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Biomedical subjects

H Ichikawa

Publications and source records attributed to H Ichikawa.

At least 109 records · Page 6Linked to original sources
PubMed2000

Effect of vitamin E on aspirin-induced gastric mucosal injury in rats.

We investigated the effect of vitamin E on aspirin-induced gastric mucosal injury in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups and were fed for 20 weeks with a diet containing <0.1 mg/100 g of alpha-tocopherol (vitamin E-deficient), 2 mg/100 g of alpha-tocopherol (normal and vitamin E-sufficient), or 50 mg/100 g of alpha-tocopherol (vitamin E-supplemented). In vitamin E-deficient rats, oral administration of aspirin (200 mg/kg) plus HCI created more severe hemorrhagic erosions than in other rats. Vitamin E-deficient rats had higher levels of thiobarbituric acid reactive substances, myeloperoxidase activity, and cytokine-induced neutrophil chemoattractant in the gastric mucosa. Flow cytometry showed that CD18 expression on stimulated neutrophils was higher in vitamin E-deficient rats than in vitamin E-supplemented rats. These results suggest that vitamin E protects against aspirin-induced gastric mucosal injury by inhibiting lipid peroxidation and accumulation of activated neutrophils.

Animals↗
PubMed2000

Mouse Peg9/Dlk1 and human PEG9/DLK1 are paternally expressed imprinted genes closely located to the maternally expressed imprinted genes: mouse Meg3/Gtl2 and human MEG3.

BACKGROUND: Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of imprinted genes has been extensively carried out to identify the genes responsible for imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed imprinted genes (Pegs). We compared the resulting expression profiles of parthenogenetic and fertilized control embryos to identify novel imprinted genes. RESULTS: A novel paternally expressed mouse imprinted gene, Peg9/Dlk1, was identified. Consistent with this finding, the paternal expression of its human homologue, PEG9/DLK1, was also confirmed. These two genes form imprinted gene clusters with the reciprocally imprinted mouse Meg3/Gtl2 and human MEG3 genes that we first identified on distal chromosome 12 and chromosome 14q32, respectively. CONCLUSIONS: As DNA chip technology allows us to quickly screen a large number of genes, using this technology to search for imprinted genes could accelerate the identification of genes responsible for human and mouse genetic diseases. Dlk1 and DLK1, which encode transmembrane proteins, have six EGF-like repeats and show homology to the Delta gene in Drosophila melanogaster. Because of its homology to mammalian Delta homologues, PEG9/DLK1 may contribute to the scoliosis phenotype observed in maternal uniparental disomy 14 (mUPD14) patients.

Animals↗
PubMed2000

Neutrophil activation in immunoadsorption.

Immunoadsorption therapy (IAT) is used in the treatment of autoimmune diseases. Although IAT has been reported to modify humoral immunity by inducing chemokines and activating complements, much remains unknown about the biological effects of IAT on cellular components in peripheral blood. To define the influence of IAT on leukocytes, we determined leukocyte L-selectin (CD62L) and Mac-1 (CD11b) as parameters for activation of leukocytes in peripheral blood during IAT. Peripheral leukocyte L-selectin and Mac-1 were determined continuously by flow cytometry in 6 patients with neuroimmunological disorders in whom IAT was conducted using a Plasma Flow OP-05 (Asahi Medical Corp., Tokyo, Japan) as a plasma separator and Immusorba TR-350 (Asahi Medical Corp., Tokyo, Japan) as an adsorption column. Expression of neutrophils (PMN) L-selectin was decreased 30 min after starting IAT, with the decreases particularly marked at the end of IAT, while expression of mononuclear cells (MNC) L-selectin slightly increased during IAT. Expression of PMN Mac-1 was markedly increased at the end of IAT, whereas expression of MNC Mac-1 did not change during IAT. Leukocyte counts decreased 30 min after starting IAT, and then increased to the initial level or higher in parallel with L-selectin downregulation and Mac-1 upregulation on PMN. L-selectin downregulation and Mac-1 upregulation on PMN suggested that activation of PMN associated with changes in peripheral leukocyte counts occurred during IAT and might play some role in modulating the human circulating blood and immune systems.

Adolescent↗
PubMed2000

Novel variant of p230 trans-Golgi network protein identified by serum from Sjögren's syndrome patient.

Trans-Golgi network (TGN) protein p230 is a peripheral membrane protein associated with the cytoplasmic face of the TGN. TGNp230 is an extensively coiled-coil protein with flexible amino- and carboxyl-terminal ends, associates with non-clathrin-coated vesicles arising from the TGN, and is implicated in vesicle biogenesis. Here we used an autoimmune serum from a patient with S ogren's syndrome to clone partial cDNAs from a human hepatoma HepG2 expression library. The partial cDNAs encoded a novel amino-terminal splice variant of TGNp230. Specific reactivity of the autoimmune serum for p230 is supported by immunofluorescene staining of the Golgi apparatus, immunoblotting of a > 200-kDa HeLa cell protein, and reactivity with a bacterially expressed GST-p230 fusion protein. The alternative splicing occurs within the first proline-rich domain of p230. It comprises a deletion of 30 bp followed immediately by an additional 66 bp absent in the published sequence. RT-PCR analysis indicated that the splicing occurs independently of previously reported carboxyl-terminal splicing, and that this novel splice variant is more frequent than the previously reported p230. The novel splice variant of p230 is also located at the TGN. We propose that p230 splice variants may be implicated in selection of cargo molecules for vesicles arising from the TGN.

Alternative Splicing↗
PubMed2000

The significance of serum homocysteine levels in diabetic patients on haemodialysis.

BACKGROUND: Atherosclerotic diseases are the major cause of mortality and morbidity in patients on haemodialysis (HD). Furthermore, the prognosis of diabetic patients on HD is especially poor due to atherosclerotic complications. Because homocysteine (Hcy), a sulfur-containing amino acid, is emerging as an important risk factor for atherosclerosis in patients with end-stage renal disease, we examined the significance of serum Hcy levels in diabetic patients on HD. METHODS: We measured total serum Hcy levels (tHcy) in 31 patients with diabetes mellitus on HD (DM group) and 37 non-diabetic patients on HD (N group), adjusting for age and HD duration. Linear regression analysis was used to assess the correlation of multiple variables to tHcy. RESULTS: The proportion of atherosclerotic disease in the DM group was significantly higher than in the N group. However, serum tHcy, serum creatinine and per cent creatinine generation rate in the DM group were significantly lower than in the N group. In the DM group, serum tHcy was positively correlated with creatinine, albumin and per cent creatinine generation rate, respectively. This was not the case in the N group. CONCLUSIONS: The demethylation pathway in methionine metabolism in the liver, which is linked directly to the creatinine generation system, may be disturbed in diabetic patients on HD. This may be the reason why serum tHcy and creatinine in diabetic patients on HD are lower than in non-diabetic patients on HD. Therefore, it is necessary to consider the possibility of an altered relation between serum tHcy and vessel disease when evaluating the atherogenic risk in diabetic patients on HD.

Aged↗
PubMed2000

Perinatal risk factors related to neurologic outcomes of term newborns with asphyxia at birth: a prospective study.

OBJECTIVES: The incidence of poor neurologic outcomes was studied in term newborns who had suffered severe asphyxia at birth. METHODS: Subjects were 152 newborns admitted to the NICU with a low Apgar score at 1 or 5 minutes. A 1-year prospective follow-up of neurological outcomes was carried out by a questionnaire survey concluded between April 1, 1996 and March 31, 1998. RESULTS: 1) The incidence of a poor neurologic outcome, including 15 neurologic sequelae and 6 deaths, was 13.8% among the subjects. 2) The risk of a poor outcome was increased by 13-fold in neonates with adverse neurological signs and 31-fold in those with hypoxic ischemic encephalopathy. CONCLUSION: The incidence of poor neurologic outcome was very high among term infants with low Apgar scores. These infants were 10 times to 20 times more likely to die, or to survive with permanent disabilities, than were infants without low Apgar scores.

Adult↗
PubMed2000

[New theory predicting molecular shapes (deviation of framework and orbital from those of norm)].

The aim of this paper is to understand why the molecule has its own structure (optimized geometry) which differs from the standard one (norm). Basic strategy to obtain the optimized geometry is to start from the norm. The emphases are 1) a theory predicting polarization exemplified by norbornene HOMO distortion and 2) when we apply any theory of 1), what framework should we use? The latter is very important due to the fact that the optimized geometries of cations and anions differ greatly from the norms. For polarization, we have elaborated "in-bond orbital method." The method is based on the well-known correlation between separated atoms and united atom and able to represent polarization within minimum basis set only by the first-order perturbation theory. For cationic and anionic hydrocarbons, a new method consisting of an assumption and a few recipes is developed. Although the assumption that the framework distortion surpasses the orbital distortion (polarization) is based solely on organic chemist's intuition, this method correctly suggests the structure (framework) to which the in-bond orbital method should be applied. All of the optimized geometries used in this study are obtained by HF/6-31 + G*.

Anions↗
PubMed2000

Increase of calmodulin III gene expression by mu-opioid receptor stimulation in PC12 cells.

Calmodulin (CaM) is a principal multifunctional mediator of Ca2+ signaling in cells. It is reported that morphine increases CaM contents in mouse brain. However, the precise mechanism of CaM induction by morphine is unknown. We investigated the changes of CaM by opioid receptor stimulation in mRNA and protein levels. Expression of CaM was increased in dose- and time-dependent manners by morphine with RT-PCR assay in PC12 cells, and naloxone inhibited the effect of morphine. The expression was also increased with DAMGO (mu-opioid agonist), but not by DPDPE (delta) and U50488 (kappa). Northern blot analysis revealed that the CaMIII gene was responsive to morphine or DAMGO. CaM protein increased by DAMGO were distributed in both soluble and membranous fractions in the cells. Taken together, the data suggest that morphine induces the expression of CaMIII gene through mu-opioid receptor stimulation.

Analgesics, Opioid↗
PubMed2000

[Successful total gastrectomy of gastric cancer in a congenital factor V deficient patient].

Congenital factor V deficiency is a very rare hereditary coagulation disorder. Total gastrectomy in a patient with factor V deficiency has not been reported in Japan. A 71-year-old woman visited our hospital because of gastric cancer and gallbladder stone. A preoperative screening examination revealed severe anemia, prolonged prothrombin time (35.1 sec.) and activated partial thromboplastin time (109.8 sec.) The value of factor V was 8%. Her parents had a consanguineous marriage. The level of factor V in her two children and a grandchild were lower than the normal limit. We transfused fresh blood and fresh frozen plasma (FFP) preoperatively in order to improve anemia and prothrombin time and activated thromboplastin time. Operating carefully with transfused FFP and fresh blood, we performed total gastrectomy with cholecystectomy successfully. There was no serious tendency to hemorrhage during the operation and the postoperative period. Enough FFP should be transfused during the pre- and postoperative period, paying attention to pulmonary or cardiac failure in elderly patients. Postoperatively, during FFP should be used for 3-10 day with under careful observation of wound bleeding.

Adenocarcinoma↗
PubMed2000

[Synchronous primary triple cancers including the lung, stomach, and thyroid: a case report].

A 62-year-old man with synchronous multiple primary cancers involving the lung, stomach, and thyroid was admitted. Initially the patient's chest X-ray showed an abnormal shadow in the right middle-lobe indicating lung cancer. During preoperative examination, gastric cancer of the antrum and angle were detected. Excisional biopsy of the lymph node in the neck after chest surgery revealed thyroid cancer. A middle lobectomy with mediastinal lymph node dissection was performed for lung cancer and the histological diagnosis was moderately differentiated adenocarcinoma, pT4N2M0, stage IIIB. Gastric cancer was treated by endoscopic mucosal resection. Considering the relatively better prognosis of papillary thyroid cancer, we concluded that no further treatment to the thyroid lesion was necessary. In Japan, according to autopsy reports, triple primary cancers are gradually increasing. During the periods 1994 to 1996, the incidence of triple cancers was 0.81% of all autopsy cases reported.

Adenocarcinoma↗
PubMed2000

Studies of the metabolism of alpha-tocopherol stereoisomers in rats using [5-methyl-(14)C]SRR- and RRR-alpha-tocopherol.

We investigated the distribution and metabolism of SRR-alpha-tocopherol (SRR-alpha-Toc), synthetic alpha-Toc compared with RRR-alpha-Toc, in rats after a single oral administration of 2 mg (20 microCi) SRR- and RRR-alpha-[5-methyl-(14)C]Toc. In the liver, there was no difference in the recovery of radioactivity until 12 h after administration, and it reached a maximum of 4.4% of the dose after 12 h, but in other tissues, radioactivity derived from RRR-alpha-Toc was clearly higher than that derived from SRR-alpha-Toc after 12 h. For 96 h after administration, urinary excretions of SRR-alpha-Toc were 7.8% of the dose and significantly greater than that of RRR-alpha-Toc, which was 1.3% of the dose. On the other hand, total fecal excretions of SRR- and RRR-alpha-Toc were 87.6% and 83.0%, respectively. Therefore, radioactivity in the urine was assumed to have transferred out of the liver. Furthermore, the urine samples were hydrolyzed with 3 N methanolic HCl and analyzed by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry. The results showed that about 73% of the total radioactivity injected into HPLC was found to be 2,5,7, 8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxy chroman (alpha-CEHC), as well as RRR-alpha-Toc. Thus, there is no difference between SRR-alpha-Toc and RRR-alpha-Toc in metabolic pathways, and it is suggested that SRR-alpha-Toc discriminated in the liver is rapidly metabolized by the liver and excreted as the conjugate of alpha-CEHC in the urine.

Animals↗
PubMed2000

Endothelial cells exposed to anoxia/reoxygenation are hyperadhesive to T-lymphocytes: kinetics and molecular mechanisms.

OBJECTIVE: The objectives of this study were to 1) determine the time-course of T-lymphocyte adhesion to monolayers of human umbilical vein endothelial cell (HUVEC) that were exposed to 60 min of anoxia followed by 24 h of reoxygenation, and 2) define the mechanisms responsible for the hyperadhesivity of postanoxic HUVEC to human T-lymphocytes. METHODS: Human peripheral blood mononuclear leukocytes were isolated from heparinized peripheral blood. T-lymphocytes were obtained by negative selection using a MACS column. HUVEC monolayers were exposed to anoxia/reoxygenation (A/R), and then reacted with 51Cr -labeled T-lymphocytes in adhesion assays. RESULTS: A/R leads to an increased adhesion of T-lymphocytes to HUVEC monolayers, with peak responses occurring at 8 h after reoxygenation. This adhesion response was largely attributed to the CD4+ T-cell subset. The hyperadhesivity of A/R-exposed HUVEC was inhibited by monoclonal antibodies directed against either LFA-1, VLA-4, ICAM-1, or VCAM-1, indicating a contribution of these adhesion molecules and their ligands. Moreover, T-cell hyperadhesivity was attenuated by anti- IL-8. consistent with a role for this chemokine in the adhesion response. Protein synthesis inhibitors (actinomycin D and cycloheximide) as well as chemical inhibitors of (and binding ds-oligonucleotides to) NFkappaB and AP-1 significantly attenuated the A/R-induced T-lymphocyte adhesion responses. The kinetics of VCAM-1 on post-anoxic HUVEC correlated with the T-lymphocyte adhesion response. CONCLUSIONS: A/R elicits a T-lymphocyte-endothelial cell adhesion response that involves transcription-dependent surface expression of VCAM-1.

Antibodies, Monoclonal↗
PubMed2000

[A relationship between a psychosomatic and a skin condition in patients with atopic dermatitis].

Atopic dermatitis (AD) has been clinically well-known to be frequently exacerbated by some psychosomatic stress. In this study, we examined a relationship between a psychosomatic and a skin condition in patients with AD. Visual analogue scale (VAS) for the grade of general physical condition, mental stress and others were reported daily for themselves, while skin physiological parameters, resident skin bacteria and a psychological questionnaire (POMS) were measured every 2 weeks. It was observed that tense-anxious and depressive scores of POMS tended to correlate with skin conductance, a skin clinical score and a number of total skin bacteria and others. These results suggest that changes of psychosomatic condition reciprocally correlate with the exacerbation and improvement of skin symptom in patients with AD.

Adolescent↗
PubMed2000

[A case of atopic dermatitis which showed correlation of psychological state and lesions--changes of value of psychological test, skin lesion and NK cell activity].

The relationship between psychological state and skin lesions of atopic dermatitis were investigated with a 31-year-old male patient. He had severe atopic dermatitis which became worse with psychological stress. A psychological test, profile of mood states (POMS), was performed on him every 2 weeks. Peripheral lymphocytes and natural killer (NK) cell activity were investigated at some points. When the psychological state showed more depressive, anxiety, anger, fatigue and confusion, the skin lesions became worse and recovered after the psychological states turned well. Correlation was shown between itch and stress or fatigue by a visual analogue scale (VAS) (p < 0.001). NK cell activity decreased during the worse psychological state and recovered during the near normal psychological state, although, the lymphocyte count and CD4/8 ratio in peripheral blood did not change during the study. These results suggest that some patients with atopic dermatitis should be treated psychologically in addition to standard dermatological treatment.

Adult↗
PubMed1999

Peptide 19-immunoreactive primary sensory neurons in the rat trigeminal ganglion.

Peptide 19-immunoreactivity (PEP 19-IR) was examined in the trigeminal ganglion (TG) of the adult rat. A half of TG neurons were immunoreactive(IR) for PEP 19. PEP 19-IR neurons were mostly medium-sized to large. 66% of TG neurons > 600 microm(2) and 38% of those in the range 300-600 microm(2) showed the IR. TG neurons <300 microm(2) were mostly devoid of PEP 19-IR (86%). A double immunofluorescence method revealed the coexpression of PEP 19 and calcium-binding proteins. 31% and 16% of PEP 19-IR neurons exhibited parvalbumin- and calbindin D-28k-IRs, respectively. Conversely, a half of parvalbumin- (53%) and calbindin D-28k-IR (55%) neurons coexpressed PEP 19-IR. PEP 19-IR neurons were mostly IR for S100 (91%) and 80% of S100-IR neurons showed PEP 19-IR. Virtually all (99%) PEP 19-IR neurons were devoid of calcitonin gene-related peptide (CGRP)-IR. The molar tooth pulp contained PEP 19-IR nerve fibers. In the root pulp, PEP 19-IR nerve fibers projected straight until they reached the coronal pulp. Accompanied by blood vessels, these nerve fibers ascended toward the pulp horn. They formed nerve plexuses in the subodontoblastic layer, and reached the base of the odontoblastic layer. However, PEP 19-IR nerve fibers could not be observed within the odontoblastic layer, predentine or dentine. The distribution of these nerve fibers was similar to that of parvalbumin-IR ones. In the TG, PEP 19-IR was found in 34% of primary sensory neurons retrogradely labeled from the molar tooth pulp. 80% of PEP 19-IR tooth pulp TG neurons coexpressed parvalbumin-IR. An immunoelectron microscopic method revealed that a half of radicular axons showed PEP 19-IR. 80% of myelinated axons exhibited PEP 19-IR, whereas 20% of unmyelinated ones showed the IR. In the subodontoblastic layer, PEP 19-IR nerve fibers mostly lost myelin sheath or Schwann cell ensheathment. At the base of the odontoblastic layer, PEP 19-IR neurites made close contact with odontoblasts. PEP 19-IR nerve endings could not be observed in other oro-facial tissues. The coexpression of PEP 19 and CaBPs suggests that low-threshold mechanoreceptors contain PEP 19-IR in the TG. It is also likely that PEP 19-IR TG neurons include myelinated nociceptors.

Animals↗
PubMed1999

The coexistence of TrkA with putative transmitter agents and calcium-binding proteins in the vagal and glossopharyngeal sensory neurons of the adult rat.

The presence of the neurotrophin receptor, TrkA, in neurochemically identified vagal and glossopharyngeal sensory neurons of the adult rat was examined. TrkA was colocalized with calcitonin gene-related peptide (CGRP), parvalbumin, or calbindin D-28k in neurons of the nodose, petrosal and/or jugular ganglia. In contrast, no TrkA-immunoreactive (ir) neurons in these ganglia colocalized tyrosine hydroxylase-ir. About one-half of the TrkA-ir neurons in the jugular and petrosal ganglia contained CGRP-ir, whereas only a few of the numerous TrkA-ir neurons in the nodose ganglion contained CGRP-ir. Although 43% of the TrkA-ir neurons in the nodose ganglion contained calbindin D-28k-ir, few or no TrkA-ir neurons in the petrosal or jugular ganglia were also labeled for either calcium-binding protein. These data show distinct colocalizations of TrkA with specific neurochemicals in vagal and glossopharyngeal sensory neurons, and suggest that nerve growth factor (NGF), the neurotrophin ligand for TrkA, plays a role in functions of specific neurochemically defined subpopulations of mature vagal and glossopharyngeal sensory neurons.

Age Factors↗
PubMed1999

Formula optimization based on artificial neural networks in transdermal drug delivery.

The promoting effect of O-ethylmenthol (MET) on the percutaneous absorption of ketoprofen from alcoholic hydrogels was evaluated in rats in vitro and in vivo. Furthermore, a novel simultaneous optimization technique incorporating an artificial neural network (ANN) was applied to a design of a ketoprofen hydrogel containing MET. When a small quantity of MET (0.25-0.5%) was added to the hydrogels, the permeation of ketoprofen increased remarkably, compared with the control. On the other hand, little change in permeation was observed when small amounts of menthol were used (<1%), and at least 2% menthol was required to obtain a promoting efficiency comparable with 0.25% MET. The partitioning of ketoprofen from the hydrogel to the skin was improved by the addition of a small amount of MET, whereas the diffusivity of the drug was enhanced at higher concentration of MET (0.5-1%). For the optimization study, the amount of ethanol and MET were selected as causal factors. A rate of penetration (R(p)) and lag time (t(L)) and total irritation score (TIS) were selected as response variables. A set of causal factors and response variables was used as tutorial data for ANN and fed into a computer. Nonlinear relationships between the causal factors and the response variables were represented well with the response surface predicted by ANN. The optimization of the ketoprofen hydrogel was performed according to the generalized distance function method. The observed results of R(p) and TIS, which had a lot of influence on the effectiveness and safety, coincided well the predictions.

Animals↗