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1.
J Tissue Eng Regen Med ; 11(9): 2516-2524, 2017 09.
Article in English | MEDLINE | ID: mdl-27061496

ABSTRACT

Cultured epithelial autograft (CEA) therapy has been used in clinical applications since the 1980s. However, there are some issues related to this treatment that still remain unsolved. Enzymatic treatment is typically used in the collection of epithelial keratinocyte sheets, but it tends to break the adhesion and basement membrane proteins. It is thought that the loss of proteins after enzymatic treatment is responsible for the poor survival of transplanted cell sheets. Our laboratory has developed a temperature-responsive culture dish that does not require enzymatic treatment to harvest the cells. In this study, we compare morphological and survival results from rat epithelial keratinocyte cell sheets harvested by temperature-reducing treatment (TT sheets) against cell sheets harvested by enzymatic (dispase) treatment (DT sheets). TT sheets preserve keratin structure in better conditions and express higher levels of collagen IV and laminin 5 than DT sheets. In order to evaluate cell sheet survival after transplantation, we created an in vivo transplant model. Keratinocyte sheets obtained from GFP-positive animals were transplanted into athymic rats. The survival rate 7 days after transplantation of TT sheet was higher than that of DT sheets. Collagen IV and Laminin 5 expression was observed in the TT sheet transplantation group. These results indicate that the remaining basement membrane proteins are important for initial attachment and cell survival. We believe that the cell sheet harvesting method using temperature-responsive culture dishes provides superior cell survival and can solve one of the roadblocks in CEA therapy. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Basement Membrane/metabolism , Cell Separation/methods , Extracellular Matrix Proteins/metabolism , Keratinocytes , Skin , Animals , Cell Survival , Keratinocytes/metabolism , Keratinocytes/transplantation , Rats , Rats, Nude , Rats, Sprague-Dawley , Rats, Transgenic , Skin/injuries , Skin/metabolism , Skin/pathology
2.
Ann R Coll Surg Engl ; 99(4): 332-336, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27659357

ABSTRACT

Introduction Radiotherapy is not commonly used for the treatment of gastric cancer in Japan, where surgery is the standard local treatment. We report the results of chemoradiotherapy in patients with advanced or recurrent gastric cancer which was deemed difficult to treat surgically. Methods Twenty-one patients with gastric cancer (including sixteen with advanced/recurrent gastric cancer and five with poor general condition) underwent chemo-radiotherapy, for whom the therapeutic efficacy, toxicity and survival period were analysed. Results The tumour response to chemoradiotherapy was categorised as complete, partial, stable or progressive in 5, 9, 3, and 4 patients, respectively, with an overall response rate of 67%. No serious complications such as gastrointestinal perforation or bleeding occurred, and no cardiac, hepatic or renal dysfunction developed during the follow-up period. The mean survival time was 19.8 months (range, 3-51 months). One patient died of another disease, 18 died of primary cancer and the cause of death was unknown in 2 patients. Conclusions Chemoradiotherapy appears to be an effective treatment for localised gastric cancer without distant metastases, but further studies are needed to determine the indications for chemoradiotherapy and late adverse effects, as well as the chemotherapy regimens to be used.


Subject(s)
Adenocarcinoma/therapy , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Neoplasm Recurrence, Local/therapy , Oxonic Acid/therapeutic use , Radiotherapy, Conformal/methods , Stomach Neoplasms/therapy , Tegafur/therapeutic use , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Cisplatin/administration & dosage , Drug Combinations , Female , Fluorouracil/administration & dosage , Humans , Japan , Male , Retrospective Studies , Stomach Neoplasms/pathology , Survival Rate
3.
J Oral Rehabil ; 38(6): 423-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20958342

ABSTRACT

To determine the sources of lip closing pressure (P(LC) ) generation during passive spoon feeding, we used a fine pressure transducer glued into a wooden spoon, as well as electromyography (EMG) of the upper and lower lips and the submental muscle complex, in normal adult volunteers (average age 24·5 years). An assistant fed a seated subject 0·6 mL of yogurt and then withdrew the spoon from the subject's closed mouth. The spoon was held at an angle of 0° (i.e. in the naso-auricular plane) during serving and at either 0° or 60° during withdrawal. We detected simultaneous increases in P(LC) and in EMG activity in the lips and the submental muscle complex. The maximum P(LC) was significantly higher at 60° [65 ± 11 g cm(-2) (mean ± s.e.m)] than at 0° (42 ± 8 g cm(-2)). The former was correlated with the maximum EMG amplitude, which was analysed by using the mean of the root-mean-square EMG and presented as a percentage of the maximum EMG obtained in the lower lip region and the submental muscle complex during subsequent swallowing in each subject. In conclusion, in healthy adult subjects, perioral muscles of the lower lip region and the submental muscle complex participate in P(LC) generation, particularly at a steep spoon withdrawal angle. The results suggest that a steep withdrawal angle not only increases P(LC) but also promotes these muscles' activities in passive spoon feeding.


Subject(s)
Cooking and Eating Utensils , Enteral Nutrition/instrumentation , Facial Muscles/physiology , Lip/physiology , Neck Muscles/physiology , Adolescent , Adult , Dental Stress Analysis , Electromyography , Female , Humans , Male , Pressure , Transducers, Pressure , Young Adult
4.
Gut ; 54(3): 330-5, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15710978

ABSTRACT

BACKGROUND: Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process. AIMS: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription. SUBJECTS: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis. METHODS: We identified the IL-8 -251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay. RESULTS: IL-8 -251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 -251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in -251A carriers than in T/T carriers. In the in vitro assay, IL-8 -251A showed enhanced promoter activity in response to IL-1beta or tumour necrosis factor alpha. CONCLUSIONS: The IL-8 -251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.


Subject(s)
Helicobacter Infections/complications , Helicobacter pylori , Interleukin-8/genetics , Polymorphism, Genetic , Stomach Diseases/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Asian People/genetics , Duodenal Ulcer/microbiology , Female , Gastritis/microbiology , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Promoter Regions, Genetic , Stomach Neoplasms/microbiology , Stomach Ulcer/microbiology
5.
Scand J Gastroenterol ; 39(8): 709-16, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15513353

ABSTRACT

BACKGROUND: In Japan, where the incidence of gastric cancer is high, Helicobacter pylori infection could affect gastric acid secretion differently from that in Western countries. The aim of this study was to investigate the relationship between H. pylori infection, acid secretion, aging, and gender in normal Japanese subjects. METHODS: The study comprised 193 Japanese subjects who had undergone routine endoscopy. Gastrin-stimulated acid output was performed during the routine endoscopic examination using the endoscopic method of gastric acid secretory testing (EGT: endoscopic gastrin test), which has been reported previously. H. pylori status was determined by histology, rapid urease test, and serology. RESULTS: Mean EGT values were 3.9 +/- 1.5 mEq/10 min in H. pylori-negative men, 1.6 +/- 2.5 in H. pylori-positive men, 2.2 +/- 0.9 in H. pylori-negative women, and 1.5 +/- 1.2 in H. pylori-positive women. Although acid secretion was lower in H. pylori-positive subjects compared with H. pylori-negative subjects in both men and women, the decrease was more marked in men with H. pylori infection. Multiple linear regression analysis showed that aging is positively associated with gastric acid secretion in the H. pylori-negative subjects, whereas a negative association was found between them in the H. pylori-positive subjects. CONCLUSIONS: In Japanese subjects, aging affects gastric acid secretion differently depending on the status of H. pylori infection. H. pylori infection showed a stronger inhibitory effect on the acid secretion in men than in women. This gender-related difference in the susceptibility of acid secretion to H. pylori infection may explain the higher rates of gastric cancer in men in Japan.


Subject(s)
Aging/physiology , Gastric Acid/metabolism , Helicobacter Infections/physiopathology , Helicobacter pylori , Sex Characteristics , Adult , Aged , Antibodies, Bacterial/blood , Endoscopy, Gastrointestinal , Female , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastrins , Gastritis/microbiology , Gastritis/physiopathology , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter Infections/pathology , Helicobacter pylori/immunology , Helicobacter pylori/isolation & purification , Humans , Japan , Male , Middle Aged , Reference Values , Stomach Neoplasms/virology
6.
Eye (Lond) ; 18(5): 474-7, 2004 May.
Article in English | MEDLINE | ID: mdl-15131677

ABSTRACT

AIMS: To compare the newly devised fluorescein angiography (FA) - guided indocyanine green angiography (ICGA) with conventional ICGA for detecting feeder vessels in subfoveal choroidal neovascularization (CNV). METHODS: The detection of feeder vessels was attempted in 86 AMD patients with subfoveal CNV: 44 (age 70.4+/-4.5 years) underwent conventional ICGA (control group) and 42 (age 70.9+/-4.0 years) underwent an FA-guided ICGA (FA-guided group) using a double-detector scanning laser ophthalmoscope (SLO). In the control group, indocyanine green (ICG) was injected simultaneously with fluorescein. The patients were instructed to gaze forward localizing the fovea at the centre. In the FA-guided group, fluorescein sodium was injected a few minutes prior to ICG, and the patients were instructed to fixate in the appropriate direction by referring to the ongoing FA on the monitoring screen. In both groups, a 20 degrees visual angle was used to capture good images of feeder vessels in ICGA and, in case ICGA missed the first images of the entire CNV filling, an additional injection of ICG was given in the late phase to record the choroidal filling again. The overall detection rate, single-injection detection rate, double-injection rate and examination time were analysed using Fisher's direct exact probability test or Mann-Whitney's U-test. RESULTS: There was no significant difference in the overall detection of feeder vessels between the two groups (50% in the control group and 52.3% in the FA-guided group; P=0.49 with Fisher's direct exact probability test). However, in the FA-guided group, the single injection detection rate was significantly higher (45.1 and 15.9%, respectively; P<0.001 with Fisher's direct exact probability test); significantly less double injections were required (7.1 and 50%, respectively; P=0.003 with Fisher's direct exact probability test); and significantly shorter examination times were needed (9.6+/-3.7 and 14.1+/-6.8 min, respectively; P=0.02 with Mann-Whitney's U-test). CONCLUSION: FA-guided ICGA is effective for detecting feeder vessels of subfoveal CNV, minimizing the amount of ICG injected and the examination time compared to conventional ICGA.


Subject(s)
Choroidal Neovascularization/pathology , Coloring Agents , Fluorescein Angiography/methods , Indocyanine Green , Aged , Choroid/blood supply , Coloring Agents/administration & dosage , Fovea Centralis , Humans , Indocyanine Green/administration & dosage , Injections , Time Factors
7.
Aliment Pharmacol Ther ; 19(11): 1181-8, 2004 Jun 01.
Article in English | MEDLINE | ID: mdl-15153171

ABSTRACT

BACKGROUND: Although profound hypochlorhydria is considered to be an important risk factor for development of gastric cancer, long-term effect of Helicobacter pylori eradication on its reversibility remains uncertain. AIM: To clarify the change in acid secretion after eradication in a long-term follow-up over 5 years in patients with profound hypochlorhydria. METHODS: Twenty-three H. pylori-positive patients with hypochlorhydria (<0.6 mmol/10 min) were enrolled prospectively. Assessment of gastrin-stimulated acid output and histologic evaluation of biopsy specimens were performed prior to, and 1, 7 months after eradication. Subsequently, gastric acid secretion was assessed for long-term period over 5 years after eradication in 12 patients. RESULTS: Gastric acid secretion was reversed to normal range in nine of 23 patients (39%) at 7 months after eradication. In the long-term follow-up, gradual and significant recovery in gastric acid secretion was observed up to 2 years post-therapy. However, there was no additional increase during the last 3 years of 5-year follow-up period, leaving the acid secretory levels subnormal in the majority of the patients. CONCLUSIONS: This long-term follow-up study suggests that the pathologic process has already progressed to an irreversible stage in the majority of H. pylori-positive patients with marked body atrophy and profound hypochlorhydria.


Subject(s)
Achlorhydria/complications , Gastric Acid/metabolism , Helicobacter Infections/drug therapy , Helicobacter pylori , Achlorhydria/metabolism , Aged , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Clarithromycin/therapeutic use , Drug Therapy, Combination , Female , Follow-Up Studies , Helicobacter Infections/complications , Humans , Male , Metronidazole/therapeutic use , Middle Aged , Omeprazole/therapeutic use , Treatment Outcome
8.
Aliment Pharmacol Ther ; 16 Suppl 2: 187-90, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11966540

ABSTRACT

BACKGROUND: Helicobacter pylori infection is a major cause of the progress of gastric glandular atrophy, a high-risk background factor in the development of gastric cancer. Regression of gastric atrophy is critical to prevention of cancer by H. pylori eradication treatment. However, it is controversial whether gastric atrophy regresses after H. pylori eradication. AIM: To determine the most sensitive and appropriate biopsy site for evaluation of regression of atrophy after treatment. SUBJECTS AND METHODS: Thirty-eight patients who showed regression of gastric atrophy in histology after treatment were investigated. Four biopsy specimens from the lesser and greater curvatures in the antrum and corpus were evaluated before and after treatment according to the Updated Sydney System. RESULTS: Regression of atrophy after treatment was seen in 30 of 38 biopsy specimens from the lesser curvature of the corpus (79%), and this site was most sensitive. Odds ratio of this site to the others was 8.28. Regression of atrophy in this site was observed at 12.2 months in the younger patients and 15.9 months in the elder patients. CONCLUSION: Biopsy sampling from the lesser curvature of the corpus is the most sensitive and appropriate for evaluation of regression of gastric atrophy after H. pylori eradication treatment.


Subject(s)
Gastric Mucosa/pathology , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/isolation & purification , Adult , Aged , Atrophy/drug therapy , Biopsy , Female , Gastric Mucosa/drug effects , Helicobacter Infections/drug therapy , Humans , Male , Middle Aged
9.
Int J Urol ; 8(9): 483-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11683967

ABSTRACT

BACKGROUND: To elucidate the most efficient topical therapy for carcinoma in situ of the bladder, the efficacy of intravesical mitomycin C plus doxorubicin therapy was compared with bacillus Calmette-Guerin (BCG) therapy. The clinical behavior of the tumor was analysed according to the histological grade. METHODS: Forty-two patients with carcinoma in situ of the bladder were randomized to intravesical BCG (21 patients) or mitomycin C plus doxorubicin sequential therapy (21 patients) as first line treatment. The non-responders underwent the subsequent instillation of the other intravesical therapy alternately. Of the patients, 27 had grade 2 and 15 had grade 3 cancer. RESULTS: Both topical therapies were equally effective with initial response rates of 86% (18/21) for BCG and 81% (17/21) for mitomycin C plus doxorubicin, irrespective of the tumor grade. Of seven initial non-responders, five patients achieved a complete response by subsequent instillation, resulting in a total response rate of 95%. After a mean follow-up of 47 months, five patients (12%) developed disease progression. The progression rates were not different between the topical therapies, but were significantly higher in grade 3 than in grade 2 cases. CONCLUSION: It appears likely that mitomycin C plus doxorubicin instillation has an equivalent efficacy to BCG as the initial therapy of carcinoma in situ and the combination of them would be the most efficient treatment for the disease. Moreover, histological grading would be clinically useful in defining the tumor characteristics and behavior of carcinoma in situ of the bladder.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , BCG Vaccine/therapeutic use , Carcinoma in Situ/drug therapy , Carcinoma, Transitional Cell/drug therapy , Doxorubicin/administration & dosage , Mitomycin/administration & dosage , Urinary Bladder Neoplasms/drug therapy , Aged , Carcinoma in Situ/mortality , Carcinoma in Situ/pathology , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
10.
J Immunol ; 167(8): 4504-10, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11591777

ABSTRACT

Mannose-binding lectin (MBL) is a C-type lectin involved in the first line of host defense against pathogens and it requires MBL-associated serine protease (MASP) for activation of the complement lectin pathway. To elucidate the origin and evolution of MBL, MBL-like lectin was isolated from the plasma of a urochordate, the solitary ascidian Halocynthia roretzi, using affinity chromatography on a yeast mannan-Sepharose. SDS-PAGE of the eluted proteins revealed a major band of approximately 36 kDa (p36). p36 cDNA was cloned from an ascidian hepatopancreas cDNA library. Sequence analysis revealed that the carboxy-terminal half of the ascidian lectin contains a carbohydrate recognition domain (CRD) that is homologous to C-type lectin, but it lacks a collagen-like domain that is present in mammalian MBLs. Purified p36 binds specifically to glucose but not to mannose or N-acetylglucosamine, and it was designated glucose-binding lectin (GBL). The two ascidian MASPs associated with GBL activate ascidian C3, which had been reported to act as an opsonin. The removal of GBL-MASPs complex from ascidian plasma using Ab against GBL inhibits C3-dependent phagocytosis. These observations strongly suggest that GBL acts as a recognition molecule and that the primitive complement system, consisting of the lectin-proteases complex and C3, played a major role in innate immunity before the evolution of an adaptive immune system in vertebrates.


Subject(s)
Carrier Proteins/metabolism , Complement Activation , Complement C3/metabolism , Lectins/metabolism , Urochordata/immunology , Amino Acid Sequence , Animals , Carrier Proteins/blood , Collectins , Digestive System , Evolution, Molecular , Gene Library , Lectins/blood , Lectins/isolation & purification , Mannose-Binding Protein-Associated Serine Proteases , Molecular Sequence Data , Protein Binding , Sequence Homology, Amino Acid , Serine Endopeptidases/metabolism
11.
Clin Sci (Lond) ; 101(5): 485-91, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11672453

ABSTRACT

The 17 beta-hydroxysteroid dehydrogenases (17 beta HSDs) play an important role in the regulation of intracellular levels of biologically active sex steroid hormones in various human tissues. To date, eight distinctive 17 beta HSD enzymes have been cloned and characterized in humans. Among these isoenzymes, 17 beta HSD type 2 (17 beta HSD2) catalyses the conversion of testosterone into androstenedione and/or oestradiol into oestrone in various tissues, and it has thus been suggested to be involved in the biological inactivation of these sex steroids. The human gastrointestinal tract and liver are considered as the principle sites of inactivation and metabolism of various forms of orally administered sex steroids. We therefore examined 17 beta HSD2 expression and activity in human adult non-pathological gastrointestinal tract in order to clarify further the biological significance of this enzyme. A total of 80 specimens (40 from males and 40 from females) of normal oesophageal, stomach, duodenal, ileal, colonic and rectal tissues were examined for immunohistochemistry. Altogether, 17 tissue specimens were used for enzyme assay, and eight for RNA analysis. 17 beta HSD2 activity was detected in the stomach, duodenum, ileum, colon and rectum. 17 beta HSD2 mRNA was most abundant in the small intestine. 17 beta HSD2 immunoreactivity was localized almost exclusively to the absorptive epithelium, which may be involved in the inactivation of excessive endogenous and exogenous active sex steroids. Results from the present study thus suggest that the human gastrointestinal tract is an important sex steroid metabolizing organ in humans.


Subject(s)
17-Hydroxysteroid Dehydrogenases/metabolism , Gastric Mucosa/enzymology , Intestinal Mucosa/enzymology , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/metabolism , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Oligonucleotide Probes , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Spectrophotometry
12.
Gut ; 49(3): 330-4, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11511552

ABSTRACT

BACKGROUND: Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly. AIMS: We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects. SUBJECTS: A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis. METHODS: The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test. RESULTS: H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. Among H pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis. CONCLUSION: In Japan, erosive reflux oesophagitis occurs most often in the absence of H pylori infection and gastric hyposecretion. Even in the presence of H pylori infection, reflux oesophagitis is more likely to develop in patients without gastric hyposecretion. H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.


Subject(s)
Esophagitis, Peptic/complications , Gastric Acid/metabolism , Helicobacter Infections/complications , Helicobacter pylori , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Esophagitis, Peptic/metabolism , Female , Helicobacter Infections/metabolism , Humans , Male , Middle Aged , Statistics, Nonparametric
13.
J Immunol ; 166(10): 6444-51, 2001 May 15.
Article in English | MEDLINE | ID: mdl-11342671

ABSTRACT

Complement activation and tissue deposition of complement fragments occur during disease progression in lupus nephritis. Genetic deficiency of some complement components (e.g., Factor B) and infusion of complement inhibitors (e.g., Crry, anti-C5 Ab) protect against inflammatory renal disease. Paradoxically, genetic deficiencies of early components of the classical complement pathway (e.g., C1q, C4, and C2) are associated with an increased incidence of lupus in humans and lupus-like disease in murine knockout strains. Complement protein C3 is the converging point for activation of all three complement pathways and thus plays a critical role in biologic processes mediated by complement activation. To define the role of C3 in lupus nephritis, mice rendered C3 deficient by targeted deletion were backcrossed for eight generations to MRL/lpr mice, a mouse strain that spontaneously develops lupus-like disease. We derived homozygous knockout (C3(-/-)), heterozygous (C3(+/-)), and C3 wild-type (C3(+/+)) MRL/lpr mice. Serum levels of autoantibodies and circulating immune complexes were similar among the three groups. However, there was earlier and significantly greater albuminuria in the C3(-/-) mice compared with the other two groups. Glomerular IgG deposition was also significantly greater in the C3(-/-) mice than in the other two groups, although overall pathologic renal scores were similar. These results indicate that C3 and/or activation of C3 is not required for full expression of immune complex renal disease in MRL/lpr mice and may in fact play a beneficial role via clearance of immune complexes.


Subject(s)
Complement C3/physiology , Glomerulonephritis/immunology , Immune Complex Diseases/immunology , Albuminuria/urine , Animals , Antigen-Antibody Complex/blood , Autoantibodies/blood , Autoimmune Diseases/genetics , Autoimmune Diseases/mortality , Autoimmune Diseases/pathology , Complement C3/deficiency , Complement C3/genetics , Cryoglobulins/metabolism , Fluorescent Antibody Technique, Indirect , Genetic Carrier Screening , Genotype , Glomerulonephritis/genetics , Glomerulonephritis/mortality , Glomerulonephritis/pathology , Immune Complex Diseases/genetics , Immune Complex Diseases/mortality , Immune Complex Diseases/pathology , Immunoglobulin G/blood , Immunoglobulin Isotypes/blood , Kidney/chemistry , Kidney/immunology , Kidney/pathology , Mice , Mice, Inbred C57BL , Mice, Inbred MRL lpr , Mice, Knockout , Phenotype
14.
Aliment Pharmacol Ther ; 15(6): 813-20, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11380319

ABSTRACT

BACKGROUND: The role of acid secretion in reflux oesophagitis which may develop after H. pylori eradication is not well known. AIM: To investigate the participation of altered gastric acid secretion and the presence of hiatal hernia in the development of reflux oesophagitis after eradication therapy for H. pylori. SUBJECTS AND METHODS: A total of 105 patients with H. pylori infection, but without reflux oesophagitis at the time of eradication therapy, were followed prospectively for 7 months after the clearance of this microorganism. Gastric acid secretion was assessed by endoscopic gastrin test, and the presence of hiatal hernia by endoscopy. RESULTS: Reflux oesophagitis developed in 11 out of 105 (10.5%) patients when examined at 7 months after the eradication therapy. The incidence was correlated significantly with the increase in gastric acid secretion after the eradication of H. pylori, and was significantly higher in the patients with hiatal hernia (20%) than in those without it (0%). CONCLUSIONS: Increased acid secretion after H. pylori eradication is an important risk factor of reflux oesophagitis, especially in patients with hiatal hernia.


Subject(s)
Esophagitis/etiology , Gastric Acid/metabolism , Gastroesophageal Reflux/complications , Helicobacter Infections/drug therapy , Adult , Esophagitis/epidemiology , Esophagitis/pathology , Female , Gastroesophageal Reflux/etiology , Helicobacter Infections/complications , Helicobacter pylori/isolation & purification , Helicobacter pylori/pathogenicity , Hernia, Hiatal/complications , Humans , Incidence , Male , Middle Aged , Prospective Studies , Risk Factors
15.
Enzyme Microb Technol ; 28(6): 515-521, 2001 Apr 05.
Article in English | MEDLINE | ID: mdl-11267646

ABSTRACT

Immobilization of cycloisomaltooligosaccharide glucanotransferase (CITase) and its application in the production of cycloisomaltooligosaccharides (CIs) from dextran were studied. Among various carrier materials examined, the enzyme adsorbed physically on Chitopearl BCW-3505 showed the highest activity (1.75 U/ml carrier). The activity remaining was 35%. The maximum CI yield in batch reactions at 0.2, 2 and 10% dextran was 28, 24 and 12%, respectively. The maximum CI yield at 2% dextran (24%) was slightly less than that with the free enzyme under the same conditions (26%). The concentration of linear oligosaccharides, the byproducts in the reaction mixture, was greater with the immobilized CITase than the free enzyme. The immobilized CITase was less thermostable than the free enzyme by about 10 degrees C. The pattern of influence of Ca(2+) concentration on the thermostability differed between the free and immobilized CITase. A Ca(2+) concentration of 50-100 mM was optimum for the thermostability of the immobilized CITase, 10-50 mM for the free enzyme. CIs were produced continuously by a column system packed with the immobilized enzyme at 40 degrees C with a space velocity (SV) of 6 h(-1). The three quarters life time was 4 weeks. We think that relatively long life time at fast SV was accomplished and CI production cost by this method should be lower than the batch reaction. This is the first report on immobilization of CITase.

16.
Int J Urol ; 8(3): 137-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11260341

ABSTRACT

An extremely rare case of solitary fibrous tumor of the prostate is presented. The patient underwent a radical retropubic prostatectomy and has remained well with no evidence of recurrence during the last 18 months. This is the fifth reported case of such a lesion arising in the prostate.


Subject(s)
Neoplasms, Fibrous Tissue/pathology , Prostatic Neoplasms/pathology , Adult , Humans , Male
17.
Appl Microbiol Biotechnol ; 57(4): 534-40, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11762601

ABSTRACT

A mutant of Corynebacterim glutamicum ('Brevibacterium flayum') ATCC14067 with a reduced H+-ATPase activity, F172-8, was obtained as a spontaneous neomycin-resistant mutant. The ATPase activity of strain F172-8 was reduced to about 25% of that of the parental strain. Strain F172-8 was cultured in a glutamic-acid fermentation medium containing 100 g/l of glucose using ajar fermentor. It was found that glucose consumption per cell during the exponential phase was higher by 70% in the mutant than in the parent. The respiration rate per cell of the mutant also increased to twice as much as that of the parent. However, the growth rate of the mutant was lower than that of the parent. Under those conditions, the parent produced more than 40 g/l glutamic acid, while the mutant hardly produced any glutamic acid. Instead the mutant produced 24.6 g/l lactic acid as the main metabolite of glucose. Remarkably, the accumulation of pyruvate and pyruvate-family amino acids, i.e., alanine and valine, was detected in the mutant. On the other hand, the parent accumulated alpha-ketoglutaric acid and a glutamate-family amino acid, proline, as major by-products. It was concluded that the decrease in the H+-ATPase activity caused the above-mentioned metabolic changes in strain F172-8, because a revertant of strain F172-8, R2-1, with a H+-ATPase activity of 70% of that of strain ATCC14067, showed a fermentation profile similar to that of the parent. Sequence analyses of the atp operon genes of these strains identified one point mutation in the gamma subunit in strain F172-8.


Subject(s)
Corynebacterium/metabolism , Glucose/metabolism , Glutamic Acid/metabolism , Proton-Translocating ATPases/physiology , Dicyclohexylcarbodiimide/pharmacology , Ethanol/pharmacology , Operon
18.
Pediatr Neurol ; 23(2): 177-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11020647

ABSTRACT

A 6-year-old female patient with acute disseminated encephalomyelitis associated with poliomyelitis vaccine virus is reported. She had a history of high fever, headache, and gait disturbance. Neurologic examination confirmed spastic triparesis, urinary incontinence, diminution of tactile sensation, and vision deterioration. Hemography, serum laboratory findings, and urinalysis were normal. The cerebrospinal fluid was clear, with normal pressure, 9 leukocytes/mm(3), and 27 mg/dL protein, but the myelin basic protein was elevated to 10.7 ng/mL. T(2)-weighted magnetic resonance imaging disclosed multifocal high-intensity lesions of the spinal cord. The serum polio virus type 2 antibody titer was raised in the acute phase, and polio vaccine virus type 2 was detected in viral cultures of the cerebrospinal fluid and pharynx swab and had undergone an A-G neurovirulence mutation at nucleotide 481. Finally, she had human leukocyte antigen (HLA)-Cw3 and HLA-DR2, to which multiple sclerosis is related in Japan. Thus the cause of ADEM may have been related to her HLA type.


Subject(s)
Encephalomyelitis, Acute Disseminated/virology , Poliovirus Vaccine, Oral/adverse effects , Poliovirus/immunology , Child , Encephalomyelitis, Acute Disseminated/blood , Encephalomyelitis, Acute Disseminated/diagnosis , Female , HLA-DR2 Antigen/blood , Humans , Poliovirus Vaccine, Oral/cerebrospinal fluid
19.
Breast Cancer ; 7(2): 142-8, 2000.
Article in English | MEDLINE | ID: mdl-11029786

ABSTRACT

BACKGROUND: The temperature of the skin remains elevated long after breast-conserving treatment with irradiation, perhaps because evaporative cooling is impaired. We investigated physiological changes of the irradiated skin and reevaluated the radiosensitivity of sweat glands on a functional basis to determine whether severe complications can be predicted. METHODS: Breast and axillary skin temperatures were measured with thermography and sweat production in response to local thermal stimuli was measured on the basis of changes in electrical skin resistance with a bridge circuit in 45 women before, during, and after breast irradiation for breast cancer. RESULTS: Breast and axillary skin temperatures were significantly increased after irradiation. In response to cutaneous thermal stimuli, the electric skin resistance of nonirradiated areas decreased significantly because of sweating, but that of irradiated areas was unchanged. CONCLUSION: Impairment of sweating may play an important role in skin damage after irradiation. Although glandular tissue is not usually radiosensitive, the results of our functional assessment suggest that sweat glands are more radiosensitive than expected.


Subject(s)
Breast Neoplasms/radiotherapy , Skin Temperature/radiation effects , Sweating/radiation effects , Adult , Aged , Axilla , Breast Neoplasms/surgery , Electric Impedance , Female , Humans , Mastectomy, Segmental , Middle Aged , Radiotherapy/adverse effects , Thermography
20.
J Pathol ; 192(2): 243-50, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11004702

ABSTRACT

Helicobacter pylori (HP)-infected gastric mucosa displays a conspicuous infiltration of mononuclear cells as well as neutrophils. RANTES is a potent chemoattractant peptide for memory T lymphocytes and eosinophils. RANTES protein concentration and the numbers of RANTES-, CD45RO-, and major basic protein (MBP)-positive cells were therefore evaluated in the gastric mucosa from 51 patients with HP-positive chronic gastritis before and after HP eradication and from 22 HP-negative healthy volunteers. RANTES protein concentration was significantly elevated in HP-positive cases and remained high after HP eradication. The numbers of RANTES-, CD45RO-, and MBP-positive cells were significantly increased in HP-positive cases and were well correlated with RANTES protein levels. All tended to decrease after HP eradication, but did not reach the level of HP-negative cases, even at 24 months after HP eradication. It was concluded that persistent expression and secretion of RANTES were closely related to residual infiltration of memory T lymphocytes and eosinophils, for a prolonged period after HP eradication. This seems to be an important mechanism of prolonged gastric mucosal immune response against HP infection, even after HP eradication, and of persistent mucosal damage and atrophy.


Subject(s)
Chemokine CCL5/physiology , Eosinophils/physiology , Helicobacter Infections/immunology , Helicobacter pylori , Neutrophil Infiltration/physiology , T-Lymphocytes/physiology , Adult , Case-Control Studies , Chemokine CCL5/analysis , Enzyme-Linked Immunosorbent Assay , Female , Gastric Mucosa/immunology , Humans , Immunity, Mucosal/physiology , Immunohistochemistry , Leukocyte Common Antigens/physiology , Male
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