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Biomedical subjects

T Krebs

Publications and source records attributed to T Krebs.

At least 19 recordsLinked to original sources

Mycobacterium genavense infection in a patient with long-standing chronic lymphocytic leukaemia.

We describe the first case of disseminated infection with Mycobacterium genavense in an HIV-seronegative patient with a chronic haematological disorder. Our patient, an 80-year-old woman, had been under long-term treatment with chlorambucil (partially in combination with prednisone) for B-cell chronic lymphocytic leukaemia (B-CLL). When she developed general fatigue and progressive anaemia, as well as progressive lymphadenopathy and splenomegaly, bone marrow biopsy revealed granulomas with acid-fast bacilli, and cultures of both bone marrow and blood grew M. genavense. The patient's CD4+ cell count was approximately 100 microL(-1). Treatment with clarithromycin, ethambutol and rifabutin resulted in improvement of anaemia and general health as well as in regression of lymphadenopathy and splenomegaly.

Aged↗

Helical computerized tomography arteriography for evaluation of live renal donors undergoing laparoscopic nephrectomy.

PURPOSE: Traditionally, live renal donors are evaluated with excretory urography and renal arteriography. Helical computerized tomography (CT) arteriography offers a less invasive alternative for demonstrating necessary anatomical information before laparoscopic allograft harvest. We evaluate the accuracy of helical CT arteriography in depicting renal vascular anatomy with an emphasis on the detection of arterial and venous anomalies. MATERIALS AND METHODS: Imaging studies were done on 175 patients according to a standard CT arteriography protocol with early arterial phase scanning (14 to 20-second delay), and 1 mm. axial and 3-dimensional maximum intensity projection reconstructions. Renal vascular anatomy was mapped with attention to aberrant arterial and venous anatomy. Intraoperative findings were correlated at laparoscopic donor nephrectomy. RESULTS: There was overall agreement between CT arteriography and laparoscopic findings in 163 cases (93%). Supernumerary renal arteries were identified in 40 cases (23%). Sensitivity, specificity and accuracy of CT arteriography for arterial anatomy were 91, 98 and 96%, respectively. Cases with less than 2 mm. accessory arteries or early branching single vessels simulating dual arteries were misdiagnosed. Venous anomalies occurred in 11 patients (6.3%). Sensitivity, specificity and accuracy of CT arteriography for venous anatomy were 65, 100, and 97%, respectively. Misdiagnoses included early venous bifurcations and supernumerary tributary veins, which were poorly opacified. CONCLUSIONS: Helical CT is highly accurate and specific for the demonstration of renal arterial anatomy. Poor opacification resulted in a lower sensitivity for venous anatomy. Overall, helical CT provides essential anatomical information, and is an alternative to standard urography and arteriography.

Adult↗

Absence of chronic effect of exposure to short-wave radio broadcast signal on salivary melatonin concentrations in dairy cattle.

A pilot study was conducted to investigate the influence of electromagnetic fields in the short-wave range (3-30 MHz) radio transmitter signals on salivary melatonin concentration in dairy cattle. The hypothesis to be tested was whether EMF exposure would lower salivary melatonin concentrations, and whether removal of the EMF source would be followed by higher concentration levels. For this pilot study, a controlled intervention trial was designed. Two commercial dairy herds at two farms were compared, one located at a distance of 500 m (exposed), the other at a distance of 4,000 m (unexposed) from the transmitter. At each farm, five cows were monitored with respect to their salivary melatonin concentrations over a period of ten consecutive days. Saliva samples were collected at two-hour intervals during the dark phase of the night. As an additional intervention, the short-wave transmitter was switched off during three of the ten days (off phase). The samples were analyzed using a radioimmunoassay. The average nightly field strength readings were 21-fold greater on the exposed farm (1.59 mA/m) than on the control farm (0.076 mA/m). The mean values of the two initial nights did not show a statistically significant difference between exposed and unexposed cows. Therefore, a chronic melatonin reduction effect seemed unlikely. However, on the first night of re-exposure after the transmitter had been off for three days, the difference in salivary melatonin concentration between the two farms (3.89 pg/ml, CI: 2.04, 7.41) was statistically significant, indicating a two- to seven-fold increase of melatonin concentration. Thus, a delayed acute effect of EMF on melatonin concentration cannot completely be excluded. However, results should be interpreted with caution and further trials are required in order to confirm the results.

Animals↗

[Development of a mandibular model for evaluating and optimizing the design of osteosynthesis materials using finite element analysis].

The present study was designed to investigate biomechanical and clinical changes in the mandibular complex by means of finite element analysis. An analytical model developed from human native mandibles was used for this model, CT image data were transferred to a computer, and an edge extraction program generated the cross-section of bone by specifying a range of CT values for each slice. Pixel data from the CT scan were converted into a vector of points (x, y, z) which can specify the boundaries of bone. Lateral surfaces are defined by stacking up the slices and making use of the vectorized data. The constructed model was used as input data for the finite element analysis. The models were solved for stresses and forces. The highest principal stresses occurred at the bite point, anterior aspects of the coronoid processes, symphyseal region, and right and left sides of the mandibular corpus. For further investigation muscular structures have to be integrated to establish a model, which can be analysed under multivariate aspects.

Biomechanical Phenomena↗

Mesenchymal-epithelial interactions and transforming growth factor-beta expression during mouse prostate morphogenesis.

To explore the role of transforming growth factor-beta (TGF beta) isoforms and other growth-related genes during prostate morphogenesis in the mouse, we examined mRNA levels in fetal day 17 urogenital sinus, mesenchyme (UGM), and epithelium (UGE) as well as in the ventral, dorsal, and anterior lobes of the adult prostate. In addition, we used antiserum specific for extracellular TGF beta 1 in immunohistochemical studies to localize accumulation of the TGF beta 1 isozyme in the above tissues as well as those derived from fetal day 19 and neonatal mouse prostate. Differential patterns of expression in fetal and adult tissues were seen. TGF beta 1, -beta 2, and -beta 3 expression was substantially elevated in UGM compared to that in UGE, yet only TGF beta 1, not TGF beta 2 or TGF beta 3, mRNA levels were sustained in adult prostate tissues. High levels of accumulation of TGF beta 1 were demonstrated by immunohistochemistry in the mesenchymal compartment compared to those in the epithelial compartment throughout development. Interestingly, the highest levels of TGF beta 1 appeared in areas of active epithelial duct formation and delineated the mesenchymal architectural changes necessary for ductal network formation. Additional studies revealed that levels of mRNAs for other genes involved in tissue remodeling and growth were also elevated in UGM compared to those in UGE. Tissue plasminogen activator, urokinase plasminogen activator, androgen receptor, and c-myc mRNA levels were also elevated in UGM compared to UGE. Interestingly, whereas tissue plasminogen activator mRNA levels, like those of TGF beta 2 and -beta 3, were barely detectable in adult prostatic tissues, mRNA levels for urokinase plasminogen activator, androgen receptor, and c-myc were readily detected and expressed in a lobe-specific fashion. Overall, these data indicate that expression of TGF beta 1 isoforms and other growth-related genes is associated with mesenchymal cells in areas of active morphogenesis during prostate development and provide objective molecular and cellular information regarding mediators of mesenchymal-epithelial interactions in prostate.

Animals↗

[Long-term results after infrainguinal arterial reconstruction in patients with type 2 diabetes mellitus and without diabetes mellitus].

The influence of type II diabetes on the success rate of arterial bypass operations in the leg was assessed in a prospective study, since 1984, of long-term results of infrainguinal arterial reconstruction in 67 type II diabetics (41 men and 26 women; mean age 71.2 [47-90] years) and compared with 133 nondiabetics (90 men and 43 women; mean age 71.5 [45-91] years). All had a bypass for chronic critical ischaemia of the legs. Graft patency, leg preservation and survival rate were calculated and compared by the actuarial method. Coronary heart diseases and cerebral ischaemia were a little more common in the diabetic group, but the incidence of heart failure was the same (20%). A venous bypass was used in 73% of diabetics, polytetrafluoroethylene grafts in 27% (nondiabetics: 79% and 21%). Bypass occlusions occurred in 9 diabetics and in 24 nondiabetics (not significant). During the observation period of 5 years 37 diabetics (55%) and 39 nondiabetics (29%) died (P less than 0.001). These data indicate that the results of infrainguinal arterial bypass operations are equally good in diabetics and nondiabetics. Amputation was avoided in 80% of legs at risk in both groups. Primary amputation is indicated only in exceptional circumstances.

Aged↗

Elevated transforming growth factor-beta 1 and beta 3 mRNA levels are associated with ras + myc-induced carcinomas in reconstituted mouse prostate: evidence for a paracrine role during progression.

Mouse prostate reconstitution is a useful model for studying the progression of ras + myc-induced carcinomas. When these oncogenes were introduced into both the epithelial and the mesenchymal compartments, poorly differentiated adenocarcinomas resulted. Restricted introduction of both oncogenes into the epithelium produced epithelial hyperplasia. Malignancies were produced in two out of 17 cases of selectively transformed epithelium, suggesting that the hyperplastic condition represents a premalignant phenotype. Restricted introduction of both oncogenes into the mesenchyme produced only mesenchymal dysplasia. Transforming growth factor-beta 1 (TGF-beta 1) and beta 3 (TGF-beta 3) mRNA levels were elevated in the ras + myc-induced carcinomas when compared to the normal controls or to the epithelial hyperplasias. In contrast, TGF-beta 2 mRNA levels were similar in all control and ras + myc-induced carcinomas. Elevated TGF-beta 1 mRNA levels were also found in mesenchymal dysplasia pointing to a potential paracrine activity by the ras + myc transformed mesenchyme. We conclude that elevated TGF-beta 1 and beta 3 are correlated with progression to malignancy and that mesenchyme derived TGF-beta 1 may play an important role in the promotion of ras + myc-induced carcinomas in this model system.

Animals↗

Experimental oncogene induced prostate cancer.

The mouse prostate reconstitution model exploits the ability of the fetal urogenital sinus to differentiate into a mature prostate when grafted under the renal capsule of an adult isogenic male host. By use of a recombinant retroviral vector, the ras and myc oncogenes are introduced singly or in combination into the fetal urogenital sinus--resulting in distinct phenotypes of prostatic pathology: dysplasia (caused by ras), hyperplasia (caused by myc) and frank carcinomas (caused by a combination of ras+myc). This unique experimental model creates in vivo conditions that mimic the natural initiation and progression of cancer. An expanded MPR protocol allows restricted retrovirus infection of the mesenchyme or epithelial compartments to evaluate paracrine activities. It enables almost unparalleled flexibility in addressing fundamental questions in prostate cancer. We have identified genetic variance in the susceptibility to tumour induction between two different strains of mice (mimicking the observation of racial variability in the predisposition to clinical prostate cancer). The MPR model supports data from other tumour models and implicates TGF-beta 1 and TGF-beta 3 as being strongly associated with tumour progression. Finally, with this model, we have established clonal prostate adenocarcinomas to study directly the affects of castration on gene expression. Not only are TGF-beta 1 and TGF-beta 3 mRNA levels increased in association with malignancy but they are also further enhanced by castration treatment. Based on these experimental studies, we believe that TGF-beta 1 and TGF-beta 3 expression strongly influences the progression of prostate cancer. This information will hopefully impact on the development of more effective therapy for this important malignancy.

Adenocarcinoma↗

[Infra-inguinal arterial reconstruction: in situ or reversed venous bypass?].

Since 1984 one of our surgeons treated 154 patients for infrainguinal arterial insufficiency. The patients had a mean age of 72 years and suffered from multiple concomitant diseases. The indication for operation consisted in a chronic critical ischemia in every case. 98 reversed (RV) and 56 in situ (IS) vein bypasses had to be implanted. No statistical significant differences could be found concerning survival, graft patency and limb salvage (life table analysis). Nearly half of our patients died during the 5 year observation period. The cumulative 5 year graft patency and limb salvage rate was 86% and 89% in the RV and 80% and 84% in the in situ group.

Aged↗

[The value of suprageniculate femoro-popliteal polytetrafluoroethylene prosthesis in surgical treatment of chronic arterial occlusive disease].

From January 1982 to December 1989, 74 patients with chronic critical ischemia were treated with an above knee-femoropopliteal PTFE-Bypass. The 5-year cumulative patency rate was 48%, the cumulative limb salvage rate 66%. In the same observation period 40 patients with a reversed saphenous vein above knee-Bypass were also followed-up. In this group the cumulative 5-year patency rate amounted to 77% and the limb salvage rate to 100%. The autogenous saphena magna is the conduit of choice for lower extremity artery bypass grafting. It showed in above knee reconstructions statistically significant superior results in comparison to PTFE grafts.

Adult↗

Comparison of ultrasensitive methods for the measurement of IgE.

Because the study of human IgE synthesis and regulation requires exquisitely sensitive and rapidly performed methods for assay of in vitro IgE production, we compared 4 methods for radiometric immunoassay (RIA) of human IgE: double antibody RIA (DARIA), ultrasensitive enzymatic RIA (USERIA), sensitive paper radioimmunosorbent test (SPRIST) and microtiter solid-phase RIA (MSPRIA). IgE protein was measured in serum samples and cord bloods. The USERIA and the MSPRIA consistently detected levels of IgE as low as 27-35 pg/ml. The DARIA and SPRIST were less sensitive. Comparison of the USERIA and the MSPRIA favored the latter because: (1) it is a more rapidly performed assay, (2) it involves fewer manipulations, and (3) it has less variability. We conclude that the MSPRIA for IgE is superior to the other methods both as a research tool for measuring minute quantities of IgE protein (as in tissue culture supernatants) and for measuring IgE in serum samples where concentrations fall below 1 ng/ml (0.42 IU/ml; 1 IU = 2.4 ng).

Humans↗

Identification of the prosthetic group of urocanase. The mode of its reaction with sodium borohydride and of its photochemical reactivation.

Urocanase from Pseudomonas putida and from beef liver were isolated by modifying described procedures. Both enzymes were inactivated and labeled on treatment with tritiated sodium borohydride and gave, upon subsequent hydrolysis, a radioactive acid. The previously reported identity of this acid as 2-hydroxybutanoic acid was disproved by several criteria. Other hydroxy acids were also proved to be different from the radioactive acid derived from urocanase. A large portion of the radioactive material from P. putida was found to be nicotinic acid by 1H NMR spectroscopy, gas-liquid chromatography of its methyl ester, and co-crystallization with authentic reference compounds both as the acid and as the hydrazide. A significant portion of the radioactive material derived from beef liver urocanase also co-crystallized with nicotinic acid. Sodium borohydride-treated inactive urocanase was partially reactivated by light. The action spectrum of the photoreactivation showed a maximum at 330 nm. Treatment of urocanase with sodium borodeuteride followed by hydrolysis afforded a sample of nicotinic acid which carried deuterium mainly in position 6. Both the reversible reducibility of urocanase and its action spectrum of photoreactivation suggest that urocanase contains an enzyme-bound nicotinamide nucleotide molecule which is essential for enzymic activity.

Animals↗

Synthesis of stereospecifically deuterated phenylalamines and determination of their configuration.

1. Starting from trans-cinnamic acid a chiral (-)3-phenyl-[2,3-2H]propionic acid has been synthesized using Clostridium kiuyveri cells as catalyst. 2. The chiral dideuterated acid has been converted by chemical methods to a mixture of (2R) and (2S)-phenyl[2,3-2H]-alanine. 3. By means of 1H nuclear magnetic resonance spectroscopy and the action of D and L-amino acid oxidase the configuration of the phenylalamine has been shown to be (2R, 3S) and (2S, 3S), respectively. The labelled phenylalanine is thus sterically and isotopically homogenous at position 3 but heterogenous at position 2.

Amino Acid Oxidoreductases↗