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Biomedical subjects

R Kodama

Publications and source records attributed to R Kodama.

At least 19 recordsLinked to original sources
PubMed1997

Helicobacter pylori infection accelerates human gastric mucosal cell proliferation.

Helicobacter pylori causes chronic atrophic gastritis and intestinal type gastric cancer arises against a background of atrophic gastritis. Increased proliferation of epithelial cells is an important indicator of increased risk for gastric adenocarcinoma. We investigated gastric mucosal cell proliferation in H. pylori-associated gastritis and the effect of eradication therapy on this proliferation in 45 patients endoscopically diagnosed (31 with persistent eradication and 14 in whom H. pylori) recurred. H. pylori status was determined by culture and histology in biopsied specimens from the gastric antrum and corpus. Eradication of the infection was defined as reversal to negative on both tests. In vitro Ki-67 immunostaining of endoscopic biopsy specimens was used to measure mucosal cell proliferation in H. pylori-associated gastritis before and after therapy. The proliferative zone was defined as the distance of Ki-67-positive gastric epithelial cells between the highest and the lowest cells. In patients in whom H. pylori was eradicated, cell proliferation in both the antral and corpus mucosa had decreased 4 weeks after completion of the eradication therapy (P < 0.01, P < 0.001), and 6 months later, it had markedly decreased (P < 0.05, P < 0.05) and returned to normal. In patients in whom H. pylori recurred, only antral epithelial cell proliferation was reduced 4 weeks after eradication therapy, but when H. pylori recurred, determined by culture and histology, cell proliferation level was the same as that before eradication. These results suggest that H. pylori infection accelerates cell proliferation in gastric mucosa and may play a causal role in the chain of events leading to gastric carcinoma.

Amoxicillin↗
PubMed1996

Helicobacter pylori infection delays the healing of acetic acid-induced gastric ulcer in Japanese monkeys.

To clarify the relationship between Helicobacter pylori and the healing of gastric ulcers, we investigated the healing of acetic acid-induced gastric ulcers in the antral mucosa of Japanese monkeys (n = 5) infected with H. pylori and in control monkeys without H. pylori infection (n = 6). Using H. pylori-infected Japanese monkeys as an experimental model, gastric ulcers were induced endoscopically with acetic acid. Healing of ulcers and factors that influenced healing were studied. Continuous colonization with H. pylori was confirmed in the infected group throughout the observation period; no H. pylori were isolated from the gastric mucosa of the control group. White scarring was not observed in any infected monkeys 4 weeks after ulcer formation, but was observed in one (20%) of five monkeys at 6 weeks and in all five monkeys eight weeks after ulcer formation. In the control group, white scarring was observed in one (16.7%) of six monkeys at 4 weeks and in six monkeys at 6 (P < 0.01 vs infected group) and 8 weeks. The ammonia concentration of the gastric secretions and the grade of inflammation were significantly increased in the H. pylori-infected group compared with the control group (P < 0.01 and P < 0.001, respectively). The volume of intracellular PAS-positive substance was decreased (P < 0.025-0.01) at the ulcer margin in the infected group compared with the ulcer margin in the control group. The proliferation of gastric epithelial cells was markedly accelerated at the ulcer margin in the infected group compared with the ulcer margin in control group (P < 0.025-0.01). Our results strongly suggest that H. pylori infection delays the healing of gastric ulcers.

Acetic Acid↗
PubMed1996

Sofalcone for treatment of Helicobacter pylori infection.

It is difficult to regard sofalcone as a single drug for the treatment of Helicobacter pylori infection. However, sofalcone exerts multiple effects against H. pylori: it has antibacterial activity, induces morphological changes, inhibits adhesion to gastric mucin and inhibits lipolytic activity. The safety profile of sofalcone even on long-term administration is well established. Therefore, it may be possible to establish a new triple therapy for H. pylori infection using sofalcone combined with antibacterial drugs and proton pump inhibitors.

Anti-Bacterial Agents↗
PubMed1996

Atopic dermatitis successfully treated by eradication of Helicobacter pylori.

A relationship between allergic diseases and Helicobacter pylori infection has recently been noted. We report a case of atopic dermatitis and H. pylori infection in a 14-year-old girl. She had had widespread diffuse skin erythema with erosions and pigmentation since the age of 3 years. Endoscopically, there was chronic antral gastritis with H. pylori infection and histological eosinophilic infiltration. A high titer of H. pylori-specific IgG was present in serum. She was treated with a proton pump inhibitor (lansoprazole 60 mg), an antibiotic (clarithromycin 800 mg), and plaunotol (a mucosal protective agent, 480 mg) for 2 weeks to eliminate the infection. After 10 days of treatment, erythema and itching were more widespread and vesicle formation was seen on the foot. Generalized skin lesions abated a few days later. After eradication of the bacterium by the treatment, eosinophils decreased from 38.8% to 19.0%, and the clinical signs of atopic dermatitis almost disappeared. Serum gastrin level and the pepsinogen I/II ratio were normalized and histological findings of gastric mucosa showed improvement. H. pylori-specific IgE antibody, analyzed by the Western blot method, gradually decreased with the eradication treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Isolation of a novel chick homolog of Serrate and its coexpression with C-Notch-1 in chick development.

Intercellular signaling mediated by the transmembrane proteins, Notch as receptor and its ligands, Delta and Serrate, plays essential roles in the developmental fate decision of many cell types in Drosophila. The Notch genes are highly conserved both in invertebrates and in vertebrates, suggesting that Notch pathway regulates cell fate decisions during vertebrates development. Notch, Delta and Serrate homologs in chicken have been cloned (Henrique et al., Nature 375: 787-790, 1995; Myat et al., Dev. Biol. 174: 233-247, 1996). We isolated a novel chick homolog of Drosophila Serrate, named C-Serrate-2, and examined its expression patterns during the early chick development using whole-mount in situ hybridization. C-Serrate-2 transcripts were detected in several tissues including the forebrain, the myotome and the apical ectodermal ridge (AER) of the limb bud of a 4-day-old chick embryo. In most of the regions where C-Serrate-2 was expressed, C-Notch-1 was also expressed. Our observations suggest that Serrate-2-Notch-1 signaling plays a role in a variety of morphogeneses during the chick development.

Amino Acid Sequence↗
PubMed1995

From lens regeneration in the newt to in-vitro transdifferentiation of vertebrate pigmented epithelial cells.

Through studies to clarify the cellular origin of lens regeneration in the newt, the pigmented epithelial cells of the iris and the retina of many vertebrate species have been shown to possess a dormant potency to transdifferentiate into the lens. The method of in-vitro culture of pigmented epithelial cells has been optimized to enable detailed studies of the transdifferentiation process by molecular techniques. Growth factors and extracellular matrix components are found to be important in the control of the transdifferentiation process. New systems for in-vitro culture are introduced, while prospects for renewed in-vivo studies using newts are given.

Amphibians↗
PubMed1995

[Preparation of specific antiserum of secretin and its use in time-resolved fluoroimmunoassay].

We have prepared a specific anti-secretin antiserum and developed a sensitive time-relevant fluoroimmunoassay (TR-FIA) for secretin. An anti-secretin antiserum was produced in rabbit by immunization with synthetic secretin C-terminal 8 residue conjugate to chicken serum albumin as antigen. The TR-FIA was based on the competition between free secretin and biotinylated secretin as a tracer for rabbit anti-secretin antibodies on a goat anti-rabbit IgG antibody coated microtiter plate. After separation of bound and free fractions, a solution of europium (III) ion chelate labeled streptavidin (Eu-SA) was added to the biotinylated secretin bound on the microtiter plate. The microtiter plate was washed and then Eu-SA activity was measured by time-resolved fluorometry. In this TR-FIA, the measurable range of secretin was from 2.5 to 100 pg/assay and the specificity was less than 0.01% against other peptide hormones. For the measurement of secretin in the human plasma, a sample was required for the pretreatment in order to separate from interfering substances. The mean recovery of secretin using commercially reverse phase column was 80.2% (n = 11). The plasma secretin concentrations of normal subjects and those with various diseases could be measured by this proposed TR-FIA.

Animals↗
PubMed1995

Transforming growth factor-beta 1 induces morphological changes accompanied by extracellular matrix reconstitution in cultures of avian retinal pigmented epithelial cells.

The mechanisms of cell differentiation have been extensively studied with an avian retinal pigmented epithelial cell (PEC) culture system. Transforming growth factor-beta (TGF-beta) has been reported to have stimulatory or inhibitory effects on differentiation depending on tissue type. Although the mechanism by which TGF-beta exerts diverse effects is unknown, changes in the extracellular matrix (ECM) are believed to be related to the effects of TGF-beta. Therefore, the effects of TGF-beta 1 on the cellular morphology and the distribution of ECM components such as laminin, tenascin, fibronectin, and types I and IV collagens were investigated in confluent cultures of differentiated PECs during a period of 6 days. We found that differentiated PECs with polygonal morphology and pigmented granules changed to pleomorphic and less pigmented cells 4 days after the addition of TGF-beta 1. These changes were preceded by changes in the distribution of ECM components, particularly laminin and tenascin after 2 days. The effects of TGF-beta on the differentiation of PECs are discussed.

Animals↗
PubMed1995

[Serum pepsinogen response to therapy for Helicobacter pylori associated gastro-duodenal disease].

We investigated the effect of H. pylori therapy on serum concentrations of pepsinogens on 87 patients of gastro-duodenal disease. In addition, we intended to see whether serum pepsinogen can serve as markers of response to H. pylori eradication. In 48 successfully eradicated cases, there was a significant decrease in gastritis score, and was a significant fall in serum pepsinogen II (PG II) level, and was a significant increase in pepsinogen I/II ratio (PG I/II ratio). In contrast, no change in gastritis score, PG II, and PG I/II ratio were observed in 39 unsuccessfully eradicated patients. No change in serum pepsinogen I (PG I) level was observed in both groups. In provisional successfully eradicated cases in PG II of decrease greater than 30% in after treatment, there was a sensitivity of 83.3% and a specificity of 89.7%. For the PG I/II ratio of increased greater than 30% in after treatment, the sensitivity was 95.8%, and the specificity was 94.9%. These findings suggest that PG II, PG I/II ratio can be useful for clinical evaluation of eradication therapy.

Adolescent↗
PubMed1995

Influence of Helicobacter pylori infection and the effects of its eradication on gastric emptying in non-ulcerative dyspepsia.

AIM: The aim of the present study was to clarify the effects of Helicobacter pylori infection and its eradication on gastric emptying. SUBJECTS AND METHODS: Out of a total of 52 patients with non-ulcerative dyspepsia, 34 H.pylori-positive patients were enrolled. Antimicrobial drugs for the eradication of H. pylori were administered to 19 out of the 34 H. pylori-positive patients. Gastric emptying was evaluated according to the acetaminophen method. Inflammatory changes and intracellular periodic acid-Schiff-positive substances in the antral mucosa were examined in biopsy specimens. RESULTS: Although gastric emptying was significantly prolonged in the patients with non-ulcerative dyspepsia compared with the control group (P < 0.01), there was no difference in gastric emptying between H. pylori-positive and -negative patients, with all patients showing significantly less gastric emptying than the control group. The H. pylori eradication rate was 58% (11 out of 19) and gastric emptying improved significantly in seven patients whose infection was eradicated and whose dyspeptic symptoms disappeared. The ammonia concentration in gastric juice, inflammatory changes in the gastric mucosa and the index of periodic acid-Schiff-positive substances improved significantly when H. pylori was successfully eradicated compared with patients in whom eradication was unsuccessful. As gut hormones may affect gastroduodenal motility associated with H. pylori infection, we also studied the levels of serum gastrin and cholecystokinin. In the patients whose infection was eradicated, serum gastrin decreased significantly, but the cholecystokinin level did not change significantly, although there was a non-significant trend for cholecystokinin to increase. CONCLUSIONS: These results suggest that delayed gastric emptying is partly associated with H. pylori infection and that the infection may contribute to the development of non-ulcerative dyspepsia.

Adult↗
PubMed1995

General pharmacology of the new antimuscarinic compound vamicamide.

The general pharmacology of the new antimuscarinic compound vamicamide (FK176, (+/-)-(2R*, 4R*)-4-dimethylamino-2-phenyl-2- (2-pyridyl)valeramide, CAS 132373-81-0) was investigated using mice, rats, guinea pigs and dogs, and was in part compared with that of oxybutynin hydrochloride (oxybutynin, CAS 1508-65-2), a similar type of compound. 1. Vamicamide induced mydriasis after oral administration (p.o.) of 10 mg/kg or more, and suppressed defecation after 32 mg/kg or more in the general activity and behavior test with rats. 2. Vamicamide increased spontaneous locomotor activity in mice at 32 mg/kg or more (p.o.) and suppressed tonic convulsions in the electroconvulsive shock test with mice at 100 mg/kg. The compound at 10-100 mg/kg (p.o) did not show significant effects on hexobarbital-induced anesthesia, pentetrazole-induced convulsions and pain response by Haffner's method in mice, body temperature in rats or spontaneous electroencephalogram (EEG) in rabbits. On the other hand, oxybutynin increased high voltage slow waves of spontaneous EEG in rabbits at 32 mg/kg or more (p.o.) and prolonged hexobarbital-induced anesthesia time in mice at 100 mg/kg. 3. Vamicamide in concentrations of 0.001-1% (1 x 10(-4)-1 x 10(-1) g/ml) did not show local anesthetic effect on the corneal reflex test with guinea pigs. The compound in concentrations of 1 x 10(-5) and 1 x 10(-4) g/ml also had no effects on contractions of the isolated rat diaphragm caused by electrical stimulation of the phrenic nerve. 4. Vamicamide on the highest concentration of 1 x 10(-4) g/ml augmented contractions of isolated rat vas deferens induced by noradrenaline, resting tonus of the isolated guinea pig trachea, and contractile force of spontaneous movement of the isolated rat nonpregnant uterus. The compound at 1 x 10(-4) g/ml had no significant effects on KCl-induced contraction of the isolated rat thoracic aorta. 5. Vamicamide elevated systemic blood pressure and increased heart rate but had no effects on respiratory movement of the chest in conscious dogs at an oral dose of 10 mg/kg or more. The compound in intraduodenal (i.d.) doses of 3.2-32 mg/kg had no effect on femoral blood flow in anesthetized dogs. Vamicamide augmented contractile force and reduced beating rate in isolated guinea pig atria at a concentration of 1 x 10(-5) g/ml or more. Oxybutynin increased heart rate at 3.2 mg/kg or more (p.o.), and elevated blood pressure at 10 mg/kg or more in conscious dogs. 6. Vamicamide slightly inhibited small intestinal transit in rats at 3.2 mg/kg or more (p.o.). On the other hand, oxybutynin inhibited the transit in rats at 0.32 mg/kg or more. 7. Vamicamide had no effects on urine volume, urinary excretion of Na+, K+, Cl- and uric acid in rats at an oral dose of 100 mg/kg or less, or on renal function in anesthetized dogs at an i.d. dose of 32 mg/kg or less. 8. Vamicamide showed no effects on bleeding time in mice at 100 mg/kg p.o., rabbit platelet aggregation induced by adenosine diphosphate or collagen at 1 x 10(-4) g/ml, blood coagulation systems in rats at 100 mg/kg p.o., or hemolysis on rabbit blood at a concentration of 1% or less. Thus, vamicamide in the doses used inhibited gastrointestinal motility, and caused mydriasis as effects possibly due to its anticholinergic action. The compound had no effects on the central nervous system, cardiovascular system, renal functions, or blood system.

Animals↗
PubMed1994

Gene regulation and differentiation in vertebrate ocular tissues.

Molecular biological techniques have contributed greatly to the study of vertebrate ocular tissues. The specification of ocular tissues has been shown to be closely related to the expression of transcription factors encoded by genes such as Pax6 and microphthalmia. Lens-specific expression of the delta 1-crystallin gene is controlled by factors, such as delta EF1, binding to its enhancer sequences. Retinal activity of the glucocorticoid hormone receptor is regulated by its binding with another transcription factor. Degeneration of photoreceptors in a retinal disease, retinitis pigmentosa, can be caused by the introduction of a mutated opsin gene into mice. In addition, the process of transdifferentiation in ocular tissues has been described at the level of gene expression.

Animals↗
PubMed1994

A comparative analysis of the costs of administration of an OSCE (objective structured clinical examination).

BACKGROUND: The objective structured clinical examination (OSCE) has become an accepted technique for the evaluation of clinical competence in medicine. Although advances have been made in our knowledge of the psychometric aspects of the OSCE, extremely little has been written about feasibility and cost issues. Given the current economic imperative to control costs and the extremely scant literature on the costs of developing and administering an examination in medicine, the authors felt it timely and relevant to explore issues related to the cost of the OSCE. METHOD: In 1991-92 and in 1992-93, costs and time requirements to implement and administer a structured oral (SO) examination and a six-station OSCE for a surgical clerkship at the University of Toronto Faculty of Medicine were gathered by review of invoices, interviews with those involved, and perusal of diaries kept by staff. RESULTS: To develop and administer the six-station OSCE, 327.5 hours of staff and faculty time were required for each rotation of surgical clerks (8.2 hours per student). The SO examination required 110 hours of staff and faculty time (2.75 hours per student). Direct expenses for the OSCE amounted to U.S. $6.90 per student per station, compared with no direct expense for the SO examination. CONCLUSION: The OSCE was more time-consuming and more expensive in human and material costs than the SO examination. However, costs of the OSCE can be substantially reduced from approximately U.S. $35 to U.S. ! per student per station if test developers, standardized patients, support staff, and examiners can donate their time. The authors compare the costs and time requirements of their OSCE with those of other OSCEs reported in the literature, and they provide guidelines to assist educators in deciding whether the costs of an OSCE are justifiable in the educators' individual settings.

Clinical Clerkship↗
PubMed1994

Combination therapy with clarithromycin and sofalcone for eradication of Helicobacter pylori.

OBJECTIVE: To clarify the efficacy of combination therapy with clarithromycin and sofalcone for eradication of Helicobacter pylori. DESIGNS: We studied 42 patients with H. pylori-positive gastroduodenal diseases, who were divided into two groups according to treatment period. Group 1 comprised 27 patients (seven with gastric ulcers, 14 with duodenal ulcers and six with gastritis) treated with a combination of clarithromycin (200 mg, three times a day) + sofalcone (100 mg, three times a day) for 3 weeks. Group 2 comprised 15 patients with chronic active gastritis treated with the same doses of clarithromycin + sofalcone but for only 2 weeks (group 2). The H. pylori status of all patients was assessed by culture, rapid urease test and histological examination at the end of treatment and 4 weeks after the end of treatment. The gastritis score, the index of intracellular periodic acid-Schiff-positive substance in the antral mucosa and the ammonia concentration in gastric secretions were also estimated before and after treatment. RESULTS: In group 1, with over half the patients excluded from the follow-up, H. pylori was eradicated in nine out of 13 patients (69.2%) compared with six out of the complete group of 15 (40.0%) patients in group 2, without serious side effects. In these patients, significant improvements were seen in the gastritis score (P < 0.025), the index of periodic acid-Schiff-positive substances in the antral mucosa (P < 0.025) and the ammonia concentration in gastric secretions (P < 0.02) after treatment. CONCLUSION: These results suggest that modification of the treatment regimen is needed, with higher doses of clarithromycin and combination therapy with proton-pump inhibition.

Ammonia↗
PubMed1994

Establishment of an animal model for chronic gastritis with Helicobacter pylori: potential model for long-term observations.

OBJECTIVES: To assess the suitability of an established experimental model for chronic gastritis associated with Helicobacter pylori for use in long-term observations. DESIGN: In a 3-year follow-up study of acute gastritis induced by H. pylori using an established experimental model with Japanese monkeys, we compared H. pylori-infected animals (n = 6) with a non-infected control group (n = 7). Colonization by H. pylori, gastritis scores, volume of intracellular periodic acid-Schiff-positive substances and the height of antral glands were investigated every 3 months for 3 years and compared with those of a control group. RESULTS: In the infected group, persistent colonization with H. pylori was demonstrated by culture and histological examinations. Gastritis scores were significantly higher than those of the control group, and the histological findings were quite similar to those of chronic active gastritis observed in humans. Simultaneously, significant decreases in the contents of periodic acid-Schiff-positive substances and in the height of antral glands were also demonstrated in infected animals. CONCLUSION: In Japanese monkeys, persistent colonization with H. pylori caused chronic gastritis quite similar to that observed in humans, thus providing a suitable animal model for evaluating the long-term prognosis of H. pylori infection.

Animals↗
PubMed1994

The loss of gap junctional cell-to-cell communication is coupled with dedifferentiation of retinal pigmented epithelial cells in the course of transdifferentiation into the lens.

Retinal pigmented epithelial cells (PECs) of the chick embryo can be cultured as a monolayer of melanized hexagonal cells. Modifications of the culture condition make the cells lose most of the phenotypes and further transdifferentiate into lentoid bodies within a few weeks. Ultrastructural observations showed that PECs and the lentoids have gap junctions with distinct morphology. Diffusion of a fluorescent dye confirmed the presence of gap junctions in both phenotypes. However, cells in the intermediate stage of transdifferentiation, which show neither the phenotype of the PEC nor that of the lentoid and are called dedifferentiated PECs here, have almost no gap junction structure. We propose the possibility that the dedifferentiation of PECs and the loss of cell-to-cell communication are tightly coupled events. This cell culture system is a suitable material for further studying this relationship by cellular and molecular approaches.

Animals↗