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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 55 records · Page 3Linked to original sources

Engineered IGF-I expression induces glandular enlargement in the murine prostate.

IGF-I has been implicated as a factor that may predispose one to prostate cancer and to benign prostatic hypertrophy (BPH). We established murine IGF-I transgenic mice under the control of rat probasin promoter and analysed the histology of the murine IGF-I-overexpressing prostate. Immunohistochemically, IGF-I was expressed in prostatic epithelial cells or basement membranes of the ventral, dorsal and lateral lobes in a line of IGF-I transgenic mice, but not in their control littermates. The anterior lobe did not express IGF-I. IGF-binding protein-3 (IGFBP-3), inhibitory to the mitogenic action of IGF-I, was detected in epithelial cells of prostatic ventral lobes, but not in those of the dorsal, lateral or anterior lobes of IGF-I transgenic mice. In controls, IGFBP-3 was not detected in epithelial cells of any prostatic lobe. Macroscopic prostatic size and the appearance of IGF-I transgenic mice were comparable with those of their control littermates of the same age. With a computed morphometric analysis, epithelial glands and intraglandular lumens in the prostatic lobes except the ventral lobe were smaller at 17 Months of age than at 14 Months both in IGF-I transgenic mice and controls. Glands and intraglandular lumens in the ventral prostatic lobes of IGF-I transgenic mice expressing more IGF-I protein in the prostate than controls were dense and enlarged similar to cysts compared with those of non-transgenic littermates without showing epithelial growth. Glands and lumens in the dorsal and lateral lobes of the IGF-I transgenic mice were also larger than controls at 14 and/or 17 Months of age. Glands in the anterior prostatic lobe of the IGF-I transgenic mice were not morphologically or morphometrically different from those of non-transgenic littermates. In conclusion, IGF-I transgenic mice under the control of rat probasin promoter showed more dense and enlarged epithelial glands in their prostatic ventral, dorsal and lateral lobes.

Aging↗

Mapping soil-transmitted helminths in Southeast Asia and implications for parasite control.

Establishing the current status and distribution of soil-transmitted helminths is essential for developing and implementing parasite control. Although Southeast Asia is known to have a high prevalence of infection, a precise estimate of the total disease burden has not been fully described. Here, we use Geographical Information Systems (GIS) to collate and map recent published surveys on soil-transmitted helminth epidemiology and distribution for this region. Distinct geographical variation was observed, which is suggested to reflect climatic variation, as well as behavioral differences. However, for much of the region few data are available, and therefore it proved necessary to generate predictions of the distribution of soil-transmitted helminths using remotely sensed (RS) satellite sensor environmental variables. A significant finding was the importance of land surface temperature in influencing the distribution of Ascaris lumbricoides and Trichuris trichiura. Spatial analyses using RS satellite sensor data were then used to generate predictive maps of infection risk. This information provided the basis for an estimate of the population at risk of infection and the numbers requiring treatment. These applications of GIS and remote sensing provide a good basis for developing control of soil-transmitted helminths in the region.

Animals↗

Developmental expression of carbonic anhydrase-related proteins VIII, X, and XI in the human brain.

Three cDNA homologues of carbonic anhydrase with unknown biological functions have been reported: carbonic anhydrase-related proteins (CA-RP) VIII, X, and XI. In the present study, we produced monoclonal antibodies to these CA-RPs and studied their regional and cellular distributions in the human adult and fetal brains by immunohistochemical analysis. In the adult brain, CA-RP VIII was expressed in the neural cell body spreading to most parts of the brain. CA-RP X was expressed in the myelin sheath and its expression was shown in the cytoplasm of cultured tumor cells by immunocytochemical analysis. CA-RP XI was expressed in the neural cell body, neurites, and astrocytes in relatively limited regions of the brain. In the fetal brain, CA-RP VIII and XI were expressed in the neuroprogenitor cells in the subventricular zone as early as the 84th day of gestation and subsequently detected in the neural cells migrating to the cortex. CA-RP X first appeared in the neural cells in the cortex at the 141st day. In the choroid plexus, the epithelial cells gave CA-RP VIII and XI expressions in both adult and fetal brains. From the findings in the present study on the distribution and the developmental expression of CA-RP VIII, X, and XI in the human brain we suggest that these CA-RPs play roles in various biological process of the CNS.

Adult↗

Effect of hot water extract from Agaricus blazei Murill on antibody-producing cells in mice.

We investigated the immunopotentiating activities of boiled water-soluble extracts from desiccated Agaricus blazei Murill (ABM). Effect of ABM extract on antibody production was investigated by method of hemolytic plaque-forming cells (PFC) against sheep red blood cells (SRBC) antigen. ABM extracts significantly (p<0.01) increased the number of PFC in spleen with intraperitoneal administration at doses of 25 mg/kg as compared with control group. The populations of Mac-1- or CD25-positive cells significantly (p<0.01, p<0.001) increased, but in CD19-positive cells, there were no differences in ABM-treated mice as compared with control mice. The expressions of IL-6 and IL-1beta mRNA were augmented by ABM extract in both peritoneal macrophages and spleen cells. These results suggested that ABM extract might be an effective stimulator for T cell and macrophage to IL-1beta and IL-6 release, resulting in augmentation of antibody production against SRBC antigen.

Agaricus↗

Observation of fluorapatite formation under hydrolysis of tetracalcium phosphate in the presence of KF by means of soft X-ray emission and absorption spectroscopy.

The effect of fluoride on the hydrolysis of tetracalcium phosphate (TTCP; Ca4(PO4)2O) in 0.1 mol/l KH2PO4 containing 62-83 mmol/l KF was studied with the help of X-ray fluorescence measurements. Fluorine X-ray emission and absorption spectra of the final product of hydrolysis and reference samples (CaF2 and Ca5(PO4)3F) were measured at Beamline BL-2C of Photon Factory (PF, Tsukuba). Based on these measurements we concluded that hydrolysis of TTCP in the presence of KF converts it into fluorapatite. Formation of CaF2, which is often found in the hydrolysis of hydroxyapatite at high fluoride concentration, was not observed.

Journal Article↗

Suspected delayed immune recovery against cytomegalovirus after reduced-intensity stem cell transplantation using anti-thymocyte globulin.

A reduced-intensity hematopoietic stem cell transplantation (RIST) regimen was developed to induce immunosuppression to facilitate the engraftment of donor cells. However, there have been concerns that the incidence of opportunistic infection may increase after this procedure. To address this problem, we retrospectively analyzed the medical records of 24 RIST recipients who were treated over a recent 16-month period for comparison with 31 recipients of conventional allogeneic transplantation (CST). The RIST regimen consisted of cladribine (0.66 mg/kg), busulfan (8 mg/kg), and rabbit anti-thymocyte globulin (ATG; 5-10 mg/kg). All of the patients received allogeneic peripheral blood stem cells from an HLA-identical or one-locus mismatched related donor. Although the incidence of positive CMV antigenemia was comparable between the two groups (58% vs 68%), RIST patients developed positive antigenemia significantly sooner than did CST patients (P = 0.01) and showed higher initial and maximum antigenemia values (P = 0.026 and P = 0.003, respectively). These findings may suggest that immune recovery against CMV was delayed after our RIST procedure, but this did not directly translate into an increase in clinically significant CMV disease. Early therapeutic intervention with ganciclovir might play a role in preventing the progression of early CMV infection to CMV disease.

Adolescent↗

Gastrin interferes with the differentiation of gastric pit cells and parietal cells.

BACKGROUND: Gastrin is known to have stimulatory effects on gastric mucosa; however, long-term effect of gastrin stimulation is not well known. AIM AND METHODS: To investigate the long-term effect of hypergastrinaemia, we established hypergastrinaemic transgenic mice by introducing a mutated human gastrin gene. Homozygously transgene-expressing mice showed serum gastrin levels of more than 600 pg/mL. RESULTS: Neither progastrin nor glycine-extended gastrin titre elevation were observed in hypergastrinaemic transgenic mice. Stomachs from the 30-35-week-old transgenic mice were 30-50% heavier and their mucosa were markedly thicker than those of the controls. The hypertrophic gastric mucosa of hypergastrinaemic transgenic mice consisted of elongated pits with widespread proliferative zones, and comprised depleted glandular regions. In situ hybridization study indicated that expression of H, K-ATPase mRNA in parietal cells of hypergastrinaemic transgenic mice was markedly decreased. By gastrin binding assay in vivo, specific gastrin binding sites were observed in the mid-glandular region of hypergastrinaemic transgenic mice that consisted mainly of prepit cells. CONCLUSIONS: These results suggest that long-term stimulation of gastrin increases the expression of CCK-B/gastrin receptors in the less-differentiated pit cells that are the main component of elongated gastric units, and lessens the well-differentiated characteristics of parietal cells.

Animals↗

Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in peripheral blood T cells from systemic lupus erythematosus patients.

We have reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR zeta) was decreased in two systemic lupus erythematosus (SLE) patients with an abnormal TCR zeta lacking exon-7. To examine further the TCR zeta defect and any possible relationship with specific clinical features, we studied the expression of TCR zeta in peripheral blood T cells from 44 patients with SLE, 53 with other rheumatic diseases (30 rheumatoid arthritis (RA), 11 systemic sclerosis (SSc) and 12 primary Sjögren's syndrome(SjS)) and 39 healthy individuals. Flow cytometric analysis demonstrated a significant decrease in the expression of TCR zeta in SLE (P < 0.001), but not in the other rheumatic diseases. Immunoprecipitation experiments confirmed that the expression of TCR zeta in SLE T cells was decreased dramatically (normal: 111.4 +/- 22.6%, SLE: 51.6 +/- 37.4%, P < 0.0001). The decrease in TCR zeta did not correlate with disease activity, or with the dose of prednisolone (PSL). There were, however, three SLE patients in whom the level of TCR zeta expression normalized after treatment, suggesting that mechanisms responsible for the TCR zeta defect appear to be heterogeneous. These results confirm the defective expression and altered tyrosine phosphorylation of TCR zeta in a large proportion of SLE patients, suggesting that it may play an important role in T cell dysfunction in SLE.

Adult↗

Abnormal expression and function of Fas ligand of lacrimal glands and peripheral blood in Sjögren's syndrome patients with enlarged exocrine glands.

The objective of our study was to investigate the possibility of Fas ligand protein abnormalities in certain types of Sjögren's syndrome patients with enlarged exocrine glands. Fas ligand expression by lymphocytes infiltrating the lacrimal glands and by peripheral blood monocytes in Sjögren's syndrome patients with enlarged exocrine glands was assessed immunohistologically and by immunoblotting. Cytotoxicity of peripheral blood monocytes and sensitivity to steroids in Sjögren's syndrome patients with enlarged exocrine glands were studied by functional assay. Minimal Fas ligand expression was detected in the lymphocytes of the lacrimal glands and a decreased level of Fas ligand was found in peripheral blood monocytes as assessed by immunoblotting. Functional assay confirmed the decreased cytotoxicity of lymphocytes in Sjögren's syndrome patients with enlarged exocrine glands, and that it is not affected by anti-Fas ligand antibody. By contrast, the sensitivity of lymphocytes in Sjögren's syndrome patients with enlarged exocrine glands to steroids was increased. These observations suggest that abnormal expression and function of Fas ligand occurs in Sjögren's syndrome patients with enlarged exocrine glands.

Adrenal Cortex Hormones↗

Characteristic transfer of colostrum-derived biologically active substances into cerebrospinal fluid via blood in natural suckling neonatal pigs.

The characteristic transfer of colostral components into cerebrospinal fluid (CSF) via serum after natural suckling has been studied by sodium dodecyl sulphate (SDS) electrophoresis, two-dimensional electrophoresis, immunoblot and enzyme linked immunosorbent assay methods in non-suckling pigs. Total protein concentrations in the serum increased immediately after first suckling, reached a peak value at 12 h, corresponding to a 2.3-fold compared with pre-suckling level. The protein concentration in CSF also increased and reached peak value at 6 h corresponding to 1.6-fold compared with presuckling level. IgG in serum not detected before suckling, increased steeply after suckling, IgG, IgM and IgA transported into the serum were observed in completely intact form by immunoblot method. The IgG transported into serum was quickly transferred into CSF after natural suckling in contrast to the case of bovine IgG. Serum concentration of transferrin was maintained at high level before suckling and was not changed by suckling. Transferrin also detected in CSF was not changed by suckling. Bovine lactoferrin (Lf) administered into the intestinal lumen was transported into serum (0.01%) and also detected in CSF after 6 h as undegraded form (3.1%). Thus, homologous IgG and bovine Lf are transported into CSF, suggesting that the transport of macromolecules into CSF is selective in neonatal pigs.

Animals↗

Adenoviral insulin gene therapy prolongs survival of IDDM model BB rats by improving hyperlipidemia.

Diabetes is frequently associated with hyperlipidemia, which results in atherogenic complications. Insulin-dependent diabetes mellitus (IDDM) model BB/Wor//Tky (BB) rats exhibit both hyperglycemia and hyperlipidemia and die within 3 weeks after the onset of diabetes unless insulin therapy is given. We performed insulin gene therapy in BB rats with adenovirus vectors through the tail vein. After infusion, plasma triglyceride levels dropped quickly and maintained low levels for 1 week, whereas blood glucose levels showed a slight decrease. The survival period of diabetic BB rats was prolonged to up to 75 days by infusing insulin gene-expressing adenoviral vectors. We suggest that the control of hyperlipidemia can be a life-saving measure when combined with hyperglycemia control in the treatment of diabetes.

Adenoviridae↗

Horizontal transfer of the plant virulence gene, nec1, and flanking sequences among genetically distinct Streptomyces strains in the Diastatochromogenes cluster.

Evidence for the horizontal transfer of a pathogenicity island (PAI) carrying the virulence gene nec1 and flanking sequences among Streptomyces strains in the Diastatochromogenes cluster is presented. Plant-pathogenic, thaxtomin-producing Streptomyces strains, previously classified as S. scabiei based on the conventionally used phenotypic characteristics, were found to be genetically distinct from the type strain of S. scabiei based on DNA relatedness and 16S rDNA sequence analysis. Pairwise DNA-DNA hybridizations between some of these strains and the S. scabiei type strain were as low as 36%, a value much below what is conventionally accepted for species identity (70%). The sequence of the nec1 gene, however, was identical in all the S. scabiei and S. scabiei-like strains tested, irrespective of their DNA relatedness to the type strain of S. scabiei, their geographic origin, or the isolation host. Furthermore, a 26-kb DNA fragment including and flanking nec1 was also conserved among these strains based on restriction and Southern analyses. These data indicate that the etiology of potato scab is more complex than previously recognized; this result has important implications for potato scab management strategies. Previous research has suggested that horizontal transfer of a PAI was the mechanism for evolution of pathogenicity in S. acidiscabies and S. turgidiscabies, species that lie outside of the Diastatochromogenes cluster. Data presented here support this model and indicate that PAI transfer also has occurred frequently in species closely related to S. scabiei.

Arachis↗

Myofiber expression of class I major histocompatibility complex accompanied by CD8+ T-cell-associated myofiber injury in a case of canine polymyositis.

A 7-year-old female Labrador Retriever dog showed extreme muscular weakness, muscle wasting, dysbasia, and mild dysphagia. An elevated value of creatine kinase (335 IU/liter) in the serum was detected. Electromyographic findings included increased insertional activity, fibrillation potentials, and bizarre high-frequency repetitive potentials. Histopathologic examination of skeletal muscles revealed myofiber necrosis and phagocytosis, regeneration of myofibers, and perivascular, perimysial, and endomysial infiltrations of lymphocytes, macrophages and plasma cells. Immunohistochemical evaluation demonstrated that infiltrative cells in the early stage of myositis were CD8+ T-cells and that an increased expression of major histocompatibility complex (MHC) class I was apparent on the surface of nonnecrotic muscle fibers. In contrast, many CD3+ cells (T cells) and HLA-DR-positive macrophages and B lymphocytes were found in the severely affected areas. These results suggest that both expression of MHC class I and CD8+ T-cell infiltration may play an important role in initiation of myositis. These histopathologic findings resemble those reported in naturally occurring polymyositis in humans.

Animals↗

Transport of colostral macromolecules into the cerebrospinal fluid via plasma in newborn calves.

The objective of this study was to investigate the transfer of bovine colostral macromolecules especially the lactoferrin (Lf), transferrin (Tf), immunoglobulin G (IgG), and epidermal growth factor (EGF) from the gastrointestinal tract to the cerebrospinal fluid (CSF) via systemic circulation in newborn calves. Cannulae were placed into the jugular vein and cisterna magna to collect blood and CSF, respectively at various time points. The colostrum, plasma, and CSF were analyzed by ELISA, SDS-PAGE, two-dimensional PAGE, and Western blotting. The concentration of total protein, Lf, Tf, and IgG in plasma averaged 47 mg, 204 ng, 101 microg and 15 microg/ml before colostrum feeding and increased to the peak values of 64 mg, 2413 ng, 820 microg, and 4608 microg/ml 8 h after feeding, respectively. Before colostral feeding CSF, total protein, Lf, Tf, and IgG averaged 0.44 mg, 10.3 ng, 0.31 microg, and 0.11 microg/ml, but peak values after feeding averaged 2.0 mg, 173 ng, 71 microg and 72 microg/ml after 10 h, respectively. Immunologically, six EGF-positive protein bands were detected in colostrum as well as in three bands higher density in plasma and CSF after colostral feeding. This study revealed that the colostral macromolecules were not only absorbed into the systemic circulation, but also some of them including Lf, Tf, IgG, and EGF-like proteins were transported into the CSF in a time-dependent manner through blood-CSF or blood-brain barrier of the newborn calves.

Animals↗

Cliniconeuropathologic findings of familial frontal lobe epilepsy in Shetland sheepdogs.

We examined an epileptic focus by electroencephalography (EEG) by using an international 10-20 electrode system in 11 Shetland sheep dogs affected with familial idiopathic epilepsy. We also performed an evaluation of the amino acids in the cerebrospinal fluid (CSF) and a pathologic examination of the brains of 8 dogs that died from status epilepticus. Continuous electroencephalography demonstrated that an epileptic focus was initially detected in the frontal lobe, particularly the internal area, and that paroxysmal foci developed diffusely in other lobes of affected dogs with recurrent convulsions. The EEG analyses indicated spike and sharp wave complexes, which were considered to be paroxysmal discharges. An increased value for glutamate or aspartate was found in the CSF of some epileptic dogs. Histologically, acute neuronal necrosis and astrocytosis were distributed predominantly in the cingulate cortex and internal area of frontal cortex, less frequently in other areas of the cerebrum. The results of this study suggest that, initially, the dogs have an epileptic focus in the frontal lobe, and that the focus extends gradually to other areas of the cerebrum. Based on the distribution of neuronal necrosis and astrocytosis, acute neuronal damage may be related to the superexcitation of neurons following epilepsy.

Amino Acids↗

Preparation of sterol-imprinted polymers with the use of 2-(methacryloyloxy)ethyl phosphate.

Steroid-selective polymers were prepared by the molecular imprinting technique, using 2-(methacryloyloxy)ethyl phosphate as functional monomer. The retentivity and selectivity of the obtained imprinted polymers were evaluated by liquid chromatography. The cholesterol-imprinted polymer showed higher affinity for cholesterol than that for cholesterol derivatives. The selectivity of the imprinted polymer was superior to the imprinted polymer prepared with the conventional functional monomer, 2-(trifluoromethyl)acrylic acid. Estradiol was also imprinted and gave similar results, demonstrating that 2-(methacryloyloxy)ethyl phosphate would be suitable for imprinted polymers of cholesterol and related compounds.

Cholesterol↗

A case of clinically and neuropathologically atypical corticobasal degeneration with widespread iron deposition.

A 65-year-old woman was admitted to our hospital for forgetfulness, depression and eccentric behavior that had been first noticed 2 years prior to admission. She showed memory impairment, perseveration and repeated violent actions, but no limb-kinetic apraxia. She died 12 years after the onset of symptoms. At autopsy, the unfixed brain weighed 820 g. Atrophy was circumscribed in the frontal lobe on both sides. The globus pallidus and the caudate nucleus were markedly atrophic and gold yellow in color, and the substantia nigra was strikingly pale. The cortical area showed neuronal loss and status spongiosus of the second and third cortical layers with ballooned neurons. Marked neuronal loss was observed in the dorsomedial nucleus of the thalamus, Meynert basal nucleus and substantia nigra. With Holzer stain, fibrillary gliosis was found to be severe in the frontal lobe, globus pallidus, subthalamic nucleus, hippocampus, dorsomedial nucleus of thalamus, substantia nigra, pontine tegmentum and inferior olivary nucleus. With Bielschowsky-Hirano stain, neurofibrillary tangles were observed in the cortex, hippocampus, substantia nigra, dentate nucleus, subthalamic nucleus, pontine nucleus, the inferior olivary nucleus, dorsomedial nucleus of the thalamus and, to a lesser extent, the neostriatum. Strikingly numerous argyrophilic and tau-positive threads were present in the cerebral white matter. These neuropathological findings corresponded to corticobasal degeneration, but lesions characteristic of progressive supranuclear palsy were also found. Moreover, widespread iron deposition throughout the central nervous system was the most striking finding of the present case. To our knowledge, such a case has not been reported in the literature to date.

Basal Ganglia↗

NGF induces neurite outgrowth via a decrease in phosphorylation of myosin light chain in PC12 cells.

The relationship between phosphorylation of myosin light chain (MLC) and neurite outgrowth induced by nerve growth factor (NGF) was studied in PC12 cells. Inhibitors of Rho kinase, HA-1077 or Y-27632 also induced neurite outgrowth. As already reported botulinum exoenzyme C3 which inactivates Rho protein also induced neurite outgrowth. Calyeulin A, an inhibitor of phosphatase counteracted both NGF- and C3- induced neurite outgrowth. Treatments of both NGF and C3 resulted in significant and transient decrease in phosphorylated MLC. These results suggest that NGF induces neurite outgrowth of PC12 by a transient decrease in phosphorylated MLC which is brought about by activation of MLC phosphatase via inhibition of Rho-Rho kinase pathway.

Animals↗