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Biomedical subjects

Kazunari Murakami

Publications and source records attributed to Kazunari Murakami.

At least 19 recordsLinked to original sources

Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura.

BACKGROUND: A relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has previously been reported. We determined the prevalence of H pylori infection in Japanese patients with chronic ITP and the effect of its eradication on platelet count. METHODS: The study population comprised 53 Japanese adults with chronic ITP and a platelet count of less than 100 x 10(3)/ micro L. A (13)C-urea breath test was performed to determine H pylori infection status. Those patients who were H pylori positive gave written informed consent and received eradication therapy. The effect of H pylori eradication on platelet count was evaluated up to 6 months after therapy. Clinical parameters were compared between responders to the therapy (increase in platelet count) and nonresponders, as well as between H pylori-positive and -negative patients. RESULTS: Of the 53 patients with chronic ITP in the study, 39 (74%) were H pylori positive. Of the 32 infected patients who received treatment, H pylori was successfully eradicated in 27 patients (84%). In 10 (37%) of these patients, this resulted in a favorable platelet response. A partial response was seen in 5 additional patients (19%). A significant (P<.001) increase in platelet count was demonstrated in patients in whom H pylori was successfully eradicated but not in patients who were unsuccessfully treated or in untreated patients. Current corticosteroid therapy was reported more often in nonresponders than in responders. CONCLUSION: Eradication of H pylori may prove effective in increasing platelet count in H pylori-positive patients with chronic ITP.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Duodenal gangliocytic paraganglioma treated with endoscopic hemostasis and resection.

Gangliocytic paragangliomas are exceedingly rare tumors that arise in close proximity to the papilla of Vater. There are few reports of the endoscopic resection of duodenal gangliocytic paraganglioma. A 61-year-old woman was admitted with a complaint of melena. Endoscopic examination revealed a pedunculated submucosal tumor with erosion in the third portion of the duodenum. Hemostasis, using a gold probe, was performed. Nine days later, we successfully resected the tumor, using endoscopic polypectomy. To determine the depth of tumor invasion, endoscopic ultrasonography was used. The size of the tumor was 3.0 x 2.5 x 1.0 cm. A total of 25 cases of duodenal gangliocytic paraganglioma have been reported in Japan. Generally, this tumor is considered benign. However, resection was performed in many patients because preoperative diagnosis was impossible. In Japan, no previous studies have reported using endoscopic hemostasis, to our knowledge. Our patient is the fourth in Japan to be treated by endoscopic resection. We report on our patient, with a review of the literature.

Duodenal Neoplasms↗

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients.

OBJECTIVE: Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. METHODS: This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori-cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. RESULTS: Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). CONCLUSIONS: Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.

Alcohol Drinking↗

Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in mice.

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Spontaneous esophageal submucosal hematoma in which the course could be observed endoscopically.

A 66-year-old man was hospitalized after vomiting blood after inducing vomiting using his fingers due to laryngeal discomfort. Upper digestive tract endoscopy revealed a large, dark red mass that connected from the upper esophagus to the lower esophagus. Esophageal submucosal hematoma was diagnosed using endoscopy, X-ray images, a small-diameter ultrasonic probe, and chest CT scanning. Pain from the epigastrium to the larynx disappeared after 3 days. Melena occurred on Day 3. Endoscopic examination revealed that the hematoma had collapsed over a wide area. Endoscopic examination after one week showed that the mucous membrane covering the hematoma had peeled away revealing an extensive shallow ulcer in the esophagus. Endoscopic examination after one month confirmed the ulcer had scarred and healed.

Aged↗

Spontaneous dissection of the superior mesenteric artery in four cases treated with anticoagulation therapy.

Reports of spontaneous dissection of the superior mesenteric artery are rare. Diagnosis in the acute stage has been considered difficult, but we encountered four cases from November 1998 to November 2001. All four cases were diagnosed using abdominal CT scanning in the acute stage and could be treated conservatively. All patients were provided anticoagulation therapy upon fasting. The mean period of continuous abdominal pain was 10.2 days, the mean period of fasting was 27.2 days, and the mean number of in-hospital days was 44.5. There is no established opinion on treatment, but conservative treatment is considered possible if there are no symptoms or if it has not been aggravated.

Aortic Dissection↗

[Second-line eradication therapy for H. pylori infection].

The widespread use of eradication therapy for Helicobacter pylori has lead to an increase in antibiotic-resistant strains and the problem of retreatment in cases of eradication failure. Retreatment in cases of eradication failure has achieved relatively good results with regimens containing bismuth compounds and tetracyclines in the world, but consensus has not been reached in Japan and each institution has its own policy. An triple therapy consisted of proton pump inhibitor, amoxicillin and metronidazole has been reported to show a good cure rate as a second line therapy in Japan, but metronidazole has not been approved by the Japanese regulatory authority for use against bacterial infections, including H. pylori, despite its worldwide use as an antimicrobial agent in H. pylori eradication regimens.

Amoxicillin↗

Influence of anti-ulcer drugs used in Japan on the result of (13)C-urea breath test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: The (13)C-urea breath test (UBT) is a simple breath test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the antiulcer drugs used in Japan on the results of UBT were determined. METHODS: The subjects of the study were 64 adult volunteers who tested positive for H. pylori infection by the serum antibody method. Eight classes of anti-ulcer drugs used in Japan were administered at their usual doses to these subjects: lansoprazole, a proton pump inhibitor (PPI); nizatidine, an H(2)-receptor antagonist (H(2)RA); and polaprezinc, ecabet sodium, rebamipide, teprenone, cetraxate hydrochloride, and sucralfate, all mucoprotective agents. The study drugs were randomized for administration to the subjects, and each of the drugs was administered for 14 consecutive days. The UBT was performed on days 0, 14, and 21. RESULTS: The mean Delta(13)C per thousand in the lansoprazole group was significantly decreased on day 14, to below 10 per thousand, in 4 of 16 subjects, and in 1 of the 4 subjects, the test result was negative, with the Delta(13)C per thousand falling to 1.7 per thousand. The value returned to baseline 1 week after the discontinuation of lansoprazole. The other drugs administered had no significant effect on the result of the UBT, except that the mean Delta(13)C per thousand showed a tendency to decrease after the administration of ecabet sodium and rebamipide. CONCLUSIONS: Administration of a PPI may produce a false-negative UBT result, while other anti-ulcer drugs, for the most part, have little effect on the result of the UBT when used alone. The (13)C-urea breath test (UBT) is a simple test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the anti-ulcer drugs used in Japan on the results of the UBT were determined.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Is the recurrence of Helicobacter pylori infection after eradication therapy resultant from recrudescence or reinfection, in Japan.

BACKGROUND: Reinfection of Helicobacter pylori after eradication is rare in developed countries but most often occurs within 1 year. In the present study, we attempted to differentiate between reinfection and recrudescence of H. pylori strains between 6 months and 6 years after successful eradication in Japan, a country with a high prevalence of H. pylori infection. MATERIALS AND METHODS: After successful eradication of H. pylori, 274 patients were followed up by endoscopy and urea breath test. In recurrent patients, H. pylori strains isolated initially and after recurrence were compared using PCR-based restriction fragment length polymorphism (RFLP) analysis. RESULTS: Recurrence of H. pylori occurred in 15 of 274 patients (5.5%) at 6 months after eradication and the annual recurrence rate was 2.0% per patient year (between 1 and 6 years). PCR-based RFLP analysis of H. pylori strains isolated initially and after recurrence showed that 62.5% (at 6 months) and 100% (after 1 years) of bacteria were of different strains. CONCLUSION: Reinfection of H. pylori was not as rare at 6 months after eradication as reported previously, and up to 6 years after eradication, the annual reinfection rate is 2.0% per patient year in Japan.

Adult↗

Ileal schwannoma in which blood loss scintigraphy was useful for diagnosis.

An 85-year-old woman was hospitalized with severe melena of unknown origin. Upper gastrointestinal (GI) endoscopy and lower GI endoscopy did not detect the origin and we could not establish any diagnosis. To explore the bleeding site, 99mTc-HSA blood loss scintigraphy was performed and a tumor of the small intestine was suspected. Fluoroscopic examination of the small intestine and abdominal CT scan confirmed an ileal tumor measuring 4x3 cm. The mass was a well-demarcated tumor about 80 cm proximal to Bauhin's valve. Partial resection of the ileum was carried out and the tumor was histologically diagnosed as schwannoma. Thereafter, there has been no recurrence of melena nor metastasis of the tumor. It is thought that blood loss scintigraphy is a useful method for unexplained exacerbation of melena.

Aged↗

[Culture method for H. pylori].

In the five diagnostic tests for H. pylori infection recommended by the Japanese guideline, culture method may be the most difficult in clinical use, because of taking 3 to 5 days for growth, requiring a lot of skill and equipment, and having a possibility of false negative. On the other hand, it has merits of having a specificity of 100%(direct demonstration of the presence of H. pylori), allowing further investigation of the organism (determining its sensitivity to antibiotics, investigating its virulence factors, and typing it for epidemiological purposes). This method is necessary for the cases in whom strains are needed its sensitivity to antibiotics. Considering of increase of CAM-resistant H. pylori in the future, culture method should be necesary in the diagnosis of H. pylori.

Bacteriological Techniques↗

Analysis of p53 mutations and Helicobacter pylori infection in human and animal models.

BACKGROUND: p53 gene mutations are believed to play a critical role in the development of gastric carcinoma. We examined the relation between Helicobacter pylori infection and p53 gene mutations of the gastric mucosa in human and animal models. METHODS: To detect the original p53 DNA sequences of the Japanese monkey and Mongolian gerbil, the p53 genes of these animals were amplified using the nested polymerase chain reaction method with primers for the human p53 gene. Direct DNA sequencing of exons 5, 6, 7, and 8 of the p53 genes was performed by the dideoxy terminator method for gastric mucosa of humans, the Japanese monkey, and the Mongolian gerbil. The expression of p53 was examined immunohistochemically in a Japanese monkey model. RESULTS: Mutations of the p53 gene were identified in 52.4% of human H. pylori-positive mucosa and in 100% of monkey H. pylori-positive mucosa. However, no mutations of the p53 gene were found in the H. pylori-positive gastric mucosa of Mongolian gerbils. There were no mutations in H. pylori-negative gastritis mucosa of humans, monkeys, or Mongolian gerbils. Nuclear staining of p53 was seen in the glandular cells of the H. pylori-infected mucosa of Japanese monkeys, especially in the neck region of the glands. CONCLUSIONS: These findings demonstrate that the H. pylori infection can induce p53 point mutations in humans and the Japanese monkey and appear to be involved in the pathway leading to dysplasia or carcinoma. However, our direct DNA sequencing method showed no p53 mutations in the Mongolian gerbil model at present. Further studies with this model are needed.

Animals↗

Long-term Helicobacter pylori infection in Japanese monkeys induces atrophic gastritis and accumulation of mutations in the p53 tumor suppressor gene.

BACKGROUND: Helicobacter pylori is accepted as a definite human gastric carcinogen from an epidemiological point of view despite insufficient experimental data. Although we previously showed that the number of p53 immunopositive cells in the atrophic gastric mucosa of H. pylori-infected Japanese monkeys gradually increased over time, data on p53 gene mutations were not obtained in that study. To obtain direct evidence of carcinogenesis associated with H. pylori infection, we investigated whether p53 gene mutations are present in the gastric mucosa of a nonhuman primate model susceptible to H. pylori. MATERIALS AND METHODS: Using the DNA from gastric tissues obtained from six H. pylori-uninfected monkeys of different ages, nucleotide sequence of the wild-type p53 gene was determined by amplification of exons (Ex) 5, 6, 7 and 8 and sequencing. Gastric specimens obtained from eight Japanese monkeys that had been infected with H. pylori for different lengths of time (1.5-7.5 years), were analyzed for mutations in exons 5-8 of p53. RESULTS: In the six H. pylori-uninfected monkeys, nucleotide sequences of p53 Ex 5-8 were completely common and no mutations were noted. However, among the monkeys that were infected with H. pylori over various periods of time, there was an accumulation of p53 nucleotide (amino acid) substitutions as the gastric atrophy score increased. CONCLUSIONS: We conclude that the appearance of p53 gene mutation may be closely associated with the degree of gastric mucosal atrophy, which depends on the duration of H. pylori infection. Searching for p53 gene mutations may be useful for studying the progression of gastric carcinogenesis associated with H. pylori.

Animals↗

Enterocromaffin-like cell tumor induced by Helicobacter pylori infection in Mongolian gerbils.

BACKGROUND: Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori-infected stomachs of Mongolian gerbils for a long time. MATERIALS AND METHODS: Five-week-old-male Mongolian gerbils were infected with H. pylori ATCC 43504 with cagA gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals. RESULTS: In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes. CONCLUSIONS: H. pylori infection caused not only gastric carcinomas but also enterochromaffin-like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids.

Adenocarcinoma↗

Intraperitoneal immunization led to T cell hyporesponsiveness to Helicobacter pylori infection in mice.

During Helicobacter pylori infection, T cell response is critical in the development of active gastritis and in protective immunity against infection. We studied gastric inflammation and T cell response in H. pylori-challenged mice following an intraperitoneal immunization, using whole H. pylori lysate (HpAg) in the absence of adjuvants. H. pylori-challenged mice without immunization developed moderate to severe gastric inflammation, and splenocytes from these mice produced Th1 polarizing cytokines in response to HpAg and Con A during the acute infection. On the other hand, immunized-challenged mice (those inoculated with H. pylori following immunization) had little or no gastric inflammation despite persistent H. pylori colonization. Our immunization primed splenocytes to produce IL-2, IFN-gamma, and IL-4 in response to HpAg and Con A before infection. However, these cells became hyporesponsive to both stimulants immediately after live bacterial challenge in terms of the production of these cytokines, especially IL-2 and IFN-gamma. CTLA-4 has been documented to be a negative regulator of IL-2 production and lymphoproliferation that induces peripheral tolerance and functions 24-72 hr after the initiation of T cell activation. Compared with challenged mice, T cells from immunized-challenged mice showed higher levels of CTLA-4 expression at 72 hr after oral challenge. These data suggested that our immunization inhibited the development of H. pylori-associated gastritis and induced T cell hyporesponsiveness to H. pylori infection, which might be mediated by the early induction of CTLA-4 following challenge.

Abatacept↗

Interferon therapy for hepatitis C virus (HCV)-related advanced chronic hepatitis after treatment of recurrent hepatocellular carcinoma: a successful case.

A complete response was obtained by interferon (IFN) therapy for hepatitis C virus (HCV)-related advanced chronic hepatitis after curative treatment of initial and recurrent hepatocellular carcinoma (HCC). The patient is alive 73 months after diagnosis of initial HCC and is in a tumor-free state 53 months after diagnosis of the last HCC. This case suggest that it is possible to suppress recurrence and to prolong the life of patients with HCV-related advanced chronic hepatitis, if a complete response is obtained by means of IFN therapy after the curative treatment of the recurrent HCC.

Aged↗

Helicobacter pylori and gastric carcinoma--from the view point of animal model.

Many epidemiological studies have shown a strong association between chronic Helicobacter pylori infection and subsequent development of gastric carcinoma in humans. To confirm this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection has recently been achieved in the Japanese Monkeys and Mongolian gerbil models, with results demonstrating that the sequential histopathological changes in the gastric mucosa are closely mimic the gastric mucosal changes caused by H. pylori infection in humans. Gastric mucosa infected with H. pylori exhibited significantly higher gastritis score, reduction in glandular height, increase in the number of Ki-67 positive cells and over expression of p53 protein and p53 gene mutation in the Japanese Monkey Model. In the Mongolian gerbil model, H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens such as MNU and MNNG, and also demonstrated that H. pylori infection alone can result in the development of gastric carcinoma. However, diagnostic criteria of gastric carcinoma in animal models remain in the great discussion. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.

Animals↗