Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 595 records · Page 33Linked to original sources

PubMed1995

Endoscopic ultrasonographic abnormalities and lower esophageal sphincter function in reflux esophagitis.

Endoscopic ultrasonography of the lower esophagus was performed in 25 patients with reflux esophagitis and 13 age-matched controls. Thickening of the esophageal wall and abnormalities of its architecture were detected. As these morphological changes became more extensive, the lower esophageal sphincter pressure and the decrease of sphincter pressure on relaxation were both progressively reduced. There was a significant correlation between morphological abnormalities and lower esophageal function. Our results suggest that inflammatory damage to the muscle layer of the lower esophagus may impair lower esophageal sphincter function further, especially in patients with advanced esophagitis.

Aged↗

PubMed1995

Expression of myotonic dystrophy protein kinase in biopsied muscles.

We present expression of myotonic dystrophy protein kinase (DM-PK) on biopsied muscles by immunocytochemistry using antibody against synthetic DM-PK peptide antigen. Immunolocalization of DM-PK was observed in neuromuscular junctions, muscle spindle, and sarcoplasm on both normal and DM muscles. DM-PK expression of sarcoplasm was present in adult normal and DM muscles. In Duchenne and Becker muscular dystrophies, DM-PK was intensively expressed in cytoplasm on immature regenerating fibers. DM-PK is initially produced in cytoplasm of regenerating fibers and migrates toward sarcoplasm with maturity of muscle cell.

Adult↗

PubMed1995

Endothelium-derived relaxing factors in the kidney of spontaneously hypertensive rats.

Acetylcholine (ACh)-induced vasodilation is mainly due to endothelium-derived nitric oxide (EDNO) and hyperpolarizing factor (EDHF). To explore the mechanisms underlying attenuated endothelium-dependent vasodilation in hypertensive arteries, we measured the EDNO released from isolated kidneys of spontaneously hypertensive rats (SHR) using a sensitive chemiluminescence assay system of NO. ACh-induced renal vasodilation was significantly smaller in SHR than in the normotensive control, Wistar-Kyoto rats (WKY). However, ACh-induced NO release did not differ between SHR and WKY (10(-7) M: SHR +37 +/- 2 [SE] vs. WKY +32 +/- 4 fmol/min/g kidney). Perfusion with a 20 mEq/L high-K+ buffer, which is reported to inhibit action of EDHF, significantly reduced ACh-induced vasorelaxation in WKY but not in SHR, resulting in identical renal perfusion pressure in SHR and wKY under these conditions. These results indicate that attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF rather than that in EDNO.

Acetylcholine↗

PubMed1995

Dependence of collateral and small airway resistances of CO2 and volume in dog lobes.

We examined the hypothesis that collateral channels were identical within small airways and ducts, therefore both should respond similarly to chemical and mechanical stresses. A double lumen catheter was wedged into a segmental bronchus of the dog and humidified air or 10% CO2 in air (Vs) flowed at a segmental bronchial pressure (Pb) of 2 cm H2O. A small circular area about 1 cm diameter was peeled from the wedged segment and covered with a capsule glued to the surrounding pleura for measuring either a small airway flow (Vsaw) or capsule pressure (Pcap). Collateral resistance (Rcoll) and small airway resistance (Rsaw) were calculated as Rcoll = Pb/(Vs-Vsaw), Rsaw = (Pb-Pcap)/Vsaw, respectively. Hypocapnia (air) resulted in increases in Rcoll and Rsaw, while hypercapnia (10% CO2) generally had the opposite effect. Gcoll and Gsaw both increased linearly with lung volume (VL). The pattern of the responses of Rsaw closely paralleled those of Rcoll to local hypercapnia and hypocapnia, and to changing VL, implying that the major sites of resistance along collateral channels and along the airways are functionally and structurally similar.

Airway Obstruction↗

PubMed1995

Serum tissue inhibitor of metalloproteinases in patients with systemic sclerosis.

BACKGROUND: One of the suggested contributory factors to the development of dermal fibrosis is a decrease in collagenase activity, which may be related to levels of serum tissue inhibitors of metalloproteinase-1 (TIMP-1). OBJECTIVE: The aim of this study was to determine the clinical significance of serum TIMP-1 levels in systemic sclerosis (SSc). METHODS: We measured serum TIMP-1 concentration in 62 patients with SSc, 11 patients with systemic lupus erythematosus, 14 patients with rheumatoid arthritis, and 22 members of a normal control group. The clinical features of the patients with SSc and elevated TIMP levels were examined. RESULTS: The mean TIMP-1 level in the patients with SSc was significantly higher than that in the members of the control group or the patients with systemic lupus erythematosus or rheumatoid arthritis. In 44% of the patients with SSc the serum TIMP-1 level was elevated. The mean serum TIMP-1 level in patients with diffuse cutaneous SSc (dSSc) was significantly higher than that in those with limited cutaneous SSc. The patients with dSSc and elevated serum TIMP-1 levels showed a significantly greater incidence of lung fibrosis and anti-topoisomerase I antibody than those with normal serum TIMP-1 levels. The TIMP-1 level and diffusing capacity for carbon monoxide in the patients with SSc were negatively correlated. Increased mitogenic activity on dermal fibroblasts caused by serum from patients with dSSc was partially blocked by anti-TIMP-1 IgG. CONCLUSIONS: These findings suggest that serum TIMP-1 level is a useful indicator of disease activity in patients with SSc and that TIMP is involved in the pathogenesis of SSc.

Adolescent↗

PubMed1995

Hydroa vacciniforme-like lymphomatoid papulosis in a Japanese child: a new subset.

An 8-year-old Japanese girl had a 9-month history of a self-healing papulovesicular eruption on her face, scalp, and neck that resembled hydroa vacciniforme (HV). Histologically, there was a dense infiltration of small lymphocytic cells and scattered large atypical cells expressing CD30. Study of gene rearrangement showed no monoclonality in the infiltrating cells. To our knowledge, this is the second case of lymphomatoid papulosis with clinical features resembling HV. However, we also found descriptions in the literature of two other Japanese children with malignant lymphoma who both initially had clinical features resembling HV. These findings suggest that these cases of HV-like disease constitute a subset of lymphomatoid papulosis that is highly likely to progress to malignant lymphoma.

Child↗

PubMed1995

Selective depletion of cyclin-dependent kinases is associated with Fas-mediated apoptosis in human leukemia T-cell lines.

The Fas/Apo-1 molecule is a member of tumor necrosis factor/nerve growth factor (TNF/NGF) receptor family and is able to induce apoptosis in various type of malignant cells, including most of the human leukemia T-cells. We previously demonstrated that the Fas-resistant variants may exist in highly Fas-sensitive human leukemia T-cell lines. The surface expression of Fas antigen was unchanged in the variant cells, suggesting the requirement of the cytoplasmic mechanism to exert apoptosis. In the present study, we examined the changes in cytoplasmic proteins of the Fas-sensitive and Fas-resistant cells after stimulation with anti-Fas antibody, 2D1. In Western blotting analysis, we found that the stimulation of Fas-sensitive cells with 2D1, but not resistant variants, induced a repression of cyclin-dependent kinases (cdks), p34cdc2 and p33cdk2, along with apoptosis. There was no alteration in the expression of bcl-2, HSP70, HSP90, and cyclin proteins examined. This observation seemed specific to Fas-mediated apoptosis, because calcium ionophore A23187 or sodium azide failed to repress the expression of cdks. These results indicate that the specific depletion of cdks, most likely due to proteolysis, may play a role in Fas-mediated apoptosis.

Antibodies, Monoclonal↗

PubMed1995

Minimal somatic instability of CTG repeat in congenital myotonic dystrophy.

The molecular basis of myotonic dystrophy was identified as an unstable trinucleotide (CTG) repeat in the 3' untranslated region of an mRNA encoding a member of the protein kinase family. Unstable DNA was analyzed from various tissue samples of a patient with severe congenital myotonic dystrophy. In BamHI- or BglI-digested DNA, a normal band plus differently expanded ones were identified in various tissue samples. These observations demonstrated somatic instability of the repeat in a congenital myotonic dystrophy patient.

Blotting, Southern↗

PubMed1995

In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity.

BACKGROUND: Water-soluble fullerenes have recently been shown to exhibit considerable in vitro biological activity including cytotoxicity, site-selective DNA cleavage and inhibition of HIV protease. To assess the potential of these compounds as drugs, studies on the in vivo behavior of fullerenes are needed. We therefore set out to synthesize a radiolabeled, water-soluble fullerene, in order to obtain data on the oral absorption, distribution and excretion of this class of compounds. RESULTS: We synthesized a 14C-labeled water-soluble [60]fullerene using dipolar trimethylenemethane, which undergoes cycloaddition to [60]fullerene. When administered orally to rats, this compound was not efficiently absorbed and was excreted primarily in the feces. When injected intravenously, however, it was distributed rapidly to various tissues, and most of the material was retained in the body after one week. The compound was also able to penetrate the blood-brain barrier. Acute toxicity of the water-miscible fullerene was found to be quite low. CONCLUSIONS: Although the water-soluble fullerenes (and possibly their simple metabolites) are not acutely toxic, they are retained in the body for long periods, raising concerns about chronic toxic effects. The fact that fullerenes distribute rapidly to many tissues suggests that they may eventually be useful to deliver highly polar drugs through membranes to a target tissue, however, and they may even have applications in the delivery of drugs to the brain. Recent advances in fullerene synthetic chemistry may also make it possible to control fullerene absorption/excretion profiles in the future.

Administration, Oral↗

PubMed1995

Laparoscopic minilaparotomy Billroth I gastrectomy with extraperigastric lymphadenectomy for early gastric cancer using an abdominal wall-lifting method.

Laparoscopic gastrectomy with extraperigastric lymphadenectomy for early gastric cancer has never been performed because of technical difficulties attributable to the lack of appropriate techniques, the high cost of laparoscopic instruments, and the need for numerous disposable stapling devices. In order to solve these problems, we have designed a method of laparoscopic minilaparotomy using an abdominal wall-lifting method, and a patient with early gastric cancer (depth of submucosa) underwent by this laparoscopic minilaparotomy distal gastrectomy with extraperigastric lymphadenectomy. During his postoperative recovery, the patient requested no narcotic analgesic, and was discharged on postoperative day 14.

Abdominal Muscles↗

PubMed1995

Effects of combination of benzylpenicillin and fosfomycin on penicillin-resistant Streptococcus pneumoniae.

The in vitro activity of benzylpenicillin in combination with fosfomycin against 51 clinical isolates of penicillin-resistant Streptococcus pneumoniae [minimal inhibitory concentrations (MICs) of benzylpenicillin > or = 0.5 mg/liter] was investigated. The fractional inhibitory concentration (FIC) index using the checkerboard method ranged from 0.38 to 0.75 (mean: 0.63). A synergy was also demonstrated in the killing curve on S. pneumoniae TW-1303 (MIC of benzylpenicillin, 2 mg/liter; MIC of fosfomycin, 32 mg/liter: FIC index, 0.38). Fosfomycin inhibited the production of all penicillin-binding proteins (PBP) except PBP 2B of S. pneumoniae TW-1303 and it decreased that of PBP 2B when it was combined with benzylpenicillin. These results suggest that the combination of benzylpenicillin and fosfomycin could be considered as the alternative treatment of penicillin-resistant pneumococcal infections.

Bacterial Proteins↗

PubMed1995

Intercellular adhesion molecule-1 (ICAM-1) in the sera of patients with Graves' disease: correlation with disease activity and treatment status.

Intercellular adhesion molecule (ICAM-1), a ligand for lymphocyte function-associated antigen-1 (LFA-1), plays an important role in a variety of immune-mediated mechanisms such as lymphocyte attachment to cultured Graves' thyroid cells. We report the detection of a soluble form of the ICAM-1 molecule (sICAM-1) in sera from patients with Graves' disease (GD) and other thyroid disorders. The mean (+/- SD) sICAM-1 concentration in 28 euthyroid control subjects was 1931 +/- 681 pmol/L. The mean sICAM-1 concentration in 25 untreated hyperthyroid patients with GD was significantly elevated (3065 +/- 890 pmol/L), and decreased significantly (2489 +/- 845 pmol/L) after treatment with antithyroid drugs and/or 131I. Of 14 GD patients who had been in remission following administration of antithyroid drugs, 12 had recurrent disease. In 10 of the 12 patients in whom GD recurred, the sICAM-1 concentration (3807 +/- 796 pmol/L) increased significantly. The mean sICAM-1 concentration in patients with hypothyroidism due to chronic thyroiditis (n = 15:2895 +/- 569 pmol/L) was significantly elevated over that of control subjects, and not different from untreated hyperthyroid patients. The mean sICAM-1 concentration in patients with subacute thyroiditis (n = 13: 3036 +/- 441 pmol/L) was significantly elevated, while the mean sICAM-1 concentration in patients with nodular goiter (n = 10: 2318 +/- 490 pmol/L) was within the normal range. These results indicate that mean serum sICAM-1 concentration was significantly elevated in patients with untreated GD, and it decreased after treatment and increased at the time of recurrence. Therefore, the elevated serum concentration of sICAM-1 in patient with GD probably reflects ongoing immune processes.

Adolescent↗

PubMed1995

Detection of antiribosomal P protein antibodies in patients with systemic sclerosis.

This study investigated the prevalence and clinical significance of anti-ribosomal P protein (anti-P) antibodies in patients with systemic sclerosis (SSc). Serum samples from 150 patients with SSc were examined by indirect immunofluorescence. ELISA and immunoblotting. Anti-P antibodies were detected in four (3%) patients with SSc. Three of the four patients showed SSc/SLE (systemic lupus erythematosus) overlap syndrome, but psychiatric disorders were not observed in these patients. By longitudinal immunoblotting analysis one patient, who was initially diagnosed with SSc, later developed anti-P antibodies along clinical manifestations of SLE. Our data suggest that anti-P antibodies are uncommon in SSc and that the presence of anti-P antibodies in patients with SSc indicates an overlap with SLE.

Adult↗

PubMed1995

Ultrasound measurement of skin thickness in systemic sclerosis.

Sclerotic skin change in systemic sclerosis (SSc) usually accompanies increased skin thickness. In order to quantify the cutaneous changes and to clarify the changes in the 'uninvolved' skin in systemic sclerosis (SSc), we measured the skin thickness on the chest, the forearms and the hands of 79 patients with SSc and 81 healthy controls with a B-mode ultrasound (30 MHz) apparatus. The thickness of the 'uninvolved', as well as the 'involved' skin in patients with SSc was significantly greater than that of healthy controls. Increased skin thickness on the forearms and/or the hands showed a 64.6% sensitivity and a 100% specificity for SSc. These results indicated that the skin which appears to be 'uninvolved' in patients with SSc is already pathologic, as shown by increased thickness. Moreover, measurement of skin thickness may be beneficial in the diagnosis of this disease at an early stage.

Adolescent↗

PubMed1995

Growth regulation in scleroderma fibroblasts: increased response to transforming growth factor-beta 1.

We investigated the responses of normal and scleroderma fibroblasts to various growth factors, especially transforming growth factor-beta 1 (TGF-beta 1). The effects of various growth factors on [3H]thymidine incorporation in normal and scleroderma fibroblasts were examined. [125I]-labeled platelet-derived growth factor (PDGF)-BB binding in scleroderma and normal fibroblasts was examined both in the presence and absence of TGF-beta 1 (1 ng/ml). Cytoplasmic protein was isolated and analyzed by Western blotting. Total RNA from fibroblasts was also isolated and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primer sets. Mitogenic responses to TGF-beta 1 (0.33-1 ng/ml) in seven scleroderma fibroblast strains were significantly greater than those in normal controls. [125I]-PDGF-BB binding to scleroderma fibroblasts was increased after TGF-beta 1 stimulation. The increased response to TGF-beta 1 was shown to be mediated through PDGF-like protein induction; TGF-beta 1-treated scleroderma fibroblasts produced greater amounts of 36-kD PDGF-like protein, which was reported previously as connective tissue growth factor (CTGF), than did TGF-beta 1-treated normal fibroblasts. TGF-beta 1 treatment also upregulated PDGF-alpha receptor expression in scleroderma fibroblasts but not in normal dermal fibroblasts. mRNA expression of CTGF and PDGF-alpha receptor was correlated with the above protein expression. These observations suggest that the increased growth response to TGF-beta 1 in scleroderma fibroblasts is mediated through the induction of CTGF and PDGF-alpha receptor.

Cell Division↗

PubMed1995

Significant correlation between connective tissue growth factor gene expression and skin sclerosis in tissue sections from patients with systemic sclerosis.

The role of some growth factors and cytokines in the pathogenesis of systemic sclerosis (SSc) has been suggested. In particular, the contribution of transforming growth factor beta in the progression of skin sclerosis is suspected. Connective tissue growth factor (CTGF) was originally identified in human umbilical vein endothelial cells, and a recent study has revealed that human skin fibroblasts produce CTGF after stimulation with transforming growth factor beta. In the present study, the distribution of CTGF gene expression in tissue sections from patients with SSc was investigated by digoxigenin-labeled in situ hybridization. Strong CTGF mRNA signals were observed in the fibroblasts in sclerotic lesions, especially in the deep dermis, of the skin specimens from patients with SSc, whereas there was no expression in the skin from normal controls. The number of fibroblasts with positive hybridization signals was more abundant in the dermis from the sclerotic stage than in that from the inflammatory stage. Our findings indicate a correlation between CTGF gene expression and skin sclerosis and support the hypothesis that transforming growth factor-beta plays an important role in the pathogenesis of SSc, because transforming growth factor beta is the only inducer for CTGF identified to date.

Adolescent↗

PubMed1995

T-cell receptor gene structures of HLA-A26-restricted cytotoxic T lymphocyte lines against human autologous pancreatic adenocarcinoma.

We isolated two cytotoxic T lymphocyte (CTL) lines, which were independently obtained by mixed lymphocyte-tumor cell culture from tumor-infiltrating lymphocytes of a patient with pancreatic adenocarcinoma. Both lines behaved identically in all the functional aspects tested and appeared to be HLA-A26-restricted. We analyzed their T cell receptor (TCR) gene structures, including V-(D)-J junctional sequences, which are unique to each T-cell clonotype and contribute to TCR diversity. Each line consisted of a clonal T-cell expressing V alpha 18 and V beta 7. The alpha chain gene was composed of V alpha 18/J alpha F/C alpha and the beta-chain gene, of V beta 7.1/D beta/J beta 1.4/C beta 2. The sequences were all in-frame and therefore should yield functional transcripts. The junctional sequences were identical between the two lines. These data suggested that the two CTL clones having the same CDR3 had descended from a common precursor lymphocyte. The clonal expansion of CTL lines with the identical CDR3 implies that they are directed against the same tumor antigen, which seemed to be immunologically dominant in the specific interaction between the CTL and the autologous pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMed1995

Gene expressions of protein tyrosine phosphatases in regenerating rat liver and rat ascites hepatoma cells.

mRNA levels for ten protein tyrosine phosphatases (PTPs), PTP-S, PTPH1, PTP-1, GLEPP1, LRP, PTP1D, PTPG1, PTP gamma, PTP delta, and LAR, were determined during regeneration of rat liver, and mRNA levels for 5 PTPs, PTP-S, PTP-1, PTP gamma, PTP delta, and LRP, were determined in three lines of rat ascites hepatoma cells. In regenerating rat liver, the expression patterns of PTP genes after partial hepatectomy could be classified into four groups. In group 1 (PTP-S and PTPH1), the mRNA levels increased rapidly, reached a maximum 7 h after partial hepatectomy, remained at a plateau for 1-2 days and then decreased gradually. In group 2 (PTP-1, GLEPP1, and LRP), the mRNA levels showed two peaks on days 1 and 5, and then decreased gradually. In group 3 (PTP1D and PTPG1), the mRNA levels increased rapidly, reached a maximum at 7 h, remained high for several days, and then did not decrease but rather increased after day 7. In group 4 (PTP gamma, PTP delta, and LAR), the mRNA levels remained constant for the first 5 days and increased over the control levels after day 7. In rat ascites hepatomas, gene expression of non-receptor-like PTPs (PTP-S and PTP-1) showed various neoplastic alterations, whereas mRNAs of receptor-like PTPs (PTP gamma, PTP delta, and LRP) were lost or drastically decreased.

Amino Acid Sequence↗