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T Iwama

Publications and source records attributed to T Iwama.

At least 91 records · Page 5Linked to original sources
PubMed1996

Ampullary carcinoma in familial adenomatous polyposis: report of a case.

We report the case of a 48-year-old man with familial adenomatous polyposis (FAP) who was found to have ampullary carcinoma 6 years after undergoing total colectomy. The patient was examined periodically after colorectal surgery except for duodenoendoscopy because he had also previously undergone distal gastrectomy with gastrojejunal anastomosis for a duodenal ulcer at 27 years of age. An ampullary lesion was suspected on blood chemistry and detected by computed tomography scan and ultrasonography although the patient showed no clinical symptoms. A pancreatoduodenectomy was performed and the histological examination revealed well-differentiated adenocarcinoma with no metastasis to the regional lymphnodes. Long-term periodic surveillance of the upper gastrointestinal tract including the papilla of Vater is therefore important for FAP patients who have undergone prophylactic colectomy.

Adenocarcinoma↗
PubMed1996

Repeat coronary angioplasty as the treatment of choice for restenosis.

A prospective study was performed to determine whether multiple repeat coronary angioplasty can achieve final lesion patency after restenosis. Between 1983 and 1992, 1455 lesions (excluding acute myocardial infarction or total occlusion) were successfully dilated for the first time. Only 941 (68%) of the 1385 lesions followed up showed improved coronary flow (< or = 70% stenosis) after the first procedure. However, 1248 (93%) of 1345 lesions showed improved coronary flow after angioplasty had been repeated as many as three times, and 1268 (94%) of 1345 did so after as many as six procedures. Only 23 (1.6%) lesions required four or more procedures, and 20 of them showed final patency. These findings indicate that repeat angioplasty can be used as a reasonable treatment strategy for restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1996

Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer.

BACKGROUND & AIMS: Microsatellite instability (replication error [RER]) is a characteristic of tumors in hereditary nonpolyposis colon cancer (HNPCC), but the mechanism of HNPCC carcinogenesis is not yet understood. To clarify the nature of HNPCC tumors, RER and genetic changes were compared between HNPCC and non-HNPCC tumors. METHODS: RER and genetic changes were analyzed in 21 HNPCC, 389 familial adenomatous polyposis, and 206 sporadic tumors using polymerase chain reaction, single-strand conformation polymorphism, sequencing, and Southern hybridization. RESULTS. in HNPCC, 95% tumors at all stages showed RER positivity (altered loci, 4.3 of 5). In familial adenomatous polyposis and sporadic tumors, RER positivity (1.7 of 5) was 3% in adenoma and intramucosal carcinoma, 13%-24% in invasive carcinoma, and 35% in carcinoma metastasized to liver. Fifty percent of RER-positive HNPCC tumors had both germline and somatic mutations of hMSH2 or hMLH1 gene, whereas 6% of RER-positive non-HNPCC had somatic mutation. APC, p53, and K-ras-2 mutations and loss of heterozygosity of tumor-suppressor genes were significantly less frequent (P = 0.03 to 0.0006) but transforming growth factor beta type II receptor mutation was significantly more frequent (P = 0.000001) in HNPCC than in non-HNPCC. CONCLUSIONS: RER positivity occurs from an early stage of carcinogenesis in HNPCC but in later stages in non-HNPCC. Most HNPCC tumors may develop through different genetic changes from those in the adenoma-carcinoma sequence, although a certain percentage develops through APC mutation.

Adaptor Proteins, Signal Transducing↗
PubMed1996

The relevance of hemodynamic factors to perioperative ischemic complications in childhood moyamoya disease.

Of 124 children younger than 15 years who underwent surgery for moyamoya disease, 21 (16.9%) experienced perioperative ischemic complications that could not be unequivocally attributed to the surgery. Eleven of the 21 patients experienced infarctions, and 10 experienced reversible ischemic neurological deficits without new lesions, as revealed by computed tomographic scans. An examination of the patients' perioperative clinical and laboratory data revealed that the mean values of intra- and postoperative minimum arterial carbon dioxide pressure, maximum arterial carbon dioxide pressure, and mean arterial pressure were similar in patients with and without ischemic complications. However, in patients with perioperative complications, the incidence of preoperative transient ischemic attacks (TIAs) and intra- and postoperative hypercapnia (maximum arterial carbon dioxide pressure > 45 mm Hg) was significantly higher. In addition, 7 of the 11 perioperative infarctions occurred in patients with frequent preoperative TIAs and intra- and postoperative hypercapnia. Cerebral blood flow studies with preoperative acetazolamide loading showed that the new infarctions were located in areas in which the cerebral blood flow had been compromised. Our results suggest that the occurrence of frequent preoperative TIA is an important indicator of the instability of the cerebral hemodynamics and of the risk of perioperative ischemic complications. To prevent these complications, preoperative management aimed at stabilizing the hemodynamic status is very important. Children who have moyamoya disease and who experience frequent preoperative TIAs are at risk for ischemic brain damage caused by hypercapnia as well as hypocapnia and hypotension. The establishment and maintenance of normocapnia with normotension are highly desirable for the perioperative management of moyamoya disease in children.

Adolescent↗
PubMed1996

Vasoreactive effect of acetazolamide as a function of time with sequential PET 15O-water measurement.

The accurate assessment of vascular flow reserve is crucial for the evaluation of risk among patients with cerebrovascular disease. In six patients with unilateral occlusion of the internal carotid artery and one patient with unilateral occlusion of the middle cerebral artery (mean +/- S.D. age = 68 +/- 3 years), we measured cerebral blood flow (CBF) after the administration of 940 MBq 15O-water using a remotely controlled power injector. Studies were performed at rest, after 10 min, and then 10, 20 and 30 min after the administration of 1 mg acetazolamide to evaluate the vasoreactive effect, as reflected by an increase in CBF. Sixteen regions of interest (ROIs) were drawn over the CBF images. These ROIs were as follows in each hemisphere: Area I, four areas in the cortical middle cerebral arterial territory (superior frontal, frontal, temporal and parietal areas); Area II, four areas of the deep middle cerebral and vertebral arterial territory (occipital area, basal ganglia, thalamus and cerebellum). Taking normalized resting CBF to be 100%, the mean CBF measured 10, 20 and 30 min post-injection using sequential positron emission tomography was as follows: Area I, 141.4 +/- 16.3, 127.7 +/- 15.3 and 128.2 +/- 17.4% for non-occluded sites and 116.3 +/- 22.8, 112.7 +/- 16.4 and 114.9 +/- 17.1% for occluded sites; Area II, 143.4 +/- 14.5, 126.2 +/- 10.4 and 125.0 +/- 12.9% for non-occluded sites and 141.9 +/- 28.9, 126.0 +/- 20.5 and 124.1 +/- 17.1% for occluded sites. A significant difference in mean CBF was noted between the non-occluded and occluded sites in Area I, the most marked difference of 25.1% being observed 10 min after the administration of the acetazolamide. We conclude that for an accurate assessment of vascular reserve in patients with cerebrovascular disease, CBF should be measured 10 min post-administration of the acetazolamide.

Acetazolamide↗
PubMed1996

Loss or somatic mutations of hMSH2 occur in hereditary nonpolyposis colorectal cancers with hMSH2 germline mutations.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a major cancer susceptibility syndrome known to be caused by the inheritance of mutations in DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2. To investigate the role of genetic alterations of hMSH2 in HNPCC tumorigenesis, we analyzed 36 Japanese HNPCC kindreds as to hMSH2 germline mutations. Moreover, we also examined somatic mutations of hMSH2 or loss of heterozygosity at or near the hMSH2 locus in the tumors from the hMSH2-related kindreds. Germline mutations were detected in five HNPCC kindreds (5/36, 14%). Among them, three were nonsense mutations, one was a frameshift mutation and the other was a mutation in an intron where the mutation affected splicing. Loss of heterozygosity in four and somatic mutations in one were detected among the eight tumors with hMSH2 germline mutations. All these alterations were only detected in genomic instability(+) tumors, i.e., not in genomic instability(-) ones, indicating that mutations of hMSH2 were responsible for at least some of the tumors with genomic instability. These data establish a basis for the presymptomatic diagnosis of HNPCC patients, and constitute further evidence that both DNA mismatch repair genes and tumor suppressor genes may share the same requirement, i.e., two hits are necessary to inactivate the gene function.

Alleles↗
PubMed1996

Frequent microsatellite instabilities and analyses of the related genes in familial gastric cancers.

Microsatellite instability or replication error seems to be related to defective DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2, which have been identified as causative genes of hereditary nonpolyposis colorectal cancers (HNPCC). Recently, it was reported that mutations at the simple repeated sequences in the transforming growth factor-beta type II receptor (TGF-beta RII) gene occurred in replication error-positive colorectal cancers. To determine genetic alterations in familial gastric cancers (FGC, we examined replication error using eight microsatellite DNA markers, and screened mutations in the hMSH2, hMLH1 and TGF-beta RII genes in six cases from four FGC kindreds. Moreover, hMTH1, a human homolog of the bacterial mutT gene, was also screened. Four of six (67%) cancers showed the replication error-positive phenotype, indicating that microsatellite instability is highly associated with not only HNPCC, but also FGC. No germline mutation was found in the whole coding sequences of hMSH2 and hMTH1, or in the conservative regions of hMLH1 in any patient, while one cancer DNA showed a somatic mutation at codon 682 (threonine to alanine) in hMSH2. No alteration was found at the small repeated sequences in TGF-beta RII in FGC tumor DNA. These results indicate that the carcinogenetic process of FGC may be different from that of HNPCC.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Airway hyperresponsiveness to acetylcholine induced by aerosolized arachidonic acid metabolites in guinea-pigs.

BACKGROUND AND OBJECTIVE: To investigate the role of arachidonic acid (AA) metabolites in airway hypersensitivity. METHOD: We studied the change in airway responsiveness to acetylcholine (ACh) after inhalation of some AA metabolites in guinea-pigs. RESULTS: Exposure to prostaglandin (PG) D2, thromboxane (TX) A2 mimetic U-46619, leukotriene (LT) D4 or LTE4 at concentrations which did not influence bronchial tone and blood pressure dose-dependently caused airway hyperresponsiveness. However, the change was not observed after challenge with a high concentration of PGF2 alpha. Furthermore, PGD2 and U-46619 induced an acute and short-lived increase in responsiveness, while LTD4 and LTE4 induced a slow-onset and longer-lived increase. In the tachyphylaxis study, although the tachyphylaxis for airway hyperresponsiveness provoked by PGD2 and U-46619 was not observed, airway hyperresponsiveness induced by the second LTD4 tended to decrease, and the second LTE4-induced airway hyperresponsiveness obviously diminished. In the study using antagonists and inhibitors, TX-receptor antagonist BM-13177 inhibited PGD2- and U-46619-, but not LTD4- and LTE4-induced airway hyperresponsiveness. TX synthase inhibitor OKY-046 had no effect on PGD2-, U-46619- and LTD4-induced airway hyperresponsiveness, while LTE4-induced airway hyperresponsiveness tended to be inhibited by these inhibitors. However, the LT-receptor antagonist ONO-1078 inhibited both LTD4- and LTE4-, but not PGD2- or U-46619-induced airway hyperresponsiveness. 5-lipoxygenase inhibitor AA-861 tended to prevent LTE4-induced airway hyperresponsiveness, but had no effect on PGD2-, U-46619- and LTD4-induced enhanced responses. CONCLUSION: These findings indicate that the local existence of PGD2, TXA2, LTD4 and LTE4 in the guinea-pig airway may act as an airway hyperresponsiveness-inducing factor rather than as a bronchoconstrictor. In addition, PGD2/U-46619 may stimulate the TX receptor to induce an acute and short-lived airway hyperresponsiveness, and LTD4 and LTE4, which may involve secondary mediator release, may act at the LT receptor to induce a slow-onset and longer-lived airway hyperresponsiveness, which may be associated with the induction, the development and the long duration of airway hyperreactivity.

Acetylcholine↗
PubMed1995

Somatic mutations of the adenomatous polyposis coli gene in gastroduodenal tumors from patients with familial adenomatous polyposis.

We analyzed somatic mutations of the adenomatous polyposis coli (APC), p53, and K-ras genes in gastroduodenal polyps and normal gastroduodenal mucosa from 21 familial adenomatous polyposis patients, using PCR-single-strand conformation polymorphism and direct sequencing methods. Seventy-five polyps were obtained from these patients endoscopically or surgically, and they were histopathologically diagnosed as mild adenoma, moderate adenoma, severe adenoma, adenocarcinoma, and fundic gland polyp. Examining the APC-coding region where somatic mutations in colorectal tumors are known to be clustered, we detected 47 somatic mutations. The frequency of mutation detected was 6 of 9 (67%) in ampullary adenomas, 1 of 2 (50%) in ampullary adenocarcinoma, 11 of 24 (46%) in non-ampullary adenomas, 26 of 29 (90%) in gastric adenomas, and 3 of 11 (27%) in gastric fundic gland polyps. These mutations frequently occurred at codons 1450, 1462-1465, and 1554-1556, the third being a newly found hot spot. All mutations formed stop codons that resulted in truncated APC proteins. K-ras mutation was detected only in an ampullary adenocarcinoma, and p53 mutation was not detected in any of the tumors analyzed. There was no somatic mutation detected in samples of flat mucosa that were diagnosed as normal mucosa both endoscopically and histopathologically. Frequent APC mutations in mild and small adenomas, similar to the findings in severe and large adenomas, suggested that the genetic change in the APC gene occurs in an early stage of forming gastroduodenal adenomas. Moreover, the presence of somatic APC mutations in fundic gland polyps suggests that inactivation of the APC gene plays a role not only in forming adenomas but also in forming hyperplastic polyps in fundic gland mucosa, and there may be some additional steps to the adenoma-carcinoma sequence.

Adenomatous Polyposis Coli↗
PubMed1995

The Ca2+ influx induced by beta-amyloid peptide 25-35 in cultured hippocampal neurons results from network excitation.

Although a neurotoxic role has been postulated for the beta-amyloid protein (beta AP), which accumulates in brain tissues in Alzheimer's disease, a precise mechanism underlying this toxicity has not been identified. The peptide fragment consisting of amino acid residues 25 through 35 (beta AP25-35), in particular, has been reported to be toxic in cultured neurons. We report that beta AP25-35, applied to rat hippocampal neurons in culture, caused reversible and repeatable increases in the intracellular Ca2+ concentration ([Ca2+]i), as measured by fura 2 fluorimetry. Furthermore, beta AP25-35 induced bursts of excitatory potentials and action potential firing in individual neurons studied with whole cell current clamp recordings. The beta AP25-35-induced [Ca2+]i elevations and electrical activity were enhanced by removal of extracellular Mg2+, and they could be blocked by tetrodotoxin, by non-N-methyl-D-aspartate (NMDA) and NMDA glutamate receptor antagonists, and by the L-type Ca2+ channel antagonist nimodipine. Similar responses of bursts of action potentials and [Ca2+]i increases were evoked by beta AP1-40. Responses to beta AP25-35 were not prevented by pretreatment with pertussis toxin. Excitatory responses and [Ca2+]i elevations were not observed in cerebellar neuron cultures in which inhibitory synapses predominate. Although the effects of beta AP25-35 depended on the activation of glutamatergic synapses, there was no enhancement of kainate- or NMDA-induced currents by beta AP25-35 in voltage-clamp studies. We conclude that beta AP25-35 enhances excitatory activity in glutamatergic synaptic networks, causing excitatory potentials and Ca2+ influx. This property may explain the toxicity of beta AP25-35.

Amyloid beta-Peptides↗
PubMed1995

Germ line mutations of hMSH2 and hMLH1 genes in Japanese families with hereditary nonpolyposis colorectal cancer (HNPCC): usefulness of DNA analysis for screening and diagnosis of HNPCC patients.

Mutations in hMSH2 and hMLH1 genes were analyzed in patients from 11 Japanese families that had been diagnosed as carrying hereditary nonpolyposis colorectal cancer (HNPCC) by clinical examination. Germ line mutations of hMSH2 gene were identified in 5 independent families in which colorectal (87% of patients), endometrial (30%), ovarian (17%), gastric (14%), and other cancers existed. Five mutations detected between codons 136 and 811 included single-base substitutions (C-->T and T-->G), a T deletion, and an A insertion, all of which produced stop codons resulting in truncated proteins, and an A-->T substitution at splice donor site of exon 5 which resulted in deletion of this exon. Moreover, one HNPCC family was presumed to have germ line mutation of hMSH2 gene because a somatic mutation of hMSH2 gene was detected in a cancer from a patient in this family. In addition to these 11 families already diagnosed with HNPCC, 3 new families with germ line mutations of hMSH2 gene and hMLH1 gene were found through analysis of DNA from patients who had multiple cancers with alteration in microsatellite DNA. These mutations included an AG deletion at codons 877-878 of hMSH2 gene, an AAG deletion at codons 616-618 of hMLH1 gene, and a C-->T single-base substitution at codon 217 of hMLH1 gene. Seven of eight germ line mutations found in this study are new mutations that have not been reported previously. In families in which germ line mutations were identified presymptomatic examination was then carried out using polymerase chain reaction single-strand conformation polymorphism analysis of DNA from peripheral blood, and the result was the detection of family members predisposed to HNPCC who did not yet show signs of cancer. These results indicate the value of DNA analysis in the screening and diagnosis of HNPCC patients and families.

Adult↗
PubMed1995

Peri-operative complications in adult moyamoya disease.

The incidence and causes of peri-operative haemodynamic complications in adult Moyamoya disease were examined by reviewing 55 surgically treated adult patients. Ninety-nine craniotomies were performed in these patients, and eight peri-operative complications (four infarctions, two haemorrhagic infarctions and two reversible ischaemic neurological deficits without a new lesion) were seen. All of the eight haemodynamic complications arose in the initially affected hemispheres regardless of the side of operation. Some nonsurgical haemodynamic risk factors, i.e., hypercapnia, hypocapnia and hypotension/hypovolaemia, were noted in all of the eight cases, although the statistical analysis could not clarify the relevance of such factors to peri-operative complications. Surgical factors which might be responsible for the complications were noted in three cases. Sparing vital collateral vessels and minimum brain retraction as well as avoidance of non-surgical haemodynamic risk factors are considered to be essential to prevent peri-operative haemodynamic brain damage in adult Moyamoya disease.

Adolescent↗
PubMed1995

Long-term angiographic follow-up of lesions patent 6 months after percutaneous coronary angioplasty.

To determine long-term angiographic prognosis after successful angioplasty (< 50% residual stenosis, > or = 20% reduction of stenosis, and no major complications), coronary angiography was performed 2 to 4 years after angioplasty in patients who were < or = 70 years old at the time of treatment and who showed patency (< or = 50% stenosis) 6 months after the initial procedure. Among 407 lesions that were dilated in 333 patients between 1983 and 1989, 298 (73.2%) lesions were reviewed by long-term angiography after 177 +/- 34 weeks. At long-term follow-up, 4 (1.3%) lesions were totally occluded, 3 (1.0%) had severe stenosis (> or = 75% stenosis), 9 (3.0%) had mild stenosis (> 50% to < 75% stenosis), and 282 (94.6%) were patent (< or = 50% stenosis). The percentage of stenosis of patent lesions decreased from 24% +/- 14% at 6 months to 21% +/- 13% at long-term follow-up (p < 0.0001). No specific clinical or angiographic characteristics were identified in patients with severe stenosis at long-term follow-up. These findings indicate that when patency is obtained 6 months after angioplasty, a 95% long-term patency rate with regression of stenosis can be expected.

Adult↗
PubMed1995

In vivo sulfhydryl modification of the ligand-binding site of Tsr, the Escherichia coli serine chemoreceptor.

The Escherichia coli chemoreceptor Tsr mediates an attractant response to serine. We substituted Cys for Thr-156, one of the residues involved in serine sensing. The mutant receptor Tsr-T156C retained serine- and repellent-sensing abilities. However, it lost serine-sensing ability when it was treated in vivo with sulfhydryl-modifying reagents such as N-ethylmaleimide (NEM). Serine protected Tsr-T156C from these reagents. We showed that [3H]NEM bound to Tsr-T156C and that binding decreased in the presence of serine. By pretreating cells with serine and cold NEM, Tsr-T156C was selectively labeled with radioactive NEM. These results are consistent with the location of Thr-156 in the serine-binding site. Chemical modification of the Tsr ligand-binding site provides a basis for simple purification and should assist further in vivo and in vitro investigations of this chemoreceptor protein.

Bacterial Proteins↗
PubMed1995

Increase in respiratory resistance after exercise in conscious guinea pigs. As a model for exercise-induced asthma.

We have developed an experimental model for exercise-induced asthma (EIA) using conscious guinea pigs. Respiratory resistance (Rrs) was measured before and after exercise (running). When a 0.05% lipopolysaccharide (LPS) was inhaled by guinea pigs which had been pretreated with a corticosteroid biosynthesis inhibitor metyrapone (50 mg/kg, i.v.), Rrs significantly increased 24 h after exercise. Metyrapone had no effect, however, on the LPS-induced increase in the numbers of macrophages, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF). In order to examine the role of airway inflammation, the effects of murine recombinant interleukin-5 (mrIL-5) and platelet activating factor (PAF) were investigated in guinea pigs. The exercise-elicited increase in Rrs was observed 24 h later than the treatment with mrIL-5 in metyrapone-treated animals. The number of macrophages, eosinophils and neutrophils increased in the BALF of mrIL-5-treated animals. In contrast, a 0.05% PAF aerosol caused an increased number of eosinophils in BALF, but did not affect Rrs after exercise in either metyrapone-treated or non-treated animals. Moreover, to evaluate the value of this model as a pharmacological tool, the effect of ketotifen and prednisolone on the exercise-induced increase in Rrs was investigated. Prior administration of ketotifen and prednisolone showed a tendency to prevent, or clearly inhibited, the exercise-induced increase in Rrs in animals treated with the combination with LPS and metopyrone.

Airway Resistance↗
PubMed1995

Studies on anti-allergic action of AH 21-132, a novel isozyme-selective phosphodiesterase inhibitor in airways.

The effects of AH 21-132, a type III and IV phosphodiesterase (PDE) inhibitor, on allergic reactions in the airway were studied by comparing them with the effects of rolipram, a type IV PDE inhibitor, and aminophylline, a non-selective PDE inhibitor. The following results were obtained: 1) AH 21-132, rolipram and aminophylline inhibited the antigen-induced contraction of isolated guinea pig tracheal muscle in vitro. 2) AH 21-132 and aminophylline inhibited antigen-induced histamine release from human lung tissue fragments. 3) Antigen-induced accumulation of inflammatory cells including eosinophils and macrophages in mice bronchoalveolar lavage fluid was clearly inhibited by AH 21-132 and rolipram, but not by aminophylline. 4) AH 21-132, rolipram and aminophylline inhibited immediate phase bronchocostriction induced by either an intravenous or an aerosol challenge of antigen in guinea pigs. 5) AH 21-132 and rolipram inhibited the aeroantigen challenge-induced late phase increase in the airway resistance in guinea pigs, but aminophylline did not. These results suggest that AH 21-132 has an anti-allergic effect in the airway and that these actions may be beneficial for the treatment of allergic bronchial asthma.

Aminophylline↗
PubMed1995

Effects of NIP-502 on antigen-induced bronchial responses and allergic reactions in animal models.

We examined the effect of a newly synthesized pyridazinone derivative, NIP-502 [4-chloro-5-(3-ethoxy)-4-phenoxybenzamine)-3(2H)-pyridazinone], on antigen-induced bronchial responses and allergic reactions in several animal models. NIP-502 (10 mg/kg, p.o.) inhibited the antigen-induced immediate asthmatic response in passively sensitized guinea pigs. The inhibitory effect was also observed in metyrapone (an inhibitor of 11 beta-hydroxylase)-pretreated guinea pigs. NIP-502 improved ovalbumin (OA)-induced airway hyperresponsiveness to acetylcholine and inhibited the OA-induced increase in the number of inflammatory leukocytes in the bronchoalveolar lavage fluid. These inhibitory effects on OA-induced responses were similar to those of prednisolone. NIP-502 also showed an inhibitory effect on the passive cutaneous anaphylactic reaction in rats but did not inhibit the reversed cutaneous anaphylactic reaction, reversed Arthus reaction or delayed type hypersensitivity reaction. On the other hand, prednisolone showed broad inhibitory effects except for the reversed cutaneous anaphylactic reaction. In the in vitro study, NIP-502 (30 microM) significantly inhibited Formyl-Met-Leu-Phe-induced superoxide anion production by the guinea pig alveolar macrophages. These results indicate that the inhibitory effects of NIP-502 on bronchial responses are similar to those of prednisolone, but this compound seemed to act more selectively on the respiratory tract than prednisolone. Because of its effectiveness against a variety of bronchial responses, NIP-502 may be useful in the treatment of bronchial asthma.

Aminophylline↗