Biomedical subjects

F Ullrich

Publications and source records attributed to F Ullrich.

At least 19 recordsLinked to original sources

PubMed2005

Performance of calorimetric methods for the investigation of microbial systems in combination with additional sensors.

Calorimetric methods are used in combination with online oxygen measurement (using an amperometric sensor) and determination of the optical density (using a fibre optic sensor) to investigate microbial growth behaviour. The calorimetric curves of different batch experiments show a characteristic and reproducible course. Changes in the slope of the DeltaT-time curves indicate the effects of limiting factors on the microbial activity during the cultivation. A first limitation could be correlated with the depletion of oxygen in the medium; a second correlates with the depletion of the carbon source. Measurements of optical density in some cases provide reliable information about the growth of a microorganism culture. Our measurements show a good correlation of the universal calorimetric signal (heat-time curve) to the signal of the miniaturised photometric (OD) sensor.

Calorimetry↗

PubMed2002

Diffuse large B-cell lymphoma: a clinicopathologic analysis of 444 cases classified according to the updated Kiel classification.

The purpose of this study was: to compare the survival of diffuse large B-cell lymphomas (DLBCL) stratified according to the up-dated Kiel classification. A retrospective study of a cohort of 1378 cases was organized in 1996 by the Non-Hodgkin's Lymphoma Classification Project, and the DLBCL were classified according to the updated Kiel classification. The distribution of the different types and subtypes was as follows: centroblastic (CB, 85.4%), composed of the polymorphic (CB-PM, 58.6%), monomorphic (CB-MM, 17.1%) and multilobated (CB-ML, 9.7%) subtypes; immunoblastic (IB, 11.2%), with (8.3%) or without (2.9%) plasmacytoid differentiation; and anaplastic large cell lymphoma (ALCL) of B-cell type (3.4%). The rate of diagnostic agreement between pathologists was 78% for CB and 65% for IB lymphoma. The 5-year overall survival (OAS) for the entire group was 47% and the 5-year failure-free survival (FFS) was 42%. No significant differences in survival were found between the three major groups (CB, IB, ALCL). However, the 5-year OAS and FFS of patients with DLBCL not containing immunoblasts (CB-MM+CB-ML) was 51 and 52%, respectively, and was significantly better than the survival of those containing immunoblasts (CB-PM+IB+ALCL), which was 44 and 38% (p = 0.06 and p = 0.037), respectively. These results did not appear to be due to differences in the clinical features of the two groups, and was most significant for patients with low stage or low risk disease. However, histologic subtyping was not an independent risk factor for the entire group by multivariate analysis. In conclusion, patients with CB-MM and CB-ML (without immunoblasts) had a significantly better OAS and FFS than those with CB-PM, IB and ALCL (with immunoblasts). Therefore, we conclude that additional studies are still needed to further evaluate the importance of immunoblastic differentiation in DLBCL.

Adolescent↗

PubMed2002

Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin's Lymphoma Classification Project.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is rare in most parts of the world. Therefore, we have evaluated the 96 cases of PTCL diagnosed within the Non-Hodgkin's Lymphoma Classification Project (NHLCP) (1378 cases) for their geographical distribution, pathologic features and diagnostic reliability, as well as clinical presentation and outcome. MATERIALS AND METHODS: Diagnoses of all cases were rendered independently by five experienced hematopathologists based on morphology only, and after introduction of the immunophenotype and clinical data. Divergent diagnoses were jointly discussed and a final consensus diagnosis was established in each case. Reliability of the diagnoses was evaluated statistically, and the clinical features and outcome were analyzed according to the consensus diagnoses. RESULTS: Seven per cent of all non-Hodgkin's lymphoma (NHL) cases reviewed were classified as PTCL and the frequency varied from 1.5% to 18.3% in different countries. The interobserver agreement with the consensus diagnosis of PTCL was 86% in the Revised European-American Lymphoma (REAL) classification, but the designation of subtypes was less reliable. Diagnostic reliability improved from 41% to 86% after immunophenotyping, but did not improve further with the addition of detailed clinical data. Clinically, angiocentric nasal lymphoma presented in young females (median age 49 years) at extranodal sites, but with few adverse risk factors, whereas angioimmunoblastic lymphoma presented most often in older males (median age 65 years) at nodal and extranodal sites with numerous risk factors. The 5-year overall and failure-free survivals for patients with PTCL treated with doxorubicin (Adriamycin)-containing regimens were only 26% and 20%, respectively. Both failure-free and overall survival were strongly correlated with the performance status and International Prognostic Index scores at presentation, but differences in survival were not observed between the major histological types. However, within the PTCL 'not otherwise specified' category, but not angioimmunoblastic lymphoma, the number of transformed blasts was prognostically relevant. CONCLUSIONS: PTCLs can be diagnosed reliably by experienced hematopathologists, but immunophenotyping is absolutely necessary. Currently, all types of PTCL should be considered high-grade lymphomas. An increased ability to distinguish T-lymphocyte subsets is needed in order to better subclassify the PTCLs for therapeutic and prognostic purposes.

Adolescent↗

PubMed2001

Systemic anaplastic large-cell lymphoma: results from the non-Hodgkin's lymphoma classification project.

Anaplastic large-cell lymphoma (ALCL) is a heterogeneous process that may have a T-cell, B-cell, or indeterminant (null) phenotype and which may or may not express the anaplastic lymphoma kinase (ALK) oncoprotein. Because the clinical significance of these variants of ALCL is unclear, we evaluated the cases of ALCL-T/null and ALCL-B identified in the Non-Hodgkin's Lymphoma Classification Project. We evaluated 1,378 cases of non-Hodgkin's lymphoma (NHL), and a consensus diagnosis of ALCL-T/null was made in 33 patients (2.4%) with a diagnostic accuracy of 85%. Compared to 96 patients with other forms of peripheral T-cell lymphoma (PTCL), those with ALCL-T/null were significantly younger, less likely to have advanced-stage disease or bone marrow involvement, more likely to have a low International Prognostic Index score, and had a significantly better survival. Among those with ALCL-T/null, there were no significant differences in the clinical features or survival on the basis of ALK expression. A consensus diagnosis of ALCL-B was made in 15 patients (1.1%), and the diagnostic accuracy was 67%. However, compared to 366 patients with other forms of diffuse large B-cell lymphoma (DLBCL), those with ALCL-B were no different with regard to clinical features or survival. We conclude that patients with ALCL-T/null have favorable prognostic features and excellent survival and should be separated from those with other forms of PTCL for prognostic and therapeutic purposes. In contrast, patients with ALCL-B appear to be similar to those with other forms of DLBCL.

Adult↗

PubMed1999

The smoking cessation efficacy of varying doses of nicotine patch delivery systems 4 to 5 years post-quit day.

BACKGROUND: This study was undertaken to evaluate the long-term smoking cessation efficacy of varying doses of transdermal nicotine delivery systems 4 to 5 years post-quit day. METHODS: A follow-up study was conducted 48 to 62 months after quit day among patients who were enrolled in the Transdermal Nicotine Study Group investigation. The latter study included group smoking cessation counseling and randomized assignment to 21, 14, or 7 mg nicotine patches or placebo patches. Seven of nine smoking cessation research centers participated in the long term follow-up investigation. RESULTS: The self-reported continuous quit rate among patients originally assigned 21 mg (20.2%) was significantly higher than rates for patients assigned 14 mg (10.4%), 7 mg (11.8%), or placebo patches (7.4%). Log rank survival analysis found no difference in relapse rates after 1 year postcessation. Smokers under age 30 years were significantly less likely to be abstinent at long term follow-up compared to smokers > or = 30 years of age (3 vs 13%, respectively). Mean weight gain in confirmed continuous quitters was 10.1 kg in men and 8.0 kg in women. Of the 63 continuous abstainers surveyed, 30 respondents (48%) reported that they no longer craved cigarettes, and no individual reported daily craving for cigarettes. CONCLUSIONS: Nicotine patch therapy with 21 mg/day patches resulted in a significantly higher long-term continuous abstinence rate compared to lower dose patches and placebo. Relapse rates among the various treatment conditions were similar after 1 year postcessation.

Administration, Cutaneous↗

PubMed1998

Estrogen profiles in postmenopausal African-American women in a wheat bran fiber intervention study.

High dietary fiber intake has been hypothesized to lower blood estrogen concentrations, an effect thought to be beneficial for decreasing breast cancer risk. This study investigated the association between dietary supplementation of wheat bran and circulating estrogen levels in postmenopausal African-American women participating in a community intervention trial. Seventeen postmenopausal women (aged 63 +/- 1.6 yr) participated in the study. Nutritional status was assessed and blood and 24-hour urine samples were collected before and after five to six weeks of daily supplementation of the diet with 35 g of wheat bran cereal (11.6 g insoluble dietary fiber) marked with 28 mg of riboflavin. Riboflavin confirmed that all postmenopausal participants adhered to the intervention protocol. Nine of the 17 postmenopausal women were taking some form of estrogen replacement therapy (PM-ERT). Baseline hormone levels in the PM-ERT group did not significantly change after the dietary intervention. Estradiol (96.8 +/- 20.3 vs. 113.8 +/- 23.3 pg/ml), androstenedione (0.47 +/- 0.06 vs. 0.45 +/- 0.06 ng/ml), and sex hormone-binding globulin (SHBG, 107 +/- 13.5 vs. 106.6 +/- 13.3 nmol/l) levels remained constant. In the eight postmenopausal women who were not receiving exogenous hormones (PM), wheat bran consumption was not associated with predicted decreased levels of estradiol (25.7 +/- 2.7 vs. 31.0 +/- 1.9 pg/ml), estrone (38.3 +/- 10.1 vs. 39.3 +/- 10.6 pg/ml), and androstenedione (0.78 +/- 0.08 vs. 0.68 +/- 0.11 ng/ml) or with increased concentrations of SHBG (35.2 +/- 6.4 vs. 34.8 +/- 6.5 nmol/l). Participants receiving ERT had baseline and postintervention levels of estradiol and SHBG significantly higher and androstenedione significantly lower than those not receiving ERT. No association between wheat bran supplementation and hormone levels was found in PM or PM-ERT African-American participants. These results in postmenopausal women are in contrast to findings of earlier studies in premenopausal women indicating that wheat bran fiber decreases serum sex hormones. Estrogen levels in postmenopausal women are only 5-10% of those in premenopausal women; therefore, a high wheat bran fiber diet alone may not be sufficient to depress these low levels even further.

Aged↗

PubMed1997

Lengthening spells of uninsurance and their consequences.

The lengths of time adults are without health insurance have increased since 1988, as shown by data from 1,235 household interviews completed during 1992 in Nebraska. Rural residents without insurance have experienced longer such spells than their urban counterparts. Thus, while rates of uninsurance are nearly the same between urban and rural residents, important differences exist. The relationship between insurance status and physician utilization is consistent during the five years (1989 to 1993) covered in this study. Continuously insured persons have the most physician visits, followed by those intermittently insured, followed by those continuously uninsured. The number of physician visits was expected to increase when respondents moved from uninsured to insured status. However, among urban respondents, the number of visits declined; among residents in rural frontier counties (fewer than six person per square mile) and for respondents in rural nonfrontier counties, there was no significant difference. This study points out some differences between rural and urban populations regarding insurance status, even when the overall rates of uninsurance are equal.

Adult↗

PubMed1997

Potassium and magnesium retaining triamterene derivatives.

This work represents a summary of studies carried out with potassium and magnesium retaining triamterene derivatives. The synthesis, analytics and physico-chemical characteristics of those substances are described. Furthermore, the relationships between the chemical structure and electrolyte excretion, pharmacokinetics, metabolism and toxicity are demonstrated. An expanded model regarding the mode of action of triamterene and its derivatives is also presented.

Animals↗

PubMed1996

Potassium and magnesium retaining potency and efficacy of triamterene and analogues in conscious saline-loaded rats.

The effect of triamterene and analogues on the acute renal excretion of K+ and Mg2+ was investigated in conscious saline-loaded rats. The maximum retention (Emax) value of the potassium and magnesium retaining efficacy is almost independent of the structure of the compound and depends only on the initial basal value of ion excretion (E0). Triamterene and analogues display a comparable magnesium retaining efficacy. This can be explained by activity against the same renal Mg2+ transportation system. There was a relation between the ED50 values for the potassium and magnesium retaining properties of triamterene derivatives. Both the potassium and the magnesium retaining potency are dependent on the basicity as well as on the lipophilicity of the side chain of the triamterene derivatives. The part of the molecule responsible for the antimagnesiuretic properties of the derivatives seems to be sensitive to steric influences.

Animals↗

PubMed1995

Investigations on the acute toxicity of acidic and basic triamterene derivatives.

Acidic and basic triamterene derivatives were evaluated with respect to their acute toxicity. After single intravenous application in mice, derivatives with a basic side-chain were much more toxic than compounds with an acidic side-chain. There is a significant correlation between the potassium retaining properties (measured as ED50) and the acute toxicity (measured as LD50) of the substances. The low acute toxicity after oral application of the compounds can be explained by their low oral bioavailability.

Animals↗

PubMed1994

Serine 90 is required for enzymic activity by tRNA-guanine transglycosylase from Escherichia coli.

An Escherichia coli mutant described by Noguchi et al. [Noguchi, S., et al. (1982) J. Biol. Chem. 275, 6544-6550] contains tRNA lacking the hypermodified wobble nucleoside queuosine (Q) due to an inactive tRNA-guanine transglycosylase (TGT). TGT catalyzes the posttranscriptional base exchange of the Q precursor preQ1 with the genetically encoded guanine in tRNA(Asp,Asn,His,Tyr). The mutant tgt gene was cloned and sequenced; it contained a single point mutation resulting in the change of serine 90 to phenylalanine. Overexpression of the mutant gene yielded TGT(S90F) that showed a reduced solubility and did not purify in the same fashion as the wild-type enzyme. TGT(S90F) has no detectable enzymic activity. To determine whether serine 90 performs a catalytic role in the TGT reaction or whether the loss of activity was caused solely by a conformational change of the enzyme, we used site-specific mutagenesis to construct serine-to-alanine (S90A) and serine-to-cysteine (S90C) mutants. Both S90A and S90C mutants were purified in a manner identical to that used for the wild-type enzyme. SDS-PAGE of dimethyl suberimidate-cross-linked mutants showed a pattern identical to that of the wild-type TGT, indicative of a trimeric quaternary structure. Native PAGE of wild-type and mutant TGTs in the absence and presence of substrate tRNA exhibited band shifts indicating that both mutants retain the ability to bind tRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1994

Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome.

Facial morphometry using computerised image analysis was performed on patients with growth hormone receptor deficiency (Laron syndrome) from an inbred population of southern Ecuador. Morphometrics were compared for 49 patients, 70 unaffected relatives, and 14 unrelated persons. Patients with growth hormone receptor deficiency showed significant decreases in measures of vertical facial growth as compared to unaffected relatives and unrelated persons with short stature from other causes. This report validates and quantifies the clinical impression of foreshortened facies in growth hormone receptor deficiency.

Adolescent↗

PubMed1992

Preparation and diuretic properties of novel amiloride analogues.

Fifteen novel amiloride analogues were synthesized and their diuretic properties compared to amiloride and triamterene in white wistar rats. Whereas none of the 6-substituted derivatives exhibited significant natriuretic and antikaliuretic effects, five of the compounds modified in the 2-position were found equal or better than standards. The results are discussed with respect to chemical structure and physiochemical properties.

Amiloride↗

PubMed1992

Effects of a new pteridine derivative on urinary sodium, potassium and magnesium excretion in conscious saline-loaded rats.

1. Two recently synthesized pteridine derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.

Animals↗

PubMed1992

Synthesis, natriuretic, antikaliuretic and antimagnesiuretic properties of an acidic triamterene derivative.

2,4,7-Triamino-6-(4-methanesulfonamidophenyl) pteridine (RPH 3048) is a new acidic triamterene derivative. Relevant physico-chemical constants were determined (solubility at pH 7.4 = 3.7 mg/l; logP at pH 7.4 = 0.2) and pharmacokinetic as well as pharmacodynamic properties were investigated, using male Wistar rats. After intravenous application of the test substances urine was collected, its volume and electrolyte composition determined, and the urine recovery of the drugs was analysed. The comparison of RPH 3048 with triamterene (CAS 396-01-0) revealed almost equipotent natriuretic and potassium-retaining effects for both drugs and an additional relative magnesium-sparing activity of RPH 3048. The urine recovery of RPH 3048 after 6 h was higher (20.6%) than that of triamterene (12.9%). No metabolite of RPH 3048 could be detected in the urine whereas a triamterene metabolite was found. Due to its good solubility in alkaline medium RPH 3048 could be dissolved (at pH 11-12) and then administered intravenously together with a loop diuretic (furosemide). Urinary electrolyte excretion following administration of two different combinations of RPH 3048 and furosemide (combination A: 12.5 mumol/kg RPH 3048 and 25 mumol/kg furosemide; combination B: 25 mumol/kg RPH 3048 and 25 mumol/kg furosemide) was compared to urinary electrolyte excretion of a control group and a group only treated with furosemide (25 mumol/kg). The additional application of RPH 3048 reduced in both groups potassium and magnesium excretion to control level but did not compromise furosemide induced natriuresis. In contrast to earlier investigations these results suggest that it is possible to develop acidic triamterene derivatives with potent antikaliuretic effects.

Animals↗

PubMed1991

In vitro testing of triamterene derivatives for antiarrhythmic activity.

A series of para-substituted triamterene derivatives (Table 1) were evaluated for their antiarrhythmic properties in vitro. Pharmacological evaluation of the compounds and some class-I- (quinidine, lidocaine, and propafenone) as well as class-III-antiarrhythmic drugs ((+/-)-sotalol and amiodarone) was carried out by measuring the functional refractory period (FRP), the maximal driving frequency (MDF) and the force of myocardial contractions (FC) of electrically stimulated guinea pig atria. The increase in FRP and the decrease in MDF was most pronounced with the class-I-antiarrhythmic drugs, but these compounds showed the typical negative inotropic effects, too. For the class-III-antiarrhythmics only a weak influence on FRP and MDF could be demonstrated, while FC was not altered in the presence of (+/-)-sotalol and amiodarone. Neutral substituted triamterenes like compounds 2-5 as well as most of the benzyltriamterene derivatives showed similar or stronger effects on FRP and MDF as (+/-)-sotalol and amiodarone. With the exception of 4 and 5, these effects were combined with an increase of FC. Compounds 6 and 7, well known-potent diuretics, showed no influence to FRP, MDF and FC. Therefore, we conclude different mechanisms for the antikaliuretic and cardiac activity.

Animals↗

PubMed1991

Antiarrhythmic properties of triamterene derivatives in the coronary artery ligated rat model.

Triamterene and several triamterene derivatives were tested for antiarrhythmic activity in the coronary artery ligated and reperfused (CAL-R) rat. The class-III antiarrhythmic drugs (+/-)-sotalol and amiodarone, the class-I antiarrhythmics lidocaine and quinidine as well as the potassium sparing diuretic amiloride were used as reference drugs. Triamterene at the highest dose (30 mumol/kg) revealed a 100% protection against ventricular fibrillation (VF), whereas at 10 mumol/kg no antiarrhythmic activity for triamterene could be found. For compound 4 (10 mumol/kg) a 75% protection against VF could be demonstrated, while 2, 3, and 5 revealed only a 25% protection. Compared to the reference drugs, triamterene and the derivatives 2-5 are more potent than (+/-)-sotalol, but less potent than lidocaine, quinidine and amiodarone. For amiloride as well as for the potent potassium retaining triamterene derivative 6 no antiarrhythmic activity could be shown. Therefore, we conclude different mechanisms responsible for the potassium sparing and antiarrhythmic properties of triamterene and its derivatives.

Animals↗

PubMed1991

Structure and organization of Escherichia coli genes involved in biosynthesis of the deazaguanine derivative queuine, a nutrient factor for eukaryotes.

The plasmid pPR20 contains the gene tgt, which encodes tRNA guanine transglycosylase (Tgt), on a 33-kbp DNA insert from a region around 9 min on the Escherichia coli linkage map. The plasmid was subcloned to determine the sequence and organization of the tgt gene. Tgt is a unique enzyme that exchanges the guanine residue with 7-aminomethyl-7-deazaguanine in tRNAs with GU(N) anticodons. After this exchange, a cyclopentendiol moiety is attached to the 7-aminomethyl group of 7-deazaguanine, resulting in the hypermodified nucleoside queuosine (Q). Here we give the complete sequence of a 3,545-bp StuI-BamHI DNA fragment where we found the tgt gene and three previously unknown genes encoding proteins with calculated molecular masses of 42.5 (Tgt), 14, 39, and 12 kDa. The gene products were characterized on sodium dodecyl sulfate gels after synthesis in a combined transcription-translation system. The mRNA start sites of the open reading frames (ORFs) were determined by primer extension analysis. Plasmids containing the ORF encoding the 39-kDa protein (ORF 39) complemented a mutation in Q biosynthesis after the Tgt step. This gene was designated queA. The genes are arranged in the following order: ORF 14 (transcribed in the counterclockwise direction), queA, tgt, and ORF 12 (all transcribed in the clockwise direction). The organization of the promoter sequences and the termination sites suggests that queA, tgt, and ORF 12 are localized on a putative operon together with the genes secD and secF.

Amino Acid Sequence↗