Munehiro Honda

Teikyo University, Edo, Tōkyō, Japan

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Publications (10)18.49 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Menin is lost by the sequential inactivation of both MEN1 alleles in subsets of non-hereditary endocrine tumors as well as those associated with multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant hereditary cancer syndrome characterized by multiple tumors including parathyroid, pituitary and enteropancreatic endocrine tumors. Loss of menin has been reported to be associated with lowered caspase 8 expression and resistance to apoptosis in murine fibroblasts and in pancreatic islet tumors arising in heterozygous MEN1 gene knockout mice, the animal model of the human MEN1 syndrome. We confirmed by menin-knockdown experiments with specific siRNA that menin is crucial for caspase 8 expression in human culture cells while overexpression of menin did not increase caspase 8 protein over basal levels. We then examined expression of menin, caspase 8 and cyclin-dependent kinase inhibitors p27(Kip1) and p15(Ink4b) by Western blotting in human parathyroid tumors surgically resected from patients with MEN1 and those with non-hereditary primary hyperparathyroidism. The menin and p27(Kip1) expression levels were correlated with MEN1 mutation status that was confirmed by DNA analysis. The caspase 8 and p15(Ink4b) protein levels were variable among tumors, and were not correlated with menin protein levels. These findings suggest that human endocrine tumors lacking menin may not always exhibit lowered caspase 8 expression and hence may not be resistant to apoptosis-inducing therapy.
    Endocrine Journal 01/2010; 57(9):825-32. DOI:10.1507/endocrj.K10E-085 · 2.00 Impact Factor
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    ABSTRACT: We report a case of diabetic mastopathy in an elderly woman with type 2 diabetes. The patient was a 69-year-old woman diagnosed with type 2 diabetes at the age of 33 years. She had been treated with insulin for 25 years, however, her blood glucose had been poorly controlled. She noticed bilateral breast lumps in September 2002. Mammography of the breast showed increased density in the glandular pattern and architectural distortion without focal mass and microcalcification. Ultrasonography of the breast showed an irregular-shaped hypoechoic mass with an acoustic shadow. As malignancy needed to be excluded, core needle biopsy was performed in the left breast and diabetic mastopathy was confirmed pathologically. Diabetic mastopathy is usually a complication of pre-menopausal type 1 diabetes and develops in a unilateral breast. This case developed in bilateral breasts in an elderly type 2 diabetic patient.
    Internal Medicine 02/2007; 46(18):1573-6. DOI:10.2169/internalmedicine.46.6191 · 0.90 Impact Factor
  • Munehiro Honda · Miyuki Ishibashi ·

    Nippon rinsho. Japanese journal of clinical medicine 10/2006; Suppl 3:274-8.
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    ABSTRACT: Here, we report a case of acute liver dysfunction complicated with uncontrollable glycemia due to insulin antibody. The patient was admitted to our hospital due to diabetic ketoacidosis. He was administered insulin immediately, however, his fasting plasma glucose level remained unstable despite the insulin treatment. Blood biochemistry revealed severe liver dysfunction, although no markers including hepatitis virus or autoantibodies associated with autoimmune liver diseases were detected. The 125I-insulin binding rate was high (54%). The characteristics of insulin antibody in this patient were similar to the antibodies of IAS patients, therefore we administered oral glucocorticoid against insulin antibody. The reduction in the 125I-insulin binding rate and the binding capacity of the high affinity site of insulin antibodies were balanced after oral glucocorticoid therapy. In addition, preprandial subcutaneous regular insulin was switched to lispro insulin. Postprandial plasma glucose levels were relatively improved by lispro insulin. The etiology of acute liver dysfunction was unknown, however, we believe that the combination of oral glucocorticoid and lispro insulin was suitable and useful for preventing recurrent liver dysfunction in this patient.
    Internal Medicine 02/2006; 45(21):1225-9. DOI:10.2169/internalmedicine.45.6009 · 0.90 Impact Factor
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    ABSTRACT: A rare case of primary hyperparathyroidism associated with primary aldosteronism and breast cancer is reported. A 44-year-old woman was admitted to our hospital to undergo surgical removal of breast cancer. She had hypertension with low serum potassium, and slightly but significantly elevated serum calcium levels. Further studies demonstrated an enlarged left superior parathyroid gland and a left aldosterone-producing adrenocortical adenoma. Blood pressure was controlled with spironolactone and nifedipine, and left mastectomy was done for breast cancer. The pathological diagnosis was scirrhous breast carcinoma. Although the postoperative course was uneventful, her serum calcium gradually and progressively rose to higher levels. Left superior parathyroidectomy and left adrenalectomy were then performed simultaneously. The pathological diagnoses of the resected parathyroid gland and adrenal gland were parathyroid chief cell adenoma and adrenocortical adenoma with hyperplasia of zona glomerulosa, respectively. To clarify if the occurence of these tumors may be related to MEN1 gene mutations, we analyzed MEN1 gene in this patient, and found a loss of heterozygosity of the MEN1 locus in the parathyroid adenoma and breast cancer. Thus, we conclude that an alteration of the MEN1 gene and/or another tumor suppressor gene located at the MEN1 locus on chromosome 11q13 may be responsible for the development of parathyroid adenoma and breast cancer in our patient suggesting that the clinical spectrum of MEN1 might include breast cancer. In addition, serum calcium should be interpreted with caution in primary aldosteronism, because hypercalcemia may be masked in the presence of aldosterone excess.
    Internal Medicine 05/2004; 43(4):310-4. DOI:10.2169/internalmedicine.43.310 · 0.90 Impact Factor
  • Munehiro Honda · Miyuki Ishibashi ·
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    ABSTRACT: The gastroenteropancreatic endocrine tumor is relatively rare tumor that originate from pancreas, duodenum, and a variety of neuroendocrine cells. The differential diagnosis and preoperative localization of the tumor are important, because surgical resection of the tumor is the first choice of treatment. Of these tumors, insulinomas and gastrinomas are usually small in size (less than 2.0 cm), and methods of preoperative localization such as ultrasonography, computed tomography or magnetic resonance imaging often fail to identify them. These tumors often malignant, and tumors as small as 1 to 2 mm might develop lymph node metastases especially in gastrinomas. Recent studies have shown that selective arterial calcium stimulation test and hepatic venous sampling using intraarterial calcium injection as the insulin secretagogue are useful for detection of small insulinomas, and the selective intraarterial injection of secretin test combined with venous sampling (Imamura technique), for detection of small gastrinomas. In addition, somatostatin-receptor scintigraphy is widely used in Western countries. Moreover, detection of the tumor during operation using ultrasonography delivered much better results than preoperative diagnoses. These tumors may be associated with multiple endocrine neoplasia type 1, and MEN1 gene mutation analysis is necessary in those patients.
    Gan to kagaku ryoho. Cancer & chemotherapy 04/2004; 31(3):337-41.
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    ABSTRACT: A malignant pheochromocytoma is described in a 71-year-old man. Osseous metastases became manifest 12 years after successful removal of the primary tumor which originated in paraganglionic tissue near the right adrenal gland. Although the patient had no symptoms of catecholamine excess initially, hypertension, tachycardia and excessive sweating appeared several months before his death, concomitantly with a sharp increase in noradrenaline secretion due to an accelerated growth of metastatic tumors. Since there is no histologic criterion of malignancy in this neoplasm, it would be prudent to consider every case of pheochromocytoma as potentially malignant and to follow-up carefully for a long time after removal of the primary tumor.
    Internal Medicine 11/2000; 39(10):820-5. DOI:10.2169/internalmedicine.39.820 · 0.90 Impact Factor
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    ABSTRACT: Menin is a protein product of a tumor supressor gene MEN1, mutations of which are responsible for multiple endocrine neoplasia type 1, an autosomal dominant familial cancer syndrome. We determined the nucleotide sequence of the Drosophila menin cDNA using RT-PCR and RACE, and confirmed it by direct sequencing of genomic DNA. Gene expression of Drosophila menin was detected by Northern blot analysis in adult and embryo as two types of transcripts, one identical in size to the cDNA, and the other larger but detected only in embryo. The Drosophila menin gene was composed of five exons in which the protein was encoded in exon 2 through 5, and spanned approximately 6.3 kb. The deduced amino acid (AA) sequence of Drosophila menin consisted of 751 AAs with a calculated molecular mass of 81.7 kDa, and showed 44-47% identity to human, rat, mouse and zebrafish menin over the entire length. Among the AA residue substitutions that have been reported as disease-associated missense mutations and single AA deletions, 53 out of 71 were completely conserved in Drosophila. The presence of menin ortholog in insect indicates that menin is an evolutionally conserved protein with a fundamental role in biological processes.
    Molecular and Cellular Endocrinology 11/2000; 168(1-2):135-40. DOI:10.1016/S0303-7207(00)00307-5 · 4.41 Impact Factor
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    ABSTRACT: To determine whether familial isolated hyperparathyroidism (FIHP) is a variant of multiple endocrine neoplasia type 1 (MEN1) we analyzed the MEN1 gene in such a kindred. The study included the 70-year-old proband and nine relatives. Blood was drawn for biochemical evaluation and germline mutation analysis by direct sequencing of the MEN1 gene amplified by PCR. A hyperplastic parathyroid gland obtained from a family member served for a loss of heterozygosity (LOH) study. Three members from two generations in this kindred were found to have primary hyperparathyroidism, while none had clinical or biochemical evidence of MEN1, MEN2 or hyperparathyroidism--jaw tumor syndrome. Analysis of germline DNA in the proband showed a missense mutation (GGC-->GAC) at codon 305 in exon 7 of the MEN1 gene that predicts an amino acid change from glycine to aspartic acid (G305D). This mutation segregated with primary hyperparathyroidism in the kindred, and, in addition, there were two asymptomatic mutant-gene carriers at relatively advanced ages. In contrast, the mutation was not detected in genomic DNA from five unaffected individuals and from 50 healthy subjects. The LOH study showed a loss of the wild-type allele, which confirmed that a functional defect of the MEN1 gene product, menin, is etiological for FIHP. FIHP is a genetically heterogeneous disease with a subset linked to MEN1, most likely representing a variant of MEN1. The late onset and the reduced penetrance of disease found in this kindred may be related to the site and the type of mutation, although the precise mechanism involved is unknown at present.
    European Journal of Endocrinology 02/2000; 142(2):138-43. DOI:10.1530/eje.0.1420138 · 4.07 Impact Factor
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    ABSTRACT: Menin is a protein product of a tumor supressor gene MEN1, mutations of which are responsible for multiple endocrine neoplasia type 1, an autosomal dominant familial cancer syndrome. We isolated rat menin cDNA clones from a fetal rat brain cDNA library. We also determined the nucleotide sequence of the protein coding region of mouse menin cDNA, which was partly registered in the expressed sequence tag (EST) database. Deduced amino acid sequences of rat and mouse menin are highly homologous to human menin. All of the previously reported disease-associated missense mutations and single amino acid deletions were observed at the residues that are conserved among these three species. Rat MEN1 transcripts were detected not only in the endocrine tissues but also in the tissues of the nervous, digestive, reproductive and immune systems. The MEN1 transcripts were abundantly expressed in the developing rat brain on day 14–18 of gestation. Immunoblotting and immunocytochemical analysis of the COS-7 cells transfected with a rat menin-expression vector revealed that the translated product has a molecular mass of approximately 70 kDa, and is localized mainly in the nucleus. These findings are consistent with those reported on human menin.
    Molecular and Cellular Endocrinology 10/1999; 156(1-2-156):25-33. DOI:10.1016/S0303-7207(99)00150-1 · 4.41 Impact Factor

Publication Stats

133 Citations
18.49 Total Impact Points


  • 2006-2007
    • Teikyo University
      Edo, Tōkyō, Japan
  • 2004
    • Teikyo University Hospital
      Edo, Tōkyō, Japan
  • 2000
    • National Research Institute for Child Health and Development, Tokyo
      Edo, Tōkyō, Japan
    • National Cancer Center, Japan
      Edo, Tōkyō, Japan