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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 541 records · Page 30Linked to original sources
PubMed1993

Dissociation of HSP70 and HSC70 heat shock mRNA inductions as an early biochemical marker of ischemic neuronal death.

A significant dissociation of HSP70 and HSC70 heat shock mRNAs after a 10-min transient forebrain ischemia in gerbil was found only in the hippocampal CA1 neurons which eventually die after the initial ischemic insult, while other hippocampal neurons such as the dentate granule and the CA3 cells which survive ischemia expressed both mRNAs cooperatively. The dissociation was observed as early as after 8 h of reperfusion, a period far shorter than 3-4 days, when the cell death becomes pathologically evident. Thus, the dissociation may serve as a set of early biochemical markers for ischemic neuronal cell death.

Animals↗
PubMed1993

Preferential expression of HSC70 heat shock mRNA in gerbil heart after transient brain ischemia.

Inductions of mRNAs for heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 were examined in the cerebral cortex, cerebellum, heart, lung, kidney, and liver of gerbils after a 10-min transient forebrain ischemia. HSP70 mRNA was normally expressed in a small amount in the cerebellum, lung, and kidney, but was not expressed in the heart or liver in a detectable amount. A very small amount of HSP70 mRNA was also present in the cerebral cortex. HSC70 mRNA was normally present in all the organs examined with a variety in the amount. Eight hours after the cerebral ischemia, the level of HSP70 mRNA increased in the cerebral cortex, lung, and kidney. HSC70 mRNA levels also increased in all the organs. However, the increase of HSC70 mRNA was remarkable in the heart. Transient cerebral ischemia caused subsequent hyperthermia. Treatment of gerbils with an artificial hyperthermia without cerebral ischemia increased the HSP70 and HSC70 mRNA levels as well. However, the HSC70 mRNA level in the heart after cerebral ischemia was much higher than that in the case with hyperthermic treatment. These results suggest that HSC70 mRNA was preferentially induced in the heart after transient forebrain ischemia that was not only due to the subsequent hyperthermia.

Animals↗
PubMed1993

Eradication of metastatic tumour cells from lymph nodes by local administration of anti-CD3 antibody.

The possibility of in vivo removal of metastatic tumour cells from lymph nodes by local intradermal administration of an anti-CD3 monoclonal antibody (mAb) was examined. Murine tumour cells in the lymph nodes were completely eradicated by intradermal injections of the mAb. This treatment was effective for removal of Lewis lung cancer cells from lymph nodes, but not for removal of subcutaneous tumours of this cell line. This treatment induced in vivo cytotoxicity in the regional lymph nodes against the syngeneic tumour cells. The following in vitro studies suggested that the cytotoxicity was probably mediated mainly by CD4+ T cells, with slight participation of CD8+ T cells. Normal lymph node and spleen cells showed cytotoxicity after in vitro incubation with the mAb for 2 days. Cell sorting with a fluorescein-activated cell sorter showed that CD4+ T cells developed during the incubation to lyse syngeneic tumor cells directly by themselves, macrophages not being involved in this tumour cell lysis. The lytic activity was detected in the cellular fractions, but not in the culture supernatants of these T cells. Furthermore, it was completely blocked by specific antiserum for tumour necrosis factor-alpha (TNF alpha). An immunoprecipitation study revealed that these T cells expressed TNF alpha molecules of 26 kDa, but not of 17 kDa, suggesting that tumour cell lysis was caused by membrane-integrated integrated TNF alpha molecules. These results strongly suggest that local administration of anti-CD3 antibody is a very effective and appropriate procedure for eradication of metastatic tumour cells from regional lymph nodes.

Animals↗
PubMed1993

Effects of pH on brain energetics after hypothermic circulatory arrest.

The pH management that provides optimal organ protection during hypothermic circulatory arrest is uncertain. Recent retrospective clinical data suggest that the pH-stat strategy (maintenance of pH at 7.40 corrected to core temperature) may improve brain protection during hypothermic cardiopulmonary bypass with a period of circulatory arrest in infants. The impact of alpha-stat (group A) and pH-stat (group P) strategies on recovery of cerebral high-energy phosphates and intracellular pH measured by magnetic resonance spectroscopy (A, n = 7; P, n = 5), organ blood flow measured by microspheres, cerebral metabolic rate measured by oxygen and glucose extraction (A, n = 7; P, n = 6), and cerebral edema was studied in 25 4-week-old piglets undergoing core cooling and 1 hour of circulatory arrest at 15 degrees C. Group P had greater cerebral blood flow during core cooling (54.3% +/- 4.7% versus 34.2% +/- 1.5% of normothermic baseline, respectively; p = 0.001). The intracellular pH during core cooling showed an alkaline shift in both groups but became more alkaline in group A than in group P at the end of cooling (7.08 to 7.63 versus 7.09 to 7.41, respectively; p = 0.013). Recovery of cerebral adenosine triphosphate (p = 0.046) and intracellular pH (p = 0.014) in the initial 30 minutes of reperfusion was faster in group P. The cerebral intracellular pH became more acidotic during early reperfusion in group A, whereas it showed continuous recovery in group P. Brain water content postoperatively was less in group P (0.8075) than in group A (0.8124) (p = 0.05). These results suggest that compared with alpha-stat, the pH-stat strategy provides better early brain recovery after deep hypothermic cardiopulmonary bypass with circulatory arrest in the immature animal. Possible mechanisms include improved brain cooling by increased blood flow to subcortical areas, improved oxygen delivery, and reduction of reperfusion injury, as well as an alkaline shift in intracellular pH with hypothermia in spite of a stable blood pH.

Acidosis↗
PubMed1993

Effect of methylprednisolone and prostacyclin on bronchial perfusion in lung transplantation.

In an experimental investigation using modified unilateral lung transplantation in pigs, the effects of systemic administration of methylprednisolone and prostacyclin on bronchial mucosal blood flow were assessed. Laser Doppler velocimetry (LDV) and radioisotope studies using radiolabeled erythrocytes (RI) were employed to measure blood flow at the donor main carina and upper lobe carina after 3 hours of reperfusion. The recipient carina was used as a reference point. Five groups of 6 animals each were studied. Group I served as control. In group II, methylprednisolone (20 mg/kg) was administered to the recipient. In group III, prostacyclin (4 ng.kg-1.min-1) was given to the recipient, and in group IV, prostacyclin (100 micrograms intravenously) was administered to the donor. In group V, prostacyclin was given to the recipient and the donor animals as in groups III and IV, respectively. In group I, bronchial blood flow at the donor main carina was 37.6% +/- 2.2% (LDV) and 44.1% +/- 14.8% (RI) of reference blood flow. No significant differences were found between the controls and groups II, III, and IV. In group V, bronchial blood flow was markedly increased both at the donor main carina (LDV, 39.8% +/- 6.2%, p = 0.12; RI, 55.7% +/- 11.4%, p < 0.2) and the donor upper lobe carina (LDV, 65.8% +/- 5.4%, p < 0.05; RI, 76.8% +/- 21.3%, p < 0.2). We conclude that systemic administration of prostacyclin to the donor and recipient results in marked improvement of bronchial blood flow and may reduce the incidence of bronchial complications after lung transplantation.

Animals↗
PubMed1993

Protective effect of bifemelane hydrochloride on ischemic hippocampal CA1 neuronal damage in the gerbil: relation to induction of HSP70.

A protective effect of bifemelane hydrochloride (BF) on hippocampal CA1 neuronal death in gerbils was investigated following transient forebrain ischemia in relation to the induction of 70-kd heat shock protein (HSP70) and its mRNA. Histological examination showed that the neuronal density of the hippocampal CA1 sector treated with 10 and 30 mg/kg of BF (i.p.) was higher than that of the vehicle (p < 0.05 and p < 0.01, respectively) at 7 days after ischemia. Immunohistochemistry against HSP70 protein and in situ hybridization for the mRNA revealed that the inductions of immunoreactive HSP70 and the mRNA were remarkably reduced and limited in the brain hippocampi treated with BF (30 mg/kg) as compared with vehicle-treated animals. These data indicate that BF possesses a protective effect against ischemic injury to the vulnerable CA1 neurons. The possible mechanisms of the protection are discussed.

Animals↗
PubMed1993

Differential projections to the raphe nuclei from the medial parabrachial-Kölliker-Fuse (NPBM-KF) nuclear complex and the retrofacial nucleus in cats: retrograde WGA-HRP tracing.

After injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP, 2 x 30 nl) [corrected] into the nucleus raphe magnus (NRM) of 6 cats, a number of retrogradely labelled neurons were observed in the rostral pons, mainly in the pontine pneumotaxic area, i.e., the medial parabrachial and Kölliker-Fuse (NPBM-KF) nuclear complex, and the tegmental field. In addition, a cluster of labelled cells was observed in the retrofacial nucleus (RFN) and its adjacent areas in the medulla. Control injections of the same volume of WGA-HRP into the medullary magnocellular tegmental field (2 mm lateral to the NRM) resulted in a much lower number of labelled neurons in the areas described above, and the labelled cells in the tegmental fields were predominant ipsilateral to the injected side. Injections into the nucleus raphe pallidus caudal to the NRM resulted in a diffuse distribution of labelled neurons, mainly in the tegmental fields of the pons and medulla. This study demonstrates that the NRM receives specific convergent projections from the NPBM-KF complex and the RFN in the medulla. It is suggested that these pathways are involved in the control of respiration.

Afferent Pathways↗
PubMed1993

Tracing of corticospinal fibers by extracellular pressure-injection of biocytin into the motor cortex in rats.

The aim of this study was to determine if biocytin, a low molecular analog of biotin, could reliably label details of corticospinal fibers at the lumbar level in rats. Biocytin (5%) was injected extracellularly by pressure into the unilateral hindlimb area of the motor cortex. Frozen sections of the injection sites and the lumbar segments were incubated with avidin-horseradish peroxidase (HRP). Terminal labeling of corticospinal fibers at the lumbar segments could be observed within 2-3 days of the injection. These results indicate that anterograde tracing with biocytin can be applied to label axons in a long tract such as the corticospinal tract in rats. Biocytin stain provided a view of a higher level of detail than wheat germ agglutinin (WGA)-HRP.

Animals↗
PubMed1993

Disturbance of a mitochondrial DNA expression in gerbil hippocampus after transient forebrain ischemia.

Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome c oxidase subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively decreased in the hippocampal CA1 neurons of gerbils from 1 to 3 h of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days. The activity of cytochrome c oxidase (COX) protein also showed the early decrease in the CA1 cells, and was followed by the reduction of the level of COX-I DNA after 2 days. However, the activity of succinic dehydrogenase (SDH), a mitochondrial enzyme that is encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells, and significantly decreased at 7 days. These results suggest that disturbance of mitochondrial DNA expression occurred in the CA1 neurons at the early stage of reperfusion, and was aggravated in the course of time. The disturbance could cause progressive failure of energy production of the cells that eventually results in the neuronal cell death.

Animals↗
PubMed1993

Changes of mitochondrial DNA and heat shock protein gene expressions in gerbil hippocampus after transient forebrain ischemia.

Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome C oxidase (COX) subunit I (COX-I), which is encoded by mitochondrial (mt) DNA, progressively decreased in the hippocampal CA1 neurons of gerbils from 3 h of reperfusion after 3.5 min of transient forebrain ischemia and completely disappeared at 7 days. The activity of COX protein also showed an early decrease in CA1 cells and was followed by reduction of the level of COX-I DNA after 2 days. However, succinic dehydrogenase, an mt enzyme encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells and significantly decreased at 7 days. The mRNA for mt heat shock protein (HSP) 60 began to increase at 3 h in the CA1 cells and was sustained until 1 day. The mRNAs for 72-kDa heat shock protein and 73-kDa heat shock cognate protein, which are located mainly in the cytoplasm, were induced together in the CA1 cells with a peak at 1-2 days. These results suggest that a disturbance of mt DNA expression occurred in the CA1 neurons at the early stage of reperfusion and was aggravated over the course of time. The disturbance could cause progressive failure of energy production of the cells that eventually results in neuronal cell death.

Animals↗
PubMed1993

Acceleration of HSP70 and HSC70 heat shock gene expression following transient ischemia in the preconditioned gerbil hippocampus.

To evaluate the mechanism of tolerance to ischemia, inductions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs in gerbil hippocampus were compared with in situ hybridization between cases of a single 3.5-min period of forebrain ischemia and a 3.5-min period of ischemia 2 days after 2-min pretreatment with ischemia. Immunohistochemistry for HSP70 protein and morphological studies were also performed in the same brains up to 7 days after the reperfusion. Following a single 3.5-min period of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. However, the hippocampal CA1 cells produced only a minimum of HSP70 protein, and the cells were almost lost by 7 days. Following 3.5 min of ischemia after 2-min pretreatment, large populations of the CA1 cells survived at 7 days. The peak time of the HSP70 and HSC70 mRNA induction shifted to an earlier period of reperfusion in all hippocampal cells as compared with the case of a single episode of ischemia. The peak of HSP70 and HSC70 mRNA induction shifted from 1 day to 3 h in the CA1 cells. The CA1 cells produced strongly immunoreactive HSP70 from 3 hr to 2 days. These results suggest that pretreatment with an initial period of ischemia (for 2 min) accelerated HSP70 and HSC70 gene expression at the transcriptional level, ameliorated the translational disturbance of HSP70 mRNA to protein, and saved the CA1 cells from subsequent lethal ischemia (for 3.5 min). These changes of heat shock gene expression might play important roles in the acquisition of ischemic tolerance of hippocampal CA1 neurons.

Animals↗
PubMed1993

Comparative in vivo study on the healing qualities of four different presealed vascular prostheses.

PURPOSE: The purpose of this article is to assess the healing qualities of presealed knitted polyester prostheses. METHODS: Thoracic aortic replacement was performed with grafts with four different coating materials-collagen (CP), albumin (AP), and two with gelatin (GP1/GP2)-in four groups of 15 pigs each. Two weeks, 6 weeks, and 6 months after operation, five pigs of each group were killed. Healing quality was assessed by morphometric analysis of the remaining coating, the extent of tissue ingrowth, and the thickness of the inner layer. RESULTS: The sealant was rapidly absorbed in all prostheses except for the AP (remaining coating at 2 weeks: GP1 22.1%, GP2 34.7%, and CP 68.0% vs AP 97.1% [p < 0.05]), remaining coating at 6 weeks: GP1/GP2 0% and CP 2.5% vs AP 76.7% (p < .01). At 6 months, remaining coating was only detectable in AP (21.5%). At 2 weeks the extent of tissue ingrowth ranged from 65.7% in GP1 and 75.3% in CP to 80% in GP2 versus 8.9% in AP (p < 0.05). There was a slow increase of tissue ingrowth until the sixth postoperative week (GP1 74.4%, GP2 85.0%, and CP 91.3% versus AP 19.6% [p < 0.01]). Thickness of the internal layer varied from 0.11 to 0.21 mm at 2 weeks in all grafts studied and from 1.02 mm (AP) and 1.28 mm (GP2) to 1.39 mm (GP1), versus 0.41 mm in the CP (p < 0.01) after 6 months of implantation. CONCLUSIONS: The type of coating significantly influences the healing properties of knitted polyester prostheses. When used for thoracic aortic replacement in pigs, AP coating clearly results in inferior healing compared with GP1/GP2 or CP impregnation, with digestion of the coating material and tissue ingrowth used as parameters. The thinnest internal layer was found in the CP prostheses, reflecting superior healing properties of this coating in the model studied.

Absorption↗
PubMed1993

The murine cot proto-oncogene: genome structure and tissue-specific expression.

We cloned and analyzed the murine cot proto-oncogene and examined its tissue-specific expression in fetal, newborn and adult mice. Genomic cot DNA consists of eight exons, spanning more than 25 kb, and all intron-exon borders are well conserved as compared to the human homolog. Analysis of the full-length cot cDNA revealed that it contained an open reading frame of 1,401 nucleotides, like human cot proto-oncogene. The sequence identity between murine and human cot gene is 84.4% at the nucleotide level and 93.9% at the deduced amino acid level. On northern blot analysis of poly (A)+ RNA, the cot message was detected at 2.9 kb in size. Expression of the cot gene was observed in many tissues from fetal to adult mice, though the level of expression was low in all tissues examined.

Amino Acid Sequence↗
PubMed1993

Antimetastatic activity of polymeric RGDT peptides conjugated with poly(ethylene glycol).

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n = 2 to 4), at a dose of 500 micrograms exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)11, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)11 was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG-(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and anti-metastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis ("anti adhesion therapy").

Amino Acid Sequence↗
PubMed1993

Effects of halothane on the synthesis of neurotransmitter amino acids in mouse brain.

The effects of halothane on the synthesis of the three major neuroactive amino acids (gamma-aminobutyric acid, aspartate and glutamate) and glutamine, which is closely related metabolically, were investigated in mouse brain using a labelled precursor ([13C]glucose) and a gas chromatography-mass spectrometry system. The ratios of newly synthesized amino acids were increased relative to baseline values when animals were exposed to 1% halothane, and decreased when they were exposed to 2% halothane. These findings suggest that halothane affects the synthesis of neurotransmitter amino acids in a concentration-dependent manner, without discrimination between excitatory and inhibitory amino acids.

Animals↗
PubMed1993

[A case of spontaneous bacterial peritonitis with ascites caused by hypoproteinemia after a massive bleeding from a gastric ulcer].

A case of spontaneous bacterial peritonitis (SBP) developed in an old man whose ascitic fluid was related neither to portal hypertension nor nephrotic syndrome, but with severe hypoalbuminemia emerged after a massive bleeding from a gastric ulcer in a malnutrition state. Ascitic fluid, increasing day by day, yielded Enterobacter cloacae and Bacteroides fragilis. Though autopsy was not carried out because of refusal of his family, neither liver necropsy, nor abdominal CT scan nor repeated abdominal ultrasonography showed findings suggesting existence of liver cirrhosis. In the presence of his ascites, the extent of a chemiluminescence (CL) response of polymorphonuclear cells from volunteers was significantly lower than that of his serum. This report shows that SBP can develop in a patient with ascites unrelated to portal hypertension when ascitic fluid induces little CL response.

Aged↗