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T Albrecht

Publications and source records attributed to T Albrecht.

At least 73 records · Page 4Linked to original sources
PubMed1997

Increased frequency of specific locus mutation following human cytomegalovirus infection.

The effect of human cytomegalovirus (HCMV) infection on the frequency of mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus was studied in Chinese hamster lung V79 cells. When V79 cells were infected with HCMV (strain AD169) at multiplicities of 0.1 to 50 plaque forming units (PFU) per cell the presumptive mutation frequency, as determined by the number of 6-thioguanine-resistant (TGr) colonies, was increased up to 16.8-fold (P < 0.005), depending on the multiplicity of infection. Increases in the mutation frequency at the hprt locus were also observed for other laboratory-adapted HCMV strains (C-87, Davis) and for low passage clinical isolates (82-1, 84-2). The expression time required for the maximum increase in TGr colonies was 3 days and was consistent among the HCMV strains evaluated in this study. UV-irradiation of HCMV stock up to a dose of 9.6 x 10(4) ergs/mm2 increased the mutation frequency, but further exposure to UV light or to heat (56 degrees for 30 min) significantly decreased the frequency of TGr-resistant colonies, suggesting that expression of HCMV genes was involved in the mutation process. HCMV-induced TGr cells demonstrated substantially reduced (> 96%) incorporation of [3H]hypoxanthine. PCR analysis of the hprt locus demonstrated deletions in 9 of 19 HCMV-induced TGr colonies randomly selected for further study, while 2 of 17 spontaneously developed TGr colonies demonstrated deletions. Although insertions were not detected in spontaneously developed clones, 3 of 19 HCMV-induced TGr clones had insertions in the hprt gene. Neither HCMV-specific DNA sequences nor HCMV-specific proteins were detected in the TGr clones obtained after HCMV infection. Infection of V79 cells with HCMV also increased their sensitivity to mutation with N-methyl-N'-nitro-N-nitrosoguanidine, giving a synergistic enhancement of the mutation frequency. These results indicate that HCMV infection has the capacity to induce mutations in the cellular genome and increase the sensitivity of infected cells to mutation by genotoxic chemicals. Although inactivated HCMV particles are responsible for a modest increase in the mutation frequency, expression of HCMV genes is associated with a substantial enhancement of the mutation frequency.

Animals↗
PubMed1997

Pre-operative classification of abdominal aortic aneurysms with spiral CT: the axial source images revisited.

OBJECTIVE: The differentiation of supra-, juxta- and high infrarenal abdominal aortic aneurysms (AAA), which is essential for good surgical management, remains problematic. This prospective study assessed the value of highly overlapping vs. contiguous axial spiral computed tomography (CT) reconstructions in the pre-operative assessment of AAA. PATIENTS AND METHODS: Thirty-five patients with abdominal aortic aneurysms were studied with spiral CT (10 mm collimation, pitch 1). Axial reconstructions were performed at 2 and 10 mm increments and compared with surgical findings. Using each protocol, the aneurysms were classified as infra-, juxta- or suprarenal. Observers also assessed visualization of main and accessory renal artery origins and identification of other surgically relevant vascular anomalies. RESULTS: The 2 mm protocol correctly identified 29/31 infrarenal, 3/3 juxtarenal and 1/1 suprarenal aneurysms; two infrarenal aneurysms were overestimated as suprarenal. The 10 mm protocol correctly classified 25/31 infrarenal, 3/3 juxtarenal and 1/1 suprarenal aneurysms; five infrarenal aneurysms were overestimated as juxtarenal (n = 3) or suprarenal (n = 2) and one case was equivocal. Correct classification was thus 94% using the 2 mm protocol and 83% with the 10 mm protocol (P = 0.063). All 70 main renal artery origins were visualized with the 2 mm protocol, while the 10 mm protocol missed six (P = 0.03) The 2 mm protocol identified 10 accessory renal arteries, four of which were missed by the 10 mm protocol. Both protocols demonstrated five surgically relevant venous anomalies. CONCLUSION: Spiral CT with highly overlapping axial reconstructions correctly classified 94% of abdominal aortic aneurysms; overlapping reconstructions were particularly useful in differentiating high infrarenal from juxtarenal aneurysms.

Aged↗
PubMed1997

Hypertensive heart disease: quantitative evaluation of response to therapy with cine MR imaging.

RATIONALE AND OBJECTIVES: To assess the ability of cine magnetic resonance (MR) imaging to help detect and quantity changes in left ventricular parameters in patients receiving antihypertensive therapy. MATERIALS AND METHODS: After undergoing baseline cine MR imaging of the heart, 16 (12 men, four women) hypertensive patients participating in a prospective drug trial began isradipine therapy. Follow-up serial cine MR imaging was performed at 3 months and 6 months. Myocardial mass, end-systolic volume, end-diastolic volume, stroke volume, and ejection fraction were measured. Results from transaxially acquired three-dimensional data sets and monoplanar imaging were compared. RESULTS: Three dimensional data showed reductions of 11% in end-systolic volume (P = .0051) and 17% in end-diastolic volume (P = .0023). These changes were not detected with monoplanar imaging. Changes in myocardial mass, stroke volume, and ejection fraction were not statistically significant. CONCLUSION: Three-dimensional cine MR imaging can depict small yet statistically significant reductions in left ventricular volumes in response to antihypertensive therapy.

Adult↗
PubMed1997

Human cytomegalovirus infection results in altered Cdk2 subcellular localization.

Human cytomegalovirus (HCMV) stimulates numerous cellular pathways upon infection. One of these pathways involves activation of cyclin E/Cdk2. Recent reports have demonstrated that Cdk2 is retained in the cytoplasm of cells arrested in GO by serum deprivation, sequestered from its regulatory subunit cyclin E which is located within the nucleus. Cdk2 rapidly enters the nucleus and becomes active upon stimulation of these cells with serum growth factors. The ability of HCMV to activate cyclin E/Cdk2 in both serum-arrested cells and contact-inhibited cells suggests that HCMV infection may also result in the translocation of Cdk2 into the nucleus. In this report, we demonstrate that Cdk2 is sequestered in the cytoplasm of cells arrested in GO by contact inhibition, as well as those arrested by serum deprivation. HCMV infection results in translocation of Cdk2 from the cytoplasm into the nucleus within 24 h of infection, both in serum-arrested and contact-inhibited cells.

CDC2-CDC28 Kinases↗
PubMed1997

Power Doppler US of the normal prepubertal testis: does it live up to its promises?

PURPOSE: To assess whether power Doppler ultrasound (US) improves the detection of flow in normal prepubertal testes. MATERIALS AND METHODS: Seventy-two normal testes of 38 prepubertal boys (age range, 2 weeks to 12.5 years) were scanned with color and power Doppler US (7-MHz transducer). The two modalities were compared subjectively to determine which one was more sensitive for detection of flow. Only reproducible intratesticular flow signals were considered positive; capsular flow was disregarded. RESULTS: Power Doppler US depicted flow in 50 testes (69%), while color Doppler US depicted flow in 47 testes (65%, not statistically significant). Power and color Doppler US combined depicted flow in 57 testes (79%), which was significant when compared with color Doppler US alone (P = .002). Detection of flow was subjectively easier with power Doppler US in 10 of 72 testes, while it was easier with color Doppler US in 14 of 72 testes. Motion artifacts were greater with power Doppler US. CONCLUSION: Power Doppler US was equally sensitive as conventional color Doppler US in the detection of flow in normal prepubertal testes. Combining both modalities improved detection of flow in 14% of cases and may be useful in excluding torsion in children. For a positive preoperative diagnosis of torsion in children, radionuclide scintigraphy remains the imaging modality of choice.

Artifacts↗
PubMed1997

Novel activation of gamma-interferon in nonimmune cells during human cytomegalovirus replication.

This is the first study documenting the induction of gamma-interferon (IFN-gamma) in human embryonic fibroblasts during human cytomegalovirus (HCMV) replication. Infection of cells with HCMV resulted in the consistent production of IFN-gamma RNA, as determined by RT-PCR and Northern blot analysis. Western blot analysis of cell lysates and immunoprecipitates from the cultural fluids of infected cells demonstrated the presence of IFN-gamma at the protein level. Induction of IFN-gamma required infectious HCMV, since high-dose ultraviolet inactivation of the virus stock eliminated IFN-gamma production. Further, IFN-gamma induction appears to be a late event in the virus replication cycle, since inhibition of HCMV DNA synthesis (e.g., phosphonoacetic acid) blocked the increase in IFN-gamma. Soluble factor(s) released from HCMV-infected cells apparently did not contribute to the induction of IFN-gamma, since virus stocks from which virus had been removed by sedimentation did not induce production of IFN-gamma. The appearance of IFN-gamma at late stages of HCMV infection and its elimination in the presence of an inhibitor (Actinomycin D) of RNA synthesis indicate a true transcriptional induction of this lymphokine at the RNA and protein levels. The significance of IFN-gamma production with regard to the replication and pathogenesis of HCMV in vitro and in vivo will require further investigation.

Blotting, Northern↗
PubMed1996

Human cytomegalovirus inhibits cellular DNA synthesis and arrests productively infected cells in late G1.

Human embryonic lung fibroblasts (LU) can be productively infected with human cytomegalovirus (HCMV). During the course of productive infection, the virus elicits a number of responses that resemble certain aspects of G1 cell cycle progression. The virus activates cyclin E/Cdk2 kinase in both subconfluent, serum-arrested, and density-arrested cultures. Activation of cyclin E-dependent kinase is due, in part, to induction of cyclin E and, in part, to inhibition of the cyclin kinase inhibitors, Cip1 and Kip1. However, G1 progression is incomplete in HCMV-infected cells. Neither cyclin A nor cyclin D is induced, and cellular DNA synthesis does not occur if one takes care to avoid addition of fresh serum to serum-starved cultures. The data indicate that the virus induces a state of late G1 arrest, in which cyclin E/Cdk2 activates nucleotide metabolism and other biosynthetic processes that are necessary for viral replication. Failure to activate host cell DNA synthesis ensures that the virus will have uncompleted access to such precursors.

CDC2-CDC28 Kinases↗
PubMed1996

Cationic lipid mediated transfer of c-abl and bcr antisense oligonucleotides to immature normal myeloid cells: uptake, biological effects and modulation of gene expression.

Uptake and biochemical and biological effects of antisense oligodeoxynucleotides (ODN) specific for c-abl and bcr genes were studied in normal immature myeloid cells. CD34-positive cells were purified by positive and negative selection and cultured in liquid culture for 7 days. These cells were then incubated with ODNs, either alone or in combination with cationic lipids. The uptake of ODNs was enhanced by the use of cationic lipids. In addition, very low concentrations of ODNs in combination with cationic lipids were capable of specifically inhibiting the expression of the c-abl gene. In contrast, no effects were seen on the expression of bcr. However, despite the effective blocking of c-abl expression, no changes in cellular growth patterns were observed in liquid culture or in a colony-forming assay. We conclude tht the use of cationic lipids might enhance the gene-regulatory effects of ODNs by increasing their uptake into normal hematopoietic cells.

Antigens, CD34↗
PubMed1996

Primary proliferating immature myeloid cells from CML patients are not resistant to induction of apoptosis by DNA damage and growth factor withdrawal.

Induction of apoptosis by growth factor deprivation or gamma-irradiation-induced DNA damage was directly studied in proliferating primary haemopoietic cells derived from CD34-positive cells of 13 CML patients and 12 normal controls. CD34-positive cells were cultured in the presence of appropriate concentrations of SCF and G-CSF for 5-7 d. After gamma irradiation with 500 rad or growth factor deprivation, the fraction of apoptotic cells was assessed by two independent methods applying either measurement of cells incorporating FITC-labelled dUTP by terminal transferase or assessment of the fraction of cells with a less than 2N DNA content in flow cytometry. Proliferating CML cells were not resistant to the induction of apoptosis either after gamma irradiation or subsequent to growth factor deprivation. A similar fraction of normal and CML cells underwent apoptosis 48 h after withdrawal of growth factors. CML cells displayed an increased susceptibility to induction of apoptosis after DNA damage. A significantly higher proportion of apoptotic cells were detected in samples derived from CML patients after irradiation with 0.5 Gy. These results, in conjunction with conflicting observations by other investigators, on the induction of apoptosis by gamma irradiation in various bcr-abl positive cells, suggest that bcr-abl-dependent effects on apoptosis strongly depend on the cells used. Our observations in CML cells derived exclusively from newly diagnosed CML patients demonstrate that bcr-abl expression per se is not sufficient to induce resistance to apoptosis.

Apoptosis↗
PubMed1996

Cyclin E/Cdk2 activity is controlled by different mechanisms in the G0 and G1 phases of the cell cycle.

The experiments described in this report were undertaken to define the parameters that regulate cyclin E/cyclin-dependent kinase 2 (Cdk2) kinase activity in mitotically quiescent, serum-starved fibroblastic cells and in cells that had been stimulated to enter the cell cycle and progress through G1 into S phase. We have analyzed the expression of cyclin E and Cdk2, the extent to which these two proteins form complexes, and the enzymatic activity of cyclin E/cdk2 kinase. Particular attention was focused upon subcellular localization and the effect of compartmentalization on the association between cyclin E and Cdk2. In addition, we have examined the interaction of cyclin E/Cdk2 complexes with two well-characterized inhibitors of Cdk2 kinase activity, Cip1 and Kip1. This represents the first report in which all of these parameters have been measured simultaneously in a single, normal diploid cell line. In G0 cells, there is abundant cyclin E and Cdk2, yet there is little or no detectable Cdk2-dependent histone H1 kinase activity. After serum stimulation, there is a rapid increase in the amount of cyclin E that is bound to Cdk2, although there is no significant change in the abundance of either the cyclin or the Cdk. Immunocytochemical data indicate that cyclin E, Cip1, and Kip1 are located within the nuclei of cell in G0, but very little Cdk2 is observed within the nuclei of serum-starved cells. Cdk2 rapidly enters the nucleus upon serum stimulation. The abundance of the cyclin E/Cdk2 complex increases to the extent that the binding capacity of Cip1 is exceeded about 8-12 h after serum stimulation. The abundance of Kip1 decreases at the same time that the Cip1 threshold is exceeded, so that cyclin E/Kip1-containing complexes decrease by 90% within 8-12 h. Cyclin E/Cdk2 kinase activity begins to increase rapidly thereafter, reaching a maximum level about 16 h after serum stimulation. We have been unable to detect histone H1 kinase activity in complexes that contain cyclin E bound to Kip1 or Cip1. We conclude that compartmentalization is the predominant barrier to activation of cyclin E-dependent kinases in quiescent cells. Cip1 and Kip1 serve to prevent premature activation of cyclin E/Cdk2 complexes that form during G0 or early G1.

CDC2-CDC28 Kinases↗
PubMed1994

Psychosocial oncology research. Where we have been, where we are going, and why we will not get there.

Quality of life, symptom management, and social support are the traditional foci for the practice of psychosocial oncology and clinical research into the behavioral and psychologic aspects of cancer. The current paradigm for research in this area primarily assesses patient responses to cancer related stressors and the means of ameliorating the negative aspects of those responses. However, clinically meaningful interventions have been the exception, rather than the rule. The authors think that the central event initiating a stressful response is the interaction between the patient and physician conveying the diagnosis, prognosis, or treatment plan. The authors think addressing the initial event in a cascade of responses is an important prerequisite for progress in this area.

Attitude of Health Personnel↗
PubMed1994

Human cytomegalovirus infection increases the number of ouabain-binding sites in human fibroblasts.

Infection of permissive human embryo fibroblasts (MRC-5) with human cytomegalovirus (HCMV) increased the number of copies of the Na+,K(+)-ATPase (the Na+ pump) in the plasma membrane, measured as ouabain-binding sites. The increase was preceded by cell enlargement by about 24 hr, becoming significant between 48 and 72 hr after infection. Reduction in Na+ or Cl- concentration in the culture media immediately after infection partially prevented the increase in the number of ouabain-binding sites. The effect was reversible upon restoring Cl- or Na+ to the incubation medium, but withdrawal of either ion at 24 or 48 hr PE failed to prevent the increase in the number of binding sites. These results suggest that the processes that resulted in the increase of copies of the Na+,K(+)-ATPase required both Na+ and Cl- during the first 24 hr PE. Amiloride and ethylisopropylamiloride, two inhibitors of Na+ transport mechanisms of the plasma membrane have been previously shown to reduce the amount of virus yields and to prevent the onset of cytomegaly (Fons et al., 1991, Proc. Soc. Exp. Biol. Med. 196, 89-96). We show here that these agents partially block the increase in ouabain-binding sites caused by HCMV infection.

Amiloride↗
PubMed1994

[High-resolution 3-D imaging in MR tomographic knee joint diagnosis. Correlation with arthroscopy].

84 knee joints were examined by a 3-dimensional MR method and the results correlated with subsequent arthroscopy. The findings showed good demonstration of the normal anatomical structures and excellent reliability for the diagnosis of meniscus tears (sensitivity 91%, specificity 95%), cruciate ligament lesions (sensitivity 90%, specificity 99%) and serious cartilage damage (sensitivity 100%, specificity 100%). Demonstration of mild cartilage damage (sensitivity 60%, specificity 99%) was better than with a spin echo technique but is not yet optimal. It is concluded that, by using a 3-dimensional technique, time-consuming spin echo sequences can be abandoned. Significant advantages of the 3-D method are the speed of the examination, narrow section thickness, marked flexibility in contrast rendering and the ability for multiplanar reconstruction.

Adolescent↗
PubMed1994

Alteration in the coding potential and expression of H-ras in human cytomegalovirus-transformed cells.

CMV-transformed cell lines demonstrated a greater level of H-ras RNA (7.5- to 9.5-fold) relative to the level for H-ras in parental cells. Nuclear run off assays showed that the RNA levels for the H-ras gene were regulated at the level of transcriptional initiation. The increased RNA levels for H-ras correlated with the level of p21rasVal-12 in transformed cells, while p21rasVal-12 was below the level of detection in nontransformed cells using Western blot analysis. In addition, an activating mutation was identified in both alleles of the first exon, codon 12 of H-ras resulting in a G:C to T:A transversion in all transformed cell lines examined in this study. These results suggest that the mutated H-ras may be one of the components by which an oncogenic phenotype is maintained in these CMV-transformed cells.

Base Sequence↗