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Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 145 records · Page 8Linked to original sources
PubMed2000

[Three cases of Mycobacterium avium lung disease in an iron foundry].

We report three cases of M. avium lung disease, all occurring in the same iron foundry over a 5-year period. Case 1: A 38-year-old man was admitted to our hospital because of abnormal chest x-ray shadows observed during a routine checkup. M. avium complex was isolated from the sputum and a CT scan showed multiple nodular shadows with cavities. Case 2: A 63-year-old man presented with dyspnea. Chest CT showed nodular shadows in both upper lobes. M. avium complex was isolated from his sputum. Case 3: A 62-year-old man was hospitalized for treatment of diabetes mellitus. A nodular cavitary shadow* OK?* in the right upper lobe was observed in the radiograph. CT scanning demonstrated a nodular shadow with thick pleural indentation. M. avium was isolated from the sputum and gastric juices. There were similarities in the radiographic findings in all cases: nodular shadows with cavities in the upper lung fields. These findings differed from those in another M. avium infection in the lung which occurred in a middle-aged woman. We suspected inhalation of an aerosol contaminated by M. avium complex. There have hitherto been no reports of group infections in healthy persons. We suspected the same environmental source for the infection.

Adult↗
PubMed2000

[Results of surgery in Mycobacterium avium complex pulmonary disease].

Recently, several studies have revealed the usefulness of surgical therapy for nontuberculous mycobacterial (NTM) disease. We have encountered and taken many opportunities for surgical therapy in Mycobacterium avium complex (MAC) disease. From April 1995 through March 1999, 14 patients with MAC disease underwent 16 pulmonary resections. NTM was diagnosed at our hospital in all subjects according to the criteria of the American Thoracic Society. There were 8 women and 6 men, with a mean age of 54 years. The most common indications for surgery were localized lesion (7 cases), severe symptoms (5 cases) and progressive disease (2 cases). Twelve patients were receiving multidrug chemotherapy, 10 of whom were also receiving clarithromycin. The mean period of preoperative chemotherapy was 17 months. Ten patients had a variety of symptoms, with some combination of cough, sputum, hemosputum, dyspnea, fever and anorexia. About 30% of the symptoms were improved after preoperative chemotherapy. The symptoms disappeared in all except one patient, who underwent pneumonectomy. After surgery, all patients attained a sputum-negative status. Nine patients underwent 11 partial resections, comprising 3 thoracotomies and 8 video-assisted thoracic surgeries (VATS). There was no operative mortality. Re-operation was performed in a patient with bronchopleural fistula after initial surgery. Currently, 2 months after the last operation, we have encountered no other severe complication and no relapse. Surgery may play an important role in treatment of MAC disease. We recommend partial resection with VATS for localized MAC disease.

Adult↗
PubMed2000

[A case of malignant lymphoma showing a stratum of lymphoma cells].

A 74-year man suffered an artificial pneumothorax of the right lung because of pulmonary tuberculosis 41 years before. He was admitted, and enlargement of chronic pyothorax was noted in chest radiography in 1998. A 67Ga scintigram revealed uptake at the site of the chronic pyothorax. Cytological findings of the pleural effusion included many atypical lymphocytes. We suspected the presence of a malignant lymphoma and performed a biopsy under thoracoscopy, but could not arrive at a diagnosis. Therefore, resection of the chronic empyema was performed. Histological examination demonstrated the layer of lymphoma cells covering the wall of empyema between the layers of necrotic and connective tissue. Lymphoma cells were stained with L 26, which is known as a B cell marker. We diagnosed diffuse large cell lymphoma (B cell type). No case like this case has ever been published of malignant lymphoma bearing a layer of lymphoma cells. This case is thought to show early-phase malignant lymphoma complicated with chronic pyothorax after artificial pneumothorax. Malignant lymphoma should be suspected when chronic pyothorax undergoes enlargement, even if CT scanning or MRI does not show typical findings.

Aged↗
PubMed1999

Role of cytochrome c as a stimulator of alpha-synuclein aggregation in Lewy body disease.

alpha-Synuclein is a major component of aggregates forming amyloid-like fibrils in diseases with Lewy bodies and other neurodegenerative disorders, yet the mechanism by which alpha-synuclein is intracellularly aggregated during neurodegeneration is poorly understood. Recent studies suggest that oxidative stress reactions might contribute to abnormal aggregation of this molecule. In this context, the main objective of the present study was to determine the potential role of the heme protein cytochrome c in alpha-synuclein aggregation. When recombinant alpha-synuclein was coincubated with cytochrome c/hydrogen peroxide, alpha-synuclein was concomitantly induced to be aggregated. This process was blocked by antioxidant agents such as N-acetyl-L-cysteine. Hemin/hydrogen peroxide similarly induced aggregation of alpha-synuclein, and both cytochrome c/hydrogen peroxide- and hemin/hydrogen peroxide-induced aggregation of alpha-synuclein was partially inhibited by treatment with iron chelator deferoxisamine. This indicates that iron-catalyzed oxidative reaction mediated by cytochrome c/hydrogen peroxide might be critically involved in promoting alpha-synuclein aggregation. Furthermore, double labeling studies for cytochrome c/alpha-synuclein showed that they were colocalized in Lewy bodies of patients with Parkinson's disease. Taken together, these results suggest that cytochrome c, a well known electron transfer, and mediator of apoptotic cell death may be involved in the oxidative stress-induced aggregation of alpha-synuclein in Parkinson's disease and related disorders.

Acetylcysteine↗
PubMed1999

Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation.

Responses to increased oxidative stress may be the common mechanism responsible for the varied cytopathology of Alzheimer disease (AD). A possible link in support of this hypothesis is that one of the most striking features of AD, the abnormal accumulation of highly phosphorylated tau and neurofilament proteins, may be brought about by extracellular receptor kinase (ERK) whose activation is a common response to oxidative stress. In this study, we demonstrate that activated ERK is specifically increased in the same vulnerable neurons in AD that are the site of oxidative damage and abnormal phosphorylation. These findings suggest that ERK dysregulation, likley resulting from oxidative stress, could play an important role in the increased phosphorylation of cytoskeletal proteins observed in AD.

Adult↗
PubMed1999

Role of zinc released by stimulation in rat amygdala.

The movement and role of actively functioning zinc, i.e., vesicular zinc, in the amygdala was studied, based on the data that 65Zn is localized in the limbic system, which may correspond to the regions with high densities of zinc-containing neuron terminals. When release of 65Zn into the extracellular space was examined 2 hr or 25 hr after injection of 65ZnCl2 into the amygdala, 65Zn release was facilitated by stimulation with high K+ 2 hr after injection, but not 25 hr after injection. Even 25 hr after 65Zn injection into the amygdala, approximately 95% of total 65Zn in the brain was detected in the injected area. These results suggest that zinc released into the extracellular space in the amygdala is not readily restored to the presynaptic vesicles. Moreover, to chelate zinc in the extracellular space (and in the synaptic vesicles) in the amygdala, the amygdalae were perfused with 10 microM diethyldithiocarbamate during behavioral tests for odor recognition. The olfactory sensation was temporarily disturbed by the perfusion. These results suggest that vesicular zinc is essential to the function of the amygdala, e.g., olfactory function.

Amygdala↗
PubMed1999

Stress signal to survival and apoptosis.

This investigation focused on whether apoptosis can be observed in some heart diseases. Apoptosis was examined immunochemically using monoclonal antibodies such as p53, Bcl-2 and cyclin E, A, and B1 in parallel with flow cytometry. Left ventricular myocardium was obtained at autopsy from 40 patients with acute myocarditis (AM; N = 10, 6 males, 4 females, mean age 56 +/- 13 years), chronic myocarditis (CM; N = 10, 5 males, 5 females, mean age 48 +/- 16 years), dilated cardiomyopathy (DCM; N = 10, 7 males, 3 females, mean age 60 +/- 11 years), and no heart disease (Cont; N = 10, 5 males, 5 females, mean age 63 +/- 14 years). Cell cycle analysis of myocytes by flow cytometry revealed that the relative content of G2M phase in acute myocarditis was far higher than those in other heart diseases (AM, 12.3 +/- 3.7%; CM, 5.2 +/- 4.5%; DCM, 6.3 +/- 4.0%; Cont, 3.4 +/- 1.8%; Mean +/- SD). Expression of p53 was observed mainly in myocytes from chronic myocarditis. Expression of Bcl-2, on the other hand, was detected in myocytes from acute myocarditis. Results suggest that apoptosis may play some role in the repairing process of myocardial inflammation.

Acute Disease↗
PubMed1999

Late retinal complications of radiation therapy for nasal and paranasal malignancies: relationship between irradiated-dose area and severity.

PURPOSE: Radiation-induced cataract, once a notorious ocular complication of radiation therapy, is no longer considered a severe complication, because visual acuity can be restored by surgical treatment without significant complications. Late retinal complications of retinopathy and glaucoma, for which there is no effective method of treatment, have become serious complications of radiotherapy of the head and neck. We retrospectively investigated the risk of late retinal complications of radiotherapy for nasal and paranasal malignancies according to the radiation dose and area of the retina irradiated. METHODS AND MATERIALS: Between October 1982 and May 1996, 43 eyes of 25 patients were exposed to fractionated external-beam irradiation for treatment of advanced nasal and paranasal cancer. None of the patients had tumor invasion into the eyes. The patients were followed ophthalmologically for a minimum of 2 years (range 2.0-11, mean 4.5, median 3.3). The radiation dose and area of the retina irradiated were estimated from the dose distribution figures calculated using the portal films and CT scan. RESULTS: Major late adverse effects of radiotherapy were observed in the retina in 9 of 43 eyes (in 8/25 patients). Radiation retinopathy was observed in 7 eyes, and the cumulative incidence was 25%. The median interval before the onset of symptoms attributable to retinopathy was 32 months (range 16-60). Neovascular glaucoma developed in 3 of the 43 eyes, with a cumulative incidence of 7%. The median period to the onset of symptoms attributable to glaucoma was 22 months (range 16-26). Obstruction of the central retinal artery was observed in 1 eye. The irradiation doses to the retinas that developed late complications ranged between 54-75 Gy (mean 61, median 61). No patients who received less than 50 Gy developed retinal complications. The retina in 21 eyes was exposed to a dose of 50 Gy or more. In 13 of the 21 eyes, 60% or more of the retina was irradiated, and 8 of the eyes (62%) in this group (> or = 50 Gy, > or = 60%) developed severe retinal complications, whereas such complications only developed in 1 of the 8 eyes (13%) in the other group (> or = 50 Gy, > or = 60%). The results suggest that the radiation dose and area irradiated are the most important factors in the development of severe complications. CONCLUSION: Radiation-induced retinopathy and glaucoma are more serious late complications than cataracts, which are easily treated with surgery. We investigated the risk of late retinal complications of radiotherapy, and our findings suggested that the radiation dose and area irradiated are the most important factors in the development of severe complications. We recommend that the radiation dose and area of the retina irradiated be minimized in patients at risk of eye complications, and the patients should be closely followed by periodic ophthalmologic testing after treatment.

Adult↗
PubMed1999

Bleomycin hydrolase immunoreactivity in senile plaque in the brains of patients with Alzheimer's disease.

Bleomycin hydrolase (BH), a cysteine protease belonging to the papain superfamily, is one of the candidate beta secretases. We performed immunohistochemical studies of Alzheimer's disease (AD) brains using an antibody to BH. Polyclonal antibody to BH immunostained neocortical neurons. The immunoreactivity was also found in senile plaques in AD. These results may suggest a role of BH in amyloid formation.

Alzheimer Disease↗
PubMed1999

Release of zinc from the brain of El (epilepsy) mice during seizure induction.

Brain distribution after i.v. injection of 65ZnCl2 into El mice, an animal model of genetically determined epilepsy, was studied by autoradiography to study the utilization of zinc in the brain. The distribution of 65Zn in the brain of El mice 6 days after injection was almost the same as that of ddY (normal) mice, suggesting that the uptake of zinc by the brain of El mice is normal. To study the movement of zinc in the brain in the course of seizure induction, the concentrations of 65Zn in the brain of seizure-afflicted and untreated control El mice were compared 20 days after 65Zn injection. The concentration of 65Zn in the brain of seized El mice was overall lower than that of control El mice; the concentration of 65Zn was decreased notably in the piriform cortex and amygdaloid nuclei complex during convulsion. These results suggest that the release of zinc from the El mouse brain is enhanced during convulsion. The decrease in actively functioning zinc in the brain may be associated with the increase in susceptibility to seizure in the El mouse.

Animals↗
PubMed1999

Genetic evidence for oxidative stress in Alzheimer's disease.

The cause and proximal consequences of Alzheimer's disease (AD), a progressive debilitating dementia remain largely unknown. Nonetheless an increasing number of genetic risk factors, including most recently bleomycin hydrolase, have been shown to be associated with the disease, offering the hope of revealing the mechanism of disease pathogenesis. Here we show that bleomycin hydrolase, known to be induced in an oxidative environment, is specifically increased in neurons marked for degeneration in AD. These findings support a key proximal role for bleomycin hydrolase, and oxidative stress in AD.

Adolescent↗
PubMed1999

Manganese uptake into rat brain during development and aging.

Manganese (Mn) is an essential metal and plays an important role in the brain. To evaluate Mn uptake into the brain during development and aging, 54Mn concentrations in the brain of rats aged from 5 days to 95 weeks were measured after injection of 54MnCl2. 54Mn concentration in the brain of 5-day-old rats was the highest of all age groups tested. The liver and blood of 5-day-old rats also showed the highest 54Mn concentrations among the age groups. These results suggest that Mn is required in a high amount during infancy and that a sufficient Mn supply is critical for normal brain development. The high uptake of Mn into the brain of neonatal rats may be due to high levels of Mn in the blood, which may be supplied from the liver. In the 5-day-old brain, 54Mn was relatively concentrated in the hippocampal CA3 and dentate gyrus and the pons. In the aging brain, 54Mn was relatively concentrated in the inferior colliculi, olivary nuclei and red nuclei.

Aging↗
PubMed1999

Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-synuclein in vitro.

The precursor of non-amyloid beta protein component of Alzheimer's disease amyloid (NACP/alpha-synuclein), found in Lewy bodies of Parkinson's disease (PD), is a presynaptic protein genetically linked to some familial types PD. Mechanisms of abnormal NACP/alpha-synuclein aggregation in neurodegenerative diseases are unclear. Since oxidative stress might play a role in PD pathogenesis, we investigated the role of iron and peroxide in NACP/alpha-synuclein aggregation. Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Ferrous ion was not effective by itself, but it potentially aggregated NACP/alpha-synuclein in the presence of hydrogen peroxide. NACP/ alpha-synuclein aggregates displayed strong thioflavine-S and congo-red reactivity, reminiscent of amyloid. This study suggests that NACP/alpha-synuclein aggregation might be closely related to oxidative reactions which may play a critical role in neurodegeneration in disorders with Lewy bodies.

Alzheimer Disease↗
PubMed1999

Characterization of the 4C8 antigen involved in transendothelial migration of CD26(hi) T cells after tight adhesion to human umbilical vein endothelial cell monolayers.

In extravasation of T cells, little is known about the mechanisms of transendothelial migration subsequent to the T cells' tight adhesion to endothelium. To investigate these mechanisms, we developed a monoclonal antibody (mAb), termed anti-4C8, that blocks transmigration but not adhesion in a culture system in which high CD26-expressing (CD26(hi)) T cells preferentially migrate through human umbilical vein endothelial cell (HUVEC) monolayers cultured on collagen gels. Anti-4C8 reacted with all CD3(+) T cells and monocytes but not neutrophils or HUVECs. The structure defined by this antibody was an 80-kD molecule. The mAb at 1 mug/ml inhibited 80-90% of migration of CD3(+) T cells through unstimulated and interferon gamma-stimulated HUVEC monolayers without interfering with adhesion and cell motility. When added to the cultures after the adhesion, anti-4C8 completely blocked subsequent transmigration of adherent T cells. Phase-contrast and electron microscopy revealed that T cells are arrested at the intercellular junctions of HUVECs in the presence of anti-4C8. Anti-4C8 exhibited agonistic effects on resting T cells without other stimuli under culture conditions in which anti-4C8 can stimulate T cells. First, in the checkerboard assay using collagen gels, the antibody promoted chemokinetic migration of the cells in a dose-dependent manner from 0.1 to 10 mug/ml. The predominant population of T cells that migrated into collagen gels with impregnated anti-4C8 were CD26(hi). Second, solid-phase-immobilized anti-4C8 induced adhesion of T cells to the substrate, often with polarizations in cell shape and large pseudopods rich in filamentous (F-) actin. Third, soluble anti-4C8 augmented F-actin content preferentially in CD26(hi) T cells when added to T cells at a high dose of 10 mug/ml. Finally, both anti-4C8-induced chemokinetic migration and transendothelial migration were inhibited by pretreatment of T cells with pertussis toxin. These findings suggest that stimulation via the 4C8 antigen increases cell motility of CD26(hi) cells with profound cytoskeletal changes through signaling pathways including G proteins. The 4C8 antigen may be involved in preferential transmigration of CD26(hi) cells adherent to HUVECs.

Actins↗
PubMed1999

Interaction between CD45-AP and protein-tyrosine kinases involved in T cell receptor signaling.

CD45-AP associates specifically with CD45, a protein-tyrosine phosphatase essential for antigen receptor-mediated signal transduction. CD45 modulates the activity of Src family protein-tyrosine kinases involved at the onset of antigen receptor-mediated signaling by dephosphorylating their regulatory tyrosyl residues. We have shown that lymphocyte responses to antigen receptor stimulation are impaired in CD45-AP-null mice. To examine the possibility that CD45-AP coordinates the interaction between CD45 and its substrates, we investigated the associations of CD45-AP with several protein-tyrosine kinases. Endogenous CD45-AP coimmunoprecipitated with Lck and ZAP-70 in both CD45-positive T cells and their CD45-negative variants after stimulation by antigen receptor ligation. Concomitantly, CD45 coimmunoprecipitated with Lck and ZAP-70 after T cell receptor-mediated stimulation of CD45-positive cells. Recombinant CD45-AP exhibited specific binding to Lck and ZAP-70 protein-tyrosine kinases, but not to Fyn or Csk, in lysates of both CD45-positive and -negative T cells. Specific interactions were demonstrated between the respective recombinant proteins as well. These results demonstrate that CD45-AP associates directly and selectively with Lck and ZAP-70 in response to T cell receptor-mediated stimulation. The associations of CD45-AP with Lck and ZAP-70 may mediate the functional interactions of these kinases with CD45 during antigen receptor stimulation.

Animals↗
PubMed1999

Clinical significance of serum p53 antibody detection on chemosensitivity assay in human colorectal cancer.

BACKGROUND AND OBJECTIVES: Alteration of the p53 gene product occurs frequently during progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. METHODS: A total of 22 patients with primary colorectal cancer who underwent surgical treatment were examined for chemosensitivity with iable tumor samples using the Histoculture Drug Response Assay (HDRA). Serum samples of these patients for p53 antibodies were obtained before tumor resection and assayed in duplicate using an enzyme-linked immunosorbent assay kit. RESULTS: The inhibition index of 5-fluorouracil and cis-diamminedichloroplatinum (CDDP), determined by the HDRA method, in the seropositive group was significantly lower than that in the seronegative group (P < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-fluorouracil and CDDP were revealed depending on the presence of serum p53 antibodies. CONCLUSIONS: Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simpler method which correlates with chemosensitivity and may contribute to the selection of favorable chemotherapeutic strategies for colorectal cancer.

Adenocarcinoma↗