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Biomedical subjects

S Ullrich

Publications and source records attributed to S Ullrich.

At least 37 records · Page 2Linked to original sources
PubMed2000

Tumor rejection and immune memory elicited by locally released LEC chemokine are associated with an impressive recruitment of APCs, lymphocytes, and granulocytes.

The human beta chemokine known as LEC (also called NCC-4, HCC-4, or LMC) displays chemotactic activity for monocytes and dendritic cells. The possibility that its local presence increases tumor immunogenicity is addressed in this paper. TSA parental cells (TSA-pc) are poorly immunogenic adenocarcinoma cells that grow progressively, kill both nu/nu and syngeneic BALB/c mice, and give rise to lung metastases. TSA cells engineered to release LEC (TSA-LEC) are still able to grow in nu/nu mice, but are promptly rejected and display a marginal metastatic phenotype in BALB/c mice. Rejection is associated with a marked T lymphocyte and granulocyte infiltration, along with extensive macrophage and dendritic cell recruitment. NK cells and CD4+ T lymphocytes are uninfluential in TSA-LEC cell rejection, whereas both CD8+ lymphocytes and polymorphonuclear leukocytes play a major role. An antitumor immune memory is established very quickly after rejection, since 6 days later 75% of BALB/c mice were already resistant to a TSA-pc challenge. Spleen cells from rejecting mice display specific cytotoxic activity against TSA-pc and secrete IFN-gamma and IL-2 when restimulated by TSA-pc. The ability of LEC to markedly improve recognition of poorly immunogenic cells by promoting APC-T cell cross-talk suggests that it could be an effective component of antitumor vaccines.

Adenocarcinoma↗
PubMed2000

[Acute effects of alcohol and chronic alcoholism as causes of violent crime].

To study the influence of alcohol and psychosocial variables on delinquent behavior, we coded data from the psychiatric evaluation of 254 defendants using a standardized score sheet, analyzing correlations between acute intoxication at the time of the crime (ICD 10:F10.0), diagnosis of alcohol dependency according to ICD 10 (F10.2), psycho-biographical variables, criminal history, and parameters relating to the index offence. We found that 64.6% of all defendants studied were intoxicated when committing the crime and 25.6% suffered from alcohol dependency. Alcohol intoxication correlated to occurrence of violent crime, cruelty in committing the index offence, and earlier convictions. Logistic regression, with demographic and psychosocial variables entered as covariables, revealed acute alcohol intoxication but not alcohol dependency as a predictor of violent crime (odds ratio 2.3, P = 0.02). Alcohol intoxication and dependency were also independent predictors of earlier convictions (intoxication, odds ratio 4.4, P = 0.0001; dependency, odds ratio 3.6, P = 0.003). Our findings support the hypothesis that acute alcohol intoxication, not dependency, influences violent crime in a direct manner. However, alcohol dependency predicts criminal recidivism.

Acute Disease↗
PubMed2000

[Imaging of vitreoretinal adhesions in the partner eye of patients with penetrating macular foramina in optical coherence tomography].

BACKGROUND: Vitreoretinal adhesions play a crucial role in the development of a macular hole. To visualize vitreoretinal adhesion we used optical coherence tomography to investigate fellow eyes of patients with macular holes. METHODS: In a prospective study we scanned the retina in 188 patients with a macular hole stage III or IV (Gass classification). The foveal shape and vitreous were classified into grades. RESULTS: Of the 188 patients 45% showed no vitreous reflex, 45% a partial vitreous detachment with foveolar adhesions, and 10% a vitreous detachment with complete separation from the fovea. While eyes with normal foveolar shape displayed partial vitreous detachment in 33%, this figure rose to 66% in eyes with a macular hole stage I. CONCLUSION: Diffuse thickening of the fovea is followed by an intraretinal split and formation of a cyst. The shape of the foveolar adhesion suggests that continuing anteroposterior vitreal traction leads to a retinal break and formation of a full-thickness macular hole.

Aged↗
PubMed2000

Flow cytometric techniques to characterise physiological states of Acinetobacter calcoaceticus.

Monitoring biotechnological processes involves acquiring information about key metabolic events and, ideally, single cell states should be determined to obtain comprehensive data on the physiological status of the surveyed population. In this paper, growth stages of the strain Acinetobacter calcoaceticus 69-V were characterised at the single cell level using flow cytometry. Four methods for analysing bacterial cellular characteristics by fluorescence were compared with respect to their sensitivity to changes in the physiological states induced by changing micro-environmental conditions. DNA analysis was confirmed to be highly informative with regard to the multiplication activity of the population. Measuring the membrane potential related fluorescence intensity (MPRFI) and the rRNA content were found to be useful for describing high-active cell states. A method for the measurement of the fluidity related fluorescence intensity (FRFI) was developed, since it allowed changes in the fluidity of the bacterial membrane to be detected, and thereby provided a valuable means of tracking adaptation of the population to micro-environmental deviations from optimal growth conditions.

Acinetobacter calcoaceticus↗
PubMed2000

EPC syntheses and structure-activity relationships of hypoglycaemic semicyclic amidines.

A series of homochiral sterically hindered mono- and bicyclic amidines was prepared as hypoglycaemic agents by lethargic reaction of O-methylcaprolactim and 3-ethoxy-2-azabicyclo[2.2.2]oct-2-ene, respectively, with homochiral cis-2-substituted cyclopentane amines provided by asymmetrical reductive amination of racemic 2-substituted cyclopentanones. All compounds, except the cyclohexylmethyl-isoquinuclidone derivative which inhibited secretion at 100 microM, significantly stimulated insulin secretion 2-8-fold at 10 microM and 100 microM in INS-1 cells. The most potent activator was the 2-cyclopentyl-substituted caprolactam derivative 5e. The stimulatory effects on secretion increased with rising steric hindrance of both the amidine alpha-carbon and the bicyclic amidine moiety itself. Enantiomeric discrimination was observed for the 2-¿(cis-2-bulkysubstituted cyclopentyl)iminohexahydroazepine halides 5e and 5f and for the 3-¿(cis-2-substituted cyclopentyl)imino-2-azabicyclo¿2.2.2ŏctane halides 6a and 6c. The amidines depolarized INS-1 cells and generated action potentials, accompanied by a decrease of membrane conductance. Simultaneously [Ca(2+)](i) increased, probably due to Ca(2+)-entry through voltage-dependent Ca(2+)-channels. At high concentrations, where inhibition of secretion was observed, ¿Ca(2+)(i) still rose upon application of the amidines, indicating an additional inhibitory pathway downstream to the elevation of ¿Ca(2+)(i). Even at high concentrations (100 microM), the amidines had no toxic effects on insulin secreting INS-1 cells.

Amidines↗
PubMed2000

Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids.

Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's immune system in controlling the devastating course of metastatic renal cell carcinoma. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a 'mixed response', and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.

Aged↗
PubMed2000

Central corneal thickness determined with optical coherence tomography in various types of glaucoma.

AIMS: To evaluate central corneal thickness determined by optical coherence tomography (OCT) in various types of glaucoma, and its influence on intraocular pressure (IOP) measurement. METHODS: Central corneal thickness (CCT) was determined by using OCT in 167 subjects (167 eyes). 20 had primary open angle glaucoma (POAG), 42 had low tension glaucoma (LTG), 22 had ocular hypertension (OHT), 10 had primary angle closure glaucoma (AC), 24 had pseudoexfoliation glaucoma (PEX), 13 had pigmentary glaucoma (PIG), and 36 were normal. RESULTS: CCT was significantly higher in ocular hypertensive subjects (593 (SD 35) microm, p <0.0001) than in the controls (530 (32) microm), whereas patients with LTG (482 (28) microm, p < 0. 0001), PEX (493 (33) microm, p <0.0001), and POAG (512 (30) microm, p <0.05) showed significantly lower readings. There was no statistically significant difference between the controls and patients with PIG (510 (39) microm) and AC (539 (37) microm). CONCLUSIONS: Because of thinner CCT in patients with LTG, PEX, and POAG this may result in underestimation of IOP, whereas thicker corneas may lead to an overestimation of IOP in subjects with OH. By determining CCT with OCT, a new and precise technique to measure CCT, this study emphasises the need for a combined measurement of IOP and CCT in order to obtain exact IOP readings.

Aged↗
PubMed2000

Effects of adrenaline and tolbutamide on insulin secretion in INS-1 cells under voltage control.

The aim of the present study was to investigate whether mechanisms distal to the regulation of Ca2-influx are involved in tolbutamide-induced stimulation and adrenaline- and somatostatin- induced inhibition of insulin secretion in INS-1 cells. Using the patch clamp method, the membrane voltage was either kept constant at -70 mV, or Ca2+-influx was activated by short depolarising pulses to 0 my. These pulses induced an increase in cellular capacitance (Cm) caused by fusion of secretory granules with the plasma membrane. Tolbutamide did not alter, neither Cm under voltage clamp at -70 mV nor increases of Cm due to voltage pulses. The inhibitors of secretion, adrenaline and somatostatin, counteracted the augmentation of [Ca2+]i which was induced by glucose, tolbutamide and forskolin. In the voltage clamp mode, however, where no changes of [Ca2]i. were observed, adrenaline but not somatostatin inhibited the increase of Cm caused by depolarizing voltage pulses. The adrenaline effect on Cm was dependent on the addition of GTP to the pipette solution. When GTP was replaced by GDPbetaS or GTPgammaS, the effect of adrenaline on Cm was abolished. The blockade of calcineurin, by the addition of calcineurin inhibitory peptide (CIP) to the pipette solution, did not affect the adrenaline-induced inhibition of Cm. Moreover. After incubation of the cells with deltamethrin, a calcineurin inhibitor, the stimulation of secretion was attenuated, but the adrenaline-induced inhibition was not affected. Our results suggest that adrenaline-induced inhibition of insulin secretion involves a site of action directly related to the exocytotic membrane fusion. In contrast, the stimulator tolbutamide and the inhibitor somatostatin had no direct effect on exocytosis in INS-1 cells.

Cell Line↗
PubMed1999

Violence, criminal behavior, and the EEG: significance of left hemispheric focal abnormalities.

The authors studies the relationship of EEG abnormalities and violent criminal behavior in 222 defendants referred for psychiatric evaluation. There was no connection between the number of violent offenses and EEG abnormalities in general. Focal abnormalities, however, especially of the left hemisphere, were related to a significantly higher number of violent offenses. In many cases these abnormalities were accompanied by mental retardation, epilepsy, or earlier brain damage. The findings suggest that impairment of left hemisphere functions may enhance the propensity for violent behavior in a subgroup of offenders.

Adolescent↗
PubMed1997

Adrenaline inhibits depolarization-induced increases in capacitance the presence of elevated [Ca2+]i in insulin secreting cells.

Cell capacitance (Cm), cell conductance (Gm), access conductance (Ga) and membrane voltage (Vm) were measured simultaneously in insulin secreting cells using the dual frequency method. Depolarization and stimulation of the cells with secretagogues increased Cm. EGTA abolished the increase in [Ca2+]i and prevented the rise of Cm. Adrenaline inhibited the augmentation of Cm without lowering [Ca2+]i. In pertussis toxin pretreated cells adrenaline had no effect. Thus, stimulation of insulin secretion is accompanied by an increase in Cm. Inhibition of exocytosis by adrenaline occurs even in the presence of elevated [Ca2+]i, i.e. at a more distal step of exocytosis.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Preparation and characterization of recombinant tissue inhibitor of metalloproteinase 4 (TIMP-4).

TIMP-4, a novel human tissue inhibitor of metalloproteinase, was identified and cloned (Greene, J., Wang, M., Raymond, L. A., Liu, Y. E., Rosen, C., and Shi, Y. E. (1996) J. Biol. Chem. 271, 30375-30380). In this report, the production and characterization of recombinant TIMP-4 (rTIMP4p) are described. rTIMP4p, expressed in baculovirus-infected insect cells, was purified to homogeneity by a combination of cation exchange, hydrophobic, and size-exclusion chromatographies. The purified protein migrated as a single 23-kDa band in SDS-polyacrylamide gel electrophoresis and in Western blot using a specific anti-TIMP-4 antibody. Inhibition of matrix metalloproteinase (MMP) activities by rTIMP4p was demonstrated in five MMPs. Enzymatic kinetic studies revealed IC50 values (concentration at 50% inhibition) of 19, 3, 45, 8, and 83 nM for MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9, respectively. Purified rTIMP4p demonstrated a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. Thus, TIMP-4 is a new enzymatic inhibitor in MMP-mediated extracellular matrix degradation and may have therapeutic potential in treating cancer malignant progression.

Breast Neoplasms↗
PubMed1997

Forebrain overgrowth (fog): a new mutation in the mouse affecting neural tube development.

Forebrain overgrowth, fog, is a spontaneous autosomal recessive mutation in the mouse producing forebrain, lumbo-sacral, and facial defects. The defects appear to result from excessive growth or cellular proliferation leading to abnormalities in neural tube closure. Three unique features of the mutant are: (1) the growth of telencephalon cells into the surrounding mesenchyme, (2) presence of an encephalocele through the midline cleft in some mutants, and (3) dissociation of the tail defect from the caudal neural tube defect. We used an intersubspecific intercross between mice carrying the fog mutation and mice from an inbred Mus musculus castaneus strain (CAST/Ei) to map the fog mutation to mouse Chromosome 10 near D10Mit262 and D10Mit230 in a region with several potential candidate genes.

Abnormalities, Multiple↗
PubMed1997

The effect of recombinant human granulocyte macrophage colony stimulating factor after chemotherapy of various tumors.

Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) has been successfully used in different clinical settings. We evaluated the tolerability of rhGM-CSF treatment in addition to its efficacy in preventing myelosuppression and reducing infectious complications after standard-dose chemotherapy of various tumors. Of the patient group analyzed (n = 308), 75% had solid tumors and 25% had hematological malignancies. In 27.9% of these patients an infection occurred after the first cycle of chemotherapy and between 8.2 and 19.0% in later cycles with a mean duration of fever (above 38.5 degrees C) of 3.6 days. Treatment with rhGM-CSF was well-tolerated. After the completion of treatment, the investigators assessed the efficacy of rhGM-CSF in 83.7% of the patients as 'very good' or 'good', and as 'moderate' or 'bad' in only 11.5% of patients as well as the tolerability as 'very good' or 'good' in 87.0% of the patients and in 9.4% 'moderate' or 'bad'. We conclude that rhGM-CSF proved to be an effective and well-tolerated tool in preventing myelosuppression and infectious complications after standard-dose chemotherapy of various tumors.

Antineoplastic Agents↗
PubMed1996

DNA double strand breaks in epidermal cells cause immune suppression in vivo and cytokine production in vitro.

UV irradiation of the skin causes immune suppression by a mechanism involving epidermal cytokines. To determine the role of epidermal DNA damage in immune suppression, we used HindIII restriction endonuclease encapsulated in liposomes to cause DNA strand breaks in epidermal cells in vivo and in vitro. Topical application of HindIII in liposomes to murine skin in vivo impaired the induction of contact hypersensitivity responses initiated either locally or at distant sites and impaired the function of APCs. Unlike UV-B radiation, however, treatment of mice with HindIII in liposomes before contact sensitization did not induce tolerance or transferable suppression. The liposome-encapsulated HindIII caused double strand breaks in DNA and induced IL-10 and TNF-alpha production when added to cells of a murine keratinocyte line in vitro. Topical application of liposomal HindIII also induced TNF-alpha in the epidermis of mice. Liposomes containing heat-inactivated HindIII or an endonuclease specific for pyrimidine dimers in DNA did not exhibit these effects. These results support the hypothesis that DNA damage is a trigger for the production of cytokines that modulate immune responses. They also suggest that immune suppression and suppressor cell induction are separate consequences of cutaneous injury that require different stimuli.

Animals↗
PubMed1996

Adrenaline-, not somatostatin-induced hyperpolarization is accompanied by a sustained inhibition of insulin secretion in INS-1 cells. Activation of sulphonylurea K+ATP channels is not involved.

Adrenaline and somatostatin inhibit insulin secretion via pertussis toxin (PTX)-sensitive mechanisms. Since glucose-stimulated release involves inhibition of ATP-sensitive K+ (K+ATP) channels and activation of Ca2+ influx, we took advantage of the glucose-sensitive, insulin-secreting cell line INS-1 to investigate whether inhibitors of insulin release modulate membrane voltage and K+ATP channel activity in cell-attached patch-clamp experiments. We found that adrenaline, through alpha2-adrenoceptors, and somatostatin counteracted glucose-induced depolarization and action potentials. As expected, these effects were mediated via PTX-sensitive G proteins since PTX pretreatment of the cells eliminated the effects of adrenaline and somatostatin on membrane voltage. When INS-1 cells were activated by adding both the K+ATP channel inhibitor tolbutamide and the adenylyl cyclase activator forskolin, adrenaline and somatostatin still repolarized the plasma membrane. Single-channel measurements in the cell-attached mode revealed that tolbutamide closed a 40 to 70 pS K+ channel which was neither reopened by adrenaline nor by somatostatin. In parallel cell preparations, insulin secretion was measured by radioimmunoassay. Insulin release induced by glucose, forskolin and tolbutamide was abolished by adrenaline. In contrast, somatostatin attenuated insulin secretion by only 30%. After comparing the potency of adrenaline and somatostatin on membrane voltage and on insulin secretion, it is concluded that the repolarizing effect of adrenaline on membrane voltage is not sufficient to explain its potent inhibitory effect on insulin secretion.

Adenosine Triphosphate↗
PubMed1996

Effects of glucose, forskolin and tolbutamide on membrane potential and insulin secretion in the insulin-secreting cell line INS-1.

Membrane voltages (Vm) of INS-1 cells, an insulin-secreting cell line, were measured mostly using the cell-attached mode of the patch-clamp method. The cell-attached configuration allowed the cell to be kept intact. Measurement of Vm was possible because seal resistances were very high and because the membrane obviously had a sufficiently high conductance (probably via K+ channels). Resting Vm was -80 +/- 1 mV (n = 42) and was mainly determined by sulphonylurea-sensitive K+ATP channels since tolbutamide depolarized the plasma membrane in a concentration-dependent manner and generated action potentials at 50 and 100 micromol/l. D-Glucose, tested between 0.5 and 16.7 mmol/l, also depolarized the plasma membrane in a concentration-dependent manner and induced action potentials at concentrations higher than 5.6 mmol/l. Similarly, forskolin (5 micromol/l) depolarized the cells and increased the frequency of Ca2+-mediated action potentials. Insulin secretion was measured from cells growing in culture dishes, by radioimmunoassay. Glucose doubled secretion in INS-1 cells, whereas tolbutamide had no significant effect on secretion in the presence of 0.5 mmol/l and 16. 7 mmol/l glucose. At 3 mmol/l glucose, tolbutamide increased insulin release slightly. Forskolin elevated secretion twofold at a low glucose concentration. In contrast, when glucose or tolbutamide were added together with forskolin secretion was potentiated five- to tenfold. These results show that glucose induces membrane activation in INS-1 cells. Furthermore, the potent effect of tolbutamide, i.e. to depolarize the plasma membrane without inducing insulin release, leads to the conclusion that effects distal to depolarization are pivotal for secretion in INS-1 cells.

Action Potentials↗