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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 361 records · Page 20Linked to original sources
PubMed1997

Efficacy of CDDP and AGM-1470 chemotherapy against lung metastasis in rat osteosarcoma depends on the timing of combined administration.

The efficacy of combination therapy with cis-diammine-dichloroplatinum (II) (CDDP) and o-(chloroacetyl-carbamoyl) fumagillol (AGM-1470) was evaluated experimentally using a transplantable rat osteosarcoma line, previously established in our laboratory, with a high potential for metastasis. Tumor-bearing male Fischer 344 rats were administered CDDP (2.5 mg/kg) together with, or after discontinuation of, AGM-1470 treatment (10 mg/kg/body weight/week). When CDDP was administered three days after discontinuation of AGM-1470 the most pronounced antimetastatic effects were observed, although the antitumor effect was approximately the same.

Animals↗
PubMed1997

Changes in targeting efficiencies of proteins to plant microbodies caused by amino acid substitutions in the carboxy-terminal tripeptide.

It has been demonstrated that the carboxyl terminus of microbody enzymes functions as a targeting signal to microbodies in higher plants. We have examined an ability of 24 carboxy-terminal amino acid sequences to facilitate the transport of a cytosolic passenger protein, beta-glucuronidase, into microbodies in green cotyledonary cells of transgenic Arabidopsis. Immunoelectron microscopic analysis revealed that carboxy-terminal tripeptide sequences of the form [C/A/S/P]-[K/R]-[I/L/M] function as a microbody-targeting signal, although tripeptides with proline at the first amino acid position and isoleucine at the carboxyl terminus show weak targeting efficiencies. All known microbody enzymes that are synthesized in a form similar in size to the mature molecule, except catalase, contain one of these tripeptide sequences at their carboxyl terminus.

Amino Acids↗
PubMed1997

An automatic flow controller for a centrifugal blood pump.

To regulate the perfusion flow rate of a centrifugal blood pump, a microcomputer controller was developed. The computer monitored the flow rate of the pump with an electromagnetic flowmeter or an ultrasonic pulse Doppler flowmeter, rotational speed of the pump, aortic pressure, and the amount of blood in a reservoir. A discrete integral controller with a control interval of 1 s was adopted for the controller. For the safety of the control system, we added functions for detecting a clamp on the tubing, a dislocation of the flow sensor, or an inverse direction of the flow sensor. During a standby period, the computer calculated the rotational speed from aortic pressure to minimize the forward or the backward flow at the start of the pump perfusion. The automatic flow controller was used on 5 patients during cardiac operations and maintained the flow rate within +/-6% of the set point.

Algorithms↗
PubMed1997

[A case of primary HIV-1 infection].

A previously healthy 28 year old Japanese man came to us with a genital ulcer which appeared 13 days before admission to our hospital. He had subsequently fever (40 degrees C), arthralgia, a sore throat and oral aphtha 6 days before admission. He had a history of sexual contact with a female commercial sex worker one week before his illness. On the day of admission, he had shallow ulcers on the lip, tongue and penis. Initial laboratory test included leukopenia and thrombocytopenia. His fever abated 3 days after admission. His condition and bicytopenia recovered completely after 12 days of admission. Although, his serum HIV-1 antibody was negative when he was admitted, 3 months later the antibody was seroconverted. And p24 antigen and HIV-1 RNA of stocked serum were positive. Diagnosis of primary HIV-1 infection was made. Recently, HIV-1 infection has been increasing in Japan. Consideration of this disease in differential diagnosis of acute febrile illness is necessary.

Adult↗
PubMed1997

Immunocytochemical localization of chymase to cytoplasmic vesicles after rat peritoneal mast cell stimulation by compound 48/80.

The subcellular events responsible for release of mediators by mast cells may help to clarify roles for mast cells in health and disease. In this study we show that the granule-associated protease chymase is also within cytoplasmic vesicles in appropriately stimulated rat peritoneal mast cells. Rat peritoneal mast cells were recovered before or 1-10 sec after exposure to the secretogogue compound 48/80 (10 micrograms/ml) and then were examined by radioimmunoassay to quantify histamine release or were processed, using routine methods for postembedding immunoelectron microscopy, to identify the subcellular localization of chymase. In comparison to unstimulated cells, compound 48/80 stimulated cells in two independent experiments showed an increase (15%, 28%) in the surface area of the cell and a decrease (12%, 6%) in the surface area of the total granule compartment before degranulation channel formation. These global cellular changes occurred in a background of transient but significant (p < 0.01) increases in the area and number of chymase-immunoreactive vesicles per microns2 cytoplasm. These changes were detectable at 5 or 7 sec after stimulation with compound 48/80 but returned to near prestimulation levels by 9 or 10 sec after addition of compound 48/80 (total cumulative histamine release was 28% by 8 sec and 47% by 14 sec). These observations suggest that vesicles participate in the early stages of regulated secretion of chymase from rat peritoneal mast cells.

Animals↗
PubMed1997

A presenilin-1 mutation in a Japanese family with Alzheimer's disease and distinctive abnormalities on cranial MRI.

Some patients with familial Alzheimer's disease (FAD) have mutations in the presenilin-1 (PS-1) gene on chromosome 14. We report a Japanese family with AD and an Ala285Val substitution in exon 8 of the PS-1 gene. FAD in this family was characterized by relatively late onset (mean age, 50 years) and absence of myoclonus, seizures, or paratonia. Levels of tau were markedly elevated in CSF whereas CSF levels of amyloid beta protein were normal. MRI of the cranium showed marked linear signal abnormalities within white matter in the parieto-occipital lobes, consistent with cortical amyloid angiopathy of the type encountered in patients with the PS-1 gene mutation.

Alzheimer Disease↗
PubMed1997

Relationship between pharmacokinetics and the analgesic effect of indomethacin in the rat.

The relationship between the pharmacokinetic properties and the analgesic effect of indomethacin (IDM) was evaluated on a carrageenin-induced inflammation model in the rat. Rats were administered the drug in one of two ways: intravenous (i.v.) IDM bolus or i.v. IDM infusion. The analgesic activity was measured by Randall-Selitto test. No correlation was observed between the analgesic effect and the plasma IDM concentration after i.v. bolus administration of IDM. However, in the case of infusion, IDM produced a dose-dependent analgesic effect. In this paper, we demonstrated that the plasma concentration of IDM maintained by i.v. infusion had a prolonged analgesic effect on the carrageenin-induced inflammation model.

Animals↗
PubMed1997

Potential role of an endothelium-specific growth factor, hepatocyte growth factor, on endothelial damage in diabetes.

Endothelial cells are known to secrete various antiproliferative and vasodilating factors. Although injury of endothelial cells has been postulated as an initial trigger of the progression of atherosclerosis in patients with diabetes, the mechanisms of endothelial injury in diabetes are not yet clarified. Therefore, it is important to know the effects of high glucose on the factors that may influence endothelial cell growth. A novel member of endothelium-specific growth factors, hepatocyte growth factor (HGF), is produced in vascular cells. To investigate the effects of high glucose on vascular cells, we examined 1) the effects of high glucose on endothelial cell and vascular smooth muscle cell (VSMC) growth and 2) the effects of high glucose on local HGF production in endothelial cell and VSMC. Treatment of human aortic endothelial cell with a high concentration of D-glucose, but not mannitol and L-glucose, resulted in a significant decrease in cell number. Interestingly, addition of recombinant HGF attenuated high D-glucose-induced endothelial cell death. Therefore, we measured local HGF secretion of endothelial cell. Importantly, local HGF production was significantly decreased by high D-glucose treatment. In contrast, high D-glucose treatment resulted in a significant increase in the number of human aortic VSMCs, whereas local HGF production was significantly decreased in accordance with increase in D-glucose concentration. No significant changes in numbers were observed in VSMC treated with high mannitol and L-glucose. We also studied the mechanisms of local HGF suppression by high D-glucose. High D-glucose treatment stimulated transforming growth factor-beta (TGF-beta) concentration in endothelial cell and VSMC. Decreased local vascular HGF production was abolished by addition of anti-TGF-beta antibody. As TGF-beta inhibited local HGF production in endothelial cell and VSMC, increased TGF-beta induced by high D-glucose may suppress local HGF production. This study demonstrated that high D-glucose induced endothelial cell death, stimulated VSMC growth, and decreased local HGF production through the stimulation of TGF-beta production both in endothelial cell and VSMC. Overall, decrease in a local endothelial stimulant, HGF, by high D-glucose may be a trigger of endothelial injury in diabetes, potentially resulting in the progression of atherosclerosis.

Animals↗
PubMed1997

Role for C-MPL and its ligand thrombopoietin in early hematopoiesis.

Proto-oncogene c-mpl is structurally homologous with the hematopoietic growth factor receptor superfamily. The ligand for c-mpl was purified and its gene cloned. Extensive functional studies revealed that the ligand for c-mpl plays a crucial role in megakaryocytopoiesis and platelet production, hence, this ligand proved to be the long-sought hematopoietin, thrombopoietin (TPO). We briefly review here the role for TPO in early hematopoiesis, based on our in vitro data obtained using a serum-free culture system. TPO in combination with the ligand for c-kit (SF) or interleukin-3 (IL-3) but not TPO alone supported the growth of murine primitive hematopoietic progenitors. Studies on lineage expression indicated that the progenitors supported by TPO plus SF or TPO plus IL-3 are multipotential. Delayed addition experiments demonstrated that TPO has the potential to effectively support the survival of primitive hematopoietic progenitors. TPO also hastened IL-3-dependent growth of progenitors by shortening the time required for cell-cycling. While size of the colonies did not differ between colonies supported by IL-3 alone and those supported by IL-3 plus TPO, the incidence of megakaryocyte-containing colonies in cultures supported by IL-3 plus TPO was higher than that in cultures supported by IL-3 alone. Taken together, TPO as a single factor can support the survival of hematopoietic progenitors and TPO synergizes with SF or IL-3 to be active on early multipotential hematopoietic progenitors. These findings suggest that the function of TPO initially thought to be restricted to the megakaryocytic lineage proved to be greater in hematopoiesis. Reports from other laboratories regarding the involvement of TPO in early hematopoiesis are also discussed.

Animals↗
PubMed1997

Potential role of a novel vascular modulator, hepatocyte growth factor (HGF), in cardiovascular disease: characterization and regulation of local HGF system.

Since endothelial cells (EC) are known to secrete various anti-proliferative and vasodilating factors, an agent that promotes seeding or regeneration of EC may have potential therapeutic value against vascular smooth muscle cell (VSMC) proliferation. To seek an endothelium specific growth factor, we have focused on hepatocyte growth factor (HGF). HGF is belonged to a member of endothelium specific growth factors, whose mitogenic action on EC was most potent among growth factors. Moreover, the presence of local HGF system (HGF and its specific receptor, c-met) was observed in EC and VSMC of rat and human in vitro as well as in vivo. Production of local HGF production in vascular cells was regulated by various cytokines including transforming growth factor (TGF)-beta and angiotensin II (Ang II). Furthermore, HGF may be a therapeutic growth factor for the treatment of restenosis after angioplasty and arteriosclerosis obliterance, etc., as gene therapy. From these characteristics of HGF, we hypothesized that HGF might contribute to the protection or repair of vascular endothelial cells. Indeed, serum HGF concentration was significantly correlated with blood pressure, suggesting that HGF secretion might be elevated in response to high blood pressure as a counter-system against endothelial dysfunction. In this review, we discussed that HGF is a member of the endothelium specific growth factors whose serum concentration is significantly associated with blood pressure.

Animals↗
PubMed1997

Laboratory evaluation of a new membrane oxygenator with a built-in hemoconcentrator.

In order to facilitate the handling of cardiopulmonary bypass (CPB) and simplify the circuit, we have developed a new membrane oxygenator with a hemofiltration function. The hollow fiber units for gas exchange and hemofiltration were combined in concentric circles in a cylindrical housing. The total priming volume was 190 ml. Because we used a silicon-coated hollow fiber membrane for gas exchange, this oxygenator was completely resistant to serum leakage. The gas exchange and hemofiltration sections both have a blood-outside flow configuration. All blood flows in a radial direction from around the central core to the surrounding hollow fiber units, first to the hemofiltration portion and then to the gas exchange section. Filtered fluid was easily collected through a stopcock mechanism. The oxygen transfer rate was 312 ml/min at a blood flow rate of 6 L/min, and the ultrafiltration rate was 3.5 L/hour at a blood flow rate of 4 L/min with 25% hematocrit and 200 mmHg transmembrane pressure in an in vitro study. The pressure drop was 62 mmHg at a blood flow rate of 4 L/min. We found no adverse effects in an in vivo study using a mongrel dog. In conclusion, this durable combined device could achieve excellent and simplified hemoconcentration by having all the blood in the unit flow through the hemofiltration portion, and may be useful not only in CPB during open heart surgery, but also in extracorporeal membrane oxygenation.

Animals↗
PubMed1997

[A case of folie à trois].

We examined a case of a family of induced insanity (folie à trois) which is characterized by its delusion of jealousy, and reported about the establishment and disappearance process of the delusion. We examined the background of the fact that the family members shared the same delusion and the family dynamics. We concluded that induced insanity is an extended expression of family illness which appears in the process in which the family expresses its problematic theme and tries to cope with it.

Adult↗
PubMed1997

[Surgical relief of airway obstruction from a double aortic arch associated with corrected transposition of the great arteries, pulmonary atresia and bilateral patent ductus arteriosus in a neonate].

A rare 20-day-old male with double aortic arch, corrected transposition of the great arteries (cTGA), pulmonary atresia and bilateral patent ductus arteriosus (PDA) was transported to our institute because of severe respiratory dysfunction and cyanosis. The patient had been already intubated and ventilated on respirator. A echocardiography and cine-angiography demonstrated that the both sides aortic arch had almost identical sizes, originating common carotid arteries and subclavian arteries and PDAs respectively, and the descending aorta located on the left side of the mid-line. At the first surgery, the distal of the right aortic arch was divided just proximal to the descending aorta after complete tissue dissection around the arch. The divided right sided aortic arch was mobilized from posterior to anterior aspect of the bronchus. Then the right subclavian artery was divided and an original Blalock-Taussig shunt was employed. The right sided PDA was ligated. After the first surgery, respiratory dysfunction lasted for weeks mainly because of the PGE1 dependent left sided PDA. At the second surgery, left sided modified Blalock-Taussig shunt was constructed and the left sided PDA was divided. These procedures resulted in stable respiratory status and oxygen saturation. The patient was extubated three days later and now in satisfactory clinical condition.

Abnormalities, Multiple↗
PubMed1997

[Future prediction of tuberculosis incidence rates by prefecture].

We tried to predict the tuberculosis incidence rates by the year 2000 and 2005, based on the trends of incidence rates from the year 1981 to 1995 reported by the Ministry of Health and Welfare (MOHW). According to the studies conducted, the tuberculosis incidence rate in 2000 was predicted as 29.8 (95% CI: 28.7-30.8) per 100,000 population and that in 2005 was predicted as 25.2 (95% CI: 24.2-26.3 per 100,000 population in Japan. The incidence rates by prefecture in 2000 and 2005 were also predicted. The MOHW introduced some new tuberculosis control plans and has set on interim goal by the year 2000 to achieve a tuberculosis incidence at below 20 per 100,000 population. Whereas the possibility of achieving the stated incidence rate goal even by the year 2005 is very low in Japan, among prefectures, several prefectures were predicted to reach this level by the year 2000. Over several years the incidence rate in Japan has been high in the west and low in the east. However this is expected to greatly change in the future. The speed of decline in tuberculosis incidence rates has been stagnated since around 1980 with average annual declination rate from the year 1981 to 1995 was 3.3%. Among 17 prefectures, Tokyo Metropolitan had the lowest declination rate with an average annual declination rate of 1.1%. The prefecture surrounding Tokyo also showed low declination speed. This may indicate that in the future, the problems of tuberculosis will be concentrated in and around the big cities.

Forecasting↗
PubMed1997

[Surgical treatment of double outlet left ventricle].

Double outlet left ventricle (DOLV) is an uncommon congenital cardiac defect which was first reported by Sakakibara and associates. We studied anatomical aspects relevant to surgical repair in our 4 cases and additional 28 cases which had been reported on the literatures. The locations of ventricular septal defect (VSD) were subaortic in 20 cases, subpulmonary in 7, doubly-committed in 2 and unknown in 2. The positions of the aorta relative to the pulmonary artery were right or left anterior oblique in 11 cases, right or left side-by-side in 9, right or left posterior oblique in 10 and unknown in 3. The definitive surgery included Rastelli type operation in 18 cases, right ventricular outflow tract repair with closure of VSD in 6, intraventricular conduit repair in 4 and Fontan type operation in 4. In regard to the selection of the procedure, the size of right ventricle, the presence of pulmonary stenosis, the location of VSD and the relationship of the great arteries are very important. Although most of the patients underwent the Rastelli type operation, the right ventricular outflow tract reconstruction or intraventricular conduit repair could be adopted particularly in patients with posterior oblique position of the aorta relative to the pulmonary artery or subpulmonary VSD.

Adolescent↗
PubMed1997

Serum deprivation-induced apoptosis accompanied by up-regulation of p53 and bax in human aortic vascular smooth muscle cells.

Vascular remodeling, which plays an important role in atherosclerosis and hypertension, is determined in large part by the balance between cell growth and cell death by apoptosis. In this study, we studied the apoptosis of human aortic vascular smooth muscle cells (VSMC) induced by serum deprivation. Serum deprivation induced apoptosis of VSMC in a time-dependent manner. Serum deprivation resulted in the up-regulation of p53 protein, compared to treatment with 10% serum (P < 0.01), suggesting that apoptosis induced by serum deprivation may be due to the up-regulation of p53. Of importance, the protein of bax, a promoter of apoptosis, was significantly increased in VSMC treated by serum deprivation compared to treatment with 10% serum (P < 0.01). Overall, these findings demonstrated that serum deprivation induced apoptosis in human aortic VSMC, accompanied by the induction of p53 and bax, suggesting that apoptosis induced by serum deprivation may be mediated by the p53-bax pathway.

Apoptosis↗