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Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 577 records · Page 32Linked to original sources

Pathogenesis, treatment and prognosis of impending myocardial infarction and early post-infarction angina--relation between ST-segment shift during myocardial ischemia and the pathogenesis.

We studied 141 patients to evaluate the pathogenesis and clinical picture of high-risk unstable angina (UA), designated as impending myocardial infarction (IMI) in this study, or severe early post-infarction angina (PIA). IMI and PIA were diagnosed when chest pain appeared at rest and lasted 15 min or more despite extensive pharmacological therapy during hospital stay among consecutive 510 patients with UA. All patients underwent coronary angiography urgently within 72 h after chest pain, and were divided into 2 subgroups according to ST segment shifts during chest pain. In IMI, 42 patients with ST depression had higher incidences of prior myocardial infarction (MI), worsening UA, multivessel disease and complex lesions such as eccentric irregular lesion or ulceration. On the contrary, in 44 with ST elevation, new onset UA, single vessel disease and coronary thrombus (CT) were dominant. In PIA, 32 patients with ST elevation revealed higher incidences in Q wave MI, ST elevation at the MI onset, single vessel disease and CT, compared to 23 with ST depression who showed a high proportion of complex lesions. Thus, it was evident that there was a common link between the pathogenesis of IMI and PIA. The therapeutic options were also different in the groups according to ST segment shift. We conclude that ST segment shifts during chest pain may be useful for determining the pathogenesis and clinical features of high-risk UA.

Angina, Unstable↗

Inherited heterozygous protein C deficiency and dysfunctional protein S with recurrent venous thrombotic diseases: a study of three generations of a Japanese family.

We describe a rare occurrence of a family affected with venous thrombosis, exhibiting a protein C (PC) deficiency and dysfunctional protein S (PS). The propositus and his father developed recurrent venous-thrombosis. Their PC deficiency was characterized by low levels of both antigen and activity, and their dysfunctional PS was suggested by low PS activities despite the presence of normal free PS antigen. Over three generations, six family members had a PC deficiency, and three had both a PC deficiency and a dysfunctional PS. The mode of inheritance of PC deficiency appears to be autosomal dominant.

Adolescent↗

[Problems in ulcer surgery after the introduction of H2-receptor antagonists].

Recently, antisecretory drugs such as H2-receptor antagonists (H2-RA) or proton pump inhibitor have been used for peptic ulcer patients widely in Japan. However, there are possibilities that long term administration of H2-RA might cause changes in intragastric environment. The present study was designed to clarify the changes of surgical treatment in Japan Surgical Society training hospitals, before and after introduction of H2-RA. Serum gastrin and antral G-cell number was measured after administration of H2-RA (1 mg/kg 14 days continuous infusion) in rat. Also, acid secretion and gastrin response stimulated by adrenalin (40 ng/kg.min) were measured in duodenal ulcer patients. 1) In the view of surgical treatment, elective operation highly decreased after the introduction of H2-receptor antagonists, and showed the increase of the rate of emergency operation up to 70%. 2) Hypergastrinemia and antral G cell hyperplasia were observed after administration of H2-RA in rats. 3) Acid secretion stimulated by adrenalin which is considered as antral G cell dependent, showed a higher response in H2-RA treated cases than in those untreated. 4) Antrectomy was carried out in 43.4% of the patients treated with H2-RA versus 18.9% to the patients untreated.

Animals↗

[A new polar map to quantify reversible area by myocardial 201Tl single photon emission computed tomography and clinical application to patients before and after percutaneous transluminal coronary angioplasty].

In the studies of stress 201Tl single photon emission computed tomography, we have developed a computer method to discriminate reversible from irreversible defect, then quantify each area and display the area on the polar map. Initial percent uptake (%Ui) and delayed percent uptake (%Ud) were expressed as percent of the maximum uptake area and were defined as regional myocardial 201Tl uptake in initial and delayed image, respectively. The %Ud/%Ui ratio was defined as redistribution ratio (RD-ratio). The values of %Ui obtained from each pixel of short axis slices were plotted against the values of RD-ratio on XY co-ordinates. In this graphic display, normal area, ischemic viable area and non viable area were separated by the following four lines. A; The straight line (Y = 2.0-0.012X) indicating the relationship between %Ui and RD-ratio for the group with ischemic viable myocardium. B; The parallel line to A and shifted to -1.5 SD from A. C; The vertical line at 67.0% level (ischemic upper level). D; The vertical line at 27.6% level (viable lower level). Each area was discriminated by color display and calculated relative area values were displayed on the polar map. Criteria for discriminating each area were derived from the results of ischemic pre-transluminal coronary angioplasty (PTCA) lesions (n = 21) in which viability was confirmed by successful PTCA and previous results of 66 cases with single vessel disease and 16 cases of control group. This new computerized technique was applied for evaluation of another group with successful PTCA (n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Dipyridamole-thallium myocardial imaging in patients unable to exercise adequately: comparison with arm and bicycle ergometer].

We assessed the usefulness of dipyridamole-thallium myocardial imaging in patients unable to exercise adequately, compared with arm-ergometer and standard (bicycle) ergometer. Fifty-six patients with arteriosclerosis obliterans, aortic aneurysm, aortic dissection and so on, who were revealed normal imaging, were studied. Only one of 13 cases with arm-ergometer and two of 14 with bicycle ergometer reached target heart rate. Lung thallium uptake in the cases with arm-ergometer (37 +/- 9%) is higher than that with dipyridamole (29 +/- 5%). This elevation may be confused with pectoralis muscle uptake. Washout rate is 45 +/- 9% with dipyridamole and 46 +/- 12% with bicycle ergometer, respectively, though there was no significant differences. Myocardial/background counts ratio with dipyridamole (4.6 +/- 0.8%) is significantly higher than that with arm and bicycle ergometer (arm-ergometer; 3.5 +/- 0.7, bicycle ergometer; 4.2 +/- 0.9). Then, myocardial image with dipyridamole have superior quality. We concluded that dipyridamole-thallium myocardial imaging is very useful in the patients who have suboptimal exercise efforts.

Aged↗

[Large volume intraperitoneal chemotherapy as treatment for the peritoneal carcinomatosis from gastric cancer].

Gastric cancer sometimes spread to peritoneal surfaces in the absence of lymphatic or hematogenous metastases. For the treatment of peritoneal carcinomatosis, we applied large volume intraperitoneal chemotherapy (L.V.I.C.). In L.V.I.C., drugs were administered with large volume of saline through the reservoir buried in the subcutaneous tissue of the abdominal wall. We used mitomycin C (MMC), 5-fluorouracil (5-FU) and CDDP and examined the pharmacokinetics of these drugs when they were administered by this method to the patients of peritoneal carcinomatosis. A marked pharmacokinetic advantage was observed when 5-FU and CDDP were administered. AUC of these drugs were much larger than that of MMC. In vitro sensitivity test (SDI test) was useful for the selection of adequate drugs for each patient. On this method, drugs were distributed widely in the abdominal cavity and the patients could be taken this treatment repeatedly as out-patient. L.V.I.C. seems to fulfill the need for a safe, effective and acceptable delivery system of intraperitoneal chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Usefulness of 201Tl myocardial scintigraphy after dipyridamole infusion in patients with atherosclerotic vascular disease].

To determine the utility for detecting ischemic heart disease (IHD), Dipyridamole thallium myocardial images (DIP-Tl) have been performed in the 103 patients with atherosclerotic vascular disease who can't exercise fully. Of 103 patients, there were 36 patients with arteriosclerosis obliterans (ASO), 31 patients with aneurysm of the abdominal aorta (AAA), 24 patients with aneurysm of the thoracic aorta (TAA) and 12 patients with dissecting aortic aneurysm (DAA). Clinical evidence of IHD was found in 20 patients with ASO, 10 with AAA, 7 with TAA and 4 with DAA respectively. Positive evidence of DIP-Tl was identified in 66% of 41 patients who had clinical evidence of IHD, and particularly in the patients with AAA (80%) and ASO (65%). On the other hand, in the patients without clinical evidence of IHD, positive evidence of DIP-Tl was identified in 19% of 62 patients and particularly in the patients with AAA (39%). In all patients, the percentage of the positive DIP-Tl ratio was 38%. And, when the 38% patients of the positive DIP-Tl were added to the patients of the negative DIP-Tl who had clinical evidence of IHD, almost half patients (51%) were considered to be complicated with IHD. This study suggests that the atherosclerotic vascular disease is highly complicated with IHD and DIP-Tl is useful to detect IHD.

Aged↗

[Successfully treated intraoperative coronary artery spasm in a patient with type B dissecting aortic aneurysm: a case report].

A 65-year-old man with chronic type B dissecting aortic aneurysm, complicated by variant from of angina pectoris without any coronary artery obstructed disease on preoperative angiogram was operated upon through left posterolateral thoracotomy under the left heart bypass with Bio-pump system using preoperative Ca antagonists and intraoperative nitroglycerin infusion. Shortly before the end of operation the patient suddenly developed shock status definitely due to coronary artery spasm, associated with ST-elevation in II, III, aVF and bradycardia, then ventricular tachycardia, finally cardiac arrest. The patient was resuscitated by cardiac massage and administration of nifedipine and nitroglycerin. Such attacks repeated five times at ten or twenty minutes intervals. The coronary artery spasm could be successfully suppressed with the additive use of noradrenaline infusion. The patient had no attacks at all postoperatively and was discharged with good success. This case suggests that the prevention of intraoperative coronary artery spasm is essential, but if it occurs, additive use of noradrenaline infusion is effective for the cessation of coronary artery spasm.

Aged↗

Cyclic adenosine 3',5'-monophosphate suppresses interleukin 1-induced synthesis of matrix metalloproteinases but not of tissue inhibitor of metalloproteinases in human uterine cervical fibroblasts.

Interleukin 1 (IL-1) mediates many cellular functions, but the signal transduction mechanisms of its actions are not clearly understood. Here, we have examined the exact participation of cAMP in the IL-1-induced production of the precursors of matrix metalloproteinase (MMPs) and their specific inhibitor, tissue inhibitor of metalloproteinases (TIMP) in human uterine cervical fibroblasts. IL-1 significantly augmented the production of proMMP-1 (vertebrate procollagenase), proMMP-3 (prostromelysin), and TIMP without detectable changes in the intracellular level of cAMP. Dibutyryl cAMP (Bt2cAMP) and the cAMP elevating agent (forskolin) did not replace IL-1 as MMP inducers. On the contrary, the IL-1-mediated induction of proMMP-1 and proMMP-3 was significantly suppressed by treatment of the cells with Bt2cAMP, forskolin, or theophylline. The suppressive effect of Bt2cAMP on the IL-1-induced production of proMMP-1 and -3 was not due to the inhibition of zymogen secretion, but resulted from the decrease in the steady-state levels of proMMP-1 and proMMP-3 mRNAs. In contrast, Bt2cAMP slightly enhanced the IL-1-induced production of TIMP. The synthesis of proMMP-2 (72-kDa progelatinase/type IV procollagenase) was not altered by IL-1 and/or Bt2cAMP. These results suggest, first, that induction of proMMP-1 and -3 synthesis may share similar transduction pathways but they are distinct from those for proMMP-2 and TIMP synthesis and, second, that cAMP does not function as a second messenger in the MMPs' induction upon IL-1 stimulation in human uterine cervical fibroblasts. Thus, it is further suggested that the system that increases the intracellular cAMP level may be involved in negative regulation of proMMP-1 and -3 production.

Animals↗

Effects of transient forebrain ischemia and reperfusion on function of dopaminergic neurons and dopamine reuptake in vivo in rat striatum.

To clarify functional changes of dopaminergic neurons and dopamine (DA) reuptake during and after ischemia, extracellular DA levels in striatum were determined using in vivo brain microdialysis in a 4-vessel occlusion model of male Wistar rats with and without pharmacological interventions. Without interventions, the extracellular DA levels markedly increased during ischemia, but upon reperfusion, rapidly returned to control level. Infusion of tetrodotoxin, a blocker of voltage-dependent Na+ channels, was without effect on the DA surge during ischemia, but decreased the DA levels after reperfusion to the same extent as in control rats. Pretreatment with nomifensine, an inhibitor of DA reuptake, was also without effect on the surge, but reduced the rate of DA decline after reperfusion to one-fifth of the rate without the pretreatment. When nomifensine was administered 40 min after reperfusion, extracellular DA levels increased to the same extent as in control rats. Infusion of high K+ 1 h after reperfusion induced a smaller increase in extracellular DA levels than that in control rats. It took 96 h for this reduced response to high K+ stimulation to recover after reperfusion. These results suggest that the DA surge during ischemia is mainly derived from action potential-independent DA release (means dysfunction of dopaminergic neurons), although activity of DA reuptake is completely inhibited. After reperfusion, the basal function of dopaminergic neurons and activity of DA reuptake rapidly recover, but the neurons are functionally disturbed to release less DA in response to a given stimulus for several days.

Animals↗

cDNA cloning of a novel testis-specific calcineurin B-like protein.

A cDNA clone encoding a novel calcineurin B-like protein (CBLP) was isolated from a rat testis cDNA library by cross-hybridization with a calcineurin B cDNA probe. CBLP is composed of 176 amino acids and contains four putative Ca(2+)-binding domains. The overall predicted amino acid sequence homology between CBLP and calcineurin B is 82%. Northern blots showed that transcripts for CBLP are specifically and highly expressed in the testis.

Amino Acid Sequence↗

Purification and amino acid sequence of a bitter gourd inhibitor against an acidic amino acid-specific endopeptidase of Streptomyces griseus.

An inhibitor (BGIA) against an acidic amino acid-specific endopeptidase of Streptomyces griseus (Glu S. griseus protease) was isolated from seeds of the bitter gourd Momordica charantia L., and its amino acid sequence was determined. The molecular weight of BGIA based on the amino acid sequence was calculated to be 7419. BGIA competitively inhibited Glu S. griseus protease with an inhibition constant (Ki) of 70 nM, and gel filtration analyses suggested that BGIA forms a 1:1 complex with this protease. However, two other acidic amino acid-specific endopeptidases, protease V8 from Staphylococcus aureus and Bacillus subtilis proteinase (Glu B. subtilis protease), were not inhibited by BGIA. BGIA had no inhibitory activity against chymotrypsin, trypsin, porcine pancreatic elastase, and papain, although subtilisin Carlsberg was strongly inhibited. The amino acid sequence of BGIA shows similarity to potato chymotrypsin inhibitor, barley subtilisin-chymotrypsin inhibitor CI-1 and CI-2, and leech eglin C, especially around the reactive site. Although the residue at the putative reactive site of these inhibitors is leucine or methionine, the corresponding amino acid in BGIA is alanine.

Amino Acid Sequence↗

Calmodulin differentially modulates the interleukin 1-induced biosynthesis of tissue inhibitor of metalloproteinases and matrix metalloproteinases in human uterine cervical fibroblasts.

The effects of a specific calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on the synthesis of tissue inhibitor of metalloproteinases (TIMP) and precursor of matrix metalloproteinase 1/tissue collagenase (proMMP-1) and matrix metalloproteinase 3/stromelysin (proMMP-3), were examined using human uterine cervical fibroblasts in culture. When the cells were treated with human recombinant interleukin 1 alpha, the synthesis of TIMP, proMMP-1, and proMMP-3 was greatly enhanced along with the increase in the steady-state levels of mRNAs for respective proteins. The treatment of the cells with human recombinant interleukin 1 alpha and W-7 further augmented the production of proMMPs-1 and -3 and the accumulation of their mRNAs. In contrast, TIMP production and its steady-state mRNA level were reduced considerably under these conditions. Similar observations were made with another calmodulin inhibitor, trifluoperazine, but not with N-(6-aminohexyl)-1-naphthalenesulfonamide, the weakest inhibitor for calmodulin. These results indicate that calmodulin is required for the interleukin 1-enhanced synthesis of TIMP but it is a suppressor for the synthesis of proMMPs-1 and -3.

Blotting, Northern↗

Hormonal regulation of collagenolysis in uterine cervical fibroblasts. Modulation of synthesis of procollagenase, prostromelysin and tissue inhibitor of metalloproteinases (TIMP) by progesterone and oestradiol-17 beta.

Rabbit uterine cervical fibroblasts produced a large amount of matrix metalloproteinases (MMPs) such as collagenase (MMP-1) and stromelysin (MMP-3) and a small relatively amount of tissue inhibitor of metalloproteinases (TIMP). When cells were treated with progesterone or oestradiol-17 beta, both steroids concurrently decreased the level of procollagenase and prostromelysin in the culture media and the steady-state levels of the respective mRNAs. On the other hand, the level of TIMP in the culture media and the steady-state level of its mRNA were simultaneously increased by these steroids. Similarly, the suppression of production of MMPs and the augmentation of TIMP production by both steroids were observed with interleukin 1 (IL-1)-treated cells, but the action of progesterone was more effective than that of oestradiol-17 beta in the IL-1-untreated and -treated cells. These results suggest that collagenolysis in uterine cervical fibroblasts is negatively regulated by steroid hormones via the acceleration of TIMP production and the suppression of synthesis of MMPs at the pretranslational level.

Animals↗

Subrenal capsule assay using nude mice as a predictor of the response of the gastric cancer to chemotherapy.

Feasibility of utilizing human gastric cancers as first transplant generation xenografts in nude mice for determining tumor sensitivity to chemotherapeutic agents was demonstrated by applying subrenal capsule (SRC) assay. A total of 55 human gastric tumors from patients were tested in this assay. Mitomycin-C (MMC) and hexycarbamyl-5-FU (HCFU, 5-FU derivative) were selected for the treatment of these patients after surgery and also for this assay as first transplant. Evaluable rate of MMC in this assay was 92.7% and that of HCFU was 90.9%. Sensitivity of tumors to MMC was 25% and to HCFU was 32%. Correlation between response to chemotherapy of human tumors in patients and in nude mice was 78.6%. These results indicate that this assay could predict effective drugs for patients with gastric cancer.

Adenocarcinoma↗