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Biomedical subjects

M Inuzuka

Publications and source records attributed to M Inuzuka.

At least 19 recordsLinked to original sources
PubMed2002

Diagnosis of fructose-1,6-bisphosphatase deficiency using cultured lymphocyte fraction: a secure and noninvasive alternative to liver biopsy.

We report the result of enzymatic and molecular analyses, using cultured lymphocyte fractions (cultivated monocytes), of six Japanese patients (from five families) and one Italian patient with fructose-1,6-bisphosphatase (FBPase) deficiency. Enzymatic analysis demonstrated FBPase deficiency in all seven patients, including the Italian patient whose fructose-1,6-bisphosphatase activity has been reported to be normal in leukocytes but deficient in liver. Molecular analysis of the FBPase gene identified pathogenic mutations in only 8 among the total 12 alleles of six families. We have thus demonstrated the validity of using cultured monocytes as a secure and noninvasive alternative to liver biopsy for accurate diagnosis of FBPase deficiency.

Alleles↗
PubMed2002

Sterile suppurative folliculitis associated with acute myeloblastic leukaemia.

A 20-year-old woman presented with a 4-month history of follicular papules distributed over the trunk and extremities. One month later, routine blood tests were abnormal, showing acute myeloblastic leukaemia (M1 in the French-American-British classification). Skin biopsy demonstrated a dermal infiltrate of a large number of neutrophils with occasional eosinophils and histiocytes in the vicinity of the hair follicle remnants. Intermingled in the infiltrate were atypical cells that were morphologically and immunohistochemically identical to leukaemic myeloblasts. Cultures of the papules and special stains of the biopsy specimen were negative for bacteria and fungi. The follicular eruption improved promptly in response to chemotherapy for the leukaemia. We suggest that this case may represent a rare, follicular variant of neutrophilic dermatosis associated with myelogenous leukaemia.

Adult↗
PubMed2001

Lupus erythematosus profundus with unusual skin manifestation: subcutaneous nodules coexisting with eyelid plaques.

A 71-year-old Japanese woman presented with erythematous plaques on the eyelids and subcutaneous indurations or nodules with or without overlying erythema on the hands, thigh, and leg. She also had oral ulcers, arthralgia and a low grade fever. Laboratory tests revealed an elevated titer of antinuclear antibody, an increased erythrocyte sedimentation rate and anemia. Skin biopsy specimens from the hand and thigh showed lymphocytic perivascular and periappendageal infiltrates and vacuolar alterations at the basement membrane zone of the skin appendages. Moreover, there was a dense lymphocytic infiltrate deep in the dermis with extension into the subcutaneous fat, which was compatible with the diagnosis of lupus erythematosus profundus. Although the biopsy specimen from the eyelid lesion did not contain the subcutaneous fat, the changes in the dermis were essentially the same as those of the hand and thigh. The eruption as well as the other symptoms promptly responded to oral prednisolone.

Aged↗
PubMed2000

Identification of a response element for vitamin D3 and retinoic acid in the promoter region of the human fructose-1,6-bisphosphatase gene.

Fructose-1,6-bisphosphatase (FBPase) is a key gluconeogenic enzyme. The data herein show that both the enzyme activity and mRNA level of the human FBPase gene are enhanced by 9-cis retinoic acid (9cRA) and all-trans retinoic acid (atRA) as well as by 1,25-dihydroxyvitamin D3 (VD3) in human promyelocytic HL60 cells and normal monocytes in peripheral blood, which were used as an alternative source to liver for the DNA diagnosis of FBPase deficiency. To understand the molecular mechanism of this enhancing action, the 2.4 kb 5'-regulatory region of the human FBPase gene was isolated and sequenced. Using luciferase reporter gene assays, a 0.5 kb FBPase basal promoter fragment was found to confer induction by VD3, 9cRA, and atRA that was mediated by the vitamin D3 receptor (VDR), retinoid X receptor (RXR), and retinoic acid receptor (RAR). Within this region, a direct repeat sequence, 5'-TAACCTttcTGAACT-3' (-340 to -326), which functions as a common response element for VD3, 9cRA, and atRA, was identified. The results of electrophoretic mobility shift assays indicated that VDR-RXR and RAR-RXR heterodimers bind this response element. Collectively, these observations indicate that VD3 and RA are important modulators of the expression of the human FBPase gene in monocytic cells.

Blotting, Northern↗
PubMed1999

Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma.

p27Kip1, a cyclin-dependent kinase inhibitor, is a negative regulator of the cell cycle, and apoptosis is a genetically encoded program of cell death. To clarify the relationship between the cell cycle and apoptosis, we investigated expression of p27, cyclin D1 and apoptosis-related proteins (p53, Bax, Bcl-2 and c-Myc) in 60 cases of oral and oropharyngeal squamous-cell carcinoma (SCC) using an immuno-histochemical approach, and evaluated spontaneous apoptosis in vivo. Our most notable finding was that spontaneous apoptosis in the p27-positive group was significantly higher than that in the p27-negative group (p = 0.028). In addition, the percentage of p27-positive cells was clearly correlated with that of Bax-positive cells (gamma = 0.288, p = 0.028) and with that of cyclin D1-positive cells (gamma = 0.416, p = 0.002). Expression of p27 was inversely associated with the clinical stage of total tumor progression (p = 0.027). However, no correlation was found between p27 expression and the following parameters: gender, tumor size, lymph node metastasis, overall survival and disease-free survival. Our results give evidence that the action of the cell-cycle regulator p27 is closely linked with apoptosis in clinical samples from patients and indicate that over-expression of p27 might induce apoptosis in cancer cells through elevation of Bax expression, thereby acting on tumor progression.

Adult↗
PubMed1998

Parathyroid-hormone-related-protein-producing thymic carcinoma presenting as a giant extrathoracic mass.

A 53-year-old female with a 9-month history of chest pain presented with a giant anterior chest wall mass. Radiologic examination showed an anterior mediastinal tumor invading the chest wall. Serum calcium and parathyroid hormone-related protein (PTHrP) levels were extremely elevated. Biopsy specimens disclosed a squamous cell carcinoma with Hassall's corpuscle-like keratotic pearls, and an immunohistological study showed a positive staining with PTHrP. The tumor and serum PTHrP concentration markedly decreased following cisplatin-based chemotherapy and radiation. This is the first case of PTHrP producing a thymic carcinoma with the unusual presentation of a large extrathoracic mass.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Nucleotide sequence and expression of the organomercurial-resistance determinants from a Pseudomonas K-62 plasmid pMR26.

pMRA17 cloned from Pseudomonas K-62 plasmid pMR26 specified the resistance to both organic and inorganic mercurials. DNA sequence of this broad-spectrum resistant mer operon was determined. The 5504-bp sequence includes six open reading frames (ORFs), five of which were identified as merR, merT, merP, merA and merB in order by analysis of deletion mutants and by comparison with the DNA and amino acid (aa) sequences of previously sequenced mer operons. The merB encoding organomercurial lyase showed a less identity than the other mer genes with those from other broad-spectrum resistance operons. The remaining ORF named merE, located between merA and merB, had no significant homology with the published mer genes and seemed to be a new gene which may involve in phenylmercury resistance. Induction experiments and maxicell analyses of the mer-polypeptides revealed that pMRA17 mer operon expressed mercurial-inducible phenotype and the merB and merE as well as the merA were under the control of MerR which could activate not only by mercuric ion but also by organomercurials.

Amino Acid Sequence↗
PubMed1997

Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency.

Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive inherited disorder and may cause sudden unexpected infant death. We reported the first case of molecular diagnosis of FBPase deficiency, using cultured monocytes as a source for FBPase mRNA. In the present study, we confirmed the presence of the same genetic mutation in this patient by amplifying genomic DNA. Molecular analysis was also performed to diagnose another 12 Japanese patients with FBPase deficiency. Four mutations responsible for FBPase deficiency were identified in 10 patients from 8 unrelated families among a total of 13 patients from 11 unrelated families; no mutation was found in the remaining 3 patients from 3 unrelated families. The identified mutations included the mutation reported earlier, with an insertion of one G residue at base 961 in exon 7 (960/961insG) (10 alleles, including 2 alleles in the Japanese family from our previous report [46% of the 22 mutant alleles]), and three novel mutations--a G-->A transition at base 490 in exon 4 (G164S) (3 alleles [14%]), a C-->A transversion at base 530 in exon 4 (A177D) (1 allele [4%]), and a G-->T transversion at base 88 in exon 1 (E30X) (2 alleles [9%]). FBPase proteins with G164S or A177D mutations were enzymatically inactive when purified from E. coli. Another new mutation, a T-->C transition at base 974 in exon 7 (V325A), was found in the same allele with the G164S mutation in one family (one allele) but was not responsible for FBPase deficiency. Our results indicate that the insertion of one G residue at base 961 was associated with a preferential disease-causing alternation in 13 Japanese patients. Our results also indicate accurate carrier detection in eight families (73%) of 11 Japanese patients with FBPase deficiency, in whom mutations in both alleles were identified.

Amino Acid Substitution↗
PubMed1996

Progastrin-releasing peptide(31-98) in idiopathic pulmonary fibrosis and sarcoidosis.

Gastrin-releasing peptide (GRP) is present in the lung and functions as a growth factor for bronchial epithelial cells and fibroblasts. GRP may stimulate release of cytokines from alveolar macrophages. However, in interstitial lung diseases, the role of GRP has not been clarified, in part because of the instability of GRP. Progastrin-releasing peptide (ProGRP) molecules are the actual GRP gene products. ProGRP molecules contain common extension peptides(31-98) [ProGRP(31-98)], which are not homologous with other proteins unlike GRP. With the ELISA, we measured ProGRP(31-98) concentrations in sera and bronchoalveolar lavage (BAL) fluids from patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF). Significant increased ProGRP(31-98) concentrations were found in sera and BAL fluids from patients with IPF or sarcoidosis when compared with healthy subjects. Serum ProGRP(31-98) values significantly correlated with BAL fluid ProGRP(31-98) values. In IPF and sarcoidosis, the release of the actual GRP gene products is increased in the lung and the bloodstream, and GRP may play a role during the processes of inflammation and remodeling in interstitial lung diseases.

Adolescent↗
PubMed1996

Role of serine and ICE-like proteases in induction of apoptosis by etoposide in human leukemia HL-60 cells.

This study was undertaken to examine the role of proteases in etoposide-induced apoptosis of human leukemia HL-60 cells. We found the potent activity to produce internucleosomal DNA fragmentation in a 150 000 g supernatant of cell lysate which was prepared from etoposide-treated HL-60 cells undergoing apoptosis. This nuclear-DNA fragmenting activity could be detected when the supernatant was incubated with isolated nuclei under Mg2+-dependent conditions. On the other hand, we could not detect such activity in the supernatant of cell lysate from non-treated HL-60 cells. Treatment of the supernatant with a serine protease inhibitor, N-tosyl-L-phenylala-nylchloromethyl ketone (TPCK), abolished the DNA fragmenting activity. An inhibitor of interleukin 1-beta-converting enzyme (ICE), Z-Val-Ala-Asp-fluoromethyl ketone (VAD-FMK), had no effect on this DNA fragmenting activity in vitro. However, when the cells were incubated with etoposide in the presence of VAD-FMK, the formation of TPCK-sensitive DNA fragmenting activity was blocked. Our data indicate that serine and ICE-like proteases may be involved in etoposide-induced apoptosis at the different stages, and especially a serine protease may be closely associated with the final step for induction of internucleosomal DNA fragmentation during apoptosis in HL-60 cells.

Amino Acid Chloromethyl Ketones↗
PubMed1996

Infection of human papillomavirus (HPV) and p53 over-expression in human female genital tract carcinoma.

Inactivation of p53 gene products either by mutation or by complex formation with E6 oncoprotein encoded by high risk HPV appears to be a common event in cervical carcinogenesis. This study was designed to clarify this association in 41 primary cervical, 15 endometrial, 3 ovarian and one rectal carcinomas. Polymerase chain reaction analysis revealed presence of high risk HPV in 36 (88%) cervical, 5 (33%) endometrial and none of ovarian and rectal carcinomas. HPV 16 was found in 14 cervical carcinomas, HPV 18 in 19 cervical and 2 endometrial carcinomas and HPV 33 in 28 cervical and 5 endometrial carcinomas. Expression of tumor suppressor protein p53 by using polyclonal antibody CM-1, was detected in 28 (68%) cervical, 7 (47%) endometrial, 2 (66%) ovarian and one (100%) rectal carcinoma. Twenty six cervical and 3 endometrial carcinoma cases were positive for both high risk HPV and p53. We conclude that beside cervical carcinoma HPV infection is not uncommon in endometrial carcinoma and in our experimental design there is no inverse correlation between HPV infection and p53 over-expression in a variety of the tumors analysed in the present study.

Adult↗
PubMed1995

Identification of a genetic mutation in a family with fructose-1,6- bisphosphatase deficiency.

Fructose-1,6-bisphosphatase deficiency is an inheritable disorder of gluconeogenesis. Sequence analysis of the cDNA of the fructose-1,6-bisphosphatase mRNA isolated from monocytes from a girl with this disease and her consanguineous parents revealed that the patient and her parents were a homozygote and heterozygotes for an insertion of one G residue at G957GGGG961, respectively. This mutation resulted in translation of a truncated enzyme protein, and the mutant protein showed no fructose-1,6- bisphosphatase activity in an overexpression experiment in Escherichia coli. However, this mutation is located in a region of the amino acid sequence which is not well conserved among mammals. A mutagenized clone was prepared from the normal clone. The extents of substitutions and deletions of the amino acid sequence were predicted to be less in the mutagenized protein than in the mutant protein. This mutagenized clone also expressed no fructose-1,6-bisphosphatase activity, although both of two normal clones from control monocytes and a control liver sample expressed an apparently normal level of fructose-1,6-bisphosphatase activity. Thus, this mutation is concluded to be responsible for fructose-1,6-bisphosphatase deficiency in this patient.

Amino Acid Sequence↗
PubMed1995

Circulating gamma delta-T-cell-receptor-positive lymphocytes in sarcoidosis.

We investigated phenotypic surface markers of peripheral blood lymphocytes including expression of gamma delta T cell receptor (TCR gamma delta) in 185 patients with sarcoidosis and 42 normal subjects. The proportion of TCR gamma delta+ lymphocytes in peripheral blood of patients with sarcoidosis (5.5 +/- 5.4%) was significantly higher than in normal subjects (3.6 +/- 2.2%; p < 0.05). A number of patients with sarcoidosis had prominently increased levels of circulating TCR gamma delta+ lymphocytes. Successive measurements of circulating TCR gamma delta+ lymphocytes demonstrated the persistence of increased levels of circulating TCR gamma delta+ lymphocytes. We divided the patients with sarcoidosis into two groups, one with high, the other with low TCR gamma delta+ expression. Compared with the low-value group, the high-value group had significantly decreased levels of circulating CD4+ lymphocytes, decreased incidence of a positive tuberculin reaction, and higher levels of serum angiotensin-converting enzyme and lysozyme, suggesting that these two groups may differ in their immunological response and disease activity of sarcoidosis. Measurement of TCR gamma delta+ expression in the circulation seems to be useful for estimating the disease activity of sarcoidosis.

Adolescent↗
PubMed1995

[Integrins involved in tumor invasion and metastasis].

The process of tumor growth and metastasis is a complex cascade of events relating many factors. The adhesion molecules relate to the cell-cell adhesion, adhesion to the extracellular matrix or the vascular endothelium and are thought to play important roles in the invasion and metastasis of the cancer. Integrins are known as extracellular matrix receptors. The change in the expression of integrins in the cancer cells has been reported. Recent information on the role of integrins in tumor progression and metastasis is reviewed here.

Humans↗
PubMed1995

[Integrin expression and ability to adhere to extracellular matrix and endothelial cells in human lung cancers].

Tumor cell interaction with extracellular matrix and endothelial cells constitute the most crucial factor of metastasis. Integrins are one of adhesion molecules which mediate the interaction. Most lung cancers adhered strongly to extracellular matrix corresponding with expression of integrins. Three lung cancers which expressed few or no integrins had very weak ability to adhere to extracellular matrix. Strong binding to endothelial cells was found in most lines but the three lung cancers had very little ability to adhere to endothelial cells. Binding to endothelial cells were strongly inhibited by antibodies to beta-1 subunit. Lung cancers may adhere to extracellular matrix and endothelial cells through integrins, especially the beta-1 subfamily.

Cell Adhesion↗