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Biomedical subjects

Hitoshi Kanno

Publications and source records attributed to Hitoshi Kanno.

13 recordsLinked to original sources
PubMed2006

Laparoscopic surgery for gastric cancer: 5 years' experience.

The purpose of this study was to clarify the safety and value of laparoscopic surgery for gastric cancer. This retrospective study involved 101 patients with gastric cancer treated with laparoscopic surgery at the Nippon Medical School Hospital from February 2001 through July 2005. The following variables were evaluated: age, sex, comorbid conditions, tumor size, location, gross type, histological type, depth of wall invasion, and presence or absence of lymph node metastasis. The surgical variables investigated included operating time, blood loss, postoperative complications, and length of postoperative stay. Mean tumor diameter was 24.1 +/- 18.4 mm, and most tumors were located in the lower third of the stomach. Endoscopic examination revealed that 98 of the tumors were early gastric cancers. The mean operation time was 255 +/- 74 min, and mean blood loss was 128 +/- 162 g. Local gastrectomy without lymphadenectomy was performed in 13 cases, and pylorus-preserving gastrectomy with perigastric lymphadenectomy was performed in 16 cases. Distal gastrectomy with systemic lymphadenectomy was performed in 56 cases. Proximal or total gastrectomy with lymph node dissection for tumors located in the upper half of the stomach was performed in 16 cases. The mean postoperative hospital stay was 13.3 +/- 7.6 days. No patients died during the admission. Postoperative surgical complications occurred in 10 patients (10%) and consisted of anastomotic bleeding in 3 patients, pneumohypoderma in 1 patient, and remote infection in 6 patients. The only medical complication was a stroke in 1 patient. We conclude that laparoscopy-assisted gastrectomy is a safe and useful operation for most early gastric cancers. If patients are selected properly, laparoscopy-assisted gastrectomy can be a curative and minimally invasive treatment for gastric cancer.

Adult↗
PubMed2005

Ineffective erythropoiesis in mutant mice with deficient pyruvate kinase activity.

OBJECTIVE: A deficiency of pyruvate kinase (PK) is the most common cause of hereditary nonspherocytic anemia due to glycolytic enzyme defects. Red cells are poorly deformable due to adenosine triphosphate depletion in individuals with a PK deficiency and are destroyed in the microcirculation of the reticuloendothelial system, leading to extravascular hemolysis. The pathophysiology of PK deficiency has been widely studied in PK-deficient mice (PK-1(slc)). We examined the effects of a PK deficiency on erythroid progenitor maturation using these mice. MATERIALS AND METHODS: The appearance of apoptotic cells in spleen of PK-1(slc) mice was examined by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) staining. We also assayed hematopoietic stem cell colony formation in vitro in the spleen of PK-1(slc) mice, to investigate erythropoiesis, and annexin V binding, as a measure of apoptotic cells in constitutive erythroid colonies, to evaluate the maturation of erythroid progenitors. RESULTS: The number of hematopoietic progenitors including colony-forming unit erythroids, burst-forming unit erythroids (BFU-E), colony-forming unit granulocyte-macrophages, and multilineage colony-forming units in the spleens of PK-1(slc) was remarkably increased indicating hematopoiesis, and enhanced erythropoiesis in particular. TUNEL assays identified apoptotic cells in the splenic red pulp of the PK-1(slc) mice. Two-color flow cytometry detected apoptotic cells among anti-TER119-positive cells, suggesting that apoptotic cells were of erythroid lineage. Cells undergoing apoptosis were detected in cultures of BFU-E generated from bone marrow cells of PK-1(slc) mice. CONCLUSIONS: The results in this study indicate that the metabolic disturbance in PK deficiency alters not only the survival of red cells but also the maturation of erythroid progenitors, resulting in ineffective erythropoiesis.

Animals↗
PubMed2005

Cyclic polylactate inhibited growth of cloned leukemic cells through reducing glycolytic enzyme activities.

A novel supramolecular oligomer, cyclic polylactate (CPL) that was originally discovered in the culture medium of HeLa-S tumor cells, reportedly inhibits the growth of FM3A ascites tumor cells by inhibiting enzymes involved in the glycolytic pathway. We synthesized CPL containing 3- to 13-mers by prolonged heating and rapidly mixing a carbohydrate compound of the L-lactic acid monomer (C(3)H(6)O(3)) under decreased pressure, and studied its effects on the growth of the cloned leukemic cell, TF-1. CPL inhibited the growth of TF-1 cells and induced 7A6 antigen, which is expressed by cells undergoing apoptosis, on the surface of TF-1 cells. In addition, caspase 3, 8 and 9 activities of TF-1 cells were increased after exposure to CPL, indicating that CPL induces apoptotic changes in TF-1. Among the 6 glycolytic enzymes examined in this study, the activities of PFK and HK, induced by CPL, decreased. Interestingly, CPL was detected in conditioned medium of the stromal cell line, LS801, obtained from human bone marrow. This conditioned medium inhibited the growth of TF-1 cells, and induced the expression of 7A6 antigen. These findings suggest that CPL will be a useful chemotherapeutic agent against leukemia.

Bone Marrow Cells↗
PubMed2004

Molecular basis of Japanese variants of pyrimidine 5'-nucleotidase deficiency.

The type-I isoform of pyrimidine 5'-nucleotidase (P5N-I) has an important role in the catabolism of pyrimidine mononucleotides during erythroid maturation. Two alternatively spliced forms of P5N-I mRNA have been identified, and we found another alternatively spliced form in reticulocytes, which included an additional 87-bp sequence. The sequence is located 6.2-kb downstream of the exon 2 and 2.7-kb upstream of the exon 3 sequence; consequently, the P5N-I gene encodes 11 exons, which span approximately 48 kb. We identified five novel mutations in nine families with P5N-I deficiency: two missense mutations (425C, 721C), one splice mutation (339C), one 1-bp insertion (251-insA-252) and one 9-bp deletion (del 192-200). All patients were homozygous for each mutation. The mutant P5N-I with 721C (G241R) had lower affinity for cytidine monophosphate, suggesting that Gly241 is important for substrate binding. Haplotype analysis showed that 721C, which had been identified in five unrelated families, was a founder mutation. The mutant P5N was then expressed in Cos-7. The degradation of P5N with 425C (L142P) was significantly faster than a wild-type control, and proteasome inhibitors restored the stability of L142P. These data suggest that L142P increases susceptibility to the degradation by the ubiquitin-proteasome pathway.

5'-Nucleotidase↗
PubMed2004

[Histopathological study of lattice corneal dystrophy with L 527 R mutation of transforming growth factor-beta induced gene].

PURPOSE: A histopathological study of lattice corneal dystrophy with L 527 R mutation of exon 12 on transforming growth factor-beta induced gene(TGFBI). PATIENT AND METHODS: The patient was a 66-year-old woman with lattice corneal dystrophy. Gene analysis and histopathological study of corneal tissue obtained at the corneal transplantation were performed. Mutation analysis was done for exon 4, 11, and 12 on the TGFBI gene by direct sequencing. A histological study was performed by light microscopy with hematoxylin-eosin staining, dylon staining, or congo red staining, and by electron microscopy. RESULTS: Gene analysis revealed L 527 R mutation of exon 12 on the TGFBI gene. Light microscopic examination showed dylon-positive and Congo red-positive amyloid deposit from the superficial to deep layer of the corneal stroma. In transmission electron microscopy, the corneal epithelial layer, the basement membrane of the epithelium, Descemet's membrane, and the corneal endothelium were normal, but irregularity of Bowman's membrane and amyloid fibers in the corneal stroma were observed. CONCLUSION: Lattice corneal dystrophy due to L 527 R mutation showed histopathological findings similar to those of lattice corneal dystrophy type III.

Aged↗
PubMed2003

Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency.

In this study, possible adverse effects of pyruvate kinase (PK) deficiency on the maturation of erythroid progenitors were investigated. A 4-year-old Japanese girl with severe PK deficiency underwent splenectomy to reduce her need for blood transfusions. The spleen was examined a histologically, and the hematopoietic progenitors in the spleen were assayed to evaluate the extramedullary hematopoiesis of this PK-deficient subject. The number of hematopoietic progenitors including CFU-GM, BFU-E and CFU-GEMM in the spleen of the PK-deficient patient was much higher than those found in control spleens, indicating enhanced extramedullary hematopoiesis. TUNEL assay demonstrated apoptotic cells in the splenic red pulp of the PK-deficient patient. The expression of 7A6 antigen was detected in cells isolated from spleen and in cells cultured in vitro, but only in those cells that were positive for glycophorin A. These results provide evidence that the metabolic disturbances in PK deficiency affect not only the survival of red cells but also the maturation of erythroid progenitors, which results in premature cell death, i.e., apoptosis.

Apoptosis↗
PubMed2003

A novel missense mutation (1060G --> C) in the phosphoglycerate kinase gene in a Japanese boy with chronic haemolytic anaemia, developmental delay and rhabdomyolysis.

We report the case of a 3-year-old Japanese boy with phosphoglycerate kinase 1 (PGK1) deficiency (Online Mendelian Inheritance in Man entry 311800). The patient had anaemia and jaundice at birth, necessitating exchange transfusions for 2 d. After one red blood cell transfusion at age 2 months, his Hb level was 8-9 g/dl, his reticulocyte counts were 300-500 x 109/l, and his total bilirubin level was 25.65-42.75 micro mol/l. The patient suffered two episodes of respiratory infection-associated haemolytic crisis and rhabdomyolysis during early infancy. At age 3.0 years, his developmental milestones (developmental quotients measured using the Tsumori-Inage methods) score was 49% (normal 74-131%), and his height was below average by -2.0 standard deviations. The diagnosis of PGK1 deficiency was made based on his remarkably low (< 10% of normal) erythrocyte PGK enzyme activity level and the identification of a novel missense (1060G-->C) PGK1 gene mutation. This mutation results in the Ala-353Pro amino acid substitution, which has been designated PGK Kyoto. The patient developed the full clinical symptoms of PGK1 deficiency including haemolytic anaemia, myopathy, central nervous system disorder and growth retardation, which is unusual.

Anemia, Hemolytic, Congenital↗
PubMed2002

Gene expression and biological significance of hexokinase in erythroid cells.

Red blood cells (RBCs) express two hexokinase (HK) isoforms, HK-I and HK-R. Both isozymes are generated from the HK-I gene by use of an alternate promoter. Gene structure and exon-intron organization of the HK-I gene have been elucidated from a sequence of three contiguous genomic clones localized at human chromosome 10. The sequence spans about 131 kb, and consists of 25 exons, which include 6 testis- and 1 erythroid-specific exons. HK-R has been shown as an erythroid-specific isozyme whose expression is turned on in the early erythroid-progenitors and is significantly induced during their differentiation. HK-R unfolds major HK activity in immature RBCs and is rapidly degraded during the maturation process. HK-I has a porin-binding domain in its N-terminus. Recent studies have shown that HK isozymes with a porin-binding domain play a role in mitochondrial integrity, suggesting that HK-I-deficient erythroid cells might be eliminated by apoptosis. It is most likely that RBCs are most labile as a result of HK-I/R deficiency since the HK-I gene but not the other isozyme genes are expressed in fetal and adult RBCs.

Anemia, Hemolytic↗
PubMedDate not supplied

Gelatinase expression in ocular surface disorders.

PURPOSE: To determine the expression of gelatinase A [matrix metalloproteinase (MMP)-2] and gelatinase B (MMP-9) in ocular surface disorders, we carried out examinations of the eyes of patients with such disorders. METHODS: The cases consisted of a normal group comprising three eyes as the control and a patient group comprising six eyes of patients with ocular surface disorders. These groups underwent the following examinations. (1) Gelatin zymography: Tear samples taken by using the Schirmer I test were eluted and analyzed by gelatin zymography. (2) Immunohistochemical study: By using the alkaline phosphate-anti-alkaline phosphatase or avidin-biotin complex method, corneal or conjunctival tissue was examined for the presence of MMP-2, MMP-9, and membrane type 1 (MT1)-MMP, which activates MMP-2. (3) Reverse transcription-polymerase chain reaction (RT-PCR): Total RNA was eluted from the specimens, and the expression patterns of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed. RESULTS: (1) Gelatin zymography: Only the proforms of MMP-2 and MMP-9 were detected in the normal group. Both active MMP-2 and active MMP-9 were detected in all studied cases in the patient group. (2) Immunohistochemical study: In the normal group, only MMP-2-positive cells were present in conjunctival epithelium. In the patient group, cells positive for MMP-2, MMP-9 and MT1-MMP were present in the epithelium of the conjunctiva or cornea except in one thermal burn case. (3) RT-PCR: In the normal group, only MMP-2 expression was observed. MMP-2, MMP-9, and MT1-MMP mRNA expression was observed in three cases in the patient group. CONCLUSIONS: MMP-2, MMP-9, and MT1-MMP, which activates MMP-2, were expressed in the patients with various ocular surface disorders. In ocular surface disorders, therefore, the expression of gelatinases is upgraded.

Conjunctival Diseases↗
PubMedDate not supplied

A novel nonsense mutation with a compound heterozygous mutation in TGFBI gene in lattice corneal dystrophy type I.

PURPOSE: We examined transforming growth factor beta-induced (TGFBI) gene mutations in a family with lattice corneal dystrophy type I. METHODS: The proband was one of the offspring of a consanguineous marriage; 4 affected and 3 unaffected individuals of the family were investigated. Genomic DNA of each case was extracted and used for polymerase chain reaction (PCR). The exon 4, 11, and 12 of the TGFBI gene were directly sequenced. The mutations were confirmed by PCR restriction fragment length polymorphism analysis. RESULTS: There was no significant difference in phenotype between the proband and the other 2 patients, except for progression of the corneal opacity with age. R124C mutation was detected in all affected individuals. In addition, G470X, a novel nonsense mutation, was detected in the proband, resulting in the proband being a compound heterozygote with the TGFBI gene. Her unaffected daughter was found to be heterozygous for G470X. CONCLUSION: It is most likely that the novel nonsense mutation is not pathogenic, and that the mutant keratoepithelin protein with R124C is responsible for the phenotype.

Adolescent↗