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Biomedical subjects

E Sommer

Publications and source records attributed to E Sommer.

At least 19 recordsLinked to original sources

Immunomodulatory effect of shikonin derivatives isolated from Lithospermum canescens on cellular and humoral immunity in Balb/c mice.

The immunomodulatory activity of acetylshikonin (ACS) and isobutyrylshikonin (IBS) was studied in female and male inbred Balb/c mice, and in F1 hybrids (Balb/c x C3H). ACS and IBS were isolated from Lithospermum canescens Lehm. (Boraginaceae) roots. Splenocytes from mice fed 40 microg of ACS had higher proliferative potential in cultures with PHA than corresponding controls and also higher migratory in vitro activity than splenocytes obtained from control animals. ACS at a 40 microg daily dose stimulated G-v-H reaction but inhibited it at a 200 microg dose. IBS at a 40 microg dose significantly increased humoral response.

Adjuvants, Immunologic↗

Multiple effects of theobromine on fetus development and postnatal status of the immune system.

Caffeine and its active derivative, theobromine, are probably the most frequently ingested pharmacologically active substances. Considering their uninhibited transport via the placental barrier as well as immature enzymatic activities and metabolic pathways in embryos and infants resulting in the longer half-life of methyloxanthines and their accumulation, unrestrained uptake of these substances might result in noticeably more pronounced biological effects during pregnancy and the postnatal period. Our previous studies have shown that methyloxanthines are significant inhibitors of angiogenic growth factors production and angiogenesis itself. We have hypothesized that increased uptake of these substances might affect embryonal angiogenesis and, later in the postnatal period, maturation and functional activity of the offspring's immune system. The study was performed on 2-month-old Balb/c mice fed theobromine 2 or 6 mg/day during pregnancy and lactation. On day 18 of pregnancy the number and weight of embryos were assessed as was their tissue angiogenic activity, using the cutaneous angiogenesis assay. In the group of 4-week-old sucklings, body and spleen were weighed together with the trunk, and tail and limb length were measured. Six weeks after birth the splenocytes' mitogen-induced activity and their ability to induce graft-versus-host reaction as well as the humoral response to SRBC antigen were evaluated. Content of theobromine in the embryos' tissue was estimated by high liquid performance chromatography (HPLC). Theobromine feeding resulted in significant inhibition of embryo growth as assessed by their weight and decreased angiogenic activity of their tissue. The theobromine content in embryo tissue from treated groups was higher than in the controls, and the difference was close to significant. In the postnatal period the discrepancies in the treated 4-week-old group's development were also observed in the significantly shorter limbs in comparison to the controls. Moreover in the treated group of 6-week-old sucklings, considerable variations in the immune system's functional activity were registered as far as cellular and immune response were concerned. Respectively, the splenocytes' mitogen-induced proliferative activity was significantly suppressed while the graft-versus-host reaction was up-regulated, and the serum antibodies titer was elevated in correspondence to the observed spleen enlargement. We concluded that a theobromine-enriched diet affects progeny development in both prenatal and postnatal periods. Consequently, particular attention should be paid to the reduction of theobromine consumption, and most probably that of other methyloxanthines, during pregnancy and lactation.

Angiogenesis Inhibitors↗

The influence of Eleuterococcus senticosus on cellular and humoral immunological response of mice.

The influence of Eleuterococcus senticosus on cellular and humoral immune response was evaluated. The experiments were performed on animal models (Balb/c mice and F1 crossbreeds Balb/cxC3H). It was shown that Eleuterococcus has immunomodulatory properties. This substance enhanced the cellular response of the mouse immunological system (chemokinetic activity of mice spleen cells, GvH reaction). A stimulatory effect of Eleuterococcus on the humoral response (antibody production) was also observed. Eleuterococcus did not augment the angiogenic activity of human renal carcinoma cells.

Adjuvants, Immunologic↗

Inhibitory effect of Greenland shark liver oil combined with squalen and arctic birch ashes on angiogenesis and L-1 sarcoma growth in Balb/c mice.

Sharks have been claimed to be resistant to cancer and oil from their livers have been used in Scandinavian folk medicine as anti-tumor drug. Shark liver oil contains 40% or more of squalene. Fish liver oil is also rich in squalene and polyunsaturated n-3 fatty acids. The aim of this work was to determine the anti-angiogenic and anti-tumor effects of these substances, together with another Scandinavian traditional remedy--arctic birch ashes--in Balb/c mice after transplantation of syngeneic L-1 sarcoma. All substances tested, alone or in combinations, significantly diminished cutaneous angiogenesis induced by tumor cells, and tumor growth.

Animals↗

Chocolate feeding of pregnant mice influences length of limbs of their progeny.

UNLABELLED: We previously reported the inhibitory effect of various methyloxantines and phenolic compounds on tumor-induced angiogenesis and the production of angiogenic growth factors. The aim of the present work was to evaluate the effect of chocolate (CH), food containing substantial amounts of methyloxantine theobromine and polyphenols (mainly catechins), given to mice during pregnancy and the lactation period, on weight of organs, length of limbs, and bone vascular endothelial growth factor (VEGF) concentration (tested by ELISA), in 4-week old offspring. The study was performed on 2-month old Balb/c mice fed during pregnancy and lactation 400 mg of CH daily. Content of polyphenols (catechines) and theobromine in the chocolate was estimated by high liquid perforance chromatography (HPLC). Concentration of VEGF was tested by ELISA. Feeding pregnant mice chocolate produced the following effects: decrease of relative length of limbs and thigh bones in 4-week old progeny and decrease in VEGF content of offspring femoral bones. CONCLUSION: attention should be paid to possible unwanted effects of catechine- and methyloxantine-rich food and beverages during pregnancy and lactation. 200 mg of chocolate per mouse corresponds to 100 g per person.

Administration, Oral↗

Angiotensin-converting enzyme activity and angiomodulatory effects of sera in patients with diabetic retinopathy.

Aberrant neovascularization plays a crucial role in ocular complications in diabetic patients. Sera from these patients contain high levels of angiostimulatory factors, the most important of which is vascular endothelial growth factor (VEGF). Many authors have described elevation of angiotensin-converting enzyme (ACE) activity in the sera of diabetic patients. It is important to determine the possible relationship between these two phenomena. We studied ACE serum activity and VEGF concentrations in patients with type 1 and type 2 diabetes and retinopathy We also investigated the effect of their sera on cutaneous angiogenesis induced in mice by grafting healthy human mononuclear blood leukocytes. We found a negative correlation between the angiostimulatory effect and ACE level in the sera of patients with type 1 diabetes and no correlation between these two parameters in patients with type 2 diabetes. VEGF concentrations were lower and ACE activity was significantly higher in the sera of patients with type 1 diabetes than in the sera of those with type 2 diabetes.

Adult↗

Thymus and lymph node cell CD4(+) and CD8(+) marker expression and their angiogenic activity of offspring of salbutamol-treated pregnant C3H mice.

Salbutamol, beta(2)-adrenoceptor agonist is a first choice drug in preterm delivery treatment. The aim of the present study was to determine whether salbutamol can cause any alterations in neonatal immune systems and therefore should be considered in newborn care. The experiments were performed on 4-5- and 6-7-week-old female and male offspring of salbutamol-treated C3H inbred mice. Thymus and lymph node weight, cellularity and lymphatic organs, lymphocytes phenotypes and their angiogenic activity were evaluated. We observed lower thymus weight in 6-7-week-old progeny of salbutamol-treated mothers and in the same time lower thymus cell number in both age groups. Lower lymph node weight was developed in older progeny while cellularity was diminished both in 4-5- and 6-7-week-old offspring of salbutamol-treated mothers. We have not detected any changes in percentage of CD4, CD8, CD3 and CD4CD8 positive lymphocytes in progeny of salbutamol-treated mothers. As far as lymph node lymphocytes phenotype is considered we showed in both age groups lowering of CD4 and CD3 positive cells in experimental groups. In the LIA test (lymphocyte-induced angiogenesis) we showed lower lymph node cell angiogenic activity of salbutamol-treated mothers' progeny in both age groups. In the case of thymus lymphocytes we have not observed any alterations in their angiogenic activity. The differences in histological examination of thymus and lymph nodes were not detected in experimental and control groups.

Adrenergic beta-Agonists↗

Basis for nebulized antibiotics: droplet characterization and in vitro antimicrobial activity versus Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

The aims of this study were to (1) quantify the particle size characteristics of several antibiotics considered suitable for aerosol therapy after aerosolization with the PARI IS/2 nebulizer (Pari GmbH, Sarnberg, Germany) and (2) determine the degree to which in vitro antimicrobial activity of these antibiotics is maintained after nebulization. The aerosolized drugs were tobramycin sulfate, streptomycin, and imipenem, with saline solution as the control. Mean mass aerodynamic diameter of the nebulized drugs was 3.25 microns for tobramycin, 2.26 microns for imipenem, and 2.38 microns for streptomycin. In vitro tests showed that tobramycin and imipenem were unaltered in their bacteriostatic activity against strains of Escherichia coli (American Type Culture Collection [ATCC] 25922) and Staphylococcus aureus (ATCC 29213) as well as against Pseudomonas aeruginosa (ATCC 27853) with minimal inhibitory concentration (MIC) values less than 0.3 microgram/mL. Nebulized streptomycin showed significantly higher MIC values against P. aeruginosa (ATCC 27853). These results suggest that tobramycin and imipenem may be prescribed as an aerosol generated by jet nebulization (PARI IS/2) to treat S. aureus, E. coli, and P. aeruginosa infections without any risk of altering the drugs minimum bacteriostatic activity by the nebulization process. Aerosolization of streptomycin with this nebulizer may not be as effective against P. aeruginosa because it seems to alter the bacteriostatic activity.

Aerosols↗

Absence of imprinting of HLA class Ia genes leads to co-expression of biparental alleles on term human trophoblast cells upon IFN-gamma induction.

Human trophoblast cells have developed various efficient regulatory mechanisms to prevent cell surface expression of the classical HLA-A, -B, and (but not always) -C class I molecules. This allows them to escape maternal alloimmune attack during pregnancy. However, recent results have demonstrated that such a lack of expression could be reversed in villous cytotrophoblast cells purified from term placenta by in vitro IFN-gamma treatment. In this context, we investigated whether both maternal and paternal HLA class Ia antigens were co-dominantly expressed in such trophoblast cells. Using polymerase chain reaction sequence-specific primers for HLA-A and HLA-C alleles, we detected transcripts of both paternal and maternal origins, showing that these genes were not affected by genomic imprinting, at least in term placenta. After in vitro IFN-gamma treatment, the polymorphic HLA-A and HLA-B antigens of both parental origins become detectable at the cell surface, as assessed by flow cytometry and/or complement-dependent microtoxicity test. Appearance of paternal antigens on trophoblast cells upon IFN-gamma induction raises the question of the in vivo biological consequences of this phenomena, in term of materno-fetal tolerance and in particular of a potential allogeneic cytotoxic immune response.

Alleles↗

Inhibitory effect of theobromine on induction of angiogenesis and VEGF mRNA expression in v-raf transfectants of human urothelial cells HCV-29.

Neovascularisation plays a crucial role in solid tumor growth and metastasis formation. Our previous studies showed that theophylline and theobromine suppressed cutaneous neovascular reaction induced in mice by human blood leukocytes, and lung as well as ovarian cancer cells. Here, we investigated the in vivo effect of theobromine on angiogenic activity of human urothelial cell line HCV-29, v-raf transfected (mouse cutaneous assay), and the in vitro effect of this drug on VEGF, tPA, uPA and PAI mRNA expression in these cells (RT-PCR method). Theobromine suppressed angiogenesis induced in mice by HCV-29-v-raf cells, inhibited VEGF mRNA expression, and had no effect on transcription of uPA and tPA in these cells. HCV-29-v-raf transfectants do not display transcripts of PAI, in the presence or the absence of theobromine.

Animals↗

The effect of salbutamol treatment on the cellular immunity of the offspring of pregnant mice: spleen cell activity.

Preterm delivery is one of the greatest problems in obstetric care. One of the most commonly used treatments for high risk cases is salbutamol, a beta-2-adrenoceptor agonist. The aim of the present study was to determine if such treatment causes any changes in the neonatal immune system which should therefore be a concern in the care of the newborn. The experiments were performed on 4 to 5 or 6 to 7-week old female and male offspring of salbutamol-treated C3H/W inbred mice. In the first part of the study, the number of spleen cells, phenotypes and activity (phytohemagglutinin-induced proliferation, ability to induce local graft versus host reaction) were determined. We observed lowering of cell number and lowered proportions of cluster of differentiation (CD)3, CD4 and CD8 positive lymphocytes in spleens of progeny of salbutamol-treated mice. However, CD4+ to CD8+ ration was higher in the progeny of salbutamol-treated mothers than in the corresponding controls. In addition, reactivity to phytohemagglutinin and ability to induce local graft vs. host reaction were higher (popliteal lymph node test) or undisturbed (lymphocyte-induced angiogenesis test) in this group of mice.

Adrenergic beta-Agonists↗

Inhibition of angiogenesis by sulindac and its sulfone metabolite (FGN-1): a potential mechanism for their antineoplastic properties.

The nonsteroidal antiinflammatory drug sulindac (sulfoxide) is known to cause regression and prevent recurrence of adenomas in patients with familial adenomatous polyposis. The mechanism of action does not appear to require inhibition of prostaglandin synthesis since the sulfone metabolite of sulindac (FGN-1) retains the antineoplastic properties of sulindac but lacks inhibitory effects on cyclooxygenase, types 1 and 2. FGN-1 has been shown to induce apoptosis in a variety of tumor cell lines, and selective apoptosis of neoplastic cells has been proposed to account for its antineoplastic properties. Since angiogenesis is necessary for tumor progression and may be related to apoptosis, it is possible that inhibition of angiogenesis may also contribute to the antineoplastic properties of sulindac or FGN-1. In order to test this possibility, cells derived from several different types of human lung tumors were grafted intradermally in Balb/c mice. Sulindac sulfoxide and its sulfide and sulfone metabolites were administered for 3 days orally, in a daily dose of 0.025-0.5 mg, and angiogenesis was measured after 72 h using a previously described method. The results showed that sulindac sulfoxide and sulfone statistically inhibited angiogenesis.

Adenocarcinoma↗

Screening of angiogenesis inhibitors by modified tumor-induced angiogenesis (TIA) test in lung cancer.

Aberrant angiogenesis-the new vessels formation is a mandatory event in the process of tumor growth and expansion. Studies on mechanisms involved in tumor-induced angiogenesis (TIA) and on its possible inhibitors are needed in order to introduce in future new methods of tumor treatment. The aim of our study was to determine the usefulness of the modified cutaneous TIA (mice without immunosuppression) test for screening in vivo of the angiogenesis modifiers. In both models (classical and modified TIA) we demonstrated comparable angiogenesis activity following human lung cells inoculation and similar degree of neovascularization response inhibition caused by theobromine. We reported that in modified TIA model preincubation with theobromine significantly suppressed angiogenic potential of human lung cancer cells as well as the ability of those cells to produce proangiogenic cytokine-bFGF.

Adenocarcinoma↗

A subset of HLA-DR9 molecules is detected by a polymorphic monoclonal antibody on lymphoblastoid cell lines but not on peripheral blood lymphocytes.

Some mAbs recognizing polymorphic epitopes of HLA-DR molecules exhibit striking differences of reactivity with the same HLA-DR molecules expressed by different cell types. In this study, we investigated the basis for the differential reactivity of the polymorphic anti-DR mAb OHA TM901 with HLA-DR9 molecules expressed by human PBLs or LCLs. By immunoprecipitation experiments we showed that OHA TM901 recognizes a subset of HLA-DR9 molecules from LCLs. This subset corresponds to HLA-DR9 molecules containing immature-type oligosaccharides. The absence of OHA TM901 reactivity with HLA-DR9 PBLs, as revealed by cytofluorometry analysis, suggests that this subset is either not expressed or expressed at a very low level on PBLs. These results indicate that overexpression of HLA-DR molecules in immortalized LCLs could lead to cell-surface expression of underglycosylated forms which are generally not found on the cell surface of PBLs.

Antibodies, Monoclonal↗

[Contribution of the ophthalmologist to presymptomatic diagnosis of familial adenomatous polyposis (FAP)].

Familial adenomatous polyposis (FAP) represents a hereditary precancerous condition. Symptoms often appear malignant transformation only. For persons at risk early recognition of gene carriers is essential. Approximately 80% of the patients show congenital hypertrophy of the retinal pigment epithelium (CHRPE) that can be recognized before clinical manifestation of FAP. In order to predict FAP 9 patients and 10 persons at risk from 6 FAP families were examined by endoscopy, molecular genetical and ophthalmological methods. Four patients from two families each had bilaterally 4 CHRPE; four persons at risk did not have CHRPE. This is in accordance with endoscopic and molecular genetic results. The five patients and six persons at risk from the other four families did not have CHRPE, i.e., the percentage of CHRPE in the FAP patients examined was only 45%. Funduscopy permits early identification of gene carriers in families where the FAP patients have CHRPE. CHRPE is not present in persons at risk in these families, it is not necessary to conduct invasive diagnostic measures. Funduscopy should always be done in FAP patients and in persons at risk from CHRPE-positive families. An endoscopic examination should be recommended when CHRPE is observed incidentally in a person with a negative family history for FAP.

Adenomatous Polyposis Coli↗

Clinical implications from studies of HLA antigens in idiopathic nephrotic syndrome in children.

HLA class I and II antigen frequencies were determined in two large cohorts of children with idiopathic nephrotic syndrome (NS) from Southwest France (n = 199) and Southwest Germany (n = 152) and compared with unrelated healthy individuals from the same geographical areas. Strength of HLA association was expressed by the relative risk (RR) estimated by Odd's ratio. We examined 105 steroid-resistant and 242 steroid-sensitive NS patients who were subdivided in non-relapsers, infrequent relapsers and frequent relapsers or steroid-dependent patients. In steroid-sensitive patients significant associations were found with HLA-DR7 (RR 5.1 in French, 3.2 in Germans), -DQ2 (RR 4.7/2.3) and with the phenotypic combination HLA-DR3/DR7 (RR 5.6/7.7). Significant negative associations were encountered with HLA-DR2, -DR6 and -DQ1. The associations were stronger in frequent relapsers/steroid-dependent patients than in infrequent relapsers and were not significant in non-relapsers. In steroid-resistant patients the only significant association found was with the combined occurrence of HLA-DR3/DR7. We propose that in childhood NS tissue typing for selected HLA class II antigens is helpful in prediciting the clinical course.

Adolescent↗

Analysis of HLA-A/B recombinant families with new polymorphic markers.

The MHC in humans is a much studied region of the genome, the genes of which display a high rate of polymorphism and a high rate of linkage disequilibrium. Four families in which intra-class-I recombination has occurred have been analyzed with six polymorphic markers between HLA-A and -B in order to determine the full haplotypes of the whole families and to localize the points of crossover. The previously proposed order of the markers was confirmed by recombination mapping. In one family, the crossover was shown to have occurred in the 20-kb stretch of DNA bounded by the two markers (P3B and P5) between which no evidence of linkage disequilibrium was found, a region which constitutes of only about 1% of the distance between HLA-A and HLA-B. Although supportive of the suggestion of a hot spot of recombination in this region, based on the apparent lack of linkage disequilibrium between the markers P3B and P5, more such families need to be tested in order to confirm or refute this hypothesis.

Crossing Over, Genetic↗