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Biomedical subjects

S Ohara

Publications and source records attributed to S Ohara.

At least 19 recordsLinked to original sources

Studies of 13C-urea breath test for diagnosis of Helicobacter pylori infection in Japan.

In recent years Helicobacter pylori infection has been implicated in the etiology of a variety of upper gastrointestinal diseases. The aim of this multi-center trial was to search for the cut-off value of the simple 13C-urea breath test (13C-UBT) for diagnosis of H. pylori infection, and to examine the sensitivity and specificity of 13C-UBT for culture, the rapid urease test (CLO test), histology, and serological tests. Two hundred and forty-eight patients participated in this study after giving their informed consent. Endoscopic biopsy specimens were taken from gastric antrum and corpus for culture (190 patients), CLO test (222 patients), and histology (98 patients). A serological test was carried out for all patients. H. pylori infection was established when culture was positive or more than two of the tests, histology, CLO test, and serological test, were positive, and non-infection status was established when the all tests more than two tests were negative. After baseline breath samples were taken, the patients (who had fasted) were given 100mg of 13C-urea in 100ml water while sitting; they washed out the mouth with water. They were then placed in the left lateral decubitus position for 5 min, and additional breath samples were taken 10, 20, 30, 45, and 60 min after urea administration, with patients in the sitting position. One hundred and sixty-five of the 248 patients were infected, 48 were not infected, and H. pylori infection status was not evaluated in 35 by endoscopic and serological tests. Breath samples at 20 min were employed to determine the cut-off value. Using the receiver operating characteristic (ROC) curve, we determined the cut-off value for a positive UBT at 2.5 delta per thousand. The sensitivities of UBT for culture, CLO test, histology, and serological test were 98.4%, 98.6%, 100.0%, and 92.5%, and the specificities were 78.8%, 82.5%, 83.3%, and 87.3%, respectively. The cut-off value of 13C-UBT for the diagnosis of H. pylori infection was 2.5 delta per thousand; this test is a simple and noninvasive method for the diagnosis of this infection and has high sensitivity and specificity.

Adult

[Correlation between 13C-urea breath test and gastric histological findings in Helicobacter pylori positive patients].

13C-urea breath test (UBT), available for diagnosis of Helicobacter pylori (HP) in the stomach, measures the 13CO in the breath in which 13C urea is resolved in the stomach by urease derived from HP. Accordingly UBT is useful for a test of HP infection. This study is aimed at clarifying the relationship between the UBT and gastric histological findings. For this study we selected 63 patients with HP infection who showed both positive UBT and positive histological diagnosis. Briefly in the UBT procedure, the patients were given 13C-urea (100 mg dissolved 100 ml water) in a fasting state and kept in the left decubitus position for 5 minutes, and then the patients were asked to expire into testing bags before and 20 minutes after administration of the urea. Biopsy specimens were taken endscopically from the gastric antrum and the body. The specimens of all patients showed positive CLO test. HP organisms, inflammation, activity, and atrophy of the gastric specimens, were expressed in score from 0 to 3 according to the Update Sydney system. The UBT values were high correlated with the increase of HP organisms. The UBT was 11.8, 26.3, and 37/1000 in the groups with the scores of 0.1, and 2 in the number of HP organisms from the gastric body, respectively. The UBT was 19.2, 22.2, 36.1, 26.7/1000 in the groups with scores of 0, 1, 2, and 3 for the specimens from the antrum, respectively. The results show that there is a positive correlation between the UBT values and HP organisms. As a result, the UBT correlated with the activity score. Grade of gastric mucosal atrophy was expressed histologically in scores of 0,1,2, and 3. The UBT was 29.4, 19.1, 17.5, and 9.3/1000 in the groups with scores 0,1,2, and 3 in the grades of gastric atrophy from the gastric body, respectively. There was a negative correlation between the UBT values and the grade of gastric atrophy. We conclude that the UBT values which indicate the number of HP organisms can be used not only for diagnosis of HP infection but also the quantitative index of HP load.

Adult

[Results of SMANCS/Lipiodol injection therapy for multiple intrahepatic recurrence of hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) often recurs in the remnant liver after hepatectomy. Treatment is often ineffective in cases of multiple recurrence. We treated 18 cases of multiple recurrence with SMANCS/Lipiodol injection (SML). Four patients were treated with SML once, 11 patients were treated twice, and each patient was treated with three or four times with SML. The Effective rate of the 1st SML was 30%, but the effective rate of the 2nd SML was 60% in the plasma tumor marker levels. The effective rate between unilobular recurrence and bilateral recurrence was the same. A complete response was obtained in 2 cases, and partial response in 2 cases. The effective rate of SML was 4/18 (22.2%). These effective cases suffered a recurrence within a year. The cumulative survival rate at the end of the 24th month was 42.4%. Overall survival was significantly higher in the group with SML than in the group with TAE or TAI with the multiple recurrence. SML may be effective in early recurrence because these recurrent nodules are vascular-rich and there is much lipiodol accumulation. SMANCS/lipiodol injection therapy is expected to be an effective treatment in cases of early multiple recurrence after hepatectomy.

Antineoplastic Agents

Gastric mucosal blood flow response to stress in streptozotocin diabetic rats: regulatory role of nitric oxide.

To investigate cytoprotection against mucosal injuries of the stomach in patients with diabetes, we investigated gastric mucosal blood flow (GMBF), its response to a burn stress, and the involvement of nitric oxide (NO) in streptozotocin (STZ) diabetic rats. GMBF was measured by laser-Doppler velocimetry (LDV) and by the hydrogen gas clearance technique (HGC). The steady-state GMBF of STZ rats decreased according to the duration of diabetes, and insulin treatment blocked this decrease. Burn stress caused a rapid decrease in the GMBF. Reduction of the GMBF and gastric mucosal leakage of Evans blue (EB) after the burn stress were greater in the STZ rats than in the controls, but insulin treatment completely blocked this increase in EB leakage in the STZ rats. There was a significant negative correlation between the percent GMBF 3 h after the burn stress and EB leakage at the same time point. In the controls and the insulin-treated STZ rats, N-nitro-L-arginine (L-NNA), an NO synthase inhibitor, enhanced the decrease in postburn GMBF and EB leakage, but was without effect in the STZ rats. These results suggest that NO may be involved in the regulation of GMBF, and that persistent hyperglycemia may impair this regulation. These findings suggest that patients with diabetes have reduced cytoprotection against a variety of gastric mucosal injuries.

Animals

Comparative study of carbohydrate portion of gastrointestinal mucins using enzyme-linked lectin-binding assay (ELLA).

We improved the enzyme-linked lectin-binding assay (ELLA) to determine the differences in the carbohydrate chains of corpus, antral, duodenal ant colonic rat mucins. First we have improved the optimal conditions of this assay for mucins; ELLA makes possible the detection of 1.5 ng of hexose in rat gastrointestinal mucins (5-7 ng of mucins). Salt concentrations of several dozens mM are required for mucin coating on the plate. Non-ionic detergents diminish the adsorption of mucins onto the plate. Secondly we tested a set of 8 lectins to compare their binding to the gastrointestinal mucin samples. It is possible to detect crude mucins as well as purified mucins using ELLA. Gastric mucins have less Tn-antigen than duodenal and colonic mucins. Corpus and duodenal mucins have more of the H-type 2 chain than antral and colonic mucins.

Animals

Immunohistochemical studies on EGF family growth factors in normal and ulcerated human gastric mucosa.

Expression of members of the epidermal growth factor family, including epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), amphiregulin (AR), and Cripto, as well as their putative receptor, epidermal growth factor receptor (EGFR), was studied immunohistochemically in human gastric mucosa to evaluate their possible roles in cell proliferation of normal and regenerative gastric mucosa. We also examined the correlation betwen cell proliferation and EGFR by double immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and EGFR. In normal gastric mucosa, TGF-alpha, Cripto, and AR immunoreactivities were observed in the surface epithelial and parietal cells of gastric fundic glands, respectively. EGF immunoreactivity was not observed in any of normal mucosa examined. EGFR immunoreactivity was detected on foveolar cells in proliferative zones and in parietal cells. Double immunostaining revealed that EGFR immunoreactivity was distributed much more widely than PCNA immunoreactivity. PCNA positive epithelial cells adjacent to gastric ulcer margin expressed relatively intense EGFR but did not express any of the growth factors examined. On the other hand, relatively intense immunoreactivity of both TGF-alpha and Cripto was detected in PCNA-negative regenerative epithelium located distant from gastric ulcer margin. Relative immunoreactivity of AR in regenerative gastric epithelium associated with ulcer was not different from that in normal gastric mucosa. TGF-alpha, AR, and Cripto are considered to play important roles in normal gastric mucosal proliferation, and TGF-alpha and Cripto may be involved in ulcer healing, possibly via a paracrine mechanism.

Amphiregulin

[A comparative study of the effects of granisetron alone and a combination of granisetron plus steroids on CDDP-based combination chemotherapy-induced emesis--outcomes of a multicenter randomized comparative study using the central registration method. Nara Medical University Kytril Study Group].

The present investigation was conducted to examine the effects of granisetron alone and a combination of granisetron plus steroids on CDDP-based combination chemotherapy-induced emesis by multi-institutional randomized comparative trial using a central registration method. A total of 62 patients with urological cancer enrolled this study were randomized into two groups: granisetron (40 micrograms/kg) only group and granisetron (40 micrograms/kg) plus steroids (500 mg of methylprednisolone or 8 mg of dexamethasone) group. There were 31 patients eligible in the granisetron only group and 28 in the combination group. The same anti-emetic treatments were given in the recycling courses of chemotherapeutic regimens. Therefore, eligible patients of the second and the third cycle numbered 31 (17 in the granisetron only group, 14 in the combination group) and 21 (11 in the granisetron only group and 10 in the combination group). Significant inhibition of acute emesis in combination group was observed when compared with the granisetron only group in each cycle. Delayed emesis was also significantly inhibited in the combination group on Day 2 and 3 of the first cycle and on Day 2 of the second and third cycle. In addition, appetite loss was significantly reduced in the combination group on Day 2 and 3 of the first and second cycle. No adverse events were seen in either group. These results suggested that a combination of granisetron and steroids was useful for preventing CDDP-based combination chemotherapy-induced emesis.

Adult

Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma.

Helicobacter pylori (HP) infection, a cause of multifocal atrophic gastritis, is considered an important factor related to the evolution of the human gastric mucosa from normal to intestinal-type adenocarcinoma. We examined cell proliferation and both double and single strand DNA damage in situ in 35 patients undergoing gastrectomy for adenocarcinoma with HP-infected gastric mucosa by immunolocalization of Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and in situ nick translation. We also studied the distribution of intraepithelial neutrophils by elastase immunolocalization. HP infection was confirmed in all cases by serum anti-HP antibodies, ureas testing, and histopathological examination. HP-infected gastric mucosa was classified according to the degree of inflammation and intestinal metaplasia. Ki-67, terminal deoxynucleotidyl transferase-mediated labeling, in situ nick translation, and intraepithelial neutrophil indices all increased with the progression of gastritis and were highest in glands with incomplete intestinal metaplasia. All indices were lowest in gastric glands with complete intestinal metaplasia. Significant positive correlations were observed among these markers. Increased proliferative activity in HP-associated chronic gastritis in response to cell damage or injury was clearly demonstrated, suggesting that both HP-associated toxins and intraepithelial neutrophils are important in HP-related gastric epithelial injury. Increased cell turnover associated with incomplete intestinal metaplasia may result in DNA instability and subsequent development of intestinal-type gastric adenocarcinoma in HP-infected mucosa.

Adenocarcinoma

[An operated case of intractable occipital lobe epilepsy associated with calcification in the occipital lobe].

We reported a 20-year-old female of intractable occipital lobe epilepsy associated with calcification in the left occipital lobe. She developed seizures since 2 years old and electroencephalography showed paroxysmal activities on the left occipital area. At 8 years old, partial resection of the lesion and interictal spike focus under intraoperative corticography guidance was performed, but the favorable seizure outcome was not obtained. At the age of 20 years old, the frequency of her seizures has increased and admitted to our department. Preoperative evaluation with chronic invasive subdural recording showed that the ictal zone was located in the inferior (tentorial) surface and convexity of the left occipital lobe. Functional mapping involving cortical stimulation and cortical recording of pattern-reversal visual evoked potentials demonstrated that the ictal onset zone was not in the visual area. Following cortical resection of the ictal onset zone and multiple subpial transection on the surrounding cortex, she had good relief with less than one minor seizure per 1-3 months. Histological findings of the resected specimen were consistent with those of Sturge-Weber syndrome. Thus chronic invasive subdural recording may improve seizure outcome in patients whose epileptogenic area was located near the visual field.

Adult

In situ analysis of tissue dynamics and p53 expression in human gastric mucosa.

In situ tissue dynamics were studied in 12 cases of human gastric mucosa, including normal gastric body mucosa and gastric glands with intestinal metaplasia, obtained from gastrectomy specimens of adenocarcinoma. Cell proliferation was determined by Ki67 immunoreactivity. DNA fragmentation was studied in situ by TdT-mediated dUTP-biotin nick end labelling (TUNEL). In addition, p53 expression was examined by both immunohistochemistry and mRNA in situ hybridization. In the oxyntic gastric glands, Ki67 immunoreactivity was observed exclusively in the proliferative zone and TUNEL-positive cells were present predominantly in the surface foveolar epithelium. In the gastric glands with complete intestinal metaplasia, Ki67-positive cells were present in the lower portion of the glands and TUNEL-positive cells in the superficial epithelium. In the gastric glands with incomplete intestinal metaplasia, TUNEL-positive cells were detected in the lower gastric glands adjacent to cells immunoreactive for Ki67; the proportion of these gastric glands with TUNEL-positive cells (40 out of 108 glands) was significantly higher than for oxyntic glands (94 out of 620 glands) or for glands with complete metaplasia (31 out of 254 glands). Relatively strong p53 immunoreactivity and mRNA hybridization were also observed in the proliferative and apoptotic areas of gastric glands with incomplete intestinal metaplasia. These results indicate that incomplete intestinal metaplasia is associated with increased cell turnover and p53 overexpression, possibly in response to various noxious or DNA-damaging stimuli.

Apoptosis

Mechanisms for cytoprotection by vitamin U from ethanol-induced gastric mucosal damage in rats.

A comparison was made of the effects of a nonsulfhydryl compound, vitamin U (methylmethioninesulfonium chloride, MMSC), and a sulfhydryl compound, cysteine (Cys), with regard to the inducement of acute gastric mucosal damage in the presence and absence of N-ethylmaleimide (NEM), a sulfhydryl-blocking reagent. The effects of MMSC, Cys, or NEM on gastric mucin content were examined using a newly developed biochemical method. MMSC and Cys inhibited mucosal damage due to 50% ethanol. The preinjection of NEM had no effect on cytoprotection of prostaglandins, but prevented the effects of Cys and MMSC. MMSC and Cys increased surface mucin content but lessened that of deep mucin. NEM decreased surface mucin and increased deep mucin. It thus follows that sulfhydryl compounds accelerate the secretion of deep mucin and accumulate surface mucin. The cytoprotective mechanism of MMSC may thus be mediated by sulfhydryl compounds, and the increase in surface mucosal mucin may possibly be related to cytoprotection.

Animals

[Gastric mucosal atrophy and prevalence of Helicobacter pylori in reflux esophagitis of the elderly].

This study is aimed at a role of Helicobacter pylori (HP) infection in reflux esophagitis of the elderly. 46 patients with reflux esophagitis aged at older than 60 years are selected for this study with informed consent. 43 patients without reflux esophagitis, peptic ulcer, and gastric cancer are used as a control group. In reflux esophagitis, gastric mucosal atrophy is judged as closed type of endoscopic findings in all cases. In control, 27 of 43 patients were judged as open type. Serum pepsinogen I, II ratio is 4.73 +/- 1.28 which is higher significantly than 3.39 +/- 1.69 in control. Serological positive rate of HP antibody is 39.1% in reflux esophagitis. This rate is significantly lower than 62.7% in control. In conclusion, low frequency of chronic HP infection protects gastric mucosa from atrophy, and keeps secretion of gastric acid, resulting in reflux esophagitis of the elderly accompanied with various abnormal esophago-gastric functions.

Aged

[A retrospective analysis of the outcomes of patients with aneurysmal subarachnoid hemorrhages: a focus on the prognostic factors].

The authors report a clinical analysis of the outcomes of aneurysmal subarachnoid hemorrhages in 112 patients. Cerebral angiography was conducted on 85 patients. Clipping or wrapping of the aneurysm was performed on 81 patients. The overall good outcome (GR and MD in the Glasgow Outcome Scale) ratio and mortality rate were 43% and 34%, respectively. The good outcome ratio and mortality rate in operative cases were 59% and 12%, respectively. With regard to the timing of the operation, 77 cases (95%) underwent early operation and 4 cases (5%) underwent delayed operation. The good outcome ratio of patients with grade I to III at surgery using the Hunt and Kosnik grading system was 74%. There was no difference in outcome between the patients with a ruptured aneurysm in the anterior circulation and those with one in the posterior circulation. The retrospective analysis of the overall outcomes showed the risk factors as being: age over 70 years, cerebral atherosclerosis, poor grade on Hunt and Kosnik grading system and symptomatic vasospasm. Preoperative bleeding of the aneurysm, severe brain swelling at surgery, and postoperative symptomatic vasospasm were factors which worsen the outcome of surgically treated patients. Patients with more than 2 factors showed worse outcomes than those with only one factor. The utilization of these prognostic factors should be important to improve the outcome of patients with aneurysmal subarachnoid hemorrhage.

Adult

[Expression of Bcl-2 and Bax in human gastric cancer tissue].

Deregulation of bcl-2 may function as a survival mechanism in cancer cells, predisposed to cell death. Aberrant Bcl-2 expression is a frequent occurrence in chronic atrophic gastritis, gastric epithelial dysplasia and gastric cancer. Inhibition of apoptosis through Bcl-2 expression appears to be specifically associated with promotion of gastric adenocarcinoma. In addition, loss of heterozygosity of the bcl-2 gene is a common event in well-differentiated adenocarcinoma, whereas overexpression of bcl-2 gene is observed in poorly differentiated adenocarcinoma. Bax, a homologue of Bcl-2, counters the death repressor activity of Bcl-2. In our study Bax immunostaining in gastric cancer tissue is not significantly correlated with tumor histology. Possible gene therapy using bax gene is discussed.

Adenocarcinoma

Immunohistochemical study of DNA topoisomerase II in human gastric disorders.

Topoisomerase II (topo II) separates chromosomes at the end of mitosis and is also the target for various chemotherapeutic agents. Expression of this enzyme has been demonstrated to increase rapidly at the end of the S to G2/M phase and decrease after the completion of mitosis. We immunolocalized topo II in specimens of both normal and neoplastic human gastric mucosas to evaluate expression of this enzyme. Three different antibodies were used for the immunostaining of topo II (anti-topo II alpha isoform, anti-topo II beta isoform and anti-topo II alpha and -beta isoforms). There were no significant differences in topo II labeling index (LI) between frozen and paraffin-embedded tissue sections obtained from the same cases. Topo II LI was significantly correlated with Ki67 LI in all of the specimens examined. The area of cells positive for Topo II was much narrower than that of Ki67 in the normal gastric glands, and the pattern of Topo II immunolocalization in both adenomas and adenocarcinomas was also essentially the same as that of Ki67. The topo II LI values (positive cells/1000 cells) for normal gastric gland, adenoma, intestinal-type adenocarcinoma, and diffuse-type adenocarcinoma were 114.7 +/- 2.2, 266.7 +/- 18.8, 277.6 +/- 19.2, and 324.5 +/- 5.3, respectively. Significant differences in topo II LI and topo II/Ki67 index were observed between normal and neoplastic mucosas (P < 0.0001) and between adenomas or intestinal-type adenocarcinoma and diffuse-type adenocarcinoma (P < 0.001 and P < 0.01, respectively). Simultaneous measurement of topo II alpha and nuclear DNA content by two-parameter flow cytometry revealed that the Jurkat cell line established from acute lymphocytic leukemia cells expressed the enzyme in cells at other than S and G2/M phases of the cell cycle whereas topo-II alpha-positive cells were predominantly observed in S and G2/M phases of the cell cycle in the cells from normal lymph nodes. These findings suggest that dys-regulation or qualitative changes of topo II alpha expression are associated with malignancy. Topo II immunostaining can thus detect proliferating cells in routinely processed tissue sections and can indicate the altered topo II alpha expression in human cancers, which may be related to the sensitivity to topo-II-targeted chemotherapeutic agents.

Adenocarcinoma