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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 343 records · Page 19Linked to original sources
PubMed1997

Trimethyltin syndrome as a hippocampal degeneration model: temporal changes and neurochemical features of seizure susceptibility and learning impairment.

The effects of trimethyltin on the hippocampus were investigated in terms of changes in histology, depth electroencephalography, learning acquisition and memory retention, choline acetyltransferase and neuropeptides, and seizure-induced c-fos messenger RNA expression. The results were as follows. (1) Morphologically, trimethyltin produced a progressive loss of hippocampal CA3 and CA4 pyramidal cells, starting from four days after peroral treatment with trimethyltin hydroxide (9 mg/kg), as described previously. (2) Neurophysiologically, the increased seizure susceptibility to pentylenetetrazol treatment reached a maximum at four days post-trimethyltin and then declined after five days post-trimethyltin. The maximal seizure susceptibility at four days post-trimethyltin was confirmed by the immediate and long-lasting appearance of spike discharge in the hippocampus. However, this was not verified by the expression of c-fos messenger RNA in the hippocampus, which was comparable between trimethyltin-treated and control rats. (3) Behaviorally, the time-courses of aggression and learning impairment were similar to that of the seizure susceptibility. (4) Neurochemically, trimethyltin treatment caused changes of neurochemical markers, which were manifested by the elevation of neuropeptide Y content in the entorhinal cortex, and of choline acetyltransferase in the hippocampal CA3 subfield. Trimethyltin may offer potential as a tool for investigations on the relationship between neuronal death in the hippocampus and the development of seizure susceptibility and learning impairment. Alterations in glucocorticoids, glutamate and neuropeptides may all contribute to the manifestation of the trimethyltin syndrome.

Animals↗
PubMed1997

Prevention of stress-induced morphological and cognitive consequences.

Atrophy and dysfunction of the human hippocampus is a feature of aging in some individuals, and this dysfunction predicts later dementia. There is reason to believe that adrenal glucocorticoids may contribute to these changes, since the elevations of glucocorticoids in Cushing's syndrome and during normal aging are associated with atrophy of the entire hippocampal formation in humans and are linked to deficits in short-term verbal memory. We have developed a model of stress-induced atrophy of the hippocampus of rats at the cellular level, and we have been investigating underlying mechanisms in search of agents that will block the atrophy. Repeated restraint stress in rats for 3 weeks causes changes in the hippocampal formation that include suppression of 5-HT1A receptor binding and atrophy of dendrites of CA3 pyramidal neurons, as well as impairment of initial learning of a radial arm maze task. Because serotonin is released by stressors and may play a role in the actions of stress on nerve cells, we investigated the actions of agents that facilitate or inhibit serotonin reuptake. Tianeptine is known to enhance serotonin uptake, and we compared it with fluoxetine, an inhibitor of 5-HT reuptake, as well as with desipramine. Tianeptine treatment (10 mg/kg/day) prevented the stress-induced atrophy of dendrites of CA3 pycamidal neurons, whereas neither fluoxetine (10 mg/kg/day) nor desipramine (10 mg/kg/day) had any effect. Tianeptine treatment also prevented the stress-induced impairment of radial maze learning. Because corticosterone- and stress-induced atrophy of CA3 dendrites is also blocked by phenytoin, an inhibitor of excitatory amino acid release and actions, these results suggest that serotonin released by stress or corticosterone may interact pre- or post-synaptically with glutamate released by stress or corticosterone, and that the final common path may involve interactive effects between serotonin and glutamate receptors on the dendrites of CA3 neurons innervated by mossy fibers from the dentate gyrus. We discuss the implications of these findings for treating cognitive impairments and the risk for dementia in the elderly.

Animals↗
PubMed1997

Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.

We report molecular analysis of thiamin-responsive pyruvate dehydrogenase complex (PDHC) deficiency in a patient with an X-linked form of Leigh syndrome. PDHC activity in cultured lymphoblastoid cells of this patient and his asymptomatic mother were normal in the presence of a high thiamin pyrophosphate (TPP) concentration (0.4 mmol/L). However, in the presence of a low concentration (1 x 10(-4) mmol/L) of TPP, the activity was significantly decreased, indicating that PDHC deficiency in this patient was due to decreased affinity of PDHC for TPP. The patient's older brother also was diagnosed as PDHC deficiency with Leigh syndrome, suggesting that PDHC deficiency in these two brothers was not a de novo mutation. Sequencing of the X-linked PDHC E1 alpha subunit revealed a C-->G point mutation at nucleotide 787, resulting in a substitution of glycine for arginine 263. Restriction enzyme analysis of the E1 alpha gene revealed that the mother was a heterozygote, indicating that thiamin-responsive PDHC deficiency associated with Leigh syndrome due to this mutation is transmitted by X-linked inheritance.

DNA↗
PubMed1997

Dual effects of angiotensin II on the plasminogen/plasmin system in rat mesangial cells.

Previous studies indicate that angiotensin II (Ang II) stimulates extracellular matrix synthesis through induction of transforming growth factor-beta (TGF-beta) expression. Here we investigate Ang II effects on the plasmin protease system. Plasmin both degrades extracellular matrix itself and activates metalloproteinases which then degrade collagens. Plasmin production is determined by the balance between plasminogen activators (PA) and their inhibitors (PAI-1,2). The data presented here indicate that Ang II treatment of mesangial cells in culture markedly increases PAI-1 gene transcription and PAI-1 mRNA levels but does not change the half life of PAI-1 mRNA. Increased PAI-1 protein was detected 24 hours after Ang II stimulation with a concomitant decrease of PA activity. To determine whether these effects were mediated by TGF-beta, cells were coincubated with Ang II and neutralizing antibody to TGF-beta. Induction of PAI-1 at four hours was not altered but the prolonged effect of Ang II on PAI-1 protein synthesis was markedly diminished. Thus, Ang II acts both through rapid, direct transcriptional up-regulation of the PAI-1 gene and through induction of TGF-beta, providing sustained changes in the PAI-1/PA system, which would favor extracellular matrix accumulation by inhibiting turnover. These data provide further evidence that Ang II can act as a potent fibrogenic molecule independent of its effects on blood pressure.

Angiotensin II↗
PubMed1997

Early diagnosis of mucosal squamous cell carcinoma of the esophagus: including two interesting cases of superficial spreading-type and multicentric-type squamous cell carcinomas.

We reviewed 10 patients with esophageal mucosal carcinoma in order to improve the early diagnosis of the disease. Histologically seven of the 14 lesions were carcinomas in situ (epithelial cancer), and the other seven lesions were carcinomas confined to the mucosa other than epithelial cancer (muscularis mucosae cancer), all 14 lesions were squamous cell carcinomas (SCC). One of these seven mucosal SCC, which demonstrated an extensive spreading-type SCC in which the size of the SCC was 7 cm long while extending entirely around the esophageal lumen in circumferential spread, is described in detail, and multiple epithelial cancers existed separately in one case. Eleven lesions diagnosed before operation showed abnormal findings on conventional endoscopy regardless of the size and depth of transmural invasion. An additional lesion was visible with dye endoscopy as an unstained area, but it was not visible with radiography or conventional endoscopy. Dye endoscopy using Lugol solution is very important because it allows detection and evaluation of the extent of esophageal mucosal cancer.

Aged↗
PubMed1997

Molecular features of the CAG repeats of spinocerebellar ataxia 6 (SCA6).

Spinocerebellar ataxia 6 (SCA6) is an autosomal dominant spinocerebellar degeneration caused by the expansion of the polymorphic CAG repeat in the human alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4 gene). We have analyzed 60 SCA6 individuals from 39 independent SCA6 Japanese families and found that the CAG repeat length is inversely correlated with the age of onset (n = 58, r = -0.51, P < 0.0001). SCA6 chromosomes contained 21-30 repeat units, whereas normal chromosomes displayed 6-17 repeats. There was no overlap between the normal and affected CAG repeat number. The anticipation of the disease was observed clinically in all eight parent-child pairs that we examined; the mean age of onset was significantly lower (P = 0.0042) in children than in parents. However, a parent-child analysis showed the increase in the expansion of CAG repeats only in one pair and no diminution in any affected cases. This result suggests that factors other than CAG repeats may produce the clinical anticipation. A homozygotic case could not demonstrate an unequivocal gene dosage effect on the age of onset.

Adult↗
PubMed1997

Blood flow velocity of middle cerebral artery during prolonged anesthesia with halothane, isoflurane, and sevoflurane in humans.

BACKGROUND: It is not clear whether the increase of cerebral blood flow (CBF) produced by volatile anesthetics is maintained during prolonged anesthesia. In a previous study, the authors found that CBF equivalent, an index of flow-metabolism relationship, was stable over 3 h, suggesting no decay over time in CBF for 3 h during volatile anesthesia in humans. However, it may be possible that CBF changes in a parallel fashion to functional metabolic changes. In this study, to estimate the response of CBF to three volatile anesthetics, the authors used transcranial Doppler (TCD) ultrasonography to measure time-averaged mean velocity in the middle cerebral artery (Vmca). METHODS: Twenty-four surgical patients were randomly assigned to three groups to receive halothane, isoflurane, or sevoflurane (eight patients, each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5, 1.0, and 1.5 MAC before surgery and then at 1.5 MAC during surgery, which lasted more than 3 h. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 70 mmHg, using phenylephrine infusion, if necessary. TCD recordings of the Vmca were performed continuously. RESULTS: Vmca at 0.5 MAC of halothane, isoflurane, and sevoflurane was 49 +/- 19, 57 +/- 8, and 48 +/- 13 cm/s, respectively. Halothane significantly (P < 0.01) increased Vmca in a dose-dependent manner (0.5, 1.0, 1.5 MAC), whereas isoflurane and sevoflurane produced no significant dose-related changes. At 1.5 MAC for 3 h, Vmca changed significantly (P < 0.05) for the time trends, but it did not exhibit decay over time with all drugs. During burst suppression, observed electroencephalographically (EEG) on patients during isoflurane and sevoflurane anesthesia, the onset of a burst increased Vmca (approximately 5-30 cm/s), which was maintained for the duration of the burst. CONCLUSIONS: The results indicate that there was no decay in Vmca over time during prolonged (3 h) inhalation of volatile anesthetics at 1.5 MAC in humans. The fluctuation of Vmca during burst suppression on EEG at 1.5 MAC indicates that the flow-metabolism coupling occurred.

Adult↗
PubMed1997

Recovery of pancreatic tissue perfusion and ATP tissue level after reperfusion in canine pancreas grafts preserved by the two-layer method.

We examined whether pancreas grafts preserved by the two-layer method maintained adenine nucleotides pool as substrates for ATP synthesis before reperfusion and had the ability to recover pancreatic tissue perfusion and synthesize ATP promptly after reperfusion. After preservation by the two-layer cold storage method using EC for 48 h (group 1) or simple cold storage in EC for 48 h (group 2), canine pancreas grafts were autotransplanted. In controls (group 3), canine pancreas grafts were autotransplanted without preservation. Tissue adenine nucleotide concentrations were measured using high-performance liquid chromatography, and pancreatic tissue perfusions were measured using the hydrogen gas clearance method. Graft survival rates were five of five, zero of five, and five of five in groups 1, 2, and 3, respectively. Total adenine nucleotide levels before reperfusion in group 1 were almost the same as in group 2. Furthermore, ATP tissue levels in group 1 before reperfusion were also the same as in group 2. However, tissue ATP levels in group 1 after 2 h of reperfusion (6.71 +/- 1.19 mumol/g dry weight) were significantly higher than group 2 (4.51 +/- 0.51 mumol/g dry weight; p < 0.05). On the other hand, pancreatic tissue perfusions in grafts preserved by the two-layer method (group 1) after 2 h of reperfusion were significantly higher than in group 2. We conclude that oxygenation of pancreas grafts during preservation by the two-layer method allows for ATP synthesis and leads to maintenance of the grafts' ability to recover ATP levels and tissue perfusions after reperfusion.

Adenine Nucleotides↗
PubMed1997

Sympathetic denervation of myocardium demonstrated by 123I-MIBG scintigraphy in pure progressive autonomic failure.

123I-MIBG myocardial scintigrams obtained in 2 cases with pure progressive autonomic failure are presented. In the less advanced case, 123I-MIBG myocardial SPECT disclosed uptake defects of radioisotopes in both the apical region and the inferior wall and a marked decrease in uptake in the lateral wall. However, residual radioactivity was demonstrated in the anterior wall. In the terminal stage, radioactivity over the whole heart was undetectable in planar images, so as to be of no use to obtain SPECT images. These scintigrams might suggest where the sympathetic denervation began and subsequently extended to the whole myocardium in the course of the disease. In addition, 123I-MIBG scintigraphy was recommended in a case with the disease, since an unequal impairment of myocardial sympathetic nervous system has been described to probably induce fatal arrhythmias which were the cause of sudden death in this case.

3-Iodobenzylguanidine↗
PubMed1997

A monoclonal antibody (1F3) to human glomerular epithelial cells: a new marker for renal epithelial cell injury.

In order to identify a new cell surface antigen as a potential marker of renal epithelial cell injury, we produced a monoclonal antibody (Mab), 1F3, by immunizing mice with cultured human glomerular cells. Immunofluorescence (IF) and immunoelectron microscopy (IEM) studies demonstrated that 1F3-recognizing antigen (1F3 antigen) was strongly expressed on the cell surface of glomerular podocytes and very weakly on parietal epithelial cells. 1F3 antigen was not expressed in any other cells in the normal kidney. Immunoprecipitation analysis using metabolically labeled glomeruli revealed that 1F3 recognized a 125-kD protein under reducing conditions. IF studies of biopsy specimens from patients with a variety of glomerular and tubulointerstitial diseases showed that 1F3 antigen was almost negative in cellular crescents but was strongly expressed in fibrocellular crescents. When glomerular sclerosis appeared, the expression of 1F3 antigen decreased in sclerotic areas of glomeruli. 1F3 antigen became positive in atrophic tubules that were seen in diseased kidneys. Severity of tubular atrophy correlated well with the extent of tubular expression of 1F3 antigen. These results indicate that Mab, 1F3 marks phenotypic changes of renal epithelial cells under disease conditions and may be a useful marker for progressive kidney diseases.

Animals↗
PubMed1997

Differences in brain metabolites between patients with autism and mental retardation as detected by in vivo localized proton magnetic resonance spectroscopy.

We performed volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain with a 1.5 T magnet in 28 patients with autism, and compared the results with those from 28 age-matched patients with unclassified mental retardation and 25 age-matched healthy children. Peaks for N-acetylaspartate, choline and creatine, but not lactate, were observed in each group on 1H-MRS. The N-acetylaspartate/choline ratio was lower in patients with mental retardation than in patients with autism and controls (P = .05, respectively). However, there were no differences in the N-acetylaspartate/ choline ratios between patients with autism and controls, and the N-acetylaspartate/creatine and choline/creatine ratios did not differ among the three groups. These results suggest that N-acetylaspartate is decreased in patients with mental retardation and that a disorder or dysfunction of neurons in the brain exists. There also appear to be differences in the brain lesions or dysfunctions found in patients with autism and mental retardation.

Aspartic Acid↗
PubMed1997

Serum leptin concentration in cord blood: relationship to birth weight and gender.

To investigate the effect of leptin on fetal growth, serum leptin concentrations in venous cord blood were measured in 82 newborns (male = 43, female = 39, gestational age 36-42 weeks, birth weight 2,306-4,128 g). Serum leptin concentrations in cord blood ranged from 2.0 to 84.5 ng/mL (mean 19.9 +/- 17.4 ng/mL). Serum leptin concentrations in males (mean 15.3 +/- 15.6 ng/mL, range 2.0 to 79.3 ng/mL) were significantly (P = 0.011) lower than those in females (mean 25.0 +/- 18.0 ng/mL, range 2.1 to 84.5 ng/mL). Serum leptin concentrations in cord blood were positively correlated with birth weight (r = 0.555, P <0.0001), birth weight SD (r = 0.540, P <0.0001), Kaup index (r = 0.505, P <0.0001) and body weight/body height (r = 0.560, P <0.0001). The serum concentrations of estradiol and testosterone did not differ between males and females and did not correlate with the leptin concentration. It is unlikely that the gender difference in fetal leptin levels is due either to body fat content or distribution or to reproductive hormone status, but may be attributed to genetic differences between males and females.

Birth Weight↗
PubMed1997

Homozygosity for an allele carrying intermediate CAG repeats in the dentatorubral-pallidoluysian atrophy (DRPLA) gene results in spastic paraplegia.

We report a family with autosomal recessive spastic paraplegia. Patient 1 was a 37-year-old woman and patient 2 was her 35-year-old sister. They showed spastic paraplegia with mild truncal ataxia and dysarthria but no dementia, epilepsy, myoclonus, or other involuntary movements. They were the products of a consanguineous marriage but the parents were neurologically normal. We analyzed the CAG repeats of the dentatorubral-pallidoluysian atrophy (DRPLA) gene in the family members. The patients were homozygous for an allele carrying an intermediate size of CAG repeats (41 or 40 repeats) in the DRPLA gene; the parents were heterozygous for an intermediate allele and a normal allele in this gene. Homozygosity for an intermediate allele in the DRPLA gene appears to have resulted in spastic paraplegia different from any DRPLA phenotype.

Adult↗
PubMed1997

Adult-onset Krabbe disease with homozygous T1853C mutation in the galactocerebrosidase gene. Unusual MRI findings of corticospinal tract demyelination.

A 51-year-old woman developed a slowly progressive spastic paraparesis and diminished vibration sense beginning at age 38. Intellectual capacity was normal. Krabbe disease was confirmed by markedly reduced leukocyte galactocerebrosidase (GALC) activity, typical inclusions in Schwann cell cytoplasm, and an identification of the homozygous point mutation T1835C (Leu618Ser) in the GALC gene. T2-weighted MRI of the brain showed symmetric high-signal-intensity lesions in the bilateral frontoparietal white matter, the centrum semiovale, and the posterior limb of the internal capsule with sparing of the periventricular white matter. This case is unusual because of the late onset, protracted clinical course, and MRI findings of demyelination confined to the corticospinal tracts.

Age of Onset↗
PubMed1997

Expression of beta 1-integrins on activated mesangial cells in human glomerulonephritis.

beta 1-integrins, a family of cell-surface receptors, mediate cell-matrix interactions that play a critical role in tissue development and tissue remodeling after injury. In this study, to clarify the importance of beta 1-integrins in human glomerulonephritis (GN), the relationship among the glomerular expression of beta 1-integrins, their ligand matrix components, alpha-smooth muscle actin (alpha-SM actin) as a marker of activated mesangial cells (MC), transforming growth factor-beta (TGF-beta), and glomerular cellularity in two normal kidneys, ten minimal change nephrotic syndrome, 23 immunoglobulin A (IgA) GN, 13 lupus GN, and four membranous GN kidneys were studied. Immunostaining was performed on frozen sections, using monoclonal anti-alpha-SM actin antibody and polyclonal antibodies against fibronectin, collagen type IV, laminin, each subunit of alpha 1 beta 1 (collagen/laminin receptor), alpha 5 beta 1 (fibronectin receptor) and TGF-beta. Quantitation of staining indicated that the glomerular expression of alpha 1 beta 1 and alpha 5 beta 1 integrins correlated with the mesangial amounts of their ligands, collagen type IV, laminin and fibronectin (P < 0.01), alpha-SM actin (P < 0.01), and TGF-beta (P < 0.01). In addition, a correlation was observed between an increased expression of alpha 1 beta 1 and alpha 5 beta 1 integrins and the degree of glomerular cell proliferation (P < 0.01). Double immunostaining showed that activated MC expressing alpha-SM actin strongly expressed alpha 1 beta 1 and alpha 5 beta 1 integrins, and these MC phenotypic alterations paralleled the level of glomerular TGF-beta staining (P < 0.01). In conclusion, enhanced expression of beta 1-integrins by activated MC may contribute to the pathological mesangial remodeling characterized by MC proliferation and matrix deposition in human GN. Increased glomerular TGF-beta appears to be involved in these MC phenotypic changes.

Actins↗
PubMed1997

Direct and indirect thalamic afferents arising from the vestibular nuclear complex of rats: medial and spinal vestibular nuclei.

We examined the afferent pathways and terminations in the thalamus from the medial vestibular nucleus (MVe) and the spinal vestibular nucleus (SpVe) with anterograde transport of Phaseolus vulgaris leucoagglutinin (PHAL) and retrograde transport of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). Following PHAL injection into the MVe, many anterogradely labeled fibers and terminal-like boutons were recognized in the central lateral nucleus of the thalamus. Sparse projections were found in the zona incerta, the ventral lateral geniculate nucleus and the compact region of the laterodorsal thalamic nucleus. When PHAL was injected into the SpVe, labeled ascending fibers ran along the lateral lemniscus forming a loose bundle, and terminated in the medial part of the rostrocaudal extent of the medial geniculate body, and the posterior and ventral thalamic nuclei. Furthermore, a few fibers projected to the central lateral nucleus. In order to confirm the indirect thalamic afferents via the spinal trigeminal nucleus, we injected WGA-HRP into the submedius nucleus of the thalamus after PHAL injection into the SpVe. Many anterogradely labeled terminal-like boutons from SpVe were recognized apposing retrogradely labeled spinal trigeminal neurons. Thus, the present results indicate the existence of dual vestibulo-thalamic pathways; a direct projection to the thalamus, and an indirect projection to the submedius nucleus via the spinal trigeminal nucleus.

Afferent Pathways↗