Biomedical subjects

M Aihara

Publications and source records attributed to M Aihara.

At least 19 recordsLinked to original sources

PubMed2003

High frequency of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive Clostridium difficile in a hospital in Japan and risk factors for infection.

Patients hospitalized in a hospital with a high incidence of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive (A-/B+) Clostridium difficile were retrospectively investigated to determine the clinical manifestations and risk factors for infection. Of 77 Clostridium difficile isolates obtained from 77 patients during the 1-year investigation period, 30 were A-/B+ and 47 were toxin A-positive, toxin B-positive (A+/B+). By pulsed-field gel electrophoresis analysis, 23 of the 30 A-/B+ strains were outbreak-related, suggesting nosocomial spread of a single type of bacterium, which mainly affected patients in the wards of respiratory medicine, hematology and neurology. Using regression analysis, three factors were found to be associated with infection by A-/B+ isolates: (i) exposure to antineoplastic agents ( P=0.01, odds ratio [OR]=5.1), (ii) the use of nasal feeding tubes ( P=0.008, OR=5.2), and (iii) assignment to a certain internal medicine ward ( P=0.05, OR=3.0). Between patients with Clostridium difficile-associated diarrhea caused by A-/B+ strains and those with A+/B+ strains, no statistically significant difference was found in body temperature, serum concentration of C-reactive protein, leukocyte count in whole blood, frequency of diarrhea, or type of underlying disease. These results indicate that A-/B+ strains of Clostridium difficile can cause intestinal infection in humans and they spread nosocomially in the same manner as A+/B+ strains.

Adolescent↗

PubMed2003

Carbamazepine-induced hypersensitivity syndrome associated with transient hypogammaglobulinaemia and reactivation of human herpesvirus 6 infection demonstrated by real-time quantitative polymerase chain reaction.

Drug-induced hypersensitivity syndrome (HS) is a rare but severe disease with multiorgan failure. Many different precipitating factors have been reported, but the pathophysiology of HS remains unknown. However, the association of the human herpesvirus (HHV) family, particularly of HHV-6, has recently been reported in patients with HS. We report a 14-year-old boy who was diagnosed as having carbamazepine-induced HS based on the clinical course, laboratory data and results of drug-induced lymphocyte stimulation tests. In addition, the reactivation of HHV-6 was demonstrated by real-time quantitative polymerase chain reaction and by significantly increased levels of the specific antibody in his paired sera. Furthermore, transient hypogammaglobulinaemia was detected in the early stage of the disease. In addition, serum levels of interferon-gamma, interleukin (IL)-6, IL-5 and eosinophil cationic protein, which were increased on admission, decreased dramatically after steroid therapy. This is the first report of carbamazepine-induced HS associated with reactivation of HHV-6, transient hypogammaglobulinaemia, increased serum levels of inflammatory cytokines and activated eosinophils. This case might contribute to the understanding of the pathophysiology of HS.

Adolescent↗

PubMed2002

Food-dependent exercise-induced anaphylaxis: influence of concurrent aspirin administration on skin testing and provocation.

BACKGROUND: Provocation tests in patients with food-dependent exercise-induced anaphylaxis (FDEIA) are often negative, even after a sufficient quantity of the implicated food and exercise have been taken. OBJECTIVES: To investigate the effect of aspirin in provocation tests and in skin prick testing (SPT) of patients with FDEIA. Gluten as a major allergen in wheat-dependent FDEIA was also investigated. METHODS: Provocation tests and SPT with suspected foods were performed in 12 patients with FDEIA. Provocation tests were performed with combinations of foods, exercise and aspirin. Detection of gluten-specific IgE was also performed by the CAP System FEIA radioallergosorbent test, SPT and a histamine release test. RESULTS: The SPT reaction was enhanced by pretreatment with oral aspirin in five of eight (62.5) patients. Aspirin facilitated provocation in five of seven (71%) patients tested. Ingestion of wheat and aspirin without exercise provoked symptoms in two patients. Aspirin provoked symptoms even with a small amount of wheat and exercise in one patient. Only the combination of aspirin, wheat and exercise provoked anaphylaxis in one patient. Specific IgE, SPT and/or the histamine release test with gluten were positive in nine of 11 patients with wheat-dependent FDEIA. CONCLUSIONS: Aspirin enhances symptoms of FDEIA, and prior ingestion of aspirin under controlled conditions can be used to confirm FDEIA. In practice, such patients should avoid aspirin ingestion. Gluten appears to be the major allergen in these patients with wheat-dependent FDEIA.

Adolescent↗

PubMed2001

Effects of nitric oxide synthase inhibitors on vascular hyperpermeability with thermal injury in mice.

The role of nitric oxide and related synthase in thermal injury was investigated by using models of experimental burn to evaluate severity from the aspect of vascular permeability. Thermal injuries were produced in the murine right ear by pinching with a pair of preheated tweezers. Immediately thereafter, Evans blue dye was intravenously administered, and the mice injured with burns were sacrificed at various times. The burned ears were collected and hydrolyzed, and the level of extracted dye was measured as an indicator of inflammation. Vascular hyperpermeability was suppressed by the administration of nitric oxide synthase inhibitors. LNAME not only suppressed vascular hyperpermeability in thermal injuries in a dose-dependent manner but was also effective with either prophylactic or therapeutic administration. Although aminoguanidine also suppressed the inflammatory response, it had no effect on the early inflammatory phase. Nitric oxide synthase is well known to have two types of isozymes. Aminoguanidine, an inhibitor specific to inducible nitric oxide synthase, suppressed the late phase 6 h after injury, suggesting that inducible nitric oxide synthase is involved in inflammatory responses of thermal injuries. These results also demonstrated that inducible nitric oxide synthase-like protein stained the burned region immunohistochemically. Therefore, both types of enzymes mediating nitric oxide affect inflammatory responses, i.e., vascular hyperpermeability, and their regulation may lead to the development of new therapy for thermal injuries.

Animals↗

PubMed2001

Hospital outbreak of MEN-1-derived extended spectrum beta-lactamase-producing Klebsiella pneumoniae.

An outbreak of Klebsiella pneumoniae resistant to broad spectrum cephalosporins occurred in a hospital in the Kinki area in Japan. During 18 months, from February 1998 to July 1999, 23 strains were isolated from 21 patients (10 with pneumonia, 4 with urinary tract infection, 1 with sepsis, 1 with vaginosis, 1 with a wound infection, and 1 with both pneumonia and sepsis; 3 patients showed noninfective colonization with K. pneumoniae) in seven wards, including the intensive care unit. MEN-1-derived gene was detected by polymerase chain reaction from the majority of the strains. Ninety-nine strains of K. pneumoniae were isolated during this period. The isolation rate of K. pneumoniae resistant to broad spectrum cephalosporins was 21%. We distinguished three clones by pulsed-field gel electrophoresis and randomly amplified polymorphic DNA analysis, and one of them was isolated from 18 patients. The presence of an R-plasmid of more than 160 kb was confirmed by plasmid analysis, but it was not possible to obtain transconjugants from all strains. This outbreak of K. pneumoniae was immediately confirmed by genetic analysis, and it was promptly ended by the infection control procedures. This is the first hospital outbreak of MEN-1-producing K. pneumoniae in Japan.

Aged↗

PubMed2001

Contact urticaria from rice.

A 30-year-old man with atopic dermatitis had had erythema and itching of the hands after washing rice in water, though he had always eaten cooked rice without problems. Handling test with water used to wash regular rice was performed on abraded hands, and produced urticarial erythema after several minutes. Applications of water used to wash allergen-reduced rice were negative for urticarial reaction. Prick test with water used to wash regular rice was +++. However prick test reaction with water used to wash allergen-reduced rice was +. Histamine-release test of regular rice-washing water was grade 3 and that of allergen-reduced rice grade 1. In immunoblotting analysis with regular rice washing water, there were no bands with this patient. These results suggest that the allergen responsible for contact urticaria in this patient might be water-soluble, heat-unstable, and not contained in allergen-reduced rice.

Adult↗

PubMed2001

Anticonvulsant hypersensitivity syndrome associated with reactivation of cytomegalovirus.

Recently, it has been proposed that viral infection is involved in the pathogenesis of hypersensitivity syndrome. Cytomegalovirus (CMV), one of the aetiological agents of infectious mononucleosis, has never been reported as an organism associated with hypersensitivity syndrome. We describe a 64-year-old man with severe phenytoin-induced hypersensitivity syndrome associated with CMV infection. Twenty-five days after the patient was started on phenytoin, he developed high fever and a generalized erythematous rash followed by jaundice, renal failure and disseminated intravascular coagulopathy (DIC). CMV-specific IgG antibodies were significantly increased 7 weeks after the onset of clinical symptoms and the increase was associated with the appearance of CMV-specific IgM. CMV DNA was detected in the serum of the patient. Coinfection with other viruses, such as Epstein-Barr virus and human herpesviruses 6 and 7, could be excluded because antibody titres to those viruses did not increase during the clinical course of his illness. We suggest that reactivation of CMV may contribute, at least in some cases, to the development of hypersensitivity syndrome.

Anticonvulsants↗

PubMed2001

Regulation of LPS induced IL-12 production by IFN-gamma and IL-4 through intracellular glutathione status in human alveolar macrophages.

Interleukin-12 (IL-12) is secreted from monocytes and macrophages; it exerts pleiotropic effects on T cells and natural killer (NK) cells, and stimulates interferon-gamma (IFN-gamma) secretion. Glutathione tripeptide regulates the intracellular redox status and other aspects of cell physiology. We examined whether IFN-gamma and IL-4 affect the balance between intracellular reduced glutathione (GSH) and oxidized (GSSG) glutathione, as this may affect IL-12 production in human alveolar macrophages (AM). We used both AM from healthy non-smokers obtained by bronchoalveolar lavage and the monocytic THP-1 cell line in this study. Incubation of AM for 2 h with the GSH precursor N-acetylcysteine (NAC) increased the intracellular GSH/GSSG ratio, and enhanced lipopolysaccharide (LPS)-induced IL-12 secretion by AM. In THP-1 cells, NAC increased the GSH/GSSG ratio and the expression of LPS-induced IL-12 mRNA, whereas L-buthionine-[S,R]-sulphoximine (BSO) decreased these. NAC and BSO offset their own effects on the intracellular GSH/GSSG ratio and the expression of LPS-induced IL-12 mRNA. Furthermore, exposure of AM to the helper T cell type 1 (Th1) cytokine IFN-gamma or the helper T cell type 2 (Th2) cytokine IL-4 for 72 h increased and decreased the GSH/GSSG ratio, respectively. Lipopolysaccharide (LPS)-induced secretion of IL-12 in AM was enhanced by IFN-gamma but inhibited by IL-4. These results suggest that IFN-gamma and IL-4 oppositely affect the GSH/GSSG balance, which may regulate IL-12 secretion from AM in response to LPS.

Acetylcysteine↗

PubMed2001

Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students.

BACKGROUND: Food-dependent, exercise-induced anaphylaxis (FEIAn) is classified among the physical allergies. The pathophysiology of FEIAn remains unknown, as does the frequency of FEIAn in the general population. OBJECTIVE: We sought to study the epidemiology of FEIAn, especially its frequency in junior-high-school students in Yokohama, Japan. METHODS: A questionnaire asking about the occurrence of FEIAn in school students was sent to all 145 public junior-high-school nurses in Yokohama. RESULTS: One hundred thirty-two junior-high-school nurses responded to the questionnaire, and 13 (11 boys and 2 girls) cases of FEIAn among 76,229 junior-high-school students were reported. In addition, 24 (12 boys and 12 girls) subjects with exercise-induced anaphylaxis (EIAn) were detected. From this survey, the frequency of FEIAn was 0.017% in this population, and its frequency was significantly higher in boys than in girls (P < .05). The frequency of EIAn was 0.031%, and there was no difference according to sex. Only one third of junior-high-school nurses had any knowledge of FEIAn. We also performed provocation tests in 5 of the 13 cases with FEIAn after obtaining informed consent from the students and their parents and were able to confirm the diagnosis. CONCLUSION: This study showed that FEIAn and EIAn are relatively rare diseases among junior-high-school students in Yokohama. To avoid serious outcomes, we believe it is important that not only physicians but also school nurses and teachers of physical education be aware of these diseases.

Adolescent↗

PubMed2001

Liver abscess caused by Clostridium difficile.

We report the first case of an infected cyst and liver abscess caused by Clostridium difficile. It recurred 11 months later, despite therapy with vancomycin and percutaneous drainage. Administration of metronidazole following percutaneous drainage achieved a favorable outcome.

Aged↗

PubMed2001

Left-right positioning of the adult rudiment in sea urchin larvae is directed by the right side.

Indirect-developing sea urchins eventually form an adult rudiment on the left side through differential left-right development in the late larval stages. Components of the adult rudiment, such as the hydropore canal, the hydrocoel and the primary vestibule, all develop on the left side alone, and are the initial morphological traits that exhibit left-right differences. Although it has previously been shown that partial embryos dissected in cleavage stages correctly determine the normal left-right placement of the adult rudiment, the timing and the mechanism that determine left-right polarity during normal development remain unknown. In order to determine these, we have carried out a series of regional operations in two indirect-developing sea urchin species. We excised all or a part of tissue on the left or right side of the embryos during the early gastrula stage and the two-armed pluteus stage, and examined the left-right position of the adult rudiment, and of its components. Excisions of tissues on the left side of the embryos, regardless of stage, resulted in formation of a left adult rudiment, as in normal development. By contrast, excisions on the right side of the embryos resulted in three different types of impairment in the left-right placement of the adult rudiment in a stage-dependent manner. Generally, when the adult rudiment was definitively formed only on the right side of the larvae, no trace of basic development of the components of the adult rudiment was found on the left side, indicating that a right adult rudiment results from reversal of the initial left-right polarity but not from a later inhibitory effect on the development of an adult rudiment. Thus, we suggest that determination of the left-right placement of the adult rudiment depends on a process, which is directed by the right side, of polarity establishment during the gastrula and the prism stages; however, but commitment of the cell fate to initiate formation of the adult rudiment occurs later than the two-armed pluteus stage.

Animals↗

PubMed2001

Augmentation of the pharmacological action of corydalis tuber by saussurea root in isolated mouse ileum.

To understand the meaning of blending crude drugs in Chinese medicinal prescriptions, the influence of Saussurea root on the pharmacological action of Corydalis tuber was examined. Saussurea root increased the depression of acetylcholine-induced contraction caused by the hot water extract solution of Corydalis tuber in mouse ileum at low dosage, which showed no direct influence on acetylcholine. Dehydrocostuslactone in Saussurea root was characterized as the component having increasing activity and the relationship between the concentration of acetylcholine and the variation in the contraction depressed by Corydalis tuber alone or a mixture of the Corydalis tuber and dehydrocostuslactone was investigated for clarification of the mode of action.

Acetylcholine↗

PubMed2001

Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma.

PURPOSE: To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. RESULTS: Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. CONCLUSIONS: The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population.

Amino Acid Sequence↗

PubMed2001

Enhanced FGF-2 movement through human sclera after exposure to latanoprost.

PURPOSE: To determine whether exposure of sclera to latanoprost acid alters transscleral permeation by FGF-2. METHODS: Pieces of human sclera were isolated from donor eyes after death, placed in organ culture, and exposed to 50 to 200 nM latanoprost acid or vehicle for 3 days. Transscleral permeability was then assessed by placing each scleral piece into a Ussing apparatus and measuring the amount of FGF-2 that moves from the orbital side to the uveal side of the scleral piece. Transscleral permeation by 10-kDa tetramethylrhodamine-dextran also was determined, for comparison. RESULTS: Transscleral permeation by FGF-2 through sclera that had been incubated with vehicle was 1.53 +/- 0.86 x 10(-8) cm/sec. Transscleral permeation by 10-kDa tetramethylrhodamine-dextran was 1.04 +/- 0.39 x 10(-6) cm/sec. FGF-2 permeation of sclera exposed to 50, 100, and 200 nM latanoprost acid was increased by an average of 48% +/- 62%, 100% +/- 108%, and 108% +/- 79%, respectively, compared with sclera exposed to vehicle (n = 13; P < 0.05). Scleral permeation by 10-kDa dextran after exposure to 50, 100, or 200 nM latanoprost acid was significantly increased by 42% +/- 36%, 59% +/- 51%, and 65% +/- 49%, respectively (n = 14; P < 0.05). The ratio of dextran to FGF-2 permeation was approximately 90 and did not vary with 50, 100, or 200 nM latanoprost acid (P = 0.93, ANOVA). CONCLUSIONS: Exposure of sclera to latanoprost acid increases transscleral permeation by FGF-2 in human scleral organ cultures. Because this increase parallels the increased scleral permeability caused by dextran, it may reflect a general enhancement of permeability, a possibility that future in vivo studies should explore.

Aged↗

PubMed2001

Detection of prostaglandin EP(1), EP(2), and FP receptor subtypes in human sclera.

PURPOSE: To examine the expression of five prostaglandin (PG) receptors, EP(1), EP(2), EP(3), EP(4), and FP and their corresponding mRNA transcripts in human sclera and cultured human scleral fibroblasts (HSFs). METHODS: Primary cultures of HSFs were established from donor eyes. Also, sclera from human donor eyes was snap frozen and sectioned. Immunocytochemistry was performed on HSFs and tissue sections with subtype-specific antibodies to the EP(1), EP(2), EP(3), EP(4), and FP receptors. The presence of mRNA for the receptor subtypes was examined from total RNA obtained from human sclera and confirmed with restriction digest analysis. RESULTS: Positive EP(1) and FP receptor immunoreactivity was observed in fibroblasts within the sections from human sclera. In primary cultures of HSFs, EP(1) and FP labeling was observed over the entire cell surface. EP(2) immunoreactivity within HSFs was mostly present in the juxtanuclear region. RT-PCR analysis of total RNA isolated from human sclera and HSFs confirmed the presence of EP(1), EP(2), and FP receptor subtypes. The identity of the polymerase chain reaction products was confirmed by restriction enzyme analysis. No mRNA or immunoreactivity above basal levels was detected for the EP(3) and EP(4) prostanoid receptor subtypes in tissue sections or primary cultures. CONCLUSIONS: The EP(1), EP(2), and FP receptor subtypes are present in HSFs, suggesting that these cells may respond to endogenous PGs and their structural analogues through interaction with these receptor subtypes.

Adult↗

PubMed2000

New EIA technique for tyrosinase in human melanocytes and its application.

The expression of tyrosinase in melanocytes relates to skin pigmentation or depigmentation. Although many types of drugs with whitening effects are well known, neither the definite effect nor the mechanism underlying the effect has been elucidated. In this study, we attempted to develop the rapid and simple EIA technique for tyrosinase protein, then this technique was applied to normal human cultured melanocytes. When primary antibody and tyrosinase were incubated in non-coated 96-well microtitre plates for 48 hours at 4 degrees C, then the solution in tyrosinase-coated plate was further incubated for another 1 hour at 37 degrees C. Thus the best results were obtained. The developed EIA system could detect authentic tyrosinase until 0.1-1.0 ng/mL. This EIA technique could also be applied to human cultured melanocytes. The melanocytes cultured with endothelin-1 induced tyrosinase like immune reactive protein. The protein induction with endothelin-1 was suppressed by BQ 123, ETa receptor antagonists. The simple EIA technique developed for tyrosinase may give a clue to determination of the onset mechanisms underlying pigmental diseases of the skin as well as the mechanisms underlying the effects of various whitening drugs.

Cells, Cultured↗

PubMed2000

Expression of lysophosphatidic acid receptor in rat astrocytes: mitogenic effect and expression of neurotrophic genes.

Lysophosphatidic acid (LPA) is a phospholipid mediator with a variety of biological activities. It remains unknown, however, which cells in the brain express the LPA receptor. The present study was undertaken to identify cells in the rat brain expressing functional LPA receptors, and to explore biological roles of LPA in these cells. We found that the LPA receptor was most dominantly expressed in rat astrocytes, determined by LPA-induced Ca2+ imaging, and by Northern blot analyses. LPA induced a mitogenic response and expression of immediate early genes in astrocytes, through pertussis-toxin sensitive G-protein(s). LPA also stimulated the expression of various cytokine genes, including nerve growth factor, interleukin (IL)-1beta, IL-3 and IL-6. Thus, astrocytes are the major target of LPA in the brain. We propose that LPA may play important roles in neuronal development, gliosis and wound-healing process in the brain.

3T3 Cells↗

PubMed2000

Interaction between neurone and microglia mediated by platelet-activating factor.

BACKGROUND: Platelet-activating factor (PAF) is a potent phospholipid mediator that plays various roles in neuronal function and brain development. The production and release of PAF in the brain has also been reported under various pathological conditions. However, neither the cell types and mechanism responsible for the synthesis of PAF nor its target cells have been fully identified. RESULTS: Using primary culture cells derived from rat brain and a very sensitive assay method for PAF, we found that PAF was synthesized in neurones following stimulation with glutamic acid. PAF synthesis required activation of NMDA receptors and subsequent elevation of intracellular calcium ions. Microglia, which express functional PAF receptors to a high level, showed a marked chemotactic response to PAF. This chemotaxis is a receptor-mediated process, as microglia from PAF-receptor-deficient mice did not show such a response. The activation of a pertussis-toxin-sensitive G-protein and mitogen-activated protein kinase presumably plays a role in intracellular signalling leading to chemotaxis. CONCLUSIONS: Considering the cytoprotective and cytotoxic roles of microglia, PAF functions as a key messenger in neurone-microglial interactions.

Animals↗