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B Scherer

Publications and source records attributed to B Scherer.

At least 19 recordsLinked to original sources
PubMed2001

Application of hydrophobic anion-exchange phases in capillary electrochromatography.

Capillary electrochromatography (CEC) requires stationary phases that enable appropriate electroosmotic propel under various conditions. Analyte retention can be controlled through hydrophobic or electrostatic interaction with the packing material. The development and characterization of new strong anion-exchange materials with additional hydrophobic moieties (SAX/C18 mixed-mode phases) is described. The synthesis was based on polymer encapsulation of porous silica. The phases were systematically characterized by means of elemental analyses, HPLC frontal analyses and CEC experiments. The studies focused on the influence of various parameters (e.g., pH, kind of buffer, capillary wall) on the electroosmotic flow (EOF). Phases with high anion-exchange capacity generated a fast and constant EOF over a wide pH range. Long-time stability of EOF and hydrophobic retention under CEC conditions were demonstrated within the course of 100 consecutive injections. The applicability of the SAX/C18 phases in appropriate buffer systems is demonstrated for neutral, acidic and basic compounds.

Anion Exchange Resins↗
PubMed2001

Bacterial CpG-DNA triggers activation and maturation of human CD11c-, CD123+ dendritic cells.

Human plasmacytoid precursor dendritic cells (ppDC) are a major source of type I IFN upon exposure to virus and bacteria, yet the stimulus causing their maturation into DCs is unknown. After PBMC activation with immunostimulatory bacterial DNA sequences (CpG-DNA) we found that ppDC are the primary source of IFN-alpha. In fact, either CpG-DNA or dsRNA (poly(I:C)) induced IFN-alpha from purified ppDC. Surprisingly, only CpG-DNA triggered purified ppDC survival, maturation, and production of TNF, GM-CSF, IL-6, and IL-8, but not IL-10 or IL-12. Known DC activators such as CD40 ligation triggered ppDC maturation, but only IL-8 production, while bacterial LPS was negative for all activation criteria. An additional finding was that only CpG-DNA could counteract IL-4-induced apoptosis in ppDC. Therefore, CpG-DNA represents a pathogen-associated molecular pattern for ppDC. In contrast to these finding, CpG-DNA, like LPS, caused TNF, IL-6, and IL-12 release from PBMC and purified monocytes; however, differentiation of monocytes into DCs with GM-CSF and IL-4 unexpectedly resulted in refractoriness to CpG-DNA, but not LPS. Taken together, these results suggest that within a DC subset a multiplicity of responses can be generated by distinct environmental stimuli and that responses to a given stimulus may be dissimilar between DC subsets.

3T3 Cells↗
PubMed2001

Risk of prostate carcinoma death in patients with lymph node metastasis.

BACKGROUND: The presence of lymph node metastasis is a poor prognostic sign for patients with prostate carcinoma. Results of published reports on survival among patients with lymph node metastasis are difficult to assess because of treatment selections. The extent to which lymph node status will have an impact on a patient's survival is uncertain. METHODS: The authors analyzed 3463 consecutive Mayo Clinic patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy for prostate carcinoma between 1987 and 1993. Of these patients, 322 had lymph node metastasis at the time of surgery, and 297 lymph node positive patients also received adjuvant hormonal therapy within 90 days of surgery. The progression free rate and the cancer specific survival rate were used as outcome endpoints in univariate and multivariate Cox proportional hazards models. The median follow-up was 6.3 years. Progression was defined by elevation of serum prostate specific antigen (PSA) > or = 0.4 ng/mL after surgery, development of local recurrence, or distant metastasis documented by biopsy or radiographic examination. RESULTS: The 5-year and 10-year progression free survival rates (+/- standard error [SE]) for patients with lymph node metastasis were 74% +/- 2% and 64% +/- 3%, respectively, compared with 77% +/- 1% and 59% +/- 2%, respectively, for patients without lymph node metastasis. The 5-year and 10-year cancer specific survival rates were 94% +/- 1% and 83% +/- 4%, respectively, compared with 99% +/- 0.1% and 97% +/- 0.5%, respectively, for patients without lymph node metastasis. Among patients with a single lymph node metastasis, the 5-year and 10-year cancer specific survival rates were 99% +/- 1% and 94% +/- 3%, respectively. After adjustment for extraprostatic extension, seminal vesicle invasion, Gleason grade, surgical margins, DNA ploidy, preoperative serum PSA concentration, and adjuvant therapy, the hazard ratio for death from prostate carcinoma among patients with a single lymph node metastasis compared with patients who were without lymph node metastasis was 1.5 (95% confidence interval, 0.5-5.0; P = 0.478), whereas the hazard ratio for death from prostate carcinoma was 6.1 (95% confidence interval, 1.9-19.6; P = 0.002) for those with two positive lymph nodes and 4.3 (95% confidence interval, 1.4-13.0; P = 0.009) for those with three or more positive lymph nodes. There was no significant difference in the progression free survival rate among patients with or without lymph node metastasis in multivariate analysis after controlling for all relevant variables, including treatments (hazard ratio,1.0; 95% CI, 0.7-1.3; P = 0.90). CONCLUSIONS: Patients with prostate carcinoma who have multiple regional lymph node metastases had increased risk of death from disease, whereas patients with single lymph node involvement appeared to have a more favorable prognosis after radical prostatectomy and immediate adjuvant hormonal therapy. Excellent local disease control was achieved by using combined surgery and adjuvant hormonal therapy in patients with positive lymph nodes.

Adult↗
PubMed2001

Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy.

PURPOSE: We determine the importance of clinical and pathological variables for predicting biochemical progression in patients after surgery for specimen confined prostate cancer. We developed a simple scoring algorithm for biochemical progression in node negative cases and tested the algorithm performance on an independent group. MATERIALS AND METHODS: Our study included 2,518 patients with pT2N0 or pT3N0 disease treated between 1990 and 1993. Gleason score, preoperative prostate specific antigen (PSA), margin status, extraprostatic extension, seminal vesicle involvement, DNA ploidy and adjuvant treatment were primary variables analyzed univariately. The Cox proportional hazards model was used on 2,000 randomly selected patients to develop a multivariate scoring algorithm for the aforementioned factors to predict biochemical progression-free survival. The final model included Gleason score, preoperative PSA, margin status, seminal vesicle involvement and adjuvant treatment. The prognostic score derived from this model was validated by applying it to the remaining 518 patients. Harrell's measure of concordance (C) was used to compare competing models. RESULTS: For patients who did not receive adjuvant therapy the derived score based on the Cox model coefficient was Gleason +1 (PSA 4 to 10), +2 (PSA 10.1 to 20), +3 (PSA greater than 20), +2 (positive seminal vesicle) and +2 (positive margin). The score was reduced by 4 if adjuvant hormonal therapy was given and by 2 for only adjuvant radiotherapy. The 5-year progression-free survival was 94% for scores less than 5, 60% for 10 and 32% for greater than 12 (C = 0. 718). Applying the score to the independent validation data set (518) resulted in 5-year progression-free survival of 96% for scores less than 5, 53% for 10 and 30% for greater than 12 (C = 0.759). CONCLUSIONS: Progression-free survival determined by the model score group identified a wide range of risk levels for patients with specimen confined prostate cancer. This simple predictive model allows identification of patients at high risk for cancer progression with specimen confined disease who may be targeted for closer surveillance and adjuvant therapy, while those at lower risk may be simply observed.

Adenocarcinoma↗
PubMed2000

Instrumentation for capillary electrochromatography.

One of the reasons for the immense interest in capillary electrochromatography (CEC) is its feature to combine chromatographic selectivity with the high efficiency and the miniaturization potential of capillary electrophoresis (CE). The capability of commercial CE instruments to run CEC has enforced the readiness of users and researchers to work on this separation technique. Nevertheless, to fully exploit the potential of CEC, a routine CE device can certainly not fulfill all requirements. Two different approaches have been made to overcome this problem. The first was to modify commercial CE instruments for various demands. Pressurization of the packed capillary to prevent "air" bubble formation, gradient elution capabilities and thermostating devices allowing a greater flexibility in column designs have been implemented in CE instruments of several manufacturers. A completely different approach is the development of modular laboratory-made instrumentation dedicated to special CEC requirements. In order to increase mobile phase velocity and thus the speed of analysis the availability of voltages higher than 30 kV was accomplished in some of these devices. Gradient elution was achieved by either coupling of gradient LC systems or an electroosmotic generation of the changing eluent composition. When a pressure gradient is applied between both column ends in addition to the voltage gradient, a hybrid between capillary HPLC and CEC results. This chromatographic mode is named pressure-assisted electrochromatography (PEC). Either CE instruments equipped with additional HPLC pumps or modular laboratory-made devices are suitable for PEC. In CEC, sensitivity for UV detection is rather poor due to the short optical path length for on-column detection in capillary separation techniques. A special cell design with enhanced light path is presented and further principles like, e.g., fluorescence detection and coupling to mass spectrometry are discussed.

Electrophoresis, Capillary↗
PubMed1992

[Kidney failure as a consequence of sarcoidosis].

A 27-year-old man was admitted to hospital because of weight loss, fatigue and lack of appetite over the previous few weeks and cervical lymphadenopathy. Chest X-ray demonstrated several patchy infiltrates in both lungs. There was also evidence of progressive renal failure (creatinine concentration: 3,0 mg/dl) and hypercalcaemia (2,8 mmol/l). Bronchoalveolar lavage and renal biopsy confirmed sarcoidosis. Fundoscopy revealed eye involvement (several circumscribed, partly confluent, whitish nodules). Wegener's granulomatosis was excluded because no anticytoplasmic antibodies were demonstrated. Administration of steroids (at first daily 60 mg methylprednisolone) quickly resulted in a normal blood calcium level and normal renal function. These findings suggest that the early stage of sarcoidosis consists of in principle reversible functional changes. The differential diagnosis from systemic diseases is often difficult. If sarcoidosis is suspected one must search for rare organ manifestations so that therapy can be started as soon as possible.

Adult↗
PubMed1992

Cryopreservation evaluated with mitochondrial and Z line ultrastructure in striated muscle.

Single, intact, frog skeletal muscle fibres and whole frog hearts were quick-frozen on a polished, liquid-He-cooled copper block and examined in the electron microscope after freeze-substitution and freeze-fracture. In both kinds of striated muscle, collapse of the peripheral and intracristal membrane spaces in mitochondria was found to increase with increasing distance from the point of first impact (PFI) of the muscle cells on the cold copper block. The changes correlated with a previously described gradient of Z line and A band cryodamage occurring with distance from the PFI. The findings in thin sections from freeze-substituted preparations were confirmed by freeze-fracture preparations. It is concluded that, since the mitochondrial membrane changes are concurrent with, and follow the same spatial distribution of, other manifest cryoartefacts, the cryoartefactual nature of the mitochondrial changes must be excluded before functional significance is attributed to them. The collapse of mitochondrial membrane spaces as a sensitive indicator of quality of cryopreservation may apply to non-muscle cells as well.

Animals↗
PubMed1989

Does hormone analysis predict the antihypertensive response of basic medical treatment?

The antihypertensive effect of 200 mg metoprolol per day was compared to 25 mg hydrochlorothiazide over a period of four weeks. Metoprolol reduced mean arterial blood pressure from 120 +/- 13 mm Hg after placebo to 109 +/- 8 at the end of the study (n = 18; 38 +/- 12 years) (p less than 0.01). The corresponding values in the hydrochlorothiazide group were 119 +/- 13 mm Hg and 107 +/- 13 (n = 20; 33 +/- 12 years) (p less than 0.01). No significant difference between the groups was found for blood pressure at the end of the study. When blood pressure responders or non-responders of the metoprolol group were compared with the respective subgroup of the hydrochlorothiazide treated patients, no difference could be found for plasma renin activity as well as for aldosterone and PGE2- and PGF2a-excretion rates. However, when blood pressure responders were compared with non-responders within the same treatment group, plasma renin activity and PGE2-excretion rates were higher in the responder group corresponding with younger age in both treatments. Therefore high PGE2-excretion rate and high plasma renin activity might reflect a favorable vascular response to antihypertensive therapy. However, the hormonal analyses do not seem to help in the selection between a beta-blocker or a diuretic as a drug of first choice.

Adolescent↗
PubMed1988

[Kidney diseases and hypertension].

Renal disease has been recognized as both a cause and a consequence of hypertension. Renal hypertension may be of vascular and nonvascular origin. Generally, the prevalence of hypertension increases with decreasing renal function, including more than 90% of patients with terminal renal failure. However, hypertension is more often found in glomerular than in interstitial disease. The pathomechanisms operative in renal hypertension are sodium retention with concomitant volume expansion, an increase in plasma renin activity or a combination of both factors. While mechanical intervention is usually tried in renovascular hypertension and in the rare cases with "urological" causes, no causal therapy is possible in most cases of renoparenchymal disease. However, as the normalization of blood pressure is the best proved way to stop or at least retard the progression of renoparenchymal disease, pharmacological intervention is mandatory even if the medication sometimes has side effects.

Humans↗
PubMed1985

Geometry of cell and bundle appositions in cardiac muscle: light microscopy.

A strand each of cardiac conduction and working cells of the left ventricle is studied in serial sections with the light microscope to define the geometry of cell appositions that form networks of cardiac muscle cells. Anatomic and thus electrical coupling is very frequent among all cells; it is accomplished within a few hundred micrometers axially regardless at which point of the strand electrical current is assumed to originate. Most individual cardiac myocytes are not only connected in longitudinal direction but also make lateral contacts. Only a few bundles of varying diameters remain unconnected over appreciable distances of greater than 200 micron (so-called unit bundles). Thus abnormal current vectors are averted, at least in normal cardiac tissue, even if excitation were to originate from a point. Plastic thick sections studied with the light microscope were unsuitable to define cell lengths.

Animals↗
PubMed1984

Prostaglandin excretion after furosemide in normal and low-renin essential hypertension.

We examined the urinary excretion of prostaglandin (PG)E2 and PGF2 alpha before and 15 min after stimulation with the acutely vasodilating agent furosemide in 25 normotensive controls and 81 patients with essential hypertension (EH). After furosemide administration, PGE2 excretion was lower in patients with EH (P less than 0.02). Excretion rates of PGF2 alpha and of sodium, and urinary volume in hypertensive patients were not significantly different from the values found in normotensive controls. Patients with low-renin essential hypertension (LREH) had a significantly reduced excretion of both PGE2 and PGF2 alpha before and after administration of furosemide as compared to controls. The difference in PGF2 alpha excretion was also significant when LREH patients were compared to those with normal-renin essential hypertension (NREH). Patients with LREH were older and excreted less potassium than patients with NREH or normotensive controls. We conclude that the reduced PG excretion immediately after furosemide administration in patients with EH reflects a diminished capacity of the hypertensive kidney to generate prostaglandins which exert an overall vasodilating effect. Since renin secretion is under the control of renal PG formation, the decreased responsiveness of plasma renin activity (PRA) observed in patients with EH and predominantly in those with LREH may be the consequence of a decreased renal cortical PG generation. Alternatively, mechanisms that reduce both PRA and PG generation have to be considered.

Adult↗