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T Koga

Publications and source records attributed to T Koga.

At least 37 records · Page 2Linked to original sources
PubMed2003

Chemical peeling with salicylic acid in polyethylene glycol vehicle suppresses skin tumour development in hairless mice.

BACKGROUND: Chemical peeling with salicylic acid in polyethylene glycol (PEG) vehicle is used clinically to improve the cosmetic appearance of skin that has been damaged by exposure to the sun. It is well known that cancers of the skin such as basal cell carcinoma and squamous cell carcinoma may be induced by the sun. However, the carcinogenic potential of chemical peeling agents has not been studied. OBJECTIVES: To evaluate the effects of chemical peeling with 30% salicylic acid in PEG on skin tumour formation in treated vs. control mice. METHODS: To serve as a model of sun-damaged skin, hairless SKH/hr1 mice were irradiated with ultraviolet (UV) B for 14 weeks, with or without treatment every 2 weeks with 30% salicylic acid in PEG for a total of 18 weeks. RESULTS: Not only was the total number of tumours greatly reduced in the treated vs. the control mice, but skin tumour development was also slower in the treated vs. the control mice. At the final treatment, the fractions of T and B lymphocytes and natural killer cells from spleens of both groups of mice were comparable, and interferon-gamma production did not differ. CONCLUSIONS: Our findings suggest that chemical peeling with salicylic acid in PEG may help to prevent as well as to reduce the number of UVB-induced skin tumours.

Animals↗
PubMed2003

Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthma.

BACKGROUND: The 72 kDa matrix metalloproteinase 2 (MMP-2) and the 92 kDa matrix metalloproteinase 9 (MMP-9) are type IV collagenases implicated in various aspects of inflammation including accumulation of inflammatory cells, tissue injury, and development of remodelling. The role of these enzymes in the pathogenesis of asthma exacerbations is unknown. METHODS: Circulating levels of MMP-2 and MMP-9 proteins and the expression of their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP-1), were measured in 21 patients experiencing an asthma exacerbation and 21 age matched patients with stable asthma. Circulating gelatinolytic activity was compared during the asthma exacerbation and during subsequent convalescence by gelatin zymography in the same individuals. In addition, MMP-9 specific activity was quantified with a colorimetric assay which uses an artificial proenzyme containing a specific domain recognised by MMP-9 in the same paired samples. RESULTS: A significant increase in the circulating level of MMP-9 was seen in patients with an asthma exacerbation compared with patients with stable asthma (202.9 (22.0) v 107.7 (9.9) ng/ml, p=0.0003). There were no significant differences in the circulating levels of MMP-2 or TIMP-1. Gelatin zymography identified two major circulating gelatinolytic activities corresponding to MMP-2 and MMP-9, and showed that asthma exacerbations are characterised by markedly increased MMP-9 activity with no significant change in MMP-2 activity compared with the activities during convalescence in the same individuals. Direct measurement showed that MMP-9 specific activity is significantly increased during asthma exacerbations compared with subsequent convalescence (269.6 (31.7) v 170.4 (12.6) ng/ml, p=0.0099). CONCLUSIONS: Asthma exacerbations are characterised by increased circulating MMP-9 activity. This increased activity may be related to exaggerated airway inflammation and airway remodelling.

Adult↗
PubMed2003

Basal cell carcinomas in association with basaloid follicular hamartoma.

We describe a unique case of various types of basal cell carcinoma (BCC) associated with basaloid follicular hamartoma (BFH) in a 56-year-old female patient. The lesion consisted of a dark brown and elastic soft nodule and papules within the area of a birthmark on the neck. The lesion was surgically excised. Histological examination of the nodular region revealed aggregations of neoplastic basaloid cells. We diagnosed the nodule as BCC with a racemiform or reticular pattern. In addition, a specimen taken from brownish black papules within the birthmark was found to be composed of anastomosing cords of basaloid cells accompanied by infundibular cystic structures. These features were consistent with an infundibulocystic BCC. In contrast, specimens from a hamartomatous plaque showed distinctive branching strands of basaloid cells that are suggestive of BFH. Therefore, our findings indicate that several types of BCC may develop within a BFH.

Adult↗
PubMed2002

Methyl mercaptan production by periodontal bacteria.

Oral malodour is principally caused by volatile sulphur compounds (VSC) such as hydrogen sulphide, methyl mercaptan and dimethyl sulphide. Methyl mercaptan is highly toxic, and its presence within a periodontal pocket suggests involvement in the induction and/or progression of periodontal disease. Methyl mercaptan is produced from L-methionine by L-methionine- alpha -deamino- gamma -mercaptomethane-lyase (METase). METase catalyses the alpha,gamma-eliminating reaction of L-methionine, which results in the release of alpha-ketobutyrate, methyl mercaptan and ammonia. Although methyl mercaptan is produced by a variety of microorganisms, Porphyromonas gingivalis is considered to be the most potent producer. METases of P. gingivalis have been characterised and the genes responsible for their production, the mg/genes, have been sequenced. To ascertain the role of METase in P. gingivalis pathogenicity, a METase-deficient mutant strain (M1217) from P. gingivalis strain W83 was engineered. Only 7.7% of the mice infected with W83 survived 4 days after subcutaneous injection, whereas 36% of the mice infected with M1217 survived over the same time period. Many papers have reported the periodontal pathogenesis of VSC. It has been argued that methyl mercaptan may play a significant role in the pathogenicity of P. gingivalis.

Ammonia↗
PubMed2002

Prostaglandin E1 at clinically relevant concentrations inhibits aggregation of platelets under synergic interaction with endothelial cells.

BACKGROUND: The inhibitory effect of prostaglandin E1 (PGE1) on platelet aggregation is considered an important characteristic of this agent. However, the concentration of PGE1 to inhibit aggregation in vitro is higher than those of clinical use (1 ng/ml). To clarify whether PGE1 at clinically relevant concentrations inhibits aggregation under synergic action with endothelial cell-derived factors (nitric oxide and prostacyclin), we evaluated the minimum effective concentration of PGE1 to enhance the anti-aggregating activity of endothelial cells. METHODS: Inhibitory effects of PGE1 and/or the incubation buffer from cultured porcine aortic endothelial (PAE) cells on human platelet aggregation induced by 2 micro g/ml collagen were examined by turbidimetry. RESULTS: PGE1 concentration-dependently (>3 ng/ml) inhibited aggregation: the incubation buffer from PAE cells stimulated by bradykinin also inhibited aggregation. Bradykinin concentration-dependently increased the anti-aggregating activity of the PAE incubation buffer. The half-maximum effective concentration of bradykinin to inhibit aggregation (95.4+/-22.3 nM) was significantly decreased to 10.3+/-2.5 nM by 0.1 ng/ml PGE1 and to 0.9+/-0.5 nM by 1 ng/ml PGE1, respectively. These indicated that PGE1 (=0.1 ng/ml) inhibits aggregation through synergism with endothelial cells. The synergic effect of PGE1 and the anti-aggregating activity of the PAE cells preincubated with 10 micro M indomethacin for 30 min was more potent than that of these cells preincubated with 1 mM NG-nitro-L-arginine methyl ester. This suggested that the interaction of PGE1 with endothelial cell-derived nitric oxide is more powerful than that with endothelial cell-derived prostacyclin. CONCLUSION: Prostaglandin E1 (=0.1 ng/ml) inhibited platelet aggregation under synergic interaction with endothelial cells.

Alprostadil↗
PubMed2002

Immunohistochemical detection of interferon-gamma-producing cells in granuloma formation of sporotrichosis.

Granuloma formation is a common response in the skin infection of sporotrichosis. The involvement of interferon-gamma (IFN-gamma) and inducible nitric oxide synthase (iNOS) in the granuloma formation of sporotrichosis is less known. The aim of this study was to describe by immunohistochemistry the exact tissue distribution of IFN-gamma-positive cells and iNOS-positive cells in the granuloma of skin lesions from patients with sporotrichosis. Formalin-fixed paraffin-embedded skin biopsy sections from five patients were stained by immunohistochemical methods. Mixture of CD4-positive T cells and CD8-positive T cells were present in and around the granulomatous lesions. IFN-gamma-positive cells, like mononuclear lymphoid cells, were detected in the periphery of the granulomas in all samples. The pattern of IFN-gamma staining appeared to be a combination of intracellular staining in mononuclear lymphoid cells and extracellular deposition in the surrounding tissue. The majority of the epitheloid cells and multinucleated giant cells within the granuloma were identified by immunostaining for CD68. In contrast, no expression of immunoreactive iNOS was observed in those cells in all samples. These findings indicate that granulomas of sporotrichosis are coupled with Th1 response.

Antibodies, Monoclonal↗
PubMed2002

Experimental Helicobacter pylori gastric infection in miniature pigs.

An experimental Helicobacter pylori infection in miniature pigs was developed and investigated. Eighteen miniature pigs were inoculated with an H. pylori strain that has high virulence in mice at c. 5 x 10(10) cfu. H. pylori infection in miniature pigs was achieved by the administration of agar 1% in brucella broth with fetal bovine serum 10% just before inoculation. The bacterial colonisation and distribution were analysed by mapping of viable cell counts in the stomach in pigs of three different ages. The mapping assay was achieved on post-infection day 3 for the 5-day-old and 2-week-old pigs, and between days 41 and 43 for 3-month-old pigs. The highest cell counts were observed in 5-day-old pigs, which averaged 4.9 x 10(6) cfu/g of mucosa (n = 4). The bacteria were colonised mainly in the cardiac and fundus gland region in the 5-day-old and 2-week-old pigs, whereas the colonisation sites did not depend on the region in the 3-month-old pigs. Biopsy assay of the antral mucosa of a 3-month-old pig after H. pylori infection showed that this infection persisted for >22 months. Serum antibody against H. pylori was detected in the infected pigs but not in the uninfected animal. Immunostaining demonstrated the presence of bacteria on the epithelial surface of the infected pigs. A microscopic finding common to all the infected pigs, focal gastritis with infiltration of lymphocytes detected on the lesser curvature of the stomach, resembled the microscopic appearance in H. pylori-infected human patients. These results suggest that miniature pigs might be a suitable model for studying H. pylori infection.

Age Factors↗
PubMed2002

The effect of colonisation by Helicobacter pylori in Praomys (Mastomys) natalensis on the incidence of carcinoids.

An animal model of experimental gastric Helicobacter pylori infection has been developed in the Z strain of Praomys (Mastomys) natalensis; this animal has been reported to develop gastric carcinoids and adenocarcinoma spontaneously. In the present study, male and female Mastomys were killed at 1, 2, 4, 8 and 16 weeks after H. pylori inoculation. Colonisation of H. pylori was maintained in the stomachs of all animals for up to 16 weeks. H. pylori were mainly found in the antrum. Lymphoid infiltration appeared in the antral lamina propria and submucosa in all male and female animals from 4 to 16 weeks after inoculation. On microscopic examination after immunostaining for H. pylori, the organisms were detected in the antral mucus layer of the gastric epithelium. Serum immunoglobulin G specific for H. pylori could be detected 2 weeks after inoculation in female and 4 weeks after inoculation in male Mastomys, and persisted throughout the 16-week study period. At 18 months after inoculation, H. pylori positive rates for male and female Mastomys were 15 of 21 and 7 of 27, respectively. Carcinoids developed in 27 of 100 inoculated and in 49 of 100 uninoculated male, and in 5 of 100 inoculated and in 21 of 100 uninoculated female animals at 18 months after inoculation. Adenocarcinoma developed in 1 of 100 male Mastomys in both the inoculated and uninoculated groups, but in none of the female animals in either the inoculated or uninoculated groups. These results indicate that antrum-predominant colonisation by H. pylori caused the decrease in incidence of carcinoid formation in Mastomys.

Adenocarcinoma↗
PubMed2002

Reflex responses to insertion of the intubating laryngeal mask airway, intubation and removal of the ILMA.

We studied 21 patients (ASA 1 or 2) to investigate the skin vasomotor reflex (SVmR) and haemodynamic responses to insertion of an intubating laryngeal mask airway (ILMA), tracheal intubation using the ILMA and removal of the ILMA. Anaesthesia was induced with fentanyl, midazolam, vecuronium and nitrous oxide. A size 4 ILMA was inserted using the standard technique, and a silicone reinforced tracheal tube (7.5 mm, ID) was passed through it. After confirming successful intubation, the ILMA was removed using the stabilizing rod. The three procedures were performed at approximately one-minute intervals. Insertion of the ILMA, intubation and removal of the ILMA all significantly reduced the skin blood flow on the ring finger in all patients. The mean amplitudes of the SVmR were 0.46 (SD 0.29), 0.54 (0.32) and 0.68 (0.21) respectively. The magnitude of the SVmR and the haemodynamic changes induced by removal of the ILMA were significantly larger than those accompanying the other two procedures. Use of the ILMA for intubation and removal of the ILMA produces three stimuli and the removal of the ILMA produces the greatest response.

Adult↗
PubMed2002

[A review of Japanese literatures concerning surgery for lung cancer with idiopathic interstitial pneumonia].

OBJECTIVE: The aim of the present study is to investigate the perioperative management of acute exacerbation of idiopathic interstitial pneumonia (IIP) after pulmonary resection for lung cancer. METHODS: We reviewed 5 Japanese literatures published from 1992 through 1998. The present study included 50 lung cancer patients with IIP, of which 3 were our cases and 47 were reported cases. RESULTS: Within 30 days after operation, acute exacerbation of IIP occurred in 12 cases (24.0%). Preoperative profiles (gender, age, smoking status, respiratory function, pathologic stage) of the exacerbated cases did not differ from those of non-exacerbated cases. The mean intraoperative PaO2 of the exacerbated cases was significantly higher than that of non-exacerbated cases (224 +/- 45.6 Torr vs 120 +/- 41.2 Torr, p = 0.005). The rate of acute exacerbation increased with the extent of resection, that is 42.8% in pneumonectomy, 24.3% in lobectomy, and 0% in wedge resection although the difference was not significant. After acute exacerbation of IIP, all 12 cases were given high doses of steroids. However, 11 cases died due to the disease progression (mortality rate = 91.7%). CONCLUSION: In order to establish the perioperative management for prevention of acute exacerbation of IIP, multi-institutional study is warranted on the basis of the present results (intraoperative FiO2, administration schedule of steroids etc).

Aged↗
PubMed2002

Clinical significance of vascular endothelial growth factor expression in gastric cancer.

Vascular endothelial growth factor (VEGF) is an angiogenic factor in human cancer tissue. To clarify the clinical significance of this factor, we investigated the VEGF expression in early and advanced gastric cancer. This study included analysis of data on 243 patients with gastric cancer, including 118 in the early stage and 125 in the advanced stage. VEGF was immunohistochemically stained. Of 243 tumors, 102 (42%) were VEGF-positive. The VEGF-positive gastric cancers were larger, more invasive, and classified in the more advanced stage than VEGF negative ones. Patients with VEGF-positive cancers had significantly lower survival rates than did those with negative ones, both in early and advanced stages (P < 0.05, P < 0.01, respectively). The VEGF-positive isolates had more hematogenous metastases than VEGF-negative ones. Multivariate analysis revealed VEGF to be an independent prognostic factor and independent risk factor for liver metastasis. The VEGF expression in cancer cells can serve as a pertinent prognostic indicator both in early and advanced gastric cancer.

Adenocarcinoma↗
PubMed2001

Novel mutations in ABCA1 gene in Japanese patients with Tangier disease and familial high density lipoprotein deficiency with coronary heart disease.

Mutations in the ATP-binding cassette transporter 1 (ABCA1) gene have been recently identified as the molecular defect in Tangier disease (TD) and familial high density lipoprotein deficiency (FHA). We here report novel mutations in the ABCA1 gene in two sisters from a Japanese family with TD who have been described previously (S. Ohtaki, H. Nakagawa, N. Kida, H. Nakamura, K. Tsuda, S. Yokoyama, T. Yamamura, S. Tajima, A. Yamamoto, Atherosclerosis 49 (1983)) and a family with FHA. Both probands of TD and FHA developed coronary heart disease. Sequence analysis of the ABCA1 gene from the patients with TD revealed a homozygous G to A transition at nucleotide 3805 of the cDNA resulting in the substitution of Asp 1229 with Asn in exon 27, and a C to T at nucleotide 6181 resulting in the substitution of Arg 2021 with Trp in exon 47. Sequence analysis of the ABCA1 gene from the FHA patient revealed a homozygous 4 bp CGCC deletion from nucleotide 3787 to 3790 resulting in premature termination by frameshift at codon 1224. These mutations were confirmed by restriction digestion analysis, and were not found in 141 control subjects. Our findings indicate that mutations in the ABCA1 gene are associated with TD as well as FHA.

ATP Binding Cassette Transporter 1↗
PubMed2001

Heterogeneous distribution of P53 immunoreactivity in human lung adenocarcinoma correlates with MDM2 protein expression, rather than with P53 gene mutation.

Although the tumor suppressor p53 protein (P53) immunoreactivity and its gene (p53) mutation were reported to be significant prognostic indicators for human lung adenocarcinomas, little is known regarding the relationship between the heterogeneous distribution of P53 and its genetic status in each tumor focus and the clinicopathological significance. To determine how P53 is heterogeneously stabilized in patients, we compared P53 expression to both the p53 allelic mutation in exon 2 approximately 9 by polymerase chain reaction-single strand conformation polymorphism using microdissected DNA fractions, and the immunohistochemical MDM2 expression. Of the 48 positive to P53 in 118 lung adenocarcinomas examined, 10 with heterogeneous P53 expression were closely examined. The higher P53 expression foci in 7 of 10 cases were less differentiated, histologically in respective cases, and were frequently associated with fibrous stroma. Two had genetic mutations in exon 7 of the p53 gene in both the high and low P53 expression foci of cancer tissue indicating no apparent correlation between heterogeneous P53 expression and the occurrence of gene mutation. Immunohistochemical expression of MDM2 was significantly lower in high P53 expression areas (p < 0.05, the mean labeling indices of high and low P53 expression areas being 4.2 +/- 5.4% and 13.6 +/- 12.2%, respectively). In addition, among all the 118 cases examined, MDM2 expression was significantly suppressed in cases of p53 gene mutation, simultaneously with P53 overexpression, as compared with cases without both the p53 mutation and expression (p < 0.001). These findings suggest that the heterogeneous stabilization of P53 in human lung adenocarcinomas could be partly due to suppressed MDM2 expression. The overexpression of non-mutated P53 may afford a protective mechanism in human lung adenocarcinomas.

Adenocarcinoma↗
PubMed2001

Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients.

We recently reported the SART3 tumour-rejection antigen as possessing tumour epitopes capable of inducing HLA-class I-restricted cytotoxic T lymphocytes (CTLs). This study investigated expression of the SART3 antigen in breast cancer to explore an appropriate molecule for use in specific immunotherapy of breast cancer patients. The SART3 antigen was detected in all of the breast cancer cell lines tested, 30 of 40 (75%) breast cancer tissue samples, and 0 of 3 non-tumourous breast tissue samples. SART3 derived peptides at positions 109-118 and 315-323 induced HLA-A24 restricted CTLs that reacted to breast cancer cells from the peripheral blood mononuclear cells (PBMCs) of breast cancer patients. Therefore, the SART3 antigen and its peptides could be an appropriate molecule for use in specific immunotherapy of the majority of HLA-A24-positive breast cancer patients.

Adenocarcinoma↗
PubMed2001

Peyer's patches are required for oral tolerance to proteins.

To clarify the role of Peyer's patches in oral tolerance induction, BALB/c mice were treated in utero with lymphotoxin beta-receptor Ig fusion protein to generate mice lacking Peyer's patches. When these Peyer's patch-null mice were fed 25 mg of ovalbumin (OVA) before systemic immunization, OVA-specific IgG Ab responses in serum and spleen were seen, in marked contrast to low responses in OVA-fed normal mice. Further, high T-cell-proliferative- and delayed-type hypersensitivity responses were seen in Peyer's patch-null mice given oral OVA before systemic challenge. Higher levels of CD4(+) T-cell-derived IFN-gamma, IL-4, IL-5, and IL-10 syntheses were noted in Peyer's patch-null mice fed OVA, whereas OVA-fed normal mice had suppressed cytokine levels. In contrast, oral administration of trinitrobenzene sulfonic acid (TNBS) to Peyer's patch-null mice resulted in reduced TNBS-specific serum Abs and splenic B cell antitrinitrophenyl Ab-forming cell responses after skin painting with picryl chloride. Further, when delayed-type hypersensitivity and splenic T cell proliferative responses were examined, Peyer's patch-null mice fed TNBS were unresponsive to hapten. Peyer's patch-null mice fed trinitrophenyl-OVA failed to induce systemic unresponsiveness to hapten or protein. These findings show that organized Peyer's patches are required for oral tolerance to proteins, whereas haptens elicit systemic unresponsiveness via the intestinal epithelial cell barrier.

Administration, Oral↗
PubMed2001

Inhibitory effect of bovine milk lactoferrin on the interaction between a streptococcal surface protein antigen and human salivary agglutinin.

Human whole saliva induces aggregation of Streptococcus mutans cells via an interaction between a surface protein antigen (PAc) of the organism and salivary agglutinin. Bovine milk inhibits the saliva-induced aggregation of S. mutans. In this study, the milk component that possesses inhibitory activity against this aggregation was isolated and found to be lactoferrin. Surface plasmon resonance analysis indicated that bovine lactoferrin binds more strongly to salivary agglutinin, especially to high molecular mass glycoprotein, which is a component of the agglutinin, than to recombinant PAc. The binding of bovine lactoferrin to salivary agglutinin was thermostable, and the optimal pH for binding was 4.0. To identify the saliva-binding region of bovine lactoferrin, 11 truncated bovine lactoferrin fragments were constructed. A fragment corresponding to the C-terminal half of the lactoferrin molecule had a strong inhibitory effect on the saliva-induced aggregation of S. mutans, whereas a fragment corresponding to the N-terminal half had a weak inhibitory effect. Seven shorter fragments corresponding to lactoferrin residues 473-538 also showed a high ability to inhibit the aggregation of S. mutans. These results suggest that residues 473-538 of bovine lactoferrin are important in the inhibition of saliva-induced aggregation of S. mutans.

Agglutinins↗