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Biomedical subjects

A Inoue

Publications and source records attributed to A Inoue.

At least 127 records · Page 7Linked to original sources

Production of IL-6 by T cells from the femoral head of patients with rapidly destructive coxopathy (RDC).

RDC is a syndrome with unknown etiology that causes rapid destruction of a hip joint. We have investigated the production of osteoclast-activating cytokines (IL-6, IL-1alpha and tumour necrosis factor-alpha (TNF-alpha)), interferon-gamma (IFN-gamma) and IL-8 by T cells in the affected joint. The level of IL-6 produced by the T cell lines (TCL) established from the femoral head was significantly higher than that from patients' or healthy donors' peripheral blood mononuclear cells (PBMC). IL-6 production by the TCL from synovial membrane or from patients' PBMC was also significantly higher than that from healthy donors' PBMC. IL-1alpha production by the TCL from the femoral head was significantly higher than any of the other groups when all the TCL were used for the analysis. TNF-alpha production was highest in the TCL from patients' PBMC. The levels of IFN-gamma or IL-8 were not significantly different among these four groups. The plasma levels of all these cytokines except for IFN-gamma, that was rather lower, in RDC patients were not significantly different from those in osteoarthrosis or trauma patients, or healthy donors. These results suggest that T cells at the affected femoral head, and also synovial membrane to some extent, are involved in bone resorption through the production of IL-6 and probably IL-1alpha in patients with RDC.

Aged

cGMP produced in response to ANP and CNP regulates proliferation and differentiation of osteoblastic cells.

The effects of natriuretic peptides on the proliferation and differentiation of osteoblast-like cells from rat calvariae were examined. Natriuretic peptides are physiological agonists that activate receptor guanylate cyclases, namely, natriuretic peptide receptor (NPR)-A and NPR-B. Exposure of cells to atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) resulted in large increases in the rate of intracellular production of guanosine 3',5'-cyclic monophosphate (cGMP). Moreover, CNP-like immunoreactivity was detected in the conditioned medium from osteoblast-like cells, while ANP was undetectable. In cells exposed to natriuretic peptides, a dose-dependent reduction in the rate of DNA synthesis was observed. Natriuretic peptides also stimulated the activity of alkaline phosphatase (ALPase) and the expression of mRNA for ALPase and osteocalcin and the mineralization of nodules by the cultured cells. These results could be reproduced by treating cells with 8-bromo-cGMP. Endothelin-1, whose physiological functions are the opposite of those of natriuretic peptides, decreased the ALPase activity and the mineralization of nodules. In the present study, natriuretic peptides were demonstrated to promote bone formation via the action of cGMP in a signal-transduction pathway mediated by specific receptors in osteoblast-like cells.

Alkaline Phosphatase

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

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

S-methylmethionine sulfonium in fruits of citrus hybrids.

The S-methylmethionine sulfonium (MMS) concentrations in fruits of citrus hybrids were measured, and found to increase during ripening of the fruit. However, there of eleven hybrids of 'Seto unshiu' crossed with 'Morita ponkan' and four of 9 hybrids of 'Murcott' tangor crossed with 'Seto unshiu' had low MMS concentrations even at late harvest stage. Crossbreeding is useful in producing new citrus fruits that have juices with the desirable characteristics of their parents without formation of dimethyl sulfide which is an off-flavor.

Citrus

Flushing pattern and idiopathic avascular necrosis of the femoral head.

A cooperative hospital-based case-control study of idiopathic avascular necrosis of the femoral head (IANF) was carried out to clarify the involvement of smoking, drinking, flushing pattern, and other factors in the development of IANF comparing 90 cases (64 males and 26 females) without history of systemic corticosteroid use with 180 matched controls (128 males and 52 females). The results of analyses were represented only for male subjects because of small number of female cases. There was no significant difference in smoking habits, daily and cumulative number of cigarettes smoked between case and control groups. Current drinkers had obviously higher risk (OR = 11.47) of IANF compared to nondrinkers or exdrinkers. In addition, there was a consistent risk increase with increasing alcohol consumption and the highly significant dose-response relationship remained unchanged after adjustment for all other factors (chi 2 = 14.33, p < 0.001 and chi 2 = 13.24, p < 0.001 for daily and cumulative alcohol consumption, respectively). For flushing pattern, although nonflushers had a significantly elevated risk (OR = 2.08) in the univariate analysis, the association disappeared (OR = 0.73) after adjustment for alcohol and other factors. Since nonflushers tend to be heavy drinkers, perhaps, an apparent risk increase among nonflushers may be due to alcohol drinking. Body mass index (BMI) was inversely related to the development of IANF. The risk reduction was found among subjects with higher BMI and an adjusted linear trend of OR was significant (chi 2 = 6.65, p < 0.05). However, further studies were required regarding the association between flushing pattern or BMI and IANF because of a few reports. History of liver diseases and occupational history were not significantly associated with the development of IANF after adjustment for other factors.

Adult

[How to determine the best combination assay by several tumor markers?].

Combination assay by several tumor markers provides more precise diagnosis of malignancy than using a single tumor marker. The best combination assay by two tumor markers is determined as follows. MINIMIZE RFP (1-SpAorB(CA, CB)) + RFN(1-SnAorB(CA, CB)), where RFP, RFN denote the loss of false positive and false negative, respectively. SpAorB (CA, CB), SnAorB (CA, CB) are specificity and sensitivity of the combination assay by tumor markers A, B with cut-off values CA, CB.

Biomarkers, Tumor

[A case report of surgical treatment for acute mitral insufficiency associated with acute gastric lesion].

A 76-year-old female was admitted to our hospital due to anterior chest pain and dyspnea. Mitral regurgitation due to prolapse of the posterior leaflet was detected by UCG. After admission, massive gastric hemorrhage was observed. Because hemostatic therapy using endoscopy was not effective, partial gastrectomy was performed. The origin of the hemorrhage, an acute gastric ulcer, was located on the side of the minor curvature of the corpus ventriculi. After gastrectomy, the patient underwent medical treatment using an IABP, but the left heart failure was not reduced, and the pulmonary edema worsened. At 18 hours after gastrectomy, MVR was performed. The cause of regurgitation is torn chordae of the posterior leaflet. The postoperative course was good, and the patient is doing well in NYHA class 1. This case is the first report of acute mitral insufficiency associated with acute gastric lesion in Japan.

Acute Disease

[A study on the pathogenesis of hepatomegaly in patients with Crow-Fukase syndrome].

We studied pathogenesis of hepatomegaly in Crow-Fukase syndrome. Hepatocytes were isolated from BALB/c mice and cultured with serum or ascites of three patients with Crow-Fukase syndrome. After 24 hours culture, total number of hepatocytes was counted. The levels of human hepatocyte growth factor (h-HGF) in the serum were also measured. In the hepatocyte culture study, the numbers of hepatocytes after 24 hours cultured in the serum of two patients were significantly larger than those of the control group. When the hepatocytes were cultured with patients' serum after corticosteroid therapy, the survival numbers were markedly reduced. The serum levels of h-HGF in our three patients were 0.62, 0.52, 0.53 ng/ml respectively. They were all slightly higher than normal values (< or = 0.39 ng/ml). Our study indicates that in the serum or ascites of patients with Crow-Fukase syndrome, there may be some humoral factors other than h-HGF, which promote proliferation of hepatocyte or protect hepatocyte.

Aged

[A study of soluble form of L-selectin in blood of patients with neuroimmunological disorders].

Members of the selection family mediate the first step of leukocyte-endothelial cell interaction in inflammatory lesion. We have examined the soluble form of L-selectin (sL-selectin) in patients with neuroimmunological disorders (48 multiple sclerosis, 2 Balo's sclerosis, 18 Guillain-Barré syndrome, 7 Miller-Fisher syndrome, 8 chronic inflammatory demyelinating polyneuropathy, and 25 human T-lymphotropic virus type-1 associated myelopathy). The levels of sL-selectin were measured by monoclonal antibody-based enzyme immunoassay on serum samples taken from patients with neuro immunological disorders. The level of sL-selectin were significantly decreased in the blood of patient with inactive stage of multiple sclerosis (MS), Guillain-Barré syndrome (GBS), and human T-lymphotropic virus type-1 associated myelopathy (HAM). The levels of sL-selectin in the sera of patients with active phase of MS tended to be high, but not significantly increased. The levels of sL-selectin, however, in the sort of patients with Balo's concentric sclerosis tended to be decreased. Thus, the findings that the serum concentrations of sL-selectin were decreased in stable phase of MS and acute phase of GBS and HAM suggest that sL-selectin may be differently involved in between patients with MS and patients with GBS or HAM.

Adult

Fibrosarcoma of the toe: a destructive lesion of the distal phalanx.

A rare case of well differentiated fibrosarcoma occurring in the left second toe is described in a 12-year-old boy who presented with a destructive lesion that had almost totally destroyed the distal phalanx, except for the epiphysis. Amputated specimens showed microscopic evidence of proliferation of uniform spindle cells arranged in both fascicles and a characteristic herringbone pattern with a small number of mitotic figures. This tumor did not show any specific immunoreactivity except for vimentin and had basic ultrastructural characteristics of fibroblasts and myofibroblasts. The tumor was treated by amputation at the middle phalanx level and had not recurred 3 years later. From the presenting radiographic features, some benign neoplasms and reactive lesions were considered in the differential diagnosis. Only results from the pathologic examination were useful in reaching a correct diagnosis.

Amputation, Surgical

Determination of the prognostic significance of unscheduled cyclin A overexpression in patients with esophageal squamous cell carcinoma.

The expression of cyclin A protein was retrospectively investigated in 124 patients with human esophageal squamous cell carcinoma with immunohistochemical techniques using antibody to cyclin A protein (BF683). Of 124 tumors, 49 (39.5%) exhibited positive staining in cancer cells with this antibody. Staining was observed predominantly but not exclusively in the nucleus. A significantly higher degree of association of immunoreactivity with this antibody was detected for advanced types of tumors (stages I, II, III, and IV) than for early tumors (stage 0; P < 0.05). Patients with cyclin A immunopositivity had a significantly poorer survival rate than did other patients (P < 0.01). These findings provide the first evidence for frequent and unscheduled overexpression of cyclin A protein in human esophageal cancer and suggest the possibility that alteration of cyclin A overexpression is associated with tumor progression and patient prognosis for esophageal cancers.

Aged

Reciprocal regulation by cyclic nucleotides of the differentiation of rat osteoblast-like cells and mineralization of nodules.

The effects of cAMP and cGMP on the differentiation of osteoblast-like cells derived from rat calvariae and on the formation of bone in vitro were studied. Continuous culture of osteoblast-like cells in the presence of 8-bromo-cyclic AMP (8-Br-cAMP) resulted in the dose-related inhibition both of the synthesis of cellular alkaline phosphatase (ALPase), which is known as a marker of osteoblastic differentiation, and of the formation of mineralized nodules, which is a model of the formation of bone in vitro. By contrast, 8-bromo-cyclic GMP (8-Br-cGMP) promoted the synthesis of ALPase and the formation of mineralized nodules. Northern blot analysis revealed that these cyclic nucleotides modulated the steady-state levels of mRNAs for ALPase and osteocalcin, a bone-matrix protein that is specifically produced by osteoblast. The present results indicate that cAMP and cGMP act reciprocally to regulate osteoblastic differentiation and the subsequent formation of mineralized nodules.

8-Bromo Cyclic Adenosine Monophosphate

70-kDa heat shock cognate protein interacts directly with the N-terminal region of the retinoblastoma gene product pRb. Identification of a novel region of pRb-mediating protein interaction.

Retinoblastoma protein (pRb) functions as a tumor suppressor, and certain proteins are known to bind to pRb in the C-terminal region. Although the N-terminal region of pRb may also mediate interaction with some proteins, no such protein has been identified yet. We demonstrated previously the in vivo protein association between pRb and 73-kDa heat shock cognate protein (hsc73) in certain human tumor cell lines. In this report we analyzed the interaction between these two proteins in vitro. Our data showed that hsc73 interacts with the novel N-terminal region of pRb; that is, pRb binds directly to hsc73 and dissociates from hsc73 in an ATP-dependent manner. By using deletion mutants of cDNA encoding pRb, the hsc73 binding site of pRb was determined to be located in the region (residues 301-372) outside the so-called A pocket (residues 373-579) of this tumor suppressor protein. This finding was compatible with the fact that the adenovirus E1A oncoprotein, which is known to bind to the E2F binding pocket region of pRb, could not compete with hsc73 for the binding. Furthermore, phosphorylation of pRb by cyclin-dependent kinase inhibited the binding of pRb to hsc73. These data suggest that hsc73 may act exclusively as the molecular chaperone for nonphosphorylated pRb. As a result, hsc73 may function as a molecular stabilizer of nonphosphorylated pRb.

Adenosine Triphosphate

Intradural extramedullary ependymoma. A case report.

STUDY DESIGN: The present study illustrates a rare case of ependymoma of the spinal cord. OBJECTIVES: An encapsulated intradural extramedullary ependymoma of the cervicothoracic spinal cord in a 24-year old woman is reported. SUMMARY OF BACKGROUND DATA: Ependymoma is a glial tumor arising in the central nervous system. Intradural extramedullary ependymoma of the spinal cord is rare, and two cases were reported previously. METHODS: The woman presented with myelopathy below C6. Magnetic resonance imaging showed an intradural tumor from C4 to T3 and no other lesion in the central nervous system. At surgery, the extramedullary tumor apparently was not attracted to the spinal cord or dura mater. Gross total removal was easily achieved under the operating microscope. RESULTS: Histologic examination revealed the encapsulated tumor as an anaplastic ependymoma. Almost complete neurologic recovery was obtained. CONCLUSION: The encapsulated appearance, lack of an apparent attachment to the central nervous system, and absence of signs of the primary neoplastic process within the brain or spinal cord suggested that the tumor arose from ectopic ependymal cells.

Adult

Isolation and characterization of a peptide isomerase from funnel web spider venom.

A novel peptide isomerase was purified from the venom of funnel web spider, Agelenopsis aperta. The complete primary structure of the isomerase has been established by sequence analyses of polypeptide chains, assignments of disulfide bridges, carbohydrate analyses, and mass spectrometry of sugar chains. The isomerase was found to be a 29-kDa polypeptide that consists of an 18-residue light chain and a 243-residue heavy chain connected by a single disulfide bridge. The heavy chain contains three intramolecular disulfide bridges and one N-linked oligosaccharide chain with a simple trimannosyl core structure. A sequence homology search showed a significant similarity of the enzyme with serine proteases, particularly around a putative catalytic triad of the isomerase. The isomerase specifically interconverts the configuration of Ser46 of a 48-amino-acid peptide, omega-agatoxin-TK, and the conversion rate from L-Ser to D-Ser was approximately two times faster than the reverse reaction.

Amino Acid Isomerases