PubMed Health⌕ Search

Biomedical subjects

A Kanzaki

Publications and source records attributed to A Kanzaki.

At least 19 recordsLinked to original sources
PubMed2001

Loss of heterozygosity of nucleotide excision repair factors in sporadic ovarian, colon and lung carcinomas: implication for their roles of carcinogenesis in human solid tumors.

The deficiencies of nucleotide excision repair (NER) factors are genetic diseases, xeroderma pigmentosum (XP) increasing risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (LOH) analysis for the XP, XPA, XPB, XPC, XPD, XPE, XPF, XPG and the transcription-coupled repair factor, Cockayne syndrome B (CSB) revealed that NER factors were abnormal in 62.1 % of ovarian tumors (18/29), 16.7% of colon (2/12) and 22.2% lung (2/9) carcinomas. Furthermore, 13.8% of ovarian, 8.3% of colon and 22% of lung carcinomas exhibited LOH for NER factors without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCAI, BRCA2 and DCC. Although both microsatellite instability and LOH of NER factors were observed in some cases, there was no strong association between them in the present study. These observations raise the possibility that alterations of NER factors may be frequent in human sporadic carcinomas. Further study should be needed to find the direct evidence of NER gene abnormalities in human sporadic carcinoma tissues.

Chromosome Aberrations↗
PubMed2001

Different features of angiogenesis between ovarian and breast carcinoma.

Angiogenesis assessed by immunohistochemical staining for endothelial cells has been widely accepted as an independent prognostic factor in human breast carcinoma. However, the clinicopathologic significance of angiogenesis is still being argued in ovarian carcinoma. Therefore, we retrospectively analyzed the clinicopathologic significance of angiogenesis in ovarian carcinoma compared with that in breast carcinoma. After vessels were stained with CD34-monoclonal antibody, the areas with the highest number of intratumoral microvessels were assessed in a 200x field in 42 ovarian carcinoma and 41 breast carcinoma. Intratumoral microvessel density (IMD) in ovarian carcinoma was significantly lower than that in breast carcinoma. Further, the difference of IMD from tumor to tumor in ovarian carcinoma was smaller than that in breast carcinoma. IMD was correlated with tumor grade, but not with other clinicopathologic variables in ovarian carcinoma. Although the patients with high-IMD tumor revealed a poorer prognosis than those with low-IMD tumor in breast carcinoma, IMD had no influential effects on the survival of the patients with ovarian carcinoma. Our comparative analysis of IMD in ovarian carcinoma with that in breast carcinoma indicates that angiogenesis may play an important role in the transient of ovarian neoplasms, but not in the progression of ovarian carcinomas, and that the biological roles of angiogenesis might be different, depending on histologic subtype.

Adult↗
PubMed2001

Allelotype analysis of gallbladder carcinoma associated with anomalous junction of pancreaticobiliary duct.

Anomalous junction of pancreaticobiliary duct (AJPBD) patients has an increased risk of gallbladder and bile duct carcinomas. However, the relevance of carcinoma with AJPBD is not fully clarified. We performed analysis of loss of heterozygosity (LOH) at p53 locus and immunohistochemistry of p53 and K-ras gene mutation in five cases of gallbladder carcinoma associated with AJPBD. LOH of p53 locus and overexpression of p53 were detected in two out of five (40%) and five out of five (100%), respectively, in the present study. K-ras gene mutation at codon 12 and 13 was not detected (0%, 0/5). These results suggest that aberrations of p53 are involved in carcinogenesis of gallbladder carcinoma associated with AJPBD. Next, in order to find the genetic events besides K-ras mutation and overexpression of mutant p53 in this disease, LOH analysis was performed using 72 microsatellite markers. High frequency of allelic loss (> 50%) was found on 2p (81.8%), 4p (50%), 4q (50%), 8q (60%), 9q (50%), 10p (50%), 14p (60%), 14q (50%), 16p (60%), 19p (50%), 21p (50%) and Xp (66.6%). The highest deletion regions on chromosome 2p24 (3/3, 100%), 14q22 (3/4, 75%) and 21q22 (3/4, 75%) were found. The present study suggests that gallbladder carcinoma associated with AJPBD has high frequent allelic loss and has two new regions which may harbor putative tumor suppressor genes.

Aged↗
PubMed2001

Prevalence of homozygous deletions of the parkin gene in a cohort of patients with sporadic and familial Parkinson's disease.

Mutation of the parkin gene is a cause of familial Parkinson's disease of the autosomal recessive form; however, its significance in all Parkinson's disease cases is unclear. Deletions in the parkin gene were found in only 2.2% of 184 Japanese patients with Parkinson's disease. However, deletions were present in 25.0% and 40.0% of the patients with juvenile-onset (< 40 y) and with familiality, respectively. On the other hand, deletions were not found in any adult-onset cases (> 40 y). Half of the patients with parkin gene-related Parkinson's disease lacked both heredity and consanguinity.

Age of Onset↗
PubMed2001

Ankyrin gene mutations in japanese patients with hereditary spherocytosis.

We studied mutations of the ankyrin-1 (ANK-1) gene of genomic DNA from Japanese patients with hereditary spherocytosis (HS). Forty-nine patients from 46 unrelated families were included in this study. Of these patients, 19 cases from 16 unrelated families had HS of autosomal-dominant inheritance, and 30 patients had non-autosomal-dominant HS. Fifteen mutations of the ANK-1 gene pathognomonic for HS were identified: 4 nonsense mutations, 7 frameshift mutations, and 4 abnormal splicing mutations. These 15 mutations have not been previously reported. The frameshift mutations were found from exon 1 to exon 26, corresponding particularly to the band 3-binding domain of ankyrin. The nonsense mutations, on the contrary, were present mostly at the 3'-terminal side, especially in the spectrin-binding domain and the regulatory domain. The patients with ankyrin gene mutations tended to be more anemic with a higher level of reticulocytosis than those without these mutations. Fifteen silent mutations of the ANK-1 gene, most of which have previously been detected in HS patients in Western populations, were also found. The allele frequency of these silent mutations in the HS patients was nearly identical to that in normal subjects. There was no difference between the Japanese and Western populations in the allele frequency of these gene polymorphisms in healthy subjects or HS patients.

Alleles↗
PubMed2001

Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair.

While investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a region that included the gene implicated in the hereditary disease xeroderma pigmentosum (XPG, also known as Ercc5). Complementation with wild-type XPG restored the drug sensitivity. Xeroderma pigmentosum cells deficient in the NER genes XPG, XPA, XPD or XPF were resistant to Et743, and sensitivity was restored by complementation with wild-type genes. Moreover, studies of cells deficient in XPC or in the genes implicated in Cockayne syndrome (CSA and CSB) indicated that the drug sensitivity is specifically dependent on the transcription-coupled pathway of NER. We found that Et743 interacts with the transcription-coupled NER machinery to induce lethal DNA strand breaks.

Animals↗
PubMed2001

Expression of multidrug resistance-related transporters in human breast carcinoma.

The expression levels of mRNA for multidrug resistance 1 (MDR1) gene, multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP), which confer multidrug resistance in vitro, were examined in 43 untreated breast carcinoma patients, of whom 38 subsequently received doxorubicin-based chemotherapy after surgery, in order to elucidate the roles of these genes in drug resistance in vivo. The mRNA levels were determined using a semi-quantitative reverse-transcription polymerase chain reaction method in breast carcinoma tissues including at least 80% carcinoma cells. The expression level of BCRP gene was low and did not vary markedly in comparison with that of MDR1, MRP1 or LRP gene. The expressions of MDR1 and MRP1 genes were correlated with each other, but the expression of BCRP or LRP gene did not correlate with that of other genes. These four gene expressions were independent of age, TNM categories and the status of progesterone or estrogen receptor. The expression levels of these four genes were not related to the relapse or prognosis of the 38 patients treated with doxorubicin-based chemotherapy. P-glycoprotein (P-gp) / MDR1, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Expression of multidrug resistance associated transporters (MDR1, MRP1, LRP and BCRP) in porcine oocyte.

Transporters such as P-glycoprotein (MDR1), multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP) are associated with multidrug resistance in various carcinoma cell lines. The expression of these molecules has been also characterized in human normal tissues. However, the expression of these molecules in oocyte is still unclear. In order to obtain more insight into the physiological role of these transporters, their expression in porcine oocyte were examined by reverse transcriptase-polymerase chain reaction. MDR1, MRP1 and LRP genes, but not BCRP gene were found to be expressed in porcine oocyte. After the subcloning and sequence analysis of MDR1, MRP1 and LRP genes, the high homology of these transporters were observed between porcine and human gene. These findings suggest that MDR1, MRP1 and LRP play an important physiological role(s) in an oocyte.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Characteristic features of the genotype and phenotype of hereditary spherocytosis in the Japanese population.

Hereditary spherocytosis (HS) is the most common hemolytic anemia of congenital origin in the Japanese population. Among 844 cases of 520 kindred with congenital red cell membrane disorders studied at the Kawasaki Medical School in the last 25 years (1975-1999), 407 cases (48.2%) of 215 kindred had HS. Among the recent 60 kindred with HS, autosomal dominant (AD) transmission was proven in 19. The remaining 41 non-AD HS included 1) homozygous patients with autosomal recessive inheritance, 2) HS patients with de novo gene mutations, and 3) mild HS with AD inheritance. The extent of clinical severity in the non-AD HS cases was nearly identical to that in the AD cases. The incidence of membrane protein abnormalities in our 60 Japanese HS kindred was unique: there were lower ankyrin deficiencies (7%), moderate band 3 deficiencies (20%), and much higher protein 4.2 deficiencies (45%), with 28% of unknown etiology. The incidence of membrane protein deficiencies corresponded to that determined by gene analyses; i.e., mutations mostly in band 3 and/or in protein 4.2 genes and fewer ankyrin gene mutations. In the band 3 gene, 11 mutations pathognomonic for HS were identified (3 frameshift and 8 missense mutations). There were 5 mutations of the protein 4.2 gene (3 missense mutations, 1 nonsense mutation, and 1 splicing mutation) pathognomonic for HS. On the other hand, 2 missense mutations were detected in the ankyrin gene in this study. The genetic abnormalities in our HS patients correlated well with the phenotypic ultrastructural abnormalities of red cell membranes in situ. Ankyrin mutations (ankyrin Marburg and ankyrin Stuttgart with frameshift mutations) were associated mostly with a disrupted cytoskeletal network, and band 3 mutations (band 3 Kagoshima with frameshift mutation) typically demonstrated anomalies of intramembrane particles (IMPs). Protein 4.2 mutations (homozygotes of protein 4.2 Nippon) with complete protein 4.2 deficiency showed abnormalities of both the cytoskeletal network and IMPs.

Animals↗
PubMed2000

[Roussy-Lévy syndrome with a duplication on peripheral myelin protein gene (PMP22)].

A 51-year-old woman with autosomal dominant inheritance presented with finger tremor, atrophy of the dorsal interosseous muscles, and pes cavus. No muscular atrophy was noted in either leg. The deep tendon reflexes were only present for the biceps muscle of the arm, although they were decreased. Progression was extremely slow. Biopsy of the sural nerve revealed onion bulbs. The patient was diagnosed as a case of Roussy-Lévy syndrome. Her father and son had same symptoms. Typical Charcot-Marie-Tooth disease type 1A (CMT 1A) was also detected in the same family. All 4 cases revealed duplication of the PMP22 gene. In view of the molecular genetic findings, her Roussy-Lévy syndrome was considered to resemble CMT 1A.

Charcot-Marie-Tooth Disease↗
PubMed1999

Elliptocytosis in myelodysplastic syndrome associated with translocation (1;5)(p10;q10) and deletion of 20q.

Acquired elliptocytosis is a red blood cell abnormality occasionally associated with myelodysplastic syndrome (MDS). A Japanese male with MDS who presented with elliptocytosis had mild anemia and hypercellular bone marrow with three lineage-dysplasia. He was diagnosed with refractory anemia of MDS. Cytogenetic analysis of bone marrow cells showed 47,XY,+1,der(1;5)(q10;p10),t(1;5) (p10;q10),del(20)(q11) in 70% of the analyzed cells. Analysis of red blood cell membrane proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed normal electrophoretic patterns with no quantitative abnormalities of each protein. Del(20q) and/or t(1;5)(p10;q10) might be associated with elliptocytosis in this patient.

Aged↗
PubMed1999

Late expression of red cell membrane protein 4.2 in normal human erythroid maturation with seven isoforms of the protein 4.2 gene.

The expression of protein 4.2 in normal human erythroid cells was studied utilizing erythroblasts from bone marrow and erythroid cells cultured by the two-phase liquid culture method from burst-forming unit erythroid (BFU-E) in peripheral blood. As opposed to spectrin, which was expressed in erythroid progenitors or very early erythroblasts, protein 4.2 was first detected in late erythroblasts with a morphology nearly identical to orthochromatic erythroblasts. Among the various major membrane proteins, the expression of protein 4.2 was the latest. At the gene level, protein 4.2 gene mRNA was expressed in early erythroblasts. During normal erythroid maturation, the expression of seven different protein 4.2 gene products was observed by Southern blot analysis. These seven gene products appeared to be derived from protein 4.2 gene in the presence or absence of skipping of the 90 bp in exon 1, exon 3, and/or exon 5, as judged by deduction from the protein 4.2 sequence. Therefore, it can be speculated that protein 4.2 is expressed after the cytoskeletal network has been constructed and assembled with integral proteins in the membrane lipid bilayer.

Blood Proteins↗
PubMed1999

Germline mosaicism of MPZ gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis.

We report on two sisters with Dejerine-Sottas syndrome (DSS) who had a heterozygous Gly 167 Arg mutation in the myelin protein zero (MPZ) gene and hereditary stomatocytosis (HSt). Genetic haplotype analysis suggested that the allele with the MPZ gene mutation originated from maternal lineage. However, the parents, who were normal clinically and electrophysiologically, had no mutation in the MPZ gene. Therefore, the MPZ gene mutation in these sisters was due to germline mosaicism of the MPZ gene in their mother. Stomatocytosis was detected in their mother and a sister who had no neurological symptoms, and therefore autosomal dominant HSt was suspected in this family. As stomatocytosis is very severe in our patients with DDS, we speculate that the association of DSS with stomatocytosis is coincidental but may have additively affected erythrocyte morphology. To our knowledge, these are the first familial cases of DSS with a mutation due to germline mosaicism of the MPZ gene to be reported.

Adult↗
PubMed1999

Immunohistochemical identification of erythroid precursors in paraffin embedded bone marrow sections: spectrin is a superior marker to glycophorin.

AIM: To investigate whether spectrin can be used as an immunohistochemical marker for erythroid precursors in routinely processed paraffin embedded bone marrow sections. METHODS: Bone marrow biopsies and clot sections were stained with rabbit antihuman erythrocyte spectrin antibodies, specific for erythroid cells as shown by western blotting and bone marrow smears, and compared to sections stained with antiglycophorin monoclonal antibodies (JC159 and Ret49f). RESULTS: Antispectrin antibodies resulted in diffuse cytoplasmic staining of early erythroblasts and membranous staining of late erythroblasts as well as erythrocytes. In haematopathological samples, immature erythroid cell clusters were clearly identified. In contrast, antiglycophorin monoclonal antibodies resulted in only membranous staining of late erythroblasts, and faint staining of early erythroblasts. CONCLUSIONS: Spectrin may be a superior marker to glycophorin for the identification of erythroid precursors in paraffin embedded sections.

Biomarkers↗
PubMed1999

[Two cases of sporadic juvenile Parkinson's disease caused by homozygous deletion of Parkin gene].

Parkin gene, which is one of the causes of familial Parkinson's disease, was cloned in 1998, and it was found that mutations of this gene induces familial Parkinson's disease of autosomal recessive form (AR-JP). Clinical studies have revealed that almost cases of AR-JP are consanguineous or hereditary. However, AR-JP may also be caused by marriage between two carriers. We therefore investigated the existence of a homozygous deletion in the parkin gene in 10 patients with juvenile Parkinson's disease with the onset of age younger than 40 years without consanguinity or heredity. A large delection of the gene was found in 2 of the 10 patients with sporadic Parkinson's disease, and both of these deletion were exon 4. The present study clearly suggests that juvenile Parkinson's disease in Japan may be caused by abnormalities in parkin gene regardless of family history or consanguinity.

Age of Onset↗
PubMed1998

Homozygous missense mutation (band 3 Fukuoka: G130R): a mild form of hereditary spherocytosis with near-normal band 3 content and minimal changes of membrane ultrastructure despite moderate protein 4.2 deficiency.

The characteristics of phenotypic expression were studied in a Japanese family with hereditary spherocytosis and an extremely rare homozygous missense mutation of the band 3 gene (band 3 Fukuoka: G130R). The homozygous unsplenectomized proband was a 29-year-old male with compensated haemolytic anaemia (red cell count 4.21 x 10(12)/l, reticulocytes 278 x 10(9)/l, and indirect bilirubin 44 micromol/l). His red cell band 3 (B3) protein demonstrated a 9.3% reduction and his protein 4.2 (P4.2) level was substantially reduced (45.0%), compared to normal subjects. P4.2 protein was composed mostly of a wild type (72 kD) with a trace of 68 kD peptide. The binding properties of the mutated B3 to normal P4.2 were significantly impaired, which probably resulted in the substantial reduction of P4.2 in this proband, since no abnormalities were detected on the P4.2 gene. Electron microscopy (EM) using the freeze-fracture method demonstrated a mild decrease in intramembrane particles (IMPs) of near-normal size (8 nm in diameter) with no substantial increases in their oligomerization. Their distribution on the membrane P face was almost normal, although most of the IMPs could represent the homozygously mutated B3 protein. EM (quick-freeze deep-etching method) disclosed a skeletal network of near-normal size and size distribution of the skeletal units, suggesting that the mutated B3 protein itself did not have much effect on the skeletal network in situ. Therefore the reduced P4.2 content (45% of that of normal subjects), which remained on the red cell membrane of this proband, appeared to be nearly sufficient for maintaining the normal structure of the skeletal network and IMPs in situ, contrary to the marked abnormalities in both IMPs and the skeletal network in complete P4.2 deficiencies.

Adult↗