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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 649 records · Page 36Linked to original sources

Multiple fixed drug eruption caused by iomeprol (Iomeron), a nonionic contrast medium.

Most cases of drug eruption caused by nonionic contrast media (NICM) reported to date have been of the erythema multiforme type. Herein we report the first case of multiple fixed drug eruption (FDE) caused by iomeprol (Iomeron(R)). A 67-year-old woman developed multiple pea-sized erythematous papules on the trunk and extremities 4 days after receiving 100 ml of iomeprol for a computed tomography examination. Some of the papules coalesced, forming 7 large plaques on the limbs. Six months later, the patient was mistakenly administered iomeprol again. On the following morning, erythematous plaques admixed with vesicles recurred at the same sites as during the previous episode. In both episodes, the lesions cleared leaving pigmentation that faded with 6 weeks. Both patch testing and an intradermal test with iomeprol on lesional pigmented skin were positive. The present case indicates that NICM may cause multiple FDE and that repeated administration of the causative agent may increase the severity of the eruption.

Aged↗

Circadian variation in nasal reactivity in children with allergic rhinitis: correlation with the activity of eosinophils and basophilic cells.

BACKGROUND: In allergic rhinitis, the major symptoms of runny nose, sneezing, and stuffy nose tend to become worse upon waking up in the morning, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether the worsening of allergic rhinitis in the morning is associated with changes in the activity of inflammatory cells. METHODS: Nasal reactivity to methacholine was assessed twice in 8 children with allergic rhinitis and 8 healthy control subjects at 6.00 a.m. and 3.00 p.m. The amounts of eosinophil cationic protein (ECP), histamine and tryptase in induced nasal secretions and peripheral blood were also measured. RESULTS: Nasal reactivity to methacholine was higher at 6.00 a.m. not only in patients but also in healthy controls. Serum ECP and plasma histamine levels showed no circadian patterns. On the other hand, significantly higher levels of inflammatory activation products were found in nasal secretions at 6.00 a.m., thus showing a direct association with nasal reactivity. CONCLUSION: These results suggest that the circadian variation in nasal reactivity is associated with changes in the activity of eosinophils and basophilic cells in the nasal mucosa.

Adolescent↗

Genetic dissection of lupus pathogenesis: a recipe for nephrophilic autoantibodies.

Sle1 and Sle3 are 2 loci that confer susceptibility to lupus nephritis in the NZM2410 strain of mice. Our previous work has shown that B6.NZMc1 mice, congenic for Sle1, exhibit loss of tolerance to chromatin but do not develop any pathogenic autoantibodies or disease. B6.NZMc7 mice, congenic for Sle3, exhibit low-grade polyclonal B- and T-cell activation, elevated CD4/CD8 ratios, and mildly penetrant glomerulonephritis. In contrast to these monocongenics, the present study reveals that B6.NZMc1|c7 mice, bicongenic for Sle1 and Sle3, exhibit splenomegaly, significantly expanded populations of activated B and CD4(+) T cells, and a robust, variegated IgG autoantibody response targeting multiple components of chromatin (including double-stranded DNA), intact glomeruli, and basement membrane matrix antigens. As one might predict, these mice, particularly the females, exhibit highly penetrant glomerulonephritis. These findings lend strong support to a two-step epistatic model for the formation of pathogenic, nephrophilic autoantibodies in lupus. Whereas loci such as Sle1 may serve to breach tolerance to chromatin, full-blown pathogenic maturation of the autoantibody response appears to require additional input from other loci (such as Sle3) and gender-based factors.

Animals↗

Immunohistochemical staining patterns of MUC1, MUC2, MUC4, and MUC5AC mucins in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum.

We studied the distribution of the four human apomucins MUC1, MUC2, MUC4, and MUC5AC in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum using immunohistochemical techniques, with the aim of comparing and contrasting their patterns of expression. A series of 12 hyperplastic polyps, 27 serrated adenomas, and 20 traditional adenomas was studied. No significant change in apomucin expression was observed in traditional adenomas compared with normal colorectal epithelium, except for MUC5AC, which was present in 12 of the adenomas (60%) and only 20% of the normal samples. In both hyperplastic polyps and serrated adenomas, MUC2 and MUC5AC mucin expression was consistently and markedly increased. In 50% of the hyperplastic polyps, MUC4 was reduced but in the remaining cases was similar to normal. Loss of MUC4 expression was observed in all serrated adenomas. MUC1 was not increased in the hyperplastic polyps but increased expression was seen in 17 of the serrated adenomas (63%). Similar altered distribution patterns of MUC2, MUC4, and MUC5AC were seen in hyperplastic polyps and serrated adenomas, whereas traditional adenomas showed little change from normal patterns of expression. Although hyperplastic polyps are commonly defined as benign lesions without neoplastic potential, the similar phenotypes of hyperplastic and serrated adenomas and the existence of mixed polyps suggest that these lesions may represent a histogenetic continuum.

Adenoma↗

Proliferation and differentiation of unilocular fat cells in the bone marrow.

Fat cells contribute not only to systemic lipid metabolism, but also to osteogenesis and hemopoiesis in the bone marrow. The present study represents the first attempt to culture mature unilocular fat cells of the bone marrow. Two methods devised in our laboratory were employed: one is the "ceiling culture method" that utilizes the floating property of the cells; the other, a three-dimensional collagen gel matrix culture that captures unilocular fat cells in the gel matrix. Using these methods, the proliferation of unilocular fat cells from the bovine metacarpal bone marrow was demonstrated. First, we confirmed the proliferative ability of unilocular fat cells derived from the bone marrow, using autoradiography to study 3H-thymidine incorporation into the nuclei. The unilocular fat cells de-differentiated into fibroblast-like fat cells and then proceeded to proliferate. When they underwent a contact inhibition of growth, re-differentiation from fibroblast-like fat cells into unilocular fat cells occurred at a high rate. A specific enzymatic marker of the fat cell, alpha-glycerophosphate dehydrogenase activity related to lipogenesis, was then demonstrated in the cultured fat cells. We examined the functional reactivity of the fat cells by treatment with insulin and cyclic-AMP, and both lipogenesis and lipolysis were also confirmed in them. We concluded that unilocular fat cells from the bone marrow de-differentiated, proliferated and re-differentiated in culture. The present results may help to clarify the various functions of fat cells in the bone marrow.

Adipocytes↗

Anticonvulsant activity of paeonimetabolin-I adducts obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis.

Seventeen thiopaeonimetabolin-I adducts were obtained as mixtures of diastereoisomers after incubation of paeoniflorin with Lactobacillus brevis in the presence of various thiols. The anticonvulsant activity of the adducts was investigated in mice using the maximal subcutaneous pentylenetetrazol seizure test and sodium valproate (1.5 mmol/kg) as a positive control. Thirteen adducts showed dose-dependent prolongation of latencies of clonic and tonic convulsions. Maximal protection against convulsions was effectively demonstrated by 8-(n-hexylthio)paeonimetabolin I (8) and 8-benzoylthiopaeonimetabolin I (18) at doses of 0.125 and 0.25 mmol/kg, respectively, while 100% protection was only achieved at 0.5 mmol/kg of 8-cyclopentylthiopaeonimetabolin I and 8-(p-tolylthio)paeonimetabolin I. The principal anticonvulsant activity of the diastereoisomers of 8 and 18 was attributed to their 7S-isomers [ED50 values of 0.09 and 0.12 mmol/kg, and protective indices of 5.0 and 4.0 for 8 (7S) and 18 (7S), respectively], while the 7R counterparts [8 (7R) and 18 (7R)] showed a muscle relaxation effect.

Analysis of Variance↗

[Microcirculation in the nasal mucosa].

The nasal mucosa has important physiological roles, including the removal of foreign bodies and the warming and humidification of inspired air. The microcirculation in the nasal mucosa facilitates the above processes and plays a role in the periodic swelling and shrinking of the nasal mucosa. In the present article, we reviewed the unique vascular architecture of the nasal mucosa, the complicated feature of innervations by the sympathetic, parasympathetic and sensory nerves, the actions of some chemical mediators released under some pathologic conditions, and the state of microcirculation in the nasal mucosa in cases of nasal allergy and cold exposure. Although it is likely that the sympathetic neurotransmitter norepinephrine has a major role in controlling the microcirculation in the nasal mucosa, the physiological or pathophysiological roles of other transmitters such as neuropeptide Y, ATP, acetylcholine, and vasoactive intestinal polypeptide seem to be minor and vary between species. Nevertheless, nitric oxide, which is shown to be released from parasympathetic neurons, is believed to have some physiological and/or pathophysiological role. Unfortunately, we have yet to describe the mechanism of nasal congestion. Further study of the function of nasal congestion in various illnesses could result in the alleviation of unpleasant symptoms.

Animals↗

[Availability of 2VO rats as a model for chronic cerebrovascular disease].

We have established a chronic cerebral hypoperfusion model that is produced by permanent occlusion of bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus 1-3 days after 2VO and infarctions in the striatum 7 days after 2VO. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule-associated protein 2 (MAP2). Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after 2VO. Marked increase in GFAP staining in astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. In the 8-arm radial maze performance, the 2VO rats showed a higher rate of errors than the sham-operated control during repeated training periods. THA (9-amino-1,2,3,4-tetrahydroacridine), a cholinesterase inhibitor and GTS-21 (3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride), a central nicotinic acetylcholine-receptor agonist improved the learning impairment in the radical maze task of 2VO rats. GTS-21 administration exerted a protective effect against the neuropathological changes that followed 2VO. Taken together, the 2VO rat appears to be a useful model for investigating the pathophysiology of human dementia and to elucidate the therapeutic potential of drugs for this disease.

Animals↗

Histamine release induced by immobilization, gentle handling and decapitation from mast cells and its inhibition by nedocromil in rats.

The effect of immobilization, gentle handling and decapitation on the level of plasma histamine in Wistar rats was investigated. Mast cell deficient (Ws/Ws) rats were used to characterize the source of elevated histamine in plasma by stress, and the effect of nedocromil, a mast cell stabilizer, on histamine release was assessed in these models in vivo. The plasma histamine concentration of freely moving rats was 93.0+/-2.3 pmol/ml. Gentle handling produced a transient increase in plasma histamine level by 1.9-fold, whereas immobilization resulted in a longer-lasting elevation by 2.6-fold compared to that in the freely moving rats. Decapitation increased the plasma histamine level by 10- to 16-fold compared with that in the freely moving rats. No increase in plasma histamine was found in Ws/Ws rats exposed to stress. Nedocromil inhibited the increase in plasma histamine level induced by stress in a dose-dependent manner. These findings suggest that stress induces histamine release from mast cells in Wistar rats and the extent of this histamine release increases with the severity of stress. Nedocromil proved to be a good pharmacological tool to inhibit stress-induced release of mediators from mast cells.

Animals↗

Influence of chronic treatment with imipramine on mRNA levels in rat brain: elevation of glyceraldehyde-3-phosphate dehydrogenase levels.

The differential display method was used to identify the intrinsic factor that changes its mRNA expression level in rat brain after a 14-day oral administration of 20 mg/kg imipramine. The expression of a 180-bp band was markedly enhanced by imipramine. The results of sequencing and a data base search revealed that the isolated clone was glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with a one-base difference. Enhancement of the expression by imipramine was observed in the amygdala. Quantitative PCR showed that imipramine treatment significantly elevated the GAPDH/beta-actin ratio in the cortex. These findings suggest that long-term treatment with imipramine stimulates GAPDH mRNA expression.

Adrenergic Uptake Inhibitors↗

Hypertriglyceridemia in rats induced by consumption of a food-derived carcinogen, 2-amino-1-methyl-phenylimidazo[4,5b]pyridine (PhIP).

2-Amino-1-methyl-phenylimidazo[4,5b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine produced in cooked meat and fish, is known to be a carcinogen for rats and mice. This study provides the first evidence for hypertriglyceridemia in rats exposed to PhIP, suggesting its potential risk to induce not only carcinogenesis, but also atherosclerosis, and highlighting the potential importance of PhIP for humans.

Animals↗

Urinary gonadotropin peptide as acute phase reactant: transient elevation after operation for digestive diseases.

OBJECTIVE: In order to characterize urinary gonadotropin peptide (UGP) as an acute phase reactant, we focused on the UGP levels after surgical operation. DESIGN: Fifty cases of gastrointestinal cancer, 4 cases of cancers of other organs and 13 cases of benign digestive diseases were enrolled into this study. METHODS: UGP levels were measured using an enzyme immunoassay before and after surgery. RESULTS: Fifty-four (80.6%) of the 67 cases studied showed transient elevations of UGP. Both urinary interleukin (IL)-6 and LH levels were also increased transiently in 49 cases (73.1%). All of these three factors were increased in 38 cases (56.7%), and in 32 (84.2%) of these 38 cases, the order of peak appearance was as follows: IL-6, LH, and UGP. The UGP levels in the group of total gastrectomy were significantly higher than those in the group of partial gastrectomy. CONCLUSIONS: These results suggest that UGP shows a transient peak after surgery, correlating with levels of cytokines such as IL-6. UGP may be an acute phase reactant, and its levels are correlated with the grade of surgical stress.

Acute-Phase Reaction↗

Molecular diagnosis of hypophosphatasia with severe periodontitis.

Hypophosphatasia (HOPS) is an inherited disorder characterized by the defect of skeletal mineralization due to tissue-nonspecific alkaline phosphatase (TNSALP) deficiency. In this study we analyzed the TNSALP gene from a Japanese patient with HOPS, his parents, his brother, and unrelated normal controls. The proband is a 25-year-old Japanese male diagnosed with childhood hypophosphatasia. The patient reported premature exfoliation of the deciduous teeth and severe periodontal destruction of the permanent dentition. Genomic DNA was extracted from peripheral leukocytes of subjects. Eleven pairs of the polymerase chain reaction (PCR) primers were used to amplify the coding exons according to the published sequence data of the TNSALP gene. The PCR amplified samples were subjected to PCR-single strand conformation polymorphism (SSCP) analysis and PCR-allele specific oligonucleotide (ASO) analysis. In PCR-SSCP analysis of the patient's genomic DNA, the fragments containing exons 9 and 10 revealed abnormal mobilities. These abnormal mobilities (exons 9 and 10) were also found from his mother and father's genomic DNA, respectively. The sequencing analysis of the abnormal bands extracted from the SSCP gel showed a T to C transition at nucleotide position 1155 (T1155C) in exon 9 and G1320A in exon 10. PCR-ASO analysis confirmed these missense point mutations. PCR-ASO analysis also confirmed that mutation-specific oligonucleotides corresponded to the new mutations and did not hybridize with PCR products from normal control genomic DNAs. These results indicated that the proband was a compound heterozygote who inherited T1155C mutation in exon 9 from the mother and G1320A mutation in exon 10 from the father. Both of them are new missense point mutations and appear to cause significant changes in the structure and function of TNSALP.

Adult↗

Experimental autoimmune thyroiditis induced by thyroglobulin-pulsed dendritic cells.

Dendritic cells (DCs), which are the most effective professional antigen-presenting cells (APCs), initiate and regulate immune responses. In this report, we examine the role of DCs in the induction of autoimmune thyroiditis. Experimental autoimmune thyroiditis (EAT) induced by immunization with thyroglobulin (Tg) plus adjuvant is considered to be an animal model of autoimmune thyroiditis, and is categorized as a T cell-mediated autoimmune disease. To examine the contribution of DCs to EAT, naive DCs were purified from high responder B10BR mice and pulsed with various concentrations of porcine Tg (pTg). These pTg-pulsed DCs were transferred without adjuvant to syngenic BIOBR mice to induce EAT. Mice that had received pTg-pulsed DCs showed thyroiditis, and the degree of thyroiditis induced was positively correlated to the amounts of pTg used for the incubation (pulsing) of DCs. The severity of thyroiditis was also correlated to the amounts of anti-pTg IgG2a antibodies and IFN-gamma in the recipient sera, but not to IL-4 or IL-10, indicating that Th1 cells are mainly activated by pTg-pulsed DCs and attributable to the pathogenesis of EAT.

Animals↗

Size-adjustable titanium plate for reconstruction of the sella turcica. Technical note.

A size-adjustable plate constructed of pure titanium is proposed for use in the reconstruction of the sella turcica. The plate is composed of two semicircular pieces that are connected by a hinge located at the top of the plate. Using an applicator, the plate is inserted into the sella turcica in a closed position. The same applicator is then used to open and secure the plate. The titanium causes minimal ferromagnetic artifacts on postoperative magnetic resonance imaging. Preliminary findings indicate a possible clinical use for this plate in the reconstruction of the sella turcica when no suitable piece of bone is available.

Adenoma↗

Using motor tasks to quantitatively judge 3-D surface curvatures.

The primary objective of this study was to quantitatively investigate the human perception of surface curvature by using virtual surfaces and motor tasks along with data analysis methods to estimate surface curvature from drawing movements. Three psychophysical experiments were conducted. In Experiment 1, we looked at subjects' sensitivity to the curvature of a curve lying on a surface and changes in the curvature as defined by Euler's formula, which relates maximum and minimum principal curvatures and their directions. Regardless of direction and surface shape (elliptic and hyperbolic), subjects could report the curvature of a curve lying on a surface through a drawing task. In addition, multiple curves drawn by subjects were used to reconstruct the surface. These reconstructed surfaces could be better accounted for by analysis that treated the drawing data as a set of curvatures rather than as a set of depths. A pointing task was utilized in Experiment 2, and subjects could report principal curvature directions of a surface rather precisely and consistently when the difference between principal curvatures was sufficiently large, but performance was poor for the direction of zero curvature (asymptotic direction) on a hyperbolic surface. In Experiment 3, it was discovered that sensitivity to the sign of curvature was different for perceptual judgments and motor responses, and there was also a difference for that of a curve itself and the same curve embedded in a surface. These findings suggest that humans are sensitive to relative changes in curvature and are able to comprehend quantitative surface curvature for some motor tasks.

Adult↗

Sensitivity of shuttle vector plasmid pZ189 DNA to carbon ion beams.

The sensitivity of shuttle vector plasmid pZ189 DNA to carbon ion beams was studied under dry conditions. This plasmid contains the supF gene that can be used in mutagenesis analysis. The survival curve of the plasmid had both a shoulder and exponential parts, and showed a D10 value of about 17 kGy for both Escherichia coli wild-type and DNA repair-deficient mutant (UV-sensitive) strains. Therefore, it was assumed that the excision repair system was not effective for repairing DNA lesions induced by irradiation with carbon ion beams.

Carbon↗