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Biomedical subjects

C Fukushima

Publications and source records attributed to C Fukushima.

16 recordsLinked to original sources

In vitro responses to antigen stimulation: comparison between human lung parenchyma resected from asthmatic patients and non-asthmatic patients.

BACKGROUND: The airway of asthmatic patients is hyperresponsive to various stimuli in vivo. There are, however, only a few reports that compared the in vivo responsiveness of asthmatic patients and non-asthmatic subjects to those of lung parenchyma in vitro. OBJECTIVES: To compare the contractile response, release of various chemical mediators, and responsiveness to drugs in samples of lung parenchyma excised from asthma patients with those of non-asthmatic subjects. METHODS: Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to mites. The strip was suspended in a magnus bath containing a buffer solution. Parenchymal contraction was induced by PGF2 alpha. After washing, the baseline concentrations of thromboxane B2 (TXB2), leukotriene (LT), and histamine were measured in each bath and then contraction was induced by the addition of a mite antigen. The concentrations of TXB2, LT, and histamine were measured after contraction. The inhibitory effects of TXA2 synthetase inhibitor (DP-1904) and TXA2 receptor antagonist (AA-2414) were also evaluated in both tissue samples. RESULTS: There were no significant differences between lung parenchymal tissues of asthmatic and non-asthmatic patients with regard to PGF2 alpha-induced contraction, antigen-induced contraction, release of chemical mediators, and the response to drugs. CONCLUSION: Unlike the response in vivo, there are no differences in the response to stimuli in vitro between lung parenchymal tissues of asthmatic and non-asthmatic patients.

Aged

Sodium cromoglycate inhibits antigen-induced cytokine production by peripheral blood mononuclear cells from atopic asthmatics in vitro.

BACKGROUND: Several anti-allergic anti-inflammatory drugs are used for the treatment of asthma including glucocorticosteroids (GCS), sodium cromoglycate (SCG), leukotriene (LT) inhibitors, and LT receptor antagonists. The major mechanism of the anti-inflammatory action of GCS is inhibition of cytokine production by T-lymphocytes: however, the mechanisms of anti-inflammatory effects of SCG are still unclear. OBJECTIVE: We elucidated the anti-inflammatory effects of SCG by investigating its effects on cytokine production by peripheral blood mononuclear cells (PBMCs) obtained from atopic asthmatics. METHODS: Peripheral blood mononuclear cells were obtained from seven atopic asthmatics and sensitized with Dermatophagoides farinae (DJ) or concanavalin A (ConA). We compared the effects of SCG on interleukin (IL)-5 and interferon (IFN)-gamma production by sensitized PBMCs with that of dexamethasone (Dex). Based on their clinical concentrations, we compared the effects of 10(-6) to 10(-4) M of SCG to those of 10(-6) M Dex. RESULTS: Stimulation with ConA increased the production of IL-5 and IFN-gamma. Dex significantly inhibited the production of both cytokines but SCG showed no inhibitory effects. On the other hand, Df stimulation increased IL-5 production only. Dermatophagoides farinae-induced overproduction of IL-5 was inhibited by SCG and Dex. CONCLUSIONS: Our results suggested that SCG has antigen-specific anti-allergic inflammatory effects.

Adult

Effect of synthetase inhibitors and receptor antagonists in antigen-induced contraction of human lung parenchyma.

BACKGROUND: Chemical mediators induce bronchoconstriction, enhance vascular permeability, and promote inflammation. The use of synthetase inhibitors and receptor antagonists of these mediators may be useful in the treatment of asthma. OBJECTIVES: We evaluated the role of chemical mediators in mite antigen-induced contraction in resected human lung parenchyma using synthetase inhibitors and receptor antagonists for these mediators. METHODS: Resected human lung parenchymal specimens were passively sensitized with serum obtained from patients with asthma showing an IgE RAST score for mites > or = 5. The specimens were suspended in Magnus bath filled with buffer. After confirmation of contraction using PGF2 alpha, buffer or synthetase inhibitors or receptor antagonists of various chemical mediators were added. Contraction of parenchyma was induced by the addition of mite antigen, and the concentration of thromboxaneB2 (TXB2), leukotriene (LT), and histamine was measured before and after contraction. RESULTS: Thromboxane A2 (TXA2) synthetase inhibitors significantly inhibited TXB2 release but not contraction. Leukotriene synthetase inhibitors significantly inhibited both LT release and contraction. The magnitude of the inhibitory effect was in the order of LT receptor antagonist > 5-lipoxygenase inhibitor > TXA2 receptor antagonist > PAF antagonist, TXA2 synthetase inhibitor, antihistamine > cyclooxygenase inhibitor. CONCLUSION: Among chemical mediators, LT appears to be the most closely involved in the immediate antigen-induced contractile response in resected human lung parenchyma. Receptor antagonists produced a more marked inhibition of antigen-induced contraction than synthetase inhibitors.

Aged

Recurrent lymphocytic hypophysitis: case report.

OBJECTIVE AND IMPORTANCE: Lymphocytic hypophysitis is being recognized with increasing frequency, but the long-term course is not well known. Recurrence of lymphocytic hypophysitis after a long interval has never been reported. CLINICAL PRESENTATION: A 53-year-old woman presented with central diabetes insipidus. Magnetic resonance imaging (MRI) revealed an intrasellar lesion. Transsphenoidal biopsy yielded a diagnosis of lymphocytic hypophysitis. Regression of the lesion was confirmed by follow-up MRI. The patient lived normally, with gradual improvement of diabetes insipidus, until she suddenly became aware of a visual defect, which developed into bitemporal hemianopsia 2 years after the biopsy. MRI revealed a larger sellar lesion extending to the hypothalamus. However, the adenohypophysial function remained normal and the mild diabetes insipidus continued unchanged. INTERVENTION: Prompt corticosteroid treatment was remarkably effective. The visual defect disappeared during steroid therapy, and a significant reduction of the lesion was revealed by MRI. CONCLUSION: It is suggested that long-term follow-up with endocrinological and radiological studies may be necessary in cases of lymphocytic hypophysitis. Recurrent cases should be promptly treated with steroids when a definitive histological diagnosis had been confirmed.

Anti-Inflammatory Agents

Aspirin-induced asthma as a risk factor for asthma mortality.

We have recently reported severe airway obstruction and bronchial hyperresponsiveness (BHR) in fatal asthma compared with patients without a history of near-fatal asthma. Based on these findings, we evaluated whether aspirin-induced asthma (AIA) is a risk factor for asthma mortality by analyzing pulmonary function and BHR. FEV1.0% and methacholine inhalation threshold were significantly lower in the fatal asthma group compared with the AIA and non-AIA groups. However, there were no significant differences between the AIA and non-AIA groups. Our results suggested that AIA is not a risk factor for asthma mortality if avoidance of aspirin and aspirin-like drugs is assured.

Adult

Inhibitory effect of thromboxane A2 synthetase inhibitor, DP-1904, on antigen-induced contraction of human lung parenchyma.

BACKGROUND: Several mediators are released from mast cells during allergic reactions. These substances cause contraction of airway smooth muscles, increase the permeability of blood vessels, and enhance mucous secretion. Among these mediators, thromboxane A2 (TXA2) has a particularly strong bronchoconstrictive effect. OBJECTIVES: We examined antigen-induced contraction of excised human lungs and the suppressive effects of TXA2 synthetase inhibitor on TXA2 release. METHODS: Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to the mite. They were suspended in magnus baths, to which buffer and 10(-4) to 10(-8) M of DP-1904, an inhibitor of TXA2 synthetase, were added. Following the measurement of TXB2 and leukotriene (LT) concentrations in each bath, parenchymal contraction was induced by the addition of a mite antigen. The concentration of TXB2 and LT was measured after contraction. RESULTS: Antigen-induced release of TXB2 was significantly suppressed by DP-1904 in a concentration-dependent manner. DP-1904 did not inhibit parenchymal contraction and the release of LT. CONCLUSIONS: Antigen-induced parenchymal contraction was not suppressed by inhibition of TXA2 release, suggesting that DP-1904 may not be effective in asthma.

Aged

[Effects of traumatic subarachnoid hemorrhage on pathological properties in diffuse brain injury: a comparison with aneurysmal subarachnoid hemorrhage].

As a result of recent advances in continuous monitoring equipment, it has been reported that vasospasm (VS) and delayed ischemic neurological deficit (DIND) occur as frequently in traumatic subarachnoid hemorrhage (TSAH) as in subarachnoid hemorrhage due to ruptured intracranial aneurysm (ASAH), and these VS and DIND have been reported to affect the outcome of TSAH adversely in many cases. When we compared TSAH secondary to diffuse brain injury (DBI) with ASAH, however, these two conditions were evidently different from each other in nature. Then we compared laboratory data, clinical course, and outcomes of TSAH associated with DBI with those of ASAH, to determine whether TSAH results in poor outcomes of DBI. On CT scans, patterns of SAH distribution were different from each other, and SAH was detected in 76% of the patients with ASAH on day 4, whereas only 2.0% of the patients with TSAH had detectable SAH on day 3. The incidence rates of detectable SAH in both groups remained significantly different from each other after day 2. The cerebral blood flow (CBF) decreased to around 75% of the normal flow in the acute stage of ASAH, and it decreased further to around 65% in the subacute stage. In TSAH, in contrast, CBF varied widely among the patients. The average CBF decreased to about 70% in the acute stage, and then it increased to around the lower limit of the normal range in the subacute stage. The urinary output and serum concentration of low molecular protein compositions in TSAH were markedly different from those in ASAH. In addition, the contour of a low density area (LDA) in CT scans in the subacute-chronic stage was the same as that of the area supplied by the artery being constricted due to cerebro-vascular spasm in ASAH. In TSAH, in contrast, hardly any LDA had a form that was suggestive of this conjuction, with cerebro-vascular spasm and the incidence rate of LDAs was significantly different from that for ASAH. About 30% of the patients with ASAH had ventricular enlargement, which was diagnosed as normal pressure hydrocephalus by cisternography, in the chronic stage. Surgical shunting was effective for these patients. In TSAH, ventricular enlargement was observed in more than 50% of the patients, but almost none of these patients underwent surgical shunting, because it resulted from cerebral atrophy. Regardless of causes of SAH, the severer SAH was, the more often patients had a poor outcome. The outcome of TSAH was, however, significantly poorer than that of ASAH. When SAH was traumatic, it disappeared by the time VS developed and, in addition, changes in CBF and the form and incidence rate of LDAs were different from those in ASAH. We concluded that, although TSAH is an adverse prognostic factor for DBI, it does not contribute to poor outcomes of DBI by giving rise to DIND caused by VS.

Acute Disease

Genital burns and vaginal delivery.

Obstetric complications may result from burn scarring in the genital area. Women in developing countries typically squat around cooking fires, and burns are common. This recent case in Nepal describes obstructed labor in a young woman whose genital area had extensive scarring from a cooking fire injury. Proper antenatal assessment by health care providers can reduce the risk to mothers and infants of the consequences of a birth canal damaged or obstructed by burn scarring.

Adolescent

Developmental regulation of rat serine dehydratase gene expression: evidence for the presence of a repressor in fetal hepatocytes.

To determine why the rat serine dehydratase gene becomes transcriptionally activated just after birth, we examined the interactions of DNA binding proteins of fetal and adult rat livers with the serine dehydratase gene promoter by DNase I protection analysis and gel mobility shift assay. Several binding regions of nuclear proteins were found to be common to fetal and adult livers and interaction of factors with the characteristics of Sp1 or NF-Y was suggested. Two additional regions, named regions B and I, were specific to fetal liver. These regions contain GATA-like sequences and competition experiments by gel mobility shift assay suggested that the fetal liver-enriched factor binds to the GATA-like sequences. The function of the regions B and I in transcription regulation was investigated in fetal and adult hepatocytes by transient DNA transfer experiments with serine dehydratase-chloramphenicol acetyltransferase fusions. These experiments showed that these regions functioned as negative cis-acting elements in fetal hepatocytes, but not in adult hepatocytes.

Animals

Effect of the centrally acting muscle relaxant tizanidine on spinal reflexes: involvement of descending noradrenergic systems.

Experiments were performed on intact and spinalized rats anesthetized with urethane and alpha-chloralose. In intact rats, administration of tizanidine (0.1 mg/kg, i.v.) decreased the mono- (MSR) and polysynaptic reflex potentials (PSR). Blood pressure was initially elevated and then lowered by tizanidine. Although pretreatments with hexamethonium and phentolamine prevented the tizanidine-induced decrease in blood pressure, the depressant effects of tizanidine on the reflexes remained. The alpha 2-antagonist idazoxan inhibited the tizanidine-induced decrease in spinal reflexes, suggesting that central alpha 2-adrenoceptors are involved in the depression of the reflexes. In spinalized rats, tizanidine transiently increased the MSR and gradually decreased the PSR. Blood pressure was elevated transiently by tizanidine. Although the hypertensive effect of tizanidine was inhibited by phentolamine, the effect of tizanidine on the PSR did not change. Prazosin blocked the stimulatory effect of tizanidine on the MSR and caused a rapid decrease of the PSR, suggesting that spinal alpha 1-adrenoceptors are involved in the enhancement of the reflexes. These results suggest that the depressant effects of tizanidine on spinal reflexes are due to the supraspinal and spinal effects of the drug, and not to changes in blood pressure.

Adrenergic alpha-1 Receptor Antagonists

Identification of glucocorticoid- and cyclic AMP-responsive elements of the rat serine dehydratase gene: difference in responses of the transfected and chromosomal genes.

Transcription of the gene coding for serine dehydratase (SDH, EC 4.2.1.13) in rat liver is induced 3-4 fold by glucocorticoids plus glucagon, but not by either hormone alone. For identification of the DNA elements mediating the glucocorticoid- and cyclic AMP-regulated expression of the SDH gene, primary cultures of adult rat hepatocytes were transfected with a fusion gene consisting of the 2.15 kb 5'-flanking sequence of the SDH gene linked to the coding sequence of the gene for chloramphenicol acetyltransferase (CAT). CAT assay demonstrated that transient expression of the SDH-CAT fusion gene was inducible by either dexamethasone or dibutyryl cyclic AMP, but that the effects of these inducers were not additive or synergistic. These results suggest that some structural organization of the DNA influences the hormonal actions in regulation of gene expression.

Animals

Diagnostic problems in chronic eosinophilic pneumonia.

To identify the problems involved in the diagnosis of chronic eosinophilic pneumonia (CEP), clinical findings were analysed for 43 patients diagnosed clinically or pathologically with CEP during the past 10 years. About 28% of patients showed peripheral blood eosinophilia and a typical pattern of pulmonary oedema on chest X-ray at initial examination. Eosinophilia was demonstrated in peripheral blood in 86% of patients, in bronchoalveolar lavage (BAL) in 100%, and in transbronchial lung biopsy (TBLB) specimens in 64% of patients. Peripheral blood tests, BAL, and TBLB were all positive for eosinophilia in 60% of patients. BAL was the single test most likely to be positive among the diagnostic tests used in the present study. When CEP is suspected clinically, an understanding of which site is examined by each of the diagnostic tests and of the likelihood of a positive result in each test will facilitate the selection of the most appropriate tests for individual patients.

Adult

Repeated alcohol intake changes circadian rhythm of ambulatory blood pressure.

The blood pressure of 7 clinically healthy volunteering social drinkers was studied while they consumed, with a crossover design for 5 days, either 40 g of alcohol by day or fruit juice, with the two spans on alcohol and juice being separated by a one-week washout. Whereas the rhythm-adjusted mean was not changed, a clear statistically significant increase in the circadian double amplitude was found. The study provides a model for a rapidly achieved circadian amplitude hypertension which may precede an elevation of the overall blood pressure mean in the natural course of the disease.

Adult