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Biomedical subjects

H Hirata

Publications and source records attributed to H Hirata.

At least 109 records · Page 6Linked to original sources

Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

Animals↗

Long-term time course of regional changes in cholinergic indices following transient ischemia in the spontaneously hypertensive rat brain.

Using an animal model of forebrain ischemia in spontaneously hypertensive rats (SHR) by 3-h bilateral carotid occlusion, and various indices of the cerebral cholinergic system were assessed for periods up to 24 weeks. The lesions observed histologically in the hippocampus of SHR 2 weeks after ischemia were less severe than those in the frontal cortex. Marked elevation of acetylcholine concentration was transiently observed in the frontal cortex, hippocampus and thalamus + midbrain at 2 weeks, and in the striatum at 1-4 weeks after ischemia. Choline acetyltransferase activity remained unchanged in all regions throughout the experimental period except for a minimal decrease in the frontal cortex at 4 weeks. Choline esterase (ChE) activity was slightly decreased in the frontal cortex at 2-4 weeks after ischemia but recovered by 8 weeks. A decrease in the hippocampus was seen at 8 weeks. The B(max) for the M1-receptor was significantly reduced by 2 weeks in the frontal cortex and by 4 weeks in the hippocampus. Low B(max) values in both regions persisted through week 24. These delayed hippocampal changes in the ChE activity and M1-receptor in SHR were similar to those of the very much delayed changes in M1-receptor previously reported in the gerbil model for transient ischemia. In contrast, Wistar-Kyoto rats (WKY), used as normotensive controls, exhibited no histological or biochemical changes for up to 24 weeks. The difference between SHR and WKY may depend on the more severe cerebral blood flow depletion during carotid ligation in the former. The chronic state of SHR after the transient ischemia may be a useful pathophysiological model for human cerebral infarctions with hypertension.

Acetylcholine↗

Congenital triggering of the index finger at the A2 pulley.

A case of trigger index finger is reported. The diagnosis was made in the neonatal intensive care unit. The proximal interphalangeal joint (PIP) was locked in a flexed position. A nodular thickening of the flexor tendon was felt at the A2 pulley level. Surgery revealed thickening of both the A2 pulley and the radial slip of the flexor superficialis tendon. Division of the A2 pulley released the PIP joint locking.

Finger Joint↗

A case of primary localized amyloidosis of the penile urethra.

Primary localized amyloidosis of the penile urethra is rare. We report a case in which the urethra was obstructed by amyloid tissue without evidence of systemic amyloidosis. After urethral dilatation, the patient reported a markedly improved urinary stream with minimal dysuria.

Aged↗

Inhibitory effect of an intellectual task on breathing after voluntary hyperventilation.

We investigated the effects of an intellectual task on posthyperventilation (PHV) breathing by using a video game. Eight normal subjects were placed in a supine positions. The game task by itself led to increase ventilation compared with the control tasks via an increase in the average inspiratory flow rate (P < 0.01) and the respiratory frequency (P < 0.001). After hypocapnic voluntary hyperventilation (VHV), the task led to a decrease in the 1-min PHV breathing level compared with the control tasks after VHV [after VHV, first 60 s average minute ventilation while watching television and while playing a video game are 5.54 +/- 2.91 (SD) and 2.05 +/- 1.40 l/min, respectively; P < 0.01]. Only one subject showed PHV apnea for at least 10 s during the control protocol, whereas seven of the same eight subjects showed PHV apnea while performing the task. After isocapnic VHV, the task still led to a decrease in PHV breathing compared with the control tasks. However, this decrease was smaller than in the hypocapnic studies and was only significant during the first 15 s of recovery. These results suggest that increased activity in the higher centers of the central nervous system has an inhibitory effect on PHV breathing at a time when the effects of short-term potentiation after VHV, hypocapnia, and perhaps other mechanisms would be expected to be acting on breathing.

Adult↗

Decreased aqueous-flare reaction to repeated applications of prostaglandin E2 to the cornea in pigmented rabbits.

To evaluate the effect of single or repeated topical applications of prostaglandin E2 (PGE2) to the cornea on the blood-aqueous barrier, we have measured the extent of flare in the anterior chamber of rabbit eyes at various time intervals. PGE2 was applied to the cornea for 4 min with the use of a glass cylinder in pigmented rabbits. Aqueous flare was measured by a laser flare cell meter. The flare intensity following the second application of 25 or 50 micrograms/ml of PGE2 was smaller than that following the first application. When 50 micrograms/ml of PGE2 was applied every day for 6 days, the flare intensity decreased significantly day by day. After consecutive applications of 10 micrograms/ml of PGE2 at hourly intervals, flare intensity increased up to 3 h, remained elevated from 3 to 5 h, and decreased thereafter. Repeated applications of 10 micrograms/ml of PGE2, every hour for 14 h every Monday, significantly decreased flare intensity week by week. Weekly applications of 50 micrograms/ml of PGE2 did not change flare intensity. This study indicates that the extent of the breakdown of the blood-aqueous barrier in the rabbit eye, as measured by the development of flare in the anterior chamber, is reduced with repeated PGE2 application.

Administration, Topical↗

Disappearance of differences in nutrient intake across two local cultures in Japan: a comparison between Tokyo and Kyoto.

Nutritional survey was conducted in a winter season of 1992 3 by collecting seventy-one 24-hour food duplicate samples from three groups of middle-aged women (22 to 25 subjects per group) in traditional residential areas in the cities of Tokyo (two groups) and Kyoto (one group), two cultural centers in Japan known to have different food customs. The analysis in terms of intake of nutrients such as energy, carbohydrate, protein, lipid, minerals, vitamins and fibers did not show significant difference among the three groups studied. Sodium chloride intake also did not differ. Daily consumption of food materials (evaluated as classified in terms of, e.g., cereals, meat, fish and vegetables) was similar. Relative weight of three meals and snacks in energy intake did not vary among the groups. Consumption of milk and bread as indicators of intake of non-traditional food was also comparable among the groups. The observation as a whole suggests that the different food custom once known to be present between the two local cultures is no longer detectable. Nationwide extensive transport of food materials is discussed as one of possible causes.

Animals↗

Effects of efonidipine, nicardipine and captopril on proteinuria in aged spontaneously hypertensive rats.

Previous studies have shown that antihypertensive drugs attenuate the progression of proteinuria by their treatments from young age, but few have examined their effects on impaired renal function in older age. In the present study the calcium antagonists efonidipine ((+/-)-2-[benzyl (phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3, 2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxyla te hydrochloride ethanol, CAS 111011-76-8, NZ-105) and nicardipine, and an angiotensin-converting enzyme inhibitor, captopril, were examined for their effects on heavy proteinuria in aged spontaneously hypertensive rats (SHR). Efonidipine (20 mg/kg), nicardipine (20 mg/kg) and captopril (30 mg/kg) were orally administered once a day for 4 weeks. The urinary protein excretion (UproE) increased with age (54.9 mg/kg/day at 24 weeks of age to 170.8 mg/kg/day at 36 weeks). The increased UproE was significantly suppressed by daily administration of efonidipine or captopril as compared to that in the non drug treated control group. The UproE in the nicardipine group was maintained at a slightly lower level than in the control. The histological examination showed that the damages of the kidneys were slightly suppressed by efonidipine and captopril. These findings indicate that efonidipine as well as captopril reduce proteinuria in aged SHR and the effect was stronger than that of nicardipine. This beneficial effect of efonidipine on proteinuria suggests its usefulness in antihypertensive therapy.

Aging↗

Evidence for corticotropin-releasing hormone projections from Barrington's nucleus to the periaqueductal gray and dorsal motor nucleus of the vagus in the rat.

The present study used anterograde and retrograde tract tracing and immunohistochemistry to determine the efferent projections of corticotropin-releasing hormone (CRH) neurons of Barrington's nucleus in the rat. Injections of Phaseolus vulgaris-leucoagglutinin into Barrington's nucleus resulted in anterograde labeling in the dorsal motor nucleus of the vagus, periaqueductal gray, medial thalamic nuclei, lateral hypothalamus, paraventricular nucleus of the hypothalamus, lateral preoptic area, and lateral septum. The retrograde tract tracer, fluorogold, injected into the lumbosacral spinal cord labeled many, but not all, CRH-immunoreactive neurons in Barrington's nucleus. Moreover, some Barrington's neurons that were retrogradely labeled from the spinal cord were not CRH-immunoreactive. Several CRH-immunoreactive Barrington's neurons were retrogradely labeled by fluorogold injections into the periaqueductal gray, and these were located predominantly in the dorsal part of the nucleus. Additionally, some CRH-immunoreactive Barrington's neurons were retrogradely labeled from fluorogold injections into the dorsal motor nucleus of the vagus. In contrast, fluorogold injections into the lateral hypothalamus, lateral preoptic area, or lateral septum did not result in double labeling of CRH-immunoreactive neurons in Barrington's nucleus. These results suggest that many, but not all, CRH-containing neurons of Barrington's nucleus project to the lumbosacral spinal cord. In addition to their previously documented projections to the spinal cord, these neurons may be a source of CRH in the periaqueductal gray and dorsal motor nucleus of the vagus. CRH projections of Barrington's nucleus may play a role in behavioral or autonomic aspects of stress responses, in addition to their proposed role in micturition.

Animals↗

A novel insertion sequence (IS)-like element of the thermophilic bacterium PS3 promotes expression of the alanine carrier protein-encoding gene.

A novel insertion sequence (IS)-like element was found in the 5'-upstream region of the alanine carrier protein-encoding gene (acp) in the thermophilic bacterium PS3 chromosomal DNA. The sequence contained an open reading frame (ORF) encoding a polypeptide of 369 amino acids which revealed high similarity with ORFs from IS891 from the cyanobacterium Anabaena and IS1136 from Saccharopolyspora erythraea. The direction of transcription was the same as that of acp, and typical inverted and direct repeats characteristic of IS were found in both the 5' and 3' region of the ORF. Southern hybridization analysis of the chromosomal DNA revealed that multiple copies of the ORF sequence were contained in the PS3 genome. This element might well be a member of a new IS family including IS891 and IS1136, and we have designated this element IS1341. The analysis of acp expression in Escherichia coli cells indicated that IS1341 promotes the expression of acp.

Amino Acid Sequence↗

Methamphetamine-induced serotonin neurotoxicity is mediated by superoxide radicals.

Methamphetamine (METH) causes deleterious effects in brain monoaminergic systems. Evidence has accumulated to suggest that these effects may be mediated via the overproduction of the superoxide radicals. We have recently shown that METH-induced dopamine (DA) depletion is attenuated in copper-zinc superoxide dismutase (CuZnSOD) transgenic (Tg) mice. In the present study, we have used receptor autoradiographic studies of [125I]RTI-55 labeled serotonin (5-HT) uptake sites to evaluate the effect of a two dosing schedule (5 mg/kg or 10 mg/kg x 4) of METH on striatal 5-HT uptake sites in nontransgenic (Non-Tg), heterozygous (Hetero) and homozygous (Homo) SOD-Tg mice. The low dose caused no significant changes in striatal 5-HT uptake sites in any of the groups. The high dose caused marked decreases (-74%) in striatal 5-HT uptake sites in Non-Tg mice. In contrast, 5-HT uptake sites showed only a 31% decrease in homozygous SOD-Tg mice whereas heterozygous SOD-Tg mice showed 63% depletion. These results show that increased SOD activity can protect against METH-induced neurotoxicity in striatal serotonergic terminals. These data provide further evidence for a role of oxidative stress in the neurotoxic effects of METH.

Animals↗

Complete primary structure and phosphorylation site of the 65-kDa macrophage protein phosphorylated by stimulation with bacterial lipopolysaccharide.

There is ample evidence that intracellular protein phosphorylation is a mandatory event in the process of macrophage activation by LPS, yet how this event is initiated and what roles the phosphorylated proteins are assigned to are poorly understood. We previously isolated a 65-kDa cytosolic protein (pp65) that was phosphorylated specifically in LPS-stimulated murine macrophages. In the present study, the complete primary structure of pp65 was determined on the basis of the cDNA containing an open reading frame of 1881 bases. The sequence of pp65 revealed that it is a murine homologue of human L-plastin, recently identified as a novel transformation-induced polypeptide of neoplastic human cells, and that it contains a unique series of Ca2+, calmodulin, and actin binding domains. A single phosphorylated peptide was isolated from the tryptic digest of pp65 by reverse-phase HPLC. From the amino acid sequence of the dodecapeptide Gly-Ser-Val-Ser-Asp-Glu-Glu-Met-Met-Glu-Leu-Arg, the phosphorylation site of pp65 was located at the N-terminal region adjacent to the first Ca2+ binding domain. This sequence contains a repeat of the casein kinase II motif Ser-Xxx-Xxx-Glu/Asp and, together with the preceeding Arg residue, constitutes the consensus sequence Arg-Xxx-Ser for cAMP-dependent protein kinase (PKA) and protein kinase C (PKC), but not mitogen-activated protein kinase (MAPK)-specific motif is found. These results, taken together with previous observations on the process of macrophage activation by LPS, demonstrate that pp65 is phosphorylated by an LPS-induced protein kinase other than MAPK and exerts its function on the cytoskeleton in a Ca2+/calmodulin-dependent manner.

Amino Acid Sequence↗

Value of a dynamic MR scan in predicting vascular ingrowth from free vascularized scapular transplant used for treatment of avascular femoral head necrosis.

We have treated three patients with avascular osteonecrosis using vascularized scapular bone graft. To predict blood perfusion in both the diseased femoral head and the transferred bone, all the hips were followed up using dynamic magnetic resonance (MR) scans, performed 1 and 7 months after surgery. In the present cases, it was shown that conventional enhanced MR imaging sometimes depicts increased intensity in bone marrow without blood perfusion due to the leakage of gadolinium-DTPA (Gd-DTPA) from the capillaries surrounding the avascular tissue. It was found that Gd-DTPA remaining in the dead bone marrow resulted in a false-positive image. By contrast, the dynamic MR scan evaluated only those images taken before the leakage. This is one of the advantages of the dynamic study, which reflects actual blood flow in the bone. The fast rise in the time-intensity curve following bolus injection of Gd-DTPA indicates that there is fast blood perfusion in the bone. The dynamic MR scan has demonstrated that there is little blood perfusion in the diseased bone 1 month after the operation and that vascular ingrowth from the transferred bone flap proceeds gradually between 1 and 7 months after surgery. These findings indicate that the dynamic MR scan is very useful in demonstrating vascular ingrowth after surgery in avascular necrosis of the femoral head and can be a reliable monitoring technique for anastomotic patency of the vascularized bone flap.

Adolescent↗

Elongation of wallerian degenerating nerve with a tissue expander: a functional, morphometrical, and immunohistochemical study.

The purpose of this experimental study was to investigate the usefulness and mechanism of the expansion of wallerian degenerating nerve. The study consisted of two experiments: Experiment I, functional and morphometrical analysis, and Experiment II, immunohistochemical analysis. In Experiment I, the rat nerve crush model was used to assess the effects of mechanical expansion of wallerian degenerating nerves on axonal regeneration. In Experiment II, the rat sciatic nerve cut model was used to investigate the effects of nerve expansion on Schwann cell events in wallerian degenerating nerves. In both experiments, nerve expansion was carried out between days 5 and 9 after nerve injury, using a rubber tissue expander placed beneath the sciatic nerve. In Experiment I, rats were divided into the following three groups according to the volume of saline injected: control group (nerves were crushed, without saline injection); 8-ml injection group; and 11-ml injection group. Functional recovery was assessed using the sciatic functional index until 54 days after nerve injury. Rats in all three groups showed good functional recovery, and the morphometrical analysis revealed no significant differences among the three groups. In Experiment II, anti-S-100 protein polyclonal antibody and anti-proliferating cell nuclear antigen monoclonal antibody were used to identify proliferating Schwann cells. Rats were divided into two groups: control group (nerves were cut, without expansion) and nerve expansion group. In the control group, proliferating Schwann cells were observed only between days 3 and 7. By contrast, these cells continued to be seen in the expanded nerves until day 16. These results suggest that the expansion of wallerian degenerating nerve does not have a deleterious effect on the axon-promoting property of Schwann cell tubes and that the expansion is dependent not only on the viscoelasticity of the nerves but also on enhanced proliferation of Schwann cells.

Animals↗

Superoxide radicals mediate the biochemical effects of methylenedioxymethamphetamine (MDMA): evidence from using CuZn-superoxide dismutase transgenic mice.

The subacute and long-term biochemical effects of methylenedioxymethamphetamine (MDMA) were assessed in homozygous and heterozygous transgenic (Tg) mice that carry the complete sequence of the human copper-zinc (CuZn) superoxide dismutase (SOD) gene. Non-transgenic (Non-Tg) mice showed significant decreased in striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels both at 24 h and at 2 weeks after a single injection of MDMA (50 mg/kg). Heterozygous SOD-Tg mice showed DA depletion only at the 24 h time point. In contrast, homozygous SOD-Tg mice show no DA or DOPAC depletion at either the 24 h or at the 2 week time points. Moreover, three injections of MDMA (50 mg/kg) given 24 h apart also caused marked reduction of striatal DA and DOPAC in Non-Tg mice when these substances were measured 2 weeks after the last MDMA injection. That injection schedule also caused small decreases in DA levels in the heterozygous animals but no changes in the homozygous mice; DOPAC levels were not affected in the heterozygous nor in the homozygous SOD-Tg mice. Furthermore, the multiple injection schedule caused significant decreases in DA and DOPAC in female Non-Tg mice but not in the two strains of transgenic mice. Neither the single dose nor the multiple dose schedule of MDMA injections affected striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in any of the three strains of mice. These results support previous observations that MDMA-induced biochemical effects are observed in the DA systems of mice, whereas these effects are seen in the 5-HT systems of rats. The present observations also document for the first time a role for the production of superoxide radicals in these effects of MDMA. These mice are an important tool for dissecting pathways involved in drug-induced neurotoxicity.

3,4-Dihydroxyphenylacetic Acid↗