peaks; one from a group containing a small number of sequences with a fairly high degree of homology to the NCRs of MC-NB-I, and the other from a group containing a large number of sequences with little homology. These results indicate that the flanking segments are preferentially co-segregated with MYCN by a non-random mechanism.

Alleles↗