Search PubMed⌕ Search

Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 73 records · Page 4Linked to original sources
PubMed2001

Double switch operation for superior-inferior ventricles.

Superior-inferior ventricles are a rare cardiac malformation characterized by the two ventricles lying one above the other instead of side by side. Consequently, the interventricular septum that separates such ventricles is horizontal, and anomalies of the atrioventricular valves and the ventriculoarterial relations are almost always present. This complex anomaly is difficult to manage with an operation, so few cases have been reported. We describe a successful experience in which we performed a double switch operation, consisting of the Senning and Jatene procedures, for this rare malformation accompanied by double-outlet right ventricle [S,L,L]. This is the first report we have been able to locate of a double switch operation for superior-inferior ventricles.

Adolescent↗
PubMed2001

Gene therapy in vascular medicine: recent advances and future perspectives.

Gene therapy is emerging as a potential strategy for the treatment of cardiovascular diseases, such as restenosis after angioplasty, vascular bypass graft occlusion, and transplant coronary vasculopathy, for which no known effective therapy exists. The first human trial in cardiovascular disease was started in 1994 to treat peripheral vascular disease using vascular endothelial growth factor. In addition, therapeutic angiogenesis using the vascular endothelial growth factor gene was applied in the treatment of ischemic heart disease. The results from these clinical trials seem to exceed expectation. Improvement of clinical symptoms in peripheral arterial disease and ischemic heart disease has been reported. At least five different potent angiogenic growth factors have been tested in clinical trials to treat peripheral arterial disease or ischemic heart disease. In addition, another strategy for combating disease processes, to target the transcriptional process, has been tested in a human trial. Transfection of cis-element double-stranded oligodeoxynucleotides is an especially powerful tool in a new class of antigen strategies for gene therapy. Transfection of double-stranded oligodeoxynucleotides corresponding to the cis sequence will result in the attenuation of the authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-elements, with subsequent modulation of gene expression. Genetically modified vein grafts transfected with a decoy against E2F, an essential transcription factor in cell cycle progression, revealed apparent long-term potency in human patients. This review focuses on the future potential of gene therapy for the treatment of cardiovascular disease.

Angioplasty↗
PubMed2001

Early anchoring collagen fibers at the bone-tendon interface are conducted by woven bone formation: light microscope and scanning electron microscope observation using a canine model.

To clarify the early process of recovery at the bone-tendon interface, we used light microscopy and SEM to examine the process of anchoring of collagen fibers to bone in a canine model. At two weeks, tendon, scar tissue, woven bone and lamellar bone were present at the insertion site. SEM revealed anchoring of collagen fibril bundles of the scar to the woven bone. By 4 weeks, the number of anchoring fibers had increased and a parallel arrangement of fibers was observed. SEM demonstrated deep penetration of fibers into the woven bone layer. In addition, the fibers were observed to project into and intermingle with the scar tissue. By 6 weeks, the anchoring fibers had developed fully and were distributed densely over the interface. SEM also revealed that the collagen fibril bundles in the scar tissue had connected with the collagen fibrils of the woven bone by way of the anchoring bundles. The woven bone was identifiable throughout the early stages of recovery as the interface between soft tissue and hard tissue. Throughout all experimental periods, no staining was observed at the interface of the tendon and bone by Saffranin-O. The formation of woven bone was important during early recovery of the tendon-bone interface prior to the completion of fibrocartilage-mediated insertion.

Animals↗
PubMed2001

The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.

The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.

Amino Acid Sequence↗
PubMed2001

Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease.

Hepatocyte growth factor (HGF) exclusively stimulates the growth of endothelial cells without replication of vascular smooth muscle cells, and acts as a survival factor against endothelial cell death. Recently, a novel therapeutic strategy for ischemic diseases using angiogenic growth factors to expedite and/or augment collateral artery development has been proposed. We have previously reported that intra-arterial administration of recombinant HGF induced angiogenesis in a rabbit hindlimb ischemia model. In this study, we examined the feasibility of gene therapy using HGF to treat peripheral arterial disease rather than recombinant therapy, due to its disadvantages. Initially, we examined the transfection of 'naked' human HGF plasmid into a rat hindlimb ischemia model. Intramuscular injection of human HGF plasmid resulted in a significant increase in blood flow as assessed by laser Doppler imaging, accompanied by the detection of human HGF protein. A significant increase in capillary density was found in rats transfected with human HGF as compared with control vector, in a dose-dependent manner (P < 0.01). Importantly, at 5 weeks after transfection, the degree of angiogenesis induced by transfection of HGF plasmid was significantly greater than that caused by a single injection of recombinant HGF. As an approach to human gene therapy, we also employed a rabbit hindlimb ischemia model as a preclinical study. Naked HGF plasmid was intramuscularly injected in the ischemic hindlimb of rabbits, to evaluate its angiogenic activity. Intramuscular injection of HGF plasmid once on day 10 after surgery produced significant augmentation of collateral vessel development on day 30 in the ischemia model, as assessed by angiography (P < 0.01). Serial angiograms revealed progressive linear extension of collateral arteries from the origin stem artery to the distal point of the reconstituted parent vessel in HGF-transfected animals. In addition, a significant increase in blood flow was assessed by a Doppler flow wire and the ratio in blood pressure of the ischemic limb to the normal limb was observed in rabbits transfected with HGF plasmid as compared with rabbits transfected with control vector (P < 0.01). Overall, intramuscular injection of naked human HGF plasmid induced therapeutic angiogenesis in rat and rabbit ischemic hindlimb models, as potential therapy for peripheral arterial disease.

Animals↗
PubMed2001

CD30+ lymphoproliferative disorder: primary cutaneous anaplastic large cell lymphoma followed by lymphomatoid papulosis.

CD30+ large anaplastic lymphoid cells are seen in anaplastic large cell lymphoma (ALCL), and also in lymphomatoid papulosis (LyP) and other lymphoproliferative disorders. It can be difficult precisely to categorize these disorders with CD30+ cells. We report a case of primary cutaneous CD30+ ALCL with systemic metastases in whom the clinical disease subsequently evolved into LyP. The patient was initially administered cisplatin and etoposide and made a good response. Eighteen months later, recurrent, self-healing cutaneous small nodules appeared around the original tumour site without any systemic involvement. Histopathological examination of the recurrent lesions revealed infiltration with a mixture of cells that included neutrophils, eosinophils and CD30+ large anaplastic cells cytologically identical with those in the primary lesion. The anaplastic cells in both the primary and recurrent lesions were positive for monoclonal antibodies CD30, CD25 and a monoclonal antibody directed against the chimeric protein p80(NPM-ALK). These observations suggest the possibility that the ALCL and the subsequent LyP represent different clinical manifestations of proliferation of the same clone.

Adult↗
PubMed2001

Length and width of the tendinous portion of the palmaris longus: a cadaver study of adult Japanese.

We examined 72 forearms of 36 cadavers to measure the length and width of the tendinous portion of the palmaris longus in adult Japanese. The palmaris longus muscles were absent in both arms in 1 cadaver and in a unilateral arm in 1 cadaver. Double palmaris longus muscles were found in 1 arm in another cadaver. Most cadavers had a typical palmaris longus muscle and tendon shape. The mean length and width of the tendons were 124.6 +/- 17.0 and 4.5 +/- 0.7 mm, respectively, in male specimens and 108.3 +/- 16.4 and 4.0 +/- 0.7 mm in female specimens, respectively. The mean lengths of the forearms were 240.0 +/- 12.6 mm in male specimens and 218.8 +/- 14.6 mm in female specimens. There was a statistically significant correlation between the lengths of the palmaris longus tendon and forearm. These results indicate that one can estimate the length of palmaris longus tendons before surgical intervention.

Adult↗
PubMed2001

Anxiety and pain suppress the natural killer cell activity in oral surgery outpatients.

OBJECTIVE: Psychological stress has an influence on natural killer cell (NK) activity, which plays a central role in protection against microbial infection and cancer. Anxiety concerning cancer is a typical type of psychological stress observed in patients and is associated with various diseases. In this study, we examined whether anxiety about cancer reduces the NK activity or quality of life (QOL), or both, of outpatients. PATIENTS AND METHODS: NK activity was determined by means of a 4-hour 51 chromium-release assay, and a QOL questionnaire by the World Health Organization called QOL-BRIEF was also used. One hundred forty-four patients were asked a variety of questions about anxiety with respect to cancer and pain on their first visit to the outpatient clinic of our Department of Oral Surgery. RESULTS: The NK activity in patients with anxiety about cancer was significantly lower (P < .001) than that in those with no such anxiety. In contrast, NK activity was not influenced by any other factor tested, including differences in diseases and QOL scores. CONCLUSION: Anxiety about cancer may be one of the primary factors for suppression of NK activity in oral surgery outpatients.

Adult↗
PubMed2001

Surgical intervention for anomalous origin of the left coronary artery from the pulmonary artery: the Tokyo experience.

BACKGROUND: Few studies after surgical repair of the anomalous origin of the left coronary artery have reported the importance of the mitral annuloplasty or the long-term results. METHODS: Between January 1982 and March 2000, 29 patients with anomalous origin underwent surgical intervention at our institution (direct aortic reimplantation in 19 and Takeuchi procedure in 10). Age at the time of operation ranged from 2 months to 24 years (median, 29.3 months), and 9 patients were infants. Twenty-four patients had varying degrees of mitral incompetence. Simultaneous mitral annuloplasty at the anterolateral commissure was performed in all 24 patients with incompetence. RESULTS: There were 2 hospital deaths among the infants, and no late deaths. Mean follow-up was 100 +/- 57 months, and the actuarial survival was 93.1% at 10 years (70% confidence limits, 87-99). Cardiothoracic ratio at discharge was not decreasing significantly (P =.35); however, this value 5 years after the operation showed the significant decrease (P =.003) versus preoperative value. Preoperative mitral incompetence decreased in all but one of the operative survivors with mitral annuloplasty at the last follow-up. The left ventricular fractional shortening z-score was not normalized at discharge but was normalized in the late period. CONCLUSION: These data demonstrate that impaired left ventricular function normalized in the long term (even if it was below normal immediately after operation) after 2-coronary repair. We recommend that the simultaneous mitral annuloplasty should be performed at the time of operation for patients who have mitral incompetence with anomalous origin of the left coronary artery.

Adolescent↗
PubMed2001

Establishment of a local cooling model against spinal cord ischemia representing prolonged induction of heat shock protein.

OBJECTIVES: Paraplegia is one of the serious complications of thoracoabdominal aortic operations. Regional hypothermia protects against spinal cord ischemia although the protective mechanism remains unknown. We attempted to create a simple model of local cooling under transient spinal cord ischemia and evaluated the effect using functional and histologic findings. METHODS: Male domesticated rabbits were divided into 3 groups: control, normothermic group (group N), and local hypothermic group (group H). A balloon catheter was used for spinal cord ischemia by abdominal aortic clamping. A cold pack attached to the lumbar region could lower the regional cord temperature initially. Neurologic function was evaluated by the Johnson score. Cell damage was analyzed by observing motor neurons with the use of hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated deoxy-uracil triphosphate biotin in situ nick end labeling (TUNEL), and immunoreactivity of heat shock protein. RESULTS: Physiologic estimation showed that local hypothermia improved the functional deficits (group N, 1.3 +/- 0.9; group H, 4.9 +/- 0.3; P =.0020). Seven days after reperfusion, there was a significant difference in the motor neuron numbers between groups N and H (group N, 7.2 +/- 1.9; group H, 20.4 +/- 3.2; P =.0090). The number of TUNEL-positive motor neurons was reduced significantly (group N, 7.2 +/- 2.4; group H, 1.0 +/- 0.7; P =.0082). Heat shock protein immunoreactivity was prolonged up to 2 days after reperfusion in the hypothermic group. CONCLUSIONS: These results suggest that local hypothermia extended the production of heat shock protein in spinal cord motor neurons after reperfusion and inhibited their apoptotic change.

Animals↗
PubMed2001

Coarctation of the aorta and ventricular septal defect: should we perform a single-stage repair?

BACKGROUND: Optimal management for coarctation of the aorta and ventricular septal defect remains controversial. The current study was undertaken to determine outcome, including recoarctation after 2-stage repair, at our institution. METHODS: Between 1984 and 1998, 79 patients younger than 3 months with coarctation and ventricular septal defect underwent 2-stage repair at our institution. The first-stage operation consisted of subclavian flap angioplasty and pulmonary banding. The median age at the time of first operation was 28 days (range, 4-90 days), and median weight was 3.2 kg (range, 1.2-5.1 kg). Hypoplastic aortic arch was present in 27 patients, and coexisting anomalies were present in 13 patients. After a mean interval of 10.4 +/- 9.6 months, they underwent a second-stage repair, with closure of the ventricular septal defect and pulmonary debanding. RESULTS: There were 2 hospital deaths and 4 late deaths. Mean follow-up was 9.2 +/- 4.9 years (range, 2.0-18.3 years), and actuarial survival was 92.3% at 10 years (95% confidence interval, 86.6%-98.3%). Age at first operation, body weight, hypoplastic arch, and coexisting anomalies had no significant influence on overall mortality. Freedom from recoarctation rate was 90.4% at 10 years (95% confidence interval, 83.7%-97.2%). CONCLUSION: To diminish mortality and the recoarctation rate and also to decrease the possibility of complications related to circulatory arrest and allogeneic blood transfusion, 2-stage repair is still an effective technique for coarctation of the aorta associated with ventricular septal defect.

Actuarial Analysis↗
PubMed2001

Delayed hemispheric neuronal loss in severely head-injured patients.

Recent experimental studies have revealed that traumatic brain injury as well as ischemic brain injury can cause chronic progressive neuronal damage. In the present study, we demonstrate previously unreported delayed cerebral atrophy on computerized tomography (CT) scans in severely head-injured patients. Seventeen severely head-injured patients who required mild hypothermia to control intracranial hypertension after the failure of conventional therapies were retrospectively analyzed. All 17 patients survived more than 1 year. Delayed neuronal loss (DNL) was observed in only eight of the 17 patients. Eight patients with DNL required longer durations of mild hypothermia to control intracranial hypertension than nine patients without DNL. Six of these eight patients with DNL achieved functional recovery despite progressive atrophic changes demonstrated on CT scans. On CT scans, DNL was characterized by (1) the sudden appearance at several months postinjury of a low-density area in the hemisphere ipsilateral to the injury; (2) the preservation of essential cortical structure although related white matter structures showed severe atrophic changes; and (3) no spread of the low-density area to the contiguous territory of the other main cerebral artery. It is concluded that focal primary injury to underlying brain, if severe enough, can result in delayed hemispheric atrophy.

Adolescent↗
PubMed2001

Angiotensin converting enzyme inhibitor restrains inflammation-induced vascular injury in mice.

OBJECTIVES: Recent advances in molecular genetics made the mouse model important for studying the genetic basis of hypertension and vascular diseases such as the components of the renin-angiotensin system. This study was undertaken to investigate the role of angiotensin converting enzyme (ACE) in the mouse vascular injury model. DESIGN AND METHODS: Inflammation-induced vascular injury was created by placing a polyethylene cuff around the femoral artery of 12-14-week-old male FVB/N mice. Cuffed arteries were harvested and applied to reverse transcriptase-polymerase chain reaction analysis and immunohistochemistry for ACE. Subsequently, the effects of an ACE inhibitor, perindopril (3 mg/kg per day), on neointimal thickening were examined 2 weeks after cuff placement The influence of a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg per day) on the effects of perindopril was also examined. RESULTS: ACE mRNA expression increased in a time-dependent manner up to 2 weeks after cuff placement. Immunoreactive ACE was localized in the endothelium in the intact artery, while positive staining was observed in the medial and neointimal layer as well as in the periadventitial region of the cuffed artery. The intimamedia area ratio was significantly decreased by perindopril treatment (vehicle, 0.75+/-0.10; perindopril, 0.32+/-0.04; P< 0.05). The effect of perindopril was abrogated by coadministration of L-NAME whereas L-NAME alone did not affect the intima-media ratio (L-NAME, 0.66+/-0.11; perindopril + L-NAME, 0.72+/-0.09). CONCLUSIONS: This study provides evidence that ACE plays a role in cuff-induced neointimal thickening in mice. Nitric oxide may contribute, at least in part, to the inhibitory effects of perindopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Enhanced expression of heat shock proteins in leukocytes from trauma patients.

BACKGROUND: Heat shock proteins (HSPs) play essential roles as molecular chaperones in cells to assist in the repair of degenerated proteins. The expression of HSPs in polymorphonuclear leukocytes (PMNLs) following insult has not been delineated. The objective of this study was to clarify the serial changes in HSP expression in PMNLs from trauma patients. METHODS: Fifty severely injured patients (mean Injury Severity Score of 31.8 +/- 10.8) and 17 healthy volunteers were included as study subjects. Blood samples were serially obtained at three time points: days 0 to 1, days 2 to 5, and days 6 to 14 after the trauma event. We measured expressions of HSP27, HSP60, HSP70, and HSP90 in permeabilized PMNLs by flow cytometry using a monoclonal antibody generated against each HSP and fluorescein isothiocyanate-conjugated antimouse immunoglobulins as secondary reagents. We also evaluated the expression of HSP70 mRNA in PMNLs by Northern blot hybridization and the expression of HSP70 in PMNLs by fluorescence microscopy. RESULTS: Expressions of HSP27, HSP70, and HSP90 in PMNLs from trauma patients were significantly greater than in PMNLs from healthy volunteers in all three periods (days 0-1, days 2-5, and days 6-14). The expression of HSP60 in PMNLs from trauma patients was significantly greater than normal expression on days 2 to 5 and days 6 to 14. The values for HSP27, HSP60, and HSP70 on days 2 to 5 were significantly higher than those on days 0 to 1. The expression of HSP70 mRNA in PMNLs was significantly enhanced for as long as 2 weeks after trauma compared with that in normal volunteers. CONCLUSION: Severe trauma causes demonstrated enhanced expression of HSPs in PMNLs during the acute phase. This enhanced expression of HSPs may regulate PMNL functions.

Adolescent↗
PubMed2001

Decoy oligodeoxynucleotides as novel cardiovascular drugs for cardiovascular disease.

Gene therapy is emerging as a potential strategy in the treatment of cardiovascular disease such as restenosis after angioplasty, vascular bypass graft occlusion, and transplant coronary vasculopathy, for which no known effective therapy exists. One strategy for combatting disease processes is to target the transcriptional process. Application of DNA technology such as antisense strategy to regulate the transcription of disease-related genes in vivo has important therapeutic potential. Recently, transfection of cis-element double-stranded oligodeoxynucleotides (= decoy) as a powerful tool in a new class of antigene strategies for gene therapy was reported. Transfection of double-stranded oligodeoxynucleotides corresponding to cis sequence will result in the attenuation of authentic cis-trans interaction, leading to the removal of transfactors from the endogenous cis-elements with subsequent modulation of gene expression. This "decoy" strategy is not only a novel strategy for gene therapy as an antigene strategy, but also a powerful tool for the study of endogenous gene regulation in vivo as well as in vitro. In this review, we focus on the future potential of decoy oligodeoxynucleotide-based gene therapy in the treatment of cardiovascular disease.

Cardiovascular Agents↗
PubMed2001

Prevalence of Giardia lamblia infection in household dogs.

A total of 1035 household dogs were examined for the presence of Giardia lamblia (G. lamblia) in their feces. Fecal samples from 151 (14.6%) of the dogs were positive for Giardia. The protozoan was more often detected in soft feces (26.4%) than in normal (10.0%) or diarrheic feces (13.7%) (p < 0.001 and p < 0.01, respectively). The forms of the organisms obtained from the 151 dogs were cysts (77.5%), trophozoites (9.9%), or both cysts and trophozoites (12.6%). Dogs kept indoors had a higher prevalence (18.5%) of Giardia than dogs kept outdoors (4.8%) (p < 0.001). Giardia infection was also more prevalent in 1-6 months old puppies (21.7%) compared to other groups (2.4%-7.5%) (p < 0.001). The prevalence of Giardia in dogs originally purchased from pet shops or breeding kennels was extremely high (21.5%) compared to that of dogs from individual households (4.3%) (p < 0.001). With regard to human public health, the high infection rate of Giardia in puppies and dogs kept indoors is a serious problem because G. lamblia in infected dogs may have zoonotic potential. No reports of human giardiasis transmitted from dogs have been made. However, the results of this study suggest that the risk of Giardia transmission from household dogs to humans is not negligible. Pet owners should be taught appropriate hygiene measures to prevent Giardia transmission from dogs to humans.

Animals↗
PubMed2001

Persistent plaques and linear pigmentation in adult-onset Still's disease.

A 25-year-old Japanese man presented with high spiking fever, arthralgia and a skin rash. A pruritic edematous erythema with persistent plaques was found mainly on the trunk; these lesions persisted even when the fever subsided, with prominent linear pigmentation. As marked neutrophilia and a high level of serum ferritin were detected, a diagnosis of adult-onset Still's disease (AOSD) was made, even though the persistent eruption was not characteristic of the disease. Oral prednisolone, together with low-dose methotrexate, was given with good results. In the literature, a similar atypical rash has been reported in 11 cases in Japan. All of them required high-dose administration of corticosteroids or other immunosuppressive agents. Severe systemic complications were seen in 3 patients, and 2 cases died of the disease. Persistent plaques and linear pigmentation are some of the manifestations of AOSD, which cannot be overlooked. This appearance could be an indication that suggests an increased risk of systemic complications and a prolonged time to clinical remission.

Administration, Oral↗