Mechanisms of inflammation: symposium of the Sonderforschungsbereich (SFB 244), Hannover, Germany, 4-5 June 1998.
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Animals↗
Biomedical subjects
R E Schmidt
Publications and source records attributed to R E Schmidt.
MRI of focal cortical dysplasia.
We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain.
Cerebral Cortex↗
The IgG Fc receptor family.
IgG immune complexes are of central importance in the humoral immune system and strongly implicated in the pathogenesis of hematologic and rheumatic autoimmune disorders. Cross-linking of receptors for the Fc domain of IgG antibodies (FcgammaRs) triggers a wide variety of effector functions including phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators, as well as immune complex clearance and regulation of antibody production. In this way, FcgammaR provide an essential feedback between the humoral and cellular immune response. In the past, significant advances have been made in the molecular dissection of FcgammaR function using cellular transfection systems. Current approaches designed to target and change individual FcgammaR genes in mice have given further insight into their specific contributions to systemic processes, also indicating them to be important immunoregulatory receptors involved in various disease states of allergy, autoimmunity, and inflammation. Future work on targeting FcgammaR binding sites in combination with humanized FcgammaR mouse models will lead to novel therapeutic strategies in the treatment of IgG-mediated human disease in which FcgammaR activation plays an integral part.
Anemia, Hemolytic↗
Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus. SLE Study Group.
Previously it has been suggested that the presence of antibodies against dsDNA of the IgA class may define a subset of systemic lupus erythematosus (SLE) patients suffering from nephritis and arthritis. Therefore, these autoantibodies were measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients with SLE, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found to be associated with parameters of disease activity such as elevated erythrocyte sedimentation rate and consumption of complement component C3, and the clinical parameters vasculitis, with necrosis and erythema, but not with nephritis and arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients, and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic parameter in patients with SLE.
Antibodies, Antinuclear↗
IgM anti-dsDNA antibodies in systemic lupus erythematosus: negative association with nephritis. SLE Study Group.
Antibodies against dsDNA of the IgM class were measured in sera of 352 patients with systemic lupus erythematosus, 81 blood donors and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgM anti-dsDNA antibodies were found in 52.3% of the sera from patients with systemic lupus erythematosus, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 37 laboratory parameters was calculated. There was a highly significant negative correlation between IgM anti-dsDNA antibodies and nephritis as well as all the laboratory parameters indicating renal disease (elevated serum creatinine concentration, proteinuria, erythrocyte casts in the urine). IgM anti-dsDNA antibodies indicate protection of lupus patients against the development of lupus nephritis. Further experiments will show whether application of IgM anti-dsDNA antibodies is effective in treating lupus nephritis.
Antibodies, Antinuclear↗
Effects of beta-adrenoceptor-blockade on stress-induced adrenocorticotrophin release in humans.
We investigated the mechanisms of stress-induced alterations in adrenocorticotrophin (ACTH) release. Tandem parachutists received either a placebo or the beta-adrenoceptor antagonist propranolol prior to a first time parachute jump. Blood samples were drawn 4 h before, immediately after, and 1 h after the jump. Cortisol and catecholamine concentrations displayed a significant stress-induced increase in both groups. The ACTH plasma concentrations significantly increased in the placebo and the propranolol group, with significantly more pronounced changes in the propranolol-treated subjects compared to the placebo group. These data demonstrated a stress-induced increase of ACTH plasma concentrations in humans that was enhanced by beta-blockade.
Adrenergic beta-Antagonists↗
Modulation of innate immune functions by intracerebroventricularly applied neuropeptide Y: dose and time dependent effects.
Centrally applied neuropeptide Y (NPY) interacts with the autonomic nervous system and the hypothalamo-pituitary-adrenal (HPA) axis activity. Since these physiological systems have been shown to modulate innate immune functions, the effects of intracerebroventricular (i.c.v.) NPY administration on leukocyte subsets in the blood, spleen and intravascular pool of the lung, blood granulocyte chemiluminescence response, and splenic natural killer (NK) cell-mediated lysis were studied in Lewis rats. Concentration-dependent NPY effects were tested at 15 min and 24 h post i.c.v. injection at dosages of 10(-6) M, 10(-9) M, and 10(-12) M. Time dependent effects were investigated at 15 min, 1 h and 24 h after i.c.v. administration of 10(-9) M NPY. Compared to saline controls, an increased number of granulocytes and NK cells in the blood, associated with a decreased granulocyte function and NK cytotoxicity was observed 15 min following NPY infusion. This initial immunosuppression was followed by long lasting stimulatory effects of NPY on the functional capacity of both cell populations when tested at 1 h and 24 h. The dosage of i.c.v. 10(-6) M NPY produced no changes, whilst 10(-9) M produced maximal, and 10(-12) M still significant effects. Results provide evidence that centrally applied NPY influences innate immunity in a dose and time dependent fashion. Cell mobilization from the vascular marginal pool is likely to be an underlying mechanism for the initial immunosuppression.
Animals↗
Cyclosporine A affects open field behavior in DA rats.
Since the introduction of Cyclosporine A (CsA) for immunosuppression in solid-organ transplantation, the rate of allograft rejection has decreased substantially. However, treatment with CsA induces neuropsychological complications in patients, including affective disorders such as anxiety, disorientation, depression, aggression, paranoia, and apathy. These CsA-induced affective side effects cannot be extensively studied in humans. Therefore, this study investigates the effects of intraperitoneal CsA (20 mg/kg) injections on the open-field behavior of male Dark Agouti (DA) rats 1, 6, 12, and 23 h after drug administration on 3 consecutive days. CsA induced an increase in emotionality in DA rats 6 h after injection, reflected by decreased ambulatory activity in the open field and increased defecation. In addition, a decrease in rearing activity was observed 12 h after CsA administration. These behavioral alterations are discussed in the view of changes in cytokine profiles induced by CsA.
Animals↗
Primary combined immunodeficiency, growth retardation, and disturbed sexual development: a novel syndrome of congenital impairment of the cellular immune system and the endocrine system.
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Abnormalities, Multiple↗
GB virus C/hepatitis G virus infection: a favorable prognostic factor in human immunodeficiency virus-infected patients?
To investigate a possible influence of GB virus C (GBV-C) in immunocompromised patients, the prevalences of GBV-C RNA and anti-E2 antibody in 197 human immunodeficiency virus (HIV)-infected patients and in 120 control blood donors were studied. GBV-C RNA was detected in 33 of 197 HIV-infected patients (16.8%) compared with 1 in 120 blood donors (0.8%) (P < .001). Previous exposure to GBV-C (anti-E2 antibody-positive) was shown in 56.8% of HIV patients and in 9% of blood donors. GBV-C viremia was not associated with hepatitis. Despite approximately equal duration of HIV infection in all subgroups, the CD4 cell counts were significantly higher in GBV-C-viremic patients (344 cells/microL) compared with exposed (259 cells/microL) and unexposed (170 cells/microL) patients (P = .017 and P < .001). Furthermore, Kaplan-Meier analysis demonstrated significantly better cumulative survival in GBV-C RNA-positive HIV-infected patients, suggesting that GBV-C might be a favorable prognostic factor in HIV disease.
AIDS-Related Opportunistic Infections↗
Neurotrophin sensitivity of prevertebral and paravertebral rat sympathetic autonomic ganglia.
Prevertebral and paravertebral sympathetic autonomic ganglia respond differently to a large number of experimental and clinical insults. The selective involvement of subpopulations of sympathetic neurons may reflect differences in their response to neurotrophic substances. To test this hypothesis, we investigated the response of prevertebral and paravertebral rat sympathetic ganglia to selected neurotrophic substances in vivo and in vitro and identified the ganglionic distribution of neurons expressing high affinity neurotrophin receptor mRNAs. Dissociated cultures of embryonic prevertebral and paravertebral ganglionic neurons showed comparable responses to NGF deprivation and only small differences in their response to rescue with other trophic substances. In situ hybridization studies of adult rat sympathetic ganglia using probes specific for the high-affinity neurotrophin receptor transcripts trks A, B, and C demonstrated that neurons in both prevertebral and paravertebral sympathetic ganglia express predominantly trkA receptors in vivo. In addition, increased tyrosine hydroxylase (TOH) activity was induced only by doses of neurotrophic substances that activate trkA and showed only small differences between neonatal prevertebral and paravertebral ganglia. Although small differences in the sensitivity of pre- and paravertebral sympathetic neurons to various neurotrophins have been identified in our studies, they are unlikely, in isolation, to explain major differences in the sensitivity of these ganglia to neuropathologic processes.
Aging↗
Effect of sorbitol dehydrogenase inhibition on experimental diabetic autonomic neuropathy.
The polyol pathway and its dependent biochemical pathways are thought to play a role in the pathogenesis of diabetic neuropathy. We have developed an animal model of diabetic autonomic neuropathy characterized by neuroaxonal dystrophy involving ileal mesenteric nerves and prevertebral sympathetic superior mesenteric ganglia (SMG) in chronic streptozocin-diabetic rats. Our previous studies have shown a salutary effect of aldose reductase inhibitors on experimental autonomic neuropathy, suggesting a role for the polyol pathway in its pathogenesis. In the current studies we have examined the effect of the sorbitol dehydrogenase inhibitor (SDI) CP-166,572, which interrupts the conversion of sorbitol to fructose (and reactions dependent on the second step of the polyol pathway) resulting in markedly increased levels of sorbitol in peripheral nerve. Fourteen weeks of treatment with CP-166,572 resulted in a dramatically increased frequency of neuroaxonal dystrophy in ileal mesenteric nerves and SMG. Although lesions developed prematurely and in greater numbers in SDI-treated diabetics than untreated diabetics did, their anatomic distribution and ultrastructural appearance were identical to that previously reported in long-term untreated diabetics. CP-166,572 treatment did not produce neuroaxonal dystrophy in control animals despite the fact that sciatic nerve sorbitol levels were markedly increased, reaching the same levels as untreated diabetic animals. Treatment of diabetic rats for 14 weeks with the aldose reductase inhibitor zopolrestat resulted in a significant decrease in the frequency of neuroaxonal dystrophy compared with untreated diabetics.
Animals↗
Stress-induced endocrine and immunological changes in psoriasis patients and healthy controls. A preliminary study.
BACKGROUND: Clinical observations suggest that psychological stress can induce exacerbation of psoriasis. It is hypothesized that these stress effects on the course and outcome of psoriasis are caused by neuroendocrine modulation of immune functions. Therefore we investigated the cardiovascular, endocrine and immunological response to a laboratory stressor in psoriasis patients and healthy controls. METHODS: Untreated (n = 7) and PUVA-treated (n = 4) psoriatics and healthy controls (n = 7) were exposed to a brief laboratory stressor (public speaking and mental arithmetic). Heart rate and blood pressure, catecholamine, cortisol, and DHEA plasma concentration, as well as distribution of T and NK lymphocytes were analyzed before, immediately after and 1 h after stress exposure. RESULTS: Heart rate and blood pressure increased in all three groups during stress exposure with the most pronounced changes in PUVA-treated patients. Psoriasis patients displayed higher adrenaline values but diminished cortisol and DHEA plasma concentrations compared to controls. NK cell numbers (CD16+, CD56+), but not T lymphocyte subsets, increased immediately after stress exposure in untreated patients and controls. This effect was significantly diminished in PUVA-treated patients. CONCLUSIONS: The data of this pilot study indicate an enhanced stress-induced autonomic response and diminished pituitary-adrenal activity in psoriasis patients. PUVA treatment seems to interfere with the cardiovascular and NK cell response to acute psychological stress. Future studies will analyze the stress-induced neuroimmunological mechanisms in psoriatics in more detail.
Adult↗
[Definition of an immunologic deficiency state].
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Diagnosis, Differential↗
Axonal cytoskeletal pathology in aged and diabetic human sympathetic autonomic ganglia.
Prevertebral sympathetic ganglia develop markedly enlarged argyrophilic neurites as a function of age, gender and diabetes. Immunolocalization studies demonstrate their preferential labeling with antisera to highly phosphorylated 200 kDa neurofilament (NF-H) epitopes, NPY, peripherin and synapsin I, but not to hypophosphorylated NF-M and NF-H or MAP-2. The immunophenotype of dystrophic neurites in conjunction with the results of histochemical and ultrastructural studies are consistent with the terminal axonal and/or synaptic origin of neuritic dystrophy in the sympathetic ganglia of aged and diabetic human subjects.
Adolescent↗
[Rhabdomyolysis in antiretroviral therapy with Lamivudin].
HISTORY AND CLINICAL FINDINGS: Six weeks after antiretroviral treatment with lamivudin (a nucleoside analogue) had been started (300 mg daily) in a 31-year-old man with AIDS developed pain and weakness in his muscles. On admission he had myalgia on pressure and movement as well as weakness of the entire body musculature, especially of the arms. The history and findings suggested bacterial or HIV-associated myositis. INVESTIGATIONS: Creatinekinase activity (4442 U/l) and myoglobin concentration (3250 micrograms/l) were greatly increased, while creatine (96 mumol/l) and C-reactive protein (22 mg/l) levels were only slightly raised. Serology was negative for acute and bacterial infections and autoimmune myositis. Magnetic resonance imaging and biopsy indicated marked rhabdomyolysis without myositis. DIAGNOSIS, TREATMENT AND COURSE: After excluding other causes, lamivudin and other drugs were discontinued, drug-induced rhabdomyolysis being suspected. This and the administration of prednisolone (100 mg daily) improved the symptoms. Creatinekinase activity and myoglobin level became normal within 14 days. On renewed administration of lamivudin creatinekinase and myoglobin concentrations in serum doubled to 180 U/l and 110 micrograms/l, respectively. Cessation of medication once again restored them to normal. CONCLUSION: Rhabdomyolysis is a serious but rare side effect of lamivudin treatment. Appropriate biochemical monitoring should therefore be undertaken when it is used in the treatment of HIV-positive patients.
Acquired Immunodeficiency Syndrome↗
Endocrine testicular function in HIV-infected outpatients.
We investigated endocrine testicular function in 100 HIV-infected men who were grouped according to the CDC criteria. Progression of the disease was associated with a 27% decrease in plasma oestradiol, which was the only parameter that was weakly correlated with CD4 cell count (r = 0.312, p <0.05). Individual data showed a decreased plasma concentration of total and free testosterone in 35% and 26% of the subjects, respectively, but we could not demonstrate an increased frequency of hypogonadism going along with a progression of the stage of disease. There was no significant correlation between androgen, SHBG or FSH levels and duration of HIV-infection, BMI or CD4 cell count. Hypergonadotropic hypogonadism was associated with an euthyroid sick state in a 15% subgroup of patients reporting a decrease in libido. Plasma T3 was significantly correlated with testosterone (r = 0.419, p <0.01) and mean plasma T3 was significantly decreased in 8 subjects suffering from erectile impotence. Thus, hypogonadism occurs frequently in HIV-infected outpatients. Like euthyroid sickness it does not seem to be a predictor for progression of the disease but an indicator of actual state of health.
Adult↗
Peripheral nerve regeneration through silicone chambers in streptozocin-induced diabetic rats.
The silicone chamber model was used to evaluate peripheral nerve regeneration (PNR) in streptozocin (STZ)-induced diabetic rats. Diabetic and control animals underwent sciatic nerve transection and silicone chamber implantation establishing gaps of various lengths between the transected nerve ends. In animals with 5 and 10 mm gaps, diabetes was induced in experimental rats 1 week before surgery, and the animals were sacrificed 3 weeks after surgery. In animals with 8 mm gaps, diabetes induction occurred 3 days after surgery, and they were sacrificed after 7 weeks. Diabetic rats with 10 mm gaps demonstrated an impaired ability to form bridging cables, the initial step of regeneration through chambers. Morphometric studies of bridging cables between transected nerve ends demonstrated a significant reduction in the mean endoneurial area in diabetic animals with 5 and 8 mm gaps compared to controls. The number of regenerated myelinated axons in the chamber was significantly decreased in diabetic rats with 8 and 10 mm gaps. The mean myelinated fiber area in the regenerated cables of the diabetic group was significantly decreased with 5 mm gaps and significantly increased with 8 mm gaps compared to controls. Size-frequency histograms of regenerated myelinated fiber areas suggest a delay in the maturation of small caliber axons. Schwann cell migration across 5 mm gaps was examined with S-100 immunohistochemistry. The total distance of Schwann cell migration into cables from both proximal and distal ends was significantly reduced in diabetic animals. Characterization of PNR across gaps through silicone chambers in diabetic rats showed impairment in multiple aspects of the regenerative process, including cable formation, Schwann cell migration, and axonal regeneration.
Animals↗