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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 19 recordsLinked to original sources

Central noradrenergic inhibition of gastric motility in rats.

The roles of central noradrenergic mechanisms in the regulation of gastric motility were investigated in urethane-anesthetized rats in whom an intragastric balloon had been placed. Noradrenaline 100 nmol administered intracerebroventricularly (i.c.v.) significantly decreased spontaneous contractions of the stomach and this decrease in gastric motility was not observed in bilaterally vagotomized animals. Intracisternally administered (i.c.) noradrenaline (10 nmol) induced a decrease in gastric motility comparable to that elicited by noradrenaline 100 nmol i.c.v. Phentolamine 10 nmol i.c. but not the same dose of propranolol i.c. significantly antagonized the noradrenaline (10 nmol)-induced inhibition of gastric motility. These results suggest that alpha-adrenoceptor-mediated noradrenergic mechanisms in the brain stem are involved in the inhibitory regulation of gastric motility.

Animals

Detection of fecal blood by colloidal gold agglutination using an anti-human hemoglobin monoclonal antibody.

Monoclonal antibodies to human hemoglobin were produced and a colloidal gold agglutination method has been developed for detection of fecal occult blood. Since hemoglobin is composed of the tetramer, alpha 2 beta 2, a single monoclonal antibody-labeled colloidal gold can agglutinate with hemoglobin. The lowest detectable hemoglobin concentration was 0.5 micrograms/ml. A total of 785 fecal samples were determined using colloidal gold agglutination and compared with latex agglutination. The colloidal gold agglutination detected blood in 75 samples, whereas latex agglutination detected blood in 76 samples, and among them 70 were positive in both methods. Overall agreement between the two methods was 98%.

Agglutination

Surgical results and complications of goniosynechialysis.

Goniosynechialysis (GSL) was performed in 70 eyes with primary angle-closure glaucoma in which the intraocular pressure (IOP) could not be controlled with laser or surgical iridectomy. Following GSL, the IOP was maintained at below 20 mmHg, with and without eye drops, in 34 (87%) of 39 aphakic eyes and in 13 (42%) of 31 phakic eyes. In 8 of 10 eyes, all of which were phakic and the first GSL procedure was not effective, IOP could be controlled by a second GSL procedure combined with lens extraction. Life-table analysis showed a significant difference between the probable success rate, after 5 years, between the phakic and aphakic groups. Postoperative tonographic C values showed improvement in outflow facility. However, frequently encountered complications were exudation of fibrin and minor hemorrhage. Our results suggest that a combination of GSL and extraction of the lens may be necessary to control refractory angle-closure glaucoma.

Adult

The glomerular mesangium: capillary support function and its failure under experimental conditions.

We present a structural analysis of the ability of the biomechanical unit consisting of mesangium and glomerular basement membrane to maintain normal capillary architecture in the face of mechanical challenges due to high intraglomerular pressures. Capillary support function may be considered in terms of the stabilization of local form (development of wall tension against capillary dilation) and global form (centripetal fixation of capillary loops to maintain higher order form). The pathologic consequences of the loss of this support are illustrated by way of experimental models of mechanical mesangial failure. Such failure may express itself as mesangial widening, increased transmesangial macromolecule "traffic," ballooning of capillary segments, and unfolding of capillary loops. Mechanisms are described by which these structural changes may lead to segmental glomerular sclerosis.

Animals

Glomerular damage after uninephrectomy in young rats. I. Hypertrophy and distortion of capillary architecture.

Uninephrectomy (UNX) results in a higher incidence of focal glomerular sclerosis (FGS) in young rats than it does in adults. The reason for this higher susceptibility in young animals is not fully understood, but this does suggest that UNX in young rats may represent a particularly promising model in which to study the development of FGS. In the present study 10-day-old rats were subjected to UNX. After 4, 12 and 24 weeks, glomerular hypertrophy, structural lesions and function were analyzed in comparison with sham-operated controls. Up to the twelfth week, remnant kidney growth and glomerular growth proceeded in parallel; thereafter, kidney growth ceased, whereas glomerular growth continued undiminished. Twenty-four weeks after UNX, glomerular tuft volume in experimental animals exceeded that in controls by 80%. Twelve weeks after surgery, total GFR in UNX rats was approximately 80% of that in controls, a value maintained until the end of the observation period. Twenty-four weeks after surgery, heavy proteinuria was present in UNX animals. Structural abnormalities in glomeruli of UNX animals were already encountered 12 weeks after surgery; they were present to a much lesser extent in controls. In UNX animals these proceeded to the FGS stage by the end of the observation period. Three major groups of glomerular lesions were observed: (1) changes in the width and shape of glomerular capillaries. (2) changes in podocyte structure, and (3) tuft adhesions to Bowman's capsule with or without segmental sclerosis. The structural changes are analyzed in this and an accompanying paper [1]. The present paper deals with the widespread formation of irregular, giant capillary loops. They occur predominantly at the tuft periphery with a clear predilection for the vascular pole region. They are not a result of compensatory growth, but rather an expansion of single capillaries due to failure of the mesangium. Local disconnection of the mesangium from its anchoring points at the GBM leads to bulging and "coalescence" of capillary loops, resulting in abnormally-shaped vascular channels. This process is associated with a rearrangement of the corresponding mesangium. In our view, the appearance of dilated capillaries represents a local event pivotal to the development of more severe lesions, such as tuft adhesions and FGS.

Animals

Glomerular damage after uninephrectomy in young rats. II. Mechanical stress on podocytes as a pathway to sclerosis.

In a preceding study [1], we showed that within six months after UNX in young rats, glomeruli in the remnant kidney undergo a sequence of serious changes which finally lead to focal segmental glomerulosclerosis (FGS). The formation of abnormally-shaped capillary channels was shown to result from local mesangial failure and is considered to be a nidus for the development of more severe lesions. In the present paper, the development of characteristic lesions in podocyte structure is described and analyzed. Concomitant with overall glomerular growth after UNX, a pronounced hypertrophy of podocytes was observed, while the mean number of podocytes per glomerulus did not change. It appears that podocytes cannot sustain the same degree of growth as the tuft as a whole; podocyte hypertrophy is soon followed by maladaptive changes which eventually lead to cell destruction. The following sequence of pathologic changes can be suggested: cell bodies enlarge in volume and area associated with a dramatic attenuation to cytoplasmic sheets. Primary processes are thinned out and frequently extend to remote capillaries. As a whole, the capillary area served by a single podocyte is dramatically enlarged. Furthermore, the expanding cytoplasmic sheets (derived from podocyte cell bodies) cover an increasingly large proportion of the outer capillary surface, that is, of the filtration area. Consequently, an increasing amount of filtrate is delivered into the subcellbody space. Obstruction of the efflux of this filtrate into the urinary space causes bulging of the overlying cytoplasmic sheets into pseudocysts. Podocytes overlying abnormally-shaped and dilated capillary channels are generally the most seriously affected. Tuft hypertrophy, pseudocyst formation and local capillary expansion cause wide-spread apposition of podocytes to Bowman's capsule. Appositions are a prerequisite for the development of tuft adhesion. Local detachment of a podocyte from the GBM in those areas allows access of parietal cells to the GBM. In early adhesions the connection of the tuft to Bowman's capsule is established by single parietal cells which attach to both the GBM and the basement membrane of Bowman's capsule. An adhesion is considered as a nidus for segmental sclerosis; as the adhesion progresses, the related tuft regions turn into sclerosis. In the present model FGS develops exclusively in areas of tuft adhesion.

Animals

T cell activation and T cell receptor variable region gene usage in measles.

T cell activation and T cell receptor variable (V) regions were studied with monoclonal antibodies in peripheral blood lymphocytes from 22 patients with measles. Increased (greater than 5%) activated T cells (HLA-DR+ CD3+ cells) were noted in 14 of the 22 patients. Elevations of V beta 5+ and V beta 8+ T cells were observed in two and four patients, respectively, and appeared to be associated with T cell activation. The duration of fever was significantly prolonged in those with increased (greater than 10%) activated T cells (p less than 0.01). These results suggest that T cell activation and the preferential expansion of V beta 8+ and V beta 5+ T cells are associated with the pathogenic process of measles.

Adolescent

Myocardial uptake of 111In monoclonal antimyosin Fab in detecting doxorubicin cardiotoxicity in rats. Morphological and hemodynamic findings.

BACKGROUND: The therapeutic value of doxorubicin (DOX) is limited by its cardiotoxicity, which is dose dependent. To improve the detection of such myocardial damage, this study was designed to determine whether the 111In antimyosin antibody Fab could serve as a marker for cardiotoxicity in treated versus control rats on the basis of comparative morphological and hemodynamic findings. METHODS AND RESULTS: DOX was administered by intravenous injection to rats at a dose of 3 mg.kg-1.week-1 for 5 weeks. Three weeks after the final injection, an intravenous dose of 111In antimyosin, 740 kBq (20 microCi), was administered, and tissue distribution of the radioisotope (percent kilogram dose per gram) was assessed in 48 hours. Myocardial uptake of radioactivity by both ventricles was more prominent in the DOX-treated rats than in control rats (p < 0.001). The heart-to-blood and heart-to-lung uptake ratios were markedly higher in the treated rats than in controls (p < 0.001). As the severity of the myocardial damage increased, there was a progressive increase in myocardial uptake. There was a strong correlation between the severity of myocardial damage and the ventricular end-diastolic pressure (r = 0.84 and r = 0.83 in the left and right ventricles, respectively). On microscopic immunoautoradiography of the DOX-treated heart, there was a specific immunolocalization of the radiotracer in the injured myocytes but no radioactivity in the control myocytes. CONCLUSIONS: 111In antimyosin antibody appears to be a useful immunoradiotracer in detecting cardiac damage induced by DOX administration and in assessing the severity of cardiotoxicity. These data reinforce the clinical observation that myocardial imaging using 111In antimyosin Fab is able to provide information to guide the course of patients receiving DOX treatment.

Animals

Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in vivo as well as in vitro in Salmonella infection.

Gamma delta T cell receptor-positive cells (gamma delta T cells) have recently been implicated to play a role in the protection against infectious pathogens. Serial studies on gamma delta T cells in 14 patients with salmonella infection have revealed that the proportions of gamma delta T cells (mean +/- SD: 17.9 +/- 13.2%) in salmonella infection were significantly increased (P less than 0.01) compared with 35 normal controls (5.0 +/- 2.6%) and 13 patients with other bacterial infections (4.0 +/- 1.4%). Expansion of gamma delta T cells was more prominent in the systemic form (28.9 +/- 10.8%) than in the gastroenteritis form (10.5 +/- 7.9%) of salmonella infection (P less than 0.01). Most in vivo-expanded gamma delta T cells expressed V gamma 9 gene product. Increased activated (HLA-DR+) T cells were observed in all the six patients with the systemic form and four of the seven with gastroenteritis form. Especially in the six with systemic form, gamma delta T cell activation was significantly higher than alpha beta T cell activation at the early stage of illness (P less than 0.01). When peripheral blood lymphocytes from normal individuals were cultured with live salmonella, gamma delta T cells were preferentially activated and expanded and most of them expressed V gamma 9. Purified gamma delta T cells also responded to live salmonella in vitro. The present study suggests that human gamma delta T cells play a role in the protection against salmonella infection in vivo.

Adolescent

Studies on autoimmunity for T-cell-mediated beta-cell destruction. Distinct difference in beta-cell destruction between CD4+ and CD8+ T-cell clones derived from lymphocytes infiltrating the islets of NOD mice.

Six CD4+ and three CD8+ islet-reactive T-cell clones were established from lymphocytes infiltrating the pancreatic islets of NOD mice. Two of six CD4+ T-cell clones responded to NOD islet cells only, not to spleen cells. The remaining four clones responded to both islet cells and spleen cells from NOD mice, but not to cells from other strains of mice, including SJL, C3H, C57BL/6, and DBA/2 mice. None of the CD4+ T-cell clones had a cytotoxic effect on the cultured islet cells. On the other hand, all of the CD8+ T-cell clones showed both a proliferative response and a cytotoxic effect on the islet cells, with the restriction of MHC class I H-2Db. Electron microscopic studies revealed that islet-specific CD4+ T-cells attached closely to islet cells but did not destroy them. In contrast, CD8+ T-cell clones showed pseudopodialike protrusions into beta-cells, but not alpha- or delta-cells, leading to selective destruction of beta-cells. CD8+ CTLs could not be isolated from islets of NOD mice less than 10 wk of age, even if the islets showed lymphocytic infiltration, whereas CD4+ T-cells could be isolated from islets of these younger NOD mice. On the basis of these observations, we concluded that CD4+ and CD8+ T-cells interact differently with beta-cells at different stages in T-cell--mediated beta-cell destruction. CD4+ T-cells may secrete cytokines, which in turn activate effector cell populations, whereas CD8+ T-cells may act as a final effector directly involved in beta-cell destruction.

Animals

[The long-term effect of high-dose beclomethasone dipropionate on the pituitary-adrenal function].

The pituitary-adrenal function was studied in seven asthmatic subjects who had been received daily inhalations of 800 to 1,000 micrograms of beclomethasone dipropionate (BDP) over a year. None of the subjects had taken oral corticosteroids for at least six months prior to the study. As indices of pituitary-adrenal function, 1) circadian rhythm of plasma ACTH and cortisol, 2) urine 17-OHCS and 17-KS, and 3) the response of cortisol in rapid ACTH test were examined. All subjects showed normal circadian rhythms of plasma ACTH and cortisol levels. Urinary 17-OHCS and 17-KS excretions over a 24-hour period were also within the normal range. Plasma cortisol levels in the rapid ACTH test were significantly increased and judged as normal responses in all subjects. These results indicate that long-term treatment with BDP ranging from 800 to 1,000 micrograms/day induces no suppressive effect on the pituitary-adrenal function.

Adrenocorticotropic Hormone

[A case report of simultaneous procedure of Cabrol's operation and aortic arch replacement: method to reduce the duration of ischemic cardiac arrest].

A 57-year-old female underwent simultaneous Cabrol's operation and aortic arch replacement for aortic dissection. She was admitted with complaint of back pain. Aortography demonstrated acute dissecting aneurysm of the ascending, arch and descending aorta (DeBakey type I) as well as aortic valve regurgitation (Seller's II degree). The operation was undertaken using cardiopulmonary bypass (CPB) under hypothermia with selective cerebral perfusion. A new method to reduce the duration of ischemic cardiac arrest was applied. Initially a low-porosity woven Dacron tube graft (8 mm) was anastomosed to coronary arteries. Blood of CPB was perfused to this graft. This coronary perfusion contributed to shorten ischemic cardiac arrest time and cardiac function was favorable. This method to reduce the duration of ischemic cardiac arrest brought about good result.

Aortic Dissection

[Influence of thiopental administration on peripheral circulation during cardiac surgery with extracorporeal circulation].

The influence of thiopental administration on peripheral circulation during cardiac surgery with extracorporeal circulation was examined. The subjects were 28 patients who were divided into one group of 14 patients receiving thiopental and the other group of 14 patients receiving no thiopental. The time lag of changes in peripheral temperature (sole) from that in central temperature (forehead) according to the deep body temperature determination, and base excess were used as indices of the quality of the peripheral circulation. A single shot of thiopental at a dose of 4 mg.kg-1 was initially given i.v. at the start of extracorporeal circulation and subsequently thiopental at a dose of 2 mg.kg-1.hr-1 was continuously infused i.v. up to the time of the aortic declamping. The results indicate a significantly smaller lag in the group receiving thiopental than in the group receiving no thiopental. Base excess was maintained within normal limits in the former group compared with negative base excess in the latter group as well as a significantly smaller requirement of postoperative catecholamine in the former group. The above findings suggest that thiopental administration during cardiac surgery with extracorporeal circulation is not only useful for maintaining peripheral circulation, but also beneficial for post-operative cardiac function.

Aged

[Arterial switch operation for transposition of the great arteries without use of prosthetic material].

For transposition of the great arteries (TGA), arterial switch operation (ASO) is theoretically preferable to atrial switch operation, since the left ventricle is established as the systemic ventricle and sinus node function is maintained. However, ASO is a delicate operation requiring the transfer of the coronary arteries. Use of prosthetic material for reconstruction of the neo-pulmonary artery causes postoperative supra-valvular pulmonary arterial stenosis. Five neonates and young infants with TGA underwent ASO without the use of prosthetic material by the technique reported by Pacifico et al. Three patients with simple TGA ranged in age from 10 to 27 days, and in weight from 2.9 to 3.9 kg. Two patients with TGA and ventricular septal defect ranged in age from 41 to 63 days, and in weight from 2.8 to 4.2 kg. There were no deaths, either early or late, and all patients are well 7 to 21 months after surgery. Catheterization and Doppler echocardiographic studies performed in all patients showed that pressure gradient between the right ventricle and pulmonary artery decreased significantly during mean follow-up period of 14 months. These results suggest excellent growth of the pulmonary artery after surgery.

Aorta

[A case of allergic bronchopulmonary candidiasis treated with amphotericin B inhalation].

A 77-year-old man underwent emergency admission for nocturnal asthmatic attack. Although his asthmatic attack improved within a few days with treatment including systemic corticosteroid, bilateral recurrent infiltrative shadows developed in his chest roentgenogram in association with a further exacerbation of dyspnea. Various antibiotic agents were given; however, the pulmonary infiltration did not improve. He was transferred to our department with the diagnosis of intractable pneumonia. C. albicans was detected in the sputum, and both IgE antibody and precipitating antibody specific for C. albicans were positive. Immediate cutaneous reactivity to C. albicans was positive even with a million-fold dilution of antigen extract C. albicans was also detected in bronchoalveolar lavage fluid. A diagnosis of allergic bronchopulmonary candidiasis was made. Chest roentgenographic findings as well as clinical symptoms improved with inhalation of 50 mg of amphotericin B.

Administration, Inhalation