Biomedical subjects

T Shimoyama

Publications and source records attributed to T Shimoyama.

At least 145 records · Page 8Linked to original sources

PubMed1998

Pathologic changes in the glandular stomach and duodenum in an H. pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model following Hirayama's method to investigate gastric diseases associated with H. pylori infection. We orally administered the culture broth of H. pylori ATCC 43504 to 8-week-old male Mongolian gerbils. After this, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks some of them were sacrificed for histopathologic examination and H. pylori culture. H. pylori colonization in the glandular stomach was seen in all the infected gerbils but only a few H. pylori were detected histologically. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. In addition, we found intestinal metaplasia and gastric ulcers from 12 and 24 weeks, respectively. There was mild to moderate inflammation in the duodenum but no ulcerative lesions or gastric metaplasia were observed. Some histologic findings were similar to those in humans, but inflammation occurred mainly in the deep mucosa and submucosa. This is a good animal model for H. pylori-associated gastric diseases but not for duodenal ulcers or gastric metaplasia. It might be useful for investigating the pathogenesis of H. pylori infection in the stomach.

Animals↗

PubMed1998

Healing of cimetidine-resistant Ménétrier's disease by eradication of Helicobacter pylori infection.

We report a case of Ménétrier's disease associated with hypoproteinemia who was successfully treated by eradication of Helicobacter pylori infection. A 26-year-old woman had diffuse giant gastric folds with proven protein leakage from the stomach. She received cimetidine, famotidine, and omeprazole for more than 3 months with little benefit. H. pylori infection was detected, and she was treated with clarithromycin (200 mg three times a day), lansoprazole (30 mg/day), and ecabet sodium (1.5 g twice a day) for 2 weeks. After starting the treatment, rapid increase of serum albumin and IgG levels were observed. The treatment resulted in eradication of H. pylori infection, and serum albumin and IgG levels returned to normal. Histologic specimens also showed the improvement of the irregularly elongated gastric pits with inflammatory infiltrates after the treatment. This case report suggests that eradication of H. pylori is recommended therapy for the immediate improvement of Ménétrier's disease associated with hypoproteinemia.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1998

Primary Sjögren's syndrome followed by chronic myelogenous leukemia: a case report with a ten year history.

We describe a female patient with primary Sjögren's syndrome who subsequently developed chronic myelogenous leukemia. The patient received a bone marrow transplant (BMT) from a genotypically HLA-identical brother after pre-transplant preparation with busulfan and cyclophosphamide. Eighteen weeks later, cutaneous and mucosal chronic graft-versus-host disease developed, followed by death 11 months after transplantation. Anti-Ro/SS-A antibodies disappeared within 6 months post-BMT, but antinuclear antibodies remained positive through the post-transplant course.

Adult↗

PubMed1998

Inflammatory pseudotumor in the mandibular retromolar region.

An unusual pseudosarcomatous lesion of the oral mucosa is described in a 43-year-old woman. It presented as an aggressive ulcerative mass in the mandibular retromolar gingiva of one month's duration. The lesion was composed of florid myofibroblastic and fibrohistiocytic proliferations with infiltrative margins in an inflammatory background and was considered to be an inflammatory pseudotumor. Although the tumor appeared to have been incompletely excised, the patient remains free of disease at 1 year follow-up.

Adult↗

PubMed1998

Therapeutic cytapheresis for inflammatory bowel disease.

Cytapheresis therapy has recently been investigated as a treatment for several diseases, especially autoimmune related diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. The removal of leukocyte components has been performed by the centrifugal method; however, using fiber technology or column technology, leukocyte components can be removed simply, and these technologies are more effective than the centrifugal method in removing numbers of cells. Each of 3 types of leukocytapheresis methods removes a different kind of cell in its therapeutic principle. Thus, if we understand what kind of cells should be removed, we can choose the best method for removing leukocytes. For this reason, the authors propose an international standard for unifying names. The therapy that makes use of a centrifuge to selectively remove about 40% of neutrophils and more than 60% of lymphocytes may be called a lymphocyte removal therapy, lymphocytapheresis (LCA). Using cellulose acetate beads in a G-1 granulocyte removal column, granulocytes and monocytes are removed but not lymphocytes, so we suggest calling this granulocytapheresis (GCAP). In addition, using a leukocyte removal filter, the Cellsorba leukocyte removal filter, 99% of both granulocytes and monocytes and about 70% of lymphocytes are removed. We propose calling this leukocytapheresis (LCAP). In the near future, we hope that we will be able to select one of these methods for cytapheresis for each disease pathogenesis or cellular immune abnormality. Presently, a lot of research is on-going to analyze how cytapheresis is effective for the immune related diseases. The mechanism of cytapheresis will be clarified by investigators. We strongly believe that cytapheresis therapies offer good news to those patients suffering from incurable diseases as well as their physicians.

Humans↗

PubMed1998

Complications of leukocytapheresis.

Recently leukocytapheresis (LCAP) has attracted attention as a new therapy for ulcerative colitis. We reviewed the complications associated with LCAP carried out in our department during the period from December 1992 to September 1997. There were side effects during 195 (9.9%) of the 1,978 sessions performed, involving 47 (51.1%) of the 92 patients treated. Moderate reactions, which caused considerable discomfort to the patients and required the transient interruption of the administration or some medical treatment depending on the state, occurred during 31 (1.6%) of all therapy sessions, involving 15 (16%) patients. All patients recovered soon and never fell into a life-threateningly severe state. They also did not have any symptoms afterwards. The common side effects were nausea, vomiting, fever, chills, and nasal obstruction. Reactions such as palpitations, respiratory distress, or chest oppressions were common, especially when heparin sodium (HS) was used as the anticoagulant. The type and frequency of side effects depended somewhat on the length of the therapy series or the duration of one session. Other complications such as clotting in the leukocyte removal filter and/or blood line during administration were encountered frequently. These latter problems occurred during 46% of all sessions, but most of them had little significance. Sessions in which HS was used as the anticoagulant showed more severe clotting than those in which nafamostat mesilate (NM) was used. In our series, we experienced a relatively low rate of serious complications. We require, of course, careful observation during and after each session.

Adult↗

PubMed1998

Chemokine mRNA expression in gastric mucosa is associated with Helicobacter pylori cagA positivity and severity of gastritis.

AIM: To investigate the association between the quantity of gastric chemokine mRNA expression, severity of gastritis, and cagA positivity in Helicobacter pylori associated gastritis. METHODS: In 83 dyspeptic patients, antral and corpus biopsies were taken for semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and histological grading of gastritis. Gastritis was evaluated by visual analogue scales. Quantities of chemokine (IL-8, GRO alpha, ENA-78, RANTES, MCP-1) RT-PCR products were compared with G3PDH products. Each sample was also evaluated for the presence of cagA and ureA mRNA by RT-PCR. RESULTS: mRNA expression of all five chemokines was significantly greater in H pylori positive than in H pylori negative mucosa. In H pylori positive patients, in the antrum C-X-C chemokine mRNA expression was significantly greater in cagA positive patients than in cagA negative patients, but there were no significant differences in C-C chemokine mRNA expression. In H pylori positive patients, chemokine mRNA expression in the corpus was less than in the antrum. In contrast to the antrum, only GRO alpha mRNA expression was significantly greater in cagA positive infection. Polymorphonuclear cell infiltration was correlated with C-X-C chemokine mRNA expression. Significant correlations were also found between bacterial density and C-X-C chemokine mRNA expression. CONCLUSIONS: In H pylori infection, C-X-C chemokines may play a primary role in active gastritis. Infection with cagA positive H pylori induces greater gastric chemokine mRNA expression in the antral mucosa, which may be relevant to the increased mucosal damage associated with cagA positive H pylori infection.

Antigens, Bacterial↗

PubMed1998

CagA seropositivity associated with development of gastric cancer in a Japanese population.

BACKGROUND/AIMS: Infection with Helicobacter pylori strains possessing the cagA gene is associated with increased risk of gastric cancer of the intestinal type. The aims of this study were to investigate whether CagA seropositivity is associated with increasing risk of gastric cancer in a Japanese population that has a much higher incidence of gastric cancer than western populations. METHODS: Eighty one gastric cancer patients and 81 sex and age matched endoscopically evaluated controls were studied. Histologically, 62 cancers were of the intestinal type and 76 were early gastric cancer. Serum CagA IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA) using purified recombinant CagA protein as antigen. Polymerase chain reaction (PCR) analysis for cagA in H pylori isolates (n = 80) showed that the CagA ELISA had a sensitivity of 83.3% (controls) and 72.5% (cancers). RESULTS: CagA seropositivity was 60% (49 of 81) in cancer patients and 44% (36 of 81) in controls. The odds ratio for the risk of cancer if CagA seropositive was 1.93 (95% confidence interval (CI) 1.01 to 3.68; p < 0.05). In the 57 H pylori positive cancer patients and their matched H pylori positive controls, the odds ratio for the risk of cancer if CagA seropositive was 2.2 (95% CI 1.04 to 4.65; p < 0.05). CONCLUSIONS: These results suggest that CagA seropositivity is associated with increased risk of gastric cancer in Japanese populations.

Adult↗

PubMed1998

Evaluation of Helicobacter pylori vacA genotype in Japanese patients with gastric cancer.

AIM: To examine the vacA genotypes of Helicobacter pylori strains in Japan and to define whether any specific genotype was associated with gastric cancer. METHODS: The allelic variation of vacA gene was studied using a recently introduced polymerase chain reaction based vacA genotyping system. RESULTS: 80 H pylori strains were isolated from gastric biopsies of 40 patients with gastric cancer and 40 control subjects in a Japanese population. All strains were s1/m1 subtype and 79 of 80 strains were classified as s1a subtype. CONCLUSIONS: The recently proposed vacA genotyping system is applicable to Japanese H pylori strains and most strains have the s1a genotype, associated with increased virulence. While the high frequency of s1a/m1 vacA genotype might play a role in the increased incidence of atrophic gastritis and gastric cancer in Japanese subjects, it precludes its use as a predictor of clinical outcome of H pylori infection in Japan.

Adult↗

PubMed1998

Adrenal hemorrhage associated with Klebsiella oxytoca bacteremia.

Septic adrenal hemorrhage is classically caused by meningococcemia. An autopsied case is presented of a 45-year-old man with adrenal hemorrhage due to Klebsiella oxytoca bacteremia following placement of a central venous catheter. He died 5 hours after developing disseminated intravascular coagulation (DIC). The bacterial entry site may have been the catheter. The cause of death was considered to be pulmonary edema due to bacteremia rather than adrenal insufficiency due to hemorrhage. Septic adrenal hemorrhage should be recognized as a subtype of sepsis rather than adrenal insufficiency, and may be caused in conditions of severe sepsis with DIC, independent of the microorganic variety.

Adrenal Gland Diseases↗

PubMed1998

Rapid diagnosis of oral tuberculosis by amplification of Mycobacterium DNA from paraffin embedded specimens.

The polymerase chain reaction (PCR) assay is a powerful tool for quick diagnosis of various infectious diseases. We applied this technique as well as conventional histopathological examination to diagnose oral tuberculosis. Ziehl-Neelsen staining of oral mucosal specimens often fails to detect Mycobacterium (M.) tuberculosis due to the low number of bacteria in the tissue. Specific primers and probes were synthesized based upon the nucleotide sequence of the 65 kDa membrane protein of M. tuberculosis. DNA extracted from the paraffin-embedded tissue was amplified using taq polymerase. PCR assay detected M. tuberculosis in 5 of 6 samples. Although the gene segments from these species were quite similar, the gamma 32P labeled noligonucleotide probes distinguished between M. tuberculosis and M. fotuitum by southern blot hybridization. In all specimens that were Ziehl-Neelsen negative, M. tuberculosis DNA was detected by PCR. These results suggest that PCR is a useful means of diagnosing mycobacterium infection.

Adult↗

PubMed1998

Bacterial factors and immune pathogenesis in Helicobacter pylori infection.

Virulent Helicobacter pylori strains which have been clinically associated with severe outcome induce increased gastric mucosal immune responses. Although several bacterial pathogenic factors have been shown to have a considerable role in H pylori infection, variability in host immune responses may also contribute to mucosal damage in H pylori associated gastritis.

Antigens, Bacterial↗

PubMed1998

[Peptic ulcer disease and hemorrhagic gastritis with H. pylori infection].

Most of gastroduodenal diseases are associated with Helicobacter pylori infection. Cure of H. pylori infection may lead complete remission of recurrence of gastric and duodenal ulcer, and suppress the development of atrophic gastritis, gastric cancer and MALT lymphoma. H. pylori infection and hemorrhagic gastroduodenal diseases are reviewed.

Animals↗

PubMed1998

Pathological changes in glandular stomach of Helicobacter pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model, following Hirayama's method, to clarify gastric diseases associated with H. pylori infection. We administered the culture broth of H. pylori ATCC 43504 orally to 8-week-old male Mongolian gerbils. After H. pylori inoculation, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks, they were killed for histopathological examination, H. pylori culture, and serum antibody measurement. H. pylori colonization in the glandular stomach was seen in all the infected gerbils, but only a few H. pylori were detected histologically. The serum antibody titer in the H. pylori-inoculated group increased gradually in comparison with controls. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. We also found intestinal metaplasia and gastric ulcers from 12 and 24 weeks after inoculation, respectively. Some histological findings were similar to those in humans, but the chronic inflammation in the gerbils was present mainly in the deep mucosa and submucosa. This appears to be a good animal model for H. pylori-associated gastric diseases and it may be useful for investigating the pathogenesis of H. pylori infection.

Animals↗

PubMed1998

Helicobacter pylori infection affects gastric ulcer healing in Japanese monkeys.

Although peptic ulcer frequently recurs in the presence of Helicobacter pylori infection, the effects of H. pylori on ulcer healing have yet to be studied in detail. Using an animal model, we examined the effects of H. pylori infection on the healing of peptic ulcer in Japanese macaques. Forty-four Japanese macaques, aged 5 years, were randomly divided into two groups, an H. pylori-infected group and a control group, with 22 animals in each. A total of 10(9) colony forming units per ml of an H. pylori strain clinically isolated from patients positive for the cagA gene, the vacA gene, and vacuolizing toxin production, was inoculated into the stomachs of the monkeys to induce H. pylori-associated gastritis. The monkeys were examined by endoscopy, and then 0.1 ml of 10% ammonia solution was injected into the angulus to produce an active ulcer. Endoscopic observations was performed every week for 8 weeks. Acid-reducing drugs and other cytoprotective agents were not administered during the 8-week observation period. No difference in the healing of the ulcers was seen between the two groups from the first to the third week. However, a significant delay in healing was noted in the H. pylori-infected group from the fourth week on wards (P < 0.05). At the sixth week, the proportion of ulcers in the S2 stage (presence of a complete scar) was 0% in the H. pylori-infected group and 38% in the control group, again indicating that healing was significantly delayed in the H. pylori-infected group (P = 0.0187). By the eighth week, the proportion of ulcers in S2 stage had increased to 18% in the H. pylori-infected group and 67% in the control group (P = 0.0719). In Japanese macaques with persistent H. pylori infection in the stomach, the speed of repair of the ulcer surface was reduced, leading to delayed ulcer healing, compared with the controls.

Animals↗

PubMed1997

Mucosal blood flow and generation of superoxide in rat experimental colitis induced by succinic acid.

As we consider succinic acid to be an exacerbating factor in ulcerative colitis, we investigated its influence on rat colonic mucosa in terms of mucosal blood flow and superoxide generation. We measured mucosal blood flow by the hydrogen gas clearance method and superoxide generation by the chemiluminescence method, and observed histopathological findings to determine the effects of succinic acid. After the instillation of succinic acid of any concentration tested to the colon, mucosal blood flow decreased. Histopathologically, the higher the concentration of succinic acid, the greater was the erosion formation in the colonic mucosa, while significant polymorpho-nuclear cell infiltration superoxide generation from colon tissue were observed with 0.01% succinic acid compared with higher or lower concentrations. Succinic acid, at fecal concentrations found in active stage ulcerative colitis, appears to be implicated in mucosal injury, mediated by a decrease in colonic mucosal blood flow and infiltration of superoxide-generating polymorpho-nuclear cells into the mucosa.

Animals↗

PubMed1997

Exacerbated autoimmune hepatitis successfully treated with leukocytapheresis and bilirubin adsorption therapy.

A 58-year-old man with subacute fulminant onset of autoimmune hepatitis (AIH) was treated by leukocytapheresis (LCAP) and bilirubin adsorption therapy (BAT), rather than by administration of high-dose corticosteroids as he had mild glucose intolerance, and a definitive diagnosis of AIH was not obtained on admission; further, there was a risk of viral infection. After initiation of the therapies, serum transaminases and bilirubin, immunoglobulins, anti-nuclear antibodies, and rheumatoid factor decreased rapidly, as did the initially high levels of activated cells and several pro-inflammatory cytokines. Liver inflammation observed on liver biopsy settled during the course of the therapies, with no adverse side effects. A pause in the therapies was associated with deterioration; however, restoration of apheresis was followed by normalization. Remission was sustained throughout the period monitored, except for a recurrence 14 months after discharge, which was successfully resolved by two additional LCAP sessions. These results suggest that LCAP influences the causal mechanism(s) of exacerbation of AIH.

Adsorption↗

PubMed1997

Immunobiological activities of chemically defined lipid A from Helicobacter pylori LPS in comparison with Porphyromonas gingivalis lipid A and Escherichia coli-type synthetic lipid A (compound 506).

Helicobacter pylori lipid A, characterised by a glucosamine beta (1-6) disaccharide 1-(2-aminoethyl)phosphate acylated by (R)-3-hydroxyoctadecanoic acid and (R)-3-(octadecanoyloxy)octadecanoic acid at the 2- and 2'-positions, respectively, exhibited no or very low endotoxic activities, i.e. lethal toxicity in galactosamine-loaded mice, pyrogenicity for rabbits and the activity of the Limulus test compared with Escherichia coli-type synthetic lipid A (compound 506), which possesses beta-(1-6)-linked glucosamine disaccharide 1,4'-bisphosphate, with two acyloxyacyl groups at the 2'- and 3'-positions and two 3-hydroxytetradecanoyl groups at the 2- and 3-positions. The endotoxic properties of H. pylori lipid A were also a little weaker than those of the low endotoxic lipid A of P. gingivalis, which has 1-phospho beta-(1-6)-linked glucosamine disaccharide with 3-hydroxy-15-methylhexadecanoyl and 3-hexadecanoyloxy-15-methylhexadecanoyl groups at the 2- and 2'-positions, respectively. Further, the mitogenic activity of H. pylori lipid A in murine splenic mononuclear cells was also less than those of P. gingivalis lipid A and compound 506. However, H. pylori lipid A induced comparable production of interleukin-6 (IL-6) by human peripheral blood mononuclear cells (PBMC) compared with P. gingivalis lipid A and compound 506. H. pylori lipid A also increased human natural killer cell activity, and strongly agglutinated rabbit erythrocytes. However, the lipid As of H. pylori and P. gingivalis showed lower activities in inducing tumour necrosis factor alpha (TNF-alpha) production by human PBMC and IL-8 production by human gingival fibroblasts than that of compound 506. The structural feature of H. pylori lipid A may be associated with low endotoxic properties and potent immunobiological activities.

Animals↗