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Biomedical subjects

E Yamada

Publications and source records attributed to E Yamada.

At least 19 recordsLinked to original sources
PubMed2005

Neuronal intranuclear hyaline inclusion disease showing motor-sensory and autonomic neuropathy.

BACKGROUND: Neuronal intranuclear hyaline inclusion disease (NIHID), a rare neurodegenerative disease in which eosinophilic intranuclear inclusions develop mainly in neurons, has not yet been described to present as hereditary motor-sensory and autonomic neuropathy. METHODS: Patients in two NIHID families showing peripheral neuropathy were evaluated clinically, electrophysiologically, and histopathologically. RESULTS: In both families, patients had severe muscle atrophy and weakness in limbs, limb girdle, and face; sensory impairment in the distal limbs; dysphagia, episodic intestinal pseudoobstruction with vomiting attacks; and urinary and fecal incontinence. No patients developed symptoms suggesting CNS involvement. Electrophysiologic study showed the reduced motor and sensory nerve conduction velocities and amplitudes, and also extensive denervation potentials. In sural nerve specimens, numbers of myelinated and unmyelinated fibers were decreased. In two autopsy cases, eosinophilic intranuclear inclusions were widespread, particularly in sympathetic and myenteric ganglion neurons, dorsal root ganglion neurons, and spinal motor neurons. These neurons also were decreased in number. CONCLUSION: Patients with neuronal intranuclear hyaline inclusion disease (NIHID) can manifest symptoms limited to those of peripheral neuropathy. NIHID therefore is part of the differential diagnosis of hereditary motor-sensory neuropathy associated with autonomic symptoms. Intranuclear hyaline inclusions in Schwann cells and in the myenteric plexus may permit antemortem diagnosis of NIHID.

Aged↗
PubMed2005

Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii rat.

AIMS/HYPOTHESIS: The spontaneously diabetic Torii (SDT) rat has recently been established as a model of type 2 human diabetes mellitus. Male SDT rats develop severe diabetic ocular complications. This study investigated the nature of the ocular complications in this model and addressed the question of whether the SDT rat is a good model of human proliferative diabetic retinopathy. METHODS: Male SDT rats aged 50 weeks were studied for a period of 8 months. Under deep anaesthesia, one eye of each animal was enucleated following perfusion with fluorescein dextran and a retinal flat mount was prepared to study vascular structure. The other eye was enucleated and investigated histologically by haematoxylin-eosin and azan staining and by immunohistochemistry using antibodies against vascular endothelium (Griffonia simplicifolia isolectin B4 antibody) and vascular endothelial growth factor (VEGF). RESULTS: From the vascular structure study, 17 of 32 rats (53%) showed proliferative retinopathy without vascular non-perfusion. The histological study revealed traction retinal folds in rats with proliferative retinopathy. Azan staining showed some proliferative matrix in rats with normal retinal structure and those with proliferative retinopathy compared with normoglycaemic controls. Staining with Griffonia simplicifolia isolectin B4 antibody showed no specific vascular changes in any of the rats, while VEGF staining revealed higher immunoreactivity in the retina of rats with normal retinal structure and those with proliferative retinopathy, but only low immunoreactivity in the control animals. CONCLUSIONS/INTERPRETATION: There appear to be differences between the SDT rat model of diabetic retinopathy and human proliferative diabetic retinopathy, as the SDT rat develops retinal neovascularisation without retinal ischaemia. This very unique display of ocular neovascularisation may be caused by increased expression of VEGF.

Animals↗
PubMed2001

Fibroblast growth factor-2 decreases hyperoxia-induced photoreceptor cell death in mice.

Fibroblast growth factor-2 (FGF2) has neurotrophic effects in vitro and in vivo. It has been demonstrated to decrease photoreceptor cell death in rats exposed to constant light and in rats with an inherited defect in retinal pigmented epithelium (RPE) phagocytosis, but the effects of intravitreous injections of FGF2 in mice are equivocal. In this study, we used transgenic mice with increased expression of FGF2 in photoreceptors (rhodopsin promoter/FGF2 transgenics) to investigate the effects of sustained increased expression of FGF2 in mice with various types of photoreceptor degeneration, including rd mice that are homozygous for mutated phosphodiesterase beta subunit, Q344ter mice that undergo photoreceptor degeneration because of expression of mutated rhodopsin, and mice exposed to 75% oxygen for 1 or 2 weeks. At P21, the outer nuclear layer was markedly reduced in rd mice or Q344ter mice regardless of whether they inherited the rhodopsin promoter/FGF2 transgene. However, after 2 weeks of exposure to 75% oxygen, outer nuclear layer thickness was significantly reduced in littermate control mice compared to FGF2 transgenic mice (P = 0.0001). These data indicate that increased expression of FGF2 in photoreceptors protects them from hyperoxia-induced damage, but does not decrease cell death related to expression of mutated proteins involved in the phototransduction pathway. This suggests that FGF2 protects photoreceptors from oxidative damage, which may play a role in complex genetic diseases such as age-related macular degeneration.

Aging↗
PubMed2001

International Study of Asthma and Allergies in Childhood: validation of the rhinitis symptom questionnaire and prevalence of rhinitis in schoolchildren in São Paulo, Brazil.

Written questionnaires (WQ) have been widely used in epidemiologic studies. In order to yield comparable results, they must be validated after translation to another language. The International Study of Asthma and Allergies in Childhood (ISAAC) WQ has been previously validated by a comprehensive study, but its validation in Brazil has not been performed. Our objectives were to validate the rhinitis component of the ISAAC's self-applicable WQ following its translation to Portuguese, and to determine the prevalence of rhinitis and related symptoms among Brazilian children living in the city of São Paulo. A group of 10 pediatricians and 10 pediatric allergists graded the questions from 0 to 2 and established a maximum score for each question. The WQ was answered by parents or guardians of children 6-7 years of age with rhinitis (R) (n = 27) and of control children of the same age without rhinitis (C) (n = 27). The WQ was also completed by adolescents 13-14 years of age with rhinitis (R) (n = 32) and without rhinitis (C) (n = 32). Half of these individuals answered the same WQ after 2-4 weeks, to ensure reproducibility. Cut-off scores of 4 and 3 were identified for the 6-7- and 13-14-year-old groups, respectively, as scores predictive of rhinitis. The prevalence of rhinitis was 28.8% in the group of 3005 children 6-7 years of age and 31.7% in the group of 3008 children 13-14 years of age, respectively. Using the global cut-off score, these prevalences were even higher, in the order of 34.7% and 40.7%, respectively. In conclusion, the rhinitis component of the ISAAC WQ was proven to be reproducible, adequate and able to discriminate children and adolescents with and without rhinitis, and revealed that the prevalence of rhinitis among Brazilian children living in the city of São Paulo was as high as the prevalence of rhinitis in other areas of the world.

Adolescent↗
PubMed2001

Effect of acetate on glycogen replenishment in liver and skeletal muscles after exhaustive swimming in rats.

Immediately after exhaustive swimming, rats were given one of the following orally: distilled water (W), glucose (G); acetic acid (A); citric acid (C); glucose and acetic acid (GA); and glucose and citric acid (GC), and they were killed 2 h after ingestion (each trial: n=4). Exhaustive exercise resulted in a significant reduction of the glycogen store in the gastrocnemius muscle. The glycogen stores in the liver were significantly higher following ingestion in groups GA and GC, in the gastrocnemius in groups G, GA and GC, and in the soleus in group GC, than immediately post exercise. These results suggest that oral acetic acid with glucose can facilitate liver glycogen restoration during the early period of recovery, and that acetate has about the same physiological effects as citrate on glycogen replenishment.

Acetic Acid↗
PubMed2001

Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture.

To investigate whether amiodarone increases interleukin-6 (IL-6) production in thyrocytes, human follicles obtained from subtotally thyroidectomized patients with Graves' disease were cultured in serum-free medium supplemented with various concentrations of bovine thyrotropin (bTSH) and amiodarone. The follicles gradually formed monolayer cells and secreted triiodothyronine (T3), thyroglobulin (Tg), and IL-6 for at least 14 days. TSH dose-dependently increased T3 and Tg but not IL-6 levels in the conditioned medium. Amiodarone exerted no significant effect on T3, Tg, or IL-6 concentrations at 0.1-1 microM. In contrast, at 10-20 microM, it decreased T3 and Tg, but increased IL-6 levels, and these changes were accompanied by increased expression of IL-6 mRNA. Amiodarone-induced IL-6 production was inhibited by prednisolone at 10(-7) M. Electron microscopic examination revealed that the thyroid follicles in the suspension culture remained intact at 1 microM, but that cytotoxic effects (decreased microvilli and increased onion-like inclusion bodies) occurred at higher concentrations (10-25 microM). These in vitro findings indicate that amiodarone does not impair thyroid function at clinically attainable serum levels (1 microM), but exerts cytotoxic effect by inducing the production of a proinflammatory cytokine (IL-6) at higher concentrations. Because amiodarone-induced IL-6 production was inhibited by prednisolone, it is reasonable to administer glucocorticoids to patients with amiodarone-induced destructive thyrotoxicosis (type II).

Amiodarone↗
PubMed2001

Synthesis of a nitrogen analogue of salacinol and its alpha-glucosidase inhibitory activity.

A nitrogen analogue 4 of the naturally occurring sulfonium ion salacinol (1), a potent alpha-glucosidase inhibitor isolated from the Ayruvedic medicine Salacia reticulata, was synthesized and its inhibitory activity against alpha-glucosidase tested. Substitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably. The solid-state stereostructure of the related compound (5) was determined on the basis of single crystal X-ray measurement.

Animals↗
PubMed2001

TIMP-1 promotes VEGF-induced neovascularization in the retina.

Proteolysis of vascular basement membranes and surrounding extracellular matrix is a critical early step in neovascularization. It requires alteration of the balance between matrix metalloproteinases (MMPs) and proteins that bind to and inactivate MMPs, tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 has been demonstrated to inhibit neovascularization in chick chorioallantoic membranes. However, TIMP-1 has also been shown to either promote or inhibit cell proliferation and migration in different settings. To determine whether genetic alteration of the MMP/TIMP-1 ratio would alter retinal neovascularization, we crossed mice that express vascular endothelial growth factor (VEGF) in photoreceptors with TIMP-1-deficient mice or mice that overexpress TIMP-1. Compared to VEGF transgene-positive/TIMP-1-sufficient mice, VEGF transgene-positive/TIMP-1-deficient mice showed smaller neovascular lesions. There was also no difference between the two groups of mice in the appearance of the neovascularization by light or electron microscopy. Compound VEGF/TIMP-1 transgenic mice had increased expression of both VEGF and TIMP-1 in the retina, and had more neovascularization than mice that had increased expression of VEGF alone. These gain- and loss-of-function data suggest that alteration of the TIMP-1/MMP ratio modulates retinal neovascularization in a complex manner and not simply by altering the proteolytic activity and thereby invasiveness of endothelial cells.

Actins↗
PubMed2001

Kinetic analysis of prepulse facilitation of calcium currents in hamster submandibular ganglion neurons.

The calcium ion influx through voltage-dependent calcium channels (VDCCs) has a vital role in the control of neurotransmitter release and membrane excitability. The modulation of VDCCs controls the extent of calcium entry and thus provides a way of regulating neuronal function. Prepulse facilitation is a phenomenon in which a strong depolarizing pulse induces a form of the VDCCs that exhibits an increased opening probability in response to a given test potential that persists for several seconds after repolarization. In this study, we have studied the characterization of prepulse facilitation of VDCCs currents (Ica) in hamster submandibular ganglion (SMG) neurons, using whole-cell patch clamp recordings. In SMG neurons, application of a strong depolarizing prepulse caused a Ica. In 8 SMG neurons, rate of facilitation was 1.1 +/- 0.1. The greatest value of prepulse facilitation was obtained with prepulse to +100 mV, 10 ms duration in this neuron. The magnitude of facilitation was dependent on changing the interval between the -prepulse and the +prepulse and reached a maximum at a interval of 500 ms.

Animals↗
PubMed2001

International Study of Asthma and Allergies in Childhood (ISAAC): prevalence of asthma and asthma-related symptoms among Brazilian schoolchildren.

We have studied the prevalence of asthma and its symptoms using a standard written questionnaire (WQ) designed for the International Study of Asthma and Allergies in Children (ISAAC). The WQ (questions 1 through 8 related to asthma) was applied to 13,604 children aged 6-7 years from six Brazilian cities: Porto Alegre (South, N = 2,976), Curitiba (South, N = 1,664), São Paulo (Southeast, N = 3,005), Uberlândia (Southeast, N = 3,002), Itabira (Southeast, N = 1,551) and Recife (Northeast, N = 1,406). At the age of 13-14 years the WQ was applied to 20,554 schoolchildren living in Porto Alegre (South, N = 3,198), Curitiba (South, N = 3,008), São Paulo (Southeast, N = 3,008), Uberlândia (Southeast, N = 3,001), Itabira (Southeast, N = 2,134), Salvador (Northeast, N = 3,119) and Recife (Northeast, N = 3,086). The parents of the younger children answered the WQ, whereas the adolescents answered the questionnaire themselves. The response rates were 72% and 93% for the 6-7-year-old children and for the 13-14-year-old children, respectively. There was a slight predominance of male children in the population studied. In the group of 6-7-year-olds, the prevalence of physician diagnosed asthma was 7.3% for boys and 4.9% for girls: in the group of 13-14-year-olds the rates were 9.8% and 10.2%, respectively. Asthma severity was similar for both age groups, and wheezing following exercise was more frequent among the adolescents. In keeping with studies from other parts of the world, comparison between reported symptoms and diagnosed asthma revealed a significantly lower frequency of diagnosed asthma, suggesting that in the study population, asthma is underdiagnosed.

Adolescent↗
PubMed2000

Insertional mutation of the murine kisimo locus caused a defect in spermatogenesis.

Spermatogenesis is a developmental process that occurs in several phases and is regulated by a large number of gene products. An insertional transgenic mouse mutant (termed kisimo mouse) has been isolated that results in abnormal germ-cell development, showing abnormal elongated spermatids in the lumina of seminiferous tubules. We cloned the disrupted locus of kisimo and identified a novel testis-specific gene, THEG, which is specifically expressed in spermatids and was disrupted in the transgenic mouse. The yeast two-hybrid screening method revealed that THEG protein strongly interacts with chaperonin containing t-complex polypeptide-1epsilon, suggesting that THEG protein functions as a regulatory factor in protein assembly. Our findings indicate that the kisimo locus is essential for the maintenance of spermiogenesis and that a gene expression disorder may be involved in male infertility.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Molecular cloning and characterization of a novel human STE20-like kinase, hSLK.

We have cloned a human counterpart to a guinea pig STE20-like kinase cDNA, designated human SLK (hSLK), from a human lung carcinomatous cell line A549 cDNA library. hSLK cDNA encodes a novel 1204 amino acid serine/threonine kinase for which the kinase domain located at the N-terminus shares considerable homology to that of the STE20-like kinase family. The C-terminal domain of hSLK includes both the coiled-coil structure and four Pro/Glu/Ser/Thr-rich (PEST) sequences, but not the GTPase-binding domain (GBD) that is characteristic of the p21-activated kinase (PAK) family, polyproline consensus binding sites, or the Leu-rich domain seen in the group I germinal center kinases (GCKs). Northern blot analysis indicated that hSLK was ubiquitously expressed. hSLK overexpressed in COS-7 cells phosphorylates itself as well as myelin basic protein used as a substrate. On the other hand, hSLK cannot activate any of the three well-characterized mitogen-activated protein kinase MAPK (ERK, JNK/SAPK and p38) pathways. Moreover, hSLK kinase activity is not upregulated by constitutive active forms of GTPases (RasV12, RacV12 and Cdc42V12). These structural and functional properties indicate that hSLK should be considered to be a new member of group II GCKs.

Amino Acid Sequence↗
PubMed2000

In vivo osteogenic durability of cultured bone in porous ceramics: a novel method for autogenous bone graft substitution.

BACKGROUND: Bone marrow cells differentiate into bone-forming osteoblasts when cultured in medium supplemented with 15% fetal bovine serum, ascorbic acid, beta-glycerophosphate, and dexamethasone. METHODS: To investigate in vivo osteoblastic activity and bone matrix formation by cultured bone marrow cells, Fischer rat marrow cells were cultured for 2 weeks in porous hydroxyapatite (HA) and then subcutaneously implanted into 7-week-old male syngeneic rats. The implants were harvested after 8 and 52 weeks for biochemical and histological analyses. RESULTS: At both times, formation of lamellar bone accompanied by regeneration of marrow were seen in many of the HA pores. When a fluorochrome (calcein) was administered at 50 weeks after implantation, it was detected in the pores of implants harvested at 52 weeks. Osteoclastic resorption followed by new bone formation was seen in some pores at 52 weeks, indicating that bone remodeling was continuing. The alkaline phosphatase activity of implants harvested at 52 weeks was comparable to that at 8 weeks, whereas the osteocalcin content of the implants harvested at 52 weeks was about twice that at 8 weeks. CONCLUSION: These results demonstrated that there was persistent in vivo osteogenic and hematopoietic activity in the prefabricated bone/HA constructs, and indicated that normal bone tissue was regenerated after grafting of the constructs, which were brittle before implantation. Tissue engineering using HA and cultured marrow cells culture may provide an alternative method of bone transplantation for patients with skeletal disorders, although further in vivo and in vitro experiments are needed.

Alkaline Phosphatase↗
PubMed2000

Cell injury unmasks a latent proangiogenic phenotype in mice with increased expression of FGF2 in the retina.

Fibroblast growth factor-2 (FGF2) is a potent mitogen for vascular endothelial cells and exogenous administration of FGF2 stimulates angiogenesis. However, increased expression of FGF2 in the retina does not cause angiogenesis. One possible explanation is that FGF2 may not be capable of initiating angiogenesis unless it is administered in pharmacologic levels or there is coexpression of another angiogenic factor. Alternatively, there may be control mechanisms that sequester FGF2 in vivo, preventing it from manifesting its in vitro angiogenic activity. We tested the first hypothesis by crossing mice that express FGF2 in the retina with mice that express vascular endothelial growth factor (VEGF) in the retina. Surprisingly, despite comparable levels of VEGF expression, mice that expressed both FGF2 and VEGF had significantly less neovascularization than mice that expressed VEGF alone. The second hypothesis was tested by treating Rho/FGF2 transgenic mice with low-intensity laser photocoagulation that disrupts photoreceptors, but does not rupture Bruch's membrane, or intense laser that ruptures Bruch's membrane. In Rho/FGF2 transgenics, but not wild type mice, choroidal neovascularization developed in areas of low-intensity laser. Both wild type and transgenic mice developed choroidal neovascularization in areas of intense laser that ruptured Bruch's membrane, but the area of neovascularization was significantly greater in transgenics. These data suggest that increased retinal expression of FGF2 is angiogenic only when it is accompanied by cell injury that overcomes sequestration control mechanisms.

Animals↗
PubMed2000

Photoreceptor-specific expression of platelet-derived growth factor-B results in traction retinal detachment.

Expression of platelet-derived growth factor (PDGF)-A and PDGF-B is increased in patients with proliferative retinopathies in which traction retinal detachments occur. Previous studies have demonstrated that increased expression of PDGF-A in the retina of transgenic mice results in retinal gliosis due to proliferation of astrocytes with different retinal phenotypes based on the time of onset and location of the PDGF-A production. In this study, we investigated the effects of PDGF-B in the retina using gain-of-function transgenic mice that express PDGF-B in photoreceptors. These mice show proliferation of astrocytes, pericytes, and, to a lesser extent, endothelial cells, resulting in ectopic cells on the surface and extending into the retina. The sheets of cells exert traction on the retina resulting in traction retinal detachments similar to those seen in humans with proliferative retinopathies. These studies suggest that PDGF-B has more dramatic effects in the retina than PDGF-A, because it acts on additional cell types, in particular on pericytes, which have a highly developed contractile apparatus. These studies in the retina suggest a means that could be used in other tissues throughout the body to achieve graded PDGF effects. They also provide a new model of traction retinal detachment that can be used to investigate new treatments for patients with proliferative retinopathies.

Animals↗
PubMed2000

Platelet-derived growth factor-A-induced retinal gliosis protects against ischemic retinopathy.

Retinal astrocytes are located in the nerve fiber layer and along retinal blood vessels and have been hypothesized to participate in the induction and maintenance of the blood-retinal barrier. Platelet-derived growth factor-A (PDGF-A) is normally produced by retinal ganglion cells and is involved in astrocyte recruitment and proliferation. We used gain-of-function transgenic mice that express PDGF-A in photoreceptors to explore the roles of PDGF-A and astrocytes in the retina. Transgene-positive mice developed glial infiltration of the inner retina and had significantly less oxygen-induced retinal vascular closure and no neovascularization compared with littermate controls, which had prominent vascular closure and neovascularization. The increased survival of endothelial cells in transgenic mice in the face of oxygen-induced down-regulation of vascular endothelial growth factor was accompanied by an increase in astrocyte-derived fibroblast growth factor-2. Therefore, PDGF-A increases retinal astrocytes, which promote the survival of endothelial cells as well as their expression of barrier characteristics.

Animals↗
PubMed2000

Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization.

Retinal vasculogenesis and ischemic retinopathies provide good model systems for study of vascular development and neovascularization (NV), respectively. Vascular endothelial cell growth factor (VEGF) has been implicated in the pathogenesis of retinal vasculogenesis and in the development of retinal NV in ischemic retinopathies. However, insulin-like growth factor-I and possibly other growth factors also participate in the development of retinal NV and intraocular injections of VEGF antagonists only partially inhibit retinal NV. One possible conclusion from these studies is that it is necessary to block other growth factors in addition to VEGF to achieve complete inhibition of retinal NV. We recently demonstrated that a partially selective kinase inhibitor, PKC412, that blocks phosphorylation by VEGF and platelet-derived growth factor (PDGF) receptors and several isoforms of protein kinase C (PKC), completely inhibits retinal NV. In this study, we have used three additional selective kinase inhibitors with different selectivity profiles to explore the signaling pathways involved in retinal NV. PTK787, a drug that blocks phosphorylation by VEGF and PDGF receptors, but not PKC, completely inhibited retinal NV in murine oxygen-induced ischemic retinopathy and partially inhibited retinal vascularization during development. CGP 57148 and CGP 53716, two drugs that block phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on retinal NV. These data and our previously published study suggest that regardless of contributions by other growth factors, VEGF signaling plays a critical role in the pathogenesis of retinal NV. Inhibition of VEGF receptor kinase activity completely blocks retinal NV and is an excellent target for treatment of proliferative diabetic retinopathy and other ischemic retinopathies.

Aging↗