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Biomedical subjects

E Klotz

Publications and source records attributed to E Klotz.

At least 37 records · Page 2Linked to original sources

The mechanism of somatic hypermutation studied with transgenic and transfected target genes.

Somatic hypermutation of Ig genes is beginning to be understood in molecular terms. Ig transgenes have served as model test genes and been shown to mutate, just as endogenous genes, with a peak of mutation over the VJ region and a sparing of the C region. The levels of somatic mutation appear to be related to the expression of the transgenes. DNA hypermethylation of modified Ig transgenes interferes with both expression and somatic hypermutation. Test substrates consisting of bacterial lacZ alpha or supFtRNA inserted within x transgenes were shown to be rescuable as expressible bacterial plasmids, but did not seem to be targeted. A synthetic sequence consisting of alternating restriction enzyme sites, that cannot be subject to methylation, was found to be a reliable transgenic substrate for easy assay of somatic mutation. The generation of a transgenic mouse with a x transgene in which the transcriptional promoter has been duplicated upstream of the C region has given new clues to the mutation mechanism. In this transgene, transcripts initiate from both the C region and the V region promoters, and both regions, but not the sequences between them, are hypermutated. These results suggest that somatic hypermutation is linked to the initiation of transcription. A model is proposed in which somatic mutation is dependent on transcription coupled DNA repair.

Animals↗

N region diversity of a transgenic substrate in fetal and adult lymphoid cells.

The rearrangement of immunoglobulin (Ig) and T cell receptor (TCR) genes requires the activity of an as yet undefined V(D)J recombinase. One component of the recombinase appears to be a terminal transferase which may be involved in the addition of untemplated nucleotides (N regions) to the V(D)J joints. It has been observed that rearranged Ig and TCR genes isolated from fetal liver have few if any N regions, whereas in the adult mouse, these genes have a large number of untemplated nucleotides. The presence of N regions greatly alters the composition of the third hypervariable, complementarity determining region of the respective proteins, thus playing a major role in the conformation of the binding site. It was possible that, for functional reasons, N region-containing Ig and TCR genes were not permissible at the fetal stage of development. We have produced transgenic mice with a rearrangement test gene which, after V-J recombination, does not result in the production of functional Ig or TCR proteins. We report here that the rearrangement products have no N regions in fetal liver, but that the majority of joints in adult lymphoid tissues have N additions. The study is also an interesting demonstration of the randomness of rearrangements and the enormous variability that can be created from a single pair of V and J sequences.

Animals↗

Rearrangement and expression of immunoglobulin genes in transgenic mice.

Transgenic mice are discussed which carry a rearrangement test transgene. The methylation status of the transgene varies, depending on the background mouse strain. When the transgene is bred into the C57BL/6 strain, it is completely methylated and not rearranged in lymphoid organs. After several generations of crossing into DBA/2 or SJL the transgene becomes unmethylated and rearranges at high frequency. A strain specific modifier of DNA methylation (Ssm-1) was mapped close to the Friend virus susceptibility locus (Fv-1) on mouse chromosome 4. Rearranged transgenes from spleen, bone marrow and thymus of adult mice or fetal liver were cloned and sequenced. A great variety of joints was found, with about 1/3 being in the correct reading frame. Small deletions into the V- and J-coding ends as well as N region additions contributed to the variability. The fetal joints showed no N regions. Since no functional immunoglobulin (Ig) gene can be created from this artificial test gene, the data indicate that the rearrangement mechanism of the fetus differs from that of the adult.

Animals↗

[Radiation exposure during defecography].

The introduction of a new radiological method requires the assessment of the advantage-risk ratio. On measuring the radiation doses during defecography, skin entrance and gonadal exposure values were found to be lower than during well-known and well-established examinations of the small pelvis, such as colon enema and CT of the lower abdomen. Defecography, as a radiological tool for diagnosing the anorectal function is, therefore, also suitable for young persons.

Defecation↗

[Icteric cholestasis as an early symptom in Hodgkin's disease].

Initial symptoms in a hitherto healthy 23-year-old man were jaundice (bilirubin 21.7 mg/dl) and pruritus, but extensive radiological, endoscopical, microbiological and laboratory investigations failed to reveal the cause. Stool culture positive for Salmonella agona suggested intrahepatic cholestasis resulting from a Salmonella cholangitis. However, antibiotic treatment was not successful. As he was in generally good health the patient declined further investigations. He returned two years later because of fatigue, lack of appetite and weight loss. Further tests now revealed lymphogranulomatosis in stage IVb of the nodular sclerosing type. The case demonstrates that cholestasis as an isolated early symptom of Hodgkin's disease can precede by years any further signs of the disease.

Adult↗

Spiral volumetric CT with single-breath-hold technique, continuous transport, and continuous scanner rotation.

Continuous computed tomographic (CT) scanning of organ volumes during a single breath hold was studied. The authors modified the table feed mechanism of a continuously rotating CT scanner to allow patient transport at low, but accurately controlled, speeds (0.1-11.0 mm/sec) during continuous 1-second scanning. An algorithm was designed to reconstruct artifact-free images for arbitrary table positions from the helical data by interpolating between adjacent scans. Section sensitivity profiles were enlarged; the section width for a 10-mm section and a speed of 10.0 mm/sec was increased by a factor of 1.3, compared with the nominal value. Clinical examples were presented for studies of lung nodules and studies enhanced with contrast medium. Major advantages are the possibility of continuous scanning of extended volumes within a breath-hold period and retrospective, arbitrary selection of anatomic levels.

Humans↗

Digital flashing tomosynthesis (DFTS)--a technique for three-dimensional coronary angiography.

Digital Flashing Tomosynthesis (DFTS) represents a technique for three-dimensional (3D) coronary angiography. Four ECG-gated simultaneously flashed X-ray tubes generate a multiperspective digital substraction image as DFTS multiangiogram for 3D reconstruction and visualization. Computerized morphologic and morphometric quantitative analysis can be performed including videodensitometry. Postmortem coronary angiography of 30 human hearts with suspected coronary artery disease was performed by 35-mm cine technique and by DFTS. The results of angiographic measurements in 50 stenotic arterial segments were compared with the histologic reference and show excellent regression results with correlation coefficients of more than 0.95 (p less than or equal to 0.0001). No significant differences in standard errors of estimates between the techniques were found. DFTS yields an accuracy in depiction of the coronary arteries and angiographic estimation of arterial lumen equivalent to 35-mm cineangiography. DFTS images can be directly used for visual interpretation and for computerized morphologic and morphometric quantitative analysis. DFTS technology reduces the amount of radiation exposure, the amount of contrast medium, and the time of the procedure. DFTS offers the possibility to obtain 3D images of the coronary artery tree.

Aged↗

Iotrolan versus iopamidol: a controlled, multicenter, double-blind study of lumbar and direct cervical myelography.

Iotrolan is a new nonionic, dimeric contrast medium that is distinguished by its special physicochemical and low chemotoxic properties. It displays near isotonicity with blood and cerebrospinal fluid in all clinically used concentrations (190, 240, and 300 mg I/ml). The controlled, double-blind study of iotrolan versus iopamidol presented here shows that iotrolan is significantly superior to the monomeric contrast medium in lumbar and direct cervical myelography. Use of the dimeric contrast medium reduced not only the incidence of side effects, but also their severity and duration. The chemotoxicity of contrast media commonly used was significantly less with iotrolan in all neuroradiologic diagnostic studies of the spine. The diagnostic quality of lumbar and direct cervical myelography with iotrolan was high. In this randomized, double-blind study versus iopamidol, iotrolan proved to be the safer and better myelographic agent for contrast studies of the spinal canal.

Adolescent↗

Reference values for trabecular and cortical vertebral bone density in single and dual-energy quantitative computed tomography.

The validity of reference values for vertebral bone mineral density (BMD) reported in the literature has frequently been questioned. The introduction of dual-energy methods, new calibration systems, and automated image evaluation algorithms, has also made it necessary for us to re-evaluate BMD values in a normal population. We present patient selection criteria, CT measurement and evaluation protocols and results of single energy (SEQCT) and dual energy quantitative CT (DEQCT) for trabecular (tBMD) and cortical (cBMD) bone density in 135 males and 139 females. For SEQCT, tBMD loss rates of 1.7 and 1.8 mg/ml per year for males and females, respectively, were determined by linear regression. The respective DEQCT data show smaller decrements with age. Different statistical models for tBMD in females were tested; models based on a multiphase variation of tBMD yielded an improvement of the fit. For cBMD the percent rate of loss with age is much smaller than for tBMD; females showed a significantly higher loss rate than males, however. A comparison of our results with published data is included.

Absorptiometry, Photon↗

Generation of a subtraction mask for digital angiography based on the movement of the coronary arteries.

A synthetic mask technique for angiography of coronary arteries was experimentally studied, using conventional 35 mm film sequences of coronary arteries. The method makes use of the fact that because of the movement of the heart vessels different parts of the background will be hidden. The background is extracted from two or more neighbouring frames by computer assistance and afterwards used for a subtraction mask. The experiments showed that the synthetic masks are of a good accuracy, the background anatomy is markedly reduced and the contrast is increased.

Angiography↗

Vertebral bone mineral analysis: an integrated approach with CT.

In the assessment of vertebral bone mineral density (BMD) with quantitative computed tomography, accuracy is limited by systematic errors caused by beam-hardening effects and unknown marrow and fat concentrations in trabecular bone. Reproducibility depends on precise repositioning of the patient, selection of the region of interest (ROI), and apparatus stability. In an integrated approach, these error sources were taken into account. Dual-energy methods are incorporated and tested to avoid systematic errors. Contour-detection algorithms for automated ROI determination that work reliably and offer improved reproducibility and efficiency are presented. A new design of reference phantom with solid tissue-equivalent materials provides calibration in BMD units and checks apparatus stability. Dual-energy methods are necessary to achieve accuracy of 5% or better. Automated ROI definition and reference phantom methods are mandatory for reproducibility of 2% or better.

Algorithms↗

[Material-selective imaging and density measurement using the dual-energy method. I. Principles and methodology].

The principles of the Dual Energy method are discussed from two perspectives: a clear illustration of the method and an exact presentation of the principles involved. The principles apply to both radiography and computed tomography. The method was implemented on a CT scanner (SOMATOM DR, Siemens AG). Dual Energy images enable highly selective imaging based on the determination of density values for calcified and soft tissue. Images may also be reconstructed that are based on other parameters such as electron density and effective atomic number. The degree to which selective imaging is possible is discussed. Examples of Dual Energy clinical applications for radiography and computed tomography are presented. More detailed information will be available in future contributions.

Humans↗

[Current state of the Würzburg database for radiotherapy].

Initially the data bank, which serves for the follow-up organization and for scientific studies, is briefly introduced. Then the possible analyses are described. Two types of possible evaluations can be distinguished. For the first type of evaluation, a subprogram has to be developed for every topic. A great number of questions can be answered by assembling the subprograms. These evaluations mostly dispose of a direct access to the data bank, so that the information desired is immediately available. For the second type of evaluation, the features of a group of patients have been determined with the aid of the data bank and have been stored then. A simple questioning language allows the establishment of any condition limiting the patient groups and its transmission to a statistical program package. Some examples are given to describe the possibilities of the statistical program developed especially for medical studies which makes it possible to perform analyses according to the life table method, too.

Database Management Systems↗

[Experiences with processing control in the radiology department of a large municipal hospital].

Processing control is an important part of quality control in X-ray diagnostics. From 1 July 1984 to 31 December 1985 the processing of 10 of the 11 processors in the Radiology Department at the Augsburg Municipal Hospital was controlled regularly on a total of 304 days. The speed index was at 95.8%, the contrast index at 96.1% within the limits recommended by the Federal German DIN standard. Processing control has proved meaningful and effective in keeping processing on a constant level. It also indicates where to look for the reasons for poor image quality. It takes less than 5 minutes to carry out the processing control of one processor. Processing control is a task of the radiographer.

Germany, West↗

[Examination and patient management in x-ray diagnosis using a computerized hospital communication system].

Concept, realization and our 2-year experiences in the routine use of a computerized data-processing communications system supporting the central radiology department in a 1,625-bed, municipal hospital are discussed. Via the hospital ward-linked terminal network, routine X-ray examination is so ordered that individual medical case information is provided, which certifies qualified clinical and diagnostic procedure along with good patient preparation and transportation. Complete information and documentation are also ensured. It was shown that good motivation among involved radiologists and their close working-association with other departments are mandatory from the start to maintain exact time schedules and satisfactory completion of ordered X-ray procedures. Subsequently, the assistence of computerized data processing is accepted for routine use, as time goes by, insofar as it is appropriate by used.

Computers↗

[Selective coronary angiography via flashing tomosynthesis].

To assess the value and significance of short-term tomosynthesis in judging the pathological condition of coronary vessels, the authors examined 34 patients with coronary heart disease. In comparison with 35 mm cinecoronary angiography, all angiographically determined vascular occlusions and stenoses were identified via short-term tomosynthesis. Comparison of the degrees of stenoses yielded good correlation (r = 0.85). Short-term tomosynthesis offers the advantage of employing smaller amounts of contrast medium to be injected; furthermore, the examination period is shorter, and exposure to radiation is also significantly less.

Cineangiography↗

First clinical results with digital flashing tomosynthesis in coronary angiography.

Digital flashing tomosynthesis (D-FTS) investigations have been performed using a new nonlinear reconstruction algorithm. It is called extreme-value decoding and produces significantly less artefact than back projection used commonly in tomosynthesis. The reduction of artefact allows the use of tomosynthesis based on only four projections in the case of dilute objects, i.e. objects with only a small number of high absorbing voxels. This condition can be realized in angiography by cancelling soft-tissue and bones by subtraction (e.g. DSA technique). The new technique has been carried out in 10 patients with coronary artery disease after investigation with standard 35 mm cineangiography. For the recording step of the D-FTS images we have used a multiple X-ray source. For the digital nonlinear reconstruction step we have used a VAX 11/780 computer. The estimated degree of stenosis found by D-FTS tomograms shows good accordance with the cineangiographic studies. The amount of contrast medium, the X-ray dose, and the investigation time are significantly reduced, because D-FTS requires only a single pre- and post-injection multiple perspective-image for each coronary artery.

Cineangiography↗

Coronary angiography with flashing tomosynthesis.

Thirty-four patients with coronary artery disease were studied with standard 35 mm coronary cineangiography and flashing tomosynthesis, to assess the value of the latter technique to detect stenotic coronary arteries. All occluded vessels and all coronary stenoses seen by cineangiography were also found by flashing tomosynthesis. A correlation coefficient of r = 0.85 (P less than 0.001) was determined between the degrees of stenosis obtained by the two techniques. With flashing tomosynthesis, less contrast medium was needed, the investigation time was shorter, and the radiation exposure markedly reduced. At present, dynamic events, such as collateral blood flow, cannot be evaluated. We conclude that coronary arterial stenoses and occlusions can be reliably evaluated by flashing tomosynthesis. Further technological developments are necessary for the technique to gain clinical acceptance.

Adult↗