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Biomedical subjects

H Ichikawa

Publications and source records attributed to H Ichikawa.

At least 73 records · Page 4Linked to original sources

A novel strategy of decoy transfection against nuclear factor-kappaB in myocardial preservation.

BACKGROUND: Nuclear factor-kappaB (NFkappaB) is critical for the transcription of multiple genes involved in myocardial ischemia-reperfusion injury. Therefore, we hypothesized that blocking NFkappaB would attenuate ischemia-reperfusion injury after prolonged myocardial preservation, resulting in an improvement in cardiac function. METHODS: Double-stranded oligodeoxynucleotides with a specific affinity for NFkappaB (NFkappaB decoy group) or a scrambled decoy group were transfected into rat hearts using a hemagglutinating virus of Japan-liposome method. After 16 hours of preservation in Euro-Collins solution at 4 degrees C, the cardiac grafts were heterotopically transplanted into recipient rats of the same strain. RESULTS: Fluorescein isothiocyanate staining showed introduction of double-stranded oligonucleotides into the nuclei of endothelial cells and cardiomyocytes. After 1 hour of reperfusion the NFkappaB decoy group showed significantly higher degrees of recovery of left ventricular function as well as significantly lower levels of serum creatine phosphokinase, myocardial water content, tissue IL-8, and neutrophil infiltration than did the scrambled decoy group (p < 0.05). CONCLUSIONS: Gene transfection of the NFkappaB decoy attenuates ischemia-reperfusion injury after prolonged heart preservation. As a result, this method appears to be a novel strategy for enhanced myocardial preservation.

Animals↗

Change of c-Myc expression and cardiac hypertrophy in patients with aortic valve replacement.

BACKGROUND: Long-term volume overload to the left ventricle (LV) due to aortic regurgitation (AR) tends to cause severe impairment in LV function that cannot be reversed even with aortic valve replacement (AVR). Recently, we reported that the protooncogene c-myc is related to the onset of the cardiac hypertrophy and LV dysfunction in patients with chronic AR. However, it is still unclear whether c-myc is related to reversibility of the cardiac hypertrophy or LV dysfunction after AVR. METHODS AND RESULTS: Twenty patients with isolated chronic AR who underwent AVR were included in this study. LV function was calculated before and after AVR. After AVR, end-systolic volume index (ESVI) and enddiastolic volume index (EDVI) were improved, but not mass index (LVMI). However, normalization of ESVI and EDVI was observed only in 12 and 9 patients, respectively. Preoperatively, c-Myc protein was expressed in the myocardium of 16 out of 20 patients with an average point count of 35+/-30%. After AVR, c-Myc protein was observed only in 2 patients. Preoperative ejection fraction (EF), ESVI, and postoperative end-systolic stress (ESS)/ESVI had significant correlation to postoperative cell diameter (CD). Percent c-Myc protein expression before the operation was significantly correlated to postoperative CD, ESVI, and ESS/ESVI. Average c-Myc expression was higher in patients who showed normalization of CD and ESS/ESVI after AVR than the patients who did not. CONCLUSIONS: These data suggest that preoperative expression of c-Myc can be indicative of the reversibility of myocardial cellular hypertrophy and LV dysfunction.

Adult↗

trkA modulation of developing somatosensory neurons in oro-facial tissues: tooth pulp fibers are absent in trkA knockout mice.

To investigate the nerve growth factor requirement of developing oro-facial somatosensory afferents, we have studied the survival of sensory fibers subserving nociception, mechanoreception or proprioception in receptor tyrosine kinase (trkA) knockout mice using immunohistochemistry. trkA receptor null mutant mice lack nerve fibers in tooth pulp, including sympathetic fibers, and showed only sparse innervation of the periodontal ligament. Ruffini endings were formed definitively in the periodontal ligament of the trkA knockout mice, although calcitonin gene-related peptide- and substance P-immunoreactive fibers were reduced in number or had disappeared completely. trkA gene deletion had also no obvious effect on the formation of Meissner corpuscles in the palate. In the vibrissal follicle, however, some mechanoreceptive afferents were sensitive for trkA gene deletion, confirming a previous report [Fundin et al. (1997) Dev. Biol. 190, 94-116]. Moreover, calretinin-positive fibers innervating longitudinal lanceolate endings were completely lost in trkA knockout mice, as were the calretinin-containing parent cells in the trigeminal ganglion.These results indicate that trkA is indispensable for developing nociceptive neurons innervating oral tissues, but not for developing mechanoreceptive neurons innervating oral tissues (Ruffini endings and Meissner corpuscles), and that calretinin-containing, trkA dependent neurons in the trigeminal ganglion normally participate in mechanoreception through longitudinal lanceolate endings of the vibrissal follicle.

Animals↗

Controlled nicorandil administration for myocardial protection during coronary artery bypass grafting under cardiopulmonary bypass.

Nicorandil is a hybrid potassium channel opener, and recent experimental studies have demonstrated its efficacy in myocardial protection against ischemia-reperfusion. This clinical study was designed to examine the myocardial protective effect of nicorandil administered during cardiopulmonary bypass. Seventy adult patients, 53 men and 17 women, undergoing elective coronary artery bypass grafting were randomly assigned to two groups, one receiving nicorandil during cardiopulmonary bypass (group N, n = 35) and the other receiving no nicorandil for control (group C, n = 35). Nicorandil was administered at each dose of 0.1 mg/kg into the cardiopulmonary bypass circuit according to the following schedule: (1) bolus injection at the initiation of cardiopulmonary bypass, (2) continuous infusion for 5 min before aortic cross-clamping, (3) bolus administration at 5 min before reperfusion, and (4) continuous infusion for 5 min before reperfusion. The time required for achieving cardiac arrest after the initial cardioplegia was significantly reduced in group N in comparison with that in group C. After aortic unclamping, the number of patients showing a significant ST segment change on the electrocardiogram was significantly fewer in group N, whereas the number of patients showing spontaneous recovery of heart beat was significantly greater. As for the myocardial protective effect, group N showed lower plasma levels of malondialdehyde, human-heart fatty acid-binding protein, and peak creatine kinase-MB, and required lower doses of catecholamine. Our results suggest that nicorandil administration during cardiopulmonary bypass provides enhanced myocardial protective effects against ischemia-reperfusion in patients undergoing coronary artery bypass grafting.

Adult↗

Plasma adrenomedullin levels in patients on hemodialysis.

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 +/- 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 +/- 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.

Adrenomedullin↗

Relationships of serum levels of insulinlike growth factors with indices of bone metabolism and nutritional conditions in hemodialysis patients.

Insulinlike growth factor (IGF) I and IGF-II are synthesized in osteoblasts and stimulate proliferation, differentiation, and matrix synthesis in these cells. There is some evidence that IGFs act on bone cells not only by paracrine but also by endocrine pathways, suggesting that circulating IGFs may be of importance for the regulation of bone metabolism. On the other hand, the serum IGF-I level is also thought to be a good indicator of the nutritional conditions in hemodialysis patients. The present study was performed to analyze the correlations of circulating levels of IGF-I, IGF-II, IGF-binding protein (IGFBP) 1 and IGFBP-3 with biochemical markers of bone metabolism and parameters of the urea kinetic model which reflect nutritional conditions in hemodialysis patients. We also examined the differences between these relationships in male and female patients on hemodialysis. Sixty-two hemodialysis patients, 36 men (male group) and 26 women (female group), were included in this study. We measured the serum levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3. The bone mineral content (BMC) of the radius was measured by dual-energy X-ray absorptiometry. We calculated Kt/V, protein catabolic rate, and percent creatinine generation rate (%CGR). We also examined the relationships between serum levels of IGFs and BMC and the parameters of the urea kinetic model. It was found that the serum levels of IGF-I in the hemodialysis patients were almost the same as those in the control group. However, the serum levels of IGF-II, IGFBP-1, and IGFBP-3 in the hemodialysis patients were significantly higher than those in the control group. In the male group, the serum IGF-I levels showed a significant correlation with both serum intact parathyroid hormone levels and BMC, but no significant correlations between these indices were found in the female group. The serum levels of both IGF-I and IGF-II showed significant correlations with %CGR in the male group, but not in the female group. Stepwise multiple regression analysis was performed to clarify the relationship between serum levels of IGFs and BMC or %CGR. It was found that age, hemodialysis duration, serum intact parathyroid hormone levels, and sex were independent factors associated with BMC. The %CGR was associated independently with serum levels of IGF-I, and IGF-II and with the presence of diabetes mellitus. In conclusion, it is thought that serum levels of IGF-I and IGF-II can be used as indices of nutritional conditions in hemodialysis patients. However, the serum IGF-I level cannot be used as a marker of bone metabolism in hemodialysis patients.

Biomarkers↗

Antioxidant potential of qizhu tang, a chinese herbal medicine, and the effect on cerebral oxidative damage after ischemia reperfusion in rats.

A traditional Chinese herbal medicine, Qizhu Tang (QZT) was studied for its in vitro antioxidant activity and the effect on cerebral oxidative damage after forebrain ischemia followed by reperfusion in rats. The QZT decoction was shown to have strong hydroxyl radical (*OH) scavenging activity (approx. 0.1 mM as Trolox equivalent) when determined by ESR using DMPO as a spin trap reagent and H2O2/UV as the *OH source. When the QZT decoction was injected into rat duodenum 2 h before cerebral ischemia, the oxidative brain damage after 45 min reperfusion was strongly inhibited in terms of two biochemical indications, thiobarbituric acid reactive substance formation and the loss of glutathione peroxidase. Since the QZT formula consists of 4 herbal constituents (Rhizoma atractylodis, Poria, Radix notoginseng and Radix astragali), each of the component herbs and their combinations were also examined for their protective effects on the cerebral ischemia/reperfusion injury and the effects were compared with their in vitro antioxidant potential. Although some of the incomplete formulas showed as strong antioxidant activities as complete QZT in vitro, only the complete QZT formula was effective in preventing cerebral oxidative injury in rats, and other preparations showed limited activity in vivo.

Animals↗

Numerical feasibility study of the fabrication of subwavelength structure by mask lithography.

Electromagnetic diffraction of a light wave by a single aperture of subwavelength width and subsequent propagation in a lossy medium are numerically investigated. This diffraction problem simulates exposure of a resist with an amplitude mask. It is found that there is the possibility of fabricating a lambda/2 structure on a resist of lambda/4 thickness, where lambda is the wavelength of the exposing light in vacuum, by conventional contact or by proximity lithography. It is also found that an air gap between a mask and a resist of up to lambda/2 does not have a significant effect on resolution. This approach permits easy and cost-effective fabrication of subwavelength structures and leads to wide availability of diffractive optical elements in the nonscalar domain.

Journal Article↗

[A case of chronic methyl bromide intoxication showing symmetrical lesions in the basal ganglia and brain stem on magnetic resonance imaging].

A 30-year-old man developed paresthesia in the feet, unstable gait and blepharoptosis subsequent to pharyngeal pain while working in a warehouse of imported fruit and vegetable fumigated with methyl bromide and cyanate. Neurological examination showed bilateral blepharoptosis, diplopia, ataxic gait and paresthesia below the inguinal region. The serum concentration of thiociane, a metabolite of cyanide, was within normal limits, but that of bromide was elevated (43.7 mg/l, normal: 3.7-8.6). Thus we diagnosed the patient as intoxication of methyl bromide. Magnetic resonance imaging of the brain (MRI) revealed bilateral symmetrical lesions of high signal intensity in the posterior region of the putamen, the subthalamic nuclei, the dorsal medulla oblongata corresponding to inferior cerebellar peduncles and vestibular nuclei, the inferior colliculi and the periaqueductal gray matter surrounding the oculomotor nucleus of the midbrain. As far as we know, this is the first report of MRI detected cerebral lesions in a case with intoxication of methyl bromide.

Adult↗

[Ataxic form of Guillain-Barré syndrome associated with anti-GD1b IgG antibody].

A 28-year-old man was admitted after developing acute onset unstable gait following acute enteritis. Neurological examination revealed mild weakness in four limbs, areflexia and ataxia. Serum obtained from the patient during the acute stage contained a high titer of anti-GD1b IgG antibody. Because the patient showed obvious cerebellar ataxia unrelated to muscle weakness, without ophthalmoplegia or proprioceptive sensory disturbance, we concluded that he had ataxic form of Guillain-Barré syndrome (GBS) (Richter, 1962). Although ataxic GBS is not an established conception, one should pay attention to the possible existence of such a rare GBS variant. It is necessary to accumulate additional case reports to clarify the association between ataxic GBS and anti-ganglioside antibodies.

Adult↗

Kheper, a novel ZFH/deltaEF1 family member, regulates the development of the neuroectoderm of zebrafish (Danio rerio).

Kheper is a novel member of the ZFH (zinc-finger and homeodomain protein)/deltaEF1 family in zebrafish. kheper transcripts are first detected in the epiblast of the dorsal blastoderm margin at the early gastrula stage and kheper is expressed in nearly all the neuroectoderm at later stages. kheper expression was expanded in noggin RNA-injected embryos and also in swirl mutant embryos and was reduced in bmp4 RNA-injected embryos and chordino mutant embryos, suggesting that kheper acts downstream of the neural inducers Noggin and Chordino. Overexpression of Kheper elicited ectopic expansion of the neuroectoderm-specific genes fkd3, hoxa-1, and eng3, and the ectopic expression of hoxa-1 was not inhibited by BMP4 overexpression. Kheper interacted with the transcriptional corepressors CtBP1 and CtBP2. Overexpression of a Kheper mutant lacking the homeodomain or of a VP16-Kheper fusion protein disturbed the development of the neuroectoderm and head structures. These data underscore the role of Kheper in the development of the neuroectoderm and indicate that Kheper acts as a transcriptional repressor.

Alcohol Oxidoreductases↗

Light and Oxygen Protective Properties of Materials Induced by Surfactant Molecular Complex Formation.

Crystalline surfactant molecular complexes, the quite stable existence of which we firmly established through X-ray structural analysis, etc., were examined with respect to the protection from UV light and oxygen provided to their additive components. Structural analysis has revealed that the complex additives are stably occluded in the mother surfactant crystal matrix. Through the examination it was confirmed that additive components in a cationic complex crystal structure were perfectly protected from both UV light and oxygen. On the other hand, in anionics the additives were perfectly safe from UV attack, but from oxygen the change was rather accelerated in comparison with the effect of that on the pure condition. Copyright 2000 Academic Press.

Journal Article↗

Analysis of genes under the downstream control of the t(8;21) fusion protein AML1-MTG8: overexpression of the TIS11b (ERF-1, cMG1) gene induces myeloid cell proliferation in response to G-CSF.

The AML1-MTG8 fusion transcription factor generated by t(8;21) translocation is thought to dysregulate genes that are crucial for normal differentiation and proliferation of hematopoietic progenitors to cause acute myelogenous leukemia (AML). Although AML1-MTG8 has been shown to repress the transcription of AML1 targets, none of the known targets of AML1 are probably responsible for AML1-MTG8-mediated leukemogenesis. In this study, 24 genes under the downstream control of AML1-MTG8 were isolated by using a differential display technique. Analysis with deletion mutants of AML1-MTG8 demonstrated that the regulation of the majority of these genes requires the region of 51 residues (488-538) containing the Nervy homology region 2 (NHR2), through which AML1-MTG8 interacts with MTGR1. Among the 24 genes identified, 10 were considered to be genes under the control of AML1, because their expression was altered by AML1b or AML1a or both. However, the other 14 genes were not affected by either AML1b or AML1a, suggesting the possibility that AML1-MTG8 regulates a number of specific target genes that are not normally regulated by AML1. Furthermore, an up-regulated gene, TIS11b (ERF-1, cMG1), was highly expressed in t(8;21) leukemic cells, and the overexpression of TIS11b induced myeloid cell proliferation in response to granulocyte colony-stimulating factor. These results suggest that the high-level expression of TIS11b contributes to AML1-MTG8-mediated leukemogenesis. (Blood. 2000;96:655-663)

Animals↗

Combined action of two transcription factors regulates genes encoding spore coat proteins of Bacillus subtilis.

During sporulation of Bacillus subtilis, spore coat proteins encoded by cot genes are expressed in the mother cell and deposited on the forespore. Transcription of the cotB, cotC, and cotX genes by final sigma(K) RNA polymerase is activated by a small, DNA-binding protein called GerE. The promoter region of each of these genes has two GerE binding sites. 5' deletions that eliminated the more upstream GerE site decreased expression of lacZ fused to cotB and cotX by approximately 80% and 60%, respectively but had no effect on cotC-lacZ expression. The cotC-lacZ fusion was expressed later during sporulation than the other two fusions. Primer extension analysis confirmed that cotB mRNA increases first during sporulation, followed by cotX and cotC mRNAs over a 2-h period. In vitro transcription experiments suggest that the differential pattern of cot gene expression results from the combined action of GerE and another transcription factor, SpoIIID. A low concentration of GerE activated cotB transcription by final sigma(K) RNA polymerase, whereas a higher concentration was needed to activate transcription of cotX or cotC. SpoIIID at low concentration repressed cotC transcription, whereas a higher concentration only partially repressed cotX transcription and had little effect on cotB transcription. DNase I footprinting showed that SpoIIID binds strongly to two sites in the cotC promoter region, binds weakly to one site in the cotX promoter, and does not bind specifically to cotB. We propose that late in sporulation the rising level of GerE and the falling level of SpoIIID, together with the position and affinity of binding sites for these transcription factors in cot gene promoters, dictates the timing and level of spore coat protein synthesis, ensuring optimal assembly of the protein shell on the forespore surface.

Bacillus subtilis↗

Neurocalcin-immunoreactive primary sensory neurons in the trigeminal ganglion provide myelinated innervation to the tooth pulp and periodontal ligament.

The distribution of neurocalcin-immunoreactive (NC-ir) primary sensory neurons was examined in the trigeminal ganglion (TG), mesencephalic trigeminal tract nucleus (Mes5) and intraoral structures. NC-ir primary sensory neurons were located in the TG but not the Mes5. The coexpression study demonstrated that virtually all NC-ir TG neurons exhibited S100-immunoreactivity (-ir). In the tooth pulp, NC-ir nerve fibers were observed in the subodontoblastic and odontoblastic layers. Immunoelectron microscopic and retrograde tracing methods revealed that myelinated pulpal axons derived from the TG mostly exhibited the ir. In the periodontal ligament, bush-like endings showed NC-ir. These endings were morphologically identical to Ruffini-like endings. The present study suggests that NC-ir trigeminal primary sensory neurons have their cell bodies in the TG. Their peripheral axons are probably myelinated. Such neurons include pulpal nociceptors and low-threshold mechanoreceptors.

Animals↗