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Biomedical subjects

Y Ohtsuka

Publications and source records attributed to Y Ohtsuka.

At least 55 records · Page 3Linked to original sources
PubMed2001

Enhancement of goblet cell hyperplasia and airway hyperresponsiveness by salbutamol in a rat model of atopic asthma.

BACKGROUND: Goblet cell hyperplasia (GCH) is a prominent feature in animal models of atopic asthma produced by immunisation and following multiple challenges with antigens. The aim of this study was to examine the effect of a beta(2) agonist on the development of GCH induced by the immune response. METHODS: Brown Norway rats were immunised and challenged with an aerosol of ovalbumin for four weeks. Salbutamol (0.5 mg/kg/day) or vehicle was continuously delivered for the four weeks using a subcutaneously implanted osmotic minipump. The density of goblet cells, other morphological changes, and airway responsiveness to methacholine were evaluated 24 hours after the final challenge. RESULTS: Treatment with salbutamol induced a more than twofold increase in the mean (SE) number of goblet cells (53.7 (7.3) vs 114.5 (11.8) cells/10(3) epithelial cells, p<0.01) while it did not significantly influence airway wall thickening and eosinophilic infiltration. Airway responsiveness to methacholine expressed as the logarithmic value of the concentration of methacholine required to generate a 50% increase in airway pressure (logPC(150)Mch) was also enhanced by the beta(2) agonist (-0.56 (0. 21) vs -0.95 (0.05), p<0.05). Additional experiments revealed that the same dose of the beta(2) agonist alone did not cause GCH in non-immunised rats and that the enhancement of GCH by salbutamol was completely abolished by simultaneous treatment with methylprednisolone (0.5 mg/kg/day). CONCLUSIONS: These data suggest that salbutamol enhances goblet cell hyperplasia and airway hyperresponsiveness in this rat model of atopic asthma.

Adrenergic beta-Agonists↗
PubMed2001

Airway responses to chronic ozone exposure are partially mediated through mast cells.

Airways inflammation and epithelial injury induced by chronic ozone (O(3)) in genetically mast cell-deficient mice (Kit(W)/Kit(W-v)) were compared with those in mast cell-sufficient mice (+/+) and Kit(W)/Kit(W-v) mice repleted of mast cells (Kit(W)/Kit(W-v)-BMT). Mice were exposed to 0.26 ppm O(3) 8 h/day, 5 days/wk, for 1-90 days. Background was 0.06 ppm O(3). Age-matched mice were exposed to filtered air for O(3) controls. Reversibility of lesions was evaluated 35 days after exposure. Compared with Kit(W)/Kit(W-v), O(3) caused greater increases in lavageable macrophages, epithelial cells, and polymorphonuclear leukocytes in +/+ and Kit(W)/Kit(W-v)-BMT mice. O(3) also caused lung hyperpermeability, but the genotypic groups were not different. Cells and permeability returned to air control levels after O(3). O(3) induced lung cell proliferation only in +/+ and Kit(W)/Kit(W-v)-BMT mice; proliferation remained elevated or increased in +/+ and Kit(W)/Kit(W-v)-BMT mice after O(3). Greater O(3)-induced cell proliferation was found in nasal epithelium of +/+ and Kit(W)/Kit(W-v)-BMT mice compared with Kit(W)/Kit(W-v) mice. Results are consistent with the hypothesis that mast cells affect airway responses induced by chronic O(3) exposure.

Air↗
PubMed2001

Cellular crescents and segmental glomerular necrosis in IgA nephropathy are indicative of the beneficial effects of corticosteroid therapy.

OBJECTIVE: Recent reports have revealed that corticosteroid (PSL) therapy has a long-term beneficial effect for stabilization of renal function in progressive IgA nephropathy. PATIENTS AND METHODS: We analyzed serum creatinine (Cr), daily proteinuria and the results of other routine laboratory examinations during a short-term course of PSL therapy in 28 cases of progressive IgA nephropathy. The cases were divided into two groups according to changes in renal function during the PSL treatment period: group I (15 cases), improved renal function; group II (13 cases), no significant change in renal function. RESULTS: In group I, serum Cr and proteinuria were significantly decreased, with maximum effects observed at 3 months of PSL therapy, and remained low during the period of treatment. In contrast, group II showed no significant changes in serum Cr levels during the period of therapy, although proteinuria was transiently decreased after 3 months of therapy. Histologically, cellular/fibrocellular (C/F) crescents and/or segmental glomerular necrosis (SGN) occurred with a significantly higher incidence in group I (87%) than in group II (46%) (p < 0.05). CONCLUSIONS: These results suggested that the early response to PSL in reducing serum Cr and proteinuria by 3 months of treatment may be clinically useful to predict the prognosis of IgA nephropathy and that C/F crescents and/ or SGN may be histologically indicative of the beneficial effects of PSL therapy in IgA nephropathy.

Adult↗
PubMed2001

[Diagnosis of H. pylori infection by PCR].

Because of its high sensitivity, polymerase chain reaction (PCR) method can be used to detect the presence of very few numbers of H. pylori organisms in gastric biopsy materials or gastric juice samples. PCR has also been applied to the detection of H. pylori organisms in the oral cavity, in stools, and in the environment. RT-PCR is useful to study the expression of H. pylori pathogenic genes and gene expression of gastric mucosal cells in response to H. pylori infection. Other PCR-based techniques, such as PCR-RFLP or real-time quantitative PCR, are now providing important information on H. pylori and pathophysiology of H. pylori infection.

Gastric Mucosa↗
PubMed2001

[Surgical treatment of refractory childhood epilepsy with special reference to the role of pediatric neurologists: introductory remarks].

There are many differences between children and adult patients regarding the selection of candidates for epilepsy surgery, decision about the timing of surgery, pre- and intra-surgical evaluation and follow-up. A comprehensive approach by an epilepsy surgery team consisting of pediatric neurologists, neurosurgeons and other medical staffs is absolutely necessary for successful surgical treatment of refractory childhood epilepsy and the improvement of the patient's quality of life. The potential risks and benefits of the surgery must be carefully weighed for each child from various aspects. Pediatric neurologists should make a more active contribution to this whole process.

Child↗
PubMed2001

Age-related clinical and neurophysiologic characteristics of intractable epilepsy associated with cortical malformation.

PURPOSE: To elucidate the relationship between the characteristics of cortical malformation (CM) and those of associated epilepsy, and also to investigate the prognostic value of the clinical and magnetic resonance imaging (MRI) findings for the seizure and mental outcome. METHODS: We studied 41 patients with CM and epilepsy, and the patients were divided according to the age at onset of epilepsy into two groups: one group of 15 patients with very early onset before age 3 months, and the other group of 26 patients with onset at 3 months or later. Statistical relationship was examined between the types of dysplastic lesions demonstrated by MRI and the age at onset of epilepsy. The effects of the onset age and the features of CM on the outcome of seizures and mental or developmental state also were analyzed. RESULTS: The very early-onset epilepsy was related to the dysplastic patterns of reduced sulci and blurred cortical-subcortical junction, which suggested focal CM, whereas the later-onset epilepsy was related to polymicrogyria. The age at onset of epilepsy was related to the poor seizure outcome, and both the onset age and wide distribution of CM were related to severe retardation. CONCLUSIONS: The type of CM influences the expression of associated epilepsy, especially its age-related features. The age at onset of epilepsy plays an important role in the seizure and mental outcome.

Adolescent↗
PubMed2000

Intralobar bronchopulmonary sequestration evaluated by contrast-enhanced three-dimensional MR angiography.

Bronchopulmonary sequestration (PS) is characterized by non-functioning lung tissue fed from one or several aberrant systemic arteries. The condition is diagnosed by visualizing the feeding arteries using non-invasive CT, MRI, colour Doppler sonography or conventional angiography. We present a 5-year-old boy in whom intralobar sequestration was diagnosed using contrast-enhanced 3D MR angiography, which visualised fine blood vessels in the thoraco-abdominal region without arterial puncture. This technique is useful for diagnosing PS.

Bronchopulmonary Sequestration↗
PubMed2000

Suppression-burst patterns in intractable epilepsy with focal cortical dysplasia.

We report on a patient with early-onset spasms in series and partial seizures associated with focal cortical dysplasia whose EEGs showed suppression-burst patterns during early infancy. These electroclinical characteristics suggested a diagnosis of Ohtahara syndrome, but the EEG findings were atypical because of the lack of suppression-burst patterns during wakefulness. In addition, the patient did not have severe psychomotor retardation. With high-dose pyridoxal phosphate therapy, seizures were suppressed and suppression-burst patterns disappeared at 2 months of age. Focal motor seizures recurred later and they often evolved into epilepsia partialis continua. Patients with early-onset intractable seizures associated with suppression-burst patterns on EEGs have several different etiologies, and these patients should be categorized according to their etiology in addition to their syndromic diagnosis.

Cerebral Cortex↗
PubMed2000

Long-term follow-up of vitamin B(6)-responsive West syndrome.

We performed a clinical and electroencephalographic follow-up study on 25 patients with West syndrome that was responsive to vitamin B(6) (eight cryptogenic patients and 17 symptomatic patients) who were older than 3 years at the last follow-up. All cryptogenic patients and 13 symptomatic patients were seizure free at the last follow-up. All cryptogenic patients and seven symptomatic patients had intelligent quotient or developmental quotient scores of 75 or higher. The recurrence of clinical seizures was always associated with increases in epileptic discharges. We could successfully discontinue pyridoxal phosphate administration in four cryptogenic and four symptomatic patients who were 1 year, 8 months to 24 years old.

Administration, Oral↗
PubMed2000

Myoclonic seizures combined with partial seizures and probable pathophysiology of secondary bilateral synchrony.

OBJECTIVE: We report on a patient who showed an unusual transition from complex partial seizures to a combination of myoclonic seizures and partial seizures, and then to isolated myoclonic seizures. The pathophysiological mechanism of the myoclonic seizures in this uncommon condition was studied. METHODS: The interhemispheric small time differences were estimated in the ictal EEG discharges of myoclonic seizures for differentiation between primary and secondary bilateral synchrony. The estimation was performed by coherence and phase analysis based on the two-dimensional autoregressive model. RESULTS: The estimated interhemispheric time differences were at most 27.4 ms. The ictal activity of the myoclonic seizures was suggested to originate from a cortical focus in the right hemisphere, which was also the origin of the partial seizures. CONCLUSION: The patient was considered to have an unusual type of myoclonic seizures with a probable pathophysiological mechanism of secondary bilateral synchrony.

Brain↗
PubMed2000

The electroencephalogram through a software microscope: non-invasive localization and visualization of epileptic seizure activity from inside the brain.

OBJECTIVE: We developed a novel non-invasive analysis to localize the source and visualize the time course of electrical activity generated inside the brain but unclear from the scalp. This analysis applies to signals with unique waveform characteristics, such as seizures. METHODS: The method extracts activity from an EEG data matrix as a spatiotemporal component having waveforms uncorrelated to the other concurrent activities. The method also provides the location and orientation of the dipole generating this activity. We applied this method to ten scalp seizures in three patients with temporal lobe epilepsy and single-focus seizures confirmed by intracerebral recordings. A realistic head model based on MRI was used for computation of field distributions. RESULTS: When seizure activity was still not visually identifiable on the scalp, the method demonstrated in all scalp seizures a source in the temporal neocortex corresponding clearly to the region of seizure activity in intracerebral recordings. Frequency characteristics of the estimated activities also resembled those of the intracerebral seizures. CONCLUSIONS: This method enables estimation of focal brain activity when its effect on scalp EEG is unclear to visual examination. It works in situations where currently available source analyses methods, which require noiseless definite activity, are not applicable.

Brain↗
PubMed2000

Transforming growth factor-beta: an important cytokine in the mucosal immune response.

Cytokines are important mediators in the intestine regulating both oral tolerance and mucosal inflammation. Central to this immune-regulatory role is the cytokine transforming growth factor-beta (TGF-beta). Oral tolerance and inflammatory responses in the gut are regulated through the balance of the Th1, Th2, and Th3 lymphocyte responses--a balance influenced strongly by TGF-beta. TGF-beta also modulates B-cell responses by increasing the production of immunoglobulin A (IgA) while decreasing the production of IgG, IgM, and IgE. In intestinal epithelial cells, TGF-beta activates signal transduction pathways resulting in the inhibition of proliferation and tumorigenesis. Currently, these signaling pathways are being dissected at the molecular level.

Journal Article↗
PubMed2000

Refractory childhood epilepsy and factors related to refractoriness.

To clarify the characteristics of refractory childhood epilepsy, we compared recent refractory cases and those of approximately 15 years ago, all of which were seen at the Okayama University Hospital. We also analyzed predictive factors related to refractoriness in the recent refractory cases. Among the recent refractory cases, the proportion of localization-related epilepsies increased, and the proportion of generalized epilepsies decreased compared to historical cases. In generalized epilepsies, the proportion of cases with Lennox-Gastaut syndrome decreased to less than half. In localization-related epilepsies, the proportion of cases with frontal lobe epilepsy increased. The proportion of cases with unknown causes decreased to less than half. Of the cases with known causes, postencephalitis/postencephalopathy and focal cortical malformation, including tuberous sclerosis, accounted for most of the cases. More of the recent refractory cases were treated with high-dose AED monotherapy, compared to more polytherapy in the cases of 15 years earlier. The following factors were related to future refractoriness: less than 1 year of age at onset of seizures, the presence of underlying pathology, status epilepticus. changes in type of epilepsy during the clinical course, and neonatal seizures. Regarding EEG findings of cases that had localization-related epilepsies at the end of follow-up, focal spike-waves associated with diffuse spike-waves on the first EEGs indicated future refractoriness.

Age of Onset↗
PubMed2000

Interstrain variation in murine susceptibility to inhaled acid-coated particles.

Epidemiologic studies have demonstrated a positive correlation between concentration of acid aerosol and increased morbidity and mortality in many urban environments. To determine whether genetic background is an important risk factor for susceptibility to the toxic effects of inhaled particles, we studied the interstrain (genetic) and intrastrain (environmental) variance of lung responses to acid-coated particle (ACP) aerosol in nine strains of inbred mice. A flow-past nose-only inhalation system was used to expose mice to ACPs produced by the cogeneration of a carbon black aerosol-sulfur dioxide (SO(2)) mixture at high humidity. Three days after a single 4-h exposure to ACPs or filtered air, mice underwent bronchoalveolar lavage, and cell differentials and total protein were determined as indexes of inflammation and epithelial permeability, respectively. To determine the effect of ACPs on alveolar macrophage (AM) function, lavaged AMs were isolated from exposed animals and Fc receptor-mediated phagocytosis was evaluated. Compared with air-exposed animals, there was a slight but significant exposure effect of ACPs on the mean number of lavageable polymorphonuclear leukocytes in C3H/HeJ and C3H/HeOuJ mice. ACP exposure also caused a significant decrease in AM phagocytosis. Relative to respective air-exposed animals, Fc receptor-mediated phagocytosis was suppressed in eight of nine strains. The order of strain-specific effect of ACPs on phagocytosis was C57BL/6J > 129/J > SJL/J > BALB/cJ > C3H/HeOuJ > A/J > SWR/J > AKR/J. There was no effect of ACP exposure on AM phagocytosis in C3H/HeJ mice. The significant interstrain variation in AM response to particle challenge indicates that genetic background has an important role in susceptibility. The effects of ACPs on AM function, inflammation, and epithelial hyperpermeability were not correlated (i.e., no cosegregation). This model may have important implications concerning interindividual variation in particle-induced compromise of host defense.

Acids↗
PubMed2000

Genetic linkage analysis of susceptibility to particle exposure in mice.

Particle-induced increases in respiratory morbidity and mortality have been observed worldwide in industrialized cities but the toxicologic mechanisms have not been elucidated. It is hypothesized that subpopulations including the elderly and individuals with cardiopulmonary disease are particularly at risk to the effects of exposure. Genetic background is another important host factor that may contribute to interindividual responsivity to particulate exposure. This study was designed to identify susceptibility loci for alveolar macrophage (AM) immune dysfunction induced by inhalation of sulfate-associated carbon particles in susceptible C57BL/6J and resistant C3H/ HeJ inbred mice. AMs were chosen for study because they represent an important component of host defense, and compromised host defense has been hypothesized to be an important factor in particle-induced respiratory morbidity. The quantitative phenotype for these studies was Fc receptor-mediated phagocytic function, an index of AM integrity. Analyses of macrophage dysfunction phenotypes of segregant and nonsegregant populations derived from these two strains indicate that two unlinked genes control susceptibility. A genome-wide linkage analysis of an intercross (F(2)) cohort identified significant and suggestive quantitative trait loci (QTLs) on chromosomes 17 and 11, respectively. Candidate susceptibility genes were identified for mice and humans by comparative mapping. Importantly, both QTLs overlap previously identified QTLs for susceptibility to another common pollutant, ozone. This is the first demonstration that genetic background is an important determinant of responsiveness to particle-induced immune dysfunction, and it has important implications for understanding the epidemiologic associations between particulates and morbidity and mortality.

Air Pollution↗