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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 271 records · Page 15Linked to original sources

The ultrastructural patterns of mast cell degranulation in Kimura's disease.

BACKGROUND: Although Kimura's disease has been considered an atopic disease because of the association of peripheral blood eosinophilia and elevated serum IgE, the mechanisms of these phenomena are still unknown. OBJECTIVE: It is now established that mast cells are a source of cytokines that are involved in eosinophil recruitment or IgE production. In order to understand the role of mast cells in Kimura's disease, we conducted ultrastructural studies. METHOD: The 45 mast cells obtained from 2 patients with Kimura's disease were classified into two subgroups: S type, with a predominance of scroll or crystal subelements in their granules, and P type, predominantly possessing a particulate or filamentous substructure. RESULTS: We observed numerous P type mast cells with focal losses of granule contents in the absence of granule extrusion in Kimura's disease. CONCLUSION: These results indicate the possibility that slow release of mediators or cytokines from mast cells by piecemeal degranulation may contribute to the pathomechanism of Kimura's disease.

Adult↗

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↗

Inhibition of the p53 tumor suppressor gene results in growth of human aortic vascular smooth muscle cells. Potential role of p53 in regulation of vascular smooth muscle cell growth.

Loss of activity of the p53 tumor suppressor gene product has been postulated in the pathogenesis of human restenosis. Although the antioncogenes p53 and retinoblastoma (Rb) susceptibility gene have been reported to play a pivotal role in cell cycle progression in various cells, the role of p53 and Rb in the growth of human vascular smooth muscle cells (VSMC) has not yet been clarified. We used antisense strategy against p53 and Rb genes by the viral envelope-liposomal method. Transfection of antisense p53 oligodeoxynucleotides (ODN) alone resulted in an increase in DNA synthesis compared with control (P<0.01). Similarly, transfection of antisense Rb ODN alone resulted in a higher DNA synthesis rate than control (P<0.01). Moreover, increase in VSMC number was only induced by transfection of antisense p53 ODN alone or cotransfection of p53/Rb ODN (P<0.01), whereas a single transfection of antisense Rb ODN had little effect on cell number. Therefore, we hypothesized that this discrepancy is due to the induction of apoptosis mediated by p53. Interestingly, apoptotic cells were markedly increased in VSMC transfected with antisense Rb ODN alone, accompanied by the induction of p53 protein. The number of apoptotic cells was attenuated by cotransfection of antisense p53 ODN (P<0.01). We finally examined the molecular mechanisms of apoptosis induced by the absence of Rb. In VSMC transfected with antisense Rb ODN, bax, a promoter of apoptosis, was significantly increased in VSMC transfected with antisense Rb ODN (P<0.01), whereas bcl-2 and Fas did not play a pivotal role in the induction of apoptosis. Overall, these data first demonstrated that the antioncogenes p53 and Rb negatively regulated the cell cycle in VSMC, suggesting that the modulation of their activity may mediate VSMC growth such as that in restenosis and atherosclerosis. The presence of p53 plays a pivotal role in the regulation of apoptosis in human VSMC growth, probably through the bax pathway. These results provide evidence that p53 is a functional link between cell growth and apoptosis in VSMC.

Analysis of Variance↗

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↗

Therapeutic efficacy of transcranial magnetic stimulation for hereditary spinocerebellar degeneration.

We applied transcranial magnetic stimulation (TMS) as a therapeutic approach for patients with spinocerebellar degeneration (SCD). The subjects were four familial SCD patients (three men and one woman) aged from 27 to 76 years old. They were genetically analysed as two spinocerebellar ataxia type 6 (SCA 6), one SCA 1, and one SCA 7. The durations of their illness ranged from 1 to 7 years. Ten consecutive magnetic pulses were delivered over the scalp corresponding to the right cerebellar hemisphere, the middle of the cerebellum and the left cerebellar hemisphere, respectively, every day for 21 days. In all patients, the time and the number of steps required for a 10 m walk examination were significantly decreased after TMS trial compared with those before TMS. The number of feasible steps in tandem gait test increased. The total length of tracing body balance for 30 seconds measured by gravinometer was significantly decreased. However, nystagmus, dysarthria or incoordination of the upper limbs did not change after TMS trial. It is of interest that the blood flow of the cerebellar hemisphere, putamen and pons were significantly increased during the TMS trial. Although we do not know the exact mechanism by which TMS improved the ataxic gait, we speculate the increase of blood flow in the cerebellum, putamen and pons takes part in the improvement. These findings suggest that TMS over the cerebellum may be an effective therapy for patients with SCD.

Adult↗

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↗

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↗

[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↗

[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↗

[A case of supravalvular mitral ring].

A two-year-old girl with supravalvular mitral ring successfully underwent the excision of the ring. The preoperative echocardiogram showed supravalvular mitral ring and almost normal mitral leaflets. We paid attention not to injury mitral valve at the excision of the ring because supravalvular mitral ring adhered to the mitral valve.

Child, Preschool↗

[Pancreatic pleural effusion accompanied by bronchopleural fistula].

In recent years, chronic massive pleural effusions have been increasingly recognized as a serious complication of pancreatitis. We describe the third reported case of a pancreatic pleural effusion accompanied by bronchopleural fistula. A 49-year-old man suffering from chronic alcohol-related pancreatitis was admitted to our hospital complaining of cough and shortness of breath. A chest x-ray film disclosed a large right pleural effusion with an air-fluid level. Ultrasonography and computed tomography of the upper abdomen demonstrated a giant pancreatic pseudocyst in the pancreatic tail and a fistulous tract reaching into the posterior mediastinum via the esophageal hiatus. Thoracentesis revealed sterile hemorrhagic fluid with markedly elevated amylase activity of 20,955 IU/l (pancreatic isozyme, 100%) and no malignant cells. A diagnosis of pancreatic pleural effusion was made. The therapy for pancreatic internal fistula is somewhat controversial. We employed conservative therapy, including hyperalimentation and chest tube drainage that successfully decreased the pleural effusion and closed the fistulous tract. Nonetheless, we were still troubled by a continuous air-leak via the drainage tube. Pleurodesis confirmed the tentative diagnosis of bronchopleural fistula and successfully stopped the air-leak. No re-accumulation of pleural effusion has been seen for 2 years. We concluded that pancreatic enzyme-rich effusions, if long-standing, may be complicated by bronchopleural fistula, thus underscoring the need for urgent drainage and initially conservative management.

Bronchial Fistula↗

[The 74th Annual Meeting Special Lecture. II. Present situation and problems of tuberculosis in Japan--its prevention, diagnosis and treatment].

1. Outline of tuberculosis epidemiology after the World War II Tuberculosis was surprisingly highly prevalent during the World War 2nd in Japan, and it was reported that the incidence of TB was as high as 698.4 in 1951. Strong TB control program has been carried out throughout the country after the new Anti-TB Law had been enacted in 1951. TB incidence decreased with the annual reduction rate of 11% up to 1976, it was one of the highest speed of TB decrease in the world. The decrease of TB is stagnating since 1977, and the incidence is still 33.9 in 1997. 2. Causes of stagnation of TB in Japan It is estimated that the annual risk of TB infection was so high as 4% in 1945 that many of the children had been infected with TB bacilli in those days. As a result, the majority of the people aged 60 years old or more at present are already infected with TB bacilli, and more than half of the new cases is being occurred among them at present in Japan. Moreover, the life span of those already infected people is extending so remarkably that the percentage of the aged is increasing and TB incidence is stagnating in Japan. The causes of the stagnation are not the spread of HIV infection or the increase of TB among the immigrants or refugees, because both of them are not so big problems in Japan. However, more severe problems of TB epidemiology in Japan are that 1. the incidence of smear positive cases didn't decrease more than these ten years, 2. the most marked stagnation of the incidence of TB is being observed among the young aged 20 to 39, 3. the incidence of TB in big cities doesn't decrease recently and 4. group infection and nosocomial TB infection is increasing recently. The author has analyzed the factors of the stagnation of TB in Japan, and come to the conclusions that it is caused by 1. the increase of the population by 3.0%, 2. the aging of the population by 41.0%, 3. the increase of compromised host (diabetes mellitus and so on) by 19.8%, and 4. other factors by 36.3%. It was considered that the main other factor is the marked stagnation of TB infection risk mainly by socioeconomic changes such as progressed urbanization and the spread of the modern housing with aluminum sash to increase the chances of TB infection in office buildings and/or private house. 3. Present problems of TB prevention, diagnosis and treatment in Japan As BCG vaccination is so widely and so repeatedly being carried out for children that the diagnosis of TB infection is almost impossible now in Japan. Accordingly the frequency and/or risk factors of TB infection in the community are not so clear. Preventive chemotherapy is given for high risk groups in Japan, but its diagnosis may become often unreliable. New techniques such as PCR, MTD, AccuProbe, RFLP and so on are used frequently in Japan, but the consideration on the false negative results of the examinations are lacking on occasion. The results of the cohort analysis of TB treatment among all the registered cases are rather satisfactory, but it was concluded that the shortening of the duration of the hospitalization and chemotherapy is advised if compared with those of Japan and those of the other developed countries.

Adult↗

Tilted perception of the subjective 'upright' in unilateral loss of vestibular function.

OBJECTIVE: To demonstrate that unilateral vestibular loss (UVL) may cause an erroneous perception of the subjective (bodily) vertical. STUDY DESIGN: Comparison of patients with UVL with age-matched controls. SETTING: The study was performed in a clinical neurophysiology laboratory. PATIENTS: Seven patients with unilateral, mixed acute, and chronic losses of vestibular function (six surgical), two patients with bilaterally absent vestibular function, one patient with a plugged posterior canal, and twenty-two healthy individuals. INTERVENTIONS: Subjects were seated, whole body restrained, in a flight simulator. The simulator executed intermittent stepwise tilts, in roll, up to 28 degrees that subjects had to correct to maintain an "earth upright" attitude using the joystick. Subjects performed in both "calm" conditions and also when the simulator was oscillating in roll at 1 Hz, 4 degrees peak displacement to simulate "turbulence." The purpose of the turbulence was to destabilize (or mask) somatosensory cues to uprightness. MAIN OUTCOME MEASURES: Accuracy of corrections of subjective attitude to earth upright after tilts. RESULTS: All subjects accepted the initial attitude of the simulator as "upright." In response to imposed tilts, normal subjects (n = 22) corrected their attitude to a mean 0.4 degrees SD 1.5 degrees (tilted slightly rightward) in calm and 0.7 degrees SD 1.3 degrees in turbulence. On average, corrections were normometric. All patients with UVL responded to imposed tilts by corrections that left them 'flying' tilted slightly to the side of their lesion, mean 3.2 degrees SD 2.5 degrees when calm, 6.4 degrees SD 2.7 degrees in turbulence (p<0.01). Their corrections were hypometric in response to imposed tilts to the lesioned side (i.e., undershooting true upright) and hypermetric in response to tilts to the intact side. CONCLUSIONS: Unilateral vestibular loss causes a "vestibular perception" of an erroneous tilt of the body that is probably caused by an imbalance of otolith signals and apparently never fully compensates. The tilt is enhanced when rapid perturbations of posture make somatosensory cues difficult to interpret. An erroneous perception of upright may contribute to vestibular ataxia, which is provoked when motion context involves rapid change.

Acute Disease↗

Molecular epidemiology of Fonsecaea pedrosoi using mitochondrial DNA analysis.

Restriction fragment length polymorphism (RFLP) of mitochondrial DNA (mtDNA) from 49 clinical Fonsecaea pedrosoi isolates (18 isolates from Japan, 17 from Madagascar, 7 from Argentina, 5 from Venezuela, 1 from Costa Rica and 1 unknown) was studied. The 49 isolates were composed of 20 isolates of Type 1, 16 of Type 2, 12 of Type 4 and 1 of a new mtDNA type, Type 7, which was closely related to Type 2. On the bases of the results of 120 isolates of the present (49 isolates) and previous (71 isolates) studies, F. pedrosoi was classified into seven mtDNA types and according to the relationship between mtDNA types and geographic origins: in Japan and probably in China, Type 1 isolates; in Zaire and Madagascar, Type 2; in Central and South America, Type 4 and Type 1. These results indicated that the geographical origin of F. pedrosoi isolate could be roughly inferred from its mtDNA type.

Chromoblastomycosis↗