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Biomedical subjects

S Tokuda

Publications and source records attributed to S Tokuda.

At least 19 recordsLinked to original sources

Mechanism of stabilization of ballooning modes by toroidal rotation shear in tokamaks.

A ballooning perturbation in a toroidally rotating tokamak is expanded by square-integrable eigenfunctions of an eigenvalue problem associated with ballooning modes in a static plasma. Especially a weight function is chosen such that the eigenvalue problem has only the discrete spectrum. The eigenvalues evolve in time owing to toroidal rotation shear, resulting in a countably infinite number of crossings among them. The crossings cause energy transfer from an unstable mode to the infinite number of stable modes; such transfer works as the stabilization mechanism of the ballooning mode.

Journal Article↗

Involvement of two plasmids in fenitrothion degradation by Burkholderia sp. strain NF100.

A bacterium capable of utilizing fenitrothion (O,O-dimethyl O-4-nitro-m-tolyl phosphorothioate) as a sole carbon source was isolated from fenitrothion-treated soil. This bacterium was characterized taxonomically as being a member of the genus Burkholderia and was designated strain NF100. NF100 first hydrolyzed an organophosphate bond of fenitrothion, forming 3-methyl-4-nitrophenol, which was further metabolized to methylhydroquinone. The ability to degrade fenitrothion was found to be encoded on two plasmids, pNF1 and pNF2.

Biodegradation, Environmental↗

Partial 10q trisomy with partial 12q monosomy.

A case of partial trisomy 10q with partial monosomy 12q is reported. The chromosomal abnormalities resulted from a paternal balanced, reciprocal translocation involving chromosomes 10 and 12, which, to the best of our knowledge, has not been previously described.

Abnormalities, Multiple↗

Downbeat nystagmus with compression of the medulla oblongata by the dolichoectatic vertebral arteries.

A case is reported of downbeat nystagmus associated with compression of the caudal brain stem by the dolichoectatic vertebral arteries, which was revealed by magnetic resonance imaging. Before surgery, the patient complained of oscillopsia at rest. Downbeat nystagmus was observed in the primary eye position and was increased in lateral gaze, especially to the left. Surgical repositioning of the left vertebral artery succeeded in resolving the downbeat nystagmus in the primary position within 1 month, and the nystagmus in all the other gaze positions almost completely disappeared over the subsequent months. Other ocular abnormalities also were improved after surgery. Thus, this case shows clear evidence of downbeat nystagmus arising from compression of dolichoectatic vertebral arteries to the medulla oblongata. Surgical neurovascular decompression of the dolichoectasia reverses the progression of symptoms if permanent neurologic damage has not already occurred.

Aged↗

The in vivo effects of opioid peptides on the murine immune response.

We have previously reported that met-enkephalin has dual immunomodulatory properties in vitro. We have continued this investigation using an in vivo system. In this study, Alzet miniosmotic pumps were loaded with either met-enkephalin, DTLET or FK 33-824 and were surgically implanted into BAF1/J mice. Twenty-four hours after pump implantation, mice were challenged with sub-optimal, optimal or supraoptimal immunizing doses of antigen. The immune response was assessed 4 or 5 days after primary immunization. FK 33-824, a met-enkephalin analogue, had no effect on the response of mice challenged with a suboptimal antigen dose. However, FK 33-824, at a pump concentration of 10(-3) M, suppressed the response against optimal challenge doses of antigen. At a pump concentration of 10(-8) M, FK 33-824 suppressed, enhanced or had no effect on the supraoptimal antigen dose-induced immune response. The suppressive effect of FK 33-824 in mice immunized with either optimal or supraoptimal doses of antigen was blocked by naloxone. Met-enkephalin and its delta opioid receptor specific analogue, DTLET, had no effect on the immune response to optimal antigen immunization. These results indicate that FK 33-824 has in vivo immunomodulatory activity and provide evidence that opioid peptides may either upregulate or downregulate the in vivo immune response depending on the strength of the response.

Amino Acid Sequence↗

Increased natural killer cell activity in a model of immunoglobulin A nephropathy secondary to chronic alcohol consumption.

We investigated natural killer (NK) cell activity in an animal model of ethanol-induced immunoglobulin A (IgA) nephropathy. Two groups, of 10 rats each, received a continuous intragastric infusion of liquid diet through a permanent cannula for 6 weeks. The alcoholic group was infused additionally with intragastric ethanol, representing from 32% to 40% of the caloric requirement. The group of control rats received an isocaloric diet supplemented with glucose instead of alcohol. IgA nephropathy was observed in all the alcoholic rats but in none of the controls. NK cell activity was investigated in the two groups by measuring the cytotoxicity of spleen cells using the chromium release method. NK cell activity was found to be significantly increased in the alcoholic rats. In view of the known modulation of IgA synthesis by NK cells, we suggest that increased NK cell activity may be a contributing factor to the high levels of circulating IgA seen in IgA nephropathy secondary to chronic alcohol consumption.

Alcoholism↗

Higher levels of erythrocyte membrane fluidity in sprinters and long-distance runners.

Erythrocyte membrane fluidity was measured in male sprinters and long-distance runners by a spin-label method. The membrane fluidity was higher in long-distance runners than in sedentary subjects for both measurements by use of two stearic acid spin labels (SAL), 12- and 16-SAL, which represent the fluidity at two different depths of lipid bilayer. In the 12-SAL measurement, higher levels were also evident in sprinters than in sedentary subjects. Increases in the C20:5, C22:5, and total polyunsaturated acyl chains were evident in membrane phospholipids, whereas the C18 and total saturated acyl chains were decreased in long-distance runners compared with sedentary subjects. Only levels of C22:5 were higher in the sprinters than the sedentary subjects. Membrane cholesterol and phospholipid classes did not differ among the three groups. A higher level of erythrocyte membrane fluidity was observed in the athletes, more obviously in the long-distance runners, which was related to the altered phospholipid acyl chain composition. The change may contribute to the beneficial effects on erythrocyte functions related to microcirculation in athletes.

Adult↗

Mucosal immune dysfunction associated with alcoholic IgA nephropathy.

We investigated the hypothesis that alcohol-induced changes of the immune system result in IgA nephropathy (IAN). Wistar rats were infused with liquid diet containing alcohol: "alcoholics." Control rats received an isocaloric diet with glucose instead of alcohol. IAN was diagnosed by mesangial IgA deposition. When compared to controls, serum IgA in alcoholic rats with IAN had a fourfold increase and a twofold increase in alcoholics without IAN. The intestinal lamina propria showed overall lymphocyte depletion in alcoholic rats. The decrease was not uniform for all the lymphocyte subgroups: it resulted in a relative increase in IgA-B cells in alcoholic rats with IAN but not in alcoholic rats without IAN. No significant differences were observed between alcoholic and control rats in the percentages of spleen lymphocyte subtypes. We suggest that dysfunction of the mucosal immune system may be related to the induction of IAN in chronic alcohol consumption.

Alcoholism↗

Evidence of altered T-lymphocyte number and proliferative responses in genetically epilepsy-prone rats.

Genetically epilepsy-prone (GEPR-9) rats exhibit decreased antibody plaque-forming cell responses following immunization. We examined the hypothesis that this immunosuppression was due to deficits in the number or proliferative responses of T-lymphocytes. Splenocyte responses to concanavalin A and pokeweed mitogen were significantly greater in GEPR-9 rats than controls. Flow cytometric analysis indicated that GEPR-9 rats possess an increase in T-cells associated with the T-helper phenotype. The increased proportion of T-helper cells in GEPR-9 rats may underlie their enhanced proliferative responses to T-cell mitogens. These results clearly indicate that the failure of the GEPR-9 rat to respond to a T-dependent antigen in vivo is not due to a lack of T-helper activity.

Animals↗

Evidence of immunosuppression in the genetically epilepsy-prone rat.

Immune system function was examined in the genetically epilepsy prone (GEPR-9) rat and non-epileptic Sprague-Dawley control rats. Significant decreases in direct and indirect plaque-forming cell responses were observed in GEPR-9 rats immunized with sheep erythrocytes. Serum levels of IgM were also decreased in non-immunized GEPR-9 rats, providing additional evidence of immunosuppression. However, total serum levels of IgG were three-fold greater in GEPR-9 rats compared to control. These results suggest that the nature of the immune system deficit in the GEPR-9 is complex and may involve an active T-cell population stimulating an overproduction of IgG leading to a diminished capacity to respond to new antigen challenges. This immunological defect may underlie the enhanced susceptibility of GEPR-9 rats to infectious agents. The specific cause of this immune dysfunction is not known. Possible etiological factors include a breakdown in the communication between cells within the immune system or an alteration of neuroendocrine modulation of immune responses.

Animals↗

Computed tomography guided stereotactic aspiration of pontine hemorrhages.

Computed tomography-guided stereotactic aspiration has been carried out in 20 patients with hypertensive pontine hemorrhage. A Komai computed tomography-guided stereotactic apparatus and a suboccipital transcerebellar approach were used. The entire operative procedures were performed under local anesthesia or neuroleptanalgesia in the semilateral position. Of 20 patients, the outcome was assessed as good in 9, fair in 4, and poor in 7. No patient deteriorated after the operation. The relationship between the preoperative clinical features and the outcome in comparison with the conservative treatment is presented.

Adult↗

Dual immunomodulation by met-enkephalin.

Met-enkephalin (MENK) is an opioid peptide that is released during physiological stress and is reported to either up-regulate or down-regulate the immune response. Our previous experiments showed the ability of 10(-7) M MENK to modulate the plaque-forming cell (PFC) response of Mishell-Dutton cultures treated with low, optimal, and large concentrations of sheep erythrocyte (SE) antigen. In the present series of experiments the PFC response was measured in splenocyte cultures challenged with incremental concentrations of SE in the presence of 10(-7) M MENK. These experiments illustrate what we consider to be true modulation, i.e., the ability of MENK to modulate immune function only during the presence of a strong immune signal. When the immune signal was strong, as represented by a strong PFC response, MENK suppressed the PFC response. Conversely, when the strongest immune signal was high-antigen suppression of the PFC response, MENK overcame the suppression and frequently returned the PFC response to a greater than optimal level. In a true modulatory fashion MENK had no effect in those regions of the dose-response curve where there was insufficient antigen to induce a strong immune signal.

Animals↗

Effect of low-dose irradiation upon T cell subsets involved in the response of primed A/J mice to SaI cells.

A/Jax (A/J) mice primed to Sarcoma I (SaI) exhibit an augmented response in association with low-dose (0.15 Gy) irradiation. This phenomenon is best demonstrated in tumour neutralization (Winn assay) or cell transfer experiments utilizing mice depleted of thymus-derived (T) cells. It is particularly dependent upon the duration of priming and the growth characteristics of the tumour in the primary host. The importance of these two variables appears to relate to their influence upon the cell types responsible for the host response, and includes both an effector and a suppressor component. Radiation-induced inhibition of the suppressor component appears responsible for low-dose augmentation and results in injury to a T cell of the Lyt-1-2+ phenotype. In Winn assays employing equal numbers of immune spleen cells and SaI cells, the smallest tumours are associated with Lyt-1-positive (Lyt-1+2- and Lyt-1+2+) cells and exposure to 0.15 Gy markedly inhibits their anti-SaI activity. Thus, even though the effect is in the opposite direction, both the effector and suppressor components of the anti-SaI response in A/J mice are exceedingly radiosensitive.

Animals↗

Modulation of the in vitro murine immune response by met-enkephalin.

The in vitro priming of mouse spleen cultures with sheep erythrocytes (SE) was used to study the modulation of immune function by met-enkephalin (MENK). In these studies, suboptimal, optimal, and supraoptimal concentrations of SE were used to manipulate the plaque-forming cell (PFC) responses of cultured spleen cells. MENK, at a concentration of 10(-7) M, was able to abolish the high antigen dose-induced suppression of the PFC response, but was unable to increase the PFC response of cultures treated with suboptimal doses of antigen. On rare occasions when the supraoptimal dose of antigen did not suppress the immune response, the addition of 10(-7) M MENK to the culture medium suppressed the PFC response. Naloxone was unable to block the effect of MENK. These results indicate that the nature of the immune response must be taken into consideration when evaluating the effect of opioid peptides on immune function. We propose that MENK possesses a dual modulatory role, with the abilities to suppress a strong immune response and reverse high antigen-induced immunosuppression.

Animals↗

The effects of cyclophosphamide and irradiation singly and in combination upon SaI growth in A/J mice.

The effects of various doses of cyclophosphamide and low-dose (15 rads) radiation upon the size of tumors caused by 10(4) Sarcoma I (SaI) cells was determined. In intact A/Jax (A/J) recipients, the effect of the two agents singly and in combination was found to be dependent especially upon the dosage of cyclophosphamide and the time of its administration in relation to tumor inoculation. In cell transfer experiments to adult thymectomized, lethally irradiated, bone-marrow-restored (ATxXBM) mice, the effects of cyclophosphamide and irradiation appeared to be either overlapping (low dosages of cyclophosphamide) or additive (dosages of cyclophosphamide greater than or equal to 50 mg/kg), suggesting that the two agents exert their influence in dissimilar fashion, perhaps by injuring different cell types with the same basic function. The most pronounced conjoint effects are seen when low dosages of cyclophosphamide are given 3 days after the adoptive transfer of spleen cells from mice pretreated with low-dose irradiation. The implications of this observation with respect to immunotherapy are discussed.

Animals↗

Differential immune response in two handled inbred strains of mice.

C57BL/10J and BALB/cJ mice, outfostered at birth to C3H/2Ibg dams were subjected to handling on days 1 through 20 of life. Their plaque forming cell (PFC) response to sheep red blood cells as adults on day 5 post-immunization was compared to the PFC response in non-handled control mice. The PFC response of handled C57BL/10J mice was significantly suppressed compared to the PFC response in non-handled mice while the response of the handled and non-handled BALB/cJ mice was not significantly different.

Animals↗