Biomedical subjects

M Akagi

Publications and source records attributed to M Akagi.

At least 37 records · Page 2Linked to original sources

PubMed1997

Inhibitor effect of apafant on bronchopulmonary responses to platelet activating factor and to antigen in rats.

Apafant (4-(2-chlorophenyl)-9-methyl-2-(3-morpholino-3-oxopropyl)-6H-thieno[3,2- f] [1,2,4]triazolo[4,3-a][1,4] diazepine, CAS 105219-56-5, WEB 2086), as a specific platelet activating factor (PAF) antagonist, inhibited PAF-induced increases of bronchial inflation pressure (delta Pi), pulmonary artery perfusion pressure (delta Pp) and microvascular permeability (wet-to-dry lung weight ratios), dose-dependently, in rats. Apafant also inhibited antigen-induced increase of delta pi, delta Pp and microvascular permeability in passively sensitized rats. Ozagrel also inhibited PAF- and antigen-induced increase of delta Pi, delta Pp and microvascular permeability. Apafant almost completely inhibited the increase of intratracheal pressure and microvascular permeability, but incompletely inhibited the increase of pulmonary artery pressure. At 1 microgram/ml, the effects of ozagrel were almost comparable to that of apafant at the same concentration, but the inhibitory effect on intratracheal pressure was less than that of apafant. Apafant inhibited PAF-induced increase in perfusate of thromboxane (TX) B2 and leukotrine C4/D4E4 (LTs), and antigen-induced increase of TXB2, LTs, PAF and histamine. Ozagrel also inhibited the PAF-induced increase of TXB2, but not the increase of LTs. Apafant inhibited antigen-induced increase of TXB2 and LTs more strongly than PAF-induced increase. The order of inhibitory effects of apafant against generation and release of chemical mediators was TXB2, LTs, PAF and histamine. These findings suggest that TXA2, LTs and PAF may contribute to the increase of intratracheal pressure and microvascular permeability, and histamine may contribute to the increase of vascular resistance in rats. Apafant may inhibit bronchopulmonary responses through PAF receptor antagonism. In addition, apafant can be considered to be useful for the treatment of some allergic diseases when the drug is employed in clinical use.

Animals↗

PubMed1996

Inhibition of cell growth by transforming growth factor beta 1 is associated with p53-independent induction of p21 in gastric carcinoma cells.

Cell cycle regulators such as cyclins, cyclin-dependent kinases (cdks) and their inhibitors control the growth of cells. SDI1/CIP1/WAF1/p21 is a potent inhibitor of G1 cdks, whose expression is induced by wild-type p53. To elucidate the mechanism of growth inhibition by transforming growth factor beta 1 (TGFbeta 1), we examined the effect of TGFbeta 1 on the expression of p21, G1 cyclins and cdks by human gastric cancer cell lines. TGFbeta 1 induced p21 expression and subsequently suppressed cdk2 kinase activity, followed by a reduction in phosphorylation of the product of the retinoblastoma tumor suppressor gene in TMK-1 cells, which are responsive to TGFbeta 1. Coimmunoprecipitation analysis demonstrated that TGFbeta 1 increased the level of p21 protein present in complexes with cdk2. In contrast, TGFbeta 1 did not induce p21 in TGFbeta 1-resistant MKN-28 cells. TGFbeta 1 did not affect the levels of p53 mRNA and protein in TMK-1 and MKN-28 cells, which contain mutated p53 genes. These mutated p53 complementary DNAs, when overexpressed, failed to activate transcription from the p21 promoter. Furthermore, TGFbeta 1 caused a reduction in the steady-state level of cyclin A protein concomitantly with inhibition of cdk2 kinase activity in TMK-1 cells. These results suggest that the growth inhibition of tumor cells by TGFbeta 1 is associated with p53-independent induction of p21, subsequent suppression of cdk activity and a decrease in cyclin A protein in TMK-1 cells.

Adenocarcinoma↗

PubMed1996

Genetic status and expression of the cyclin-dependent kinase inhibitors in human gastric carcinoma cell lines.

Deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a pivotal role in the development of diverse human cancers. We examined the genetic status and the expression of CDK inhibitors (p21, p27, p16 and p15), CDK2 and cyclins (A, D1 and E) in eight gastric carcinoma cell lines, in comparison with the status of p53 gene alterations. All the cell lines (except MKN-28) that contained a p53 gene abnormality expressed very low or undetectable levels of p21 mRNA, while the cell lines (MKN-45 and -74) with wild-type p53 gene expressed high levels of p21 mRNA. An inverse correlation was found between the level of p21 mRNA and the expression of mRNAs for CDK2 and G1 cyclins. MKN-28 was an exception; it contained mutated p53, and expressed mRNAs for p21, CDK2 and G1 cyclins at high levels. Only MKN-45 and -74, with wild-type p53, expressed considerable levels of p21 protein. Homozygous deletion of the p16 and p15 genes was detected in two (MKN-45 and HSC-39) of the eight gastric carcinoma cell lines, p16 protein was not expressed in three cell lines (MKN-28, MKN-74 and KATO-III), as well as MKN-45 and HSC-39. Rearrangement of the p15 gene was found in TMK-1. Rearrangement of the p27 gene was detected in MKN-45, although the expression of p27 protein was well preserved in all the gastric carcinoma cell lines. The expression of pRb was also preserved in all the cell lines except KATO-III. No obvious correlation was observed between the p53 gene status and the expression of p27 and p16. These findings suggest that abnormal regulation of CDK2/cyclins and CDK inhibitors might be involved in deregulated growth of gastric carcinomas.

Adenocarcinoma↗

PubMed1996

Relationship between the pulmonary artery index and physiological properties of the pulmonary vascular bed.

BACKGROUND: To clarify the physiological significance of the pulmonary artery index (PAI), we examined the relationship between PAI and physiological properties of the pulmonary vascular bed. We also examined the limitations of PAI in practical use. METHODS AND RESULTS: We examined the relationships between PAI and pulmonary vascular resistance (Rp), pulmonary arterial compliance (Cp), and the time constant (RC) of pulmonary circulation in 50 patients with congenital heart disease with decreased pulmonary blood flow. PAI was significantly related to Cp and RC (r = 0.67, r = 0.63, respectively). These correlations became more significant when we excluded patients in whom the central pulmonary arteries were disproportionately dilatated in contrast to the peripheral pulmonary arteries (r = 0.80, r = 0.70, respectively). CONCLUSIONS: PAI reflects the state of the pulmonary vascular bed, especially when the peripheral arteries develop in proportion to the central pulmonary artery.

Heart Failure↗

PubMed1996

[Clinical analysis on the course and prognosis of patients with Crohn's disease].

We analyzed 66 cases (47 males and 19 females) of Crohn's disease at Hiroshima University hospital from September 1975 to October 1994 to clarify the course and prognosis of Crohn's disease. The age at onset was 21.1 +/- 7.3 years old (mean +/- SD), terms between onset and diagnosis were 21.5 +/- 33.0 months (mean +/- SD) and observation period was 65.5 +/- 44.6 months (mean +/- SD). Sites of lesion were 18 ileum, 41 ileocolon and 7 colon. Thirty-one cases, 20 cases of which had intestinal obstruction, underwent surgical operation (12 ileum types, 18 ileocolic types, 1 colon type). The cumulative probability of surgery at one, five and ten years after onset of symptoms were 12.1%, 28.8% and 56.9%, respectively. As for cumulative probability of surgical operation at one, five and ten years after diagnosis were 25.8%, 36.7% and 74.4%, respectively. Results of the cumulative probability of surgery by anatomical involvement indicated that the ileum type had a statistically significantly higher risk than other types. In each analysis compliance to nutritional therapy was also an important prognostic factor. Overall, our results indicated that the site of lesion and the compliance to nutritional therapy were important factors which have an effect on the course and prognosis of Crohn's disease patients.

Adolescent↗

PubMed1996

Myocardial troponin T levels in patients with diabetic nephropathy.

We investigated myocardial troponin T (TnT) level as a marker for myocardial injury at various stages of diabetic nephropathy, including end-stage renal failure. One hundred and four diabetic patients were included in this study. These patients were divided into 5 groups as follows: Group I, composed of 41 patients without nephropathy who served as controls; Group II, composed of 15 patients with micro-albuminuria; Group III, composed of 15 patients with macroalbuminuria; Group IV, composed of 8 patients with renal failure who were not receiving hemodialysis; and Group V, composed of 25 patients who were receiving hemodialysis for renal failure. The following markers of myocardial injury were measured in these patients: myocardial TnT, creatine kinase (CK), myoglobin (Mb), and myosin light chain-1 (MCL-1). Our results showed that as the disease state of diabetic nephropathy advanced to renal failure, myocardial TnT levels became elevated. Group V showed significantly higher myocardial TnT levels than either Group I, Group II or Group III. Group IV showed significantly higher myocardial TnT levels than either Group II or Group III. The rate of ischemic changes on electrocardiograms also tended to increase with advance to renal failure in these patients. However, there was no correlation between myocardial TnT levels and serum Cr levels, used as an index for renal function. Myocardial TnT levels had a higher specificity for cardiac muscle than other markers for myocardial injury and are not significantly influenced by renal function. Myocardial TnT may be useful as a marker of myocardial injury for patients with chronic renal failure.

Adult↗

PubMed1996

Diagnostic significance of electrocochleogram and auditory evoked brainstem response in totally or subtotally deaf patients.

This paper examined the use of ECoG and ABR in 7 patients with totally or subtotally deaf ears. The patients included one with cortical deafness, one with psychogenic deafness, one with intrapontine hemorrhage, and 4 with acoustic neuroma. In patients with substantial hearing loss, ECoG should be performed first if retrocochlear disorders are suspected since results may be obtained even in the absence of other auditory evoked potentials. Simultaneous ABR measurements can be effective when localizing retrocochlear lesions. ECoG can also help to determine the need for preserving hearing during surgery for retrocochlear lesions by indicating the degree of cochlear function.

Adult↗

PubMed1996

Antibodies of type II collagen and immune complexes in Menière's disease.

In a previous study, we showed that endolymphatic hydrops was induced in 36% of guinea pigs immunized with type II collagen and that dominant negative summating potential (SP) was recorded for these hydropic animals. In the present study, we evaluated the levels of serum antibody to type II collagen and three other immune indexes in patients with Menière's disease, especially those who showed negative SP dominance in ECoG. Twenty-nine Menière's cases, 22 normal volunteers serving as controls, 28 rheumatoid arthritis (RA) cases, and 9 patients complaining of vertigo were examined to detect serum immune indexes. Menière's patients exhibited high values of serum anti-type II collagen antibody compared with control subjects. Furthermore, total IgG, C3, anti-type II collagen antibody and CIC were increased with the highest levels being in the RA group, followed by Menière's disease group and then the control group. These results probably reflect the extent of immune reaction development. The immune response may be generalized in RA cases and/or local in Menière's disease. These results suggest the development of certain immune status abnormalities in our cases, which lends support to the idea of immunologic disorder playing a role in the etiology of some cases of Menière's disease.

Adult↗

PubMed1996

Two unusual cases of a foreign body in the oral cavity caused by eating raw squid.

Foreign bodies are often encountered by otolaryngologists, but the oral cavity is considered a place where foreign bodies are rare because of its structural and functional features. We here present 2 cases with a foreign body in the oral cavity resulting from eating raw squid. In one of these 2 cases endoscopic examination revealed a gastric foreign body. The foreign bodies in the oral cavity were removed using forceps, together with surrounding mucous membrane. These foreign bodies were identified as sperm bulbs and discharging tube of sogittated calamary (Todarodes pacificus Steenstrup). Larva migrans of anisakiasis are to be differentiated from sperm bulbs; it is important to distinguish between the shape and size of the foreign body in our cases. If sperm bulbs are stuck in the oral cavity, it is necessary to remove them completely to ensure that inflammation is prevented. We stress the importance of checking not only anisakiasis but also sperm bulbs in humans who like eating raw squid.

Animals↗

PubMed1996

Two cases of esophageal diverticula.

Two cases of pharyngoesophageal diverticula were reported with reference to previous studies. Definite diagnosis was established by esophagography. The surgical treatment is generally conducted in accordance with Goodman-Parnes' criteria for surgical indication. We also carried out surgery on the basis of this criteria. One-stage diverticulectomy was performed and favorable results with no postoperative complications were obtained.

Aged↗

PubMed1996

[Case report of sodium valproate treatment of aggression associated with Alzheimer's disease].

Aggressive behaviors represent a major management problem in patients with dementia. Neuroleptics are commonly the selected psychotherapeutics for controlling severe aggression, especially the violent outbursts often seen in severely demented patients. But their efficacy for this problem is limited and their use is frequently complicated by side effects. Anticonvulsants such as carbamazepine have been advocated as alternatives. Although sodium valproate can also be a potential alternative, only a few cases were reported. A 69-year-old man was admitted for the control of agitation, wandering and violence. He had an 8-year history of amnesia. The mental status examination revealed severe global cognitive loss. Cranial computed tomography showed moderate brain atrophy and dilatation of bilateral temporal ventricles. A diagnosis of Alzheimer's disease was made. Initially he was treated with nuroleptics. Sulpride in doses up to 600 mg/day had no positive effect, but led to confusion and worsened aggressive behavior. Haloperidol in doses up to 4 mg/day or propericiazine 40 mg/day showed the same result as sulpiride. Carbamazepine had a moderate ameliorative effect on the agitation and violence, but the patient could not tolerate it because of muscle weakness. Then, we used sodium valproate 400mg/day and found this was effective. After one week muscle weakness appeared. Therefore, the dose was decreased to 200mg/day, achieving a blood level of 20.7 micrograms/ml. The patient's agitation was well controlled at that point and had no apparent side effects. Sodium valproate may be a useful agent in the treatment of aggression in patients with dementia.

Aged↗

PubMed1995

Expression of amphiregulin in human gastric cancer cell lines.

BACKGROUND: Amphiregulin (AR) is a novel gene of the epidermal growth factor (EGF) family. The authors have already reported that AR mRNA was expressed by human gastric carcinoma cells at various degrees, and its expression was induced by the treatment with EGF or transforming growth factor-alpha (TGF-alpha). METHODS: To elucidate the biologic role of AR in the stomach carcinogenesis, the effect of AR on the cell growth and the expression of growth factor/receptor genes in TMK-1 and MKN-28 gastric carcinoma cell lines was examined. Furthermore, to determine whether AR acts as an autocrine growth factor for gastric carcinoma cells, the authors introduced an antisense phosphorothioate oligodeoxynucleotide (S-oligo) against AR mRNA to these two cell lines. RESULTS: AR stimulated the growth of TMK-1 and MKN-28 cells in a dose dependent manner. The growth-promoting effect of AR was as potent as that of EGF or TGF-alpha. AR antisense S-oligo induced significant growth inhibition of both TMK-1 and MKN-28 cells compared with the control random S-oligo. Moreover, AR induced mRNA expression for AR itself, TGF-alpha, and EGF receptor in both cell lines. CONCLUSIONS: These results overall suggest that AR acts as an autocrine growth factor for these two gastric carcinoma cell lines and evokes the cascade induction of EGF and the TGF-alpha/receptor system.

Adenocarcinoma↗

PubMed1995

Inhibitory effect of epinastine on superoxide generation by rat neutrophils.

We studied the effects of antiallergic drugs, epinastine, ketotifen, oxatomide, mequitazine and cromolyn sodium on superoxide anion (O2-) generation from rat neutrophils. Epinastine, ketotifen, oxatomide and mequitazine dose-dependently prevented the N-formyl-Met-Leu-Phe- and phorbol 12-myristate 13-acetate-induced O2- generation, but cromolyn sodium did not prevent it. When membrane and cytosol fractions were incubated with each drug, epinastine, ketotifen and mequitazine prevented O2- generation. On the other hand, when only the membrane fraction was incubated with each drug, ketotifen and mequitazine prevented O2- generation, but epinastine did not. Epinastine may inhibit the NADPH oxidase system through the obstruction of NADPH oxidase-associated cytosol components.

Animals↗

PubMed1995

New criteria for the radical repair of congenital heart disease with pulmonary hypertension. In order to avoid postoperative residual pulmonary hypertension.

In congenital heart disease (CHD) with pulmonary hypertension (PH) resulting from high pulmonary flow, we sometimes experience patients whose PH continues even after the normalization of flow following surgery. Preoperative identification of these patients is difficult even using direct hemodynamic measurements at cardiac catheterization. The purpose of this study is to interpret the state of the pulmonary vascular bed more precisely using a new theoretical approach and to present the criteria available for avoiding residual PH. During preoperative routine catheter examination in CHD patients with PH we applied the Windkessel model to the pulmonary circulation and calculated the diastolic time constant (Td) of the pulmonary circulation. Td of Group 1 (0.50 +/- 0.03 sec), 6 patients who manifested residual PH after surgery, was higher than that of group 2 (0.23 +/- 0.14 sec), 42 patients with normalized pulmonary artery pressure after surgery. Furthermore, the relationships between Td and pulmonary blood flow (Qp) or pulmonary to systemic flow ratio (Qp/Qs) were very sensitive for distinguishing between these two groups. Group 1 was located in the left-upper quadrant of the graph of Td vs Qp or Td vs Qp/Qs relationships, whereas group 2 was located in the right-lower quadrant. The relationships between Td and Qp or Qp/Qs were considered to reflect the pathological change in the pulmonary vasculature more precisely. As a consequence, they would be very useful in understanding the state of the pulmonary vascular bed and avoiding residual PH.

Blood Pressure↗

PubMed1995

Contribution of platelet activating factor (PAF) in histamine-induced model of nasal allergy in rats.

Histamine-induced nasal hyperpermeability was measured in rats. Perfusion of histamine elicited a biphasic increase of nasal vascular permeability, and an increase of concentration of platelet-activating factor (PAF) in the perfusate. Both phases were prevented by pretreatment with diphenhydramine (1 mg/kg, p.o.), a histamine H1-receptor antagonist, and the second increase of vascular permeability was prevented by pretreatment with 3-[4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f] [1,2,4]-triazolo [4,3-alpha] [1,4] diazepin-2-yl]-1-(4-morpholinyl)-1-propane (WEB 2086) (10 mg/kg, p.o.), an anti PAF agent. The time-course of PAF-induced nasal hyperpermeability was similar to that of the second increase induced by histamine. These findings suggest that PAF released by histamine from nasal mucosa plays an important role in nasal allergy, especially in the late phase.

Animals↗

PubMed1995

Effect of loratadine on immediate and delayed type hypersensitivity reactions.

Loratadine (CAS 79794-75-5) was effective in inhibiting the contractions of the ileum induced by histamine in guinea pigs. The drug also caused an anti-acetylcholine, anti-serotonin and anti-leukotriene D4 (LTD4) effect. In addition, loratadine inhibited the synthesis of leukotrienes more potently than ketotifen. On the other hand, in in vitro studies of histamine release from rat peritoneal mast cells induced by compound 48/80 or lung fragments in actively sensitized guinea, pigs, loratadine elicited a significant inhibition at a concentration of 5 mumol/l. In ex vivo studies, the drug inhibited histamine release from lung fragments induced by concanavalin A, and significant effect lasted for 24 h when the drug was administered at a dose of 20 mg/kg. The drug inhibited LTD4 release as well as histamine from lung fragments in actively sensitized guinea pigs. Loratadine inhibited not only 45Ca uptake into the rat peritoneal mast cells but also Ca2+ release from the intracellular Ca store induced by compound 48/80 or A23187. Loratadine increased cAMP content in rat lung preparation while decreasing cGMP content. Loratadine caused no significant change in order parameter and phospholipase A2 activity. The drug was more potent than ketotifen and terfenadine in inhibiting antigen-induced increase in airway resistance in guinea pigs. In addition, the effect of loratadine on airway resistance was sustained for 12 h. Loratadine inhibited an increase in dye leakage into the nasal cavity in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1995

A comparative study of myocardial troponin T levels in patients undergoing hemodialysis.

This study included 25 patients receiving hemodialysis (HD) but in whom diabetes mellitus was not the primary disease (HD-non DM group), 25 patients receiving hemodialysis with diabetes mellitus as the primary disease (HD-DM group), and 50 patients with diabetes mellitus who had not yet been treated with hemodialysis (DM group). The following markers of myocardial injury were measured in these patients: troponin T (TnT), creatine kinase (CK), myoglobin (Mb), and myosin light chain-1 (MLC-1). No significant correlation was found between myocardial TnT and Cr in any study group. The Mb and MLC-1 values in patients receiving HD were markedly higher than normal regardless of the primary disease involvement, while myocardial TnT was found to be only slightly abnormal. These results suggest that myocardial TnT may be a more useful marker of myocardial injury in HD patients than the markers in current use. In the present investigation, myocardial TnT was the only marker that was higher in the HD-DM group than in the HD-non DM group. This suggests the possibility that the HD-DM group included more patients with arteriosclerotic lesions, such as myocardial injury.

Aged↗

PubMed1995

Role of histamine H3 receptor on hypoxia-reoxygenation-induced cardiac dysfunction in guinea pigs.

Hypoxia elicited a remarkable decrease in contractility and heart rate in isolated right atria from guinea pigs, a decrease which recovered partially during reoxygenation. Histamine content increased during hypoxia and decreased during reoxygenation. However, hypoxia induced a marked degranulation of mast cells. Pretreatment with alpha-methylhistamine (100-300 nM) recuperated control level contractility and heart rate, and prevented the hypoxia-reoxygenation-induced leakage of creatine phosphokinase (CPK). On the other hand, pretreatment with thioperamide (100-300 nM) decreased contractility and heart rate dose-dependently, and prevented recovery during reoxygenation. These data shows that cardiac histamine may play an important role in the protection against hypoxia-reoxygenation injury through the H3 receptor.

Adenosine Triphosphate↗