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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 55 records · Page 3Linked to original sources
PubMed2003

Glucosamine induces resistance to insulin-like growth factor I (IGF-I) and insulin in Hep G2 cell cultures: biological significance of IGF-I/insulin hybrid receptors.

IGF-I stimulates insulin-like actions directly through its receptor, and it also enhances sensitivity to insulin-mediated effects in vivo. These studies were undertaken to analyze the role of IGF-I, insulin, and insulin/IGF-I hybrid receptors (HRs) in mediating IGF-I and insulin signaling in cells that had been made insulin-resistant by treatment with glucosamine. Human HepG2 cells, which express IGF-I receptors, insulin receptors (IRs), and IGF-I/insulin HRs, were exposed to 20 mM glucosamine; and the effects of IGF-I and insulin in stimulating glycogen synthesis were determined. An overnight exposure to glucosamine markedly attenuated the effects of insulin and IGF-I in stimulating glycogen synthesis. To determine which receptors were mediating this effect, the ability of insulin and IGF-I to stimulate phosphorylation of their respective receptors was analyzed. An 18-h exposure to glucosamine (20 mM) caused a 75% reduction in the ability of IGF-I to phosphorylate its receptor but no change in receptor abundance. Glucosamine also caused a major reduction in insulin-stimulated receptor phosphorylation, although, unlike IGF-I, there was also a 50% reduction in IR abundance. Exposure to glucosamine also resulted in a reduction in the ability of IGF-I or insulin to stimulate phosphorylation of insulin IGF-I/HRs. The combination of insulin plus IGF-I was a more potent stimulus of HR phosphorylation than either agent alone, and this combination was also more potent in partially reversing the inhibitory effect of glucosamine. Taken together, these findings indicate that glucosamine induces a loss of sensitivity to stimulation of insulin, IGF-I, or HR tyrosine kinase activity by insulin or IGF-I. Although insulin is able to partially reverse the effect of glucosamine on IR phosphorylation, it has a very minimal effect on glucosamine-induced inhibition of HR phosphorylation. However, the combination of IGF-I and insulin induces a major increase in HR phosphorylation, even in the presence of glucosamine, suggesting that it is improving the sensitivity of the HR to insulin activation.

Carcinoma, Hepatocellular↗
PubMed2002

A patient with dementia with Lewy bodies and codon 232 mutation of PRNP.

The authors describe a patient who had a point mutation at codon 232 of the prion protein gene, resulting in the substitution of methionine for arginine (M232R). The patient developed dementia and died 6 years after its onset. Autopsy revealed dementia with Lewy bodies, not Creutzfeldt-Jakob disease. Although the M232R mutation has been reported to cause Creutzfeldt-Jakob disease, findings in our patient suggest that not all patients presenting progressive dementia with M232R mutation have Creutzfeldt-Jakob disease.

Amino Acid Substitution↗
PubMed2002

An electronic read-out circuit for time-domain terahertz imaging with photoconductive antennas.

We have developed a signal amplifier for the detection of weak repetitive pulsed signals superimposed on a large background. It is based on a double gated integrator principle with two channels locked to a sequence of alternate signal and background pulses. The circuit is compact and cost effective, and thus suitable for use in large numbers with detector arrays, for example in terahertz imaging. The performance was verified in terahertz time-domain spectroscopy based on an amplified femtosecond laser and found to be better than that of a commercial lock-in amplifier.

Amplifiers, Electronic↗
PubMed2002

Development of a THz spectroscopic imaging system.

We have developed a real-time THz imaging system based on the two-dimensional (2D) electro-optic (EO) sampling technique. Employing the 2D EO-sampling technique, we can obtain THz images using a CCD camera at a video rate of up to 30 frames per second. A spatial resolution of 1.4 mm was achieved. This resolution was reasonably close to the theoretical limit determined by diffraction. We observed not only static objects but also moving ones. To acquire spectroscopic information, time-domain images were collected. By processing these images on a computer, we can obtain spectroscopic images. Spectroscopy for silicon wafers was demonstrated.

Diagnostic Imaging↗
PubMed2002

Long-term retention of motor skill in macaque monkeys and humans.

Remarkable human performance, such as playing the violin, is often based on motor skills that, once acquired, are retained for a long time. To examine how motor skills are retained, we trained monkeys and humans extensively to perform many visuomotor sequences and examined their performance after a long retention period of up to 18 months. For both monkeys and humans, we found strong evidence for long-term retention of motor skills. Each of the monkey subjects initially learned 6-18 sequences of button presses extensively by trial-and-error for up to 18 months. After a long retention period, they were asked to perform the previously learned (OLD) sequences together with completely new (NEW) sequences. The performance for OLD sequences was much better than for NEW sequences in terms of accuracy (assessed by the number of errors to criterion) and speed (assessed by the performance time). However, the retention was interfered with in two conditions, but in selective manners: (1) Learning of other sequences during the retention period interfered with accuracy, but not speed, of performance; (2) Inter-manual transfer was absent for speed, but not accuracy, of performance. The human subjects performed basically the same task as the monkeys. Each subject initially learned one sequence of 20 button presses by trial-and-error during an 8-10 day learning session. After 16 months, they were asked to perform the previously learned sequence (OLD sequence) and additional sequences including RECENT sequences (learned one day before) and NEW sequences. Their performance was considerably better on OLD and RECENT sequences than NEW sequences. Whereas the number of errors (reflecting 'accuracy') was lower for RECENT than for OLD sequences, the performance time (reflecting 'speed') was shorter for OLD than for RECENT sequences. Interestingly, the subjects were unaware that they had experienced OLD sequences. The results suggest that a motor skill is acquired and retained in two different forms, accuracy and speed. This occurs separately but concurrently. This conclusion is consistent with the hypothesis that at least two neural mechanisms operate independently to represent a motor skill.

Adult↗
PubMed2002

A novel murine myotonia congenita without molecular defects in the ClC-1 and the SCN4A.

The authors report a new murine model for myotonia congenita designated as B6MT. This line spontaneously arose from breeding of transgenic C57BL/6CrSlc mice, irrelevant of the transgene. The B6MT mouse showed moderate to severe action myotonia, and electromyography revealed myotonic discharge. The phenotype was transmitted with autosomal recessive inheritance. Molecular genetic study of the ClC-1 and the SCN4A genes revealed polymorphism with no functional consequences.

Amino Acid Substitution↗
PubMed2002

Phosphorothioate oligonucleotides, suramin and heparin inhibit DNA-dependent protein kinase activity.

Phosphorothioate oligonucleotides and suramin bind to heparin binding proteins including DNA polymerases, and inhibit their functions. In the present study, we report inhibition of DNA-dependent protein kinase activity by phosphorothioate oligonucleotides, suramin and heparin. Inhibitory effect of phosphorothioate oligonucleotides on DNA-dependent protein kinase activity was increased with length and reached a plateau at 36-mer. The base composition of phosphorothioate oligonucleotides did not affect the inhibitory effect. The inhibitory effect by phosphorothioate oligodeoxycytidine 36-mer can be about 200-fold greater than that by the phosphodiester oligodeoxycytidine 36-mer. The inhibitory effect was also observed with purified DNA-dependent protein kinase, which suggests direct interaction between DNA-dependent protein kinase and phosphorothioate oligonucleotides. DNA-dependent protein kinase will have different binding positions for double-stranded DNA and phosphorothioate oligodeoxycytidine 36-mer because they were not competitive in DNA-dependent protein kinase activation. Suramin and heparin inhibited DNA-dependent protein kinase activity with IC(50) of 1.7 microM and 0.27 microg ml(-1) respectively. DNA-dependent protein kinase activities and DNA double-stranded breaks repair in cultured cells were significantly suppressed by the treatment with suramin in vivo. Our present observations suggest that suramin may possibly result in sensitisation of cells to ionising radiation by inactivation of DNA-dependent protein kinase and the impairment of double-stranded breaks repair.

Antineoplastic Agents↗
PubMed2002

MRI of high-grade astrocytic tumors: early appearance and evolution.

The clinical management and prognosis of patients with diffusely infiltrating astrocytomas are dependent on neuropathological grading of the tumors. The characteristics of MR images of high-grade astrocytic tumors are well known, but the early MRI appearance and the MRI evolution of high-grade astrocytic tumors have rarely been examined. We retrospectively reviewed MR images obtained from 4 months to 3 years and 3 months before admission, as well as MR images on admission, for five patients with pathologically proven high-grade astrocytic tumors (two glioblastomas and three anaplastic astrocytomas). In two patients, neoplastic lesions were not detectable on initial MRI, even retrospectively. In the remaining three patients, however, hyperintense areas with little or no mass effect were demonstrated on T2-weighted imaging. These lesions were misinterpreted as non-neoplastic processes, such as ischemic lesion or infarction, or demyelinating processes. All tumors showed gadolinium enhancement on admission, that emerged from the previously existing hyperintense areas on T2-weighted images without gadolinium enhancement, except for one de novo glioblastoma. Development of a small central cyst without gadolinium enhancement was demonstrated in one case before the emergence of an enhancing area.

Adult↗
PubMed2002

Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia.

Germ-cell tumors of the central nervous system generally develop in the midline, but the tumors can also occur in the basal ganglia and/or thalamus. However, MR images have rarely been documented in the early stage of the tumor in these regions. We retrospectively reviewed MR images obtained on admission and approximately 3 years earlier in two patients with germinoma in the basal ganglia, and compared them with CT. In addition to hyperdensity on CT, both hyperintensity on T1-weighted images and a small hyperintense lesion on T2-weighted images were commonly seen in the basal ganglia. These findings may be early MRI signs of germinoma in this region, and the earliest and most characteristic diagnostic feature on MRI was atrophy of the basal ganglia, which was recognizable before development of hemiparesis.

Adolescent↗
PubMed2002

Relationship between obsessive-compulsive disorder and chaos.

Pharmacological treatment using serotonin reuptake inhibitors is often useful for patients with obsessive-compulsive disorder (OCD). Brain imaging studies indicated that hyperactivity of the striatum observed in OCD patients is normalized after successful pharmacological treatment. But, so far, there is no available model, which can explain both of these phenomena. This report proposes a hypothesis that serotonin reuptake inhibitors can induce chaos in the activity of striatal neurons and this chaotic behavior is essential to improve OCD symptoms and normalize the hyperactivity in the striatum. Moreover, it can be explained also by this model that there exists a subtype of patients for whom pharmacological treatment is not useful. As a method, simulation using the Hodgkin-Huxley equations and the chaotic neural network, which can reproduce the chaotic behavior in the real neuron, are used.

Corpus Striatum↗
PubMed2002

Cytotoxic effects of methanol, formaldehyde, and formate on dissociated rat thymocytes: a possibility of aspartame toxicity.

Aspartame is a widely used artificial sweetener added to many soft beverages and its usage is increasing in health-conscious societies. Upon ingestion, this artificial sweetener produces methanol as a metabolite. In order to examine the possibility of aspartame toxicity, the effects of methanol and its metabolites (formaldehyde and formate) on dissociated rat thymocytes were studied by flow cytometry. While methanol and formate did not affect cell viability in the physiological pH range, formaldehyde at 1-3 mmol/L started to induce cell death. Further increase in formaldehyde concentration produced a dose-dependent decrease in cell viability. Formaldehyde at 1 mmol/L or more greatly reduced cellular content of glutathione, possibly increasing cell vulnerability to oxidative stress. Furthermore, formaldehyde at 3 mmol/L or more significantly increased intracellular concentration of Ca2+ ([Ca2+]i) in a dose-dependent manner. Threshold concentrations of formaldehyde, a metabolite of methanol, that affected the [Ca2+]i and cellular glutathione content were slightly higher than the blood concentrations of methanol previously reported in subjects administered abuse doses of aspartame. It is suggested that aspartame at abuse doses is harmless to humans.

Animals↗
PubMed2002

Active maintenance in prefrontal area 46 creates distractor-resistant memory.

How does the brain maintain information in working memory while challenged by incoming distractions? Using functional magnetic resonance imaging (fMRI), we measured human brain activity during the memory delay of a spatial working memory task with distraction. We found that, in the prefrontal cortex (PFC), the magnitude of activity sustained throughout the memory delay was significantly higher on correct trials than it was on error trials. By contrast, the magnitude of sustained activity in posterior areas did not differ between correct and error trials. The correlation of activity between posterior areas was, however, associated with correct memory performance after distraction. On the basis of these findings, we propose that memory representations gain resistance against distraction during a period of active maintenance within working memory. This may be mediated by interactions between prefrontal and posterior areas.

Adult↗
PubMed2002

Treatment of pure red cell aplasia after major ABO-incompatible peripheral blood stem cell transplantation by induction of chronic graft-versus-host disease.

This report concerns a case of long-lasting pure red cell aplasia (PRCA) with a duration of 178 days after major ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). The patient needed red blood cell transfusion every week from day 54 following PBSCT. He showed no evidence of GVHD and the dose of cyclosporin A (CsA) was reduced rapidly from day 123, followed by the development of chronic GVHD around day 145. The patient no longer needed transfusions from day 167, the reticulocyte count began to increase on day 179, and antidonor isohemagglutinin titers became undetectable. Chronic GVHD induced by tapering of CsA thus appeared to be related to improvement in PRCA.

ABO Blood-Group System↗
PubMed2002

Serum lipid profiles in Japanese women and men during consumption of walnuts.

OBJECTIVE: To determine the serum cholesterol, apolipoproteins and LDL oxidizability in young Japanese women and men during walnut consumption and to evaluate its active principle. DESIGN: Experimental study with a randomized design. SUBJECTS: Twenty healthy women and 20 healthy men. INTERVENTIONS: Subjects were randomly assigned to consume each of two mixed natural diets for 4 weeks in a cross-over design. Reference and walnut diets were designed and the walnut diet had 12.5% of the energy derived from walnuts (44-58 g/day). RESULTS: The total cholesterol and serum apolipoprotein B concentrations, and the ratio of LDL cholesterol to HDL cholesterol was significantly lowered in women and men when fed on the walnut diet, than when on the reference diet (P<or=0.05). The LDL cholesterol concentration was significantly lowered in women on the walnut diet (0.22 mmol/l, P=0.0008), whereas this decrease was not significant in men (0.18 mmol/l, P=0.078). The most prominent change in the fatty acid composition of the cholesteryl esters from serum after the walnut diet was an elevation of alpha-linolenic acid in women (76%, P<0.001) and men (107%, P<0.001). This elevation was negatively correlated to the change in LDL cholesterol in women (r=0.496, P=0.019) and men (r=0.326, P=0.138). The LDL oxidizability in women was not influenced by the diets (P=0.19). CONCLUSIONS: alpha-Linolenic acid in the walnut diet appears to be responsible for the lowering of LDL cholesterol in women. SPONSORSHIP: Kyushu University (Fukuoka, Japan) and the California Walnut Commission (California, USA).

Adult↗
PubMed2002

Characterization of 'adult-type' mast cells derived from human bone marrow CD34(+) cells cultured in the presence of stem cell factor and interleukin-6. Interleukin-4 is not required for constitutive expression of CD54, Fc epsilon RI alpha and chymase, and CD13 expression is reduced during differentiation.

BACKGROUND: In vitro-derived human mast cells exhibit different properties, depending in part on the source of progenitor cells. Most investigations have used fetal liver, cord blood or peripheral blood. Few have used adult bone marrow. OBJECTIVE: Human mast cells derived in vitro from the CD34(+) progenitors in bone marrow and cord blood that had been cultured with recombinant human stem cell factor (rhSCF) and recombinant human interleukin-6 (rhIL-6) were compared. METHODS AND RESULTS: After 12 weeks of culture, nearly all of the cells were mast cells, and nearly all of these had cytoplasmic granules containing both tryptase and chymase (MCTC type), stained metachromatically with acidic toluidine blue, and expressed CD117 on the cell surface. Both tryptase protein and mRNA were detected by two weeks of culture. Chymase mRNA and protein were detected at 4 weeks but not at 2 weeks of culture. By 12 weeks, chymase content per cell, measured by ELISA, was significantly higher (P < 0.05) in human bone marrow-derived mast cells (HBMMC) (5.6 +/- 0.9 pg) than in cord blood-derived mast cells (CBMC) (2.4 +/- 0.9 pg), whereas histamine and tryptase levels were not significantly different. Of the cluster designations tested, CD29, CD49d, CD51 and CD61 were strongly expressed on HBMMC. CD54 and Fc epsilon RI alpha also were expressed constitutively. Approximately half of CD34-sorted cells at day 0 were CD13(+) and this diminished as mast cell maturation occurred. Electron microscopy revealed that 12-week-old HBMMC had many secretory granules that contained spherical electron dense cores surrounded by electron lucent space, consistent with previous reports of immature MCTC cells developing in vivo. CONCLUSIONS: CD34(+) progenitors of human bone marrow are a rich source of mast cell progenitors capable of expressing granule and surface markers of mature mast cells in the presence of rhSCF and rhIL-6.

Antigens, CD↗
PubMed2002

Involvement of cAMP-response element binding protein in corticotropin-releasing factor (CRF)-induced down-regulation of CRF receptor 1 gene expression in rat anterior pituitary cells.

Corticotropin-releasing factor (CRF) is a major secretagogue of adrenocorticotopic hormone from the anterior pituitary and a key activator of the hypothalamic-pituitary-adrenal axis. We previously reported that CRF down-regulates expression of the CRF type-1 receptor (CRF-R1) mRNA in cultured rat anterior pituitary cells. The present study was conducted to clarify the signal transduction systems involved in CRF-induced down-regulation of CRF-R1 gene expression in the anterior pituitary. Northern blot analysis revealed that, under serum-free conditions, 10 nM CRF decreased CRF-R1 mRNA levels in cultured rat anterior pituitary cells as we reported previously. Treatment with 5 mM 8-Br-cAMP reduced CRF-R1 mRNA levels within 2 h. The mRNA level fell to 37+/-3% of the basal level at 2 h and remained low for 16 h after treatment. This CRF-induced reduction of CRF-R1 mRNA expression was inhibited completely by pretreatment with protein kinase A (PKA) inhibitor (1 microM H-89). Further examination revealed that after pretreatment with 10 microM of antisense oligodeoxynucleotide for cyclic AMP-response element binding protein (CREB), the CRF-induced inhibition of CRF-R1 mRNA was partially decreased to 79+/-4% of the control level 2 h after administration of CRF. These findings indicate that CRF may down-regulate CRF-R1 mRNA expression via a cAMP-PKA-mediated mechanism in rat anterior pituitary cells, and that CREB may mediate at least a portion of this inhibitory effect.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Changes of oligosaccharides and fatty acids in monkey hippocampus by synaptic potentiation.

We measured the release of free fatty acids and structural changes of glycoprotein glycans induced by tetraethylammonium (TEA) salt in hippocampal slices of cynomolgus monkey brain. The release of free fatty acids in the hippocampal slices occurred after synaptic potentiation by TEA in a different manner from rat hippocampus. Arachidonic acid release in monkey hippocampus occurred much faster than that in rat. Several types of glycans of monkey hippocampal glycoproteins were determined depending on the duration time after TEA treatment. 5-Mannose was increased within 2 min, while polysialoglycans were increased after 5 min or later. Comparative study of glycans of monkey and rat hippocampal slices revealed the presence of relatively larger amount of sialo- and multi-anntenary glycans in rat than in monkey. These results indicate that the depolarizing stimulation of monkey hippocampal slices induced the change of glycoprotein glycan structures and release of free fatty acids in a different manner from rat hippocampus.

Animals↗