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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 19 recordsLinked to original sources
PubMed1999

Structural Change in Dextran: Mechanism of Insolubilization by Adsorption on the Air-Liquid Interface.

To clarify the insolubilization mechanism of water-soluble dextran, the association of dextran in water was studied by dynamic light scattering measurements and a surface chemical approach. Dynamic light scattering measurements indicated that insolubilization of dextran is accompanied by a structural change in dextran. Surface tension data for dextran molecules revealed a structural change in dextran molecules at the air-liquid interface. These results suggest that insolubilization of dextran molecules occurred through an adsorption process at the air-liquid interface. Insolubilization of dextran molecules can be reduced by inhibition of this structural change in dextran molecules. The presence of boron as an impurity was found to trigger precipitation based on inductively coupled plasma mass spectrometry measurements and precipitation tests. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B.

The oncogene p3k, coding for a constitutively active form of phosphatidylinositol 3-kinase (PI 3-kinase), strongly activates myogenic differentiation. Inhibition of endogenous PI 3-kinase activity with the specific inhibitor LY294002, or with dominant-negative mutants of PI 3-kinase, interferes with myotube formation and with the expression of muscle-specific proteins. Here we demonstrate that a downstream target of PI 3-kinase, serine-threonine kinase Akt, plays an important role in myogenic differentiation. Expression of constitutively active forms of Akt dramatically enhances myotube formation and expression of the muscle-specific proteins MyoD, creatine kinase, myosin heavy chain, and desmin. Transdominant negative forms of Akt inhibit myotube formation and the expression of muscle-specific proteins. The inhibition of myotube formation and the reduced expression of muscle-specific proteins caused by the PI 3-kinase inhibitor LY294002 are completely reversed by constitutively active forms of Akt. Wild-type cellular Akt effects a partial reversal of LY294002-induced inhibition of myogenic differentiation. This result suggests that Akt can substitute for PI 3-kinase in the stimulation of myogenesis; Akt may be an essential downstream component of PI 3-kinase-induced muscle differentiation.

Animals↗
PubMed1999

Nuclear endpoint of Wnt signaling: neoplastic transformation induced by transactivating lymphoid-enhancing factor 1.

The interaction between beta-catenin and LEF-1/TCF transcription factors plays a pivotal role in the Wnt-1 signaling pathway. The level of beta-catenin is regulated by partner proteins, including glycogen synthase kinase-3beta (GSK-3beta) and the adenomatous polyposis coli (APC) tumor suppressor protein. Genetic defects in APC are responsible for a heritable predisposition to colon cancer. APC protein and GSK-3beta bind beta-catenin, retain it in the cytoplasm, and facilitate the proteolytic degradation of beta-catenin. Abrogation of this negative regulation allows beta-catenin to translocate to the nucleus and to form a transcriptional activator complex with the DNA-binding protein lymphoid-enhancing factor 1 (LEF-1). This complex is thought to be involved in tumorigenesis. Here we show that covalent linkage of LEF-1 to beta-catenin and to transcriptional activation domains derived from the estrogen receptor or the herpes simplex virus protein VP16 generates transcriptional regulators that induce oncogenic transformation of chicken embryo fibroblasts. The chimeras between LEF-1 and beta-catenin or VP16 are constitutively active, whereas fusions of LEF-1 to the estrogen receptor are regulatable by estrogen. These experiments document the oncogenicity of transactivating LEF-1 and show that the transactivation domain normally provided by beta-catenin can be replaced by heterologous activation domains. These results suggest that the transactivating function of the LEF-1/beta-catenin complex is critical for tumorigenesis and that this complex transforms cells by activating specific LEF-1 target genes.

Animals↗
PubMed1999

Cardiovascular responses elicited by linear acceleration in humans.

Although activation of otolith receptors is known to elicit cardiovascular responses in animals, it is unclear whether vestibular stimulation can evoke changes in blood pressure and heart rate (which are independent of motion sickness) in humans. In the present study, ten normal subjects and three patients with profound bilateral reduction in vestibular function, who were seated upright with the torso aligned with the gravitation vector, were subjected to fore, aft, or lateral linear acceleration (approximately 0.2 g, attaining approximately 2 m/s in 900 ms, and decelerating for 3 s at 0.07 g). The head was fixed in the upright position, pitched maximally downward (chin on chest) or maximally backward (approximately 40-50 degrees) during the accelerations. In normal subjects, all directions of linear acceleration produced an average increase in systolic blood pressure of approximately 7-9 mm Hg and a rapid decrease in the interval between R-waves of the electrocardiogram of 14-27 ms; these responses persisted for only a few seconds. In contrast, the cardiovascular responses in patients with vestibular dysfunction were much smaller (e.g., the maximal pressor response to forward linear acceleration was <4 mm Hg). Head position during accelerations had little effect on the cardiovascular responses that were elicited in the population of normal subjects. However, although the population response was similar across directions of acceleration and head positions, many individuals exhibited larger cardiovascular changes during some stimulus conditions than during others. These data suggest that vestibular stimulation during linear accelerations can produce cardiovascular responses in humans and support the hypothesis that the vestibular system contributes to maintaining stable blood pressure during movement and changes in posture.

Acceleration↗
PubMed1999

Insolubilization of water-soluble dextran.

In order to clarify the insolubilization mechanism of water-soluble dextran, comparison of water-soluble dextran and insoluble particles was carried out by detailed structural and surface chemical studies. The precipitate that form in bottled dextran solutions are composed of dextran itself, resulting from the interaction of dextran molecules (e.g., the formation of hydrogen bonds). Interaction of dextran molecules derived from a crystallized domain causes insolubilization from aqueous solution. In addition, the adsorption of dextran molecules on the air-liquid interface is the first step of insolubilization.

Calorimetry, Differential Scanning↗
PubMed1999

Involvement of the adenosine neuromodulatory system in the benzodiazepine-induced depression of excitatory synaptic transmissions in rat hippocampal neurons in vitro.

We investigated whether adenosine neuromodulation is involved in a benzodiazepine (midazolam)-induced depression of excitatory synaptic transmissions in the CA1 and dentate gyrus (DG) regions in rat hippocampal slices. Field excitatory postsynaptic potentials (fEPSPs), evoked by electrical stimulation of the CA1-Schaffer collateral or the DG-perforant path, were recorded with extracellular microelectrodes from CA1-stratum radiatum or DG-stratum moleculare in oxygenated ACSF. The initial slope of the fEPSPs was analyzed for assessing the drug effects. Midazolam (1 microM) transiently depressed CA1- and DG-fEPSPs. The fEPSPs were depressed to approximately 75% of the control values, and then gradually recovered. The depression was not affected by bicuculline, a GABAA receptor antagonist, although it was completely antagonized by aminophylline, an adenosine receptor antagonist. Dipyridamole (5 microM), an adenosine uptake inhibitor, depressed the fEPSPs in a similar manner to midazolam. An adenosine deaminase inhibitor, EHNA, also transiently depressed the fEPSPs, but in a different manner. Exogenous adenosine persistently depressed the fEPSPs. The effects of the drugs were not significantly different in the CA1 and DG regions. The results suggest that midazolam (1 microM) depresses excitatory synaptic transmissions through the adenosine neuromodulatory system by inhibiting adenosine uptake in the CA1 and DG regions of the hippocampus.

Adenine↗
PubMed1999

Elderly Japanese women with cervical carcinoma show higher proportions of both intermediate-risk human papillomavirus types and p53 mutations.

The p53 mutation has been found only in 0-6% of cervical carcinomas. In light of recent studies demonstrating that mutation of p53 gene was found in over 20% of the patients with vulvar carcinoma, a disease of elderly women and a known human papillomavirus (HPV)-related malignancy, we analysed mutation of the p53 gene in 46 women with cervical carcinomas at the age of 60 or more (mean; 71 years, range; 60-96 years). The presence of HPV and its type were analysed by polymerase chain reaction (PCR)-based assay using the consensus primers for L1 region. Mutation of the p53 gene was analysed by PCR-based single-strand conformation polymorphism and DNA sequencing technique. Point mutation of the p53 gene was detected in 5 out of 46 (11%) cervical carcinomas: 1 of 17 (6%) samples associated with high-risk HPVs (HPV 16 and HPV 18) and 4 of 27 samples (15%) with intermediate-risk HPVs (P= 0.36) whereas no mutation was found in 2 HPV negative cases. The mutated residues resided in the selective sequence known as a DNA-binding domain. The immunohistochemistry revealed the overexpression in cancer tissues positive for p53 mutation. All of the observed mutations of the p53 gene were transition type, suggesting that the mutation may be caused by endogenous mutagenesis. Although falling short of statistical significance reduces the strength of the conclusion, data presented here imply that p53 gene mutation, particularly along with intermediate-risk HPV types, may constitute one pathogenetic factor in cervical carcinoma affecting elderly women.

Adenocarcinoma↗
PubMed1999

Spontaneous splenic rupture in a patient with large hepatocellular carcinoma.

We report a 61-yr-old woman with acute circulatory failure from spontaneous splenic rupture with decompensated liver cirrhosis complicating large hepatocellular carcinoma exposed on the right liver surface. On admission, the patient was tentatively diagnosed as having rupture of the hepatocellular carcinoma, and she died 15 hours after admission despite blood transfusion. Autopsy revealed that the origin of the intraperitoneal hemorrhage was a ruptured spleen. According to a MEDLINE search of the English-language literature published between 1966 and March 1998, this is the first reported case of spontaneous splenic rupture in a patient with hepatocellular carcinoma without splenic metastasis.

Carcinoma, Hepatocellular↗
PubMed1999

[Campylobacter fetus bacteremia and thrombophlebitis in a patient with Waldenstrom's macroglobulinemia].

We report a 67-year-old male with Waldenstrom's macroglobulinemia who developed Campylobacter fetus subspesis fetus (C. fetus) bacteremia and thrombophlebitis. The patient developed a fever and pain in his left lower limb, and could not walk because of the pain. Radioisotopic venography showed thrombophlebitis in his left lower limb. His blood culture grew C. fetus. After starting intravenous PAPM/BP, his symptoms resolved promptly. In contrast to Campylobacter jejuni which is a common cause of infectious diarrhea, C. fetus infection has distinct clinical features showing systemic illness such as bacteremia and thrombophlebitis mainly occurring in immunocompromized patients. This organism should be considered as one of the possible pathogenes in the infectious complications of the immunocompromized patients.

Aged↗
PubMed1999

Removal and inactivation of hepatitis B virus from contaminated pooled plasma in a large-scale manufacturing process for factor VIII and human serum albumin.

BACKGROUND AND OBJECTIVES: The Japanese Red Cross Society recalled one lot of monoclonal-antibody-purified factor VIII (F VIII) and two lots of human serum albumin (HSA) 5 months after preparation of the final products, because of a procedural error that led to contamination by a unit of plasma positive for hepatitis B surface antigen (HBsAg). We evaluated the effectiveness of virus inactivation/removal in a large-scale process for manufacturing F VIII and HSA. MATERIALS AND METHODS: HBV DNA in the retained samples in process was measured by the polymerase chain reaction (PCR). The kinetics of virus inactivation by solvent-detergent (S/D) treatment was examined using model viruses. We also did a look-back survey of the patients who received corresponding products. RESULTS: Contaminated hepatitis B virus (HBV) DNA became undetectable beyond fraction S IV-I in the albumin process and immunoaffinity chromatography in the F VIII process, respectively. The model viruses were inactivated within 5 s by S/D treatment. There is no evidence that patients were infected by HBV after transfusion of these products. CONCLUSION: We conclude that virus inactivation/removal was effectively achieved in a large-scale manufacturing process for F VIII and HSA.

Factor VIII↗
PubMed1999

Gene transfer of human prostacyclin synthase prevents neointimal formation after carotid balloon injury in rats.

BACKGROUND AND PURPOSE: A disordered proliferative process in the vascular wall is thought to underlie the pathogenesis of restenosis after percutaneous transluminal angioplasty and carotid endarterectomy. A growth inhibitory property of overexpressed prostacyclin (PGI2) synthase (PGIS) was recently implicated in the pathological proliferation of vascular smooth muscle cells (VSMC) in vitro. Here, we investigated the effects of increased PGI2 synthesis on the pathological proliferation of VSMCs. METHODS: The cDNA encoding human PGIS was transfected into endothelium-denuded rat carotid arteries after arterial balloon injury with the use of hemagglutinating virus Japan (HVJ). HVJ liposome vector complex without PGIS cDNA was used for vehicle control. The level of 6-keto PGF1alpha, a stable hydrolyzed metabolite of PGI2, the histological distribution of the immunoreactivity for human PGIS and the ratio of neointimal/medial area were analyzed. RESULTS: In the analyses of 6-keto PGF1alpha, the level in the carotid arteries was significantly elevated 3 days after PGIS expression-vector transfection compared with that in the arteries after vehicle transfection. Seven days after human PGIS expression-vector transfection, the PGIS cDNA-transfected neointimal cells were strongly positive for human PGIS immunoreactivity in 81% sections examined. Fourteen days after the injury, the ratio of neointimal/medial area was 1.2+/-0.4 in the PGIS expression-vector transfected group, which was significantly smaller than that of the vehicle control group, 1.7+/-0.5; P<0.01. CONCLUSIONS: It was thus demonstrated that the gene transfer of human PGIS expression-vector into rat carotid arteries resulted in the increased production of human PGI2 in the vascular wall, the expression of human PGIS in the developing neointima and significantly inhibited the neointimal formation generated after balloon injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

A generalized seizure following initiation of nelfinavir in a patient with human immunodeficiency virus type 1 infection, suspected due to interaction between nelfinavir and phenytoin.

Nelfinavir, one of human immunodeficiency virus (HIV) specific protease inhibitors(PIs), is widely used for the treatment of HIV infection. Nelfinavir, which is metabolized with the cytochrome p450 isoforms, elevate the phenytoin level theoretically because nelfinavir acts as an inhibitor of phenytoin metabolism through the enzyme. However, we encountered a case of seizure recurrence caused by a lowered phenytoin level after initiation of nelfinavir. We should be aware of the change in the phenytoin level in concomitant use of nelfinavir.

Adult↗
PubMed1999

Analysis of spinocerebellar ataxia type 2 gene and haplotype analysis: (CCG)1-2 polymorphism and contribution to founder effect.

Spinocerebellar ataxia type 2 is a familial spinocerebellar ataxia with autosomal dominant inheritance. The gene responsible was recently cloned and this disorder was found to be the result of a CAG expansion in its open reading frame. We analysed 13 SCA2 patients in seven unrelated families in Gunma Prefecture, Japan. In four of the seven families, we detected CCG or CCGCCG interruptions in only the expanded alleles. Cosegregation of these polymorphisms with SCA2 patients was established within each family. Together with the results of haplotype analyses, we considered that at least two founders were present in our area and that these (CCG)1-2 polymorphisms may make analysis of founder effects easier. By sequencing analysis we found that although the number of the long CAG repeat varied in each subclone of expanded alleles, these polymorphisms did not change their configuration. This finding suggests that CCG or CCGCCG sequences are stable when surrounded by the long CAG repeat and a single CAG. Moreover, the presence of these polymorphisms may lead to miscounting the repeat size by conventional estimation using a size marker such as an M13 sequencing ladder. Therefore we should consider these polymorphisms and accurately determine the repeat size by sequencing.

Alleles↗
PubMed1999

[Undiagnosed lung cancer complicated by intracavitary aspergillosis].

A 54-year-old man was treated with an antifungal agent (itraconazole) for post-tuberculous intracavitary aspergillosis. Though clinical and radiological findings indicated that the patient's symptoms had gone into remission, aspergillosis recurred 4 months after the cessation of antifungal chemotherapy, requiring that the patient undergo an operation. Intraoperative and pathological findings revealed a squamous cell carcinoma contiguous to the cavity containing the aspergilloma. Though a few cases of aspergilloma within cavitating pulmonary carcinomas have been reported in the literature, the case of lung cancer we report was thought to arise from preformed lung scars surrounding a post-tuberculous cavity that contained an aspergilloma. Although conclusive distinctions between neoplasms and fungal infections are difficult to make, careful observation of the radiographic features is necessary when treating patients with fungus ball-type aspergillosis.

Aspergillosis↗
PubMed1999

[A case of Bentall's operation for an 11-year-old patient with Marfan syndrome].

An 11-year-old girl who was diagnosed to have Marfan syndrome in her infancy, visited us with complaints of easy fatigability and chest discomfort. She was pointed out to have acute development of annuloaortic ectasia with severe aortic regurgitation and mild mitral regurgitation. She underwent replacement of the ascending aorta and aortic valve using composite graft with prosthetic valve (Bentall's operation) and circular annuloplasty of the mitral valve. Bentall's operation for infants and children is remarkably rare because in this generation, acute development of aortic dilatation leading rupture and dissection is quite infrequent while main death is caused by mitral regurgitation.

Aorta↗
PubMed1998

The akt kinase: molecular determinants of oncogenicity.

The serine-threonine kinase Akt is a downstream target of phosphoinositide 3-kinase (PI 3-kinase); it is activated by the phosphoinositide 3-phosphate-dependent kinases PDK1 and PDK2. Certain mutated forms of Akt induce oncogenic transformation in chicken embryo fibroblast cultures and hemangiosarcomas in young chickens. This ability to transform cells depends on localization of Akt at the plasma membrane and on the kinase activity of Akt. A transdominant negative form of Akt interferes with oncogenic transformation induced by the p3k oncogene, which codes for an activated form of PI 3-kinase. Akt is therefore an essential mediator of p3k-induced oncogenicity.

3-Phosphoinositide-Dependent Protein Kinases↗