Biomedical subjects

T Flohr

Publications and source records attributed to T Flohr.

At least 19 recordsLinked to original sources

PubMed2000

Rapid and reliable quantification of minimal residual disease in acute lymphoblastic leukemia using rearranged immunoglobulin and T-cell receptor loci by LightCycler technology.

The detection of minimal residual disease (MRD) using immunoglobulin and T-cell receptor (TCR) rearrangements as PCR targets provides important prognostic information on the in vivo effectiveness of treatment in acute lymphoblastic leukemia (ALL). Here we report on the real-time quantification of MRD in 25 ALL patients using LightCycler technology. We designed and adapted allele-specific oligonucleotide (ASO)-PCR protocols that enabled the detection of >90% of the IGH, IGK, TCRD, and TCRG rearrangements observed in ALL patients. In all patients, at least two suitable markers could be identified (average, 3.4 markers/patient). We applied ASO-PCR with 35 immunoglobulin and TCR rearrangements (11 IGH, 6 IGK, 12 TCRG, and 6 TCRD) and compared the sensitivity and practicability of the LightCycler strategy with conventional ASO-PCR on a block thermocycler followed by quantification with gel electrophoresis. The LightCycler measured leukemia-specific PCR products at each cycle (real-time) by staining the PCR product with the DNA-binding dye SYBR Green I. LightCycler technology showed a higher sensitivity than the conventional method in eight cases, whereas the sensitivity of the other markers matched exactly. The detection level varied between 10(-4) and 10(-6) leukemic cells. Furthermore, we determined the MRD status of 27 bone marrow follow-up samples from 15 ALL patients by both methods and revealed comparable results. However, the LightCycler also allowed accurate quantification in samples containing relatively high levels (>10(-3)) of residual leukemia cells. The conventional ASO-PCR technique comprises various laborious and time-consuming PCR experiments and post-PCR steps to determine the number of cycles with the optimal linearity and sensitivity of the PCR. Real-time quantification through LightCycler technology obviates these post-PCR steps, provides the highest sensitivity via software analysis, and therefore represents a rapid, reliable, sensitive, and cost-effective technique for the routine monitoring of MRD in ALL patients.

Adult↗

PubMed2000

Mutation analysis of replicative genes encoding the large subunits of DNA polymerase alpha and replication factors A and C in human sporadic colorectal cancers.

We examined cDNAs of the catalytic subunit of DNA polymerase alpha (185 kDa), the 70 kDa subunit of replication protein A (single-stranded DNA-binding protein) and the 140 kDa subunit of replication factor C for mutations. Surgical specimens from 12 patients with sporadic colon cancer and normal mucosae from the same patients were investigated. In addition, we analyzed 3 human colon cancer cell lines that exhibited defects in mismatch repair (DLD-1, HCT116, SW48) and 3 colon cancer cell lines without such a defect (HT29, SW480 and SW620). For detection of mutations, we used reverse transcription of mRNA, amplification of cDNAs by PCR, analysis of single-strand conformation polymorphism and DNA sequencing. Eleven colon cancers and 6 colon cancer cell lines were analyzed for DNA polymerase alpha. Only 2 silent point mutations were detected, in 1 colon carcinoma and in cell line HCT116. Two sequence alterations of the 70 kDa subunit of replication factor A were identified in 15 specimens (9 colon carcinomas and 6 cell lines). Colon carcinomas from 2 patients (CC5MA and CC25HN) exhibited an ACA-->GCA transition in codon 351, which caused a Thr-->Ala exchange. In carcinomas CC5MA and CC8MA, a TCC-->TCT (Ser-->Ser) transition in codon 352 was observed. The deviations in codons 351 and 352 occurred in both cancer tissues and normal mucosae, suggesting a genetic polymorphism. No mutation was found in the 140 kDa subunit of replication factor C from 16 specimens (10 tumors and 6 cell lines). Point mutations were identified in the p53 tumor-suppressor gene in 4 of the 6 colon cancer cell lines and 3 of the 8 carcinoma specimens. We did not find tumor-associated DNA sequence alterations that resulted in amino acid changes in the DNA replication genes analyzed. We infer that the scarcity of mutations found is due to stringent selection, eliminating functionally impaired replication proteins.

Colorectal Neoplasms↗

PubMed2000

[Cardiac imaging with rapid, retrospective ECG synchronized multilevel spiral CT].

PURPOSE: In this paper a method for cardiac imaging with fast multi-slice CT and retrospectively ECG-gated spiral acquisition is presented. METHODS: A fast multi-slice CT system with 4 simultaneously acquired slices and 0.5 s rotation time is used (Siemens Somatom VolumeZoom). Continuous spiral data of the entire heart volume is acquired together with the patient's ECG and reconstructed with dedicated spiral algorithms providing 250 ms temporal resolution. Three-dimensional image data sets are built up from overlapping slices that are reconstructed in an arbitrary, user-defined phase of the heart cycle (e.g. diastolic phase). To evaluate the capability of the method for functional imaging complete three-dimensional image volumes are reconstructed from the same spiral data set in different phases of the heart cycle. RESULTS: A spiral data set of the entire heart volume may be acquired within a single breath-hold. Typical scan times for standard examinations with 3 mm slice width are 10-15 s, and for high-resolution CT angiographies of the coronary arteries with 1.25 mm slice width about 30-35 s. Motion-free reconstruction of the heart and coronary arteries with high spatial resolution is possible in the diastolic phase of the heart cycle. Multi-phase reconstructions from the same spiral scan data set are possible, however, motion artifacts in heart phases with fast cardiac motion may not be completely avoided. CONCLUSION: Fast multi-slice spiral CT with retrospectively ECG-gated spiral reconstruction is well suited for three-dimensional and functional imaging of the heart, especially for high-resolution imaging of calcified coronary plaques and CT-angiography of the coronary arteries.

Algorithms↗

PubMed2000

[Initial experiences with multi-slice detector spiral CT in diagnosis of arteriosclerosis of coronary vessels].

PURPOSE: Multi-row-detector-spiral-CT (MSCT) allows for 250 ms effective exposure time. The purpose of this study was to demonstrate the possibilities and limitations of this CT technology for non enhanced and contrast enhanced investigation of the coronary arteries. METHODS: Investigation of the coronary arteries without contrast medium for quantification of coronary calcifications was performed in an obese patient (140 kg) with MSCT and electron beam CT (EBCT). In 56 patients contrast enhanced CT angiography of the coronary arteries was performed to determine image quality depending on the heart rate. RESULTS: In the obese patient superior image quality could be achieved with MSCT allowing for reliable quantification of coronary calcifications. With MSCT angiography of the coronary arteries good image quality was achieved in patients with a heart rate of 59 +/- 8 beats per minute. CONCLUSION: Even if there are limitations in patients with higher heart rates with an effective exposure time of 250 ms MSCT has clear advantage of image quality in the assessment of non enhanced and contrast enhanced coronary arteries.

Adult↗

PubMed2000

Visualization and quantification of coronary calcifications with electron beam and spiral computed tomography.

This contribution reviews the pathology and morphology of coronary calcifications. It summarizes the indications for investigation of the coronary arteries. The standard protocols for scan acquisition using electron beam and conventional computed tomography are described as well as various methods for evaluation such as the traditional Agatston scoring method and the newer three-dimensional scoring algorithms. Guidelines for interpreting scores are also reviewed. Major limitations of the reproducibility of the calcium score measurement are summarized. Future aspects of multirow-detector spiral computed tomography with retrospective electrocardiographic triggering for quantifying coronary calcium are discussed.

Calcinosis↗

PubMed2000

[Cardiac multidetector-row CT: first clinical results of retrospectively ECG-gated spiral with optimized temporal and spatial resolution].

PURPOSE: The significantly improved temporal and spatial resolution of Multidetector-Row CT opens up new possibilities for cardiac imaging. A method with retrospectively ECG-gated spiral acquisition is presented. MATERIALS AND METHODS: A total of 10 patients underwent cardiac CT on a fast multi-slice CT system with 4 simultaneously acquired slices and 0.5 s rotation time (Siemens Somatom Volume Zoom). Continuous spiral data of the entire heart volume (5 studies precontrast for calcium scoring, 5 studies with contrast) were acquired together with the patient's ECG and reconstructed with dedicated spiral algorithms providing 250 ms temporal resolution. Three-dimensional image data sets were built up from overlapping slices that were reconstructed in an arbitrary, user-defined phase of the heart cycle (e.g., diastolic phase). To evaluate the capability of the method for functional imaging, complete image volumes were reconstructed from the same spiral data set in different phases of the heart cycle. RESULTS: Within a single breath-hold, a spiral data set of the entire heart volume could be acquired. Typical scan times for standard examinations with 3-mm slice width were 12-17 s, and for high-resolution CT angiographies of the coronary arteries with 1.25-mm slice width about 25-35 s. Motion-free reconstruction of the heart and coronary arteries with high spatial resolution were possible in the diastolic phase of the heart cycle. Multiphase reconstructions from the same spiral scan data set were possible. CONCLUSIONS: Fast multi-slice spiral CT with retrospectively ECG-gated spiral reconstruction is well suited for three-dimensional and functional imaging of the heart, especially for high-resolution imaging of calcified coronary plaques and CT-angiography of the coronary arteries.

Coronary Angiography↗

PubMed2000

CD34+ cell enrichment for autologous peripheral blood stem cell transplantation by use of the CliniMACs device.

Several devices for selection of CD34+ peripheral blood stem cells (PBSC) have been used during the last years for reducing tumor cell contamination of the graft. The new CliniMACS system (magnetic-activated cell separation system by Miltenyi Biotech GmbH, Bergisch-Gladbach, Germany) was recently approved for clinical use in Europe. To evaluate its purging efficiency and engraftment data in the autologous transplant, PBSC from 28 adult patients with various malignant diseases (non-Hodgkin's lymphoma, n = 17; chronic lymphocytic leukemia, n = 5; multiple myeloma, n = 4; acute lymphocytic leukemia, n = 1; medulloblastoma, n = 1) were mobilized by chemotherapy and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg per day). Thirty leukapheresis products from 28 patients with a median of 4.4 x 10(8) nucleated cells/kg body weight (bw)(range 0.6-10.8 x 10(8)/kg bw) and a median of 7.1 x 10(6) CD34+ cells/kg bw (range 2.8 to 18.8 x 10(6)/kg bw) were selected using the Cobe spectra cell separator (Cobe BCT Inc., Lakewood, CO). After the CliniMACS procedure, the median yield of CD34+ selected cells was 4.5 x 10(6)/kg (range 2.2-11.1 X 10(6)/kg bw) with a median recovery of 69.5% (range 46.9-87.3%) and a median purity of 97.7% (range 89.4-99.8%). The procedure did not alter viability of selected cells, which was tested by propidium iodide staining. So far, purified PBSC were used for autologous transplantation in 15 out of 28 patients after total body irradiation and/or high-dose chemotherapy. Median time to reach an absolute neutrophil count > 500/microl was 12 days (range 10-18 days), platelet recovery >50,000/microl occurred at day + 16 (range 11-22). With a median follow-up time of 12 months (range 3-19), 5 patients died of relapse. We confirmed the feasibility and safety of the CliniMACS CD34+ cell enrichment procedure in adult patients with autologous PBSC transplantation.

Adult↗

PubMed2000

Exact radon rebinning algorithm for the long object problem in helical cone-beam CT.

This paper addresses the long object problem in helical cone-beam computed tomography. We present the PHI-method, a new algorithm for the exact reconstruction of a region-of-interest (ROI) of a long object from axially truncated data extending only slightly beyond the ROI. The PHI-method is an extension of the Radon-method, published by Kudo, Noo, and Defrise in issue 43 of journal Physics in Medicine and Biology. The key novelty of the PHI-method is the introduction of a virtual object fpsi(x) for each value of the azimuthal angle psi in the image space, with each virtual object having the property of being equal to the true object f(x) in some ROI omegam. We show that, for each psi, one can calculate exact Radon data corresponding to the two-dimensional (2-D) parallel-beam projection of fpsi(x) onto the meridian plane of angle psi. Given an angular range of length pi of such parallel-beam projections, the ROI omegam can be exactly reconstructed because f(x) is identical to fpsi(x) in Omegam. Simulation results are given for both the Radon-method and the PHI-method indicating that 1) for the case of short objects, the Radon- and PHI-methods produce comparable image quality, 2) for the case of long objects, the PHI-method delivers the same image quality as in the short object case, while the Radon-method fails, and 3) the image quality produced by the PHI-method is similar for a large range of pitch values.

Algorithms↗

PubMed2000

Efficient correction for CT image artifacts caused by objects extending outside the scan field of view.

The purpose of this paper is to develop a method of eliminating CT image artifacts generated by objects extending outside the scan field of view, such as obese or inadequately positioned patients. CT projection data are measured only within the scan field of view and thus are abruptly discontinuous at the projection boundaries if the scanned object extends outside the scan field of view. This data discontinuity causes an artifact that consists of a bright peripheral band that obscures objects near the boundary of the scan field of view. An adaptive mathematical extrapolation scheme with low computational expense was applied to reduce the data discontinuity prior to convolution in a filtered backprojection reconstruction. Despite extended projection length, the convolution length was not increased and thus the reconstruction time was not affected. Raw projection data from ten patients whose bodies extended beyond the scan field of view were reconstructed using a conventional method and our extended reconstruction method. Limitations of the algorithm are investigated and extensions for further improvement are discussed. The images reconstructed by conventional filtered backprojection demonstrated peripheral bright-band artifacts near the boundary of the scan field of view. Images reconstructed with our technique were free of such artifacts and clearly showed the anatomy at the periphery of the scan field of view with correct attenuation values. We conclude that bright-band artifacts generated by obese patients whose bodies extend beyond the scan field of view were eliminated with our reconstruction method, which reduces boundary data discontinuity. The algorithm can be generalized to objects with inhomogeneous peripheral density and to true "Region of Interest Reconstruction" from truncated projections.

Algorithms↗

PubMed2000

Cardiac imaging by means of electrocardiographically gated multisection spiral CT: initial experience.

The authors introduce a method for cardiac investigations by using electrocardiographically gated spiral scanning with a four-section computed tomographic system. Three-dimensional images were reconstructed by means of a 250-msec temporal resolution and continuous volume coverage by using a dedicated multisection cardiac volume reconstruction algorithm. Motion-free thin-section volume images were acquired with thin sections and overlapping image increments within a single breath hold. Data segment shifts in time allowed for multiphase imaging.

Calcinosis↗

PubMed1999

Detection of mutations in the DNA polymerase delta gene of human sporadic colorectal cancers and colon cancer cell lines.

To test the hypothesis whether DNA polymerases acquire mutator properties during tumor development (mutator hypothesis), we examined DNA polymerase delta mRNA in 6 colon cancer cell lines (DLD-1, HCT116, SW48, HT29, SW480 and SW620) and 7 sporadic human colorectal cancers. For analysis we used amplification of cDNA by polymerase chain reaction, single-strand conformation polymorphism and sequencing techniques. In 5 of the cell lines, 9 mutations leading to changes of the amino acid sequence of DNA polymerase delta were detected. Most mutations were found in the cell lines DLD-1, HCT116 and SW48 for which defects in mismatch repair genes had been identified previously. In the majority of cases, wild type and mutated sequences were present. In 2 cell lines (HCT116 and SW48), a single-nucleotide deletion occurred at the same position. This resulted in a premature termination codon by which the DNA interaction domain of the enzyme was eliminated. Furthermore, sequence deviations were found in the tumor tissues of 4 colon cancer patients. Wild-type and altered sequences were present simultaneously. The deviations included missense mutations (2 cases) and silent mutations (2 cases). The missense mutations and one of the silent mutations were found in normal mucosa as well. In addition, the mutation clustered region of a tumor suppressor gene, often found to be defective in colon cancer, the adenomatous polyposis coli (APC) gene, was investigated in surgical specimens and cell lines. One carcinoma and 2 cell lines exhibited amino acid changes in both the DNA polymerase delta gene and in the mutation clustered region of the APC gene. Since most of the mutations detected in the DNA polymerase delta mRNA are likely to alter the structure of the protein, the enzyme is expected to be functionally impaired. In particular, copying fidelity might be decreased, thus contributing to the high mutation rate observed in colorectal cancer.

Aged↗

PubMed1999

[The technical bases and uses of multi-slice CT].

In this review the technical principles and applications of multi-slice CT are discussed. Multi-slice CT systems allow simultaneous acquisition of up to 4 slices by using multi-row detector systems. Intuitive geometrical arguments are used to establish the limitation to a maximum of 4 slices which is kept by all currently existing multi-slice CT systems. Two different construction principles of the detector are discussed, the "Fixed Array" detector and the "Adaptive Array" detector. The extension of conventional 360 LI and 180 LI spiral interpolation techniques to multi-slice spiral CT is explained as well as a new generalized multi-slice spiral weighting concept, the so-called "Adaptive Axial Interpolation". Several techniques to improve multi-slice spiral image quality are discussed. Finally, some examples for clinical applications are given, and the principle of ECG triggered and ECG gated cardiac examinations with optimized temporal resolution is presented. Multi-slice CT systems are a milestone with respect to increased volume coverage, shorter scan times, improved axial (longitudinal) resolution and better use of the X-ray tube output. Additionally, new clinical applications are possible such as Cardiac CT.

Electrocardiography↗

PubMed1999

Efficient object scatter correction algorithm for third and fourth generation CT scanners.

X-ray photons which are scattered inside the object slice and reach the detector array increase the detected signal and produce image artifacts as "cupping" effects in large objects and dark bands between regions of high attenuation. The artifact amplitudes increase with scanned volume or slice width. Object scatter can be reduced in third generation computed tomography (CT) geometry by collimating the detector elements. However, a correction can still improve image quality. For fourth generation CT geometry, only poor anti-scatter collimation is possible and a numeric correction is necessary. This paper presents a correction algorithm which can be parameterized for third and fourth generation CT geometry. The method requires low computational effort and allows flexible application to different body regions by simple parameter adjustments. The object scatter intensity which is subtracted from the measured signal is calculated with convolution of the weighted and windowed projection data with a spatially invariant "scatter convolution function". The scatter convolution function is approximated for the desired scanner geometry from pencil beam simulations and measurements using coherent and incoherent differential scatter cross section data. Several examples of phantom and medical objects scanned with third and fourth generation CT systems are discussed. In third generation scanners, scatter artifacts are effectively corrected. For fourth generation geometry with poor anti-scatter collimation, object scatter artifacts are strongly reduced.

Algorithms↗

PubMed1999

A mutation detected in DNA polymerase delta cDNA from Novikoff hepatoma cells correlates with abnormal catalytic properties of the enzyme.

Tumor development is characterized by accumulation of mutations. Such mutations, if induced by carcinogens in DNA polymerase genes, would confer mutator properties on the DNA replication machinery, even at later stages of development. To investigate whether DNA polymerase delta can be mutated, we compared these enzymes from highly malignant Novikoff hepatoma cells and from regenerating normal rat liver. We sequenced the DNA polymerase delta cDNA from both sources and investigated the physico-chemical properties, inhibition characteristics, and copying fidelity of the purified enzymes. The cDNA sequences examined included the entire reading frame encoding the catalytic subunit (subunit I) of DNA polymerase delta. First-strand cDNAs were prepared from total RNA of both normal rat liver and Novikoff cells by reverse transcription, and the polymerase delta sequences were amplified by the polymerase chain reaction. cDNA (3325 bp) were sequenced. A single heterozygous mutation (CGG --> CAG) has been detected in nucleotide position 1948 (codon 648) of the polymerase delta gene from Novikoff cells, resulting in an Arg to Gln change. Position 648 lies just proximal to the conserved region VI, which is part of the "fingers" subdomain of alpha-like polymerases. This subdomain is involved in dNTP binding. Upon comparison of biochemical characteristics of partially purified DNA polymerase delta from both Novikoff cells and rat liver, the following properties of the enzyme from Novikoff cells were found to be altered: (i) K(50) values for nucleotide analogs (e.g. butylphenyl-dGTP) were lower, (ii) sensitivity to various antineoplastic drugs (e.g. doxorubicin, topotecan and distamycin) was enhanced, (iii) copying fidelity was decreased when primer templates containing O(6)-methylguanine were used, and (iv) the activity of DNA polymerase delta from Novikoff tumor cells was less stimulated by lactate dehydrogenase than the enzyme from normal cells. The altered biochemical characteristics of DNA polymerase delta from Novikoff cells suggest mutator properties. We conclude that the point mutation detected in the cDNA might be causally related to the observed changes in inhibition characteristics and copying fidelity.

Amino Acid Sequence↗

PubMed1999

Subsecond multi-slice computed tomography: basics and applications.

The recent advent of multislice-scanning is the first real quantum leap in computed tomography since the introduction of spiral CT in the early 90s. We discuss basic theoretical considerations important for the design of multislice scanners. Then, specific issues, like the design of the detector and spiral interpolation schemes are addressed briefly for the SOMATOM PLUS 4 Volume Zoom. The theoretical concepts are validated with phantom measurements. We finally show the large potential of the new technology for clinical applications. The concurrent acquisition of multiple slices results in a dramatic reduction of scan time for a given scan technique. This allows scanning volumes previously inaccessible. Similarly, given volumes can be scanned at narrower collimation, i.e. higher axial resolution in a given time. From data acquired at narrow collimation, both high-resolution studies and standard images can be reconstructed in the so-called Combi-Mode. This on the one hand reduces dose exposure to the patient because repeated scanning of a patient is no longer required. On the other hand, standard reconstructions benefit from narrow collimation as Partial Volume Artifacts are drastically suppressed. The rotational speed of 0.5 s of the SOMATOM PLUS 4 Volume Zoom furthermore opens up a whole range of new applications in cardiac CT. For the first time, virtually motion-free images can be acquired even for large volumes in a single breathhold by the combination of fast rotation and ECG triggering, respectively gating. We explain the underlying concepts and present initial results. The paper concludes with a brief discussion of the impact of the new technique on image display and postprocessing.

Artifacts↗

PubMed1999

Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro.

Increased endothelial binding and emigration of monocytes play a dominant role in the pathogenesis of atherosclerosis in diabetes mellitus. Previous studies revealed that hyperlipidemia correlates with monocyte binding in vitro. The aim of this study was to characterize the monocyte-endothelial interaction of leucocytes of hyperglycemic patients with type 1 diabetes but lacking hyperlipidemia. We isolated monocytes from healthy controls and normolipidemic type 1 diabetes patients with elevated levels of HbA1c and quantified monocyte binding by an immunoilluminometric cell adhesion assay. Purity of isolated monocytes was at least 98%. Endothelial binding of monocytes from patients with type 1 diabetes was found to be significantly increased compared to controls (19.2 +/- 3.9% vs. 14.9 +/- 3.5%). This difference of monocyte binding remained unchanged if the endothelial cells were stimulated with 27.7 mmol/l glucose for seven days prior to adhesion studies (31.5 +/- 4.9% in diabetes patients vs. 25.8 +/- 4.1% in controls) whereby monocyte binding markedly increased under these hyperglycemic conditions. Furthermore, an increased CD11b expression could be demonstrated on monocytes of normolipidemic hyperglycemic type 1 diabetes patients. Thus, we suggest that hyperglycemia per se may contribute to increased monocyte binding to endothelial cells by promoting leucocyte integrin expression. Recently performed studies of our group strengthen the hypothesis that this monocyte activation is mediated by stimulation of the beta-isoform of proteinkinase C.

Adult↗

PubMed1998

An efficient Fourier method for 3-D radon inversion in exact cone-beam CT reconstruction.

The radial derivative of the three-dimensional (3-D) radon transform of an object is an important intermediate result in many analytically exact cone-beam reconstruction algorithms. We briefly review Grangeat's approach for calculating radon derivative data from cone-beam projections and then present a new, efficient method for 3-D radon inversion, i.e., reconstruction of the image from the radial derivative of the 3-D radon transform, called direct Fourier inversion (DFI). The method is based directly on the 3-D Fourier slice theorem. From the 3-D radon derivative data, which is assumed to be sampled on a spherical grid, the 3-D Fourier transform of the object is calculated by performing fast Fourier transforms (FFT's) along radial lines in the radon space. Then, an interpolation is performed from the spherical to a Cartesian grid using a 3-D gridding step in the frequency domain. Finally, this 3-D Fourier transform is transformed back to the spatial domain via 3-D inverse FFT. The algorithm is computationally efficient with complexity in the order of N3 logN. We have done reconstructions of simulated 3-D radon derivative data assuming sampling conditions and image quality requirements similar to those in medical computed tomography (CT).

Algorithms↗

PubMed1997

A mouse cytomegalovirus glycoprotein retains MHC class I complexes in the ERGIC/cis-Golgi compartments.

The principle by which mouse cytomegalovirus blocks antigen presentation in the MHC class I pathway was investigated. The responsible gene m152, encoding a type I transmembrane glycoprotein of 40 kDa, is a member of a gene family located in the right-hand terminal region of the 230 kb virus genome. Expression of m152 in murine and human cells arrested the export of mouse class I complexes from the ER-Golgi intermediate compartment/cis-Golgi compartment and inhibited lysis by cytotoxic T cells. The plasma membrane transport of human MHC class I molecules was not affected. The deletion of the cytoplasmic tail of gp40 did not lift its effect on class I molecule export, indicating that this protein differs in its functions from known immunosubversive viral gene products and represents a novel principle by which a herpesvirus shuts off MHC class I function.

3T3 Cells↗