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Biomedical subjects

T Kadota

Publications and source records attributed to T Kadota.

At least 19 recordsLinked to original sources

Development and aging of the cerebrum: assessment with proton MR spectroscopy.

BACKGROUND AND PURPOSE: MR spectroscopy allows the noninvasive evaluation of in vivo brain metabolites. Our purpose was to use this technique to assess metabolic alterations in the human cerebrum during growth, maturation, and aging. METHODS: Ninety normal human brains in subjects aged 4 to 88 years were examined with multivoxel proton MR spectroscopy. Spectra were obtained from specific voxels of 2.5 cm3 in the gray and white matter of the centrum semiovale. The ratios of N-acetylaspartate (NAA) to choline (Cho) were calculated to describe age-dependent alterations in cerebral metabolites. RESULTS: White matter NAA/Cho ratios showed rapid growth during the first decade and reached a maximum value in the second or early third decade, followed by a steady decline starting in the latter half of the third decade. The maximum peak ages for NAA/Cho were 21.9, 17.6, and 15.9 years (mean, 18.5 years) for the anterior, middle, and posterior white matter, respectively. A significant cerebral laterality of the white matter NAA/Cho was found in male subjects during development. The growth spurt and age-related decline of the white matter NAA/Cho were steeper in male than in female subjects. In contrast, the gray matter NAA/Cho showed a gradual decline with age. CONCLUSION: Proton MR spectroscopy shows significant regional and sex differences in the level of cerebral metabolites during the process of growth, maturation, and aging. This technique may play an important role in clinical applications for various conditions of metabolic disorders of the human brain.

Adolescent↗

Differential distribution of nerve terminals immunoreactive for substance P and cholecystokinin in the sympathetic preganglionic cell column of the filefish Stephanolepis cirrhifer.

Immunoreactivity for substance P and cholecystokinin-8 was examined in the nerve fibers in the central autonomic nucleus, a cell column for sympathetic preganglionic neurons, in the filefish Stephanolepis cirrhifer. Substance P-immunoreactive fibers were distributed throughout the entire rostrocaudal extent, but were more abundant in the caudal part of the column, where substance P-immunoreactive varicosities sometimes made contacts with the sympathetic preganglionic neurons. Cholecystokinin-8-immunoreactive fibers were found almost entirely in the rostral part of the column, where a dense network of varicosities was in close apposition to a considerable number of the sympathetic preganglionic neurons. Double labeling immunohistochemistry showed that substance P fibers and cholecystokin-8 fibers were entirely different, and distinct from serotonin-immunoreactive fibers. By using immunoelectron microscopy, synaptic specialization was sometimes observed between the dendrites of preganglionic neurons and varicosities immunoreactive for substance P and cholecystokinin-8. Substance P- and cholecystokinin-8 fibers were seen from the descending trigeminal tract, through the dorsolateral funiculus and the ventral portion of the dorsal horn, to the central autonomic nucleus. After colchicine treatment, substance P-immunoreactive perikarya were found in the cranial and spinal sensory ganglia. These results suggest that the sympathetic preganglionic neurons of the filefish receive innervation by substance P fibers and cholecystokinin fibers, and that the former might be of primary sensory origin. Topographical distribution of cholecystokinin-8-immunoreactive terminals in the central autonomic nucleus along the rostrocaudal extent might underlie the differential regulation of sympathetic activity via a distinct population of sympathetic preganglionic neurons.

Animals↗

Ultrastructure of the capillary pericytes and the expression of smooth muscle alpha-actin and desmin in the snake infrared sensory organs.

The infrared sensory membranes of pit organs of pit vipers have an extremely rich capillary vasculature that forms many vascular loops, each serving a small number of infrared nerve terminals. We clarified the ultrastructure of capillary pericytes in the pit membranes by scanning and transmission electron microscopy, and examined the immunoreactivity in their cytoplasm to two contractile proteins: smooth muscle alpha-actin (SM alpha-actin) and desmin. The capillary pericytes had two major cytoplasmic processes: thickened primary processes that radiate to embrace the endothelial tube and flattened secondary processes that are distributed widely on the endothelium. Coexpression of SM alpha-actin and desmin was observed in the pericytes of entire capillary segments, and SM alpha-actin was characterized by prominent filament bundles directed mainly at right angles to the capillary long axis. This expression pattern was different from that of capillary pericytes of the scales, where SM alpha-actin was expressed diffusely in the cytoplasm. In a series of electron microscopic sections, we often observed the pericyte processes depressing the endothelial wall. We also observed a close relationship of the pericytes with inter-endothelial cell junctions, and pericyte processes connected with the endothelial cells via gap junctions. From these findings, we surmised that capillary pericytes in the pit membrane have a close functional relationship with the endothelium, and through their contractile and relaxing activity regulate capillary bloodflow to stabilize production of infrared nerve impulses.

Actins↗

Neurotrophic factor expression after CNS viral injury produces enhanced sensitivity to psychostimulants: potential mechanism for addiction vulnerability.

Hypothesized risk factors for psychostimulant, amphetamine, and cocaine abuse include dopamine (DA) receptor polymorphisms, HIV infection, schizophrenia, drug-induced paranoias, and movement disorders; however, the molecular, cellular, and biochemical mechanisms that predispose to drug sensitivity or drive the development of addiction are incompletely understood. Using the Borna disease rat, an animal model of viral-induced encephalopathy wherein sensitivity to the locomotor and stereotypic behavioral effects of d-amphetamine and cocaine is enhanced (Solbrig et al., 1994, 1998), we identify a specific neurotrophin expression pattern triggered by striatal viral injury that increases tyrosine hydroxylase activity, an early step in DA synthesis, to produce a phenotype of enhanced amphetamine sensitivity. The reactive neurotrophin pattern provides a molecular framework for understanding how CNS viral injury, as well as other CNS adaptations producing similar growth factor activation profiles, may influence psychostimulant sensitivity.

Animals↗

Nervous control of blood flow microkinetics in the infrared organs of pit vipers.

The pit organ of pit vipers contains a membrane which serves as an infrared retina, processing infrared information by the degree to which the temperature of trigeminal nerve receptors (terminal nerve masses) is raised. The receptors are arranged in a monolayer array within the pit membrane and irrigated by a capillary network which both supplies energy to the terminal nerve masses and serves as a heat exchange mechanism. This mechanism maintains the receptors at a stable temperature level to increase or decrease their sensitivity and to reduce to a minimum the afterimage effect of a moving stimulus. We used a Doppler laser blood flow meter to measure the local changes in blood flow in response to a point heat source (a small soldering iron) and to direct stimuli (red and infrared lasers). Resection of any one of the trigeminal A-delta fiber trunks innervating the pit membrane abolished blood flow response in the area innervated, but resection of the main trunk between the primary neurons and the medulla left the response intact. In addition to the A-delta fibers the pit membrane contains autonomic and sensory C-fiber innervation, but preganglionic resection of parasympathetic neurons, and chemical blocking of postganglionic fibers with atropine and capsaicin had no influence on the blood flow changes. Therefore, on the basis of the rapid response time and the similarity of the blood flow curves to electrophysiological recordings from the receptors, we surmised that all blood flow changes were due to a vasomotor reaction, modulated by the terminal nerve masses directly, resulting in a change in local heat capacity that cools the stimulated receptors back to a basal temperature.

Animals↗

Distinct localization and target specificity of galanin-immunoreactive sympathetic preganglionic neurons of a teleost, the filefish Stephanolepis cirrhifer.

Immunoreactivity for galanin was examined in the sympathetic preganglionic neurons in the spinal cord, adrenal glands, sympathetic ganglia, and some sensory ganglia of the filefish Stephanolepis cirrhifer. Galanin-immunoreactive neurons were found only in the rostral part, but not in the caudal part of the central autonomic nucleus (a column of sympathetic preganglionic neurons of teleosts). Many galanin-immunoreactive nerve terminals were found in contact with neurons in the celiac ganglia and the cranial sympathetic ganglia on both sides of the body. Most neurons encircled by galanin-immunoreactive nerve fibers were negative for tyrosine hydroxylase. Galanin-immunoreactive nerve fibers were very sparse in the spinal sympathetic paravertebral ganglia. No galanin-immunoreactive nerve fibers were found in the adrenal glands. No sensory neurons of the trigeminal, vagal, or spinal dorsal root ganglia were positive for galanin-immunoreactivity. These results suggest that galanin-immunoreactive sympathetic preganglionic neurons have distinct segmental localization and might project specifically to a population of non-adrenergic sympathetic postganglionic neurons in the celiac and cranial sympathetic ganglia.

Animals↗

Serotonin-immunoreactive axons in the cell column of sympathetic preganglionic neurons in the spinal cord of the filefish Stephanolepis cirrhifer.

Serotonin-immunoreactive axonal components were observed in the central autonomic nucleus (CAN), a cell column of sympathetic preganglionic neurons in the rostral spinal cord of the filefish Stephanolepis cirrhifer. Serotonin-positive axonal varicosities were seen around neuronal perikarya through the whole rostrocaudal extent of the CAN, although their distribution pattern in the rostral CAN was different from that in the caudal CAN. Electron microscopically, serotonin-positive axonal varicosities were found to make axodendritic and axosomatic synapses on CAN neurons. Many serotonin-positive neuronal cell bodies were seen in the raphe nuclei in the lower brainstem, whereas only a few were found in the spinal cord. Thus most of serotoninergic axons within the CAN were considered to originate from the raphe nuclei in the lower brainstem.

Animals↗

Differential innervation of the goldfish tonic red muscles and twitch white muscles by neuropeptide-immunoreactive motoneurons.

Neuropeptides in the motor nerves innervating the red and white muscles of the goldfish Carassius auratus were examined. In the tonic red muscles, varicose nerve endings immunoreactive for both calcitonin gene-related peptide and substance P were found spread over the surface of the muscle fibers, but in the twitch white muscles only scattered nerve endings immunoreactive for calcitonin gene-related peptide were found. At the electron microscopic observation, dense electron products immunoreactive for calcitonin gene-related peptide and for substance P (SP) were detected in the motor nerve endings making synapses on the muscle fibers of the red muscles. In the spinal cord, all of the motor neurons showed immunoreactivity to calcitonin gene-related peptide, but the motor neurons immunoreactive for substance P were restricted to the ventrolateral group that has been shown to project predominantly to the red muscles. These results suggest that the motor neurons innervating the red and white muscles of the goldfish are distinct in their neuropeptide content. The present study also raises the possibility that SP might be related to the unique physiological properties of the tonic type red muscles, probably by direct binding to the acetylcholine receptors.

Animals↗

Whole-body metabolism of the organophosphorus pesticide, fenthion, in goldfish, Carassius auratus.

The in vivo metabolism of fenthion, an organophosphorus pesticide, and its sulfoxide (fenthion sulfoxide) was examined in goldfish (Carassius auratus). When goldfish were administered fenthion i.p. at a dose of 100 mg/kg, two metabolites were isolated from the tank water. They were identified as fenthion sulfoxide and fenthion oxon, in which > P = S of fenthion is transformed to > P = O, by comparing their mass and UV spectra, and their behavior in HPLC and TLC, with those of authentic standards. However, fenthion sulfone was not detected as a metabolite. The amounts of fenthion, fenthion sulfoxide and fenthion oxon excreted within 4 days were 2.7, 3.4 and 2.5%, of the initial dose of fenthion, respectively. Unchanged fenthion was detected in the body of the fish to the extent of 42-50% of the dose after 10 days, but fenthion sulfoxide and fenthion oxon showed very low concentrations. When fenthion sulfoxide was administered to the fish, about 70% of the dose was excreted unchanged into the tank water within 24 h, but little of the reduced compound, fenthion, was found. In contrast, fenthion was detected at 2.1% of dose in the body of goldfish as a metabolite of fenthion sulfoxide. The fact that fenthion is metabolized to the toxic oxon form in fish presumably has environmental and health implication for its use as a pesticide.

Animals↗

Microvasculature of crotaline snake pit organs: possible function as a heat exchange mechanism.

The infrared sensory membranes of the pit organs of pit vipers have an extremely rich capillary vasculature, which has been noted passim in the literature, but never illustrated or studied in detail. We rendered the pit vasculature visible in various ways, namely, by microinjection of India ink, by a combination of ink and succinate dehydrogenase staining, and by making resin casts for scanning electron microscope study. We also used transmission electron microscopy for identifying the types (arterioles, venules, capillaries) of blood vessels. Then we compared the pit vasculature with that of the retina and the dermis. Good visualization of the vasculature was obtained with both ink and resin injection. Arterioles, venules, and capillaries could be distinguished with all methods used. The monolayer vasculature was denser in the pit membrane than in the retina or skin. Each loop of the network enclosed a small number of infrared receptors so that all receptors were in contact with a capillary on at least one side. The forward-looking areas of the pit had a denser network than side-looking areas. Since infrared rays cause nerve impulses by raising the temperature of individual receptors, the capillary network functions not only as a supplier of energy but also as a cooling mechanism to reduce afterimages. Thus the denser network in the forward-looking areas causes these areas to be more sensitive and have better image resolution than the rest of the membrane.

Agkistrodon↗

Nitric oxide synthase in the glossopharyngeal and vagal afferent pathway of a teleost, Takifugu niphobles. The branchial vascular innervation.

To examine the presence of nitric oxide synthase (NOS) in the sensory system of the glossopharyngeal and vagus nerves of teleosts, nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) activity and immunoreactivity for NOS were examined in the puffer fish Takifugu niphobles. The nitrergic sensory neurons were located in the ganglia of both the glossopharyngeal and the vagal nerves. In the vagal ganglion, positive neurons were found in the subpopulations for the branchial rami and the coelomic visceral ramus, but not for the posterior ramus or the lateral line ramus. In the medulla, nitrergic afferent terminals were found in the glossopharyngeal lobe, the vagal lobe, and the commissural nucleus. In the gill structure, the nitrergic nerve fibers were seen in the nerve bundles running along the efferent branchial artery of all three gill arches. These fibers appeared to terminate in the proximal portion of the efferent filament arteries of three gill arches. On the other hand, autonomic neurons innervating the gill arches were unstained. These results suggest that nitrergic sensory neurons in the glossopharyngeal and vagal ganglia project their peripheral processes through the branchial rami to a specific portion of the branchial arteries, and they might play a role in baroreception of this fish. A possible role for nitric oxide (NO) in baroreception is also discussed.

Afferent Pathways↗

Gastrin/CCK-ergic innervation of cutaneous mucous gland by the supramedullary cells of the puffer fish Takifugu niphobles.

The supramedullary cells (SMCs) are spinal neurons lying at the dorsal surface of teleosts. In the present study, we examined whether the SMCs of the puffer fish (Takifugu niphobles) might express gastrin/cholecystokinin-immunoreactivity, as observed in some other teleosts. All the SMCs were immunoreactive for gastrin/cholecystokinin. On the other hand, many immunoreactive varicose nerve fibers were also found terminating in the mucous glands in the skin. In addition, immunoreactive fibers were sparsely distributed in the epidermal layer. No neuronal cells other than the SMCs showed gastrin/cholecystokinin-immunoreactivity centrally or peripherally. The results suggest that gastrin/cholecystokinin-immunoreactive axons in the cutaneous mucous glands and epidermal layer are axons of the SMCs. In view of the present findings, the possible nature of SMCs was discussed.

Animals↗

Characterization of [3H]5-hydroxytryptamine and [3H]spiperone binding sites in clathrin-coated vesicles from bovine brain.

Coated vesicles prepared from bovine brain cerebral cortex exhibited [3H]5-hydroxytryptamine (5-HT, serotonin) and [3H]spiperone binding activities. The binding activities were localized in the inner core vesicles. Binding reached an equilibrium level by 30-45 min at 30 degreesC, and was reversed by the addition of 100 microM 5-HT for [3H]5-HT binding or 10 microM ketanserin for [3H]spiperone binding. The saturation binding experiments indicated a single class of binding sites for [3H]5-HT and [3H]spiperone with apparent Kd values of 2.4 and 1.75 nM, respectively. The binding of [3H]5-HT was displaced by 5-HT and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), but not by ketanserin. The binding of [3H]spiperone was displaced by spiperone and ketanserin but not by 5-HT or 8-OH-DPAT even at 1 mM. The coated vesicles were shown by immunoblotting assay to contain alpha-subunits of GTP-binding proteins, Galphas, Galphai2, Galphai3, Galphao and Galphaq/11. Forskolin-stimulated adenylate cyclase activity in the coated vesicles was inhibited to 80% of the control level by 5-HT or 8-OH-DPAT. These results suggested that 5-HT1A and 5-HT2A receptors are present in bovine brain coated vesicles and that the 5-HT1A receptors are coupled to adenylate cyclase activity via GTP binding proteins.

Adenylyl Cyclases↗

Expression of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice.

Angiotensin type-1a (AT1a) receptor gene-knockout (AT1a-/-) mice exhibit chronic hypotension and renin overproduction. In the kidneys of AT1a-/- mice, the activity of neuronal type nitric oxide synthase (N-NOS) was histochemically detected by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry. The localization of renin was detected by immunohistochemistry and the results were analyzed morphometrically. The levels of N-NOS and renin mRNA in the renal cortical tissue were determined by reverse transcription-PCR and Northern blot analysis, respectively. In the renal sections from wild-type mice, NADPHd activity and N-NOS immunoreactivity were localized to the discrete region of the macula densa in contact with the parent glomerulus. In contrast, N-NOS-positive macula densa cells were distributed beyond the original location of the macula densa, occasionally extending to the opposite side of the distal tubules. The mean number of N-NOS positive macula densa cells was significantly increased in AT1a-/- mice (186 per 100 glomeruli) compared with wild-type mice (65 per 100 glomeruli). AT1a-/- mice showed 1.4-times higher N-NOS mRNA levels in the renal cortical tissues than wild-type mice. The plasma renin activity was significantly higher in AT1a-/- mice (205.5 +/- 26.1 ng/ml/hr) than in wild-type mice (8.0 +/- 0.2 ng/ml/hr). The renin-positive areas per glomerulus and renal renin gene expression were 12-times and 2.6-times higher in AT1a-/- mice than in wild-type mice, respectively. These abnormalities, however, were less remarkable in AT1a-/- mice compared with angiotensinogen-knockout mice. When AT1a-/- mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively-stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. Dietary salt loading produced a parallel decrease in plasma renin activity, renal renin-immunoreactive areas, and the levels of renin mRNA without affecting systemic blood pressure. These results provide evidence for the possible involvement of N-NOS at the macula densa in the increased renin production in AT1a-/- mice.

Angiotensin I↗

Malignant glioma. Evaluation with 3D time-of-flight MR angiography.

PURPOSE: To investigate the clinical utility of 3D time-of-flight (TOF) MR angiography (MRA) in the evaluation of pathological vessels in patients with malignant glioma. MATERIAL AND METHODS: Sixteen patients with malignant glioma (12 with glioblastoma multiforme and 4 with anaplastic astrocytoma) were examined with 3D TOF MRA before and after the injection of gadopentetate dimeglumine. The 3D TOF MRA study was compared with conventional angiography in all patients. RESULTS: The unenhanced 3D TOF MRAs successfully depicted the feeding arteries in 9 patients but failed to depict small feeding arteries in 2 patients in whom these arteries were shown by conventional angiography. The enhanced MRAs demonstrated draining veins from the lesions in 8 patients but failed to depict a draining vein in 1 patient that was shown by conventional angiography. The stereoscopic view projection effectively depicted displacements of the major cerebral arteries in 14 patients, and deep venous structures in 11 patients which almost accorded with the findings at conventional angiography. CONCLUSION: Our results indicate that 3D TOF MRA can provide an accurate visualization of pathological vascular structures and thus help establish a diagnosis in patients with malignant glioma.

Adult↗

Dietary salt loading decreases the expressions of neuronal-type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensinogen gene-knockout mice.

The present study investigates whether neuronal type nitric oxide synthase (N-NOS) in the macula densa participates in the regulation of renal renin expression during altered dietary salt intake in angiotensinogen gene-knockout (Atg-/-) mice. Wild-type (Atg+/+) and Atg+/+ mice were fed a low-salt (0.04% NaCl), normal-salt (0.3% NaCl), or high-salt (4% NaCl) diet for 2 wk. Histochemical staining for NADPH diaphorase (NADPHd) and renin were analyzed morphometrically. Levels of N-NOS and renin mRNA in renal cortical tissues were determined by reverse transcription-PCR and Northern blot analysis, respectively. In animals fed a normal-salt diet, the renal expressions of N-NOS and renin were markedly increased in Atg-/- mice compared with Atg+/+ mice. When mutant mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. These changes were paralleled by decreases in renal renin-immunoreactive areas and the levels of renin mRNA. On the other hand, salt restriction did not produce further significant increases in the renal N-NOS and renin expressions in mutant mice, whereas a parallel inverse relationship was observed between these enzyme expressions and the levels of salt intake in wild-type mice. These results suggest that the N-NOS expression in the macula densa is inversely regulated by salt intake and that the enzyme activity is functionally linked to renal renin production. Salt-modulated renal N-NOS and renin expressions are independent on angiotensin formation in Atg-/- mice.

Animals↗

[Intraarterial chemotherapy using a combination of etoposide and cisplatin for recurrent malignant lymphoma].

Superselective intraarterial infusion of etoposide and cisplatin was performed in 2 patients with recurrent malignant lymphoma which had progressed after operation, radiotherapy and chemotherapy with various anticancer agents. The tip of a microcatheter (Tracker-18) was placed in the left posterior cerebral artery in the first patient with the recurrent tumor located in the left occipital lobe and at the basilar top in the second patient with the recurrent tumor extending from the right thalamus to the pons. Etoposide (60 mg) and Cisplatin (60 mg) were each infused for 1 hour safely with a combination of intermittent infusion of nicardipine and papaverine chloride. The tumor disappeared completely after 2 courses of intraarterial chemotherapy in the first patient and after 1 course in the second patient. Intraarterial chemotherapy using a combination of etoposide and cisplatin was performed safely and showed good results.

Aged↗

NADPH-diaphorase activity in the vagal afferent pathway of the dogfish, Triakis scyllia.

Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was examined in the cranial sensory ganglia and brainstem of the banded dogfish, Triakis scyllia. Positive neurons were found in the vagal sensory ganglion projecting to the coelomic organs, but not in those projecting to the gills or the lateral line organs. Nerve terminals in the vagal lobe were also positive. No positive neurons were found in the glossopharyngeal, facial, or trigeminal sensory ganglia. These results suggest that use of nitric oxide in the vagal sensory transmission from the coelomic organs may have been maintained in the evolutionary process from fish to mammals.

Afferent Pathways↗