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Biomedical subjects

T Iwama

Publications and source records attributed to T Iwama.

At least 127 records · Page 7Linked to original sources
PubMed1993

Coexistence of somatic and germ-line mutations of APC gene in desmoid tumors from patients with familial adenomatous polyposis.

Desmoid tumors, which are locally invasive with recurrence but without metastasis, are frequently observed in patients with familial adenomatous polyposis after abdominal surgery or during pregnancy. This study analyzed mutation of the adenomatous polyposis coli gene in 8 desmoid tumors from 7 familial adenomatous polyposis patients using polymerase chain reaction-single-strand conformation polymorphism and the direct sequencing method. Seven somatic mutations, 1 somatic allele loss, and 6 germ-line mutations were detected. The majority of adenomatous polyposis coli gene mutations were deletions of 1 to 19 base pairs in exon 15, and all mutations led to the formation of stop codons. A somatic mutation with repetition of 82 base pairs from codon 1399 to 1426 was also observed in a desmoid, which was most likely caused by an error during replication or repair replication. No mutation was detected in exons 1 to 2 of H-ras, K-ras, and N-ras genes and in exons 5 to 8 of p53 gene, in these tumors. The simultaneous existence of somatic and germ-line alterations of adenomatous polyposis coli gene observed in all 8 tumors strongly suggests that inactivation of both alleles of adenomatous polyposis coli gene is involved in the development of desmoid tumors.

Adenomatous Polyposis Coli↗
PubMed1993

The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on the antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs.

The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs was studied. Ketotifen was used as a reference drug. S-1452 at doses of 1 and 3 mg/kg (per oral administration, 1 h before the injection of U-46619) clearly inhibited U-46619-induced pulmonary pressure increase. Ketotifen at a dose of 10 mg/kg did not affect U-46619-induced bronchoconstriction. S-1452 at doses of 3 and 10 mg/kg and ketotifen at a dose of 10 mg/kg inhibited the antigen-induced bronchoconstriction in guinea pigs which had been passively sensitized with guinea pig IgE antibody. S-1452 at a dose of 10 mg/kg inhibited repeated antigen provocation-induced airway hyperresponsiveness in guinea pigs. The accumulation of inflammatory cells by antigen provocation in bronchial alveolar lavage fluid (BALF) was inhibited by ketotifen but not by S-1452. These results indicate the efficacy of S-1452 on antigen-induced bronchoconstriction and antigen-induced airway hyperresponsiveness in guinea pigs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Inhibition of aspartate chemotaxis of Escherichia coli by site-directed sulfhydryl modification of the receptor.

Thr-154 of the chemoreceptor Tar in Escherichia coli is important for aspartate sensing. Taking advantage of the fact that Tar has no Cys residues, we have further investigated the role of Thr-154 by replacing it with Cys in order to subject it to SH modification. Tar-T154C retained the abilities of aspartate sensing and repellent sensing. However, when cells with Tar-T154C were treated with an SH-modifying reagent, 5,5'-dithiobis-2-nitrobenzoic acid (DTNB), they specifically lost the ability to sense aspartate; the ability was restored by the reducing reagent, 1,4-dithiothreitol. DTNB showed no detectable effect on the function of wild-type Tar or serine-replaced Tar, Tar-T154S. Thus, DTNB modifies Cys-154 of Tar-T154C in intact cells and causes a specific defect in the aspartate-sensing ability of Tar. The addition of 1 mM or higher concentrations of aspartate resulted in protection of Cys-154 from the modification; serine had no effect in this regard. These results that not only is Thr-154 important for aspartate sensing but also, it may be located at the actual aspartate-binding site.

Aspartic Acid↗
PubMed1993

The impact of familial adenomatous polyposis on the tumorigenesis and mortality at the several organs. Its rational treatment.

The authors reviewed the case records of 1050 familial adenomatous polyposis (FAP) patients who were registered at their institution. The organ-specific morbidity and mortality rates of malignant tumor in FAP patients were compared with those of the general population of Japan, and the prognosis after rectum-preserving operation also was calculated. The cumulative prevalence of colorectal carcinoma at the age of 44 years was 0.52 for men and 0.61 for women. The observed/expected morbidity ratio was 20.9 (95% confidence interval, 10.8-36.6) for thyroid carcinoma, 3.08 (2.03-7.75) for gastric carcinoma, and 295 (263-330) for colorectal carcinoma. The observed/expected mortality ratios was 250 (112-447) for periampullary and small intestinal carcinoma, 3.43 (1.77-6.0) for gastric carcinoma, and 210 (183-241) for colorectal carcinoma. The risk of rectal carcinoma after ileorectal anastomosis was 13% (8.5-17.5%) at 10 years and 37% at 20 years. The results clarified the impact of FAP on the carcinogenesis in several organs as a whole including preserved rectum, and suggested a direction of the rational treatment of FAP.

Adenomatous Polyposis Coli↗
PubMed1993

Effect of murine recombinant interleukin-5 on bronchial reactivity in guinea-pigs.

We have reported that an intratracheal injection of murine recombinant interleukin-5 (mrIL-5, 15 micrograms/0.25 ml/animal) induces the increased number of inflammatory leucocytes and epithelial cells in bronchoalveolar lavage fluid (BALF) 24 hr after administration of mrIL-5 in guinea-pigs [1]. In this paper, we have examined the effects of mrIL-5 on bronchial reactivity in guinea-pigs. An intratracheal injection of mrIL-5 (15 micrograms/0.25 ml/animal) induced airway hyperresponsiveness to acetylcholine (ACh) which was accompanied with eosinophilia and neutrophilia in blood at 24 hr in guinea-pigs. Bovine serum albumin (BSA, 15 micrograms/0.25 ml/animal) used as a reference material did not cause airway hyperresponsiveness, blood eosinophilia and neutrophilia. Prednisolone (20 mg/kg, i.p.) inhibited mrIL-5-induced airway hyperresponsiveness, eosinophilia and neutrophilia. Ketotifen (2 mg/kg, i.p.) also reduced this airway hyperresponsiveness and neutrophilia but not eosinophilia. In contrast, the injection of 2% disodium cromoglycate (DSCG) into the trachea showed the tendency of inhibitory effects against mrIL-5-induced airway hyperresponsiveness, eosinophilia and neutrophilia. The present data indicate that mrIL-5 induces airway hyperresponsiveness, blood eosinophilia and neutrophilia in guinea-pigs and that prednisolone and ketotifen inhibit mrIL-5-induced airway hyperresponsiveness accompanied with reduction of the increased number of leucocytes, suggesting that eosinophils and neutrophilia in blood may be important for the onset of bronchial hyperresponsiveness caused by mrIL-5 in guinea-pigs.

Animals↗
PubMed1993

Effects of NZ-107 on airway inflammation and cell activation in guinea-pigs.

The effects of NZ-107 on some airway inflammation models and the generation of superoxide anion (O2-) were studied in guinea-pigs. Airway inflammation was caused by intra-tracheal injection of murine recombinant interleukin-5 (mrIL-5, 15 micrograms/animal), inhalation of platelet-activating factor (PAF, 0.003%) and intra-tracheal injection of leukotriene B4 (LTB4, 10 micrograms/animal). NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) at a dose of 50 mg kg-1, intraperitoneally reduced mrIL-5- and PAF-induced eosinophilia. This compound at a dose of 25 and 50 mg kg-1 also suppressed LTB4-induced eosinophilia and neutrophilia in bronchoalveolar lavage fluid (BALF). On the other hand, prednisolone at a dose of 20 mg kg-1, i.p., prevented the increased number of macrophages, eosinophils and neutrophils induced by mrIL-5, the increased number of eosinophils induced by PAF and the increased number of eosinophils and neutrophils induced by LTB4 in BALF. Furthermore, both drugs reduced mrIL-5- or PAF-induced increase in the number of airway epithelial cells in BALF. The generation of O2- was measured by the method of cytochrome C reduction. NZ-107 (10-100 micrograms mL-1) attenuated PAF- and FMLP-induced O2- production from macrophages and reduced PAF-induced O2- generation by eosinophils but had no effect on that from neutrophils. These results indicate that NZ-107 prevents the increased number of pulmonary eosinophils and airway epithelial cells and the activation of macrophages and eosinophils, suggesting that NZ-107 may be useful as a remedy for airway inflammatory diseases such as bronchial asthma.

Animals↗
PubMed1993

Effects of MKS-492 on antigen-induced bronchoconstriction and allergic reaction in guinea pigs and rats.

Effects of R[+]-8-([1-[3,4-dimethoxyphenyl]-2-hydroxyethyl]amino) -3,7-dihydro-7-[2-methoxyethyl]-1,3-dimethyl-1H-purine-2,6-dione (MKS-492), a reported type III isozyme inhibitor of cyclic nucleotide phosphodiesterase, on antigen- or platelet activating factor (PAF)-induced bronchoconstriction and allergic reactions in guinea pigs and rats were investigated. 1) MKS-492 inhibited antigen-induced bronchoconstriction in guinea pigs. Aminophylline also inhibited the reaction. 2) MKS-492 inhibited PAF-induced bronchoconstriction and inhibited the increase in airway responsiveness to histamine in guinea pigs, although aminophylline failed to affect these reactions. 3) MKS-492 relaxed guinea pig tracheal muscle in vitro more potently than aminophylline. 4) MKS-492 inhibited leukotriene B4 (LTB4)-induced airway eosinophilia in guinea pigs. 5) MKS-492 inhibited passive cutaneous anaphylaxis and mediator-induced skin reactions in rats more potently than aminophylline. Both drugs inhibited antigen- and phospholipase A2-induced histamine release from guinea pig lung tissue. 6) MKS-492 inhibited PAF-induced O2- generation from guinea pig alveolar macrophages. These results indicate that MKS-492 is a more potent inhibitor of allergic bronchoconstriction and PAF- or LTB4-induced inflammatory reactions in guinea pigs and the allergic cutaneous reactions in rats when compared to aminophylline.

Aminophylline↗
PubMed1993

Percutaneous transluminal coronary angioplasty for acute myocardial infarction.

Between 1986 and 1991, direct coronary angioplasty was attempted in 79 patients. The procedure was successful in 76 patients (96%), unsuccessful without complications in 2 patients, and major complications occurred in 1 patient (ventricular fibrillation and cardiogenic shock). Reperfusion was obtained from 1 to 7.5 hours (mean: 3.3 +/- 1.3 hours) after the onset of chest pain. Among the 76 successfully dilated patients, there was one cardiac death and 68 had predischarge angiography (64 patent, 2 stenosed, and 2 occluded). Although only 33 of the 58 patients (57%) angiographically followed after discharge showed persistence of primary patency, 52 of the 57 (91%) followed further obtained final patency when angioplasty was repeated up to 4 times. These results indicate that direct angioplasty in the community hospital setting can achieve a high primary success rate and a low reocclusion rate.

Adult↗
PubMed1993

[Clinical efficacy of coronary angioplasty for totally occluded lesions in recent transmural myocardial infarction].

Percutaneous coronary angioplasty was used to treat the occlusive lesions responsible for prior myocardial infarction occurring 1-8 weeks previously. Angioplasty was successful in 31 of 33 patients' lesions. Follow-up angiography showed dilated lesions were patent (0-50% diameter stenosis) in 10 patients, mildly stenosed (51-74%) in 3, severely stenosed (75-90%) in 10, subtotally occluded in 2, totally occluded in 5 and one was lost to follow-up. By repeating angioplasty up to two times, the lesions became patent in 23 patients, mildly stenosed in one, totally occluded in 4, and 3 were lost to follow-up. Measuring the left ventricular function in 22 patients with patent lesions and one with mildly stenosed lesion showed the left ventricular ejection fraction was improved from 60 +/- 13.1 to 69 +/- 11.6% (p < 0.00005), and hypokinetic areas (from 18 +/- 15.1% of left ventricular wall to 11 +/- 9.9%, p < 0.05) and an akinetic area (from 11 +/- 12.5% to 4 +/- 7.3%, p < 0.002) were decreased. The findings indicate that angioplasty for totally occluded lesions within 12 weeks of infarction achieves satisfactory lesion patency and functional recovery of the infarcted myocardium.

Angioplasty, Balloon, Coronary↗
PubMed1993

[Ticlopidine may prevent subtotal or total occlusion of dilated lesions after percutaneous coronary angioplasty].

The efficacy of ticlopidine and probucol plus oryzanol for reducing restenosis after dilation was examined in 151 patients with 229 stenotic lesions treated by coronary angioplasty after complete resolution of associated acute myocardial infarction, unstable angina, and variant angina. The stenotic lesions were 90% or less in diameter and less than 10 mm in length, and residual stenosis was 40% or less after treatment. Patients were randomly assigned to receive no medication, ticlopidine (200 mg daily) and/or probucol (1,000 mg daily) plus oryzanol (300 mg daily). One hundred forty-six patients with 220 dilated lesions were examined angiographically to evaluate restenosis. The medications achieved no clear reduction in restenosis, but subtotal or total reocclusion occurred in 6 of 102 patients not receiving ticlopidine, and in none of 118 patients receiving ticlopidine (p < 0.008). Ticlopidine may prevent subtotal or total reocclusion in dilated lesions.

Angioplasty, Balloon, Coronary↗
PubMed1993

[Cavernous angioma in the cerebellopontine angle: a case report].

A rare case of cavernous angioma (CA) in the cerebellopontine angle (CPA) is reported. A 60-year-old female suffered from a right progressive sensorineural hearing loss and a successive right facial paresis over 2 years. A small mass was detected in her right CPA on CT scans. Both T1- and T2-weighted MR images demonstrated an intracanalicular lesion protruding into the CPA as being hyperintense. A small red colored lobulated tumor involving the 7th and 8th cranial nerves was found in the CPA through the suboccipital approach. The tumor contained multiple small hematomas in various stages. Biopsy with evacuation of these hematomas was selected to avoid damaging the cranial nerves. Histological examination of the specimen disclosed it as CA. Postoperatively her facial paresis improved slightly, but her hearing loss remained unchanged. Discussions were carried out concerning clinical and neuroradiological features of CA in the internal auditory canal and CPA. The present case and a previously reported 17 cases were the subjects under discussion.

Cerebellar Neoplasms↗
PubMed1992

Coronary angiography using 4-French preformed catheters--percutaneous brachial approach.

4-French performed catheter systems were developed for coronary angiography. After several new technical features were introduced, these catheters were applied in 384 outpatients between January 1989 and December 1989. Diagnostic coronary angiography was performed in all cases without major complications. In the left coronary artery, 4.0 cm left Judkins catheters were generally used; however, 3.5 cm left Judkins catheters were used if the patient was < or = 164 cm tall and left Amplatz catheters were employed for those > or = 165 cm tall. Although 4.0 cm right Judkins catheters were mainly used for right coronary arteries, there were no predictive factors for subsequent catheter selection. This technique is believed to be suited to meet the increasing demand for coronary angiography.

Adult↗
PubMed1992

Proton nuclear magnetic resonance studies on water structure in peritumoral edematous brain tissue.

Spin-lattice relaxation times (T1) of water protons and cross-relaxation times (TIS) between irradiated protein and water protons were measured to study the water structure in peritumoral edematous brain tissue of rats. Despite small changes in T1, water, and electrolyte contents, TIS values of water protons were significantly reduced in peritumoral edematous brain tissue when compared to those of the controls. Results indicate that the water structure in brain tissues may become altered at an early stage of edemic formation without causing any significant changes in cellular hydration. TIS might serve as a sensitive parameter for studying the water structure in a variety of tissues, such as in edematous brain tissue.

Animals↗
PubMed1992

Proton NMR studies on ischemic rat brain tissue.

The spin-lattice relaxation time (T1) of water protons and the cross-relaxation time (TIS) between irradiated protein protons and observed water protons were measured in order to study water-macromolecular interactions in ischemic rat brain tissues. Tissues were obtained by bilateral common carotid artery occlusion from stroke-prone spontaneously hypertensive rats. Water, Na, and K contents were measured in ischemic brain tissue at the same time. Water and Na content increased while the TIS value and K content decreased following ischemic insults. The T1 value did not change until 180 min after ischemia had been induced. Changes in the TIS value occurred earlier than changes observed for the T1 value, water, and electrolyte contents. Results indicate that the value of TIS may be useful for detecting cerebral ischemia and that the physical structure of water-macromolecular interaction may be altered soon after ischemic onset in brain tissue.

Animals↗
PubMed1992

Loss of normal allele of the APC gene in an adrenocortical carcinoma from a patient with familial adenomatous polyposis.

Endocrine neoplasms have been reported occasionally in patients with familial adenomatous polyposis (FAP). An adrenocorotical carcinoma was studied in a patient with a family history of FAP. Loss of heterozygosity (LOH) in the region close to the adenomatous polyposis coli (APC) gene was detected in this carcinoma, and evidence was obtained that there was a loss of the normal allele of the APC gene. This is the first demonstration of LOH at the APC locus in adrenocortical tumors. The present results and our previous data on LOH in a recurring desmoid tumor suggest that the heterozygous mutant/wild-type condition of the APC gene may give rise to benign tumors, and that functional loss of this gene leads to development of tumors not only in the colon but also in other various parts of the body in FAP patients.

Adenomatous Polyposis Coli↗
PubMed1992

MRI demonstration of Kernohan's notch: case report.

We report a left acute subdural haematoma caused by rupture of a left anterior cerebral artery aneurysm, which progressed to left hemiparesis. Coronal MRI was superior to CT for visualizing Kernohan's notch.

Acute Disease↗
PubMed1992

Mutations in c-K-ras 2 gene codon 12 during colorectal tumorigenesis in familial adenomatous polyposis.

Colorectal carcinomas may be induced from adenomas, or they may occur de novo. To clarify the histogenesis of colorectal carcinomas, point mutations in codon 12 of the c-K-ras 2 gene in neoplasias of familial adenomatous polyposis patients were examined. Nineteen colorectal advanced carcinomas, 135 adenomatous polyps, 9 hyperplastic polyps, and 27 normal colonic mucosae were obtained from 48 patients. In 27 normal mucosae and 9 hyperplastic polyps, a mutation in the K-ras gene was not detected. Mutations were detected as follows: 0 of 24 in adenomas with mild atypia, 10 of 77 in adenomas with moderate atypia, and 24 of 34 in adenomas with severe atypia. The incidence of mutations in c-K-ras 2 codon 12 is correlated with the degree of atypia of adenomas. However, only 5 such mutations were detected in 19 advanced carcinomas, indicating that the mutation frequency in advanced carcinomas is much lower than that in adenomas with severe atypia. If a mutation of c-K-ras 2 gene is an important component in the formation of adenocarcinoma, these results did not confirm the successive development from adenomas with severe atypia to advanced carcinomas as the main route for colorectal carcinogenesis in familial adenomatous polyposis patients.

Adenomatous Polyposis Coli↗