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Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 91 records · Page 5Linked to original sources
PubMed2000

Induction of protective immunity against pathogenic simian immunodeficiency virus by a foreign receptor-dependent replication of an engineered avirulent virus.

In AIDS vaccine strategies, live attenuated vaccines can confer good resistance against pathogenic virus infections but have the potential risk of inducing disease, whereas safer replication-negative strategies such as DNA vaccinations have so far failed to prevent the disease onset. Here, we developed a novel DNA vaccine strategy to induce restricted replication of an avirulent virus and evaluated it in a simian immunodeficiency virus (SIV) infection model. We generated a chimeric SIV, FMSIV, by replacing SIV env with ecotropic Friend murine leukemia virus (FMLV) env to confine its replication to FMLV receptor (mCAT1)-expressing cells. In primate cells lacking mCAT1, FMSIV did not replicate unless mCAT1 was introduced exogenously. Vaccination to macaques with both the FMSIV DNA and the mCAT1-expression plasmid DNA induced SIV Gag-specific cellular immune responses and resistance against pathogenic SIV(mac239) challenge more efficiently than the replication-negative control vaccination with the FMSIV DNA alone. This strategy may be useful for development of safe and effective vaccines against various kinds of pathogenic viruses.

AIDS Vaccines↗
PubMed2000

Cyclin' toward dementia: cell cycle abnormalities and abortive oncogenesis in Alzheimer disease.

Recent evidence has associated the aberrant, proximal re-expression of various cell cycle control elements with neuronal vulnerability in Alzheimer disease, a chronic neurodegeneration. Such ectopic localization of various cyclins, cyclin-dependent kinases, and cyclin inhibitors in neurons can be seen as an attempt to re-enter the cell cycle. Given that primary neurons are terminally differentiated, any attempted re-entry into the cell division cycle in this postmitotic environment will be dysregulated. Since successful dysregulation of the cell cycle is also the hallmark of a neoplasm, early cell-cycle pathophysiology in Alzheimer disease may recruit oncogenic signal transduction mechanisms and, hence, can be viewed as an abortive neoplastic transformation.

Alzheimer Disease↗
PubMed2000

65Zn localization in rat brain after intracerebroventricular injection of 65Zn-histidine.

Previous studies have shown that 65Zn uptake in the brain expressed relative to plasma 65Zn level is enhanced by histidine infusion into the blood vessel. To study the effect of histidine on zinc uptake in the brain parenchyma via the CSF, the brains of rats injected intracerebroventricularly with 65Zn-His were subjected to autoradiography. Six days after injection, the radioactivity from 65Zn-His was distributed in the major part of the brain parenchyma higher than that from 65ZnCl(2), and relatively concentrated in the hippocampal formation, globus pallidus and hypothalamus. The radioactivity of the aqueduct was also higher in the 65Zn-His group, indicating that CSF clearance of the 65Zn-His group may be lower than that of the 65ZnCl(2) group. These results suggest an enhancement by histidine on zinc uptake in the brain parenchyma via the CSF.

Animals↗
PubMed2000

Alpha2-macroglobulin gene polymorphisms show racial diversity and are not associated with Alzheimer's disease.

Two genetic markers of the plasma protein alpha2-macroglobulin, a 5 bp deletion/insertion at the 5' splice site of exon 18 (A2MI) and the GTC/ATC (VaIIO00IIe) in exon 24 (A2M2), may have roles in the development of Alzheimer's disease (AD). Genotyping and linkage analysis of these markers in 426 Japanese sporadic AD patients, 85 autopsy-confirmed Caucasian AD cases, and, as controls, 382 Japanese and 65 Caucasians who were cognitively normal and 140 Japanese Parkinson's disease patients showed racial diversity in the frequencies and relationship of the two markers. Comparison of genotype and allele frequencies, stratification of the samples by the presence of the apolipoprotein E epsilon4 allele, and logistic regression analysis revealed no association of these markers with AD in either racial group.

Aged↗
PubMed2000

Hepatic zinc response via metallothionein induction after tumor transplantation.

Based on previous findings that liver zinc and metallothionein (MT) levels increase after tumor transplantation, zinc metabolism in tumor-bearing mice was studied to clarify the role of zinc-MT in host defense systems. Zinc in the hepatic cytosolic MT fraction did not increase in tumor-bearing mice fed a zinc-deficient diet, suggesting that dietary zinc is necessary for apo-MT induction in the liver after tumor transplantation and is then incorporated into the apo-MT. When (65)ZnCl(2) was intravenously injected, liver (65)Zn levels in the tumor-bearing mice were higher than those in control mice for 72 h after the injection. Pancreatic and blood (65)Zn levels in tumor-bearing mice were lower than those in controls for 24 h (pancreas) and 6 h (blood) after the injection. These findings indicate that the hepatic zinc response via MT induction influences zinc metabolism in the body after tumor transplantation. Moreover, (65)Zn uptake in the liver of MT-deficient tumor-bearing mice was lower than that in control tumor-bearing mice 1 h after injection. (65)Zn uptake in the tumor and blood (65)Zn levels in the MT-deficient tumor-bearing mice were higher than those in the control tumor-bearing mice. Tumor weight increased more in MT-deficient mice than in control mice. The formation of zinc-MT in the liver of tumor-bearing mice might decrease blood zinc availability for tumors and other tissues, such as the pancreas.

Animals↗
PubMed2000

Relationship between brain zinc and transient learning impairment of adult rats fed zinc-deficient diet.

The relationship between brain zinc and learning behavior was studied based on the data of 65Zn localization in the hippocampal formation. Learning behavior, tested by passive avoidance performance, of 6-week-old rats improved significantly compared to that of 4-week-old rats and it was maintained at 20 weeks of age. When 8-week-old rats were fed zinc-deficient diet for 4 weeks, the learning behavior was significantly impaired. However, it was recovered to almost normal level by feeding with control (zinc-adequate) diet for 5 weeks. These results demonstrate that a proper zinc supply to the brain is necessary for improvement and maintenance of learning ability. Although an appreciable decrease in brain zinc was not observed in the rats fed zinc-deficient diet for 4 weeks, significant decrease of hippocampal zinc was observed in rats fed zinc-deficient diet for 12 weeks. Moreover, synaptosomal zinc in the hippocampal formation and cerebral cortex was significantly decreased by the 12 weeks of zinc deprivation. These results suggest that the decrease of vesicular zinc in the hippocampal formation and cerebral cortex is involved in the transient learning impairment of adults rats.

Age Factors↗
PubMed2000

Molecular cloning of mouse ganglioside sialidase and its increased expression in Neuro2a cell differentiation.

Ganglioside sialidases have been implicated in neuronal differentiation processes, including neurite outgrowth. To understand further the roles and regulation mechanisms of the sialidase in neuronal systems, we have cloned mouse ganglioside sialidase cDNA and observed its expression in Neuro2a cell differentiation. A 3339-base pair cDNA, cloned based on the sequence information of previously cloned enzymes, encodes 418 amino acids containing three Asp boxes characteristic of sialidases. Northern blot analysis revealed a 3.4-kilobase transcript expressed highly in heart but also in several other tissues including brain. In situ hybridization of mouse brain demonstrated the mRNA to be present in the cerebral cortex, as well as in the granule cell layer, Purkinje cells, and deep cerebellar nucleus of the cerebellum. Transient expression of the cDNA in COS-1 cells resulted in over 300-fold increase in sialidase activity toward gangliosides compared with the control level, with a preference for ganglioside substrate. During 5-bromodeoxyuridine-induced Neuro2a cell differentiation, the expression of the sialidase was increased as assessed by activity assays and quantitative reverse transcription-polymerase chain reaction analyses. Stable transfection of the sialidase in Neuro2a cells resulted in accelerated neurite arborization following 5-bromodeoxyuridine treatment, indicating the direct participation of this ganglioside sialidase in neuronal cell differentiation.

Amino Acid Sequence↗
PubMed2000

Altered cell-matrix associated ADAM proteins in Alzheimer disease.

Alterations in cell-matrix 'contact' are often related to a disruption of cell cycle regulation and, as such, occur variously in neoplasia. Given the recent findings showing cell cycle alterations in Alzheimer disease, we undertook a study of ADAM-1 and 2 (A Disintegrin And Metalloprotease), developmentally-regulated, integrin-binding, membrane-bound metalloproteases. Our results show that whereas ADAM-1 and 2 are found in susceptible hippocampal neurons in Alzheimer disease, these proteins were not generally increased in similar neuronal populations in younger or age-matched controls except in association with age-related neurofibrillary alterations. This increase in both ADAM-1 and 2 in cases of Alzheimer disease was verified by immunoblot analysis (P < 0.05). An ADAM-induced loss of matrix integration would effectively "reset" the mitotic clock and thereby stimulate re-entry into the cell cycle in neurons in Alzheimer disease. Furthermore, given the importance of integrins in maintaining short-term memory, alterations in ADAM proteins or their proteolytic activity could also play a proximal role in the clinico-pathological manifestations of Alzheimer disease.

ADAM Proteins↗
PubMed2000

The modified tangential irradiation technique for breast cancer: how to cover the entire axillary region.

PURPOSE: The two-portal tangential irradiation technique has usually been applied to breast cancer patients after breast-conserving surgery (1, 2) and is expected to irradiate the axillary lymph node region to some extent (3). We investigated the range of the axillary region covered by this technique and tried to devise an optimal irradiation technique (modified tangential irradiation) that would cover the axillary lymph node region properly. METHODS AND MATERIALS: We checked the status of the surgical clips left at axillary lymph node sites by reviewing the simulator films and planning CT scans of 63 patients who underwent axillary dissection of level I, I-II, or I-III lymph nodes. Then we created the modified tangential irradiation technique and applied this technique to 16 patients and checked the irradiation volume by CT scans. RESULTS: We found that all of the surgical clips on lateral-view simulator films were on the ventral side of the dorsal edge line of the humeral head. All but one clip were on the caudal side of the caudal edge line of the humeral head. Accordingly, it is possible to irradiate almost all axillary lymph node regions by setting the dorsal edge of the irradiation field on lateral-view simulator films at the dorsal edge of the humeral head and the cranial edge at the caudal edge of the humeral head. CONCLUSIONS: All breast tissue and the entire axillary lymph node region can be covered by the modified tangential irradiation technique without increasing the lung volume irradiated.

Adult↗
PubMed2000

Overexpression of heme oxygenase in neuronal cells, the possible interaction with Tau.

Increased expression of heme oxygenase-1 (HO-1) is a common feature in a number of neurodegenerative diseases. Interestingly, the spatial distribution of HO-1 expression in diseased brain is essentially identical to that of pathological expression of tau. In this study, we explored the relationship between HO-1 and tau, using neuroblastoma cells stably transfected with sense and antisense HO-1 constructs as well as with the vector alone. In transfected cells overexpressing HO-1, the activity of heme oxygenase was increased, and conversely, the level of tau protein was dramatically decreased when compared with antisense HO-1 or CEP transfected cells. The suppression of tau protein expression was almost completely reversed by zinc-deuteroporphyrin, a specific inhibitor of heme oxygenase activity. The activated forms of ERKs (extracellular signal-regulated kinases) were also decreased in cells overexpressing HO-1 although no changes in the expression of total ERK-1/2 proteins were observed. These data are in agreement with the finding that the expression of tau is regulated through signal cascades including the ERKs, whose activities are modulated by oxidative stresses. The expression of tau and HO-1 may be regulated by oxidative stresses in a coordinated manner and play a pivotal role in the cytoprotection of neuronal cells.

Alzheimer Disease↗
PubMed2000

Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders.

To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.

Animals↗
PubMed2000

Influence of transferrin on manganese uptake in rat brain.

To evaluate the influence of transferrin (Tf) on manganese (Mn) uptake in the brain, pH 8.6 buffer-treated (54)MnCl(2), which has a higher affinity for Tf than untreated (54)MnCl(2), and Tf-bound (54)Mn were prepared. When pH 8.6 buffer-treated (54)MnCl(2) and untreated (54)MnCl(2) were incubated with apo-Tf in Tris (2-amino-2-hydroxymethylpropane-1,3-diol)-HCl buffer, the percentage of the total (54)MnCl(2) bound to Tf was approximately 85% and 10%, respectively. One hour after intravenous (iv) injection of pH 8.6 buffer-treated (54)MnCl(2) and untreated (54)MnCl(2), both tracers were concentrated similarly in the choroid plexus in the ventricles and distributed in other brain regions. Six days after iv injection, both pH 8.6 buffer-treated (54)MnCl(2) and untreated (54)MnCl(2) tracers were concentrated in the superior olivary complex, inferior colliculi, and red nuclei, although the former radioactivity was lower than the latter. Moreover, Tf-bound (54)Mn was prepared and injected iv into rats. The radioactivity from Tf-bound (54)Mn, which was also concentrated in the same regions, e.g., the superior olivary complex, was the lowest of all three traces. Tf-bound (54)Mn was stable during incubation with serum for 1 hr. It is likely that more Mn is transported into the brain when Mn is not bound to Tf. When Tf-bound (54)Mn and (54)MnCl(2) were unilaterally injected into the lateral ventricle, radioactivity was distributed only around the ipsilateral ventricle in the Tf-bound (54)Mn group 7 days after injection, whereas it was distributed more extensively in the (54)MnCl(2) group. It is likely that Tf-bound Mn in the CSF is less readily transported into the brain parenchymal cells than the non-Tf-bound form. These results suggest that Mn is transported into the brain efficiently via a Tf-independent uptake system.

Animals↗
PubMed2000

Medial temporal atrophy and memory impairment in early stage of Alzheimer's disease: an MRI volumetric and memory assessment study.

Memory impairment and medial temporal lobe (MTL) involvement are the earliest and most prominent features of Alzheimer's disease (AD). A psychological assessment of memory function and an evaluation of the morphological changes in MTL structures, as found in the mild form of AD, are important for early diagnosis as well as for understanding the pathophysiology of the disease. In the present study, we aimed to evaluate correlations in these psychoanatomical changes in terms of the stage of AD. We performed MRI-based volumetric measurements of the MTL structure and neuropsychological tests, using MMSE and the Wechsler memory scale-revised (WMS-R), on 27 elderly normal subjects and 46 probable AD patients, and then checked for possible correlations between the volumetric measurements and memory dysfunction. The severity of the AD patients' condition was assessed by CDR scale. Each MTL structure decreased in volume with increasing severity of AD. In very early AD, the reduction in the amygdala volume was pronounced, while the hippocampal volumes were relatively unchanged. Neuropsychological scores also declined with increasing severity of AD. Scores on the main WMS-R subsets examined (verbal memory, visual memory, and delayed recall) decreased significantly in the very mild group, as compared with normal controls. The WMS-R test scores correlated significantly with the amygdala volumes in normal control subjects and very mild AD patients. Our findings suggest that MRI-based amygdaloid volumetric measurement provides a sensitive marker, and that the degeneration of the amygdala may begin very early in the course of AD.

Aged↗
PubMed2000

A feasibility study of chemosensitivity assay by adhesive tumor cell culture system using biopsy specimens for gastric cancer.

BACKGROUND AND OBJECTIVES: The adhesive tumor cell culture system (ATCCS) is known to produce high colony-forming efficiency. We, therefore, studied the feasibility of ATCCS for gastric cancer by use of biopsy specimens and the relationship between the results of ATCCS and histological effects of anticancer drugs. METHODS: Tumor specimens extracted by gastroendoscopic biopsy were sufficient for obtaining the result of sensitivity to at least one drug in 24 out of 30 (80%) patients. Twenty patients were administered 5-fluorouracil (5-FU) for 14 days prior to surgery, and the results of ATCCS were compared with histological changes of the resected specimens. RESULTS: The histological response rate was found to be 100% (4/4) when the 90% inhibition concentration (IC90) of 5-FU was less than 0.24 microg/ml (sensitive) and was 0% (0/3) when IC90 was greater than 0.40 microg/ml (resistant). CONCLUSIONS: Although lacking in statistical significance, the results suggest that the drug to which the tumor revealed sensitivity in the ATCCS would produce histological effects and the drug to which the tumor was resistant would have no histological effect.

Aged↗
PubMed2000

Response of feline intradental nerve fibers to tooth cutting by Er:YAG laser.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the response of intradental A- and C-fibers during tooth cutting by Er:YAG laser. STUDY DESIGN/MATERIALS AND METHODS: Bipolar electrical stimulation was applied to the cat's canine to identify functional single nerve fibers of the inferior alveolar nerve. The tip of the canine tooth was cut in 0.5-mm steps until the pulp was exposed. Teeth were alternately cut by using Er:YAG laser (50 mJ, 5 pps) and micromotor under water cooling. The nerve response recorded from the single nerve fibers during laser cutting was compared with that during micromotor cutting. RESULTS: All 26 A-fibers responded to laser cutting with high frequency of nerve firings. The nerve firing rate was significantly higher during laser cutting compared with that during micromotor cutting of superficial dentin (Chi(2) test, P < 0.05) but was not significantly different at deep dentin (P > or = 0. 05). Nine of 11 C-fibers responded to laser cutting when the deep dentin was cut. Among those nine nerve fibers, three also showed a low frequency response to laser cutting of the superficial dentin. CONCLUSION: During the tooth cutting, Er:YAG laser was more effective in activating intradental A-fibers compared with micromotor and also caused the activation of intradental C-fibers.

Animals↗
PubMed2000

Abortive oncogeny and cell cycle-mediated events in Alzheimer disease.

Alzheimer disease, the leading cause of senile dementia, is characterised by the degeneration of select neuronal populations. While the mechanism(s) underlying such cell loss are largely unknown, recent findings indicate inappropriate re-entry into the cell cycle resembling an abortive oncogeny. In postmitotic neurons, such mitotic re-entrance is deleterious and one that involves virtually the entire spectrum of the described pathological events in Alzheimer disease including, ultimately, cell death.

Alzheimer Disease↗