Biomedical subjects

I Tooyama

Publications and source records attributed to I Tooyama.

At least 91 records · Page 5Linked to original sources

PubMed1993

Morphological diversities of CD44 positive astrocytes in the cerebral cortex of normal subjects and patients with Alzheimer's disease.

The localization of CD44 was investigated immunohistochemically in postmortem human brain tissue of control subjects and patients with Alzheimer's disease. CD44 is a multifunctional cell surface glycoprotein that serves as a receptor for hyaluronic acid, collagen types I and VI, and mucosal vascular addressin. In gray matter, it was found to be associated with some astrocytes of both protoplasmic and fibrous morphology. These positively stained astrocytes were most frequently observed in association with blood vessels, and had morphologies that were highly comparable to those described with the Golgi technique. Double immunostaining for CD44 and glial fibrillary acidic protein (GFAP) revealed that a significant number of these astrocytes were positive for both antigens. However, GFAP staining was mostly confined to the cell somata and proximal processes, while CD44 staining extended to a rich and extensive array of processes. Occasional CD44 positive cells of spherical morphology with a few thin varicose processes were observed. Their processes formed thick terminations on blood vessels, suggesting that these cells are a special class of astrocyte. In Alzheimer's disease brain, the number of CD44 positive astrocytes increased dramatically. These data suggest that astrocytes have very extensive branching patterns, which are reflected by CD44 staining patterns. CD44 may be an important adhesion molecule for these astrocytic processes.

Adult↗

PubMed1993

[d-Ala2]deltorphin I-like immunoreactivity in the adult rat brain: immunohistochemical localization.

Using a specific antiserum recently raised against [D-Ala2]deltorphin I (DADTI: Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2), a highly selective ligand for delta-opioid receptors, we have previously demonstrated the occurrence of positive immunostaining in several structures of mouse brain. We describe here the neuroanatomical distribution patterns of DADTI-immunoreactive neuronal bodies, axons, and tanycytes in rat brain. Positive neuronal somata were localized mainly in the ventral mesencephalon, including the ventral tegmental area and the pars compacta of the substantia nigra. A minor population of positive somata was found in the pars reticulata and pars lateralis of the substantia nigra, raphe nuclei, supramammillary nucleus, and retrorubral reticular nucleus. All these regions, except for the supramammillary nucleus, contain dopamine cell bodies. Intensely stained positive nerve fibers could be traced along the medial forebrain bundle. Dense positive terminals were seen in the neostriatum, nucleus accumbens shell, olfactory tubercle, septal areas, cingulate, and medial prefrontal cortex. Double-immunostaining study revealed that, in the substantia nigra, almost all (97.8%) DADTI-positive neurons colocalized with tyrosine hydroxylase (TH), and the doubly stained cells occupied about one-third (29.1%) of the total population of TH-positive neurons. Only a few DADTI/TH-positive cells also stained for 28-kDa calbindin D, although many neurons double-stained for 28-kDa calbindin D and TH. In contrast, the supramammillary nucleus contained a number of DADTI-positive cells, which nearly always stained positively for 28-kDa calbindin D but did not stain for TH. The association of DADTI-like immunoreactivity with certain dopaminergic pathways seems of particular interest. A small population of DADTI-immunostained tanycytes was present in the ventral part of the third ventricle wall.

Amino Acid Sequence↗

PubMed1993

Autoradiographic study on [3H]-[D-Ala2]-deltorphin-I binding sites in the rat brain.

Previous biochemical and pharmacological studies have shown that [D-Ala2]-deltorphin-I (DADTI) has a high affinity and selectivity for delta-opioid receptors. In this study, designed to provide morphological details, the distribution of DADTI binding sites was examined by autoradiography on coronal, sagittal and horizontal frozen sections of adult rat brain. The sections were incubated with tritiated DADTI solution and exposed for 12 weeks to a 3H-sensitive film. DADTI labelling clearly demonstrated selective and high affinity binding sites of delta-opioid type in several brain regions, including olfactory system, neostriatum, nucleus accumbens, and cortical layers I-II and V-VI.

Animals↗

PubMed1993

Acidic and basic fibroblast growth factor-like immunoreactivity in the striatum and midbrain in Huntington's disease.

The immunohistochemical localizations of acidic and basic fibroblast growth factor (aFGF and bFGF) were investigated in the striatum and midbrain of Huntington's disease (HD) and control cases using specific antibodies. In the striatum of control cases, the ependymal cell layer was stained for aFGF and bFGF. In addition, a few subependymal astrocytes were positive for aFGF, and some neurons stained weakly for bFGF. In HD striatum, many astrocytes and remaining neurons were strongly stained for aFGF. aFGF-positive astrocytes were particularly conspicuous in the subependymal region of the caudate but appeared throughout the caudate and putamen. The number of bFGF-positive astrocytes was slightly increased. In contrast to the caudate/putamen, the globus pallidus, nucleus of the oculomotor nerve and substantia nigra showed very similar patterns for both aFGF and bFGF in control and most HD brains. Reports that FGF can protect against glutamate neurotoxicity, and that the FGF receptor (FGFR3), with its gene located in the HD region on chromosome 4, appears in striatal neurons, make it tempting to speculate on a possibly important role for FGF-FGFR3 interactions in HD pathology.

Adult↗

PubMed1993

High-dose ketamine does not induce c-Fos protein expression in rat hippocampus.

The effects of high-dose ketamine on the c-fos protein (c-Fos) expression were investigated in rat by an immunohistochemical technique. The administration of 100 mg/kg ketamine i.p. induced seizure-like activity (limbic seizure). No c-Fos immunoreactivity was observed in hippocampus, piriform cortex and amygdala, while it was observed in neocortex and thalamus. These findings disagree with the reports that ketamine depresses the neuronal function of the neocortex and thalamus, while it stimulates the limbic system.

Amygdala↗

PubMed1993

Human positron emission tomographic [18F]fluorodopa studies correlate with dopamine cell counts and levels.

Postmortem counts of dopaminergic cell densities in the substantia nigra (5 subjects) and striatal levels of dopamine (DA) and its metabolites (6 subjects) were determined on 1 parkinsonian (PD), 3 progressive supranuclear palsy (PSP), 1 amyotrophic lateral sclerosis, and 1 Alzheimer's case who had been positron emission tomography scanned with 6-[18F]fluorodopa during life. [18F]Fluorodopa uptake rate constants, which presumably depend on the number of functioning striatal DA terminals, were strictly proportional to cell densities (significant correlation with zero intercept) and also correlated significantly with striatal DA levels but with an intercept indicating greater losses of DA than of terminals in PSP and PD. Postmortem data on 6 PD, 1 PSP, and 9 neuronally normal controls substantiated the significant correlation between cell counts and DA levels, with the latter being the more depressed in pathological cases.

Adult↗

PubMed1993

Microglia in degenerative neurological disease.

Microglia express many leukocyte surface antigens which are upregulated in such chronic degenerative neurological diseases as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). These surface antigens include leukocyte common antigen, immunoglobulin Fc receptors, MHC class I and class II glycoproteins, beta 2-integrins, and the vitronectin receptor. Ligands for these receptors are also found. They include immunoglobulins, complement proteins of the classical pathway, T lymphocytes of the cytotoxic/suppressor and helper/inducer classes, and vitronectin. T lymphocytes marginate along capillary venules, with some penetrating into the tissue matrix. Immunoglobulins and complement proteins are synthesized locally in brain, although they may also come from the bloodstream if the blood-brain barrier is compromised. The membrane attack complex, which is formed from C5b-9, the terminal components of complement, has been identified in AD and multiple sclerosis brain tissue. In addition, proteins designed to defend against bystander lysis caused by the membrane attack complex, including protectin, C8 binding protein, clusterin, and vitronectin, are associated with damaged neuronal processes in AD. Autodestruction may play a prominent part in these 2 diseases.

Antigens, Surface↗

PubMed1993

Distribution of taurine-like immunoreactivity in the mouse liver during ontogeny and after carbon tetrachloride or phenobarbital intoxication.

The ontogenic pattern of development of taurine-like immunoreactivity (TLI) was studied in the mouse liver. The effect on adult mice of carbon tetrachloride or phenobarbital treatment was also examined. Light-microscopically, granules of TLI were first found in the liver from 17-day-old embryos, diffusely distributed throughout the lobules. These positive granules increased with age, were most numerous in the two-week-old mouse, and were notably decreased in the central region of some lobules in the three-week-old mouse. In mature mice, hepatocytes containing TLI-positive granules were distributed unevenly in each liver lobule, and were located predominantly in the peripheral region. Electron-microscopically, TLI was observed in small vesicles in the cytoplasm of hepatocytes and was found mainly in the cisternal lumen of smooth-surfaced endoplasmic reticulum. Some taurine-positive vesicles surrounding the reticulum seemed to associate with the protoplasm. Similar positive vesicles were often located near the bile canaliculi. In carbon tetrachloride-intoxicated mature mice, TLI was no longer limited to the peripheral region of lobules; hepatocytes situated in the central region of lobules also contained intense TLI. In mice injected with a small and repeated dose of phenobarbital, the distribution pattern of TLI was similar to that in the untreated group. However, in mice injected with a large dose of phenobarbital, TLI was markedly increased, especially in the central region of lobules. The results demonstrate that the distribution pattern of TLI in mouse liver changes during development, and that the pattern in mature mice is affected by intoxication with carbon tetrachloride or a toxic dose of phenobarbital.

Animals↗

PubMed1993

Columnar arrangement of beta-amyloid protein deposits in the cerebral cortex of patients with Alzheimer's disease.

The spatial pattern of beta-amyloid protein (BAP) deposits in Alzheimer's disease cerebral cortex was investigated. In cortical areas where the accumulation of BAP was relatively sparse, the deposits tended to accumulate vertically in a columnar arrangement. Typically, these aggregates consisted of both consolidated and diffuse deposits approximately 200 to 600 microns in width. Blood vessels running perpendicularly to the pial surface were sometimes observed penetrating the center of these columns, but this was not a consistent finding. These BAP extracellular aggregates might be related to the columnar organization of the cerebral cortex.

Aged↗

PubMed1993

Expression of intercellular adhesion molecule (ICAM)-1 by a subset of astrocytes in Alzheimer disease and some other degenerative neurological disorders.

Intercellular adhesion molecule-1 (ICAM-1) was localized immunohistochemically in postmortem brain tissue of Alzheimer's disease (AD), progressive supranuclear palsy, amyotrophic lateral sclerosis, Pick's disease, and controls. In controls, only capillaries were stained for ICAM-1. In affected areas of neurologically diseased brains, a subset of reactive astrocytes was also strongly stained. In addition, there were irregular, diffuse patches of positive staining in the tissue matrix. In AD, many of these patches had dense cores which corresponded with senile plaques. Double immunostaining for glial fibrillary acidic protein and ICAM-1 indicated that some reactive astrocytes at the periphery of senile plaques were positive for ICAM-1. Within such plaques, microglial aggregates were stained intensely for leukocyte function-associated antigen-1 (LFA-1), the adhesion molecule for ICAM-1. The LFA-1/ICAM-1 system appears to play an important role in the interaction of astrocytes and microglia in several neurological diseases.

Alzheimer Disease↗

PubMed1993

Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson's disease.

Basic fibroblast growth factor (bFGF) has a neurotrophic effect on mesencephalic dopaminergic neurons in vitro and in vivo. To explore whether an abnormality in bFGF expression occurs in Parkinson's disease (PD), we examined the substantia nigra (SN) of six PD and eight control cases immunohistochemically using a monoclonal antibody to bFGF. The mean number of melanin-positive neurons in sections of PD SN was 30.3% of the control mean, but the number of bFGF-immunopositive neurons was only 4.7% of the control mean. bFGF-immunoreactivity was present in only 8.2% of PD, but in 93.7% of control melanin-positive neurons. These results suggest a profound depletion of bFGF in surviving dopaminergic neurons of the SN in PD, and this depletion may be related to the disease process.

Adult↗

PubMed1993

[Fibroblast growth factors (FGFs) in neurodegenerative disorders].

Fibroblast growth factors (FGFs) are a family consisting of at least seven members, and the FGF family will continue to expand. The best studied members of this family are acidic and basic FGF (aFGF and bFGF). They are richly concentrated in brain, and have potent trophic effects for neurons and glia. I now report that expressions of aFGF and bFGF are altered in several neurodegenerative disorders such as Alzheimer disease (AD), Huntington disease (HD) and Parkinson disease (PD). In AD aFGF was upregulated in reactive astrocytes in severely affected areas. The bFGF-positive astrocytes were also increased. In addition, bFGF was detected in senile plaques, neurofibrillary tangles and neuropil threads. In AD, aFGF and bFGF showed a similar alteration pattern. A large number of aFGF- or bFGF-positive astrocytes were observed in the striatum. Some remaining neurons were strongly stained for aFGF or bFGF. In PD, marked loss of bFGF was observed on midbrain dopaminergic neurons, The depletion of bFGF preceded the loss of tyrosine hydroxylase. Since bFGF has a potent trophic effect on midbrain dopaminergic neurons, this depletion may be related to the disease process.

Alzheimer Disease↗

PubMed1993

Lactotransferrin immunocytochemistry in Alzheimer and normal human brain.

Lactotransferrin (LF) expression was investigated immunocytochemically in postmortem brain tissues of normal controls and patients with Alzheimer's disease (AD). The antibody to LF stained some neurons weakly in young adult brains, but it stained many neurons as well as the glia of all types in elderly brains. LF expression was greatly up-regulated in both neurons and glia in affected AD tissue. It was very strongly associated with such extracellular pathological entities as diffuse and consolidated amyloid deposits and extracellular neurofibrillary tangles. In addition, it was identified in a minority of intracellular neurofibrillary tangles, neuropil threads, and degenerative neurites. LF is an iron scavenger and a complement inhibitor. Up-regulation may be a defense mechanism in AD-affected brain tissue.

Adolescent↗

PubMed1992

High molecular weight basic fibroblast growth factor-like protein is localized to a subpopulation of mesencephalic dopaminergic neurons in the rat brain.

A rabbit antiserum (R917) was raised to a purified fraction of bovine brain basic fibroblast growth factor (bFGF). On Western blots of rat midbrain extract, the antiserum did not recognize low molecular weight forms of bFGF. Instead, it recognized a single band of 27-28 kDa. Immunohistochemically, the antiserum preferentially stained a subpopulation of calbindin-negative mesencephalic dopaminergic neurons. The positive somata were mainly packed in a ventral portion of the tegmentum including the A10 region, the ventral tegmental area and the pars compacta of the medial substantia nigra, but were also scattered in both the pars compacta and reticulata portions of the lateral substantia nigra. Processes of dendrites and axons were clearly visible. Terminal fields were located in striosomes, the dorsolateral rim of the neostriatum, the anterodorsal aspect of the nucleus accumbens shell, the infralimbic cortex, and the medial prefrontal cortex. These results suggest that trophic specialization in subpopulations may occur in all three of these dopaminergic projection systems, i.e. the nigrostriatal, mesolimbic and mesocortical pathways.

Animals↗

PubMed1992

Immunohistochemical study of A2B5-positive ganglioside in postmortem human brain tissue of Alzheimer disease, amyotrophic lateral sclerosis, progressive supranuclear palsy and control cases.

Localization of gangliosides positively stained by the monoclonal antibody A2B5 was investigated in postmortem brain tissue of Alzheimer disease, amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP) and control cases. In control cases, A2B5-staining was granular, appearing in selective neuronal populations. In the neocortex, the A2B5-positive neurons were distributed mainly in deep cortical layers. In the cerebellum, A2B5-positive structures were detected in processes extending from the Purkinje cell layer into the molecular layer. In Alzheimer cases, many neurofibrillary tangles, neuropil threads and dystrophic neurites were strongly A2B5-positive. In addition, aggregations of A2B5-positive granules were detected in some neurons lacking neurofibrillary tangles. Alterations of A2B5-positive gangliosides were also detected in ALS and PSP cases. In ALS cases, A2B5-positive granules were aggregated in Betz cells of the precentral gyrus. In PSP cases, globose-type neurofibrillary tangles were also strongly A2B5-positive. The results indicate that A2B5-positive gangliosides are widely but selectively distributed in human brain and may be involved in several neuropathological processes.

Aged↗

PubMed1992

A new brain glucosensor and its physiological significance.

The concentration of fibroblast growth factor (FGF), which is found in cerebrospinal fluid (CSF), markedly increases after the start of feeding. Food intake was dose-dependently suppressed by picomole doses of FGF and facilitated by anti-FGF antibody. This suppression was caused by activation of protein kinase C in glucose-sensitive neurons in the lateral hypothalamus. In situ hybridization by use of cDNA showed that acidic (a)FGF was produced in ependymal cells. The ependymal cells released aFGF by responding to glucose increase in CSF after feeding. Released aFGF diffused into the brain parenchyma and was taken by neurons. Passive avoidance was significantly more reliable after aFGF infusion into CSF. Clamping cerebral arteries in the gerbil induced ischemia, which damaged neurons in the CA1 layer of the hippocampus. Pretreatment with aFGF prevented this damage. Thus, aFGF is not only the most potent substance yet found for the suppression of feeding, but it is also extremely effective as a neurotrophic and memory facilitating substance.

Animals↗

PubMed1992

Production of antiserum to [D-Ala2]deltorphin I and its immunohistochemical application to the mouse brain.

Antiserum to haptenic [D-Ala2]deltorphin I (DADTI: Tyr-D-Ala-Phe-Asp-Val-Val-Gly.NH2), a highly selective ligand for delta opioid receptors, was produced in rabbits. By immunospot assay, the antiserum recognized 62.5 pmol DADTI but failed to react even with 4 nmol carrier protein of the immunogen. Although the antiserum reacted equally with an isomer [L-Ala2]deltorphin I, virtually no cross-reaction occurred with other analogues such as [D-Ala2]deltorphin II (Tyr-D-Ala-Phe-Glu-Val-Val-Gly.NH2) and similar peptides lacking the C-terminal glycine amide. Therefore, the major epitope for immunorecognition appeared to be in the C-terminal region which is known to be the specific domain for delta opioid receptor selectivity. Immunohistochemical study using this antiserum revealed positive neuronal structures in some specific systems of the mouse brain.

Amino Acid Sequence↗

PubMed1991

Time course of in vitro expression of NADPH-diaphorase in cultured rat brain neurons: comparison with in vivo expression.

The time course of NADPH-diaphorase expression was examined in primary cultures of rat central nervous system and in embryonic or neonatal rat brains using a histochemical method. In cerebral and brainstem cultures from 17-day-old embryonic rats, neuronal cells moderately expressing NADPH-diaphorase were first detected on about the 5th to 7th day of culturing. Both the density of positive cells and the staining intensity increased with age of cultures. The density of positive cells, calculated as a percent of the total number of cells, increased up to day 21 in cultures from both the cerebrum and the brainstem, indicating that NADPH-diaphorase is preferentially expressed in neurons with longer viability. On the other hand, virtually no intensely positive cells were detectable in cerebellar cultures at any period examined up to 21 days. In the in vivo study, moderately stained NADPH-diaphorase-positive neurons were first detected, mainly in the laterodorsal-pedunculopontine tegmental nuclei complex and partly in the striatum, in 16-day-old embryonic rat brain. At 2 days postnatal, intensely stained neurons were detectable in the cerebral cortex as well as in the tegmental nuclei complex and the striatum, indicating some delay in the in vitro, as compared to the in vivo, expression of neuronal NADPH-diaphorase.

Animals↗