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Biomedical subjects

T Yajima

Publications and source records attributed to T Yajima.

At least 91 records · Page 5Linked to original sources

Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa.

We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we report that transgenic mice expressing murine IL-7 cDNA driver by the SRalpha promoter developed chronic colitis in concert with the expression of SRalpha/IL-7 transgene in the colonic mucosa. IL-7 transgenic but not littermate mice developed chronic colitis at 4-12 wk of age, with histopathological similarity to ulcerative colitis in humans. Southern blot hybridization and competitive PCR demonstrated that the expression of IL-7 messenger RNA was increased in the colonic mucosal lymphocytes but not in the colonic epithelial cells. IL-7 protein accumulation was decreased in the goblet cell-depleted colonic epithelium in the transgenic mice. Immunohistochemical and cytokine production analysis showed that lymphoid infiltrates in the lamina propria were dominated by T helper cell type 1 CD4+ T cells. Flow cytometric analysis demonstrated that CD4+ intraepithelial T cells were increased, but T cell receptor gamma/delta T cells and CD8alpha/alpha cells were not increased in the area of chronic inflammation. Increased IL-7 receptor expression in mucosal lymphocytes was demonstrated in the transgenic mice. These findings suggest that chronic inflammation in the colonic mucosa may be mediated by dysregulation of colonic epithelial cell-derived IL-7, and this murine model of chronic colitis may contribute to the understanding of the pathogenesis of human inflammatory bowel disease.

Animals↗

Prevention of small intestinal ischemia-reperfusion injury in rat by anti-cytokine-induced neutrophil chemoattractant monoclonal antibody.

The function of cytokine-induced neutrophil chemoattractant (CINC), which is the rat counterpart to human growth-related gene product belonging to the CXC chemokine subgroup, is based principally on neutrophil-specific chemotactic activity. In addition, we previously reported that plasma CINC was elevated during the period of small intestinal ischemia-reperfusion injury, and that there was a correlation between the degree of mucosal damage and the peak level of CINC after reperfusion, suggesting that CINC may play a major role in neutrophil infiltration into the rat small intestinal ischemia-reperfusion injury site. Thus, we investigated whether administration of anti-CINC monoclonal antibodies (mAbs) reduces small intestinal ischemia-reperfusion injury. Small intestine was subjected to ischemia for 3 h by occlusion of the anterior mesenteric artery with an atraumatic vascular clump. After infusion of anti-CINC mAbs or isotype-matched mAbs, the intestine was subjected to reperfusion. The pretreatment with anti-CINC mAbs attenuated ischemia-reperfusion injury in the small intestine, in association with the reduction of tumor necrosis factor-alpha and myeloperoxidase production, and resulted in the prolongation of survival. It is concluded that CINC plays an important role in the onset of rat small intestinal ischemia-reperfusion injury. In addition, blocking the action of CINC, namely, the neutrophil chemotactic activity, may be useful in preventing ischemia-reperfusion injury in the small intestine.

Animals↗

Asymmetric imine-ene reactions: diastereofacial selective reactions with chiral glyoxylate-derived alpha-imino esters and asymmetric catalysis of enantiofacial selective reactions with prochiral alpha-imino esters.

The diastereofacial selective "imine-ene" reactions with alpha-imino esters, prepared from (-)-8-phenylmenthyl glyoxylate, are shown to provide an efficient entry to the asymmetric synthesis of alpha-amino acids. The feasibility study of the asymmetric catalysis is also reported on the enantiofacial selective ene reactions with prochiral alpha-imino esters.

Amino Acids↗

"Hexatuple" coronary bypass with in situ arterial grafts.

A fifty-seven year old male patient with severe three-vessel coronary artery disease underwent successful coronary bypass surgery in six vessels utilizing the in situ left internal thoracic and right gastroepiploic arteries. Each arterial conduit was anastomosed sequentially to as many as three coronary vessels respectively. Surgical results were excellent and the patient continues to do very well. A postoperative angiogram showed well-working arterial conduits without any anastomotic problems. Multiple sequential anastomoses of the in situ arterial conduits, although rather technically demanding, can provide better long-term results in patients requiring multiple coronary revascularization. When sequential anastomoses of the right gastroepiploic artery are being considered, the length and caliber of the artery should be evaluated by an angiogram since it varies in size compared to the internal thoracic artery.

Anastomosis, Surgical↗

The clinical significance of performing preoperative angiography of the internal thoracic artery in coronary artery bypass surgery.

This study was designed to clarify the clinical significance of and indications for performing preoperative internal thoracic artery (ITA) angiography in patients undergoing coronary artery bypass surgery. A total of 300 possible candidates for coronary artery bypass grafting (CABG) underwent ITA angiography during diagnostic catheterization. Semi-selective angiography of bilateral ITAs were performed by injecting contrast medium manually with a 5-F right Judkins coronary catheter. The posteroanterior view of the arteriograms was recorded on a 35-mm cine film or a cut-film. Unusual angiographic findings of the ITAs were observed in nine patients (3%). These findings included: an atrophic ITA in three patients with ipsilateral subclavian artery occlusions; enlarged ITAs giving collaterals to the lower extremities in one patient with extensive aortoiliac occlusive disease; occluded ITAs in one patient with Takayasu's arteritis and two patients with a history of CABG; and a small but nonsclerotic ITA in one patient. Atherosclerotic occlusive ITAs were found in only one patient. Thus, we concluded that routine preoperative angiography of the ITA is not necessary because it is rarely affected by atherosclerosis. However, it should be performed for any of the following reasons: a cervical or supraclavicular bruit; an upper extremity blood pressure difference of greater than 20 mmHg; an extensive aortoiliac occlusion; and certain disorders such as Takayasu's arteritis or Kawasaki disease, or a history of open heart surgery.

Adult↗

Confocal laser scanning microscopic study [corrected] of tartrate-resistant acid phosphatase-positive cells in the dental follicle during early morphogenesis of mouse embryonic molar teeth.

Tartrate-resistant acid phosphatase (TRAPase)-positive cells were examined during the early morphogenesis of mouse mandibular first molar teeth, using a simultaneous azo dye-coupling technique and confocal laser scanning microscopy (CLSM). CLSM of paraffin-embedded sections revealed that cells exhibiting TRAPase fluorescence appeared along the marginal region of the condensed dental mesenchyme, not yet the dental follicle, at embryonic day 12 (E12). The follicle was recognized histologically as a population of fibroblastic cells in tooth organs at E14, and TRAPase-positive cells were localized among the follicular cells. Light-microscopic observations of microsliced thick sections showed the overall morphology of the TRAPase-positive cells. A few positive cells of E13 tooth organs were oval, and the intense reaction products of TRAPase revealed complex processes on positive cells in E14 tooth organs. Three-dimensional fluorescent images of TRAPase-positive cells using microsliced sections and CLSM showed their unique morphology of long processes with small spine-like projections at E14. Thus, TRAPase-positive cells appeared in the region of the prospective follicle at the bud stage (E12 and 13) before the formation of the follicle proper. In addition, the formation of the follicle and the appearance of TRAPase-positive cells with unique morphology were correlated in their developmental stage (E14). The findings suggest that the TRAPase-positive cells may be involved in the formation of the dental follicle in early tooth morphogenesis.

Acid Phosphatase↗

Development and histologic characteristics of synovitis induced by trauma in the rat temporomandibular joint.

Histopathological changes caused by trauma to the rat temporomandibular joint synovium were examined by light microscopy. The trauma was induced by forced hypermobility of the condyle. Pathological changes of the synovium were found primarily in the anterior pouch of the upper joint compartment. The main findings included surface cell proliferation, increased capillary hyperemia, fibrin deposits on the surfaces of inflamed synovial membranes, and fibrinous adhesion between closely opposed synovial membranes. A gradual change from fibrinous adhesion to fibrous adhesion was also seen.

Animals↗

Histologic study of synovitis induced by trauma to the rat temporomandibular joint.

OBJECTIVE: The purpose of this study was to establish and histologically examine the time course of synovitis induced by trauma to the rat temporomandibular joint. STUDY DESIGN: Synovitis of the temporomandibular joints of 8-week-old male Wister rats was induced by forced condylar hypermobility, which was administered 10 times successively once a day for 10 days. Pathologic changes were observed microscopically at 2 and 5 days and 2, 4, 6, 8, 10, and 20 weeks after treatment. RESULTS: Histologic findings from the 5th day to the 6th week after treatment were characterized by multiple layers of synovial cells, an increase of dilated vasculature, fibrin deposits, and synovial adhesion. These findings were in good agreement with those reported for the human temporomandibular joint. The pathologic changes decreased with advancing time, and synovitis was not observed at 20 weeks after treatment. CONCLUSION: The present procedure for inducing synovitis of the temporomandibular joint in rats will be useful in understanding the pathogenesis of synovitis in human temporomandibular joints.

Animals↗

Effect of intermittent feeding on the development of disaccharidase activities in artificially reared rat pups.

We investigated the effect of an intermittent feeding schedule on the development of disaccharidase activities in the small intestine of artificially reared (AR) rat pups. Rat pups were fitted with an intragastric cannula at 5 days of age. A milk formula similar to the composition of rat milk was supplied by intermittent gastric infusion over the following 15-19 days. The body weight gain and plasma corticosterone levels of the AR pups matched those of pups reared naturally by dams (MR pups). At 10, 15 and 19 days of age, the small intestine from the ligament to Treitz to the ileocecal junction was divided into three segments of equal length and enzyme activities were measured in each. At the age of 10 and 15 days, sucrase and isomaltase activities were undetectable in AR pups fed according to a controlled schedule from the early postnatal period. These activities were first detected in the middle segment of the small intestine at 9 days of age in both AR and MR pups. Sucrase and isomaltase activities at the age of 19 days were diurnal in AR pups, but arrhythmic in MR pups. We conclude that artificial rearing via the intermittent gastric infusion of a milk formula containing only lactose as the carbohydrate source did not prematurely increase intestinal sucrase and isomaltase activities. Diurnal changes started from the beginning of development of these enzyme activities in AR pups.

Animals↗

Apparent depth with retinal image motion of expansion and contraction yoked to head movement.

The two main questions addressed in this study were (a) what effect does yoking the relative expansion and contraction (EC) of retinal images to forward and backward head movements have on the resultant magnitude and stability of perceived depth, and (b) how does this relative EC image motion interact with the depth cues of motion parallax? Relative EC image motion was produced by moving a small CCD camera toward and away from the stimulus, two random-dot surfaces separated in depth, in synchrony with the observers' forward and backward head movements. Observers viewed the stimuli monocularly, on a helmet-mounted display, while moving their heads at various velocities, including zero velocity. The results showed that (a) the magnitude of perceived depth was smaller with smaller head velocities (< 10 cm s-1), including the zero-head-velocity condition, than with a larger velocity (10 cm s-1), and (b) perceived depth, when motion parallax and the EC image motion cues were simultaneously presented, is equal to the greater of the two possible perceived depths produced from either of these two cues alone. The results suggested the role of nonvisual information of self-motion on perceiving depth.

Adult↗

Effects of isosorbide dinitrate on oxygen uptake kinetics in cardiac patients.

PURPOSE: Although nitrates are known to improve indices of exercise capacity in patients with coronary artery disease, their effects on oxygen uptake kinetics during the onset of exercise have not been clarified. We evaluated the acute effects of isosorbide dinitrate on the kinetics of oxygen uptake during the onset of exercise at a constant work rate in patients with coronary artery disease. METHODS: We studied 14 patients with coronary artery disease who performed 6 min of low-intensity exercise at a constant work rate on a cycle ergometer 30 min after oral administration of 10 mg of isosorbide dinitrate or placebo in a double-blind, crossover manner. Oxygen uptake was calculated from breath-by-breath analysis of respired gases. The time constant of oxygen uptake kinetics during the onset of exercise was determined by fitting a single exponential function to the oxygen uptake response. RESULTS: Heart rate was significantly increased at rest, and systolic blood pressure was significantly decreased both at rest and during exercise after administration of isosorbide dinitrate. The time constant of oxygen uptake was significantly shorter (the kinetics were faster) after administration of isosorbide dinitrate (39.4+/-10.1 vs 44.5+/-10.5 s, P = 0.038). CONCLUSIONS: Isosorbide dinitrate was found to speed the kinetics of the increase in oxygen uptake during constant work-rate exercise. The time constant of oxygen uptake, which reflects the rapidity of cardiovascular adaptation at the onset of exercise, seems to be a useful parameter of the effectiveness of therapy in patients with coronary artery disease.

Adult↗

Predictive factors of response to leukocytapheresis therapy for ulcerative colitis.

Leukocytapheresis (LCAP) using a leukocyte removal filter was performed for 8 patients with moderate to severe ulcerative colitis (UC). Significant clinical improvement was attained in 5 of 8 patients (62.5%). All of them had been suffering from moderately active colitis and received corticosteroid therapy. On the other hand, 3 patients with severely active disease and treated with little or no corticosteroid were resistant to LCAP. This result indicates that LCAP is an effective treatment for steroid-resistant cases of UC when combined with steroid therapy. LCAP alone, however, seems to have little efficacy for severely active UC.

Adult↗

Crucial role of milk-borne insulin in the development of pancreatic amylase at the onset of weaning in rats.

The development of pancreatic amylase activity was examined in rats fed in regular cages or in special cages, designed so the pups could not reach solid food to prevent weaning. In both groups, the amylase activity in zymogen granules increased in rat pups aged 14 days, peaked at 18 days, and thereafter remained at a 1.6-fold higher level than at 14 days of age. An increase in the plasma concentration of immunoreactive insulin preceded the increase of amylase activity, whereas the plasma concentration of C-peptide, indicating the secretion rate of endogenous insulin, remained unchanged. The administration of insulin at 20 ng/ml (the physiological concentration) in the milk formula caused an increase in the plasma insulin concentration of 17-day-old pups. In addition, increased pancreatic amylase activity was observed in 17-day-old rats raised on milk formula to which insulin was added. We propose that the increase of amylase activity at the beginning of weaning is dependent on the milk-borne insulin and not on the dietary change in rats.

Amylases↗

Gut hypertrophy in response to the ratios of casein and whey protein in milk formulas in artificially reared rat pups.

To elucidate the mechanism of gut hypertrophy observed in rats artificially reared (AR) on milk formulas, the effects of four refined formulas with different ratios of casein (C) and whey protein (W), CW 2:8, CW 4:6, CW 6:4 and CW 8:2, on the gut growth of AR rats were examined. Four groups of pups were infused with each formula through an intragastric cannula from age 5 to 15 days. Each of the four milk formulas showed a different character in the stomach, such as no curd, very soft curd, soft curd and hard curd, in response to an increasing ratio of C:W. There were no significant differences in body weight gain among the AR groups and mother-reared (MR) controls. The stomach growth, in weight, of AR rats increased in response to the increasing ratios of C:W. In comparison with MR controls, hypertrophy of the stomach of AR rats appeared within the formulas with higher proportions of casein than whey protein (CW 6:4 and CW 8:2), but not those with lower proportions (CW 2:8 and CW 4:6). The growth of the small intestine was also related to the increasing ratio of C:W in the formulas. A similar pattern of hypertrophy in the hindgut was seen in AR rats. There was no association between hypertrophy of the gut in AR rats and plasma triiodothyronine. The present results clearly demonstrated that the gut growth of AR rat pups was directly influenced by the diet but not by AR per se, and that hard casein-curd in the stomach might be one cause of gut hypertrophy.

Aging↗

Imaging of calcium release in inositol 1,4,5-trisphosphate-sensitive internal stores in permeabilized HSY cells using fluorescent indicators.

We described methods for imaging the IP3-induced Ca2+ release in Ca2+ storage organelles. IP3-induced changes in Ca2+ concentrations within Ca2+ stores ([Ca2+]L) in permeabilized HSY cells were monitored using the low affinity Ca2+ indicators, mag-fura-2 and mag-fura-red. The ratio images of mag-fura-2 were used to estimate the [Ca2+]L in the store. The apparent [Ca2+]L was 300-1000 microM at the cell periphery, whereas the [Ca2+]L in the cytoplasm around the nucleus was 70-150 microM. The [Ca2+]L throughout the cytoplasm was reduced by the application of 10 microM IP3 to 30-70 microM, and could be largely recovered after removal of IP3. The structure of IP3-sensitive Ca2+ stores was investigated by confocal microscopy using mag-fura-red. An IP3-induced increase in fluorescence was observed in the ER-like network and reticulum structures of the cytoplasm, and also in the nuclear envelope, suggesting that these organelles serve as IP3-sensitive Ca2+ stores. An analogous localization of the network and tubular elements of the ER was also demonstrated by electron microscopy. These observations suggest that these fluorescence techniques are useful to study the correlation between the distribution and function of Ca2+ stores.

Calcium↗

Direct transport of 2',3'-didehydro-3'-deoxythymidine (D4T) and its ester derivatives to the cerebrospinal fluid via the nasal mucous membrane in rats.

We investigated the absorption and transport of 2',3'-didehydro-3'-deoxythymidine (D4T) and its ester prodrugs from the nasal cavity in rats. The absorption of D4T and its acetate (C2-D4T) was rapid and almost complete, although the hemi-succinate (Suc-D4T) was absorbed rather slowly; the plasma concentrations of the prodrug, Suc-D4T, and regenerated D4T remained unchanged throughout the experimental period (180 min). Concentrations in the cerebrospinal fluid (CSF) following intravenous (i.v.) and intranasal (i.n.) administration were also measured. After i.n. administration, drug concentrations were higher in the fraction derived from the subarachnoid space located close to the nasal mucosa than those in the fractions located far from the nasal cavity. This difference was not found following the i.v. administration of the drugs. Following nasal administration, the intact Suc-D4T was found in the CSF at a concentration higher than that of D4T, although transport of the intact prodrug to the CSF was not observed following i.v. administration. These results suggest that direct transport of the drugs from the nasal cavity to the CSF significantly contributes to the higher concentrations in CSF of D4T and/or its ester prodrugs, and indicate the possible value of nasal administration for the treatment of patients with AIDS dementia.

Administration, Intranasal↗

Effects of orally ingested Bifidobacterium longum on the mucosal IgA response of mice to dietary antigens.

To study the effects of lactic acid bacteria on the mucosal defence against dietary protein antigens, we compared the mucosal IgA responses to beta-lactoglobulin (beta-LG) of two groups of mice fed a whey protein diet with and without a culture condensate of Bifidobacterium longum. Both total IgA and anti-beta-LG IgA levels in tissue extracts of the small intestinal wall were significantly higher in mice fed the B. longum diet for 2 weeks than in control ones. Peyer's patch (PP) cells from B. longum-fed mice had a much larger increase in in vitro IgA production than ones from control mice. Furthermore, the in vitro IgA response to beta-LG was detected only when PP cells from B. longum-fed mice were assayed. These results suggest that orally ingested lactic acid bacteria may protect a host from invasion of the intestinal mucosa by dietary antigens that have escaped enzymatic digestion in the intestine.

Animal Feed↗