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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 253 records · Page 14Linked to original sources

[Atherosclerosis].

Atherosclerotic lesions can be characterized as accumulation of cholesterol esters and pathologic reactions by various cell groups. The pathogenesis of atherosclerosis has been discussed primarily on the basis of these two phenomena. A well-known concept to explain the etiology of atherosclerosis is the theory of response to injury. According to this theory, physiologically active substances such as platelet-derived growth factor (PDGF) and macrophage colony-stimulating factor (M-CSF) are released in response to injury of the vascular wall, and these substances induce pathologic reactions by the cells constituting the vascular wall. In the presence of excessive amounts of low-density lipoprotein (LDL), denatured LDL modified by oxidation or other reactions on the vascular wall is taken up by macrophages via scavenger receptors, resulting in the formation of foam cells and accumulation of cholesterol esters. Vitamins including Vitamin C and Vitamin E may play an important role in form cell formation by preventing the oxidation.

Animals↗

Autosomal recessive hydrocephalus due to congenital stenosis of the aqueduct of sylvius.

Isolated hydrocephalus due to congenital stenosis of the aqueduct of Sylvius is almost always an X-linked recessive inherited condition. We describe a brother and sister with isolated hydrocephalus from congenital aqueductal stenosis. We believe that these two occurrences represent a rare autosomal recessive form of this abnormality. In assessing a first known occurrence of hydrocephalus with stenosis of the aqueduct of Sylvius in a family, the rare possibility of autosomal inheritance must be considered in genetic counselling.

Abortion, Therapeutic↗

[Molecular mechanism of insulin resistance in hyperlipidemia].

Several types of abnormal lipoprotein particles are observed in patients with insulin resistance: elevated VLDL-triglycerides, remnant lipoprotein, small dense LDL, reduced HDL-cholesterol. These patterns are caused by environmental and genetic factors that alter the lipoprotein metabolism. These lipoprotein abnormalities cause insulin resistance through several factors which decrease LPL and PPAR gamma, on the other hand increase ACS and MTP. It is considered that increased plasma level of FFA will closely associated with these factors and their regulations. Secretion of TNF-alpha from adipocytes increases in obesity and closely relates to the pathogenesis of insulin resistance. But the genetic mechanisms are not still clear. More studies about genetic factors which affect to lipoprotein metabolism will be needed and should be considered about the role on insulin resistance.

Humans↗

A behavioral and immunohistochemical study on the development of perirhinal cortical kindling: a comparison with other types of limbic kindling.

We have previously reported that the perirhinal cortex (PRC) plays an important role in the generalization of kindled seizures. In the present study, we kindled the rat PRC and made a comparison with amygdala (AM) and dorsal hippocampal (dHIPP) kindling. In order to produce a functional map of the seizure generalization pathway from these limbic foci, we also stained for Fos protein in sections of the PRC-, AM- and dHIPP-kindled brains using an immunohistochemistry technique. In the generalized seizures of PRC kindling the duration of afterdischarges (ADs) and the latency to forelimb clonus were significantly shorter than those of AM kindling or dHIPP kindling. Typically, the PRC-kindled rats demonstrated moving arrest or exploratory behavior for about 10 days, and then a characteristic 'rapid backward moving' behavior for 1 day, followed by the sudden appearance of generalized motor seizures. Fos protein induction after a single stimulation of the PRC is more widely observed than after a single stimulation of the AM, in that the PRC stimulation produced Fos protein expression in the temporal and parietal neocortices. Following AM and PRC kindling, the Fos-positive areas were asymmetrically propagated from the ipsilateral to the contralateral hemisphere. The contralateral PRC was primarily activated at the generalization of epileptic activity in the contralateral hemisphere. In contrast, the Fos protein distribution of the dHIPP-kindled rats was restricted to the bilateral hippocampi during the early stages, followed by the symmetrical propagation from the limbic system to the neocortex during the generalized seizures. These results indicate that the PRC plays a characteristic role in the seizure generalization of kindling.

Amygdala↗

Minimum light intensity required to suppress nocturnal melatonin concentration in human saliva.

We set out to determine the minimum intensity of light able to suppress nocturnal melatonin levels as measured in normal human saliva. Five healthy male volunteers were exposed to light at different intensities (<10, 500, 1000, 2500, and 5000 lux) in a repeated measure design. Suppression of melatonin was dependent on both light intensity and duration of light exposure. Minimum intensities of light suppressing nocturnal melatonin levels were calculated as 393, 366, 339, and 285 lux for exposure durations of 30, 60, 90, and 120 min, respectively. Minimum effective intensity and duration of light exposure showed a linear inverse relationship. These results suggest that less intensity of light than previously reported suffices to suppress melatonin in humans, and that caution is required in interpreting studies using long exposure to dim light as a background condition.

Adult↗

Cholesterol lowering in low density lipoprotein receptor knockout mice overexpressing apolipoprotein E.

Apo E is a key molecule in the lipoprotein metabolism; thus, genetic manipulation of apo E may prove useful in the treatment of hypercholesterolemia. To test the feasibility of this idea, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpress the rat apo E transgene (ETg+/+:LDLRKO), and compared their plasma lipoprotein profiles with those of nonexpressing LDLR knockout mice (ETg-/-:LDLRKO). On a normal chow diet, the mean plasma cholesterol level of ETg+/+:LDLRKO mice was significantly lower than that of ETg-/-:LDLRKO mice (189 versus 240 mg/dl, P < 0. 01). The LDL fraction was selectively reduced in the ETg+/+:LDLRKO mice. Despite the challenge with an atherogenic diet, cholesterol lowering was persistently observed and fatty streak lesions in the aortic sinus were significantly suppressed in the mice overexpressing apo E. These results imply that stimulation of hepatic production of apo E may be used as a promising adjunctive therapy for homozygous familial hypercholesterolemia.

Animals↗

Spatiotemporal measurement of free radical elimination in the abdomen using an in vivo ESR-CT imaging system.

Electron spin resonance (ESR) imaging can visualize the distribution of free radicals in living systems according to their concentrations. However, the application of ESR imaging to living animals has not been well established. Using a rapid field scan L-band ESR imaging system, we have successfully obtained two-dimensional ESR projection (xz-plane projection) and three-dimensional ESR-CT (trans-axial section along the y-axis) images of the abdomen of living mice after an injection of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) into the tail vein. The in vivo two-dimensional ESR projection imaging clearly visualized the carbamoyl-PROXYL distribution and the rapid decay process in the abdomen. Because among the viscera, the liver is most abundantly associated with a blood volume, the outline of the image can be composed mainly of this organ. We therefore attempted to find whether there will be a difference in spatiotemporal dynamics of carbamoyl-PROXYL in the abdomens between the control and the mice with liver damage by two-dimensional ESR projection. In the control mice, carbamoyl-PROXYL was almost completely eliminated from the abdomen within 5 minutes after administration. On the other hand, in mice with carbon tetrachloride-damaged livers, the decay of carbamoyl-PROXYL was markedly prolonged. Even at 5 min after administration, carbamoyl-PROXYL remained clearly visible in the abdomen. In vivo three-dimensional ESR-CT imaging showed an even distribution of carbamoyl-PROXYL throughout the whole liver, which corresponded well with the images of trans-axial sections of the murine abdomen. We have succeeded in displaying two-dimensional ESR projection and three-dimensional ESR-CT images of carbamoyl-PROXYL distribution and clearance in the abdomen of a living animal. The ESR-CT imaging technique is considered to be a powerful new tool for noninvasive investigations of the in vivo spatiotemporal dynamics of free radical distribution and elimination in the organs.

Abdomen↗

Complete and rapid peptide and glycopeptide mapping of mouse monoclonal antibody by LC/MS/MS using ion trap mass spectrometry.

Complete and rapid peptide and glycopeptide mapping of a mouse monoclonal immunoglobulin (IgG2b) were carried out by liquid chromatography/electrospray ionization ion trap-mass spectrometry/mass spectrometry (LC/ ESI IT-MS/MS). It was possible to obtain spectra of a minor glycopeptide at a quantity as low as 1.8 pmol. Reduced and carboxymethylated mouse antidansyl monoclonal IgG2b (RCM-IgG2b) was digested with lysyl-endopeptidase. Proteolytic peptides were subjected to capillary HPLC separation followed by analysis with an ion trap mass spectrometer. The complete amino acid sequence of the IgG2b was characterized by using LC/ ESI IT-MS/MS. The structures of 12 different types of O-linked oligosaccharides attached to Thr-221AH in the hinge region and those of three major types of N-linked oligosaccharides attached to Asn-297H have been characterized.

Amino Acid Sequence↗

Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.

Insulin resistance is often associated with atherosclerotic diseases in subjects with obesity and impaired glucose tolerance. This study examined the effects of insulin resistance on coronary risk factors in IRS-1 deficient mice, a nonobese animal model of insulin resistance. Blood pressure and plasma triglyceride levels were significantly higher in IRS-1 deficient mice than in normal mice. Impaired endothelium-dependent vascular relaxation was also observed in IRS-1 deficient mice. Furthermore, lipoprotein lipase activity was lower than in normal mice, suggesting impaired lipolysis to be involved in the increase in plasma triglyceride levels under insulin-resistant conditions. Thus, insulin resistance plays an important role in the clustering of coronary risk factors which may accelerate the progression of atherosclerosis in subjects with insulin resistance.

Animals↗

pH dependence of the function of sodium ion extrusion systems in Escherichia coli.

Escherichia coli has three systems for sodium ion extrusion, NhaA, NhaB and ChaA. In this study, we examined the effect of pH on the function of these transporters using mutants having one of them, and found that (1) a mutant having NhaB excreted sodium ions at pH 7.5 but not at pH 8.5, (2) the efflux of sodium ions from mutant cells having ChaA was observed at both pH 7.5 and 8.5, but the activity was lower at pH 7.5, and (3) sodium ions were excreted from mutant cells having NhaA at pH 6.5 to 8.5. The extrusion activity of cells having NhaA was higher than that of cells having NhaB or ChaA. These results indicate that NhaB functions at a pH below 8, and ChaA extrudes sodium ions mainly at an alkaline pH above 8. It was also suggested that the activity of NhaB and ChaA is not enough to maintain a low level of internal sodium ions when the external concentration of sodium ions is high, and NhaA is induced within a wide range of medium pH under such conditions.

Escherichia coli↗

Inhibition of human T-cell leukemia virus type 1 replication by antisense env oligodeoxynucleotide.

Human T-cell leukemia virus type 1 (HTLV-1) infection is associated with adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis. Inhibition of HTLV-1 transmission is important to prevent the above HTLV-1-associated diseases. We used the antisense oligodeoxynucleotides (oligos) complementary to the first splice junction, rex responsive site, gag, env, tax, rex, and p21 and evaluated the effects on the syncytium formation between HTLV-1 producing human T-cell line, C9/PL cells, and HTLV-1-uninfected human glioma cell line, U251-MG cells. The syncytium formation was significantly inhibited the virion production assayed by antisense oligos to env, tax, gag, p21, and rex, with antisense oligo to env being the most inhibitory. Antisense oligos to env and tax also inhibited reverse transcriptase activity. Antisense oligo to env may have a potential as a preventive measure of HTLV-1 replication and transmission in vivo.

Base Sequence↗

Time-dependent changes in rat hippocampal synapsin I mRNA expression during long-term potentiation.

We studied the time-dependent changes in synapsin I mRNA levels after hippocampal long-term potentiation (LTP) in rats in vivo. Following LTP induction by stimulating the perforant path, synapsin I mRNA expression in the granule cell layer of the dentate gyrus ipsilateral to stimulation increased significantly in a time-dependent manner. From 2 to 8 h after stimulation, the synapsin I mRNA levels in the ipsilateral dentate gyrus were significantly higher than those of controls subjected to a sham procedure. The synapsin I mRNA level (157.4+/-7.1% of the control level, mean+/-SEM) was at a maximum 8 h after stimulation. The synapsin I mRNA level of animals that received only test pulses did not increase significantly, compared with the control level. These results suggest that the increased level of synapsin I mRNA is related to persistent enhancement of synaptic activity within the neural networks in which dentate granule cells participate in LTP.

Animals↗

Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: nine novel mutations including T312S, a common allele that confers a mild phenotype.

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Previous studies of patients from a British-Irish population showed that the I113F mutation is the most common single mutation among MPS IVA patients and produces a severe clinical phenotype. We studied mutations in the GALNS gene from 23 additional MPS IVA patients (15 from Australia, 8 from Northern Ireland), with various clinical phenotypes (severe, 16 cases; intermediate, 4 cases; mild, 3 cases). We found two common mutations that together accounted for 32% of the 44 unrelated alleles in these patients. One is the T312S mutation, a novel mutation found exclusively in milder patients. The other is the previously described I113F that produces a severe phenotype. The I113F and T312S mutations accounted for 8 (18%) and 6 (14%) of 44 unrelated alleles, respectively. The relatively high residual GALNS activity seen when the T312S mutant cDNA is overexpressed in mutant cells provides an explanation for the mild phenotype in patients with this mutation. The distribution and relative frequencies of the I113F and T312S mutations in Australia corresponded to those observed in Northern Ireland and are unique to these two populations, suggesting that both mutations were probably introduced to Australia by Irish migrants during the 19th century. Haplotype analysis using 6 RFLPs provides additional data that the I113F mutation originated from a common ancestor. The other 9 novel mutations identified in these 23 patients were each limited to a single family. These data provide further evidence for extensive allelic heterogeneity in MPS IVA in British-Irish patients and provide evidence for their transmission to Australia by British-Irish migrants.

Australia↗

Evaluation of self-similar features in time series of serum growth hormone and prolactin levels by fractal analysis: effect of delayed sleep and complexity of diurnal variation.

We assayed the diurnal concentrations of growth hormone (GH) and prolactin (PRL) in 6 healthy male volunteers to evaluate the self-similar features in the time series of each hormone on the basis of fractal theory and to determine the fractal dimension as an index of the complexity of the diurnal variation. In addition, we assessed the effects of a 6-hour delay in the sleep period on the complexity of the diurnal variation of these hormones. There was a statistically significant fractal feature in the serum levels of GH both under the nocturnal-sleep and delayed-sleep conditions in all subjects. The time series of the serum PRL concentrations also showed a statistically significant fractal feature under the nocturnal-sleep and delayed-sleep conditions in all subjects. The fractal dimensions of the patterns of the GH or PRL levels were 1.879 and 1.929 or 1.754 and 1.785 under the nocturnal-sleep and delayed-sleep conditions, respectively. Two-way ANOVA revealed no significant difference in the fractal dimension between the two sleep conditions but did reveal a significant difference between the fractal dimensions of the GH and PRL levels. These results showed (1) that delayed sleep had no significant effect on the complexity of the diurnal pattern of these hormones, and (2) that the diurnal pattern of the GH levels was more complex than that of the PRL levels.

Adult↗