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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 73 records · Page 4Linked to original sources

Gastric and intestinal phenotypic marker expression in gastric carcinomas and its prognostic significance: immunohistochemical analysis of 136 lesions.

OBJECTIVE: It is well known that both gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. However, the clinicopathologic significance of these expressions has not yet been clarified. METHODS: We analyzed the correlations among gastric and intestinal phenotypic marker expression patterns of the tumor, clinicopathologic findings and the patient's outcome in 136 advanced gastric carcinomas. RESULTS: Phenotypic marker expression was immunohistochemically evaluated using the monoclonal antibodies 45M1 (anti-human gastric mucin; HGM), CLH5 (anti-MUC6), Ccp58 (anti-MUC2) and 56C6 (anti-CD10). All tumors were classified as gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotype. Of the 136 gastric carcinomas, 50 (36.8%), 56 (41.2%), 21 (15.4%) and 9 (6.6%) were classified as G, GI, I and UC phenotype, respectively. The G-phenotype tumors were associated with a higher rate of undifferentiated-type and infiltrative histology as compared with the I-phenotype tumors (p < 0.05 and p < 0.001, respectively). Furthermore, both univariate and multivariate analysis of survival revealed the G-phenotype tumor to be associated with a significantly poorer outcome than the I-phenotype tumor (p < 0.05). CONCLUSION: Our present results indicate that the gastric and intestinal phenotypic marker expression pattern of tumors, determined by the combination of HGM, MUC6, MUC2 and CD10 expression, is prognostically useful for patients with gastric carcinoma.

Adenocarcinoma↗

Food frequency questionnaire and a screening test.

We assessed the accuracy of a 141-item food frequency questionnaire as a screening test to detect high or low consumption of nutrients associated with cancer. Fifty-five men and 58 women participating in two population-based cohort studies in Miyagi, Japan, provided four three-day diet records over a one-year period and subsequently completed the questionnaire twice with a one-year interval. Pearson correlation coefficients between 17 nutrients measured by the diet records and the first questionnaire ranged from 0.24 to 0.85 (median 0.43), and those between the two questionnaires ranged from 0.47 to 0.91 (median 0.68). The sensitivity and specificity of the questionnaire for detecting high-alcohol, high-fat, low-calcium, and low-ascorbic acid consumers were 86.7% and 96.7%, 50.0% and 85.7%, 48.8% and 76.4%, and 61.9% and 70.0%, respectively. Receiver operating characteristic curves indicated comparable performance of the questionnaire and a three-day diet record, regarded as another screening test. The questionnaire performed poorly for other nutrients. The results indicate that our questionnaire is reasonably reproducible, comparable with the diet records, and useful as a screening test to detect high or low consumers of several nutrients associated with cancer for subsequent enrollment in dietary intervention trials or dietary counseling.

Alcohol Drinking↗

Novel non-peptide GPIIb/IIIa antagonists: synthesis and biological activities of 2-[4-[2-(4-amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiperazinyl] acetic acids.

To improve the in vitro and in vivo potency of our first low molecular weight GPIIb/IIIa antagonist 1 (TAK-029), a series of 2-[4-[2-(4-amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiper-azinyllacetic acids were synthesized through modification of the glycine moiety of 1 and evaluated for their ability to inhibit in vitro adenosine 5'-diphosphate (ADP)-induced platelet aggregation of guinea pig platelet rich plasma (PRP). Among the compounds examined, the (3S,2S)-4-methoxyphenylalanine derivative 4h showed the most potent antagonistic activity with an IC50 value of 13 nM. Dose-dependent inhibition of ex vivo platelet aggregation was achieved with oral administration of 4h (0.3-1.0 mg/kg) to guinea pigs. Complete inhibition was observed for up to 8 h, and 43% inhibition could still be observed 24 h after oral administration of 1.0 mg/kg. The long-lasting antiplatelet effect of 4h suggests that 4h would be suitable for once-a-day dosing. Structure-activity relationships (SAR) were examined in the series of the phenylalanine derivatives. An increase in the electron density around the 4-position of the phenyl ring of the phenylalanine moiety led to an increase in the antiplatelet activity, suggesting the existence of a hydrophobic and electrostatic interaction site in addition to the ionic binding sites in the GPIIb/IIIa.

Acetates↗

Orally active GPIIb/IIIa antagonists: synthesis and biological activities of masked amidines as prodrugs of 2-[(3S)-4.

To improve the in vivo potency of the potent GPIIb/IIIa antagonist 2-[(3S)-4-[(2S)-2-(4-amidinobenzoylamino)-3-(4-methoxyphenyl)propanoyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiperazinyljacetic acid (4), the amidino group was converted to an oxadiazole ring, thiadiazole ring or substituted amidoxime group. These groups were expected to be metabolized to an amidino group in vivo. The compounds synthesized were evaluated for their potency to inhibit the ex vivo adenosine 5'-diphosphate (ADP)-induced aggregation of guinea pig platelets. Among the compounds examined, the methoxycarbonyloxyamidine 8a exhibited the most potent ex vivo inhibitory activity with a fast onset and prolonged duration of action after oral administration.

Acetates↗

Extracellular ATP potentiates steroidogenic effect of adrenocorticotropic hormone in bovine adrenocortical fasciculata cells.

We examined the effect of extracellular adenosine 5'-triphosphate (ATP) on adrenocorticotropic hormone (ACTH)- and angiotensin II-induced steroidogenesis in bovine adrenocortical fasciculata cells. The low concentration of ATP (5 microM) potentiated ACTH-induced steroidogenesis synergistically. However, the purine derivative did not affect angiotensin II-induced steroidogenesis. Although adenosine (100 microM) (a metabolite of ATP) showed a weak steroidogenic effect, it did not potentiate ACTH-induced steroidogenesis. ATP also enhanced the steroidogenesis by NaF synergistically in bovine adrenocortical cells, but did not potentiate forskolin- and dibutyryl cyclic AMP-induced steroidogenesis. The stimulating effect of ACTH on cyclic AMP production was synergistically accelerated by ATP (5 microM), which has no effect by itself on cyclic AMP formation. These results suggest that extracellular ATP affected the ACTH receptor-adenylyl cyclase coupling processes, and potentiation of steroidogenesis by ACTH ensued in bovine adrenocortical fasciculata cells.

Adenosine↗

Health behaviors and their relation to metabolic control and periodontal status in type 2 diabetic patients: a model tested using a linear structural relations program.

BACKGROUND: Although it has been reported that diabetic control is beneficial in managing periodontal disease, there are few studies in the literature where the relationship between singular behavioral factors and periodontal status has been examined. The aim of this study was to examine the simultaneous interrelationships among selected medical/dental variables and 5 behavior components with general health behavior (GHB), perceived fatigue (PF), diet control (DC), regular diet (RD), and dental behavioral inventory (HU-DBI) scores, using data from a study of 102 type 2 diabetic patients. METHODS: A hypothesized model was tested by a linear structural relations program (LISREL). RESULTS: There was a significant correlation between oral health behavior and calculus accumulation (r = 0.399; P<0.001). Correlations were found between calculus and periodontal status measured by gingivitis index and probing depth (r = 0.232; P<0.05, r = 0.279; P<0.01, respectively). The final model was found to be consistent with the data (chi2 = 55.0, df = 47, P = 0.197; GFI = 0.922). Oral health behavior affected periodontal status through its effect on calculus but not plaque accumulation. General health behavior had significant effects on oral health behavior and diet behavior (P<0.05 and P<0.001, respectively). Diet behavior affected both plaque accumulation and metabolic control (P<0.05 and P<0.01, respectively). However, the result was the virtual absence of a significant pass coefficient between metabolic control and periodontal status. CONCLUSIONS: The severity of the 2 diseases seemed to be connected indirectly through health behaviors such as diet behavior and oral health behavior.

Chi-Square Distribution↗

Successful steroid therapy for cefdinir-induced acute tubulointerstitial nephritis with progressive renal failure.

A 58-year-old woman was admitted to our hospital because of renal dysfunction that continued to progress even after withdrawal of cefdinir, the presumed cause of acute renal failure. Renal histologic findings included interstitial fibrosis accompanied by moderate lymphocytic infiltration, and tubular atrophy with reduced numbers of epithelial cells. Mesangial cells and glomerular basement membranes were nearly normal. Scintigraphy with 67gallium disclosed diffuse abnormal accumulation in both kidneys. A lymphocyte stimulation test with cefdinir was positive. The patient was diagnosed with acute tubulointerstitial nephritis caused by cefdinir. Serum creatinine concentrations continued to rise after withdrawal of the drug, but steroid therapy was effective in normalizing renal function.

Acute Disease↗

46, XY pure gonadal dysgenesis: a case with Graves' disease and exceptionally tall stature.

A case of 46, XY pure gonadal dysgenesis with very tall stature was investigated. The 24-year-old, phenotypically female patient consulted our clinic because of linear growth persisting into adulthood. The patient was found to have no mutation or deletion of a sex-determining region of the Y chromosome, and also was found to have Graves' disease. Growth was arrested with height remaining at 187 cm after normalization of the thyroid function by treatment with an antithyroid agent, although follow-up to monitor growth was limited to 3 months. In some cases of gonadal dysgenesis, then, Graves' disease may contribute to an abnormally tall stature.

Adult↗

Oral health attitudes/behavior and gingival self-care level of Korean dental hygiene students.

The purpose of this study was to examine oral health attitudes/behavior and gingival self-care levels of Korean dental hygiene students (n = 271). A questionnaire known as HU-DBI (Korean version) was administered to each class. Higher scores of the HU-DBI indicate better oral health attitudes/behavior. The student's gingival self-care level was scored as excellent (+2), good (+1), questionable (0), poor (-1), or very poor (-2) according to the criteria of the Oral Rating Index (ORI) for youth. The mean score of the HU-DBI was 6.40, and that of the ORI was +0.12. Most samples scored 0 or +1. The mean HU-DBI scores of year-2 and year-3 students (7.06, and 7.61 respectively) were significantly greater than that of year-1 students (5.23) (P<0.001). Twenty-three percent of the students reported a belief that they may eventually require false teeth. Half stated that they put off going to the dentist until they had toothache. Year-1 students were more likely to have this attitude compared to year-3 students. HU-DBI scores were significantly associated with ORI scores (r = 0.315; P<0.001). The differences in the HU-DBI and ORI scores across the level of education were highly significant.

Attitude to Health↗

Staple-line reinforcement with a new type of polyglycolic acid felt.

Although various materials have been used for reinforcement in lung-volume-reduction surgery to buttress pulmonary staple-line, absorbable materials are not available for use in thoracoscopic surgery. Moreover, even nonabsorbable types of reinforcements have been used only for lung volume reduction surgery. However, elderly patients with spontaneous pneumothorax secondary to emphysematous lung are well treated with staple-line reinforcement. The authors developed a new type of polyglycolic acid felt to buttress staple-line. This felt is absorbable, easier to cut with a stapler knife than is the conventional polyglycolic acid felt, and inexpensive enough to use for various types of thoracic surgeries for emphysematous lungs in Japan, and it can be attached to staplers with a small amount of fibrin glue. These strips were used to reinforce pulmonary staple lines for resection of emphysematous lungs in 14 patients: pulmonary emphysema (n = 1), bilateral giant bullae (n = 1), ipsilateral giant bullae (n = 6), spontaneous pneumothorax with multiple bullae in an emphysematous lung (n = 5), and lung cancer in a patient with pulmonary emphysema (n = 1). There were no air leaks during surgery. Air leaks were noted in three patients after surgery. In two patients, the air leaks stopped within 2 weeks. In one patient, the air leak was found to originate from an untouched lobe during reoperation. No infection or allergic reaction developed in a patient during a mean follow-up of 12 months (range, 1 to 24 months).

Humans↗

[Complete remission of brain metastases from prostate cancer by gamma knife radiosurgery: a case report].

A 59-year-old male visited us with a chief complaint of dysuria. The serum prostate specific antigen (PSA) level was within normal limits, and intravenous pyelography and urethrocystography showed no abnormal findings. Because of his urinary retention, transurethral resection of prostate was performed under a clinical diagnosis of benign prostatic hyperplasia. The pathological diagnosis was poorly differentiated adenocarcinoma of the prostate. Not only combination hormone therapy with goserelin acetate and flutamide, but also intermittent arterial infusion chemotherapy with cisplatin (CDDP) and pirarubicin (THP) using a reservoir system was administered. Additionally total pelvic irradiation was delivered. Magnetic resonance imaging (MRI) demonstrated that his prostate was reduced to less than 50% in size and he had no difficulty in voiding. He suddenly developed dysarthria and hemiplegia 3 months later. MRI and computed tomography (CT) revealed multiple brain metastases. After the gamma knife radiosurgery, neurological findings disappeared and MRI showed dramatic shrinkage of metastatic brain tumors. Metastasis to the pancreas was recognized on CT and he died of multiple organ failure 30 months after his first visit.

Adenocarcinoma↗

Inhibitory action of gemfibrozil on cholesterol absorption in rat intestine.

This study was designed to determine whether gemfibrozil inhibits intestinal lipid absorption. Male Sprague-Dawley rats received an oral dose of 30 mg gemfibrozil/kg body weight for 14 days. Mesenteric lymph cannulation was performed, and a lipid infusion containing 40 micromol/h (35.4 mg/h) of radiolabeled triolein and 2.74 micromol/h (1.06 mg/h) of radiolabeled cholesterol with the addition of 1 mg/h of gemfibrozil was infused intraduodenally at a rate of 3 ml/h for 8 h. The lymph was collected, and the radioactivity levels of the lumen and gut mucosa were measured after the infusion. Lymph cholesterol transport was depressed in gemfibrozil-treated rats, in terms of mass measurements as well as radioactivity in a lesser degree. More radioactive cholesterol remained in the proximal portion of the intestinal lumen and mucosa in the treated rats than in the control rats. More radioactive triglycerides also remained in the proximal intestinal lumen of treated rats, although no difference in lymphatic triglyceride transport was observed between the groups. A significant portion of the radioactive cholesterol remained in the lumen in the gemfibrozil-treated rats. Gemfibrozil increased biliary cholesterol excretion. Thus, this study shows that gemfibrozil inhibits cholesterol absorption in rat intestine.

Animals↗

[Effect of professional training on dental health attitudes of Israeli dental students].

Few studies have been published regarding the importance of oral hygiene education for dental students and little is known about the influence of dental education in dental schools on students' attitudes to the subject. The objective of the present research was to examine the changes that occur in the attitudes of Israeli dental students toward their dental health during the course of their professional training. The research was based on a questionnaire developed at The Hiroshima University, Japan (The Hiroshima University Dental Behavioral Inventory, HU-DBI), and provides a quantitative estimate of the students' attitudes to their dental health. Similar studies have been carried out in several countries (Japan, Australia, Indonesia and Finland). This study was performed on students from the two dental schools in Israel, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University and The Faculty of Dental Medicine at Hebrew University, Jerusalem. Students from all six academic years (1st-6th) were requested to complete the questionnaire within two months, from the beginning of the academic year that started in October 1999. While no significant differences could be detected in the students' attitudes with regard to the dental school of their origin, female students (from both schools) showed a significantly better attitude than their male colleagues throughout the years. Results showed a significant improvement in the students' attitudes through the years of their professional training, especially between the 1st year and the clinical years (5th and 6th) of their studies. This can be related to the teaching curricula in the dental schools in Israel that emphasizes clinical issues in the two last years of study. When comparing the results of this study to similar ones that were conducted in other parts of the world, certain differences become apparent. In spite of the gradual improvement in the Israeli students' attitudes during the course of their studies, their initial attitudes (1st year) as well as their final attitudes (6th year), were the lowest compared to their colleagues from other countries (Japanese, Australian and Finnish students). Apparently, the improvement in the Israeli students' attitudes is not satisfying and a higher level of improvement should be expected. The attitudes of the Israeli students should be further improved by means of comprehensive programs that emphasize the importance of personal oral hygiene and dental health. Hopefully this will enable future improvement in the dental health of their patients, as well as improvement in the community dental health in Israel, in general.

Adult↗

[Complete cytogenetic response to interferon-alpha in a patient with chronic myelogenous leukemia undergoing hemodialysis].

We describe a complete cytogenetic response to interferon-alpha in a patient with chronic myelogenous leukemia undergoing chronic hemodialysis. Although IFN-alpha therapy has been applied to patients with chronic hepatitis C receiving hemodialysis, the pharmacokinetics of IFN-alpha in patients with poor renal function still remain unclear. In the present patient, the serum IFN-alpha concentration remained high even 48 hours after injection (42.9 IU/ml), and IFN-alpha was almost completely removed by hemodialysis (< 6 UI/ml). The patient was treated with IFN-alpha (3 x 10(6) IU, three times a week), and cytogenetic disappearance (0%) of the Ph-positive clone was confirmed 31 months after the start of therapy. Recombinant human erythropoietin (Epo) was used to treat anemia due to renal failure and IFN-alpha therapy. The anemia was controllable with Epo, and no adverse effect was observed.

Anemia↗

[Order-made therapy for early lung cancer patients].

To give optimal treatment to the patients with early lung cancer, we are trying to establish two new techniques to select the patients of poor prognosis and sensitive to the chemotherapy. To pick up the patients of poor prognosis nevertheless the early stage of their lung cancer, we are developing a new method to detect cancer cells floating in the peripheral blood flow with RT-PCR using cancer specific mRNA. To choose optimal chemotherapy regimens, we have established a new chemosensitivity testing (collagen gel droplet embedded culture drug sensitivity test: CDDST) for non-small cell lung cancer (NSCLC). Median survival time (MST) of the patients (n = 11) with unresectable NSCLC, who were given optimal chemotherapy according to CDDST, was 15.8 months and MST of those (n = 16) who did not have any sensitive agents according to CDDST was 5.6 months. There was significant difference between these two groups (p = 0.0048; logrank).

Antineoplastic Agents↗

FR167653, a cytokine synthesis inhibitor, exhibits anti-inflammatory effects early in rat carrageenin-induced pleurisy but no effect later.

We prepared a pharmacological profile of FR167653 (1-[7- (4-fluorophenyl)-1,2,3,4-tetrahydro-8-(4-pyridyl) pyrazolo[5,1-c][1,2,4]triazin-2-yl]-2-phenylethanedion sulfate monohydrate), a cytokine synthesis inhibitor, on early (5 h after irritation) and late (14-24 h after irritation) phases of rat carrageenin-induced pleurisy and on mediator-induced plasma exudation, in comparison with that of dexamethasone. In the early phase, FR167653 (30 mg/kg) and dexamethasone (0.3 mg/kg) equipotently suppressed plasma exudation and leukocyte infiltration. Furthermore, both agents significantly lowered the prostanoid levels in the exudate. Expression of cyclooxygenase-2 protein on leukocytes in the early phase of inflammation was not affected by dexamethasone, but it was suppressed by FR167653. However, FR167653 did not significantly affect the leukocyte mRNA level of cyclooxygenase-2. Both agents significantly suppressed the levels of both tumor necrosis factor-alpha and interleukin-1beta. FR167653 had a different pharmacological profile from dexamethasone in the late phase of this model in that, unlike dexamethasone, it did not affect cyclooxygenase-2 expression in mesothelial cells, the 6-keto-prostaglandin F1alpha level in the exudate or hyperplasia of mesothelium. Furthermore, unlike dexamethasone, FR167653 did not consistently inhibit mediator-induced plasma exudation. These results suggest that FR167653 or one of its analogs may be new candidates for therapy with a spectrum of activity distinct from that of current anti-inflammatory steroids.

Animals↗