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Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 289 records · Page 16Linked to original sources
PubMed1997

Increased sensitivity of scid heterozygous mice to ionizing radiation.

In the present study, acute effects of ionizing radiation on animal survival, bone marrow cells and fibroblast cell lines of scid homozygous, scid heterozygous and wild-type mice with the same C.B-17 genetic background were examined. The sensitivities to ultraviolet light (UV) and various chemicals, bleomycin, mitomycin C, N-methyl-N'-nitro-N-nitrosoguanidine, methyl methanosulphonate, 5-fluorouracil, 6-mercaptopurine, 4-nitroquinoline 1-oxide and potassium bromate) were also investigated. In addition, micronucleus testing of whole-body irradiated mice was performed. Scid heterozygous mice were found to be less sensitive than the homozygotes but more sensitive to ionizing radiation than wild-type mice, not only in vivo but also for bone marrow cells in vitro, suggesting partial dominance under both conditions. In contrast, there were no differences in sensitivity to UV light and various chemicals, as compared with wild-type and scid heterozygous cell lines, either in vitro or in the micronucleus test.

Animals↗
PubMed1997

Colonoscopy for frank bloody stools associated with cancer chemotherapy.

Diarrhea is a common complication of cancer chemotherapy, while bloody stool is rare. Pseudomembranous colitis has been reported as causing bloody diarrhea after chemotherapy. In this report, we describe nine consecutive patients who presented frank bloody stools within one month after cancer chemotherapy. Patients with a history of pelvic irradiation or with a previously identified colorectal tumor were excluded. Among nine patients, bleeding from tumor undetected before chemotherapy was seen in three, pseudomembranous colitis in four, ischemic colitis in one and methicillin-resistant Staphylococcus aureus enterocolitis in one. Of the three tumors, one was an adenomatous polyp and the other two were metastatic tumors. Two of the four patients with pseudomembranous colitis had not received antibiotics before the onset of colitis. Causes of bloody stools after chemotherapy were various and colonoscopy played an important role in diagnosis and prompt therapy.

Adenocarcinoma↗
PubMed1997

Pretreatment with topical 60% lidocaine tape reduces pain on injection of propofol.

UNLABELLED: We determined whether pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol compared with mixing intravenous lidocaine with propofol. In a randomized, double-blind trial, 90 patients were allocated to one of three groups: pretreatment with a bioocclusive dressing and administration of a premixed solution of propofol 180 mg and 2 mL of normal saline (Group A); pretreatment with 60% lidocaine tape and a premixed solution of propofol and normal saline (Group B); or pretreatment with a bioocclusive dressing and a premixed solution of propofol 180 mg and lidocaine 40 mg (Group C). The incidences of pain in Groups A, B, and C were 86.7%, 33.4%, and 20%, respectively. Group B and Group C had a significantly lower incidence of pain than Group A. There was no significant difference in the incidence of pain between Group B and Group C. There was no significant difference in the distribution of site of pain on injection of propofol among the three groups. Pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol similar to that of intravenous lidocaine mixed with propofol. IMPLICATIONS: Pretreatment with topical 60% lidocaine tape reduces the pain associated with injection of propofol, a frequently used intravenous anesthetic. This approach should increase patient comfort during induction of anesthesia.

Administration, Cutaneous↗
PubMed1997

Recovery of heart rate variability profile in patients after coronary artery surgery.

UNLABELLED: We examined the different characteristics of heart rate variability (HRV) to define the time course of HRV profile after coronary artery surgery (CAS). Spectral analysis of HRV was performed on a 512-s segment of R-R intervals of the electrocardiogram on the preoperative day and on Postoperative Days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28. Power spectral area was divided into low (0.04-0.15 Hz; LF)- and high (0.15-0.5 Hz; HF)-frequency components. Fractal slope and sympathovagal slope of 1/f characteristics of HRV were determined in two different frequency ranges (from 0.01 to 0.15 Hz and from 0.01 to 0.5 Hz, respectively). Three recovery profiles of HRV were identified. Early HRV recovery profiles (Postoperative Days 1-6) included reduction in LF, HF, and sympathovagal slope, as well as an increase in fractal slope. Subsequent HRV recovery profiles (Postoperative Days 7-21) revealed reductions in LF, HF, and sympathovagal slope. Fractal slope became normal. Later HRV recovery profiles (Postoperative Day 28) demonstrated that all spectral components of HRV remained reduced, but sympathovagal and fractal slopes became normal. These changes in the HRV profile after CAS suggest significant postoperative alterations in cardiovascular homeostasis with significant but incomplete recovery during the first 28 postoperative days. IMPLICATIONS: Heart rate variability reflects normal neural regulation of cardiac function. This variability remains depressed as long as 28 days after coronary artery bypass surgery, but can recover as early as 1 wk postoperatively. Despite implied loss of normal neural regulation of cardiac function, a specific correlation between depressed heart rate variability and outcomes was not performed.

Adult↗
PubMed1997

Genetic alterations in patients with esophageal cancer with short- and long-term survival rates after curative esophagectomy.

OBJECTIVE: The objective of this study was to ascertain the exact relation between specific oncogenes and long- and short-term survival rates in patients with esophageal cancer. SUMMARY BACKGROUND DATA: Recent developments in molecular biology have shown that several oncogenes and suppressor genes are involved in the development of esophageal cancer. However, the role of these genes still is unknown. METHODS: The clinical outcome of 84 cases of R0-resected esophageal carcinomas (from 1986-1993) and the molecular and biologic characteristics of these tumors were studied. The patients studied were divided into three groups, which were designated as follows: shortest term survivors (up to 6 months), short-term survivors (7-12 months), and long-term survivors (>5 years). These groups included 23, 17, and 44 subjects, respectively. For the genomic analysis, CyclinD1, int-2, murine double minute 2 (MDM2), retinoblastoma, p53, adenomatous polyposis coli (APC), deleted in colorectal carcinoma (DCC), and human papillomavirus were studied in these patients. The regrowth capability of primary cultures and the clinicopathologic characteristics of these patients also were analyzed. RESULTS: The CyclinD1 and int-2 genes, which are located in the 11q13 chromosome, and the MDM2 gene were related to short survival. However, the p53 mutation and human papillomavirus infection were not related to short-term survival. The average ratio of genomic abnormalities to genes examined was higher in the shortest and short-term survival groups than in the long-term survival group. Regrowth capability in primary cultures also was related to short-term survival. Among the long-term survival patients, 7 (16%) of 44 cases suffered further cancer after esophagectomy. CONCLUSIONS: These results suggest that the 11q13 amplicon and MDM2 may play an important role in the progression of esophageal cancer, and an accumulation of genomic abnormalities may result in poor prognosis. Careful follow-up testing for double cancer is needed in long-term survivors of esophageal cancer.

Chromosome Aberrations↗
PubMed1997

How are macular changes reflected in pattern visually evoked cortical potentials?

To investigate the macular contribution to the amplitude and latency of pattern visual evoked cortical potentials (PVECPs), we recorded PVECPs in patients with unilateral macular disease (retinal diseases involving the macular region) and optic neuritis. We selected patients with visual acuities better than 0.3, which is thought to be the minimum acuity to provide clearly discernible responses. The visual stimulus was a checkerboard. We varied the check size in 4 steps as 7, 14, 28, and 56 min of arc, and the contrast was 20% or 80%. The amplitude of the sinusoidal wave of steady-state VECPs (12 Hz) and the P100 component of a transient VECP (3 Hz) were measured. Significant attenuation and delay of PVECPs in the affected eye were found in the macular disease group. Macular disease may cause an increase of VECP latency. However, VECP seemed to be a more sensitive test of optic nerve disease than of macular disease, when patients had similar visual acuities.

Adult↗
PubMed1997

Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is highly homologous to genes encoding Xenopus importin, yeast SRP1 and human RCH1.

From a human fetal-brain cDNA library, we isolated and characterized a novel gene (KPNA3) encoding a protein highly homologous to certain nuclear transport proteins of Xenopus and human. The complete cDNA clone, designated karyopherin alpha 3, contained an open reading frame of 1,563 nucleotides encoding 521 amino acids. The predicted amino acid sequence showed 48%, 45% and 48% identity with Xenopus importin, yeast SRP1 and human RCH1, respectively. The similarities among these proteins suggest that karyopherin alpha 3 may be involved in the nuclear transport system. Eight repeats of the arm motif were well conserved among these proteins. The N-terminal region of the predicted karyopherin alpha 3 product was highly basic and the C-terminal region was strongly acidic. A 4.3-kb transcript was expressed in all adult human tissues examined by Northern blotting. The cDNA clone was assigned to chromosome band 13q14.3 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1997

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.

PURPOSE: A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. PATIENTS AND METHODS: Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed. RESULTS: The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). CONCLUSION: The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.

Adult↗
PubMed1997

Dynamics of actin in cardiac myofibrils and fibroblast stress fibers.

The exchangeability of actin in cardiac myofibrils and fibroblast stress fibers was investigated using fluorescent analogue cytochemistry in combination with fluorescence recovery (FR) after photobleaching. Living embryonic chicken cardiac myocytes and fibroblasts were microinjected with rhodamine (rh)-labeled muscle and nonmuscle actins. After incorporation of the fluorescent actin analogue into cellular structures, small areas of labeled structures were photobleached with a laser pulse. In cardiac myofibrils, FR in their proximal striated portions occurred at a slower rate than that in their proximal nonstriated and distal terminal portions with each rh-isoactin injected. Thus, nascent myofibrils at different developmental stages display different actin exchangeabilities. Further, in all portions of myofibrils, FR of rh-muscle actin was faster than that of rh-nonmuscle actin. This indicates that actin molecules in cardiac myofibrils cannot be readily exchanged by heterotypic nonmuscle actin. In fibroblasts, photobleaching of stress fibers yielded similar results in both their proximal mid-points and distal terminal portions, and the FR rate was consistently faster than that observed in any part of the myofibrils. This result seems to be related to the dynamic properties of actin filaments in stress fibers at all portions. Further, the fact that stress fibers possessed a similar exchange rate with muscle and nonmuscle actins appears to be related to a more primitive nature of stress fibers than myofibrils.

Actins↗
PubMed1997

Studies on aromatase inhibitors. IV. Synthesis and biological evaluation of N,N-disubstituted-5-aminopyrimidine derivatives.

In order to study the potency of the 5-aminopyrimidine skeleton as an aromatase inhibitor, we synthesized various N,N-disubstituted-5-aminopyrimidine derivatives and evaluated their aromatase-inhibitory activity (in vitro) and their inhibitory activity on pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis (in vivo). Compounds with the fluoro-substituted benzyl group showed potent aromatase inhibition. Among them, 5-[(4-cyanophenyl)(3,5-difluorobenzyl)amino]pyrimidine (5w, YM553) was a highly potent compound with an IC50 value of 0.038 nM for aromatase from human placenta. Its inhibitory effect was approximately four times greater than that of YM511. In addition, YM553 was a weak inhibitor of other enzymes involved in steroid hormone synthesis. These results indicate that YM553, as well as YM511 (a 4-amino-4H-1,2,4-triazole derivative), is a promising agent for the treatment of estrogen-dependent diseases.

Animals↗
PubMed1997

Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: synthesis and pharmacological properties of 2-phenyl-4'-[(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]benzanil ide derivatives.

A series of compounds structurally related to 4'-[(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]benzanili de was synthesized and demonstrated to have arginine vasopressin (AVP) antagonist activity for both V1A and V2 receptors. The introduction of a phenyl or a 4-substituted phenyl group into the ortho position of the benzoyl moiety resulted in an increase in both binding affinity and antagonistic activity. The 2-(4-methylphenyl) derivative (1g) exhibited high antagonistic activities for both V1A (8.6-fold) and V2 (38-fold) receptors and high oral activity (8.6-fold) compared with the 2-methyl lead compound (1a). Detail of the synthesis and the pharmacological properties of this series are presented.

Anilides↗
PubMed1997

Studies on aromatase inhibitors. II. Synthesis and biological evaluation of 1-amino-1H-1,2,4-triazole derivatives.

1-N,N-Disubstituted amino-1-H-1,2,4-triazole derivatives were prepared and evaluated for aromatase-inhibitory activity (in vitro) and for the inhibitory activity on pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis (in vivo). 1-N-para-Substituted benzylamino derivatives, having an electron-withdrawing group on the phenyl moiety, exhibited aromatase-inhibitory activity in vitro and in vivo. Among them, 1-[(4-nitrobenzyl)(4-nitrophenyl) amino]-1H,1,2,4-triazole (5b) was the most potent aromatase inhibitor. These 1-N-benzylamino derivatives also showed relatively strong inhibitory activity on aldosterone synthesis, indicating that the selectivity of these derivatives for aromatase inhibition was not sufficient in comparison with that of the 4-amino-4H-1,2,4-triazole derivatives.

Aldosterone↗
PubMed1997

Studies on aromatase inhibitors. III. Synthesis and biological evaluation of [(4-bromobenzyl)(4-cyanophenyl)amino]azoles and their azine analogs.

A series of [(4-bromobenzyl)(4-cyanophenyl)amino]azoles and their azine analogs, which have the side chain of the selective aromatase inhibitor YM511, were synthesized and evaluated for aromatase-inhibitory activity (in vitro) and for pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis inhibitory activity (in vivo). Among these aza-heterocycles, the pyrimidin-5-yl derivative (6a) was the most potent aromatase inhibitor and its in vitro inhibitory activity was comparable to that of YM511. Compound 6a also showed weak inhibitory activity on aldosterone synthesis. These data indicated that the pyrimidin-5-yl moiety is useful as a new azole fragment in place of the 4H-1,2,4-triazol-4-yl moiety of the aromatase inhibitor YM511.

Aldosterone↗
PubMed1997

Role of platelets in myocardial ischemia-reperfusion injury in dogs.

We investigated the involvement of circulating platelets in myocardial ischemia-reperfusion injury in canine autoperfused heart-lung preparations using filters to deplete platelets and/or leukocytes. The left anterior descending (LAD) coronary artery was occluded for 40 min, followed by 40 min reperfusion, in 3 groups: a leukocyte-platelet-depleted (LPD) group, in which both leukocytes and platelets were depleted; a leukocyte-depleted (LD) group, in which leukocytes alone were depleted; and a control group. There were no differences in hemodynamics or arrhythmias among groups before or during coronary occlusion. After reperfusion, the maximum rate of change in left ventricular pressure during systole and diastole was significantly higher in the LPD group than in the control and LD groups. The LPD group also showed gradual recovery of regional myocardial function and a decrease in the frequency of premature ventricular contractions. The LD group showed a slight improvement in cardiac function and arrhythmias compared with the control group. Although there was no significant difference in the pulmonary arterial plasma level of thromboxane B2 at any stage among groups, the control group showed an increase after reperfusion. These results suggest that platelets are important in reperfusion injury and that the depletion of both leukocytes and platelets effectively protects against reperfusion injury.

Animals↗
PubMed1997

Measurement of hemodynamics of auditory cortex using magnetoencephalography and near infrared spectroscopy.

Near infrared (NIR) spectroscopy, a non-invasive optical method for monitoring hemodynamics, was applied to record evoked auditory response of the human brain. Our newly developed system detected the amount of oxygenated and deoxygenated hemoglobin in the area of the local brain located beneath the probes. In the study, we used magnetoencephalography (MEG) and NIR spectroscopy to observe the blood component change near the auditory cortex. The sound stimulus of 1 kHz sine wave at 70 dB SPL was used to elicit evoked responses in both experiments. The active region of the auditory cortex was determined by MEG, and the same area was examined by the NIR system. The results from the NIR experiments showed significant increases of total hemoglobin and deoxygenated hemoglobin, indicating that both blood flow and oxygen consumption at the cortical area increased in response to the sound stimuli. The NIR recordings at the two different depths revealed that the increases of local blood flow and oxygen consumption were observed at depths ranging between 20 and 30 mm from the scalp.

Adult↗
PubMed1997

Biological activities of novel zaragozic acids, the potent inhibitors of squalene synthase, produced by the fungus, Mollisia sp. SANK 10294.

Four novel zaragozic acids, F-10863A, B, C and D, were isolated from a culture broth of the fungus Mollisia sp. SANK 10294. F-10863 compounds contain a 4,6,7-trihydroxy-2,8-dioxyobicyclo-[3.2.1]octane-3,4,5-tricarboxyl ic acid core like previously reported zaragozic acids, but the structures of the side chains are different. Recently, it was found that F-10863A is identical to zaragozic acid D3, while the other three are novel compounds. F-10863 compounds are potent inhibitors of squalene synthase like previously reported zaragozic acids, and, furthermore, they exhibit serum cholesterol-lowering activity in vivo.

Animals↗
PubMed1997

[The effect of low-rose prostaglandin E1 on circulation, respiration and body temperature during surgical anesthesia].

We investigated the effects of low-dose prostaglandin E1 (PGE1) on circulation, respiration, and body temperature during surgical anesthesia. We studied 109 adult patients undergoing upper abdominal operations under thoracic epidural combined with inhalational anesthesia. Patients were divided into 2 groups; Control group (n = 42) and PGE1 group (n = 67). In PGE1 group, PGE1 infusion was started at the rate of 0.02 microgram.kg-1.min-1 before the induction of anesthesia and was terminated at the end of surgery. There were no differences between the groups in demographic, anesthetic and surgical characteristics. After treatment with PGE1, arterial pressure decreased slightly but significantly, resulting in lower arterial pressure in PGE1 group than in control group before the induction of anesthesia. After the induction of anesthesia, however, arterial pressure decreased significantly in both groups, and the differences in arterial pressure between the groups were not observed any more during surgery. Heart rate was not different between the groups throughout the study period. Intraoperative urine output was greater in PGE1 group than in control group. PaO2/FIO2 ratio was not different between the groups both before and during anesthesia. Rectal temperature remained slightly but significantly lower in PGE1 group throughout surgery. Rectal-to-palm temperature gradient tended to be smaller in PGE1 group 1 hour after the induction of anesthesia. Low-dose PGE1 reduced arterial pressure. However, the difference in arterial pressure between the groups was so small that the difference disappeared during surgery. Meanwhile, low-dose PGE1 increased urine output, suggesting that renal blood flow was better-maintained with PGE1. In spite of several investigations reporting an unfavorable effect of PGE1 on PaO2, low dose PGE1 did not affect PaO2 in this study. Finally low-dose PGE1 reduced core temperature, though slightly, probably through redistribution of the body heat.

Adult↗