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Biomedical subjects

A Aoyama

Publications and source records attributed to A Aoyama.

At least 19 recordsLinked to original sources

Recurrent lymphangioleiomyomatosis after living-donor lobar lung transplantation.

Living-donor lobar lung transplantation (LDLLT) has been applied to patients with various end-stage lung diseases. The recurrence of pulmonary lymphangioleiomyomatosis (LAM) after lung transplantation has been rarely reported. Herein, we report a case of recurrent pulmonary LAM after LDLLT. A 24-year-old woman presented with pneumothorax and infiltrates in the left lung 1 year after bilateral LDLLT for LAM. These symptoms and radiologic findings occurred repeatedly and then improved quickly. Thereafter, computed tomography of the chest revealed a tiny emphysematous change of the subpleural region in the left lung, which was exacerbated gradually and was finally diagnosed as LAM recurrence by transbronchial lung biopsy. In previous reports of LAM recurrence, the diagnosis was made at the time of autopsy. This is also the first reported case diagnosed early, that is, when the patient was alive and her allograft had not deteriorated badly.

Adult↗

[Castleman disease in the posterior mediastinum showing atypical feature in computed tomography; report of a case].

A 41-year-old man was referred to our hospital because of an abnormal mass on a chest X-ray. An enhanced computed tomography (CT) showed a well-defined round mass (30 x 45 x 66 mm in diameter) that was heterogeneously enhanced owing to central necrotic or cystic change. A 3-dimensional CT demonstrated a couple of feeding arteries to the mass. The mass was completely resected through thoracotomy. Dissection of tight adhesion between the hypervascular mass and the surrounding tissues caused relative amount of hemorrhage during the surgery. The cystic lesion of the mass was fulfilled with brown liquid. The pathological examination revealed the mass as Castleman disease, and scattered cells in the cystic lesion.

Adult↗

[Surgical treatment of pulmonary aspergillosis].

We studied clinically upon 10 surgical cases of pulmonary aspergillosis. There were 7 male and 3 female cases, and the median age was 59 years. Seven cases had underlying bronchopulmonary diseases, and 9 cases had underlying diseases including systemic diseases, such as diabetes mellitus. There were 3 wedge resections, and 6 lobectomies, and 1 two-staged surgery (cavernostomy + muscle transposition). Eight cases whose lesion extended beyond neither chest wall nor mediastinal pleura were treated successfully by pulmonary resections almost within one lobectomy. One case, who had a cavitary lesion and multiple patchy infiltrates in the other lobes, cured by lobectomy including a main cavitary lesion and postoperative treatment with an antifungal agent. All cases returned home almost uneventfully, but 1 case of two-staged surgery died at home suddenly of massive hemoptysis. Surgical treatments of pulmonary aspergillosis are recommended when the lesions can be resected completely, that is, when patients are relatively well, lesions extend beyond neither chest wall nor hilar bronchus or vessels, and when the lungs other than the lesions are not extensively destroyed.

Adult↗

[Long-term results after surgery for aortic arch nondissection aneurysm].

Between 1990 and August 2001, 109 patients were treated surgically for nondissection fusiform or saccular aortic arch aneurysm. Fifteen patients were emergent. There were 89 male and 20 female patients (mean 71.7 +/- 6, range 49 to 84). Eight patients underwent hemiarch replacement, 57 total arch replacement, 44 distal arch replacement, which were performed with the aid of hypothermic extracorporeal circulation with antegrade selective cerebral perfusion or retrograde cerebral perfusion. The early mortality was 8.5% with elective operations and 53.3% with emergent operations. The incidence of post operative permanent neurological dysfunction was 12.8% with elective operations and 46.7% with emergent operations. The 5-year and 10-year survival rate including in-hospital deaths was 52 +/- 6% and 29 +/- 9%. The 5-year event free rate was 89 +/- 5%.

Aged↗

[Surgical treatment of Marfan syndrome; analysis of the patients required multiple surgical interventions].

Without treatment, the life expectancy of patients with Marfan syndrome is reduced by the associated cardiovascular abnormalities. In this study, we reviewed our experience of the patients with Marfan syndrome who required multiple surgical interventions to identify the optimal treatment for these patients. Between January 1986 and December 2000, 44 patients with Marfan syndrome were operated on at Shizuoka City Hospital (SCH). Among them, 10 patients (22.7%) underwent multiple surgical interventions. There were 5 male and 5 female patients with a mean age of 40.6 +/- 16.1 years at the initial surgery. Only one patient was operated on at another hospital for his first, second, and third operations. His fourth operation was carried out at SCH. The remaining 9 patients underwent a total of 14 additional surgical procedures at SCH. Computed tomography (CT) scans were taken every 6 months postoperatively, and aortic diameter greater than 60 mm was considered as the indication for the additional surgery. There were no early death and one late death. The causes of additional surgery were enlargement of true aneurysm in 6, enlargement of residual dissection in 4, new dissection in 4, false aneurysm at the coronary anastomosis of Bentall procedure in 1. In 9 patients, both ascending and descending aorta were replaced. Among these 9 patients, only 3 patients underwent total arch replacement, and remaining 6 patients had their arch left in place with or without dissection. Our current strategy of the treatment of Marfan patients with acute type A dissection is total arch replacement with an elephant trunk at the initial emergent surgery.

Adolescent↗

The Aspergillus nidulans CCAAT-binding factor AnCP/AnCF is a heteromeric protein analogous to the HAP complex of Saccharomyces cerevisiae.

The Aspergillus nidulans hapC gene was expressed as a fusion protein with MalE or glutathione-S-transferase (GST) in Escherichia coli, and used for the purification of HapC and the preparation of anti-HapC antiserum. The CCAAT-binding factor AnCP/AnCF contains a component with an approximate molecular mass of 32 kDa that cross-reacts with the antibody. The MalE-HapC fusion protein was able to replace authentic HapC in AnCP when incubated under appropriate conditions. Furthermore, reconstitution experiments with recombinant HapC, yHAP2 and yHAP5 polypeptides showed that all three polypeptides were required for the assembly of a complex capable of binding to CCAAT-containing taaG2 promoter DNA. The relationship between AnCP/AnCF and the Saccharomyces cerevisiae HAP complex is discussed.

Aspergillus nidulans↗

An Aspergillus nidulans nuclear protein, AnCP, involved in enhancement of Taka-amylase A gene expression, binds to the CCAAT-containing taaG2, amdS, and gatA promoters.

Using AnCP (Aspergillus nidulans CCAAT-binding protein) as a CCAAT-specific binding factor model, the possibility that one factor is able to recognize CCAAT sequences in several different genes in A. nidulans was examined. DNase I protection analysis showed that AnCP specifically bound to CCAAT sequence-containing regions comprising 21 to 36 bp of the taa, amdS and gatA genes. Furthermore, replacement of the CCAAT sequence with CGTAA was found to abolish the binding of AnCP and to have an inhibitory effect on taa promoter activity. This clearly demonstrates a positive function of the CCAAT element. However, amylase was induced by starch and repressed by glucose in a CCAAT-box disruptant, as in wild-type cells.

Amidohydrolases↗

Glucocorticoids regulate the expression of the stressprotein alpha B-crystallin.

alpha B-crystallin is a major component of the eye lens but is also found in many extralenticular tissues. In established fibroblasts it is synthesized in response to stress such as hyperthermia. Here we report that the treatment of NIH3T3 fibroblasts with the synthetic glucocorticoid hormone dexamethasone resulted in the accumulation of substantial amounts of alpha B-crystallin, alpha B-crystallin mRNA accumulated slowly and over a period of many days in response to prolonged hormone treatment. alpha B-crystallin promoter-reporter constructs were hormone responsive. A putative glucocorticoid response element (GRE) within the analysed promoter region could bind the glucocorticoid receptor as revealed from in vitro footprint analysis but is not involved in the hormone-mediated gene activation. Deletions of 5' flanking regions to position -465 relative to the transcription start allowed for full hormone responsiveness. A deletion from -465 to -389 abolish hormone-mediated gene induction. No sequence element closely resembling a classical GRE is present within that hormone-responsive region.

3T3 Cells↗

Remarkable activity enhancement of thermolysin mutants.

Most attempts to modify the properties of enzymes by amino acid substitution around the active sites have resulted in suppression of the biological activity, suggesting that the structure of natural enzymes should be almost optimized evolutionally to show the highest activity. In contrast, we found an interesting site of a well-known metalloendopeptidase, thermolysin (EC.3.4.24.4), where almost all the amino acid replacement causes a remarkable increase in the hydrolytic activity. Negative correlation between the activity and the thermal stability was observed. The flexibility around the substrate binding site is suggested to be a key to the correlation. Nature may have selected the amino acid at this site, which suppresses the flexibility of the molecule, to get the highest thermal stability at the expense of the activity.

Enzyme Activation↗

A potential marker protease of invasiveness, seprase, is localized on invadopodia of human malignant melanoma cells.

Seprase, a large, gelatin-degrading membrane-protease complex, is expressed at the invasive front of malignant melanoma cells on invadopodia, and its surface expression contributes to the invasive phenotype. An in vitro assay was used to determine the matrix-degrading activity of four malignant human melanoma cell lines. The lines differ in matrix-degrading activity with LOX > RPM17951 > A375 > SKMEL28. The seprase and Gelatinase A activities of these cell lines were also investigated. Seprase and active gelatinase A are found in cell membranes of LOX and RPM17951 cells but not those of SKMEL28 cells. Experiments using anti-seprase monoclonal antibodies in conjunction with a cell fractionation technique indicate that seprase consists of M(r) 97,000 polypeptides and is enriched on the ventral membrane of LOX in contact with planar extracellular matrix substratum. Confocal microscopy further substantiates our biochemical findings that seprase, as well as Gelatinase A, is localized on invadopodia membranes with a 6-fold increase of seprase and 4-fold increase of Gelatinase A intensity over the level expressed on dorsal membranes. In addition, LOX cells expressing higher levels of seprase at the cell surface, as selected by fluorescence-activated cell sorting, are significantly more degradative than LOX cells with lower seprase expression. Taken together, our data show a concordance between seprase and Gelatinase A expression on the cell surface at invadopodia and the matrix-degrading activity of human malignant melanoma cells. Seprase and major secreted proteases may act in concert to degrade components of the extracellular matrix during invasion.

Biomarkers, Tumor↗

Alpha B crystallin expression in response to hormone, oncogenes and stress.

alpha B crystallin is one of the major eye lens proteins and it is abundantly expressed in many non-lenticular tissues as well. The alpha B crystallin protein sequence is similar to that of small heat shock proteins and we could demonstrate that alpha B crystallin does indeed accumulate in response to heat shock and other forms of stress. Moreover, ectopic expression of alpha B crystallin establishes a state of thermotolerance. Glucocorticoid hormones activate the alpha B crystallin gene with a delayed kinetics. Induced expression of the Ha-ras oncogene accelerates hormone-mediated gene induction. A shorter promoter sequence is required for the ras supported hormone response. However, sustained Ha-ras oncogene expression attenuates glucocorticoid-triggered induction of the alpha B crystallin gene completely. Whereas the small heat shock protein Hsp27 is overexpressed in many human mammary carcinomas, we observed the frequent absence of alpha B crystallin in these tumors but not in the normal breast tissue. In contrast, overexpression of alpha B crystallin has been frequently observed in non-neuronal brain tumors.

Animals↗

[Thyroid function in patients with anorexia nervosa and depression].

Thyroid hormone levels were measured in 21 patients with anorexia nervosa, 15 patients with depression and 16 patients with severe depression and were compared with those in 53 normal subjects. In anorexia nervosa and severe depressed patients, serum T3, T4, fT3, fT4 and T3/T4 ratio showed significantly lower values than those in normal subjects. However there was no difference between depressed patients and normal subjects. The serum TSH levels were within normal range in all of the studied subjects. Thus, thyroid hormone levels in severe depressed patients were similar to those in anorexia nervosa and the changes were inversely related to disease conditions. The supplementation of thyroid hormones to antidepressant relieved clinical symptoms in some of the severe depressed patients. These results suggested that the changes in thyroid hormone levels in anorexia nervosa and severe depression were mainly due to impaired conversion of T4 to T3 by increased cortisol secretion through emotional stress.

Adult↗

[Changes of thyroid hormone levels during ACTH therapy in epileptic children].

To investigate the effect of ACTH on thyroid function, thyroid hormone levels were measured in twelve patients with epileptic children who were treated with ACTH. One week after daily administration of ACTH, serum T3, T4, TSH, thyroglobulin and T3/T4 ratio showed significantly lower values compared with those of pretreatment values (p < 0.001-p < 0.05). Thyroid hormone levels respectively showed negative correlation with cortisol levels before and one week after ACTH treatment respectively. Tapering of ACTH brought a rapid recovery of T3, T4, TSH and thyroglobulin levels with concomitant return of plasma cortisol levels to the normal range. These results suggested that excess ACTH suppressed thyroid hormone secretion mainly through a decreased TSH secretion and a peripheral conversion of T4 to T3 by increased cortisol levels.

Adrenocorticotropic Hormone↗

Expression of alpha B-crystallin in human brain tumors.

We have previously shown that alpha B-crystallin is a heat-shock protein which specifically accumulates in response to the expression of c-Ha-ras and v-mos oncogenes in mouse NIH 3T3 fibroblasts. Elevated levels of alpha B-crystallin mRNA or protein were shown to be associated with pathological conditions of the brain. Therefore, we have examined the expression of alpha B-crystallin in normal human brains and brain tumors by Western blot analysis. alpha B-crystallin is moderately expressed in adult but not fetal brain. Elevated levels of alpha B-crystallin expression are observed in glial tumors such as astrocytoma, glioblastoma multiforme, and oligodendroglioma. alpha B-crystallin in these tumors is predominately unphosphorylated. High amounts of accumulated alpha B-crystallin in astrocytic tumors are preferentially found in the more aggressive stages. Glioblastoma multiforme is exceptional in that high alpha B-crystallin expression is observed in only one half of the analyzed samples whereas no alpha B-crystallin could be detected in the other. These results indicate that alpha B-crystallin may be a useful biochemical marker for studying the pathogenesis of various human brain tumors.

Astrocytoma↗