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Biomedical subjects

A Takeuchi

Publications and source records attributed to A Takeuchi.

At least 109 records · Page 6Linked to original sources

Characterization of a new isoform of the NFAT (nuclear factor of activated T cells) gene family member NFATc.

The cyclosporin A (CsA)/FK506-sensitive nuclear factor of activated T cells (NFAT) plays a key role in the inducible expression of cytokine genes in T cells. Although NFAT has been recently shown to be inducible in several non-T immune cells, the NFAT gene family members characterized to date have been isolated only from T cells. To further characterize NFAT function in human B cells and to demonstrate cytokine gene specificity of NFAT proteins, we report here the isolation and characterization of a cDNA clone from the Raji B cell line. The cDNA clone encodes a new isoform, NFATc.beta, of the NFAT gene family member NFATc (designated here NFATc.alpha). The amino acid sequence of NFATc.beta differs from that of NFATc. alpha in the first NH2-terminal 29 residues and contains an additional region of 142 residues at the COOH terminus. Northern analysis using a probe encompassing a common region of both isoforms showed two mRNA species of 2.7 and 4.5 kilobase pairs, while an NFATc.beta-specific probe detected only the 4.5-kilobase pair mRNA which was preferentially expressed in the spleen. Transient expression of NFATc.beta was capable of activating an interleukin-2 NFAT-driven reporter gene in stimulated Jurkat cells in a CsA-sensitive manner. However, NFATc.beta neither bound to the kappa3 element (an NFAT-binding site) in the tumor necrosis factor-alpha promoter nor activated the tumor necrosis factor-alpha promoter in cotransfection assays. These data suggest that different members or isoforms of NFAT gene family may regulate inducible expression of different cytokine genes.

Amino Acid Sequence↗

Identification of a novel growth-promoting factor with a wide target cell spectrum from various tumor cells as catalase.

We have previously reported the purification from human erythrocyte extracts of a novel growth-promoting factor with a wide target cell spectrum. The factor has been identified as catalase. As cell extracts from a variety of tumor cell types exhibited both growth-promoting and catalase activities, the relationship between the two activities was examined using cell extracts from three different cell types, human myeloid cells (U937), human melanoma cells (A375-C6), and human B cells (Daudi). The growth-promoting and catalase activities were well correlated in these cell extracts. The antibody against human catalase absorbed not only catalase activity, but also the growth-promoting activity of extracts from these cell types. Treatment of the cell extracts from these cells with an irreversible catalase inhibitor, aminotriazole, abolished both the catalase and growth-promoting activities. In contrast, glutathione peroxidase (GSH-Px) activity was neither absorbed with the anti-catalase antibody, nor inhibited by aminotriazole. In addition, GSH-Px exhibited growth-promoting activity only in the presence of glutathione (GSH). These results, in conjunction with the effect of aminotriazole on the growth-promoting activity of catalase, suggest that catalase is the major growth-promoting molecule in the cell extracts, and H2O2-decomposing activity is important. Northern blot analysis revealed that these cells contained authentic catalase mRNA, and the mRNA level was compatible with the catalase and growth-promoting activities in the cell extracts. These results suggest that the growth-promoting activity in the tumor cell extracts is due to catalase.

Amitrole↗

An experimental model of retinal pigment epithelial and neurosensory serous detachment.

PURPOSE: The authors document an animal model of retinal pigment epithelial (RPE) detachments. METHODS: N-ethylmaleimide (NEM) and sodium iodate (sulfhydryl-alkylating agents) were injected into the vitreous of Dutch pigmented rabbits. Subretinal fluid samples were withdrawn 0.5 and 3 hours after NEM injections and analyzed for albumin content by gel electrophoresis. Selected eyes were examined histologically. RESULTS: Injections of 9.2 micrograms NEM caused wrinkling of the retina within 15 minutes, at which time fluorescein angiography revealed multifocal RPE detachments. At this stage, histologic sections showed moderate choroidal edema and RPE detachment. Elevated retinal detachments developed over the next 15 to 25 minutes. Histologic sections showed massive choroidal edema and RPE fragmentation. The albumin concentration of subretinal fluid rose from 60% of serum level at 30 minutes after NEM to 80% after 3 hours. Sodium iodate did not cause choroidal edema or RPE detachment. CONCLUSION: In rabbits, intravitreal NEM causes the rapid appearance of choroidal edema and RPE detachment, followed by serous retinal detachment. The initial effect probably is caused by an alteration of choroidal vascular permeability. The relationship of these effects to sulfhydryl alkylation is unclear because sodium iodate failed to produce RPE detachments. N-ethylmaleimide effects may model aspects of clinical RPE and serous retinal detachments.

Animals↗

When vitreous enters the subretinal space. Implications for subretinal fluid protein.

PURPOSE: Vitreous enters the subretinal space in rhegmatogenous detachments, but the protein concentration in subretinal fluid from clinical detachments is much higher than in vitreous. These experiments were designed to study short-term changes in subretinal albumin concentration after vitreous enters the subretinal space. METHODS: Retinal detachments were made in Dutch rabbits by injecting autologous liquefied vitreous (albumin concentration 244.11 micrograms/ml) into the subretinal space through a micropipette. Subretinal and vitreous fluid samples were withdrawn 0 to 4 hours later and analyzed for albumin concentration (by gel electrophoresis) and osmolality. The authors also made detachments with Hanks' balanced salt solution containing an approximate vitreal level (294.8 micrograms/ml) of fluorescein isothiocyanate albumin. RESULTS: When the authors made detachments using autologous liquefied vitreous, the subretinal albumin concentration increased to 333.3 micrograms/ml 4 hours after detachment, by which time the detachment volume had fallen to 65% of its initial level. The total amount of albumin in the subretinal space did not change significantly. Subretinal fluid osmolality remained within the range of 292 to 294 mOsm/kg despite the steady absorption of fluid from the detachment. The results were essentially the same when detachments were made with saline and fluorescein isothiocyanate albumin rather than vitreous itself. CONCLUSIONS: The subretinal concentration of albumin increases as water in subretinal fluid is absorbed across the retinal pigment epithelium. If liquefied vitreous continues to enter the subretinal space, as occurs in clinical cases of rhegmatogenous retinal detachment, this mechanism may cause albumin to accumulate.

Absorption↗

Histopathological changes in digits of dairy cows affected with sole ulcers.

Forty-eight digits of 8 dairy cows, which had been diagnosed as sole ulcers in one or two hooves, were examined histopathologically and classified into 5 grades on the basis of the severity of the circulatory disturbances and of keratogenesis. All the cows had significantly higher grades than normal cows. Although hind lateral digits were most severely damaged, there were no significant differences in the grades among claw positions except hind lateral digits. From these results, it is suggested that the cows affected with sole ulcers had some systemic factors predisposing all the digits to digital disorders.

Animals↗

Histopathological findings on ulcerative lesions of carpal and tarsal joints in Japanese black cattle.

In order to determine the pathogenesis of ulcerative lesions of the articular cartilages in Japanese Black cattle, tissue samples of the ulcerative lesion, marginal portion of the ulcer, macroscopically normal portions and synovial membranes were histopathologically examined by light microscopy, scanning electron microscopy and contact microradiography. The results are summarized as follows: (1) In the ulcerative lesions, degeneration and complete destruction of articular cartilage and its replacement with a proliferation of myelogenic connective tissue were observed. (2) In macroscopically normal portions, fissures of the articular surface and changes of the trabecular pattern in subchondral bone were present. (3) In the marginal portions of the ulcerative lesions, evidences of the repair process such as connective tissue growth from subchondral bones and articular cartilages were seen. (4) In synovial membranes, no pathological findings were observed. And (5) among the above mentioned changes, no inflammatory findings were seen. In conclusion, the ulcerative lesions of bovine articular cartilage may be regarded as the early stage of osteochondrosis to osteoarthrosis since the findings such as noninflammatory destruction or degeneration and remodeling of the joints are characteristics of the latter.

Animals↗

Postparturient change in endotoxin levels of ruminal fluid and serum in dairy cows.

The changes in the endotoxin levels of ruminal fluid and serum in postparturient cows were evaluated. Five cows were fed hay and concentrates on an individual basis (farm A) and the other 5 cows were given complete feed ad libitum (farm B) after parturition. Ruminal pH levels decreased in both groups after parturition. Subsequently, the ruminal endotoxin levels increased with the declining pH on both of the farms. The ruminal endotoxin levels were slightly higher in cows of farm B than those of farm A. Serum endotoxin levels also showed episodic fluctuations, however, there were no parallel changes between the endotoxin levels of the ruminal fluid and sera.

Animals↗

Primary brain tumors in two dogs treated by surgical resection in combination with postoperative radiation therapy.

Primary brain tumors in two dogs were surgically removed followed by postoperative radiation therapy. The two tumors were confirmed histologically to be astrocytoma and meningioma, respectively. After the surgery, the neurological status of each dog improved dramatically and a total dose of 40 Gy was delivered to the surgical site to treat residual tumor tissue. Although the dog with astrocytoma died 6 months after surgery due to unknown causes, the dog with meningioma has lived for over 24 months with a degree of neurological disorder less severe than that before treatment. These results suggested the effectiveness of this type of therapy on brain tumor in dogs and therapeutic modality should be positively planned to treat canine brain tumors.

Animals↗

Antitumor activity of natural-type human tumor necrosis factor on experimental brain tumors in rats.

The effects of intralesional injection of newly synthesized natural-type human tumor necrosis factor (nh-TNF) on experimental brain tumors in rats were investigated. The repeated injection of 5,000 U of nh-TNF into the tumor resulted in the prolongation of the survival time of the rats. More than half of the nh-TNF treated tumors were red, and were characterized by histopathological features of marked congestion of tumor vessels. Fibrin formations were also found in the tumor vessels. These histological findings were not observed in the control tumors. Furthermore, coagulative necrosis was observed in the center of some reddish tumors. Leukocytes adhering to vascular endothelium and infiltration of the leukocytes were also observed in the tumors of nh-TNF treated rats. In the immunohistochemical examination, these infiltrated cells were primarily polymorphonuclear leukocytes and macrophages. Expression of intercellular adhesion molecule-1 (ICAM-1) increased on the tumor endothelial cells after the administration of nh-TNF. These results suggest that repeated injection of nh-TNF has a therapeutic effect on brain tumors through its extensive influences on tumor vasculature.

Animals↗

The source of fluid and protein in serous retinal detachments.

PURPOSE: To investigate the source and protein content of sub-retinal fluid in self-forming experimental serous retinal detachments. METHODS: Detachments were induced in Dutch rabbit eyes using rose bengal photosensitization to cause choriocapillaris injury and thrombosis. Serous detachments formed spontaneously within the next 24 h. Subretinal fluid was withdrawn 2, 8 and 24 hrs after photosensitization, and was analyzed for osmolality and albumin content by gel electrophoresis. RESULTS: The albumin concentration in the subretinal fluid of light-induced detachments was 68% of serum level at 3 h after light damage, and rose close to serum level by 24 h. The osmolality of subretinal fluid 24 h after light damage was essentially the same as serum and vitreous fluid. CONCLUSIONS: The subretinal protein and fluid in light-induced detachments in the central retina of the rabbit must come from the choroid, since there are no intrinsic retinal blood vessels in that region of the fundus. These data demonstrate that serous retinal detachments can form from choroidal fluid.

Albumins↗

[Evaluation of the clinical usefulness of super dynamic 99mTc-HM-PAO SPECT in ischemic cerebrovascular disease--detection of hypo- and hyperperfusion area].

The purpose of this study is to assess the clinical usefulness of super dynamic SPECT of 99mTc-HM-PAO. Six patients with unilateral occlusion of middle cerebral artery (MCA) or internal carotid artery (ICA) in the chronic phase, and 5 patients with subacute cerebral infarction were studied. We used a ring-type SPECT "HEADTOME." Two types of collimator were used: a high sensitivity (HS) collimator for super dynamic scan and a high resolution (HR) collimator for static scan. First, the intravenous constant infusion of 99mTc-HM-PAO (925-1480 MBq) for 1 minute was started. After 30 seconds from the beginning of the injection, we performed the 12 seconds/frame super dynamic SPECT for 2 minutes. Then, the static SPECT for 10 minutes was done. For semiquantitative analyses, differential percentage of regional activity between affected and non-affected hemispheres was calculated in the 6th frame image of super dynamic SPECT and static SPECT image. In all 6 patients with unilateral occlusion of MCA and ICA, super dynamic SPECT images showed the better contrast of low perfusion areas in comparison with the static SPECT images. In 5 patients with subacute cerebral infarction who showed focal hyperactivities on static SPECT, focal hyperactivities (hyperperfusion or hyperemia) were displayed in 3 cases, whereas, focal hypo- or isoactivities (hypo- or isoperfusion) were shown in 2 cases on super dynamic SPECT. However, all patients with subacute cerebral infarction showed hyperfixation on static SPECT as compared with super dynamic SPECT. Although the image quality on super dynamic SPECT is not as high as that on static SPECT, cerebral hemodynamics would be detected with less backdiffusion of 99mTc-HM-PAO from the brain to blood, and with less accumulation of hydrophilic components in subacute infarct region. In conclusion, super dynamic SPECT in early distribution of 99mTc-HM-PAO using dedicated SPECT device might be helpful to detect cerebral perfusion close to true cerebral blood flow distribution.

Aged↗

Anesthesia induced in pigs by use of a combination of medetomidine, butorphanol, and ketamine and its reversal by administration of atipamezole.

OBJECTIVE: To develop an IM administrable anesthetic combination for pigs. DESIGN: Use of a combination of atropine, medetomidine, butorphanol, and ketamine (MB-K) was evaluated as an anesthetic regimen and compared with that of a combination of atropine, xylazine, butorphanol, and ketamine (XB-K). Cardiorespiratory effects of MB-K combination and use of atipamezole as a means of reversing anesthesia induced by MB-K were examined. ANIMALS: 18 castrated, mixed-breed, specific-pathogenfree pigs, aged 8 to 15 (mean, 12.1) weeks and weighing 14.5 to 26.0 (mean, 19.6) kg. were studied. PROCEDURE: Dosages of drugs used in this study were atropine, 25 micrograms/kg of body weight; medetomidine, 80 micrograms/kg; xylazine, 2 mg/kg; butorphanol, 200 micrograms/kg; ketamine, 10 mg/kg; and atipamezole, 240 micrograms/kg. RESULTS: MB-K combination proved to be more effective than XB-K combination as an anesthetic combination. After quick and smooth induction by IM administration, MB-K-induced anesthesia was sustained for 98.8 +/- 22.5 minutes (mean +/- SD, 47.4 +/- 16.5 minutes by XB-K) with accompanying muscular relaxation (91 +/- 18 minutes) and loss of pedal (82 +/- 24 minutes) and laryngeal (75 +/- 19 minutes) reflexes. Loss of these reflexes was of significantly longer duration than the loss induced by XB-K, enabled tracheal intubation, and, thus, supported major surgery for at least 30 minutes after induction. Recovery from MB-K-induced anesthesia was smooth. MB-K combination had a slight stimulative effect on cardiovascular status, and a significant depressant effect on blood gas and acid-base status, but these effects were within biologically acceptable limits. Oxygen consumption of pigs under MB-K-induced anesthesia decreased significantly. MB-K-induced anesthesia could be effectively and quickly reversed by IM or IV administration of atipamezole. CONCLUSIONS: The combination of medetomidine, butorphanol, and ketamine induces excellent surgical anesthesia in pigs, and results in moderate cardiorespiratory effects. A great advantage of the anesthetic regimen is that it can be effectively and quickly reversed by atipamezole. CLINICAL RELEVANCE: Medetomidine, butorphanol, and ketamine-induced anesthesia is available for short-term major surgery in pigs.

Adrenergic alpha-Antagonists↗

[Retroperitoneal ganglioneuroma: a case report].

We experienced a case of ganglioneuroma. A 37-year-old man was admitted to our hospital for right flank pain. Computed tomography (CT) showed a low density mass near the upper pole of the right kidney. Selective renal arteriography did not demonstrate any tumor vessels in the right kidney. An endocrinological study revealed high values of noradrenaline and dopamine in urine. Under the preoperative diagnosis of a retroperitoneal tumor or right adrenal tumor, tumor resection was performed. The tumor was found in the retroperitoneal space on surgical exploration. The histopathological diagnosis was ganglioneuroma.

Biomarkers, Tumor↗

Asymptomatic acute poststreptococcal glomerulonephritis following upper respiratory tract infections caused by Group A streptococci.

During an observation period of 1-2 years in 2 different districts in Japan, 104 patients were found to have upper respiratory infections caused by group A streptococci. Fourty-nine of these patients were followed prospectively to determine if renal involvement would occur. Twelve patients developed transient serum complement (CH50) depression and urinary abnormality, and 2 of these developed mild hypertension. The latent period was from 1-8 weeks after the streptococcal infection. Renal biopsies of the 12 patients with "asymptomatic" of "subclinical" acute poststreptococcal glomerulonephritis (APSGN) were examined by light, immunofluorescent and electron microscopy. Glomerular lesions ranged from mild proliferative changes to the classical pathology seen in APSGN. The 12 patients were followed for 10 years. Two of them developed persistent or intermittent hematuria, and renal biopsies obtained 4 years after the initial infection revealed mesangial proliferative glomerulonephritis without IgA deposits. The remaining patients showed no abnormal findings after the acute episode. These findings suggested that glomerular involvement after group A streptococcal infection is frequent and mesangial proliferative glomerulonephritis, which was found to develop in some, may rank with IgA nephropathy as a major cause of unexplained microscopic hematuria.

Acute Disease↗

The distribution of TM-316-associated surface antigen on polymorphonuclear leucocytes: an immunoelectron microscopic study.

It has been established that MoAb TM-316 recognizes an epitope on leucocytes and specifically inhibits the chemotactic behavior of leucocytes. In the present paper, the distribution of this epitope on the cell surface and in intracellular organelles was studied by immunoelectron microscopy. Leucocytes separated from the blood of healthy men and from synovial fluid from patients suffering from rheumatoid arthritis were used. They were fixed with a mixture containing paraformaldehyde, glutaraldehyde and picric acid. As the second antibody, goat anti-mouse IgM conjugated to 10 nm gold colloids was employed. In normal specimens, the epitope was found to some extent on the cytoplasmic membrane of neutrophilic leucocytes, but it was only sparsely distributed on eosinophilic and basophilic leucocytes. On activated neutrophilic leucocytes, obtained from the synovial fluid of rheumatoid arthritis patients, the immunolabeling was markedly increased. The number of sites where the epitope occurs on the surface of leucocytes is thus associated with the cell type, and also with the level of activation of the leucocytes. In order to investigate the processing of the antigen, the intracellular localization of the epitope in the neutrophilic leucocytes was also studied. The epitope recognized by TM-316 was also detected in/on the characteristic granules and Golgi stacks.

Antigens↗

A human erythrocyte-derived growth-promoting factor with a wide target cell spectrum: identification as catalase.

We have reported previously that a factor with a molecular weight of 53,000 under SDS-polyacrylamide gel electrophoresis purified from human erythrocyte extracts promoted the growth of a wide variety of cell types from different species, including T cells, B cells, myeloid leukemia cells, melanoma cells, and mastocytoma cells, as well as normal and transformed fibroblast cells. In the present study, amino acid sequence analysis revealed that this factor has homology with human catalase. The purified factor exhibited catalase activity. Catalases derived from human erythrocytes, bovine liver, Aspergillus niger, and recombinant rat liver catalase are all able to promote the growth of cells. Antibody against human catalase absorbed both the growth-promoting activity and the enzyme activity of the purified factor. In addition, treatment of the factor with an irreversible enzyme inhibitor, aminotriazole, resulted in abrogation of both the growth-promoting activity and enzyme activity. These results indicate that the growth-promoting factor is catalase, and its activity is associated with the decomposition of hydrogen peroxide.

Amino Acid Sequence↗

Chemical restraint by medetomidine-ketamine and its cardiopulmonary effects in pigs.

Chemical restraint induced by medetomidine-ketamine (M-K) combination was evaluated compared with that by xylazine-ketamine (X-K) in pigs. The duration of restraint by M-K was 49.4 +/- 13.5 min (mean +/- SD) and longer than that by X-K (34.6 +/- 17.2 min), but the difference was not significant. The effect of X-K was not stable, since one of five pigs was restrained only for 6 min. Both combinations produced muscle relaxation. The duration of muscle relaxation in M-K was 43.6 +/- 12.7 min and was significantly longer than that in X-K (21.0 +/- 14.0 min). M-K combination had a slightly stimulative effect on the cardiovascular system, but scarcely changed the respiratory parameters. This limited effect on cardiopulmonary system was an advantage of M-K combination for chemical restraint in pigs. These results indicated that M-K combination is suitable for chemical restraint with prolonged muscle relaxation and has limited cardiopulmonary effects in pigs.

Anesthetics↗