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Biomedical subjects

H Faust

Publications and source records attributed to H Faust.

At least 19 recordsLinked to original sources

Brain-derived-neurotrophic-factor (BDNF) stress response in rats bred for learned helplessness.

Stress-induced elevation of glucocorticoids is accompanied by structural changes and neuronal damage in certain brain areas. This includes reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus which can be prevented by chronic electroconvulsive seizures and antidepressant drug treatment. In the last years we have bred two strains of rats, one which reacts with congenital helplessness to stress (cLH), and one which congenitally does not acquire helplessness when stressed (cNLH). After being selectively bred for more than 40 generations these strains have lost their behavioural plasticity including their sensitivity to antidepressant treatment. We show here that in cLH rats, acute immobilization stress does not induce a reduction of BDNF expression in the hippocampus which is observed in Sprague--Dawley and cNLH rats. All animals tested exhibited elevated corticosterone levels when stressed, an indication, that in cLH rats regulation of BDNF expression in the hippocampal formation is uncoupled from corticosterone increase induced through stress. This may explain the lack of adaptive responses in this strain.

Animals↗

Administration of DAB389IL-2 to patients with recalcitrant psoriasis: a double-blind, phase II multicenter trial.

BACKGROUND: Current therapies for recalcitrant psoriasis focus on immunoregulation and targeting of activated T-lymphocytes rather than keratinocytes. Previous studies with low doses of the lymphocyte-selective fusion protein DAB389IL-2 have shown benefit to patients with psoriasis. OBJECTIVE: We examined the safety and efficacy of DAB389IL-2 in 41 volunteers receiving more frequent and higher doses than in a previous trial. METHODS: Patients were randomized to receive either placebo or 5, 10, or 15 microg/kg daily of DAB389IL-2 intravenously for 3 consecutive days each week for 4 consecutive weeks with a subsequent 4-week observation period. RESULTS: Of the placebo group, 17% (2 of 12) exhibited at least 50% improvement from baseline Psoriasis Area and Severity Index scores at the end of the study, whereas 24% of all treated patients (7 of 29) showed the same improvement. Overall, 3 of 12 (25%) patients given placebo as opposed to 12 of 29 (41%) patients treated with DAB389IL-2 improved to this same extent at some point during the study. The rate of improvement for treated patients was significantly greater than for placebo patients (p = 0.04; repeated measures ANOVA). Among treated patients, decreases in Psoriasis Area and Severity Index scores were paralleled by changes in the Physician's Global Assessment and the Dermatology Life Quality Index. Treatment in ten patients was discontinued because of adverse events. Flu-like symptoms were the most common with severity increasing at the two higher doses. Only one serious adverse event was reported. This occurred in a patient receiving 5 microg/kg daily who experienced vasospasm and a coagulopathy resulting in arterial thrombosis. CONCLUSION: Our findings are consistent with the potential antipsoriatic activity of DAB389IL-2 demonstrated in an earlier study. However, DAB389IL-2 was less well tolerated at this dosing regimen, particularly at the highest dose, and it was too toxic at these doses and schedules to be considered in the routine treatment of psoriasis.

Adult↗

Autoantibodies to C-reactive protein (CRP) and other acute-phase proteins in systemic autoimmune diseases.

Autoantibodies to CRP were reported previously in patients suffering from toxic oil syndrome. This syndrome resembles autoimmune diseases such as systemic lupus erythematosus (SLE) or systemic scleroderma. We therefore examined the prevalence of antibodies to CRP and other acute-phase proteins in autoimmune diseases, including SLE, subacute cutaneous lupus erythematosus (SCLE), systemic scleroderma (SSc), and primary biliary cirrhosis (PBC), as well as in bone marrow transplantation-induced chronic graft-versus-host disease and eosinophilia-myalgia syndrome. IgG antibodies to CRP were found in 78% of SLE and in 30% of SCLE patients, while 16% of patients with PBC were positive. In up to 45% of patients with SSc predominantly IgG antibodies to ceruloplasmin were detectable. Lack of systemic involvement as in discoid lupus erythematosus and localized scleroderma (morphea) correlated with low or absent antibody formation. However, no correlation was found between anti-acute-phase protein antibodies with liver disease or other organ involvement. Adsorption studies revealed that non-native epitopes on the CRP molecule, termed modified CRP, are the main target of antibodies. Chronic inflammatory tissue injury in systemic autoimmune disease might increase the presentation of cryptic epitopes of CRP to the threshold required for T cell activation.

Acute-Phase Proteins↗

Microcirculation in hyperglycemic patients with IDDM without diabetic complications--effect of low-dose angiotensin-converting enzyme inhibition.

In patients with insulin-dependent diabetes mellitus (IDDM) angiotensin-converting enzyme inhibitors (ACEI) have been demonstrated to have beneficial effects in the secondary prevention of microvascular complications. There are only few data available regarding the effect of ACEI on microcirculation in patients with IDDM without any microvascular complications. In addition, there is little knowledge about ACEI action during acute hyperglycemia. In a pilot study nine patients with IDDM without any clinical signs of diabetic complications (5 females, 4 males, aged 33.3 +/- 1.0 years, duration of diabetes 11.4 +/- 3.0 years, HbA1 7.2 +/- 0.2% [normal range 4.8-7.4%], BMI 21.4 +/- 0.5 [kg/m2]) received 1.25 mg of the ACEI ramipril (Delix, Hoechst Marion Roussel, Frankfurt) over 4 weeks. Nine healthy volunteers (4 females, 5 males, age 27.4 +/- 1.1 years, HbA1 5.9 +/- 0.2% (p < 0.01 vs patients), BMI 22.2 +/- 0.9 [kg/m2]) served as controls. Using nailfold capillaroscopy we determined capillary blood cell velocity (CapiFlow, Lawrenz Electronics, Sulzbach, Germany) before and during post-occlusive hyperemia (200 mmHg for 3 minutes) as a provocative test. Before and after treatment patients were studied during hyperglycemia (blood glucose 250-350 mg/dl). Treatment with low-dose ramipril resulted in a significant decrease in the time to peak capillary blood cell velocity during post-occlusive hyperemia (17.8 +/- 7.7 vs 57.4 +/- 12.8 s, p < 0.01) in hyperglycemic patients. This effect was absent in healthy volunteers. Hemodynamic and metabolic parameters remained unchanged throughout the study in both groups. These data demonstrate that low-dose therapy with the ACEI ramipril is able to improve microcirculation in hyperglycemic patients with type 1 diabetes mellitus also before microvascular complications are evident. Prospective studies are necessary to evaluate whether this effect might be clinically relevant in the primary prevention of diabetic microangiopathy.

Adult↗

Evaluation of hepatitis C virus envelope proteins expressed in E. coli and insect cells for use as tools for antibody screening.

BACKGROUND/METHODS: The two envelope proteins of hepatitis C virus, E1 and E2, were expressed in E. coli and, as secretory proteins, in Sf9 insect cells using recombinant baculoviruses. Co-infection of insect cells with E1 and E2-recombinant baculoviruses was performed, which has been shown to result in formation of E1-E2 dimers. All envelope proteins were purified by Ni2+-NTA chromatography and used for screening of serum samples in a HCV EIA assay. Serum samples of normal blood donors, chronically HCV-infected patients, a mixed titer panel and several seroconversion panels were screened and compared to test results with Cobas Core Anti-HCV EIA. RESULTS: Screening of the sera of chronically HCV-infected patients (100% positive in Cobas Core Anti-HCV EIA) revealed 10-40% anti-E1 positive sera using different Sf9-expressed, glycosylated proteins and 93% using E. coli-expressed, non-glycosylated E1 protein. When the same sera were tested with different E2 proteins expressed in Sf9 cells and in E. coli, about 70-73% showed anti-E2 reactivity. When the proteins from Sf9 cells co-infected with E1- and E2-recombinant baculoviruses were tested, 70-80% of the same sera showed anti-envelope reactivity. CONCLUSIONS: Testing of these patient antisera, and those from the well-characterized mixed titer panel BBI-PHV203, showed that recombinant E1 expressed in E. coli and co-expressed E1 and E2 proteins from Sf9 cells could be used as additional tools for anti-HCV antibody screening.

Animals↗

Growth of molluscum contagiosum virus in a human foreskin xenograft model.

Molluscum contagiosum virus (MCV) is a common pathogen causing a troublesome skin condition in many immunocompetent individuals and a widespread, disfiguring affliction in many patients with AIDS. We have successfully infected human foreskin fragments with a patient-derived isolate of MCV. This was demonstrated by exposing the foreskin pieces to a patient lesion extract and implanting the tissue under the renal capsule of athymic mice. Light and electron microscopic examination of infected implants showed the presence of cytoplasmic inclusions containing typical poxvirus particles within 2-3 weeks of implantation. Replication of MCV was established by demonstrating that viable virus was required to produce the cytopathologic effects, and viral DNA replication was demonstrated by incorporation of bromodeoxyuridine into cytoplasmic inclusions. Four additional patient extracts (representing both described MCV types) were also used to successfully infect foreskin implants. A limited number of attempts to pass virus from one infected implant to another were not successful. This system is the most rapid and reproducible for growing MCV that has been reported to date.

Animals↗

Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.

Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.

Administration, Cutaneous↗

Specificity of antinuclear antibodies in scleroderma-like chronic graft-versus-host disease: clinical correlation and histocompatibility locus antigen association.

Chronic graft-versus-host disease after bone marrow transplantation presents, in a few cases, as mild to severe scleroderma-like changes. Patients with chronic graft-versus-host disease with and without sclerodermatous skin changes were analysed for antinuclear autoantibodies (ANA) and antinucleolar autoantibodies (ANoA) and the results correlated with disease symptoms and histocompatibility locus antigen (HLA) pattern. Nineteen patients with chronic graft-versus-host disease and scleroderma-like skin changes, 18 with chronic graft-versus-host disease without scleroderma, and 17 controls on immunosuppressive treatment were screened for ANA and ANoA using enzyme-linked immunosorbent assay, immunodiffusion and immunoblot techniques. Four patients with severe scleroderma had antibodies to topoisomerase I, two had antibodies against PM-Scl, both characteristic serological findings in idiopathic systemic scleroderma. One patient had La/SSB antibodies and, in three cases, antibodies to the nucleolar antigen C23 (nucleolin) could be identified. A possible correlation between antinucleolin antibodies and disease activity was observed. HLA-A1, -B1, and -B2 were found significantly more often in patients with scleroderma-like symptoms in comparison to patients without scleroderma-like symptoms. Chronic graft-versus-host disease with scleroderma-like manifestations can be associated with the occurrence of ANA specific for idiopathic scleroderma. The development of scleroderma after bone marrow transplantation might have a HLA-linked genetic background.

Antibodies, Antinuclear↗

[Laparoscopic cholecystectomy as standard intervention in symptomatic cholecystolithiasis. Experiences with 1,277 patients].

As a result of 1277 laparoscopic cholecystectomies, which were performed as a standard procedure in uncomplicated and complicated symptomatic cholecystolithiasis, the complication-rates of conventional cholecystectomy and laparoscopic cholecystectomy are compared. It can be demonstrated, that the adoption of the principles of conventional cholecystectomy into laparoscopic technique and a careful preparation can reach the same high level of safety as the so called "gold-standard".

Adolescent↗

Sympathetic skin response abnormalities in amyotrophic lateral sclerosis.

The sympathetic skin response (SSR) was evaluated in 25 patients with amyotrophic lateral sclerosis (ALS) to assess for involvement of the autonomic nervous system. Twenty-two age-matched normals and 6 patients with muscular dystrophy served as controls. The SSR was intact in all normal volunteers and all patients with muscular dystrophy. The mean SSR latency in the ALS patients was prolonged compared to that of normals (2.29 +/- 0.28 versus 2.13 +/- 0.16 s, P < 0.05). The SSR was absent in one or both legs of 10 ALS patients (40%). Absence or abnormal latency of SSR in patients with ALS without clinical findings of autonomic failure suggests involvement of the autonomic nervous system in addition to the motor system.

Adult↗

[Sympathetic skin response--physiologic principles, normal values and clinical use].

Sympathetic skin reflex (SSR) was evaluated in the lower extremities of 60 normal volunteers aged 17 to 72 (mean age 38 +/- 16 years, 28 females, 32 males). SSR was obtainable in all volunteers and most often consisted of a biphasic wave with initial negative deflection. Mean latency was 2.16 +/- 0.20 s. Mean variation in a second repetitive measurement was 0.21 +/- 0.14 s. The SSR was not age- or sex dependent. There was a weak positive correlation of the SSR with the height of the volunteers (r = 0.271; p = 0.037). SSR was investigated in 39 patients with polyneuropathy (age 59 +/- 18). SSR was pathological in 51% on one or both legs. There was no correlation of the SSR to the aetiology nor to the type of lesion (axonal versus demyelinating polyneuropathy) nor to clinical symptoms. The applicability of the SSR is reviewed from the literature regarding polyneuropathy, erectile dysfunction, central degenerative diseases, multiple sclerosis, sympathetic reflex dystrophies, spinal and peripheral nerve lesions. SSR is briefly compared to alternative methods. SSR appears to be a reasonable method to describe a small section of the autonomic nervous system (sympathetic sudomotor function) and to calculate group differences. There appears to be no close correlation to any of the autonomic disturbances in individual patients.

Adolescent↗