Search PubMed⌕ Search

Biomedical subjects

M Ando

Publications and source records attributed to M Ando.

At least 307 records · Page 17Linked to original sources

Suppression of male-specific cytochrome P450 isoforms by bisphenol A in rat liver.

We examined the effect of bisphenol A (BPA) on microsomal cytochrome P450 (P450) enzymes in rats. Rats were treated intraperitoneally with BPA daily for 4 days, at doses of 10, 20, and 40 mg/kg. Among the P450-dependent monooxygenase activities, testosterone 2alpha-hydroxylase (T2AH) and testosterone 6beta-hydroxylase (T6BH) activities, which are associated with CYP2C11 and CYP3A2 respectively, were remarkably decreased by 40 mg/kg BPA. The levels of the control activities were 13 and 50%, respectively. Furthermore, immunoblotting showed that BPA (20 or 40 mg/kg) significantly reduced CYP2C 11/6 and CYP3A2/1 protein levels in rat liver microsomes. In addition, estradiol 2-hydroxylase (ED2H) and benzphetamine N-demethylase (BZND) activities were significantly decreased by BPA at 20 and 40 mg/kg (by 19-73%). The Km values for T2AH and T6BH in 20 and 40 mg/kg BPA-treated rats were significantly high compared with that in control rats. The Vmax for T2AH was dose-dependently decreased by BPA treatment, whereas that of T6BH was only decreased by BPA at 40 mg/kg. On the other hand, lauric acid omega-hydroxylase (LAOH) activity was significantly increased by BPA at 20 and 40 mg/kg (1.5- and 1.7-fold, respectively). Immunoblot analysis showed that 20 and 40 mg/kg BPA induced CYP4A1/2 protein expression. However, the activities 7-ethoxyresorufin O-deethylase (EROD), 7-methoxyresorufin O-demethylase (MROD), 7-ethoxycoumarin O-deethylase (ECOD), 7-benzyloxyresorufin O-debenzylase (BROD), aminopyrine N-demethylase (APND), chlorzoxazone 6-hydroxylase (CZ6H), erythromycin N-demethylase (EMND), and testosterone 7alpha-hydroxylase (T7AH) were not affected by BPA at any dose. These results suggest that BPA affects male-specific P450 isoforms in rat liver, and that these changes closely relate to the toxicity of BPA.

Animals↗

Relationship between the development of hepato-renal toxicity and cadmium accumulation in rats given minimum to large amounts of cadmium chloride in the long-term: preliminary study.

We wished to clarify the relationship between the sensitivity to induce hepato-renal toxicity and the level of cadmium (Cd) in the organs of rats exposed to minimum to large amounts of cadmium chloride (CdCl2). For this purpose, groups of female Sprague-Dawley (SD) rats, each consisting of 24 animals, were fed diet containing CdCl2 at concentrations of 0, 8, 40, 200, and 600 ppm for 2, 4, and 8 months from 5 weeks of age. All surviving rats given 600 ppm Cd were killed at 4 months because of deterioration of their general condition. Animals of this group showed anemia and decreased hematopoiesis in the bone marrow, in addition to reduction of cancellous bone in their femurs. Hepatotoxicity was observed after 2 months in the groups treated with > or = 200 ppm. By 4 months, the rats in the 600 ppm group had developed periportal liver cell necrosis. Renal toxicity characterized by degeneration of proximal tubular epithelia was apparent in the groups treated with > or = 200 ppm from 2 months, becoming more prominent in the high-dose rats at 4 months. Hepatic accumulation of Cd increased linearly with the duration of treatment. In contrast, the concentration of Cd in the renal cortex of rats treated with 600 ppm reached a plateau level of approximately 250 microg/g within the first 2 months. The renal concentration of Cd in the 200 ppm group when renal toxic lesions were first detected at 2 months ranged from 104 to 244 microg/g. No renal lesions were observed in the 40 ppm group after 8 months, despite the presence of 91-183 microg/g of Cd in the kidneys. The results thus suggest that renal toxicity would not be induced by treatment with minimum amounts of CdCl2 for periods longer than 8 months, although accumulation of Cd might gradually progress. A further 2-year feeding study of CdCl2 and Cd-polluted rice is now in progress.

Animals↗

Evaluation of clinical indexes to predict fate of pelvic nerve dysfunction.

This study was designed to evaluate posterior urethral sensation and sacral reflex evoked by posterior urethral stimulation to predict fate of pelvic nerve dysfunction. Enrolled were 24 male patients sequentially receiving the following examinations 1-3 months (postoperative) and more then 6 months (follow-up) after surgery for rectal cancer: sensory thresholds of the penile skin (SS) and the posterior urethra (SU), sacral reflex evoked by penile stimulation (BCR) and posterior urethral stimulation (UUR), and urodynamic study. Controls included 25 patients with normal voiding function before pelvic surgery. SS, SU and latencies of BCR and UUR averaged 1.9+/-0.6 mA, 5.6+/-1.8 mA, 33.3+/-4.2 ms and 65.0+/-9.3 ms in controls, respectively, and unchanged postoperatively in 13 patients with normal voiding function. Of 11 patients with voiding dysfunction whose SS and latency of BCR remained unchanged, SU increased in 7, voiding function remained unrecovered in 6 patients during the follow-up period and recovered in the remaining 5. None of four patients with nonevocable UUR recovered voiding function. Thus, unchanged SU and disappearance of UUR were useful to predict recovery and nonrecovery of postoperative voiding dysfunction, respectively.

Adult↗

Complete dorsal dislocation of the metacarpophalangeal joint of the thumb.

In the pathology of simple complete dislocation involving the metacarpophalangeal joint of the thumb, whether or not the palmar plate is interposed within the joint is controversial. Nine cases of complete dorsal dislocation of the joint were reviewed, and cadaver dissection was performed to study the pathology of this injury. Eight of the nine patients were seen within 4 days of injury and treated successfully by closed manipulation. One patient treated 7 days after the injury required open reduction. We were able to reproduce the pathological anatomy of the dislocation, wedging of the palmar plate in the joint of the cadaver. In this cadaver and in all clinical cases, radiographs showed a complete dislocation with an increased distance between the palmar edge of the base of the proximal phalanx and the metacarpal head, indicating an interposition of the palmar plate. Our study suggests that in simple complete dislocations of this joint, the palmar plate is interposed between the displaced bones.

Adolescent↗

Molecular and clinical study of 183 patients with conotruncal anomaly face syndrome.

To investigate molecular and clinical aspects of conotruncal anomaly face (CAF), we studied the correlation between deletion size and phenotype and the mode of inheritance in 183 conotruncal anomaly face syndrome (CAFS) patients. Hemizygosity for a region of 22ql1.2 was found in 180 (98%) of the patients with CAFS by fluorescence in situ hybridization (FISH) using the N25(D22S75) DiGeorge critical region (DGCR) probe. No hemizygosity was found in three (2%) of the patients with CAFS by FISH using nine DiGeorge critical region probes and a SD1OP1 probe (DGA II locus). None of these three patients had mental retardation and just one had nasal intonation, which was observed in almost all of the 180 CAFS patients who carried deletions (mental retardation, 92%; nasal voice, 88%). Nineteen of 143 families (13%) had familial CAFS and 16 affected parents (84%) were mothers. Although only two of the affected parents had cardiovascular anomalies, the deletion size in the 16 affected parents and their affected family members, who were studied by FISH analysis, was the same. It indicates that extragenic factors may play a role in the genesis of phenotypic variability, especially in patients with cardiovascular anomalies. No familial cases were found among CAFS patients with absent thymus/DiGeorge anomaly (DGA). Also, in all 18 CAFS patients with completely absent thymus/DGA and all 6 CAFS patients with schizophrenia, it was revealed that the deletion was longer distally. A study of the origin of the deletion using microsatellite analyses in 48 de novo patients showed that in 65% of CAFS patients it was maternal, while in 64% of DGA patients it was paternal. The findings of this study indicated that CAF was almost always associated with the deletion of 22ql1.2. As well as the major features of the syndrome, other notable extracardiac anomalies were found to be susceptibility to infection, schizophrenia, atrophy or dysmorphism of the brain, thrombocytopenia, short stature, facial palsy, anal atresia, and mild limb abnormalities.

Adolescent↗

Dye-coupling of melanocytes with endothelial cells and pericytes in the cochlea of gerbils.

Intercellular connections via gap junctions in the stria vascularis, which constitutes the lateral wall of the cochlear duct, were investigated by the Lucifer yellow microinjection method with the aid of a confocal laser microscope. The dye injected into an intermediate cell (melanocyte) diffused into capillary endothelial cells and pericytes as well as other intermediate cells, basal cells, and fibrocytes in the spiral ligament; whereas the dye injected into a marginal cell (epithelial cell) was confined to the injected cell. The observation of dye-coupling between intermediate cells and endothelial cells and pericytes makes likely the possibility that these cells work together to play a role in the specific function of the stria vascularis (i.e., production of the positive endocochlear potential and the endolymph) and adds endothelial cells and pericytes to the current "two-cell model" of the stria vascularis.

Animals↗

Elephant trunk procedure for surgical treatment of aortic dissection.

BACKGROUND: In surgical intervention for aortic dissection, a highly radical operation can be performed by distal anastomosis with a true lumen resulting in thrombotic closure of the dissecting lumen. In this anastomosis, the elephant trunk procedure, in which a graft is inserted into the distal true lumen, prevents blood flow leakage into the dissecting lumen at the anastomosis site and also strengthens this area. METHODS: We performed this procedure in 15 patients (8 men and 7 women). Acute aortic dissection was observed in 9 patients and chronic dissection in 6. Stanford type A dissection was diagnosed in 10 patients and type B in 5. RESULTS: Graft replacement of the ascending aorta and total aortic arch was performed in 10 patients and descending aortic replacement in 5. A graft with a diameter of 16 to 24 mm was inserted into the true lumen of the descending aorta, and the false lumen was closed. Subsequently, distal anastomosis was performed on the true lumen. There were two hospital deaths. Postoperative digital subtraction angiography showed good results in living patients, and computed tomographic scanning showed thrombotic closure in the dissecting lumen of the descending aorta. CONCLUSIONS: The elephant trunk procedure is useful for closing the false lumen of the distal aorta.

Acute Disease↗

Operation for chronic pulmonary thromboembolism accompanied by thrombophilia in 8 patients.

BACKGROUND: Medical therapy for chronic pulmonary thromboembolism is limited, and surgical treatment has become more frequent recently. We have performed pulmonary thromboendarterectomy on 8 patients with chronic pulmonary thromboembolism accompanied by thrombophilia. METHODS: The patients were 6 men and 2 women aged 21 to 56 years (mean, 35 years). Five patients had antiphospholipid syndrome, 2 had protein C deficiency, and 1 had congenital antithrombin III deficiency. The preoperative condition was New York Heart Association functional class III in 5 and class IV in 3. Hypoxemia, marked pulmonary hypertension (mean pulmonary artery pressure, 47+/-6.7 mm Hg), and low cardiac output were observed in all patients. After a median sternotomy, deep hypothermia was induced using a cardiopulmonary bypass, and pulmonary thromboendarterectomy in the bilateral pulmonary arteries was performed under intermittent circulatory arrest. RESULTS: There were no operative deaths. Long-term respiratory management was needed postoperatively by 3 patients. In the remaining 5 patients, no reperfusion injury was observed. The arterial blood oxygen concentration improved, and the mean pulmonary pressure decreased to 16+/-5.5 mm Hg. The cardiac output also increased, and New York Heart Association functional class improved to I in 4 and II in 4 patients. CONCLUSION: Pulmonary thromboendarterectomy under deep hypothermic intermittent circulatory arrest was effective for chronic pulmonary thromboembolism accompanied by thrombophilia for which medical treatment is of limited value.

Adult↗

Mortality and cerebral outcome in patients who underwent aortic arch operations using deep hypothermic circulatory arrest with retrograde cerebral perfusion: no relation of early death, stroke, and delirium to the duration of circulatory arrest.

OBJECTIVE: Our goal was to investigate factors for mortality and cerebral outcome in patients with aneurysm of the aortic arch. METHODS: From 1993 to 1996, 148 patients with aortic arch aneurysm underwent operations involving deep hypothermic circulatory arrest with retrograde cerebral perfusion. Age was 63.9 +/- 11.6 years (mean +/- standard deviation) and 52 patients were older than 70 years. Twenty-eight had acute aortic dissection. Twelve had ruptured aneurysms. Fourteen had redo operations. Seventy had aortic dissection. The aneurysms were caused by atherosclerosis in 123 patients and by other causes in 25. Median sternotomy was used in 92 and left thoracotomy in 56. Twenty-eight patients underwent replacement of the ascending aorta to the proximal arch, 62 had total arch replacement, 38 had distal arch replacement, 12 had simultaneous replacement of the distal arch and the descending aorta or thoracoabdominal aorta, and 8 had patch repair. RESULTS: Fifteen (10.1%) early deaths occurred. New stroke occurred in six (4.0%) patients and transient delirium in 37 (25.0%). The duration of deep hypothermic circulatory arrest plus retrograde cerebral perfusion was 49 +/- 17 minutes, and it was more than 60 minutes in 36 patients. Patients awoke 7.5 +/- 8.2 hours after the operation. Logistic regression analysis demonstrated that risk factors for mortality were ruptured aneurysm, chronic obstructive pulmonary disease, arterial cannulation in the ascending aorta, and stroke. Risks for stroke were ruptured aneurysm and replacement of the distal arch. Risks for delirium were age older than 70 years and atherosclerotic aneurysm. Duration of circulatory arrest plus cerebral perfusion did not correlate with length of time before the patient regained consciousness. No difference was found in mortality, stroke, and delirium between patients with and those without more than 60 minutes of circulatory arrest and cerebral perfusion. CONCLUSION: Prolonged (> 60 minutes) deep hypothermic circulatory arrest with retrograde cerebral perfusion was not a risk factor for mortality and stroke in patients who underwent surgery for aneurysms of the aortic arch. However, the prevalence of transient delirium necessitates further investigations.

Aged↗

The CLIP-substituted invariant chain efficiently targets an antigenic peptide to HLA class II pathway in L cells.

The presentation of antigenic peptides by major histocompatibility complex (MHC) class II to CD4+ T cells is crucial to initiate immune responses. We developed a new system for delivery of an antigenic peptide to the MHC class II pathway, using the invariant chain (Ii). We designed a mutated human p33-form Ii, CLIP-substituted Ii, in which streptococcal M12p55-68 (RDLEQAYNELSGEA) was substituted for CLIP (class II associated invariant chain peptide). We examined the peptide presenting function of this construct, in comparison with the previously reported C-terminal fused Ii, in which a cathepsin cleavage site and M12p54-68 was ligated to the C-terminus of Ii. Mouse L cell transfectants expressing either of these two mutated Ii along with HLA-DR4 could process and present M12p55-68 to the peptide specific and DR4-restricted CD4+ T cell clone. CLIP-substituted Ii was much more efficient in antigen presentation than was the C-terminal fused Ii. Similar to the wild-type Ii, the CLIP-substituted Ii was associated intracellularly with DR4 molecules. These results indicate that the peptide substituted for CLIP of Ii p33 bound to the groove of DR molecules in the same manner as CLIP and it was preferentially presented to the CD4+ T cell clone in the absence of HLA-DM molecules. This system may prove useful for immunotherapy with DNA vaccines or for construction of an antigen presenting cell library with diverse peptides.

Amino Acid Sequence↗

Glucocorticoids suppress basal (but not interleukin-1-supported) ovarian phospholipase A2 activity: evidence for glucocorticoid receptor-mediated regulation.

Ovulation may constitute a cyclic, inflammatory-like process, wherein the increased expression of interleukin (IL)-1 and the biosynthesis of prostaglandins may be established corollaries. In this communication we hypothesize that glucocorticoids, potent anti-inflammatory principles, may exert an antiovulatory effect by interfering with ovarian IL-1-driven prostaglandin biosynthesis. To test this hypothesis, we examined the effect of treatment with dexamethasone on the activity of ovarian phospholipase A2 (PLA2), the event-limiting enzyme in prostaglandin biosynthesis, and on the gene expression pattern of secretory and cytosolic PLA2 (sPLA2 and cPLA2, respectively). Whole ovarian dispersates from immature rats were cultured under serum-free conditions for 48 h in the absence or presence of dexamethasone. At the conclusion of this culture period, PLA2 activity was determined in cell sonicates and conditioned media. Parallel probing for sPLA2 and cPLA2 transcripts was also undertaken using a solution hybridization/RNAse protection assay. Treatment of whole ovarian dispersates with dexamethasone produced a significant (P < 0.005) decrease in basal cellular and extracellular PLA2 activity to 27 and 40% of controls, respectively. A 5-fold decrease in the basal steady state levels of sPLA2 (but not cPLA2) transcripts was also noted. Co-treatment with dexamethasone produced complete inhibition of IL-1-stimulated cPLA2 transcripts but not of IL-1-supported cellular and extracellular PLA2 activity or sPLA2 transcripts. A glucocorticoid receptor antagonist (RU486), blocked the ability of dexamethasone to inhibit basal sPLA2 transcripts and extracellular PLA2 activity. The inhibitory effect of dexamethasone proved glucocorticoid-specific in that aldosterone and 17beta-estradiol were without effect. Taken together, these observations suggest that dexamethasone is capable of inhibiting basal (but not IL-1-supported) ovarian PLA2 activity, a glucocorticoid receptor-mediated effect due, in part, to a decrease in sPLA2 gene expression. Our findings further suggest that sPLA2 and cPLA2 are differentially regulated and that they may well differ in their relative contribution to ovarian prostaglandin biosynthesis in general and to PLA2 activity in particular. To the extent that IL-1 plays a central role in the ovulatory process, these findings argue against the view that the chronic anovulatory state induced by glucocorticoid excess is due, if only in part, to suppression of ovarian IL-1-dependent PLA2 activity.

Animals↗

Postnatal vascular development in the lateral wall of the cochlear duct of gerbils: quantitative analysis by electron microscopy and confocal laser microscopy.

The development of the capillary network in the stria vascularis and in the underlying spiral ligament of gerbils was systematically and quantitatively investigated by conventional electron microscopy and confocal laser microscopy in association with vascular labeling with fluorescent gelatin. The developmental changes of capillaries in the lateral wall were observed as the following series of events. (i) At 0 days after birth (DAB) capillaries already existed in the spiral ligament as a network. (ii) At 3-9 DAB the capillary network developed into two layers starting from the scala vestibuli side to the scala tympani side; one layer was located in the stria and the other in the spiral ligament. (iii) At 9 DAB capillaries in the stria became separated from the spiral ligament, and the capillary network consisting of a two-layered structure was complete. (iv) Total capillary length and capillary density in the lateral wall increased until 9 DAB and leveled off thereafter, but changes in the relative position of capillaries in the stria toward the luminal surface of marginal cells continued until 31 DAB. On the basis of the above observations, we propose two possible mechanisms underlying the vascular development in the lateral wall: (i) the formation of new vasculature (angiogenesis), and (ii) changes in the position of cellular components relative to capillaries in association with the differentiation and maturation of marginal cells and intermediate cells.

Animals↗

Multiple pseudoaneurysms of the aortic arch, right subclavian artery, and abdominal aorta in a patient with Behçet's disease.

A 38-year-old man presented with 2 months' history of a hoarseness and aphthous stomatitis. Image diagnosis showed that he had saccular-type aneurysms of the aortic arch, right subclavian artery, and infrarenal abdominal aorta. Simultaneous total arch replacement, including reconstruction of the right subclavian artery and replacement of the infrarenal abdominal aorta, was performed. Pathologic specimen of each aneurysmal wall revealed that intima and the majority of the medial layer were absent. Chronic inflammatory process was detected in the adventitia that was compatible with diagnosis of Behçet's disease.

Adult↗

Thoracic aortic aneurysm associated with congenital bicuspid aortic valve.

Congenital bicuspid aortic valve is a relatively rare malformation. It is reported that the presence of this anomaly predisposes the patient to development of true aortic aneurysms or dissecting aortic aneurysms. Between 1981 and August 1997, 25 patients with an aneurysm of the thoracic aorta associated with congenital bicuspid aortic valve underwent surgical treatment at the authors' institution. There were 20 males and five females. The age of the patients ranged from 27 to 74 years (mean 53 years). There were 18 patients with true ascending aortic aneurysms (of which 10 presented with annulo-aortic ectasia) and seven with dissecting aortic aneurysms (four with DeBakey type I dissection, two with type II and one with type IIIb). These 25 patients constituted 2.6% (25/973) of all cases of surgical operations for aneurysms in the thoracic aorta. Aortic valve dysfunction was noted in 20 patients. The authors performed a valved conduit operation in nine patients, aortic valve replacement and wrapping of the ascending aorta in six, graft replacement of the ascending aorta in five, graft replacement of the ascending aorta and aortic arch in four, and graft replacement of the descending aorta in one. No hospital deaths occurred in the authors' patients. Pathological examination of surgical specimens of the aortic wall showed cystic medial necrosis in 11 patients and mucoid degeneration in nine. In patients with congenital bicuspid aortic valve, attention should be paid to aneurysmal dilatation and aortic dissection as complications in addition to valve dysfunction.

Adult↗

Alteration of enzymatic activities implicating neuronal degeneration in the spinal cord of the motor neuron degeneration mouse during postnatal development.

Oxidative stress is suggested as a significant causative factor for pathogenesis of neuronal degeneration on spinal cord of human ALS. We measured some enzymic activities implicating neuronal degeneration process, such as cytochrome c oxidase (CO), superoxide dismutase (SOD), and transglutaminase (TG) in spinal cord of an animal model of ALS, motor neuron degeneration (Mnd) mouse, a mutant that exhibits progressive degeneration of lower spinal neurons during developmental growth, and compared them with age-matched control C57BL/6 mice. CO activity in Mnd spinal cord decreased during early postnatal period, while SOD activity reduced in later stage. In Mnd tissue, TG activity in lumbar cord was increasing during early stage, but tended to decline in later period gradually. These biochemical alterations became evident prior to the appearance of clinical motor dysfunction which were observed in later stages of development in Mnd spinal cord.

Aging↗

Increases in fragmented glial fibrillary acidic protein levels in the spinal cords of patients with amyotrophic lateral sclerosis.

Using one-dimensional polyacrylamide gel electrophoresis, we analyzed protein fractions extracted from the spinal cords of patients with amyotrophic lateral sclerosis (ALS). Several protein bands with molecular weights of 35-55 kDa were stained with Coomassie brilliant blue much more intensely in the ALS than in the non-ALS spinal cord. Glial fibrillary acidic protein (GFAP) immunoreactivity showed a significant decrease of 50 and 45 kDa band and increase in fragmented 36 and 37 kDa bands, which represented GFAP fragments devoid of 59 and 40 residues from the N-terminal, respectively, as determined by protein sequence analysis. Immunohistochemical examination of ALS spinal cord transections demonstrated increased GFAP-stained astrocytes in the shrunken ventral horn with massive degeneration of motoneurons. These results will provide new insight into the possible role of astrocytes in the pathophysiology and/or pathogenesis of ALS.

Amino Acid Sequence↗