Biomedical subjects

K Saegusa

Publications and source records attributed to K Saegusa.

At least 19 recordsLinked to original sources

PubMed2000

Severe destructive autoimmune lesions with aging in murine Sjögren's syndrome through Fas-mediated apoptosis.

When we evaluated the age-associated changes in autoimmune exocrinopathy in a NFS/sld murine model for primary Sjögren's syndrome (SS), severe destructive autoimmune lesions developed in the salivary and lacrimal glands in the aged mice, compared with those observed in the younger model. We detected a decreased secretion of saliva and tear flow in the aged group. A significant increase of TUNEL(+)-apoptotic epithelial duct cells in the salivary glands was detected in the aged SS animal model. A higher proportion of mouse salivary gland cells bearing Fas was found in the aged group, whereas no significant changes were seen on tissue-infiltrating CD4(+) T cells bearing FasL in the salivary glands from young and aged mice. We detected an increased cleavage product of organ-specific autoantigen, 120-kd alpha-fodrin, in the aged salivary gland tissues on immunoblotting, and an increase in serum autoantibody production against 120-kd alpha-fodrin by enzyme-linked immunosorbent assay. An increase in the proliferative response of splenic T cells against organ-specific autoantigen was observed, whereas nonspecific concanavalin A responsiveness was decreased in the aged mice. In addition, a decrease in Fas expression was found on splenic CD4(+) T cells in the aged mice, and anti-Fas mAb-stimulated apoptosis was down-regulated on CD4(+) T cells. These results indicate that age-associated dysregulation of CD4(+) T cells may play a crucial role on acceleration of organ-specific autoimmune lesions in a murine model for primary SS through Fas-mediated apoptosis.

Aging↗

PubMed2000

Treatment with anti-CD86 costimulatory molecule prevents the autoimmune lesions in murine Sjögren's syndrome (SS) through up-regulated Th2 response.

Intraperitoneal administration with anti-CD86 (B7.2) MoAb into the murine model for primary SS in NFS/sld mutant mice resulted in dramatically inhibitory effects on the development of autoimmune lesions, while no significant effects were observed when the mice were administered with anti-CD80 (B7.1) MoAb. We found that spleen cells in the murine SS model treated with anti-CD86 MoAb showed a significant impairment of autoantigen-specific T cell proliferation. T cell activation markers (CD44high, CD45RBlow, Mel-14low) were significantly down-regulated in the spleen cells gated on CD4 in anti-CD86-treated mice. We detected a higher level of cytokine production of IL-4 from splenic T cells in anti-CD86-treated mice, but not of IL-2, and interferon-gamma (IFN-gamma), compared with those in the anti-CD80- and PBS-treated SS model. Moreover, serum autoantibody production against alpha-fodrin autoantigen was almost entirely suppressed in anti-CD86-treated mice. These data provide strong evidence that in autoimmune exocrinopathy resembling SS in NFS/sld mutant mice, the CD86 costimulatory molecule plays a crucial role in the initiation and subsequent progression of Th1-mediated autoimmunity in the salivary and lacrimal glands.

Animals↗

PubMed1999

Estrogen deficiency accelerates autoimmune exocrinopathy in murine Sjögren's syndrome through fas-mediated apoptosis.

Estrogenic action has been suggested to be responsible for the strong female preponderance of autoimmune diseases, but the role of estrogens in the female has not been well characterized. We evaluated the effects of estrogen deficiency in a murine model for autoimmune exocrinopathy of Sjögren's syndrome (SS). Severe destructive autoimmune lesions developed in the salivary and lacrimal glands in estrogen-deficient mice, and these lesions were recovered by estrogen administration. We detected an intense estrogen receptor in splenic CD8(+) T cells compared with that in CD4(+) T cells, and concanavalin-A-stimulated blastogenesis of splenic CD8(+) T cells with estrogens was much higher than that of CD4(+) T cells. We found a significant increase in serum autoantibody production against the organ-specific autoantigen alpha-fodrin. Moreover, an increased proportion of TUNEL+ apoptotic epithelial duct cells was observed in estrogen-deficient mice. It was demonstrated that Fas-mediated apoptosis in cultured salivary gland cells was clearly inhibited by estrogens in vitro. These results indicate that dysfunction of regulatory T cells by estrogen deficiency may play a crucial role on acceleration of organ-specific autoimmune lesions, and estrogenic action further influences target epithelial cells through Fas-mediated apoptosis in a murine model for SS.

Animals↗

PubMed1999

Requirement for splenic CD4+ T cells in the immune privilege of the anterior chamber of the eye.

Injection of antigen into the anterior chamber of the eye induces suppression of antigen-specific DTH, called anterior chamber-associated immune deviation (ACAID). It has been shown that the spleen is required for the induction of ACAID and detecting the ACAID-inducing signal from the eye. To examine the in vivo role of spleen cells, fractions of spleen cells were adoptively transferred into splenectomized mice. The present study showed that DTH was not suppressed in splenectomized mice, but was inhibited in splenectomized mice transferred with a primed CD4+ T cell-containing fraction of spleen cells. This indicates that the splenic CD4+ T cells comprise the regulatory T cells for the DTH response. When we examined the cytokine profile of the infiltrating T cells in the eye of primed mice by reverse transcriptase-polymerase chain reaction (RT-PCR), we found that they expressed IL-4, IL-10 mRNA (Th2 type), but not IL-2 and interferon-gamma (IFN-gamma) mRNA (Th1 type). By contrast, T cells which can elicit normal DTH response expressed IL-2 and IFN-gamma mRNA. These results suggest that splenic CD4+ T cells comprising the regulatory phenotype are required for the induction of ACAID, and that a DTH response to the antigen may be prevented by Th2-dominant CD4+ T cells.

Animals↗

PubMed1998

Anti-120-kDa alpha-fodrin immune response with Th1-cytokine profile in the NOD mouse model of Sjögren's syndrome.

Our recent study suggested that the 120-kDa alpha-fodrin molecule may be an important autoantigen in the pathogenesis of Sjögren's syndrome, and anti-120-kDa alpha-fodrin antibodies have been detected in patients with Sjögren's syndrome. Here we have analyzed anti-120-kDa alpha-fodrin immune responses during development of spontaneous autoimmune sialadenitis in NOD mice as a model of Sjögren's syndrome. We found specific autoantibody production against 120-kDa alpha-fodrin, and its production correlated closely with autoimmune sialadenitis. A specific T cell response of splenocytes against the 120-kDa alpha-fodrin autoantigen was observed in NOD mice from the early onset of autoimmune sialadenitis. In addition, production in vitro by splenic T cells of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), but not IL-4, was detected by enzyme-linked immunosorbent assays. We found up-regulation of local cytokine genes, including those of Th1 type (IL-1beta, TNF-alpha, IL-2, IFN-gamma, IL-6), as well as IL-10 and IL-12(p40), in the tissue-infiltrating cells during the course of autoimmune sialadenitis. These findings suggest that in spontaneous autoimmune sialadenitis in NOD mice, there may be a specific anti-120-kDa alpha-fodrin immune response in the development of autoimmune lesions resembling human Sjögren's syndrome, and that the autoreactive Th1 cells possess an up-regulated cytokine profile besides IL-10 and IL-12.

Amino Acid Sequence↗

PubMed1997

Post-column enzyme reactors for chemiluminometric detection of glucose, 1,5-anhydroglucitol and 3-hydroxybutyrate in an anion-exchange chromatographic system.

A liquid chromatographic system consisting of a co-immobilized 3-hydroxybutyrate dehydrogenase-NADH oxidase reactor and an immobilized pyranose oxidase reactor in series and a chemiluminometer was developed for the simultaneous determination of glucose, 1,5-anhydroglucitol and 3-hydroxybutyrate in plasma. The enzymes were immobilized on toresylated poly(vinyl alcohol) beads. Separation was achieved on a TSK gel SAX column (40 x 4 mm I.D.) with an eluent of 50 mM NaOH containing 30 mM sodium butyrate. The hydrogen peroxide produced was detected by measuring the chemiluminescence emitted on admixing with luminol and potassium hexacyanoferrate(III). The calibration curves were linear from 0.8 to 500 microM (7 ng-4 micrograms) for glucose, from 0.8 to 400 microM (7 ng-3 micrograms) for 1,5-anhydroglucitol and from 1 to 700 microM (5 ng-4 micrograms in a 50-microliter injection) for 3-hydroxybutyrate. The sample throughput was four per hour. The reactors were stable for at least ten days.

3-Hydroxybutyric Acid↗

PubMed1995

[Continuous monitoring of arterial blood oxygen saturation with a pulse oximeter during spinal anesthesia].

The arterial oxygen saturation was continuously monitored in 50 patients under spinal anesthesia. Of the 50 patients, low oxygen saturation below 95% and/or its decrease of more than 5% was observed in 19 patients (38%). The remaining 31 patients (62%) showed a normal oxygen saturation. Pentazocine 0.5 mg.kg-1 i.v. correlated significantly with arterial oxygen desaturation (P = 0.0001). It is possible that laparotomy is associated with the desaturation (P = 0.0582). No correlation between desaturation and the other factors (level of analgesia, position during operation, and hydroxyzine premedication) was found.

Adolescent↗

PubMed1993

Assay of enzymic O-methylation of catechol oestrogens by high-performance liquid chromatography with coulometric detection.

A simple and sensitive method for the determination of guaiaicol oestrogens enzymatically formed from 2- or 4-hydroxyoestradiol, by means of high-performance liquid chromatography with coulometric detection, has been developed. Catechol and guaiacol oestrogens were efficiently separated on a reversed-phase column, using 0.5% ammonium phosphate buffer (pH 3.0)-acetonitrile (59:41, v/v) as the mobile phase, and detected coulometrically in a screening-oxidation mode at +0.10 V and +0.35 V, respectively. The method was applied to the assay of in vitro enzymic O-methylation of catechol oestrogens. After 2- or 4-hydroxyoestradiol had been incubated with rat red blood cells in the presence of S-adenosylmethionine, the resulting guaiacols and unchanged substrate were percolated through an Extrelut-3 cartridge. The dried eluate was redissolved and directly injected. This simple procedure was as sensitive as the previously reported method using gas chromatography-mass spectrometry in a selected ion monitoring mode.

Animals↗

PubMed1993

Enzymatic O-methylation of catechol estrogens in red blood cells: differences in animal species and strains.

Enzymatic O-methylation of catechol estrogens in red blood cells has been investigated with respect to species difference. In the presence of S-adenosylmethionine, 2- or 4-hydroxyestradiol (2-OHE2 or 4-OHE2) was incubated with blood lysate obtained from rats (five strains), guinea pigs, mice, rabbits, dogs, monkeys, and humans, respectively. The yielded guaiacols and unchanged substrate were determined by gas chromatography/mass spectrometry in a selected ion monitoring mode employing the corresponding 2H4-labeled compounds as internal standards. The total amounts of guaiacols formed from 2-OHE2 and 4-OHE2 were different, being the highest (79.6% and 38.1%) in monkeys and the lowest (5.1% and 1.9%) in humans. The ratios of isomeric guaiacols formed from 4-OHE2 (4Me/3Me) were 7.6-71, while those from 2-OHE2 (2Me/3Me) were 1.4-3.2. Thus, marked differences in O-methylation of catechol estrogens were observed among animal species, but no significant strain difference was detected in rats.

Adult↗

PubMed1993

[Crosstalks onto photopeak windows of 99mTc and other radionuclide (201Tl, 123I or 111In) in simultaneous acquisitions using a scinticamera--a fundamental study through phantom experiments].

In simultaneous acquisitions of both 99mTc and other radionuclide, there are crosstalks onto those photopeak windows. Therefore, to quantify the organ uptake in scintigraphic imaging, it is important to correct the crosstalk counts. The purpose of this study is to estimate the crosstalk fractions onto each photopeak window from other radionuclide. Those crosstalk fractions were determined from pulse height spectra, which were measured by inputting signals from a scinticamera into a multi-channel (2048 ch) pulse height analyzer. Four types of collimators, which are HR (high resolution), AP (all purpose) for low energy, ME (medium energy) and HE (high energy), as well as cuboid phantoms (10 x 10 x 10 cm3) were used in this experiment. The crosstalk fractions have a tendency to show small increases at the window width of 10 to 20%, excepting at 30%, a small change for the source thickness from 1 to 7 cm, and the least with the ME-collimator. The crosstalk fractions using the ME-collimator were obtained as follows, when the source thickness and the window width were 5 cm and 15%, respectively. 99mTc and 201Tl: 9.4% onto 201Tl window and 7.3% onto 99mTc window, 99mTc and 123I: 36.1% onto 99mTc window and 14.8% onto 123I window, 99mTc and 111In: 32.6% onto 99mTc window and 6.1% onto 111In window.

Gamma Cameras↗

PubMed1992

Comparison of Indium-111-labeled leukocyte scintigraphy and Technetium-99m joint scintigraphy in rheumatoid arthritis and osteoarthritis.

This study was undertaken to evaluate the use of Indium-111-labeled leukocyte (111In-WBC) imaging compared with Technetium-99m pertechnetate (99mTcO4-) imaging in 19 patients with rheumatoid arthritis (RA) and 8 with osteoarthritis. Knee and wrist joints were evaluated for both radionuclides. The results indicated a good correlation of the clinical assessment of pain and swelling with joint uptake ratio (JUR) between 111In-WBC and 99mTcO4- in RA and osteoarthritis patients. We observed a discrepancy in both imagings in "burned out" cases. It was concluded that a JUR of 111In-WBC could distinguish active RA from inactive RA or osteoarthritis at a value of 1.15 and that the use of 111In-WBC was a more reliable procedure than 99mTcO4-.

Adult↗

PubMed1992

Tyraminelike action of succinylcholine in the isolated, blood-perfused canine atrium.

The mechanisms of succinylcholine-induced cardiac effects have not been fully elucidated. Accordingly, we studied the effects of succinylcholine on atrial rate and contractile force in the isolated canine atrium perfused with donor blood. The sinus node artery was perfused with heparinized blood from the common carotid artery of the donor dog at a constant pressure of 100 mm Hg. When succinylcholine in a dose range of 30-1000 micrograms was injected directly into the sinus node artery of the isolated atrium, increases in atrial rate and contractile force were observed in a dose-related manner. The atrial rate and contractile force were increased to 10.5% +/- 1.8% (mean +/- SEM) and 56.8% +/- 8.5% above the control values after the administration of 1000 micrograms of succinylcholine, respectively. After treatment with propranolol, the positive chronotropic and inotropic effects of succinylcholine and norepinephrine were significantly suppressed. Hexamethonium or tetrodotoxin pretreatment inhibited the cardiac effects of nicotine but did not modify the succinylcholine-induced cardiac effects. The succinylcholine-induced effects were significantly inhibited by treatment with imipramine, which also suppressed the tyramine-induced effects. We conclude that succinylcholine has cardioexcitatory properties mediated by release of catecholamine due to a tyraminelike action.

Animals↗

PubMed1991

Anti-nicotinic and anti-muscarinic actions of eperisone in the isolated canine atrium.

The effects of eperisone, an antispastic agent, on the chronotropic and inotropic responses to acetylcholine, nicotine or stimulation of intracardiac autonomic nerves were evaluated in isolated, blood-perfused canine atrium. Eperisone (10-300 micrograms) injected into the sinus node artery of the isolated atrium produced dose-related negative chronotropic and inotropic effects, which were not affected by atropine. In the same doses, eperisone inhibited the negative chronotropic and inotropic responses to an injection of acetylcholine and intracardiac parasympathetic stimulation. Eperisone also suppressed the negative followed by positive cardiac responses to nicotine, but did not modify the positive responses to intracardiac sympathetic stimulation or norepinephrine. The inhibitory effect persisted much longer for the responses to nicotine or parasympathetic stimulation than for those to acetylcholine. These results suggest that eperisone at doses that induce direct cardiac depressant effects exerts its blocking action on nicotinic receptors at parasympathetic ganglia and sympathetic nerve terminals and on muscarinic receptors at the effector cells in the dog heart.

Acetylcholine↗

PubMed1990

[Gamma-ray spectra of 201Tl-radiopharmaceuticals with a scintillation camera--crosstalk of contaminating nuclides of 200Tl and/or 202Tl onto 201Tl-photopeaks].

In cardiac imaging with 201Tl, the collimator for low energy high resolution is generally used, and also the energy window, which is set on the spectral display of a pulse height analyzer of a scintillation camera, is chosen 70 +/- 12.5 keV. The purpose of this study is to discuss those conditions in 201Tl imaging with the scintillation camera. Two types of collimators for HR (high resolution) and ME (medium energy) were used in this experiment, and we measured the pulse height spectra of 201TlCl radiopharmaceuticals in air and in a cuboid phantom, connecting a multi-channel pulse height analyzer to the scintillation camera. As a result of measuring of the pulse height spectra, two different energies of gamma rays which are not supposed to emit from 201Tl nuclide were observed, and we also identified the presence of a small amount of 202Tl (with 439 keV) and/or 200Tl (with 368 keV) from their half-life measurements. Thus, the use of the HR-collimator with 201Tl imaging is not suitable, because the shielding effects of its septa is poor to 439 keV gamma-rays, and the scattered radiation produced by the Compton interaction contributes to the principal photopeak on the pulse height spectrum. Here, we recommend the use ME-collimator instead of the HR-one, and of the window width of 76 +/- 25 keV for increasing the count rate.

Humans↗

PubMed1989

Differential vagal inhibition of the positive chronotropic and inotropic responses to cardiotonics in the isolated dog atrium.

The effects of vagal nerve stimulation on the chronotropic and inotropic responses to norepinephrine (NE), dobutamine, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and Bay k 8644 were investigated in the isolated, blood-perfused right atrium of the dog. Electrical stimulation of intramural vagal nerves evoked decreases in the sinus rate and atrial contractile force, which were maintained at almost constant levels during stimulation. Vagal stimulation consistently attenuated both the positive chronotropic and inotropic responses to NE, dobutamine, forskolin and IBMX. The vagal inhibition of the chronotropic response to each substance was greater than that of the inotropic one except that to Bay k 8644. Vagal stimulation did not depress the positive chronotropic and inotropic responses to Bay k 8644. These results, therefore, suggest that, under parasympathetic tonic conditions, NE, dobutamine, forskolin and IBMX induce a positive chronotropic effect much less than a positive inotropic effect in the isolated dog atrium. Our results also suggest that the vagal inhibition of the chronotropic response to a beta-adrenoceptor agonist is induced at intracellular sites in the cyclic AMP cascade proximal to the Ca channel activation and also at a site proximal to the catalytic unit of adenylate cyclase.

1-Methyl-3-isobutylxanthine↗

PubMed1989

Operation for the stiff elbow.

Forty two cases of stiff elbow were treated by operation. Thirty three were subsequent to trauma, seven were due to ectopic ossification after quadriplegia, and two were associated with massive ectopic ossification after long term coma following head injury. Two separate skin incisions, postero-medial or medial and anterior, were used in most cases. In the post-traumatic cases, scarred, thickened posterior oblique fibres of the medial collateral ligament were usually found. Ectopic ossification was frequently situated on the postero-medial aspect of the stiff elbows. Resection of the thickened fibres or the ectopic ossification was the most effective procedure to improve elbow flexion. The average improvement in range of motion was 59 degrees in post-traumatic cases, 72 degrees in ectopic ossification after quadriplegia and 127 degrees in ectopic ossification following coma.

Adolescent↗

PubMed1989

[Comparison of SPECT images with four kinds of 99mTc collimators].

Performance of SPECT imaging systems which use a rotating gamma camera, are affected by characteristics of the detector-collimator assembly, the data acquisition method, and the filter used in image reconstruction. The purpose of this study is to examine image qualities of SPECT with different types of low energy collimators. The SPECT imaging system in this study is a rotating gamma camera ZLC-7500 (Siemens) and a data processing unit Scintipac-700 (Shimadzu). The four types of collimators compared are UHR (ultra high resolution), HR (high resolution), AP (general all purpose), and HS (high sensitivity), with 0.27, 0.66, 1.00, and 2.06 relative sensitivity, respectively. In the case of the same collimator, the spatial resolutions measured in the slice plane showed a slight difference in the FWHM values (mean values of UHR, HR, AP, and HS were 11.3 mm, 13.6 mm, 15.8 mm, and 20.4 mm, respectively.) between the center and the circumference of the field of view, in the radial direction, but a large difference in the tangential direction, with lower FWHM values (values of UHR, HR, AP, and HS were 8.4 mm, 8.7 mm, 9.3 mm, and 10.8 mm at 12 cm from the center, respectively.). In comparison of SPECT images with the four types of collimators, except for the HS collimator, image qualities of UHR, HR, and AP collimators showed only a slight difference. From the pont of view of sensitivity and spatial resolution of the collimator, it is expected that the AP collimator would be suitable for SPeCT imaging with 99mTc.

Models, Structural↗

PubMed1988

Cardiovascular effects of dibutyryl cyclic AMP in the intact dog heart and the isolated cross-perfused right atrium.

This study used an isolated right atrial preparation, cross-perfused with arterial blood from a support dog. We investigated the effects of dibutyryl cyclic AMP (DBcAMP) on heart rate and arterial blood pressure of the support dog and on the sinus rate and atrial contractile force of the isolated perfused atrium. DBcAMP was injected into the external jugular vein of the support dog or into the sinus node artery of the isolated atrium. DBcAMP to the support dog induced a small increase and/or decrease in arterial blood pressure at a dose of 3 or 10 mg/Kg i.v. It produced a decrease, with or without an increase in blood pressure, at a dose of 30 mg/Kg i.v., and a dose-dependent increase in heart rate in the support dog. In the isolated atrium, positive chronotropic and inotropic effects were observed. Direct injection of DBcAMP (3-30 mg) into the sinus node artery of the isolated atrium induced positive chronotropic and inotropic effects, after initial brief negative effects, in a dose-dependent manner. DBcAMP did not change norepinephrine-induced positive chronotropic and inotropic effects in the isolated atrium. These results demonstrate that DBcAMP induces a decrease in systemic arterial blood pressure with increases in sinus rate and atrial contractile force, and acts additively with the norepinephrine-induced positive cardiac effects in the dog heart.

Animals↗