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Biomedical subjects

K Ohtsuka

Publications and source records attributed to K Ohtsuka.

At least 73 records · Page 4Linked to original sources
PubMed1998

Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus.

TGF-beta has marked inhibitory effects on the immune system but also serves as a costimulatory factor in the development of T cells with down-regulatory activities. This cytokine is secreted as a latent complex and converted extracellularly to its active form. We have recently learned that anti-CD2 is a potent inducer of lymphocyte-derived TGF-beta and that NK cells are the predominant source. The objective of this study was to compare levels of constitutive, anti-CD2-induced and cytokine-regulated TGF-beta produced by blood lymphocytes from patients with systemic lupus erythematosus (SLE) in comparison with healthy controls. Using a highly sensitive and specific bioassay to assess TGF-beta, we report that unstimulated PBL from SLE patients, especially the NK cell subset, produced decreased levels of active TGF-beta. In response to anti-CD2, concentrations of active and total TGF-beta were also decreased in SLE. After learning that IL-2 and TNF-alpha enhance lymphocyte production of active TGF-beta, we found that the addition of these cytokines was unable to increase active TGF-beta to normal concentrations. Although we observed that IL-10 inhibited the production of active TGF-beta, antagonism of this cytokine was unable to completely correct the defect. In two SLE patients with B cell hyperactivity, spontaneous IgG production was almost abolished by the combination of TGF-beta and IL-2. Therefore, decreased production of each of these cytokines in SLE could be important in the perpetuation of B cell hyperactivity.

Adult↗
PubMed1998

Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus.

OBJECTIVE: To determine the profile of Th1-type and Th2-type cytokines produced by mononuclear cells from patients with recent-onset systemic lupus erythematosus (SLE), prior to the initiation of treatment with corticosteroids. METHODS: Using sensitive radioimmunoassays, interleukin-4 (IL-4), IL-10, IL-12 p40, tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) released into the culture supernatants of various unstimulated and stimulated blood mononuclear cell populations from 10 SLE patients was assessed in comparison with 10 matched healthy controls studied in parallel. RESULTS: In early SLE, monocyte-enriched cells constitutively produced increased amounts of IL-10 and decreased amounts of IL-12 following stimulation. Lymphocyte-enriched cells in SLE produced decreased amounts of IFN gamma and TNF alpha following stimulation. In "rested" cells, these defects were accentuated and a defect in IL-12 production was suggested. Depletion studies suggested that CD8+ cells were a major source of TNF alpha and IFN gamma in controls, but not in SLE patients. Increased IL-4 production or abnormalities in GM-CSF production were not observed. CONCLUSION: This study suggests that even early in the course of SLE, monocyte production of IL-10 is increased and that of IL-12 is decreased. Decreased production of Th1-type cytokines in SLE may be secondary to this imbalance between IL-10 and IL-12. A contributory role of dysfunctional CD8+ cells is suggested.

Adult↗
PubMed1998

Vascular compression of the oculomotor nerve disclosed by thin-slice magnetic resonance imaging.

PURPOSE: To describe the thin-slice magnetic resonance imaging features of vascular compressive oculomotor nerve paresis. METHODS: We performed thin-slice (2 mm thick) magnetic resonance imaging of the brainstem in a 74-year-old woman with right partial oculomotor nerve paresis using spoiled gradient recalled acquisition in the steady state. RESULTS: Thin-slice magnetic resonance images disclosed that the right oculomotor nerve was compressed and dislocated superiorly and laterally by the tortuous basilar artery. No other abnormalities were observed. CONCLUSION: This is the first case report of vascular compressive oculomotor nerve paresis disclosed by thin-slice magnetic resonance imaging.

Aged↗
PubMed1998

Human leukocyte antigens associated with hyperthyroid Graves ophthalmology in Japanese patients.

PURPOSE: To evaluate the association of human leukocyte antigen (HLA) types in Japanese patients with Graves ophthalmopathy. METHODS: Japanese patients with severe ophthalmopathy (48 patients) and patients without ophthalmopathy (46 patients) were selected prospectively from 234 consecutive patients with hyperthyroid Graves disease. The criteria for severe ophthalmopathy were proptosis of 19 mm or more, or a 3-mm difference in exophthalmometry measurement between the two eyes, or diplopia at the primary eye position. The criteria for the absence of ophthalmopathy were proptosis of 16 mm or less, no diplopia, no lid retraction, and no thickening of extraocular muscles. Serologic HLA typing of class I and II antigens was performed in the two patient groups. The frequency of each HLA antigen in the two patient groups was compared to that in 767 unrelated normal healthy Japanese controls. RESULTS: The frequencies of HLA-DR14 and DQ1 were significantly higher in the patient group with severe ophthalmopathy (35% and 75%, respectively) than in healthy controls (4% and 43%, respectively; corrected P < .05), and also greater than in the patient group without ophthalmopathy (13% and 55%, respectively; P < .01). On the other hand, the frequencies of HLA-B35, B54, DR4, and DQ4 were significantly higher in the patient group without ophthalmopathy (23%, 23%, 43%, and 30%, respectively) than in the patient group with severe ophthalmopathy (13%, 15%, 25%, and 19%, respectively; P < .01). CONCLUSIONS: HLA-DR14 and DQ1 antigens may be genetic markers of predisposition to the development of severe ophthalmopathy. In addition, HLA-B35, B54, DR4, and DQ4 may be genetic markers of resistance to severe ophthalmopathy. Variation in the severity of ophthalmopathy associated with Graves disease may depend, in part, on the presence or absence of particular HLA antigens.

Adolescent↗
PubMed1998

Bilateral trochlear nerve palsy with arachnoid cyst of the quadrigeminal cistern.

PURPOSE: To report bilateral trochlear nerve palsy and its magnetic resonance imaging characteristics in a patient with an arachnoid cyst of the quadrigeminal cistern. METHOD: We performed magnetic resonance imaging of the brainstem of a 54-year-old man who had bilateral trochlear nerve palsy and mild truncal ataxia. RESULTS: Magnetic resonance imaging disclosed an arachnoid cyst of the quadrigeminal cistern with enlargement of the lateral, third, and fourth ventricles. The tectum of the midbrain and the ambient and interpeduncular cisterns were markedly compressed by the arachnoid cyst. CONCLUSION: These findings suggest that the bilateral trochlear nerve palsy in this patient was caused by the arachnoid cyst of the quadrigeminal cistern.

Arachnoid Cysts↗
PubMed1998

Immunoadsorption therapy for Fisher syndrome associated with IgG anti-GQ1b antibody.

PURPOSE: To describe the effects of immunoadsorption therapy with a tryptophan-immobilized column on Fisher syndrome associated with IgG anti-GQ1b ganglioside antibody. METHODS: Three patients with Fisher syndrome and with a high serum IgG anti-GQ1b antibody titer underwent four to nine sessions of immunoadsorption therapy with a tryptophan-immobilized column. Using enzyme-linked immunosorbent assay (ELISA), we determined the differences in IgG anti-GQ1b antibody titers. RESULTS: ELISA disclosed that the IgG anti-GQ1b antibody titers of the serum samples collected from the inlet of the column were markedly higher than those collected from the outlet for all three patients. Moreover, after completion of the immunoadsorption therapy, the patients' serum IgG anti-GQ1b antibody titers were markedly lower than they were before the immunoadsorption therapy. The patients' ophthalmoparesis decreased in severity during the therapy. CONCLUSION: These findings suggest that immunoadsorption therapy with the tryptophan-immobilized column is an effective method for removing IgG anti-GQ1b antibody from serum.

Adolescent↗
PubMed1998

Bilateral internal ophthalmoplegia as a feature of oculomotor fascicular syndrome disclosed by magnetic resonance imaging.

PURPOSE: To describe the magnetic resonance imaging features of bilateral internal ophthalmoplegia as an oculomotor fascicular syndrome. METHODS: A 55-year-old man was initially examined with bilateral photophobia. Neuro-ophthalmologic examinations disclosed preganglionic bilateral internal ophthalmoplegia. Magnetic resonance imaging of the brainstem was performed. RESULT: Magnetic resonance imaging disclosed high-intensity areas on T2-weighted images along medial portions of the bilateral oculomotor fascicles in the mesencephalon. CONCLUSION: These findings suggest that mesencephalic lesions may selectively cause bilateral internal ophthalmoplegia as a partial oculomotor fascicular syndrome.

Brain Stem↗
PubMed1998

Fisher syndrome associated with IgG anti-GQ1b antibody following infection by a specific serotype of Campylobacter jejuni.

OBJECTIVE: The purpose of the study was to describe clinical and serologic features of Fisher syndrome associated with IgG anti-GQ1b ganglioside antibody following Campylobacter jejuni enteritis. DESIGN: A clinical trial. PARTICIPANTS: Four consecutive patients with Fisher syndrome were studied. INTERVENTION: Samples of sera from four patients were tested for reactivity to GQ1b ganglioside by enzyme-linked immunosorbent assay (ELISA). Campylobacter jejuni strains isolated from samples of stool from three patients were serotyped by the method of Penner and Hennessy and that of Lior. MAIN OUTCOME MEASURES: Serum IgG anti-GQ1b antibody titer and serotypes of C. jejuni. RESULTS: Diplopia occurred 8 to 14 days after the onset of diarrhea. Campylobacter jejuni was isolated from samples of stool from all of the patients. ELISA revealed a high serum IgG anti-GQ1b antibody titer for all four patients. Two patients had high serum titers of other antiganglioside antibodies frequently related to Guillain-Barré syndrome. These two patients developed limb weakness following the onset of ophthalmoplegia. The C. jejuni serotype was Penner's serotype 2 for all three of the patients tested. CONCLUSIONS: These findings suggest that C. jejuni, especially Penner's serotype 2, enteritis could trigger development of Fisher syndrome associated with IgG anti-GQ1b antibody.

Adolescent↗
PubMed1998

Enhanced production of nitric oxide may be involved in acute hypotension during maintenance hemodialysis.

To investigate the possible involvement of endogenous nitric oxide (NO) in acute hypotension during maintenance hemodialysis, we measured the plasma concentration of the nitrate anion NO3-, a stable metabolite of NO, in 19 patients undergoing hemodialysis. We analyzed heart rate variability to estimate the relationship between autonomic nervous activity and NO production, low-frequency/high-frequency components (L/H) as a parameter of cardiac sympathetic activity, and high-frequency power as a parameter of cardiac vagal activity. Six patients developed severe hypotension (a change in mean blood pressure during dialysis > or = 20 mm Hg), four patients developed mild hypotension (a change in mean blood pressure < or = 19 mm Hg and > or = 1 mm Hg), and nine patients did not develop hypotension. The plasma levels of NO3- before dialysis were markedly elevated in the severely hypotensive group compared with the patients who showed no hypotension (566+/-122 micromol/L v 133+/-38 micromol/L; P < 0.01), and this difference disappeared midhemodialysis and after hemodialysis. The plasma concentration of NO3- before dialysis was significantly associated with both the change in mean blood pressure during dialysis (r= -0.735; P = 0.003) and the mean blood pressure after dialysis (r = -0.675; P = 0.0015). The L/H ratio was inhibited before or after dialysis in the severely hypotensive group compared with the nonhypotensive group, and hypotension during dialysis was correlated with the inhibited L/H ratio before (r = 0.784; P = 0.001) or after (r = 0.822; P = 0.001) dialysis. Plasma NO3- concentrations were correlated with the L/H ratio before (r = -0.553; P = .014) or after (r = -0.546; P = 0.015) dialysis. These results suggest that inhibited sympathetic activity is one of the causes of acute hypotension during dialysis, and the enhanced production of NO is involved in this inhibition of the sympathetic activity in patients having a hypotensive episode during dialysis. The plasma concentration of NO3- before dialysis may be a predictor of the risk of hypotension during dialysis in patients with end-stage renal disease.

Acute Disease↗
PubMed1998

Transcranial magnetic stimulation over the posterior cerebellum during smooth pursuit eye movements in man.

Recent neurophysiological experiments in the monkey have demonstrated that the flocculus and the posterior vermis, lobules VIc-VII (oculomotor vermis), are involved in the generation of pursuit eye movements. Whereas the functions of the flocculus in the control of smooth pursuit have been intensively investigated, sufficient data are not available for a profitable discussion of the functions of the oculomotor vermis in the control of smooth pursuit. We previously indicated that the posterior vermis can be electrically stimulated by a focal transcranial magnetic stimulation (TMS) device through the skull in man, and that focal TMS of the posterior vermis can modulate saccadic eye movements. In this study we investigated the effects of cerebellar stimulation on smooth pursuit metrics in man using a focal TMS device. Focal TMS was applied over the posterior cerebellum in an area approximately 7 mm lateral and caudal to the inion, where saccadic eye movements are modulated by TMS, during horizontal smooth pursuit elicited by a step-ramp target with a constant velocity of 15 degrees/s in four normal subjects. The TMS device was triggered after the onset of smooth pursuit during the initial acceleration phase (latency range = 40-80 ms) or the steady-state tracking phase (latency range = 300-340 ms). We investigated the effect of TMS on the velocity and acceleration of smooth pursuit. For smooth pursuit directed ipsilateral to the stimulation side (ipsiversive), focal TMS of the posterior cerebellum produced abrupt acceleration of pursuit in both initial acceleration and steady-state tracking phases. On the other hand, TMS produced abrupt deceleration of contraversive pursuit in both initial acceleration and steady-state tracking phases. These findings suggest that the posterior vermis controls smooth pursuit velocity in a direction-selective manner in both initial acceleration and steady-state tracking phases.

Adult↗
PubMed1998

Radiotherapy in the management of Graves' ophthalmopathy.

BACKGROUND: To report the results of radiotherapy for patients with failure, adverse reactions or relative contraindications to the use of steroids or immunosuppressants, by using newly developed quantitative indexes. METHODS: Fourteen female and six male patients with Graves' ophthalmopathy were treated with radiotherapy between 1989 and 1996. Prior to radiotherapy, eight patients received treatment with prednisone, four received immunosuppressants and four received a combination of both. Four patients with contraindications to steroids were initially managed with radiotherapy. Most of the patients received a dose of 24-28 Gy in 2 Gy fractions. We used the newly developed motility limitation index to assess extraocular motility. RESULTS: Treatment was well tolerated. There have been no late complications. All 12 patients with soft tissue signs such as edema, irritation, tearing and pain were improved. Proptosis did not improve or improved only slightly, 3 mm at best. However, proptosis in all but two has been stabilized and has not deteriorated in the follow-up period. Most of the patients have experienced an improvement of eye-muscle motility. Extraocular muscles that work for elevation were impaired more severely than the other muscles and this tended to remain. Of the 16 patients using steroids before or when radiotherapy was initiated, 15 were tapered off and only one patient required additional steroids, thus sparing the majority from steroid adverse reactions. CONCLUSION: Radiotherapy was effective in preventing exacerbations of active inflammatory ophthalmopathy in patients with Graves' disease with minimal morbidity and thus eliminated the adverse reactions associated with protracted corticosteroid use. The newly developed motility limitation index was useful in detecting delicate changes in motility of individual extraocular muscles.

Adult↗
PubMed1998

Lower than normal expression of brain nitric oxide synthase gene in the hypothalamus of deoxycorticosterone acetate-salt hypertensive rats.

OBJECTIVE: To elucidate the role of brain nitric oxide produced by neuronal constitutive nitric oxide synthase in sodium-induced hypertension. DESIGN AND METHODS: Diets containing a high (8% NaCl), a medium (2% NaCl), and a low (0.2% NaCl) sodium content were administered to Wistar rats aged 12 weeks for 10 days or 8 weeks until they were killed. Male Wistar rats administered either deoxycorticosterone acetate, 1% NaCl or both and the respective controls were killed 2 weeks (during prehypertensive stage) or 6 weeks (during hypertensive stage) after the start of treatment. The hypothalamus and lower brainstem were excised for extraction of total RNA. Reverse transcription polymerase chain reactions of constitutive nitric oxide synthase messenger RNA and glyceraldehyde-3-phosphate dehydrogenase messenger RNA were performed, and constitutive nitric oxide synthase messenger RNA levels were expressed relative to glyceraldehyde-3-phosphate dehydrogenase messenger RNA levels. RESULTS: A high sodium intake for 10 days tended to decrease constitutive nitric oxide synthase messenger RNA levels in the hypothalamus, compared with effect of a low sodium intake. Constitutive nitric oxide synthase messenger RNA levels in the hypothalamus of deoxycorticosterone acetate-salt hypertensive rats were lower than those in the control sham-operated rats. Neither alteration of sodium intake nor administration of deoxycorticosterone with and without sodium affected constitutive nitric oxide synthase gene expression in the lower brainstem. CONCLUSIONS: Expression of neuronal constitutive nitric oxide synthase gene is downregulated in the hypothalamus of deoxycorticosterone acetate-salt hypertensive rats. This lower than normal expression of neuronal constitutive nitric oxide synthase gene in the hypothalamus could be an adaptive response to sodium-induced hypertension, and suggests that nitric oxide produced by hypothalamic constitutive nitric oxide synthase plays a role in maintenance of blood pressure in relation to sodium balance in rats.

Animals↗
PubMed1998

Benzamil blockade of brain Na+ channels averts Na(+)-induced hypertension in rats.

To determine the possible involvement of brain amiloride-sensitive Na+ channels in Na(+)-induced hypertension, we investigated the effects of benzamil hydrochloride, a specific blocker of these Na+ channels, on the acute pressor mechanisms of intracerebroventricular infusion of hypertonic NaCl and the continuous pressor mechanisms of Na(+)-induced chronic hypertension, such as deoxycorticosterone acetate-salt hypertensive or stroke-prone spontaneous hypertensive rats, and of non-Na(+)-induced hypertension, such as renovascular hypertensive rats. Intracerebroventricular preinjection with benzamil (1 or 10 nmol/kg) abolished the increase in mean arterial pressure, heart rate, abdominal sympathetic discharge, and plasma vasopressin concentration induced by an acute increase in cerebrospinal Na+ concentrations at intracerebroventricular infusion of 1.5 M hypertonic NaCl. Continuous intracerebroventricular infusion of benzamil (1 or 10 nmol.kg-1.day-1) for 7 days attenuated Na(+)-induced chronic hypertension in both deoxycorticosterone acetate-salt and stroke-prone spontaneous hypertensive rats, accompanied by reduction of urinary excretion of vasopressin and norepinephrine but not in renovascular hypertensive rats. Intravenous infusion of benzamil (10 nmol.kg-1.day-1) for 7 days affected neither arterial pressure nor urinary excretion of vasopressin and norepinephrine in either model of hypertension. Benzamil-blockable brain amiloride-sensitive Na+ channels are expected to function as one of the Na+ receptors in the brain and to be involved in the pressor mechanism of Na(+)-induced hypertension.

Amiloride↗
PubMed1998

Compressive lesions of the abducens nerve in the subarachnoid space disclosed by thin-slice magnetic resonance imaging.

We evaluated the usefulness of thin-slice magnetic resonance (MR) imaging as a tool for diagnosing compressive lesions of the abducens nerve in the subarachnoid space. We performed thin-slice MR imaging of the brain stem in two patients with abducens nerve palsy. Thin-slice MR images showed the abducens nerves in the subarachnoid space and clearly showed compressive lesions of the nerves by a brain tumor in both cases. These findings suggest that thin-slice MR imaging is useful for the evaluation of compressive lesions of the abducens nerve in the subarachnoid space.

Abducens Nerve↗
PubMed1998

Radiographic features of an aneurysmal bone cyst of the orbit.

Aneurysmal bone cyst is an unusual benign solitary lesion of bone occurring rarely in the orbit. In this report, we present computed tomography and magnetic resonance images of an orbital aneurysmal bone cyst involving the frontal bone in a 16-month-old boy. The aneurysmal bone cyst exhibited bone destruction, new bone formation of the orbital roof and fluid-fluid levels in the lesion following hemorrhage. These radiographic features may be useful for diagnosing orbital aneurysmal bone cysts.

Bone Cysts, Aneurysmal↗
PubMed1998

Increased serum concentrations of human hepatocyte growth factor in proliferative diabetic retinopathy.

Human hepatocyte growth factor (hHGF) is a powerful inducer of angiogenesis. We investigated the relationship between serum hHGF concentrations and proliferative diabetic retinopathy, the major characteristic of which is retinal neovascularization. Serum hHGF concentrations were measured in diabetic (n = 135) and nondiabetic subjects (n = 80). The mean serum hHGF concentration in diabetic subjects without retinopathy was lower than that in nondiabetic subjects [0.041 +/- 0.003 ng/mL (n = 62) vs. 0.080 +/- 0.010 ng/mL (n = 80); P < 0.05], but was not different from that in diabetic subjects with background retinopathy (0.058 +/- 0.007 ng/mL; n = 26) or preproliferative retinopathy (0.048 +/- 0.010 ng/mL; n = 10). The mean serum hHGF concentration was increased in subjects with proliferative retinopathy who had not undergone photocoagulation (0.213 +/- 0.025 ng/mL; n = 24), but not in those who had undergone photocoagulation (0.040 +/- 0.008 ng/mL; n = 13). Circulating hHGF may be involved in the mechanism of neovascularization in the proliferative diabetic retinopathy, and measurement of serum hHGF may be helpful in predicting the presence of proliferative retinopathy in diabetic subjects.

Adult↗
PubMed1998

Possible involvement of calcineurin in retinoic acid-induced inhibition of leukemic HL-60 cell proliferation.

Differentiation of leukemic HL-60 cells by all transretinoic acid (ATRA) resulted in a reduced rate of growth. Cyclosporin A and FK506, at concentrations that inhibited calcineurin activity, abrogated the ATRA-induced inhibition of HL-60 cell growth but these immunosuppressants had no effect on the ATRA-induced granulocytic differentiation. Treatment with 1 microM ATRA led to a progressive increase in calcineurin phosphatase activity of HL-60 cells; the increase in this activity appeared to parallel the functional change of HL-60 cells during granulocytic differentiation. Increase in calcineurin activity was concordant with the increased expressions of calcineurin A and calcineurin B subunit proteins. The FKBP12 expression increased during ATRA-induced differentiation and expression of cyclophilin A remained unchanged. We propose that the increased expression of calcineurin is involved in the ATRA-induced inhibition of HL-60 cell proliferation, as in the case with 1,25alpha-dihydroxy-vitamin D3.

Calcineurin↗