[A case of autoimmune hepatitis with anti-phospholipid syndrome].
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Aged↗
Biomedical subjects
M Akagi
Publications and source records attributed to M Akagi.
Cloning of a mouse smoothened cDNA and expression patterns of hedgehog signalling molecules during chondrogenesis and cartilage differentiation in clonal mouse EC cells, ATDC5.
Hedgehog (hh) family proteins appear to use the conserved targets in their signalling pathway including Patched (Ptc), Smoothened (Smo), and Gli. Although Indian hedgehog (Ihh) plays an important role in endochondral bone formation, the involvement of hh signalling molecules in skeletogenesis is unknown. We cloned a mouse (m) Smo cDNA and studied the expression patterns of Ihh, Ptc, Smo, and Gli mRNAs in mouse chondrogenic EC cells, ATDC5. The deduced amino acid sequence of mSmo consisted of 793 amino acids and was 98 and 93% homologous to the rat (r) Smo and human (h) Smo, respectively. In ATDC5 cells, the expression of Ihh mRNA paralleled that of type X collagen mRNA. Smo, Ptc, and Gli mRNAs were constitutively expressed throughout chondrogenesis and the subsequent cartilage differentiation processes except for the transient decrease in Ptc mRNA at the cellular condensation stage. Our data suggest that hh signalling molecules may be involved in chondrogenesis and cartilage differentiation in ATDC5 cells.
Amino Acid Sequence↗
The mechanisms of compound 48/80-induced superoxide generation mediated by A-kinase in rat peritoneal mast cells.
This investigation was undertaken to clarify the mechanisms of superoxide anion (O2-) generation in rat peritoneal mast cells. Compound 48/80, a typical histamine liberator mediated by calcium influx, elicited O2- generation from the mast cells in a dose-dependent fashion. It was demonstrated by immunohistochemical study and Western blot analysis that the mast cells contained the 47-kDa phagocyte oxidase (p47phox) protein, which was one cytosolic component of the NADPH oxidase system. Arachidonic acid stimulated O2- generation in the mast cells, but other unsaturated fatty acids had no effect. On the other hand, 48/80-induced O2- generation was inhibited by phospholipase A2 inhibitors, such as arachidonyl trifluoromethyl ketone and manoalide. Forskolin, isoprenaline, and dibutyryl cyclic AMP inhibited the O2- generation, and KT-5720, a cyclic AMP-dependent protein kinase (A-kinase) inhibitor, markedly enhanced the O2- generation. These findings suggest that O2- is generated by a NADPH oxidase-like enzyme system in mast cells and that this enzyme system is activated by arachidonic acid released by cytosolic phospholipase A2. Thus, it is regulated by the cyclic AMP-A kinase system.
Animals↗
Anti-allergic effect of tea-leaf saponin (TLS) from tea leaves (Camellia sinensis var. sinensis).
We investigated the anti-allergic effect of tea-leaf saponin (TLS), which was a mixture of saponins separated from the leaves of Camellia sinensis var. sinensis, in guinea pigs and rats. TLS (20-100 mg/kg) dose-dependently inhibited experimentally-induced asthma, and ID50 was 61.7 mg/kg. TLS (20-100 mg/kg) dose-dependently inhibited a 48 h homologous PCA (passive cutaneous anaphylaxis) reaction, and the inhibitory effect was similar to that of tranilast. TLS (1-100 microg/ml) also inhibited the release of antigen-induced leukotriene (LT) C4 from sensitized guinea pig lung samples in a dose-dependent fashion, but did not prevent histamine release. TLS (0.01-0.5 microg/ml) inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. At higher concentrations, TLS elicited histamine release. These findings suggest that TLS may be a useful protective agent against clinical allergy, and that the inhibitory effects of TLS on mediator release are in some way related to its inhibitory effect on experimentally-induced asthma and PCA reaction.
Airway Resistance↗
[The serum zinc level in patients with tinnitus and the effect of zinc treatment].
We measured the serum zinc level in patients with tinnitus and evaluated the effectiveness of zinc in the treatment of tinnitus. Blood zinc levels were measured in 121 patients with tinnitus. All patients were examined between 1995 and 1997 at the outpatient clinic of otorhinolaryngology St. Marianna University Toyoko Hospital. Forty-seven patients who had received any drug such as a calcium channel blocker and others or had been affected by any diseases were excluded and therefore 74 patients consisting of 46 females (62%) and 28 males (38%) were investigated. Twenty two healthy volunteers served as a control group. The mean age and standard deviations for the tinnitus group and the control group were 47.8 +/- 17.1 and 31.4 +/- 8.2 years, respectively. There was a significant decrease (p < 0.0001) in serum zinc levels in patients with tinnitus compared with the control group. Because there was a significant difference (p < 0.0001) in age distribution between tinnitus and control groups, patients were selected by their age in order to neglect the effect of aging. In this situation, a significant difference (p < 0.01) was noted between the tinnitus group and control group. Low blood zinc level was defined by using the mean and standard deviation for the control group (mean-1 S.D.). We treated patients with low blood zinc levels. A total dose of 34-68 mg of Zn++ was administered daily for over 2 weeks. The degree of tinnitus was expressed on a numeric scale from 0 to 10 before and after treatment. Blood zinc levels were significantly elevated (p < 0.05) after treatment. We found a significant decrease (p < 0.01) in the numeric scale. These findings suggest that zinc is useful in at least some patients suffering from tinnitus. It is possible to classify patients with tinnitus by measuring serum zinc level and this leads to improvement of the overall treatment effect.
Adolescent↗
Improved range of flexion after total knee arthroplasty. The total condylar knee versus the KU knee.
One objective of the modification of the total condylar knee is to increase the range of flexion without compromising the durability of the prosthesis. The KU knee prosthesis was designed to improve postoperative range of motion. This prosthesis has a unique ball-and-socket joint in the center of the posterior portion of the femorotibial articulation. A retrospective comparative study was undertaken to determine whether the KU knee prosthesis had achieved its design objectives. The study was based on the clinical observation of two populations: one (the TC group: 31 joints) with total condylar prostheses and the other (the KU group; 31 joints) with KU knee prostheses. At two years postoperatively, the mean postoperative range of flexion was 94 degrees (range: 60 degrees to 120 degrees) in the TC group and 120 degrees (range: 95 degrees to 150 degrees) in the KU group. The mean postoperative range of flexion was 24 degrees better in the KU group than in the TC group (p < 0.01). The mean functional score was 76 points (range: 61 to 86) in the TC group and 81 points (range: 56 to 92) in the KU group. There were no statistically significant difference in pain, walking ability, deformity, extension lag, and activities of daily living (ADL) score between the two groups. However, a statistically significant difference was detected in the range of motion (ROM) score (p < 0.01). No major complications occurred in either of the two groups. Although the follow-up period was not long enough, the KU knee was thought to be a promising modification of the total condylar knee prosthesis.
Activities of Daily Living↗
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↗
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↗
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↗
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↗
[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↗
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↗
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↗
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↗
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↗
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↗
[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↗
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↗