[Exercise tolerance in COPD].
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Exercise Tolerance↗
Biomedical subjects
K Nagao
Publications and source records attributed to K Nagao.
A new familial adult-onset leukodystrophy manifesting as cerebellar ataxia and dementia.
BACKGROUND: Among hereditary leukodystrophies, a considerable number remain unclassified. PATIENTS AND RESULTS: We investigated the clinical course and histopathology of one patient in a family of adult-onset leukodystrophy with possible dominant inheritance. A 44-year-old man presented with cerebellar ataxia as the initial symptom, and later, dementia and hyperreflexia with ankle clonus developed. T2-weighted brain MRI showed brain atrophy and diffuse high signal intensity of the cerebral white matter and the brain stem. The patient's mother and older brother also had cerebellar ataxia and dementia, and his older brother had been diagnosed as having spinocerebellar degeneration. An older sister of our patient possibly had similar neurological symptoms of adult-onset. Our patient died of pneumonia 5 years after the onset of disease. The histopathological findings consisted mainly of patchily observed vacuolar changes in the cerebral and cerebellar white matter and the brain stem. The subcortical regions and the cortex were unaffected. It is suggested that the pathological changes began in the cerebellum, and later spread to the frontal lobe and the brain stem. In the occipital regions, the vacuolations were associated with accumulation of macrophages and astrocytosis, which implied that the vacuolations were of recent origin. CONCLUSIONS: The diagnosis in this patient is adult-onset leukodystrophy with possibly autosomal dominant inheritance. The clinicopathological features are different from those, of previously reported adult-onset leukodystrophies.
Adult↗
The effect of allergen-induced airway inflammation on airway remodeling in a murine model of allergic asthma.
OBJECTIVE AND DESIGN: We examined the effect of airway inflammation on airway remodeling and bronchial responsiveness in a mouse model of allergic asthma. MATERIALS AND METHODS: BALB/c mice were sensitized to ovalbumin (OA), and exposed to aerosolized OA (0.01, 0.1 and 1%). Twenty-four hours after the final antigen challenge, bronchial responsiveness was measured, and bronchoalveolar lavage (BAL) and histological examinations were carried out. RESULTS: Repeated antigen exposure induced airway inflammation, IgE/IgG1 responses, epithelial changes, collagen deposition in the lungs, subepithelial fibrosis associated with increases in the amount of transforming growth factor (TGF)-beta1 in BAL fluid (BALF), and bronchial hyperresponsiveness to acetylcholine. The number of eosinophils in BALF was significantly correlated with TGF-beta1 production in BALF and the amount of hydroxyproline. Furthermore, significant correlations were found between these fibrogenic parameters and the bronchial responsiveness. CONCLUSION: These findings demonstrated that in this murine model airway eosinophilic inflammation is responsible for the development of airway remodeling as well as bronchial hyperresponsiveness in allergic bronchial asthma.
Acetylcholine↗
Decrease of neurons in the medullary arcuate nucleus in myotonic dystrophy.
Respiratory insufficiency has been reported frequently in patients with myotonic dystrophy (MyD). Recent data support the hypothesis that this respiratory failure results from a primary dysfunction of the central nervous system. The medullary arcuate nucleus (ARC) has been shown to be involved in the regulation of respiration. We performed a quantitative study of neurons in the ARC in eight MyD patients, ten control subjects with other neurological diseases (control group A) and eight control subjects without neurological diseases (control group B). Alveolar hypoventilation of the central type occurred in three of the MyD patients but not in the remaining MyD patients or controls. The density of neurons in the ARC in MyD patients with hypoventilation was significantly lower than in MyD patients without hypoventilation and control groups A and B. There was no significant difference in the neuronal density of the ARC between MyD patients without hypoventilation and control groups A and B. These data suggest that the neuronal loss of the ARC is associated with the presence of hypoventilation in MyD.
Aged↗
Sialolipoma: a report of seven cases of a new variant of salivary gland lipoma.
AIMS: We propose the designation 'sialolipoma' to establish and characterize a new category of benign lipomatous tumour occurring in salivary glands. Until now, these tumours have not been regarded as a distinct entity in the salivary glands. METHODS AND RESULTS: We evaluated the clinicopathological and immunohistochemical features of seven sialolipomas among 2051 surgically resected primary salivary gland tumours deposited in our files. The seven patients with sialolipoma were five men and two women, aged 20-75 years (mean: 54.4 years). Five tumours had arisen in the parotid gland, one in the soft palate, and one in the hard palate. The tumours ranged from 10 to 60 mm (mean: 38 mm) in maximum diameter. Histologically, the tumours were characterized by a well circumscribed mass composed of glandular tissue and mature adipose elements. The adipose elements in the tumours arising in the parotid gland were more abundant than those arising in the minor salivary gland. The glandular components consisted of ductal, acinar, basal and myoepithelial cells, and closely resembled the cellular and structural compositions of normal salivary gland tissues. These findings were confirmed by immunohistochemical and ultrastructural studies. These components had no atypia, except for the presence of some minor variations, e.g. ductal ectasia with fibrosis and focal oncocytic metaplasia. In all cases, cell proliferative activity, as assessed by Ki67 (MIB1) immunostaining, was low. From these findings, it is likely that our cases were lipomas with secondary entrapment of the salivary gland elements. No recurrence was seen in all cases after superficial parotidectomy, or after surgical excision in the patients with palatal tumours. CONCLUSIONS: We regard sialolipoma as a distinct variant of salivary gland lipoma that can occur in both the major and minor salivary glands. Superficial parotidectomy, or surgical resection in the case of palatal tumours, is an appropriate treatment for this benign tumour.
Adult↗
Malignant adenomyoepithelioma of the breast: a non-tubular and matrix-producing variant.
Two women, aged 82 and 58 years old, cases 1 and 2, respectively, with the non-tubular and matrix-producing variant of malignant adenomyoepithelioma (MAM) of the breast are described. The tumors were 20 and 35 mm in diameter, respectively, and had cut surfaces with a tan-white-colored appearance and vague lobulation. Although both tumors showed marked central necrosis and a high level of mitoses, the tumor cells had relatively monomorphous nuclei and exhibited only mild atypia. The invasive component was predominantly trabecular and lobular, and the intraductal component demonstrated a focal-comedo pattern. The cytoplasm of the tumor cells was rather scanty, vacuolar or pale with ill-defined borders. The tumor in case 2 contained intermingled spindle-shaped cells. The stroma of both tumors resembled that of pleomorphic adenoma, containing a myxoid and chondroid matrix and, in case 2, cartilage and mature bone. Immunohistochemical and ultrastructural analyses of both tumors revealed dual cytological differentiation, predominantly of myoepithelial cells with secretory epithelial cells intermingled haphazardly. Although these tumors resembled metaplastic carcinomas, particularly matrix-producing carcinomas, they showed marked myoepithelial differentiation without overt tubular differentiation, a pattern quite different from matrix-producing carcinomas and from the adenomyoepitheliomas reported so far. MAM of the breast, non-tubular and matrix-producing variant, resembles epithelioid myoepithelial carcinoma of the salivary gland and has not been reported previously in the English literature.
Aged↗
Insulin administration suppresses an increase in insulin-like growth factor binding protein-2 gene expression stimulated by fasting in the chicken.
1. We examined the changes in plasma IGF-I concentration and tissue IGFBP-2 gene expression of young fasted chickens refed a commercial diet or administered bovine insulin intravenously. 2. Plasma IGF-I concentration was decreased by fasting for 2 d. Although plasma IGF-I concentration was increased by refeeding, it didn't recover to the level of chickens fed a commercial diet ad libitum. 3. Insulin administration lowered plasma IGF-I concentration compared to other groups. 4. Hepatic IGFBP-2 mRNA was increased by fasting for 2 d and decreased by refeeding for 6 h. Insulin administration also decreased hepatic IGFBP-2 gene expression stimulated by fasting to the level of refed chickens. 5. IGFBP-2 mRNA in the gizzard was increased by fasting for 2 d and tended to decrease after refeeding for 6 h. Insulin administration decreased gizzard IGFBP-2 gene expression to less than that in refed chickens. 6. There was no between-treatment difference in IGFBP-2 mRNA in the brain and kidney. 7. These results suggest that the changes in IGFBP-2 gene expression in the liver and gizzard by fasting and refeeding might be partly regulated by the alteration in plasma insulin concentration.
Animals↗
Molecular cloning of delta-4, a new mouse and human Notch ligand.
Complementary DNAs encoding a previously unidentified mouse Notch ligand and its human ortholog were isolated. The new Notch ligand contains a signal sequence, a DSL domain, eight epidermal growth factor-like repeats, a transmembrane domain, and an intracellular region, all of which are characteristics of members of the Delta protein family. The new protein was therefore designated Delta-4. Several previously unidentified sequences in both the extracellular and intracellular regions were shown to be conserved among vertebrate Delta proteins. The tissue distribution of Delta-4 mRNA resembles that previously described for Notch-4 (Int-3) transcripts. However, in situ hybridization with mouse lung revealed that Delta-4 mRNA is abundant in squamous alveolar cells that neighbor endothelial cells; Notch-4 expression is largely restricted to the latter cell type. Soluble forms of the extracellular portion of Delta-4 inhibit the apparent proliferation of human aortic endothelial cells, but not human pulmonary arterial endothelial cells.
Adaptor Proteins, Signal Transducing↗
[Demonstration of Chlamydophila pneumoniae and Chlamydia stress protein, HSP-60 in heart muscle tissue].
There has been much attention to the association between Chlamydophila pneumoniae and athrosclerosis since C. pneumoniae was demonstrated in macropharges, and vascular smooth muscle cells of atheroma tissues. There are few data demonstrating whether C. pneumoniae is present in other tissues than atherosclerotic tissues. We surveyed samples of heart tissue from 10 patients with ischemic heart disease and 10 patients with other disease by immunohistochemical staining with monoclonal antibodies against C. pneumoniae and Chlamydia stress protein 60 (C. HSP-60). In all, 11 out of 20 (55.0%) samples were positive for C. pneumoniae and 7 out of 20 (35.0%) for Chlamydia HSP-60. In patients with ischemic heart disease, positive rates were found significantly higher, that is, 9 out of 10 (90.0%) were positive for C. pneumoniae and 6 out of 10 (60.0%) for Chlamydia HSP-60. These results indicate the common presence of C. pneumoniae in heart tissue in older patients with ischemic heart diseases.
Chaperonin 60↗
Feeding unsaponifiable compounds from rice bran oil does not alter hepatic mRNA abundance for cholesterol metabolism-related proteins in hypercholesterolemic rats.
The hypocholesterolemic effect of rice bran oil (RBO) is defined in human and animal experiments which indicate the presence of active component(s) in the unsaponifiable fraction, but the detailed mechanism is not known yet. Exogenously hypercholesterolemic (ExHC) rats were fed for 2 weeks on a 0.5% cholesterol diet supplemented with 10% each of RBO, RBO-simulated oil (RBOSO) in its fatty acid composition, or RBOSO plus 0.25% unsaponifiable compounds (UC) from RBO. Rats fed RBO or the UC resulted in lowing serum and liver cholesterol concentration and preventing reduction of high density lipoproteinic-cholesterol. Dietary RBO or the UC led to an elevation of fecal neutral sterol excretion, but no significant change in fecal bile acid excretion or in hepatic abundance of mRNAs for 3-hydroxy-3-methylglutaryl-CoA reductase, cholesterol-7alpha-hydroxylase, and low density lipoprotein receptor. Besides, serum and liver alpha-tocopherol concentrations were lowered in RBO or the UC-fed rats. These results show that the UC in RBO leads to a decreased serum cholesterol concentration by interrupting the absorption of intestinal hydrophobic compounds rather than by modifying cholesterol metabolism in the liver.
Animals↗
Antiviral activity of fattiviracin FV-8 against human immunodeficiency virus type 1 (HIV-1).
A novel antiviral agent, fattiviracin FV-8, purified from the culture broth of Streptomyces microflavus strain No. 2445, showed potent antiviral activities against human immunodeficiency virus type 1 (HIV-1), herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and influenza A and B viruses. The action mechanism of fattiviracin FV-8 against HIV-1 was examined. As a result, the agent was thought to act on HIV-1 particles directly without lysis of the particles, and it affords the inhibition of viral entry into the host cells.
Animals↗
[A case of chromomycosis arising in a Japanese-Brazilian patient].
A 41-year-old Japanese-Brazilian man, living in Japan since 1991, visited our hospital in August 1998 complaining of a scaly annular erythema which had been present on his right forearm since 1996. Granulomatous inflammation was revealed in the dermis upon skin biopsy. Sclerotic cells were present within the granulomatous lesions. Fonsecaea pedrosoi was isolated from tissue cultures. The restriction fragment length polymorphism pattern of mitochondrial DNA of the causative fungus was compatible with F. pedrosoi type 1, the commonest type in Japan. Since type 4 is usually found in South America, the patient was assumed to have become infected in Japan. An oral dose of terbinafine at 125 mg/day was ineffective. 125 mg/day single dose of terbinafine reaches an average plasma concentration of only 0.69 g/ml, where as 250 mg/day reaches 0.96 micro g/ml. Because the minimum inhibitory concentration (MIC) of terbinafine against the isolated fungus was found to be 0.76 micro g/ml, the terbinafine dose was increased from 125 mg/day to 250 mg/day, which slowly led to remission. Chromomycosis is caused by several species of dematiaceous fungi, and terbinafine efficacy may vary depending on the causative fungus. MIC values may differ even within the same species. It is important to isolate the pathogenic fungus in each case and measure the MIC value to determine the optimal dose of terbinafine.
Adult↗
Analysis of the p53 gene in parotid gland cancers: a relatively high frequency of mutations in low-grade mucoepidermoid carcinomas.
Mutations and overexpression of the p53 gene and protein were analyzed in 40 cases with various types of parotid gland cancers. Mutations were found in 12 cases (30%), and low-grade mucoepidermoid carcinomas (43%) and highly malignant carcinomas including adenocarcinoma, salivary duct carcinoma, and undifferentiated carcinoma (56%) showed a relatively high frequency of mutations. Overexpression of the protein was observed in 11 cases (28%) and 4 of the 11 cases also had p53 mutations. These results suggest that mutations of the p53 gene have significance in certain types of parotid cancers irrespective of the aggressiveness of a tumor type.
Carcinoma, Mucoepidermoid↗
A two-step mechanism for free cholesterol and phospholipid efflux from human vascular cells to apolipoprotein A-1.
Smooth muscle and endothelial cells in vivo are quiescent yet exposed to high levels of lipoprotein lipids. Phospholipid (PL) and free cholesterol (FC) efflux maintain homeostasis. Smooth muscle cells (SMC) expressed high levels of ABC-1 transporter mRNA, and glyburide-dependent PL and FC efflux to apolipoprotein A-1 (apo A-1), the major protein of high-density lipoprotein. FC efflux was inhibited by vanadate and okadaic acid, while PL efflux was not. Phosphatidylcholine was the major PL transferred by both cell types. Stimulation of phosphatidylserine efflux, redistributed within the membrane by this transporter, was only minimally increased. Umbilical vein and aortic endothelial cells expressed little ABC-1 mRNA, nor did these cells promote either PL or FC efflux in response to the presence of apo A-1. To investigate the mechanism of ABC-1-dependent lipid efflux from these cells, apo A-1 was preincubated in the presence of unlabeled SMC or fibroblasts, and the conditioned medium was then transferred to endothelial cells. This medium catalyzed the efflux of FC but not of PL from endothelial cells. Such FC efflux was resistant to glyburide but inhibited by okadaic acid and vanadate. The data suggest that ABC-1-dependent PL efflux precedes FC efflux to apo A-1 and that the complex of apo A-1 and PL is a much better acceptor of FC than apo A-1 itself. Inhibition of FC but not PL efflux by vanadate and okadaic acid suggests these transfers involve different mechanisms.
ATP-Binding Cassette Transporters↗
Characterization of fission yeast cohesin: essential anaphase proteolysis of Rad21 phosphorylated in the S phase.
Cohesin complex acts in the formation and maintenance of sister chromatid cohesion during and after S phase. Budding yeast Scc1p/Mcd1p, an essential subunit, is cleaved and dissociates from chromosomes in anaphase, leading to sister chromatid separation. Most cohesin in higher eukaryotes, in contrast, is dissociated from chromosomes well before anaphase. The universal role of cohesin during anaphase thus remains to be determined. We report here initial characterization of four putative cohesin subunits, Psm1, Psm3, Rad21, and Psc3, in fission yeast. They are essential for sister chromatid cohesion. Immunoprecipitation demonstrates stable complex formation of Rad21 with Psm1 and Psm3 but not with Psc3. Chromatin immunoprecipitation shows that cohesin subunits are enriched in broad centromere regions and that the level of centromere-associated Rad21 did not change from metaphase to anaphase, very different from budding yeast. In contrast, Rad21 containing similar cleavage sites to those of Scc1p/Mcd1p is cleaved specifically in anaphase. This cleavage is essential, although the amount of cleaved product is very small (<5%). Mis4, another sister chromatid cohesion protein, plays an essential role for loading Rad21 on chromatin. A simple model is presented to explain the specific behavior of fission yeast cohesin and why only a tiny fraction of Rad21 is sufficient to be cleaved for normal anaphase.
Anaphase↗
[Diagnosis and treatment of acute myocardial infarction (AMI)].
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Humans↗
Molecular cloning of murine STAP-1, the stem-cell-specific adaptor protein containing PH and SH2 domains.
To identify the novel substrate of c-kit which is important for hematopoietic stem cell self-renewal or differentiation, CD34-low/negative, Sca-1-positive, c-kit-positive, and lineage marker-negative (CD34(low/-)Sca-1(+)c-kit(+)Lin(-)) cells were sorted by a fluorescence-activated cell sorter from mouse bone marrow cells and a yeast two-hybrid cDNA library was constructed. By screening with c-kit as bait, we cloned a novel cDNA, designed STAP-1, encoding an adaptor protein with a Pleckstrin homology domain, the Src homology 2 (SH2) domain, and a number of tyrosine phosphorylation sites. RT-PCR analysis revealed that STAP-1 expression is restricted in the bone marrow cell fraction expressing c-kit. The highest expression was observed in the CD34(low/-)Sca-1(+)c-kit(+)Lin(-) stem cell-enriched fraction. The murine myeloid cell line, M1, expressed a high level of STAP-1. However, the expression was strongly repressed in response to leukemia inhibitory factor (LIF) which induced monocytic differentiation of M1 cells, suggesting that STAP-1 is associated with the undifferentiated cell type. A two-hybrid assay indicated that STAP-1 bound not only to c-kit but also to c-fms but not to JAK2 or Pyk2. In 293 cells, STAP-1 was tyrosine-phosphorylated by activated c-kit. An in vitro binding assay suggested that the STAP-1 SH2 domain interacted with several tyrosine-phosphorylated proteins including c-kit and STAT5. These suggest that STAP-1 functions as an adaptor molecule downstream of c-kit in hematopoietic stem cells.
Amino Acid Sequence↗
Lymphatic lipid transport is not impaired in ageing rat intestine.
Lymphatic lipid transport in the intestine of adult and ageing rats was compared. Adult (8-10 months old) and old (24-26 months old) male Wistar rats were cannulated into the mesenteric lymph under ethrane anesthesia. On the following day, lipid emulsion containing 35.4 mg/h of olive oil was infused intraduodenally for 7 h and lymph collected hourly was assayed for triglyceride and apolipoprotein A-IV (apo A-IV). The results showed there was no difference in lymphatic lipid and apo A-IV transport between adult and old rats. Since apo A-IV synthesis in the enterocytes is linked to the intracellular assembly of lipoprotein, it is likely that in addition to lymphatic transport, production of chylomicrons is not impaired in ageing rats.
Aging↗