[A 67-year-old man with progressive shortness of breath].
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Aged↗
Biomedical subjects
S Yamagami
Publications and source records attributed to S Yamagami.
Prefrontal and striatal dopamine metabolism during enhanced rebound hyperphagia induced by space restriction--a rat model of binge eating.
BACKGROUND: Several lines of evidence indicate that abnormalities in brain dopamine and serotonin metabolism may play an important role in bulimia nervosa. However, the regional neurochemical mechanism of the binge eating is poorly understood. Our purpose was to elucidate brain neurochemical mechanisms of binge eating using a rat model. METHODS: The dopamine release and metabolism in the prefrontal cortex (PFC) and in the ventrolateral striatum (VLS) of rats were studied using microdialysis during enhanced rebound hyperphagia induced by space restriction (an animal model of binge eating). RESULTS: The rats showed rebound hyperphagic state when they were released from scheduled feeding (2 hours/day feeding for 7 days). The hyperphagia was further enhanced when they were put in a space-restricted cage where their mobility was restricted. Dopamine release and metabolism were increased both in the PFC and in the VLS during the enhanced rebound hyperphagia. CONCLUSIONS: These results tentatively suggest that increased dopamine release and metabolism in the PFC and in the VLS may be related to space restriction and to activation of motor function involved in feeding behavior, respectively. The enhanced rebound hyperphagia induced by space restriction may be useful as an animal model of binge eating.
3,4-Dihydroxyphenylacetic Acid↗
Cytokine profiles of aqueous humor and graft in orthotopic mouse corneal transplantation.
BACKGROUND: Cytokine profile is a key in understanding the mechanisms of allograft rejection. Cytokine expression in the aqueous humor and the correlation between the aqueous humor cells and corneal infiltrating cells are not fully understood in corneal transplantation. METHODS: Orthotopic mouse corneal transplantation was performed using BALB/c (H2d) mice as recipients, and C3H/He (H2k) and BALB/c mice as donors for allografts and isografts, respectively. Immunocytochemistry was performed on aqueous humor cells. Corneal graft was studied immunohistochemically. Cytokine gene expressions of the cells infiltrating the aqueous humor and corneal grafts were determined by the semiquantitative reverse transcription and polymerase chain reaction method. RESULTS: Interferon-gamma, interleukin (IL)-2, IL-4, and IL-10 were detected in the cells infiltrating the aqueous humor and corneal grafts at both the protein and gene expression levels. T helper 1 (Th1) cytokine expressions at the protein level, however, were consistently predominant in the rejected allografts compared to those of Th2 cytokines. The cytokine and surface marker profiles of the cells in the aqueous humor corresponded well to those of the cells infiltrating the corneal grafts. Cytokine protein and mRNA expression levels in the aqueous humor decreased rapidly. CONCLUSIONS: Allorejection in corneal transplantation is Th1 cytokine-predominant. Infiltrating cells do not express Th2 cytokine so much in allograft rejection, as compared with Th1 cytokine. The cell infiltration patterns of the aqueous humor were well correlated with those of the cornea.
Animals↗
Suppression of hyperemia after brain ischemia by L-threo-3,4-dihydroxyphenylserine.
Although several studies have shown that L-threo3,4-dihydroxyphenylserine (DOPS) may provide a neuroprotective effect against ischemic brain damage, its protective mechanism is not fully understood. Glutamate release and hippocampal blood flow in ischemia with administration of DOPS were investigated to elucidate the neuroprotective mechanism of DOPS. Pre- (but not post-) ischemic administration of DOPS rescued 73% of hippocampal CA1 neurons (p < 0.001, compared with ischemia only) 1 week after transient global ischemia in gerbils. While glutamate release induced by ischemia was not affected, the increase of hippocampal blood flow during reperfusion was significantly suppressed by DOPS. These results demonstrate that DOPS may prevent reperfusion injury by suppression of hyperemia after ischemia, resulting in neuroprotection.
Animals↗
Personality disorders in patients with eating disorders in Japan.
We assessed the prevalence of personality disorders (PD) using the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) in 36 patients with restricting anorexia nervosa, 30 patients with anorexia nervosa and bulimia nervosa, and 42 patients with bulimia nervosa. Of the 108 patients, 51% met the criteria for at least one PD. The patients with PD had more severe clinical features in terms of bulimic behaviors, concurrent depressive, anxious, and obsessive-compulsive symptoms, and psychopathology related to eating disorders compared to the patients without any PD. The patients with PD, especially borderline PD, also had more severe global functioning and greater numbers of suicidal attempts and hospital admissions. We compare these results with those reported in the Western world and discuss them cross-culturally.
Adolescent↗
Acceptance of second corneal allograft by combination of anti-VLA-4 and anti-LFA-1 monoclonal antibodies in mice.
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Animals↗
Distribution of Fos- and Jun-related proteins and activator protein-1 composite factors in mouse brain induced by neuroleptics.
The mechanisms by which the direct actions of neuroleptics are translated into therapeutic effects are unknown. We immunocytochemically investigated the expression of Fos- and Jun-related proteins and examined activator protein-1 DNA-binding activity in ddY mouse brain 120 min after the administration of haloperidol (1 mg/kg), (-)-sulpiride (20 mg/kg) and a selective dopamine D1 receptor antagonist, SCH23390 (1 mg/kg). The densities of Fos-, FosB-, Fra-1-, Jun- and JunD-immunoreactive nuclei induced by haloperidol and sulpiride in the hippocampus, piriform cortex and accumbens nucleus were higher than those in the control groups. The same regions showed higher densities of FosB-, Fra-1- and JunD-immunoreactive nuclei induced by SCH23390 compared with the control groups. We investigated further the activator protein-1 composite factors using super gel shift assays. These results suggested that induced Fos, FosB, Fra-1, Jun and JunD proteins constitute the activator protein-1 complex after the administration of haloperidol and sulpiride. In contrast, FosB, Fra-1 and JunD appear to constitute the activator protein-1 complex after the administration of SCH23390. Therefore, the diversity of activator protein-1 composite factors suggests that various kinds of gene are induced to act by some neuroleptics.
Animals↗
Developmental and regional alteration of kappa-opioid receptors in seizure-susceptible EL mouse brain.
The binding of [3H]ethylketocyclazocine ([3H]EKC) under the suppression of mu and delta sites in the brain of EL mice (seizure-susceptible) was examined to determine the relationship between seizures and the dynorphinergic system. The density of kappa-opioid receptors in the cerebrum of adult EL mice during interictal periods significantly increased, without changes in apparent affinities, compared with that of adult ddY mice (seizure-nonsusceptible; the mother strain of EL). Subsequently, the binding of 0.8 nM [3H]EKC in 8 brain regions was examined in the 2 strains. The [3H]EKC binding in 25-day-old EL mice that had no seizures significantly increased in the hippocampus and amygdala. At the age of 50 days, EL mice displayed abortive seizures, and the number of kappa sites in EL mice was significantly greater in the hippocampus, amygdala and cerebral cortex. It was further shown that the binding of [3H]EKC in 150-day-old adult EL mice during interictal periods was markedly increased in the hippocampus, amygdala, cerebral cortex and striatum, compared with the corresponding regions in ddY mice. The up-regulation of kappa receptors in the EL mouse brain may result from deficits in endogenous dynorphins, which could be involved in the pathogenesis of seizure diathesis and seizure manifestations in the EL mouse.
Animals↗
Event-related potentials in patients with obsessive-compulsive disorder.
Twenty-three unmedicated patients with obsessive-compulsive disorder (OCD) were compared with 12 unmedicated patients with social phobia (SP) and 18 age-matched normal controls (C) using a two-tone auditory oddball event-related potentials (ERP) paradigm. The OCD group showed significantly shorter P300 latencies and shorter N200 latencies for target stimuli than the SP and the C groups. The OCD patients also tended to have greater N200 negativity compared with normal controls. However, there were no significant relationships between these ERP abnormalities in OCD patients and the type or severity of their OCD symptoms. In the mean ERP waveforms, increased N200 negativity for target stimuli, as well as the provocation in the later part of N200 for non-target stimuli, were more commonly observed in the OCD and the SP groups compared with the C group. These results raise the possibility that the shorter N200 and P300 latencies in OCD patients may be an OCD-specific phenomenon that is more closely related to the biological basis for OCD, rather than the characteristics of their OCD symptoms. On the other hand, increased negativity in the N200 region, even for non-target stimuli, may represent the common abnormalities among anxiety disorders.
Adolescent↗
Lixelle adsorbent to remove inflammatory cytokines.
A beta2-microglobulin (beta2M) selective adsorbent (Lixelle) for direct hemoperfusion has been used for the treatment of hemodialysis patients with the long-term complication of dialysis related amyloidosis (DRA), but there is no significant correlation between the serum level of beta2M and the occurrence of DRA. Inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNFalpha) are related to the development of DRA. We studied the adsorptive rates of cytokines in vitro using the Lixelle adsorbent. The adsorptive rates were 98.5% for IL-1beta 98.0% for interleukin-1 receptor antagonist (IL-1RA), 82.9% for IL-6, 99.9% for IL-8, 31.2% for TNFalpha, and 46.1% for soluble TNF receptor (sTNFr), respectively. As the molecular weights of cytokines increase, the adsorptive rates decrease. The Lixelle column adsorbed beta2M and various inflammatory cytokines as well. Therefore, the removal of both beta2M and inflammatory cytokines may play an important role in the treatment of DRA.
Adsorption↗
Personality disorders in patients with obsessive-compulsive disorder in Japan.
A total of 75 patients with obsessive-compulsive disorder (OCD) were studied in order to investigate the characteristics of OCD symptoms and the comorbidity of personality disorders (PD). Contamination obsessions and checking compulsions were most commonly found in patients, of whom 53% met the criteria for at least one PD. Among comorbid PD, the anxious-fearful (cluster C) PDs, such as avoidant, obsessive-compulsive and dependent PD, were most prevalent, followed by the odd-eccentric (cluster A) PDs, such as paranoid and schizotypal PD. The patients with PD had more severe social maladaptation and concurrent depressive and anxious symptoms than the patients without any PD, despite the similar severity of OCD symptoms. These results are consistent with those reported in the Western world, and are considered to be relatively stable cross-culturally.
Adolescent↗
Direct measurement of wound temperature during phacoemulsification.
We developed a method to measure wound temperature during phacoemulsification with a thermometer and compared the temperature between pulse and nonpulse modes. In cases with partial or complete obstruction of the aspiration port, wound temperature was significantly lower in the pulse mode versus the nonpulse mode. It was ascertained that pulse mode phacoemulsification prevents thermal burn of the wound in the hard nucleus during cataract surgery. This method is useful to evaluate wound temperature during phacoemulsification under various conditions.
Animals↗
Local delivery infusion pressure is a key determinant of vascular damage and intimal thickening.
Local drug delivery following percutaneous transluminal coronary angioplasty (PTCA) may prevent restenosis by achieving higher local tissue concentrations of drugs than systemic administration. However, it remains unknown whether vascular damage and the ensuing intimal thickening is associated with the degree of infusion pressure achieved by local delivery. Therefore, local delivery of normal saline was performed using a channeled balloon catheter (Transport) to the rabbit iliac artery with different infusion pressures of 0, 3, 5, 7, and 12 atm (n=4 for each). The extent of vascular damage and the development of intimal thickening were determined histopathologically 14 days after the procedure. In 10 additional rabbits, to assess the degree of vessel penetration, local delivery of indocyanine green dye solution was performed in a similar fashion. After 1 h, the green dye penetrated deeply at the higher infusion pressures of 7 and 12 atm. The incidence of internal clastic lamina laceration and occurrence of total occlusion as a result of thrombus formation demonstrated an increase proportional to the degree of local infusion pressure. When the vascular injury score in each arterial section was plotted against the infusion pressure, a significant relation was observed (r=0.717, p<0.0001). At 0, 3, 5, 7, and 12 atm, neointimal areas of 0.160+/-0.005, 0.163+/-0.008, 0.189+/-0.017, 0.260+/-0.027, and 0.329+/-0.033 mm2, respectively, were observed. Smooth muscle cell (SMC) proliferative activity also increased in proportion to the local infusion pressure. We have demonstrated for the first time that local delivery infusion pressure itself is related to the severity of vascular damage, resulting in the development of intimal thickening and an associated increase in SMC proliferative activity. Therefore, we suggest that infusion pressure is a key determinant of vascular injury during local drug delivery, with lower pressure causing the least neointimal response.
Angioplasty, Balloon, Coronary↗
Role of Fas-Fas ligand interactions in the immunorejection of allogeneic mouse corneal transplants.
BACKGROUND: The expression of Fas ligand (FasL) in the eye has been proposed to be an important component of ocular immune privilege. Since the unusually favorable outcome of corneal transplantation is thought to result from the immune privilege of the eye, examination of the function of FasL on corneal allografts would be a test of that hypothesis. METHODS: To investigate the role of Fas-FasL interaction in corneal allografts, orthotopic corneal transplantation was performed using C57BL/6 (B6, FasL+) and B6-gld (FasL-) mice as cornea donors and BALB/c mice as recipients. The rejection rate of B6-gld grafts (FasL- group) was compared with that of normal B6 control corneas. RESULTS: The rejection rate at the final observation (8 weeks) in the FasL- group (89%) was significantly higher than in the FasL+ control group (47%). FasL expression was found on the corneal endothelium by staining with anti-FasL monoclonal antibodies. The TdT-mediated dUTP nick-end labeling assay revealed that apoptotic cells were attached to the endothelium in the control group but not in the FasL- groups. CONCLUSIONS: Apoptosis of infiltrating cells on the corneal endothelium resulting from Fas-FasL interaction plays an important role in the high success rate of corneal transplantation.
Animals↗
Mechanism of concordant corneal xenograft rejection in mice: synergistic effects of anti-leukocyte function-associated antigen-1 monoclonal antibody and FK506.
BACKGROUND: The mechanisms of corneal xenogeneic immunoreaction, as well as the potential role of immunosuppressive therapy in the suppression of corneal xenograft rejection, have not been thoroughly explored. METHODS: BALB/c mice who received orthotopic corneal transplants (Lewis rats donors) were administered intraperitoneally anti-leukocyte function associated antigen-1 (LFA-1) monoclonal antibody (mAb) or FK506 (3 mg/kg/day) or both of these immunosuppressants during a 12-day postoperative period. Histological (hematoxylin-eosin stain) and immunohistochemical evaluations of enucleated eyes were performed. Humoral immune response and delayed-type hypersensitivity (ear-swelling assay) were evaluated. RESULTS: The mean (+/-SD) graft survival time in the untreated control, FK506-treated, anti-LFA-1 mAb-treated, and combined-treatment groups was 5.8+/-0.8, 9.4+/-4.0, 8.7+/-5.0, and 67.7+/-16.4 days, respectively. In the untreated control group, mouse IgG, IgM, and C3 were expressed on the rat corneal grafts during the early postoperative phase. Flow cytometry studies revealed high titers of xenoreactive IgG and IgM antibodies. T helper 1 cytokines were expressed on xenografted corneal beds, and delayed-type hypersensitivity was induced. However, local expression of IgM, C3 and T helper 1 cytokines, serum antibodies of IgG and IgM, and delayed-type hypersensitivity were suppressed in the anti-LFA-1 mAb- plus FK506-treated group. CONCLUSIONS: Both humoral and cell-mediated immune reaction play an important role in the initial rejection in rat-to-mouse corneal xenotransplantation. The treatment with anti-LFA-1 mAb in combination with FK506 synergistically suppresses concordant corneal xenogeneic reaction.
Animals↗
Monocyte chemoattractant protein-2 can exert its effects through the MCP-1 receptor (CC CKR2B).
We studied the activities of the monocyte chemoattractant proteins MCP-1, MCP-2 and MCP-3 on human embryonic kidney 293-EBNA cells transfected with the MCP-1 receptor (CC CKR2B). At 4 nM, MCP-2 induced a Ca2+ influx which was as potent as that with MCP-1 at 4 nM, although the increase by MCP-2 became saturated at higher concentrations. In addition, all three MCPs showed dose-dependent inhibition of adenylyl cyclase activity stimulated by forskolin (IC50 values: 0.3 nM for MCP-1, 7 nM for MCP-2, and 1.5 nM for MCP-3). In conclusion, our data indicate that MCP-2 can exert its effects through the MCP-1 receptor, CC CKR2B.
Adenylyl Cyclase Inhibitors↗
Anterior chamber inoculation of splenocytes without Fas/Fas-ligand interaction primes for a delayed-type hypersensitivity response rather than inducing anterior chamber-associated immune deviation.
The inoculation of antigens into the anterior chamber (AC) of the eye induces an antigen-specific immune response that inhibits delayed-type hypersensitivity (DTH). This regulatory response is known as anterior chamber-associated immune deviation (ACAID). The ACAID response appears to be complex, as it can be elicited by a wide variety of soluble and cell-associated antigens, including foreign, self, tumor, and alloantigens. To evaluate the contribution of Fas/Fas ligand (FasL) interaction to the induction of ACAID to alloantigens, gld and lpr mutant mice were used in conjunction with normal C3H, MRL, and BALB/c mice. ACAID was induced by inoculation of non-irradiated splenocytes from donor mice into the AC of various recipients. After 1 week, recipients were primed intradermally with donor splenocytes. One week later DTH was measured by ear swelling. C3Hgld mutants lacking functional FasL did not develop ACAID after the AC inoculation of BALB/c splenocytes. Conversely, the AC inoculation sensitized these mutants. MRL/pr mutants, which lack Fas, developed ACAID following inoculation of BALB/c cells. AC inoculation of lpr splenocytes did not induce ACAID, but sensitized C3H recipients. Treatment of the AC inoculum with an anti-Fas antibody blocked ACAID induction in a transient manner, as the recipients developed ACAID later. These results show that interaction of the Fas and FasL is required to induce ACAID to allogeneic cells. In the absence of Fas expression on donor splenocytes, or FasL expression by the recipient, AC inoculation primes for a DTH response rather than inducing ACAID.
Animals↗
Specific immunosuppression of corneal allograft rejection by combination of anti-VLA-4 and anti-LFA-1 monoclonal antibodies in mice.
It has been reported that allograft rejection is mediated by a variety of adhesion molecules. Using a corneal allograft model in mice, we studied the role of very late antigen (VLA)-4 and leukocyte function-associated antigen (LFA)-1 adhesion molecules in corneal allograft rejection and the effects of monoclonal antibodies (mAbs) to them in suppressing corneal rejection. C3H/He donor corneas were transplanted into BALB/c corneal beds. The allografted mice were treated with a control mAb (M18/2), mAbs to VLA-4, or LFA-1 or their combination by i.p. injection until day 7. The expression of VLA-4, LFA-1, major histocompatibility complex (MHC) class II antigens, interleukin (IL)-2, IL-2 receptor and interferon gamma (IFNgamma) in the grafted cornea were studied immunohistochemically. Cytotoxic T lymphocyte (CTL) responses to donor alloantigens were assessed. The skins from a syngeneic donor or a third-part strain were transplanted 8 weeks after the initial keratoplasty onto the mice treated with anti-LFA-1 plus anti-VLA-4 mAbs. Fourteen of 16 allografts in non-treated mice and control mAb-treated mice became opaque by 2 weeks after transplantation. At 2 weeks, non-treated allografts showed expression of MHC class II antigens on keratocytes and mononuclear cells at the host-graft junction. Also, mononuclear cells expressing VLA-4, LFA-1, IL-2, IL-2 receptor and IFNgammawere present in the stroma at the host-graft junction. The allografts treated with either anti-VLA-4 or anti-LFA-1 alone, or anti-VLA-4 plus anti-LFA-1 remained transparent for more than 2 weeks, and the survival rates at 14 weeks was 0%, 16.7%, and 75.0%, respectively. The combined use of anti-VLA-4 and anti-LFA-1 mAbs prolonged graft survival significantly (P<0.05) at 14 weeks as compared with anti-LFA-1 mAb alone. At 3 weeks, CTL responses to donor alloantigens were depressed in mice treated with either anti-LFA-1 alone or anti-LFA-1 plus anti-VLA-4. Specific prolongation of donor-syngeneic skin was observed after treatment with the combination of these two mAbs. These results indicate that VLA-4 and LFA-1 have important roles in rejection process of corneal allografts, and that the combined use of mAbs to these molecules has remarkable effects on inducing alloantigen-specific immunosuppression in corneal transplantation.
Animals↗