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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 505 records · Page 28Linked to original sources

Diminished heat shock protein 70 mRNA induction in aged rat hearts after ischemia.

Vulnerability of aged hearts to ischemia may be due to defects in protective mechanisms provided by heat shock proteins (HSPs). To determine whether there is a defect in the induction of HSPs by ischemia in old hearts, HSP72 and HSP73 (inducible and constitutive HSP70, respectively) mRNA induction was examined in young (2-mo-old; n = 36) and old (18-mo-old; n = 32) rat hearts. Transient (10- or 20-min) ischemia was applied by tightening a snare placed around left coronary arterial branches 3 days before examination to avoid the effect of operation on induction. HSP72 mRNA was induced markedly in young hearts after 10-min ischemia, peaked at 2 h, but was induced only slightly in old hearts. HSP73 mRNA was also induced in young hearts, peaked at 4 h, but was not induced in old hearts. The mRNAs were markedly induced in old hearts as well after 20-min ischemia, which was accompanied by the induction of HSP72 protein. Thus the age-related modulation of HSP72 and HSP73 mRNAs suggests a defective sensing mechanism for ischemia in old hearts.

Aging↗

Excitatory connections between upper cervical inspiratory neurons and phrenic motoneurons in cats.

This study aimed to determine whether upper cervical inspiratory neurons (UCINs), which are localized in the intermediolateral part of the gray matter of the upper cervical segments, have propriospinal connections to phrenic motoneurons of the ipsilateral lower cervical segment in anesthetized cats. Unit action potentials of UCINs were extracellularly recorded simultaneously with ipsilateral phrenic nerve activity. To eliminate the descending influences from medullary respiratory neurons to phrenic motoneurons, bulbospinal conduction paths were temporarily blocked by focal cooling applied to the ventral caudal medulla at the pyramidal decussation level by means of a cooling thermode (1 mm tip diam). By using a spike-triggered method, during cooling phrenic nerve activities were evoked by UCIN spikes that were elicited by microinjection of L-glutamate for 20 of the 55 (36%) UCIN units examined. The onset latencies of these phrenic motoneuron responses ranged from 1.5 to 7.1 ms (mean 3.6 ms), depending on synaptic transmission delays. These results clearly demonstrate that UCINs have, at least in part, excitatory mono- and paucisynaptic connections with ipsilateral phrenic motoneurons.

Animals↗

Comparative study of the effects of cefodizime and HBW 538 in potentiating the production of reactive oxygen species by human polymorphonuclear leukocytes.

The immunomodulatory activity of cefodizime (CDZM), an aminothiazolylcephalosporin, was compared to that of HBW 538, a derivative of the CDZM side chain at position 3 (the mercaptothiazolyl group) in respect to the production of reactive oxygen species (ROS) by human whole blood and polymorphonuclear leukocytes (PMN) in vitro. Ten-fold diluted whole blood and PMN from healthy individuals were incubated with CDZM or HBW 538 alone at the concentrations of 1, 10, or 100 micrograms/ml, or CDZM or HBW 538 at 100 micrograms/ml in combination with tumor necrosis factor-alpha (TNF-alpha) at 100 U/ml or lipopolysaccharide (LPS) at 1 microgram/ml. The production of ROS was measured by a chemiluminescence (CL) assay in which luminol was added to a mixture and after which the PMN or whole blood were stimulated with nonopsonized zymosan or phorbol myristate acetate. The following results were obtained: (1) The CL responses of whole blood and PMN were slightly but not significantly enhanced by CDZM at 100 micrograms/ml, whereas both CL responses were significantly enhanced by exposure to HBW 538 at 10 and 100 micrograms/ml. (2) The enhanced PMN CL response which followed priming with TNF-alpha or LPS was not augmented by CDZM but was significantly augmented by HBW 538. These results indicate that the ability of the HBW 538 molecule to enhance the production of ROS by stimulated PMN and to act agonistically with TNF-alpha or LPS is abrogated when HBW 538 is part of the CDZM molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotaxime↗

The protective effect of L-threo-3,4-dihydroxyphenylserine on ischemic hippocampal neuronal death in gerbils.

BACKGROUND AND PURPOSE: L-Threo-3,4-dihydroxyphenylserine (DOPS) is reported to increase the nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells, and this effect is not blocked by treatment with decarboxylase inhibitor. NGF is suggested to play an important role in neuronal survival and regeneration under pathological conditions. We evaluated the possible protective effect of DOPS against hippocampal CA1 cell death after transient forebrain ischemia in gerbils. METHODS: Male mongolian gerbils were treated with DOPS (30, 100, or 300 mg/kg IP) plus benserazide (10 mg/kg IP) (n = 28) or vehicle (n = 7) before 3.5 minutes of forebrain ischemia. For histopathologic study, the animals were decapitated 7 days after recirculation, and neuronal density of the hippocampal CA1 area was counted after cresyl violet staining. For immunohistochemical study, another group of gerbils (n = 34) was recovered for 1, 3, and 8 hours and 1, 2, and 7 days, when they were decapitated. The brain sections were stained against NGF, NGF receptor, and HSP70 using the avidin-biotin-peroxidase method. RESULTS: Preservation of the hippocampal CA1 cells was found in the brains treated with 300 mg/kg DOPS plus benserazide (neuronal density, 125 +/- 24 cells per millimeter) compared with the vehicle-treated ones (49 +/- 11 cells per millimeter) (P < .01). The immunoreactive NGF was greatly reduced from 3 hours after recirculation in the vehicle group, but it was much less reduced in the 300-mg/kg-DOPS-plus-benserazide group as compared with the vehicle group. The immunoreactivity for NGF receptor was gradually induced from 1 hour after recirculation with the peak at 1 day in the vehicle group, but it was only slightly induced at 8 hours in the 300-mg/kg-DOPS-plus-benserazide group. HSP70 immunoreactivity was also induced from 3 hours with the peak at 1 day in the vehicle group. However, in the 300-mg/kg-DOPS-plus-benserazide group, the induction of HSP70 was found from 8 hours and was much less intensive. CONCLUSIONS: Treatment with DOPS is protective to the ischemic hippocampal CA1 cells, and the NGF-receptor system may play a role in this protective effect of DOPS.

Animals↗

Gamma-delta T cells in sarcoidosis. Correlation with clinical features.

This study investigated the relationship between the clinical features of sarcoidosis and the level of peripheral blood gamma-delta (gamma delta) T cells. Both the mean percentage of T cells and the mean cell number of gamma delta T cells in the peripheral blood were significantly higher in patients with clinically active sarcoidosis than in patients with inactive sarcoidosis or active tuberculosis and in normal subjects (active sarcoidosis: 18.9 +/- 17.2%, 142 +/- 130.4 cells/microliters, n = 29; inactive sarcoidosis: 7.0 +/- 3.7%, 48.7 +/- 35.0 cells/microliters, n = 16; active tuberculosis: 4.3 +/- 3.2%, 47.9 +/- 36.6 cells/microliters, n = 19; control subjects: 5.0 +/- 1.9%, 77.6 +/- 37.7 cells/microliters, n = 12). gamma delta T cells were significantly elevated in patients with sarcoidosis for 2 yr or more or those with Stage III radiographs. The level of gamma delta T cells, however, showed no correlation to the serum angiotensin-converting enzyme, a marker of active granuloma formation. gamma delta T cells were scarcely seen in bronchoalveolar lavages and in biopsy specimens, suggesting that these cells did not increase at the sites of inflammation. These findings suggest that increased levels of gamma delta T cells in the peripheral blood occur in active, long-term sarcoidosis, but that they are not directly related to granuloma formation.

Adult↗

Prevalence and pathogenesis of silent myocardial ischemia following myocardial infarction.

The objective of this study was to examine the prevalence and pathogenesis of silent myocardial ischemia during exercise following myocardial infarction. Exercise-induced myocardial ischemia was assessed by 201Tl-SPECT (single photon emission computed tomography) 4.5 weeks after acute myocardial infarction in 229 patients. Exercise-induced myocardial ischemia occurred in 109 patients (48%), and 72 (32%) had silent ischemia. Although the prevalence of multivessel coronary artery disease was similar between patients with silent and symptomatic ischemia, the size of reversible myocardial ischemia was larger in patients with symptomatic ischemia than in those with silent ischemia (21.3 +/- 3.0% vs 13.2 +/- 1.9% of LV, p < 0.05). The incidence of reversible ischemia remote from the infarct area was higher in patients with symptomatic ischemia than in those with silent ischemia (30% vs 17%, p < 0.10). The cause of silent ischemia after myocardial infarction may be closely related to the smaller size of reversible myocardial ischemia. Ischemia remote from, or adjacent to, the infarct area could be a factor in determining the presence or absence of pain.

Coronary Angiography↗

Responses to hemodynamic stress in the aged heart.

In aged individuals the incidence of heart failure is higher than in younger subjects. Ischemic events are also common in the aged heart because of changes in the coronary vasculature and myocytes caused by aging. Adaptational responses to increased hemodynamic overload and to ischemia in the aged heart are discussed at the molecular, cellular and organ levels. One characteristic of the aged heart is a limited capacity for adaptation with hypertrophy to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun by hemodynamic stress. This diminution results from the aging of the heart per se and may be modulated by extracardiac factors. An age-related diminution was also observed in the mRNA induction of heat shock proteins by transient ischemia. However, this diminished induction of immediate early genes in the aged heart was not observed after more severe stress. With regard to the coronary vasculature, the age at which pressure-overload begins seems to be one of the important factors which determine the vascularity of hypertrophied hearts. Late-onset pressure-overload decreased dilator reserve in spite of the absence of myocardial hypertrophy. Thus, the responses to stress in the aged heart are quite different from those in the young heart. The limited capacity for adaptation to hemodynamic overload and poor protective mechanisms against stress may be causes of the higher incidence of heart failure in the aged.

Aged↗

[Age-related changes in the visual function of WBN/Kob rats--an electrophysiological study].

Changes in the visual function of the male WBN/Kob rat known as diabetic strain with increasing age were studied electrophysiologically. The measurements of electroretinogram (ERG) and visual evoked potential (VEP) in male WBN/Kob rats were performed at 5, 9, 13, 17, 23, 27, 36, 45, 54, 67 and 80 weeks of age, and compared with those in male Wistar/ST rats used as control. The prolonged latencies and decreased amplitudes of a- and b- waves and oscillatory potentials of ERG in WBN/Kob rats aged over 17 or 27 weeks were recorded under the light or after 20 min dark adaptation. The visual abnormality as indicated by non-recordable ERG was obvious in WBN/Kob rats aged 67 and 80 weeks. No changes of N1, P and N2 peak latencies of VEP were recorded in WBN/Kob rats with increasing age. The amplitudes between N1 peaks and P peaks decreased remarkably in WBN/Kob rats aged 54 weeks. The amplitudes of VEP in 67 or 80 weeks old rats in which ERG disappeared showed 26 or 28% of those in 5 weeks old rats. From these results, recording of ERG and VEP suggested that the visual abnormality occurred in male WBN/Kob rats aged 67 or 80 weeks and the process of visual abnormality with increasing age was clarified.

Aging↗

Age-related changes in the visual organ of WBN/Kob rats--an ophthalmoscopical study.

Changes in the visual organ with aging were investigated non-surgically in male WBN/Kob rats, in which spontaneous diabetic mellitus commonly occurs. Male Wistar/ST rats at the ages of 5, 9, 13, 17, 23, 27, 36, 45, 54, 67 and 80 weeks were examined for changes in the peri-orbital region, eyelid, lens, corpus vitreum and ocular fundus by macroscopic inspection and fundoscopy. The area around the eyelid was stained with reddish-brown excretions from the Harderian gland. This stain was frequently observed in rats of both strains aged 54 weeks or over, showing no difference in frequency between WBN/Kob rats and Wistar/ST rats. Lens opacity was observed in male WBN/Kob rats aged 67 weeks or over, and narrowing of the retinal artery and vein in those aged 36 weeks or over. The occurrence of lens opacity was consistent with that of visual dysfunction as determined by a test of the ability to differentiate light from dark using a Y-shaped apparatus (Kiyosawa et al., 1993).

Aging↗

Panclicins, novel pancreatic lipase inhibitors. II. Structural elucidation.

Panclicins A-E are novel and potent pancreatic lipase inhibitors produced by Streptomyces sp. NR 0619. Their structures have been elucidated based on NMR and FAB-MS experiments. The relative configurations have also been determined by NMR experiments. The absolute stereochemistry has been determined by the chiral HPLC analysis of the hydrolysates of panclicins A and B and by modified Mosher's method on a derivative of panclicin A. They are structurally related to beta-lactone esterase inhibitors of microbial origin, lipstatin, valilactone, ebelactones and esterastin. Panclicins also contain a beta-lactone structure with two alkyl chains, one of which has an N-formylalanyloxy or N-formylglycyloxy substituent.

Lactones↗

[Study of clinical usefulness of an antiandrogen, TZP-4238, as a drug for treatment of benign prostatic hypertrophy--its influence on sexual function].

Using chlormadinone acetate (CMA) as the control drug, a double-blind study was carried out to examine not only the effects of 17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP-4238;) on subjective urinary symptoms but also, especially, that on the sexual function in patients with benign prostatic hypertrophy (BPH). The clinical efficacy rate in relation to the subjective urinary symptoms was about the same in the two treatment groups; 45.9% in the TZP-4238 group and 50.0% in the CMA group. However, the incidence of adverse effects on the sexual function showed a marked difference between the two groups. The TZP-4238 group revealed a lower suppressive effect on the function than the CMA group (45.1% vs. 71.4%). In relation to their causation of other adverse effects, there were no differences between the two drugs. Accordingly, in consideration of the facts that TZP-4238 with less influence on the sexual function affords a superior quality of life to elderly patients, while achieving effective treatment by means of a convenient single daily administration, TZP-4238 was surmised to be a more useful drug than CMA as an antiandrogen for the treatment of BPH.

Aged↗

[Thoracoscopic observation and diagnosis in cases of pleural, mediastinal, and pulmonary lesions].

Thoracoscopy was performed in a total of 424 patients at our institute from January 1970 to December 1993. The indications for thoracoscopy were pneumothorax (121 cases), primary lung cancer (98 cases), mediastinal tumor (45 cases), metastatic lung tumor (23 cases), pleuritis (35 cases), diffuse lung disease (38 cases), tuberculosis (20 cases), benign lung tumor (10 cases), and other (34 cases). By 1990, diagnostic thoracoscopy had been performed in 383 patients. Since 1991, thoracoscopy has been used therapeutically for spontaneous pneumothorax (24 cases), mediastinal and chest wall tumors (9 cases), pulmonary nodules (2 cases), and others (8 cases). Findings useful for diagnosis were obtained in 326 cases and biopsy was performed in 173 cases. Thoracoscopy was especially useful in the diagnosis of diffuse lung disease, pleuritis, and small pulmonary nodules. Recent advances in endoscopic equipment and refinement of thoracoscopic techniques have expanded the application of this procedure. Our experience indicates a markedly expanded role for thoracoscopy in the diagnosis and treatment of thoracic diseases, with less postoperative morbidity.

Humans↗

[Efficacy of PCR-microwell plate hybridization method (Amplicor Mycobacterium) for detection of M. tuberculosis, M. avium and/or M. intracellulare in clinical specimens].

Recently, a new kit to detect and identify mycobacteria in clinical specimens was developed by Japan Roche Co. Limited. The new method is based on amplification of DNA of mycobacteria in clinical specimens by PCR and hybridization of amplified DNA by microwell plate hybridization method, which is the "Amplicor Mycobacteria, Roche, (AMP-M)". Cooperative study was organized with 15 tuberculosis hospitals and institutions throughout Japan, and 349 clinical specimens from newly admitted tuberculosis patients and/or suspects were collected during July and August, 1993. All the specimens were examined by smear microscopy (Ziehl-Neelsen's staining), culture on Ogawa egg media, culture on variant 7H9 liquid media and by AMP-M. Excluding 25 specimens which had failed to identify the species of mycobacteria because of contamination, disability to multiply on the transplanted solid media and so on, the results of the examinations in 324 specimens consisting of 167 specimens from previously untreated cases and those of 157 specimens from previously treated cases were analysed. Main results obtained were as follows; 1. Of 70 smear positive specimens from previously untreated cases, culture positive on Ogawa media and 7H9 media, and by AMP-M positive were 59 (84.3%), 61 (87.1%) and 66 (94.3%), respectively. Of 97 smear negative specimens, culture positive were 20 (20.6%), 22 (22.7%) and 27 (27.8%), respectively. The AMP-M showed the highest positive rate in both groups. 2. The sensitivity and the specificity of AMP-M in previously untreated cases were calculated by assuming that positive on Ogawa and/or variant 7H9 media is "positive". The sensitivity was 95.8% (68/71) and the specificity was 94.8% (91/96) for M. tuberculosis in previously untreated cases. The sensitivity and the specificity for M. avium and M. intracellulare were all 100%, although the numbers observed were small. 3. So-called false positive of the AMP-M were observed in 5 cases out of 96 culture negatives on both Ogawa and variant 7H9 media. However, all 5 cases were positive by repeated AMP-M, 3 become culture positive later, and another 2 showed clinical findings consistent with tuberculosis. Hence, the authors considered that the false positive rate of the AMP-M method is to be very low in previously untreated cases. 4. Of 86 smear positive cases with history of previous chemotherapy, the positive culture on Ogawa media, variant 7H9 media and that by AMP-M method were 64 (74.4%), 77 (89.5%) and 85 (98.8%), respectively. In the smear negative cases, culture positive was 10 out of 71 (14.1%), 13 (18.3%) and 24 (33.8%), respectively.

DNA, Bacterial↗

Metallothionein genes in the nematode Caenorhabditis elegans and metal inducibility in mammalian culture cells.

Genomic DNAs of metallothionein I and II in Caenorhabditis elegans (CeMT-I and CeMT-II) were isolated by YAC library/polytene filter hybridization followed by subcloning of corresponding cosmid clones. Both genes are mapped at chromosome V. Although the similarities of 5'-flanking regions and coding regions have shown only 55-58%, the introns are split at the same position in both genes, indicating that these two genes are originally from the same gene. While several metal responsive elements are conserved among eukaryotes, only one metal responsive element was found in the promoter region in CeMT-II and not in CeMT-I. Indeed, neither of 5'-flanking regions of CeMT-I nor CeMT-II connected to chloramphenicol acetyltransferase reporter gene is responsive to heavy metals in mammalian culture cells by transient transfection analysis. These results would suggest that the metal regulatory factors in C. elegans might be different from those conserved in invertebrates and vertebrates, although the MTs in C. elegans revealed the similarities to mammalian MTs in several points.

Amino Acid Sequence↗

[Anesthetic management of patients with dilated cardiomyopathy].

Anesthetic management of patients with dilated cardiomyopathy (DCM) was analyzed. From January 1991 to June 1993, we had 7 patients with DCM; 5 patients received general anesthesia and 2 patients received spinal anesthesia. General anesthesia was induced and maintained generally with diazepam and fentanyl. There were two patients who suffered from intraoperative arrhythmia. One patient who received spinal anesthesia suffered from ventricular fibrillation suddenly before the operation and we performed cardiopulmonary resuscitation successfully but the operation was cancelled. One patient who underwent emergency operation for gastric perforation suffered supraventricular tachycardia during the operation, and we were required to use antiarrhythmic agent that was thought to be deleterious to cardiac function. There was no patient who died perioperatively. There was one patient in the group IV of classification of Inoh which predicts the highest risk of dying from cardiac failure. In conclusion, it is important to control arrhythmia during the management of patients with DCM under anesthesia.

Adult↗

Effects of hypercarbic acidotic reperfusion on recovery of myocardial function after cardioplegic ischemia in neonatal lambs.

BACKGROUND: There is continued controversy over the management of pH during ischemia and reperfusion. Calcium overload is an integral feature of the injury resulting from ischemia and reperfusion, and hydrogen ions are known to blunt Ca2+ influx into cells because H+ inhibits the Na(+)-Ca2+ exchange and the slow calcium channels. Hypercarbia is one source of H+, but elevated CO2 level is also known to be a potent coronary vasodilator, which may be beneficial during early reperfusion. This study was designed to explore the effect of respiratory and metabolic acidosis during the initial phases of reperfusion after hypothermic cardioplegic ischemia in the neonatal lamb. METHODS AND RESULTS: Forty isolated, blood-perfused neonatal lamb hearts underwent 2 hours of cold cardioplegic ischemia followed by reperfusion with blood with various pH values. pH was controlled either by altering the FICO2 in the ventilating gas to the oxygenator (groups A through D) or by adding HCl to the reperfusate (group E). pH of the initial reperfusate was 6.8 in group A, 7.1 in group B, 7.5 in group C, and 7.8 in group D. In these groups, pH values were maintained for the initial 5 minutes of reperfusion and then corrected to 7.4 over 20 minutes by changing the FICO2 to the oxygenator. In group E, HCl was added to the reperfusate to give pH 6.8 (metabolic acidosis). pH was corrected after 5 minutes of reperfusion by administration of NaHCO3 and THAM over the next 15 minutes. At 30 and 60 minutes of reperfusion, left ventricular maximum developed pressure, dP/dt, -dP/dt, maximum developed pressure at V10 (volume that gave left ventricular end-diastolic pressure of 10 mm Hg during baseline measurements), and dP/dt at V10 were measured. Coronary blood flow and oxygen consumption (MVO2) were also measured to evaluate the metabolic recovery. Group A showed better functional recovery than groups B, C, or D (maximum dP/dt V10: group A, 88.3 +/- 7.7%; group B, 69.3 +/- 10.8%; group C, 74.6 +/- 10.3%; group D, 66.1 +/- 9.4%; and group E, 73.7 +/- 13.8% at 30 minutes [P < .05]; group A, 76.1 +/- 13.6%; group B, 61.9 +/- 8.6%; group C, 63.8 +/- 5.4%; group D, 57.9 +/- 9.4%; and group E, 62.6 +/- 12.7% at 60 minutes [P < .05]). Coronary blood flow was higher in group A than in other groups (A, 177.2 +/- 29.6%; B, 144.1 +/- 18.1%; C, 127.3 +/- 18.5%; D, 150.4 +/- 24.3%; and E, 106.0 +/- 20.0% [P < .05]). There were no significant differences in MVO2. CONCLUSIONS: These data indicate that hypercarbic reperfusion (pH 6.8) for a short period after ischemia improved functional recovery after cold cardioplegic ischemia in neonatal lamb hearts but that metabolic acidosis to an equivalent pH did not improve postischemic function. Possible mechanisms for this effect include reduction of calcium loading to the myocardium through H+ inhibition of calcium uptake or the induction of coronary vasodilation by hypercarbia.

Acidosis↗

[Left ventricular characteristics after Jatene operation for transposition of the great arteries with intact ventricular septum--comparative study of neonatal primary and two stage repairs].

Left ventricular characteristics in late postoperative period after the arterial switch operation (ASO) was evaluated in fifty-nine patients with transposition of the great arteries and intact ventricular septum. They included 22 neonates who underwent a neonatal ASO (Group I) and 37 patients who underwent a two-stage ASO (Group II). Group II was subdivided into two groups according to the presence or absence of aortic regurgitation in the late postoperative period as group IIa (aortic regurgitation [-], 22 patients) and group IIb (aortic regurgitation [+], 15 patients). Age at ASO ranged from 4 to 27 days (average 12.7 days) in the group I, 5 to 43 months (average 12.7 months) in the group IIa, and 4 to 54 months (average 16.3 months) in the group IIb. Postoperative follow-up period ranged from 8 to 68 months (average 25.0 months) in the group I, 12 to 74 months (average 59.0 months) in the group IIa, and 19 to 66 months (average 48.5 months) in the group IIb. Left ventricular end-diastolic volume was significantly smaller in the group I (123 +/- 19% of normal) than the group IIa (146 +/- 38 of normal) and the group IIa (183 +/- 53% of normal). And left ventricular ejection fraction was significantly higher in the group I (67 +/- 5%) than the group IIa (62 +/- 11%) and the group IIb (58 +/- 8%). Left ventricular normalized mass was significantly smaller in the group I (85 +/- 11% of normal) than the group IIa (113 +/- 14% of normal) and the group IIb (130 +/- 9% of normal).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗