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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 253 records · Page 14Linked to original sources
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

Time course of endothelin-1 and adrenomedullin after the Fontan procedure.

BACKGROUND: The endothelium-derived vasoconstrictor endothelin (ET)-1 might contribute to the physiology of blood flow regulation and play a role in cardiovascular disease. Adrenomedullin (AM) is a potent vasodilator peptide that has major effects on cardiovascular function and has multiple biologic effects involved in cardiovascular homeostasis. Although pulmonary vascular resistance is known to be one of the most important factors to determine the indications for a Fontan procedure, the time course of the plasma cytokine before and after the Fontan procedure is not known. METHODS: Sixteen patients were divided into two groups, 8 patients (1 to 14 years) who had the Fontan procedure (atriopulmonary connection) and 8 age-matched controls who had biventricular repair with normal central venous pressure. Plasma ET-1 and adrenomedullin levels were measured in both groups immediately before cardiopulmonary bypass, immediately after cardiopulmonary bypass, and 6 and 24 hours after cardiopulmonary bypass. A thermodilution catheter was inserted during the operation, and mean pulmonary arterial pressure, pulmonary wedge pressure, and cardiac output were measured, and pulmonary vascular resistance was calculated at the same time points. Correlation between the plasma ET-1 levels and pulmonary vascular resistance data were obtained in the Fontan group. RESULTS: Plasma ET-1 levels in the Fontan group were elevated after operation and were higher than the control group at 6 and 24 hours after cardiopulmonary bypass. Plasma adrenomedullin in the Fontan group was lower than in the control group at 6 and 24 hours after cardiopulmonary bypass. A significant positive correlation was obtained between the plasma ET-1 and pulmonary vascular resistance data (r = 0.475). CONCLUSIONS: Imbalance between increased ET-1 and relatively decreased adrenomedullin after cardiopulmonary bypass in the Fontan procedure could contribute to dominant effects of ET-1, which might induce vasoconstriction after the Fontan procedure. ET-1 might play an important role in maintaining vasoconstriction after the Fontan procedure.

Adolescent↗
PubMed1999

Myocardial self-preservative effect of heat shock protein 70 on an immature lamb heart.

BACKGROUND: Heat shock proteins have been shown to enhance myocardial tolerance of ischemia-reperfusion injury and are induced in the myocardium of many animals by various stressors. METHODS: To assess the effects and time course of the inducible form of heat shock protein 70, we raised the rectal temperature of 15 neonatal lambs to 43 degrees C for 15 minutes. At 15, 30, 60, and 120 minutes and 24 hours after heat shock, hearts were subjected to immunoblot analysis for heat shock protein (hsp 72/73). Twenty-four hours after heat shock, neonatal lamb hearts (n = 8) were subjected to 2 hours of cold cardioplegic ischemia (HSP group). Eight neonatal lamb hearts without heat shock served as control. After 60 minutes of reperfusion, left ventricular systolic and diastolic function, coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and lactate levels were measured. Endothelial function was assessed by measuring in situ coronary vascular resistance response to acetylcholine and trinitroglycerine. RESULTS: The HSP group showed a significantly higher recovery of systolic function as well as MVO, and a lower lactate level compared to the control group at 60 minutes after reperfusion. Recovery of coronary endothelial function was also significantly better in the HSP group than in the control group. Inducible form of HSP 70 was expressed 15 minutes after heat shock and continued to be observed at 24 hours after the stress. CONCLUSIONS: Heat shock stress associated with the production of inducible heat shock proteins improved the recovery of ventricular function as well as endothelial function and aerobic metabolism after hypothermic cardioplegic ischemia. Induction of heat shock proteins by any means prior to planned hypothermic ischemia may lead to a new approach for myocardial protection.

Animals↗
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

Evaluation of anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]- guanine (A-5021) in mice.

The anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guani ne (A-5021) was evaluated in murine cells and in several murine models of herpes simplex virus (HSV) infection. Against HSV type 1 (HSV-1), A-5021 was 15-30- and 30-60-fold more active, and against HSV type 2 (HSV-2), it was 2- and 8-fold more active than acyclovir and penciclovir in Balb/3T3 cells, respectively. When antiviral compounds were administered orally (once daily) to mice infected intraperitoneally with HSV-1 (Tomioka), A-5021 was more active than acyclovir or famciclovir in spite of its relatively low oral bioavailability. A-5021 was as active as penciclovir when the antiviral compounds were given intravenously (three times daily) to mice infected intraperitoneally with HSV-2 (186). In mice with a cutaneous HSV-1 (KOS) infection, three times daily oral therapy with A-5021 at 25 mg/kg per day produced more significant reduction in severity of skin lesions than equivalent treatment with acyclovir or famciclovir. In mice infected intracerebrally with HSV-1 (Tomioka), complete survival was observed in the group treated intravenously with A-5021 at 25 mg/kg per day (three times daily), while more than 50% of mice died in the groups treated intravenously with acyclovir of up to 100 mg/kg per day (three times daily). Moreover, A-5021 was more effective than acyclovir in clearing infectious virus from the brain. These findings demonstrate that A-5021 has potent anti-HSV activity in several murine models.

3T3 Cells↗
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

Successful treatment of Kimura's disease with cyclosporine.

We report the case of a 29-year-old Japanese woman presenting with recurring Kimura's disease. We began treatment with cyclosporine within 7 days, the nodular lesion had almost cleared. The cyclosporine dose was then gradually reduced and discontinued after 6 months. The patient was reassessed 18 months after the cessation of treatment and there was no evidence of recurrence of the disease. We speculate that the effects of cyclosporine on T helper-2 cells improves Kimura's disease.

Adult↗
PubMed1999

Compartmentalized expression of zebrafish ten-m3 and ten-m4, homologues of the Drosophila ten(m)/odd Oz gene, in the central nervous system.

Zebrafish ten-m3 and ten-m4 encode proteins highly similar to the product of Drosophila pair-rule gene ten(m)/odd Oz (odz). Their products contain eight epidermal growth factor (EGF)-like repeats that resemble mostly those of the extracellular matrix molecule tenascin. During segmentation period, ten-m3 is expressed in the somites, notochord, pharyngeal arches, and the brain, while expression of ten-m4 is mainly restricted to the brain. In the developing brain, ten-m3 and ten-m4 expression delineates several compartments. Interestingly, ten-m3 and ten-m4 show expression patterns complementary to each other in the developing forebrain and midbrain along both rostrocaudal and dorsoventral axes, depending on developmental stages and locations.

Amino Acid Sequence↗
PubMed1999

Mitochondrial DNA analysis of Sporothrix schenckii clinical isolates from China.

Mitochondrial DNA (mtDNA) types based on restriction fragment length polymorphism (RFLP) patterns with HaeIII were investigated in clinical isolates of Sporothrix schenckii in China. In addition to 23 mtDNA types (Types 1-23) so far reported, a new mtDNA type (Type 24) was found in this study. Type 24 was divided into two subtypes, Subtype 24A and 24B based on RFLP with EcoRV. Sixty-seven isolates in China consisted of 58 isolates of Type 4, 5 of Type 6, 1 of Type 5, 1 of Type 20 and 2 of Type 24. Based on the phylogeny of the mtDNA types (Types 1-24) constructed by estimating sequence divergences of mtDNA, mtDNA types clustered into two groups: Group A (Types 1-3, Type 11, Types 14-19 and Types 22-23) and Group B (Types 4-10, Types 12-13, Types 20-21 and Type 24). These results suggest that most S. schenckii isolates in China belong to Group B.

China↗
PubMed1999

Delay in administration of CDDP until completion of AGM-1470 treatment enhances antimetastatic and antitumor effects.

The efficacy of cis-diammine dichloroplatinum (CDDP) therapy in combination with continuous administration of angiogenesis inhibitor o-(chloroacetyl-carbamoyl) fumagillol (AGM-1470) was evaluated experimentally using a transplantable rat osteosarcoma line previously established in our laboratory. AGM-1470 (2.5 mg/kg body weight/week) was administered by Alzet osmotic pumps for 2 weeks starting from 7 days after tumor inplantation and CDDP (1.25 mg/kg) was given on days 21 and 24. The number of lung metastatic nodules was counted and the wet weights of the primary tumors were measured 5 weeks after tumor inplantation. Values with administration of CDDP 3 days after discontinuation of AGM-1470 were significantly lower than when the two agents were coadministered (P < 0.05). This animal model should facilitate optimization of the timing of combination therapy.

Animals↗
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

N18 in median somatosensory evoked potentials: a new indicator of medullary function useful for the diagnosis of brain death.

OBJECTIVES: To record N18 in median somatosensory evoked potentials (SEPs) for deeply comatose or brain dead patients and to demonstrate the usefulness of N18 for the diagnosis of brain death in comparison with auditory brain stem responses (ABRs) and P13/14 in median SEPs, which have been conventionally used as complementary tests for the diagnosis of brain death. METHODS: Subjects were 19 deeply comatose or brain dead patients. Thirteen recordings were performed in deeply comatose but not brain dead conditions, and 12 recordings were performed in brain death. N18 was evaluated in the CPi-C2S lead (or other scalp-C2S leads) to obtain a flat baseline. RESULTS: N18 was preserved in 12 of 13 non-brain dead comatose recordings whereas it was completely lost for all of the 12 brain death recordings. P13/14 in median SEPs was preserved for all the comatose recordings, whereas apparent P13/14-like potentials, usually of low amplitude, were seen in nine of 12 brain death recordings-that is, frequent false positives. The ABRs already showed features which were characteristic for brain death (loss of components other than wave 1 or small wave 2) for four comatose recordings, in three of which N18 was preserved. The last result not only corresponds with the fact that ABRs can evaluate pontine and midbrain functions and not medullary function, but further supports the medullary origin of N18. In the four patients followed up for the course of progression from coma to brain death, N18s preserved in normal size during the comatose state were completely lost after brain death was established. CONCLUSIONS: The N18 potential is generated by the cuneate nucleus in the medulla oblongata in the preceding studies. N18 is suggested to be a promising tool for the diagnosis of brain death because there were no false positives and rare false negatives in the present series for detecting the remaining brain stem function.

Adult↗
PubMed1999

DISI Deformity and Post-Operative Symptoms of Scaphoid Non-Union.

The correlation between the residual dorsal intercalated segmental instability (DISI) deformity and symptoms of the wrist was investigated in 20 patients with healed scaphoid non-union who had open reduction and bone grafting. In seven patients, inlay corticocancellous bone grafting (modified Russe procedure) was performed. In four of the seven patients, an additional Herbert bone screw was used for internal fixation. The remaining 13 patients were treated with open reduction, anterior bone grafting, and internal fixation with Herbert bone screw. Average duration of follow-up period after operation was 20 months (range, 6 to 57 months). The average extension-flexion arc of the injured wrists was 129 degrees, which was 31 degrees less than that of the uninjured wrists. The average grip strength of the injured wrists was 89% of that of the uninjured wrist. Before the operation, all 20 patients were symptomatic and complained of wrist pains. Post-operatively, three patients experienced mild pains and only one complained of moderate wrist pains. Post-operative radiolunate angle ranged from 0 degrees to 34 degrees (average 10 degrees ). DISI deformity remained uncorrected in eight patients. Post-operative symptoms were compared amongst the eight patients who had DISI deformity and 12 patients who had no deformity. There was no significant difference in range of motion, grip strength, and incidence of pain between these two groups of patients. The presence of DISI deformity after bone grafting for a symptomatic scaphoid non-union was not predictive of post-operative symptoms of the wrist.

Journal Article↗