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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 523 records · Page 29Linked to original sources
PubMed1994

[Recent advances in radiotherapy for breast cancer].

Radiotherapy for breast cancer has been performed as adjuvant lymph node irradiation after radical operation, irradiation for chest wall relapse, and palliative treatment for bone, lung and brain metastases. However, attention has been paid to irradiation of the breast as a conservative treatment. The role of radiotherapy in breast conservative treatment is to reduce local relapse after shrinkage of operation, and to enhance the cosmetic outcome. The indications of this treatment, technique of irradiation, effects and side effects of irradiation, and risk of radiation-induced cancer were discussed. In Japan, we have experience with this treatment. Breast conservation treatment and modified mastectomy showed the same results in local control and survival. Sometimes the cure and most cases of relief of complaints are attained for recurrent or advanced breast cancer by radiotherapy. High dose rate brachytherapy by 192-Ir showed high local control of uncontrollable tumor by external irradiation. And hyperthermia combined with radiotherapy is also effective for superficial (less than 3 cm in depth) tumor. Even in patients with lung and or brain metastases, radiotherapy sometimes showed complete remission for years. The standard method of radiotherapy for bone and brain metastases is 30 Gy/2 wks, and the symptom relief rate is over 80%. Oncologists should be made aware of the high complaint relief rate by radiotherapy.

Brachytherapy↗
PubMed1994

Effects of cerebroplegic solutions during hypothermic circulatory arrest and short-term recovery.

UNLABELLED: Previous studies have suggested that a simple crystalloid "cerebroplegic" solution may prolong the safe duration of hypothermic circulatory arrest. We tested the hypothesis that pharmacologic modification of the cerebroplegic solution would further enhance cerebral protection. Forty-six 4-week-old miniature piglets underwent core cooling to 15 degrees C nasopharyngeal temperature and 2 hours of hypothermic circulatory arrest. Twelve animals had a 50 ml/kg dose of saline infused into the carotid artery system at the onset of hypothermic circulatory arrest and repeat doses of 10 ml/kg every 30 minutes during arrest. Eleven animals received the same initial and repeat doses of University of Wisconsin organ preservation solution and 10 received University of Wisconsin solution with 7.5 mg/L of MK-801, an excitatory neurotransmitter antagonist. In 13 control animals blood was partially drained from the piglet before 2 hours of circulatory arrest at 15 degrees C and no cerebroplegic solution was infused. All solutions were delivered at 4 degrees C. Brain temperature (n = 24) at the onset of hypothermic circulatory arrest was 15.0 degrees +/- 0.1 degrees C (mean +/- standard error). Brain temperature after cerebroplegic infusion dropped to 13.0 degrees +/- 0.3 degrees C and stayed lower than brain temperature in the control group throughout the hypothermic circulatory arrest period. Recovery of cerebral adenosine triphosphate and intracellular pH determined by phosphorus 31 magnetic resonance spectroscopy (n = 22) was significantly improved by saline infusion and was further improved with University of Wisconsin solution and University of Wisconsin solution plus MK-801 (p < 0.001). Recovery of cerebral blood flow measured by microspheres (n = 24) also was augmented by University of Wisconsin solution (p < 0.001) but not in the presence of MK-801. The vascular resistance response to acetylcholine and nitroglycerin suggested that MK-801 has a direct vasoconstrictive effect. Recovery of cerebral oxygen consumption (n = 24) was increased by University of Wisconsin solution and University of Wisconsin solution with MK-801 (p = 0.002). Brain water content (n = 46) was significantly lower in all cerebroplegia-treated groups than in controls (p < 0.001). CONCLUSION: Cerebroplegia improves short-term recovery after 2 hours of circulatory arrest in hypothermic piglets. Pharmacologic modification with University of Wisconsin solution further improves the recovery of cerebral blood flow and metabolism. MK-801 does not augment the protective effects of University of Wisconsin solution and reduces the recovery of cerebral blood flow by a direct vascular action. Modified cerebroplegia may provide a novel approach to improved cerebral protection when prolonged hypothermic circulatory arrest is necessary.

Adenosine↗
PubMed1994

Interactions between preischemic hypothermia and cardioplegic solutions in the neonatal lamb heart.

Hypothermia is believed to improve the tolerance to both ischemia and cardiopulmonary bypass and is commonly used during heart operations, particularly in the neonate. However, hypothermia also causes calcium to accumulate in the myocyte experimentally, and an increase in intracellular calcium during ischemia may worsen the effect of ischemia and impair the postischemic recovery of function. This effect of hypothermia on intracellular calcium has generally not been considered in experiments that attempt to optimize the composition of cardioplegic solutions. We have evaluated the impact of hypothermia before cardioplegic ischemia on the efficacy of two common cardioplegic solutions, one with calcium (St. Thomas' Hospital cardioplegia) and the other without calcium (glucose-potassium cardioplegia), in 37 isolated blood-perfused neonatal lamb hearts. Left ventricular maximal developed pressure, positive maximum of the first derivative of left ventricular pressure, left ventricular stiffness constant at 10 mmHg end-diastolic pressure, coronary blood flow, and myocardial oxygen consumption were measured before and 30 minutes after 2 hours of cold ischemia. After baseline measurements were made, two groups of hearts (ST-C and GK-C) had perfusion-cooling for 10 minutes to 17 degrees C myocardial temperature, and two other groups (ST-NC and GK-NC) had the same period of normothermic perfusion. Then the hearts were arrested with 4 degrees C St. Thomas' cardioplegic in groups ST-C and ST-NC and with glucose-potassium cardioplegia in groups GK-C and GK-NC. In the groups without preischemic cooling, both St. Thomas' (group ST-NC) and glucose-potassium (group GK-NC) cardioplegia resulted in a similar recovery of function compared with baseline levels (group ST-NC: developed pressure = 91.3% +/- 9.2%, dP/dt = 88.1% +/- 8.9%, left ventricular stiffness constant = 96.1% +/- 3.3%; group GK-NC: developed pressure = 89.3% +/- 6.9%, dP/dt = 82.6% +/- 8.8%, left ventricular stiffness constant = 99.4% +/- 2.0%; data are mean plus or minus the standard deviation). However, with preischemic cooling, St. Thomas' cardioplegia (group ST-C) resulted in a significantly reduced recovery of both systolic and diastolic function (developed pressure = 81.6% +/- 6.2%, dP/dt = 75.1% +/- 8.4%, left ventricular stiffness constant = 103.7% +/- 2.7%) compared with that for both glucose-potassium cardioplegia (group GK-C: developed pressure = 92.4% +/- 8.7%, dP/dt = 83.7% +/- 6.0%, left ventricular stiffness constant = 100.5% +/- 2.1%) and St. Thomas' cardioplegia without preischemic cooling (group ST-NC) (p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

[Detection of anti-granulocyte antibodies using flow cytometry].

To detect anti-granulocyte antibodies (AGAs) in the sera of granulocytopenic patients is important to study the mechanism of the disease. In this report, we studied neutrophil associated immunoglobulin (NAIg) and neutrophil binding immunoglobulin (NBIg) in patients' sera using flow cytometry (FCM). We investigated the interference of circulating immune complexes (CIC) on measuring the NAIg and NBIg. No apparent effect of CIC was observed at concentrations up to 140 micrograms/ml. NAIg and NBIg were semiquantitated by determining the relative fluorescence intensity (RFI) on a flow cytometer and the normal ranges of NAIg and NBIg were less than 15 RFI and less than 10 RFI, respectively. Of 100 sera from patients with neutropenia, 5 were positive for NBIg and 3 of them were positive for granulocyte-specific antibodies. One serum of a patient with benign chronic neutropenia showed clear specificity for NA1 alloantigen but the other 4 AGAs were not specific for NA alloantigen system. Our NAIg, NBIg screening procedure, including NA specificity testing of NBIg and detection of reactivity with normal lymphocytes using FCM, is simple and useful for measuring and studying serological and immunological characteristics of AGAs.

Autoantibodies↗
PubMed1994

Result of biventricular repair for double-outlet right ventricle.

The choice of optimal repair for many patients with double-outlet right ventricle continues to challenge the heart surgeon. We present the results of a 10-year surgical experience with the biventricular repair for double-outlet right ventricle with situs solitus and atrioventricular concordance. Preoperative anatomic findings within this population of 73 patients are detailed. These morphologic features are correlated with type of anatomic repair and clinical outcome. Patients were classified by ventricular septal defect location. Normal coronary anatomy was found in the majority of patients with subaortic and doubly-committed ventricular septal defects. Patients with subpulmonary and noncommitted ventricular septal defects had a wide variety of coronary anatomy. Patients with subpulmonary and noncommitted ventricular septal defects also had a considerably higher prevalence of aortic arch obstruction. A tricuspid-to-pulmonary annular distance equal to or greater than the diameter of the aortic annulus was found to indicate the possibility of achieving a conventional ventricular septal defect-to-aorta intraventricular tunnel repair. Tricuspid-to-pulmonary annular distance sufficient for intraventricular tunnel repair predominates in those patients with a right posterior or right side-by-side aorta. Five types of repair were used during the study period: intraventricular tunnel repair, arterial switch with ventricular septal defect-to-pulmonary artery baffle, Rastelli-type extracardiac conduit repair, Damus-Kaye-Stansel repair, and atrial inversion with ventricular septal defect-to-pulmonary artery baffle. Overall actuarial survival estimate at 8 years is 81%. The presence of multiple ventricular septal defects and patient weight lower than the median were nearly significant risk factors for early mortality (p < 0.06). Nineteen patients (26%) required 24 reoperations. Patients with subaortic ventricular septal defects were significantly reoperation free (p < 0.05). Patients with noncommitted ventricular septal defects were at significantly higher risk for reoperation during the study period (p < 0.05). The prevalence of late right or left ventricular outflow obstruction in the nonsubaortic groups is concerning. The median age at repair in this series was 0.76 years, and there was a nonsignificant trend (p = 0.13) for early mortality in patients younger than 1 year of age. These patients tended to have other serious cardiac anomalies associated with double-outlet right ventricle that necessitated early operation. On the basis of these data, we favor early repair for double-outlet right ventricle if possible.

Abnormalities, Multiple↗
PubMed1993

The human cot proto-oncogene encodes two protein serine/threonine kinases with different transforming activities by alternative initiation of translation.

The cot gene is an oncogene encoding serine/threonine kinases isolated by DNA transfection assay. In this study, we isolated cDNA for the human cot protooncogene (proto-cot gene) and examined the structure and function of its gene products. The proto-cot gene has an open reading frame encoding 467 amino acids of which the first 397 amino acids are identical to those in the corresponding part of the cot gene. The protein products of the proto-cot gene were identified as 58- and 52-kDa proteins with intrinsic protein serine/threonine kinase activity. These two protein species were suggested to be generated by alternative initiation from two AUGs. The 58- and 52-kDa proteins are both localized predominantly in the cytosol, but the 58-kDa protein has a shorter half-life than the 52-kDa protein, suggesting the importance of the amino-terminal domain in regulating the stability of the proto-Cot protein. More interestingly, the 58-kDa protein showed stronger transforming activity than the 52-kDa protein, although this activity was much weaker than that of the Cot oncoprotein. Thus, the amino-terminal domain of the Cot protein may be necessary for cellular transformation, whereas the carboxyl-terminal domain may negatively regulate the transforming activity.

Amino Acid Sequence↗
PubMed1993

Increased expression of nucleoside diphosphate kinase/nm23 and c-Ha-ras mRNA is associated with spontaneous lung metastasis in rat-transplantable osteosarcomas.

The relationship between expression of nucleoside diphosphate kinase (NDP kinase)/nm23, c-Ha-ras, and c-myc genes and metastatic potential was assessed in rat-transplantable osteosarcoma lines, derived from spontaneous and chemical carcinogen (4-hydroxyamino quinoline 1-oxide)-induced osteosarcomas in Fischer 344/NS1c rats. These osteosarcomas possess metastatic potential and highly metastatic lines spontaneous osteosarcoma-selected lung metastatic lesions and 4-hydroxyamino-quinoline 1-oxide-induced osteosarcoma-selected lung metastatic lesions were respectively established by selectively transplanting lung metastatic lesions. Northern blot analysis revealed that the levels of NDP kinase/nm23 and c-Ha-ras gene expression were increased in line with metastatic ability; thus transcript levels were remarkably greater in both spontaneous osteosarcoma-selected lung metastatic lesions and 4-hydroxyamino-quinoline 1-oxide-induced osteosarcoma-selected lung metastatic lesions highly metastatic lines than in their respective low metastatic spontaneous and chemical carcinogen (4-hydroxyamino quinoline 1-oxide)-induced osteosarcoma counterparts. c-myc mRNA expression was observed in all tumor lines, without any correlation with metastatic ability. Southern blot analysis did not show evidence of gross rearrangement or amplification of NDP kinase/nm23, c-Ha-ras, or c-myc genes suggesting regulation of their gene expression at the transcriptional and/or posttranscriptional level. These results indicate that NDP kinase/nm23 and c-Ha-ras might be cooperatively involved in a positive manner in signal transduction processes, especially involving G-protein reactions, responsible for metastasis of rat-transplantable osteosarcomas.

Animals↗
PubMed1993

Induction of HSP90 alpha heat shock mRNA after transient global ischemia in gerbil hippocampus.

Distribution of heat shock protein (HSP) 90 alpha mRNA induction after 10 min of transient global ischemia was investigated in gerbil hippocampus by in situ hybridization. A small amount of HSP90 alpha mRNA was normally present in hippocampal cells and the mRNA was further induced with a peak at 8 h after ischemia. In hippocampal CA1 cells that are vulnerable to ischemia, HSP90 alpha mRNA was continuously induced by 1 day and finally diminished at 2 days. The temporal profile of HSP90 alpha mRNA induction in hippocampal CA1 cells was similar to that of HSP70 mRNA reported previously, suggesting a cooperative role of HSP90 alpha with other HSPs after ischemia.

Animals↗
PubMed1993

[Determination of potential doubling time using in vitro continuous labeling method with bromodeoxyuridine: estimation in head and neck squamous cell carcinoma].

Using in vitro continuous labeling with bromodeoxyuridine and immunohistochemical staining, potential doubling time (Tpot) was calculated in 24 patients with head and neck carcinoma treated with radiotherapy. There was no evident correlation between Tpot and tumor response in the cases treated with external irradiation. However, in one case of T2N0 mesopharyngeal carcinoma with short Tpot, tumor was microscopically residual even though it showed good radioresponsiveness during radiotherapeutic course. Meanwhile, all patients treated with brachytherapy showed complete response in spite of various Tpot. Tpot seems significant in the selection of fractionation to control head and neck carcinoma with external radiotherapy.

Brachytherapy↗
PubMed1993

Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils.

The interaction of Fc receptors with antibody-antigen complexes activates multiple biological functions in hematopoietic cells. Recently, protein-tyrosine phosphorylation has been suggested to be involved in Fc receptor-mediated cell signaling. Here we show that the Src-like protein-tyrosine kinase Fgr, which is specifically expressed in mature myelomonocytic cells, coimmunoprecipitates with IgG Fc receptor II (Fc gamma RII), but not with Fc gamma RIII from detergent lysates of human peripheral neutrophils. Crosslinking of Fc gamma RII induced a rapid increase in the tyrosine kinase activity and comodulation of Fgr. These results suggest that Fgr is physically and functionally associated with Fc gamma RII and involved in Fc gamma RII-mediated signal transduction pathways.

Animals↗
PubMed1993

The preconditioned hippocampus accelerates HSP70 heat shock gene expression following transient ischemia in the gerbil.

To evaluate the mechanism of tolerance for ischemia, inductions of heat shock protein (HSP) 70 mRNA and immunoreactive HSP70 protein were studied in the preconditioned gerbil hippocampus. Following the single 3.5-min ischemia, HSP70 mRNA was induced in all hippocampal cells. However, the hippocampal CA1 cells produced only a minimum HSP70 protein, and the cells were almost lost by 7 days. Following the 3.5-min ischemia after 2-min pretreatment, the CA1 cells produced a strong immunoreactive HSP70 signal and large populations of the CA1 cells survived at 7 days. The peak time of the HSP70 mRNA induction shifted to earlier period of reperfusion in the CA1 cells as compared to the case with single ischemia. This accelerated change of HSP70 expression could play an important role for the acquisition of ischemic tolerance of the hippocampal CA1 neurons.

Adaptation, Physiological↗
PubMed1993

Reduction of HSP70 and HSC70 mRNA inductions by bifemelane hydrochloride after transient ischemia in gerbil brain.

The effect of bifemelane hydrochloride (BFH) on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brain was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Following 3.5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The CA1 cells were almost lost by 7 days. Treatment with BFH twice before and after ischemia (total 60 mg/kg, i.p.) reduced the induction of HSP70 and HSC70 mRNAs both at 8 h and 1 day of the reperfusion, and about half of the CA1 cells survived at 7 days. Thus, the reduction of HSP70 and HSC70 mRNA inductions after ischemia may suggest that BFH reduced intra- and/or post-ischemic stress, and protected CA1 cells from ischemic damage.

Animals↗
PubMed1993

[Subtraction and dynamic MR images of breast cancer].

The purpose of this study was to evaluate the diagnostic effectiveness of subtraction and dynamic MR imaging in patients with breast masses. In 23 breast cancers and six fibroadenomas, spin echo T1 images were obtained at 0.2 Tesla before and every minute after the intravenous injection of Gd-DTPA (0.1 or 0.2 mmol/kg). Subtraction images were obtained sequentially on the CRT monitor. All breast masses were enhanced after gadolinium and stood out as bright lesions on subtraction images. The tumor margin and its extension were more precisely evaluated on subtraction MR images than on conventional postcontrast MR images. Breast cancer showed a characteristic time-intensity curve with an early peak, in contrast to fibroadenoma, which showed a gradual increase in signal intensity. Subtraction MR imaging is a simple method for the evaluation of breast masses, and further, the time-intensity curve obtained by dynamic study is helpful in the differential diagnosis of lesions.

Adenofibroma↗
PubMed1993

Endothelin-1 induces contraction of bile canaliculi in isolated rat hepatocytes.

To examine the effects of endothelin-1(ET-1) on bile canalicular contractions, rat hepatocytes were isolated by a collagenase perfusion technique and cultured on p-n-p-vinylbenzenyl-D-lactonamide-coated dishes under serum-free conditions. The frequency of bile canalicular contractions was expressed by the percentage of the number of bile canaliculi(BC) that contracted compared to the total number of BC observed for 10 min. The treatment of the hepatocytes with ET-1 increased the frequency of contraction of the BC in a dose-dependent manner up to 2nM, control: 10.4%; 0.5nM ET-1:31.6%; 1nM ET-1:54.0%; 2nM ET-1:58.0%; 4nM ET-1:58.9%. The contraction, once it occurred, lasted for rest of the observation period. We also observed a transient increase in the concentration of intracellular Ca in cultured hepatocytes upon the addition of ET-1 to the medium. These results suggest that ET-1 plays an important role in the mortility of BC in vivo.

Animals↗
PubMed1993

Evidence for involvement of phospholipase C-gamma 2 in signal transduction of platelet-derived growth factor in vascular smooth-muscle cells.

In order to examine the mechanisms underlying smooth-muscle cell proliferation, we investigated effect of platelet-derived growth factor (PDGF) dimers on proliferation of rabbit vascular smooth-muscle cells (VSMCs) and also involvement of phospholipase C (PLC) isoforms in the signal transduction. PDGF-BB and -AB, but not -AA, stimulated cell proliferation and intracellular production of inositol trisphosphate. Northern and Western analyses demonstrated that VSMCs mainly expressed PLC-gamma 2 and PLC-delta 1 among four PLC isoforms tested. A number of cellular proteins, including PLC-gamma 2, but not PLC-delta 1, were phosphorylated on a tyrosine residue by the stimulation of either PDGF-BB or -AB. These results suggest a functional association of PDGF receptor and PLC-gamma 2 that might be responsible for PDGF-dependent VSMC growth. In addition, the expression of PLC-gamma 2 was extremely low in the primary VSMC cultures and was induced during further cultivation of the primary cultures, indicating that an acquisition of PDGF-signal-transducing components, including PLC-gamma 2, may be an important step for proliferation of smooth-muscle cells.

Animals↗
PubMed1993

Temporal profile of the induction of heat shock protein 70 and heat shock cognate protein 70 mRNAs after transient ischemia in gerbil brain.

Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after 2, 5 and 15 min of transient global ischemia in gerbil forebrain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Morphological studies were also performed at the dorsal hippocampal level of coronal sections from the identical brains until 7 days after the reperfusion. Following 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal dentate granule cells at 1 and 3 h of the reperfusion. No histological change was observed in brain cells. Following 5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The induction of HSP70 mRNA in hippocampal CA1 cells sustained until 2 days, while that of HSC70 mRNA declined gradually. Only CA1 cells were lost at 7 days of the reperfusion. Following 15 min of ischemia, the mRNAs were induced in more extensive brain regions including neocortex and thalamic nuclei. In hippocampal CA1 cells, inductions of HSP70 and HSC70 mRNAs diminished by 2 days corresponding with the neuronal damage. HSC70 mRNA induction was not so much as HSP70 mRNA induction especially in hippocampal CA1 and thalamic cells. Our results showed that HSP70 and HSC70 mRNAs were generally induced together after transient ischemia, but that the inductions were spatially and chronologically different after different periods of ischemia. The dissociation of the induction was also found in cells severely injured after 5 and 15 min of ischemia.

Animals↗