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Biomedical subjects

B Jung

Publications and source records attributed to B Jung.

At least 55 records · Page 3Linked to original sources

Recording of electrical brain activity in a magnetic resonance environment: distorting effects of the static magnetic field.

The technical limitations of electroencephalography (EEG) and flashed visually-evoked potentials (VEP) recordings in the static magnetic field of the MR system were systematically studied. A main artifact occurring in the magnetic field was found to be correlated with the heart cycle and had amplitudes in the range of EEG and VEP signals. For VEP recordings, a substantial reduction of this effect was achieved by subtraction of the averaged artifact from the averaged composed signal (VEP and artifact) resulting in the VEP signal alone. However, for continuous EEG recordings, there is no such solution, since the observed effect is not sufficiently constant in amplitude, and the standard deviation of the amplitude of the effect is often larger than the EEG amplitude.

Artifacts↗

Estrogen-responsive RING finger mRNA induction in gastrointestinal carcinoma cells following bile acid treatment.

The underlying molecular mechanisms of the tumor-promoting activity of bile acids such as chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) and the protective effect of ursodeoxycholic acid (UDCA) remain largely unclear. Using RNA arbitrarily primed PCR (RAP-PCR) for differential display, we identified, cloned and sequenced differentially expressed transcripts after treating gastric carcinoma cells (St 23132) with the bile acids CDCA, DCA and UDCA. One of these transcripts was identified to be an estrogen-responsive RING finger protein (efp) mRNA. The differential expression of efp in gastric cancer cells was confirmed by low stringency RT-PCR. efp mRNA levels were induced 3-fold in gastric carcinoma cells after CDCA and DCA treatment, whereas no change in expression was detected after UDCA treatment. Finally, treatment of the colon carcinoma cell line HT 29 with DCA resulted in a 2- to 5-fold induction of efp mRNA levels whereas UDCA did not induce efp. As expected, efp expression was also increased after 24 h of estrogen treatment. In summary, a synergy or a common pathway of tumor enhancement of bile acids and estrogen via efp in gastrointestinal carcinogenesis can be envisioned.

Bile Acids and Salts↗

Overexpression of Lerk-5/Eplg5 messenger RNA: a novel marker for increased tumorigenicity and metastatic potential in human malignant melanomas.

The Lerks, ligands of eph-related receptor tyrosine kinases, are a rapidly expanding family of genes thought to play an important role in the development and oncogenesis of various tissues. However, very little experimental evidence supports this hypothesis. Using RNA fingerprinting, we detected increased expression of Lerk-5 mRNA in human melanocytes as a response to the tumor-promoting drug 12-O-tetradecanoylphorbol-13-acetate, which suggests a possible role of the Lerks in melanoma tumorigenesis and progression. Therefore, we studied Lerk-5 mRNA expression in various melanoma cell lines and tissues of melanocytic tumors by semiquantitative reverse transcription-PCR. Modest expression of Lerk-5 mRNA was found in two melanoma cell lines derived from early primary tumors (WM35 and WM1645B); two metastatic cell lines tested showed a 3.9-fold increased transcript abundance when compared to the primary cell lines (RPMI-7951 and SK-Mel5). Progeny of a melanoma cell line with very low Lerk-5 mRNA abundance (WM35) showed a 5-fold increase in Lerk-5 mRNA expression when it was selected for higher tumorigenicity and multicytokine resistance by passaging in nude mice or repeated high-dose UVB irradiation. Consistent with these experimental data, we found high levels of Lerk-5 mRNA expression in advanced primary malignant melanomas and metastases (n = 22) but significantly lower or undetectable mRNA expression in benign melanocytic nevi (n = 9; P < 0.001). We conclude that increased Lerk-5 expression possibly reflects or induces an increased potential of growth, tumorigenicity, and metastatic abilities in human melanomas. This makes the yet to be elucidated eph-related receptor tyrosine kinase/Lerk signaling system a potential new source for molecular markers as well as a target for new therapies.

Animals↗

RNA fingerprinting displays UVB-specific disruption of transcriptional control in human melanocytes.

In mammalian cells, UV induces a limited set of early transcribed genes, which overlaps with the set of genes induced by tumor promoting drugs such as 12-O-tetradecanoyl phorbol-13-acetate (TPA). Among these are genes for transcription factors, the activation of which leads to complex secondary changes in expression of multiple target genes. How these delayed pleiotropic UV effects on transcription may contribute to initiation of melanoma skin cancer is poorly understood. We analyzed changes in the relative abundances of 1900 transcripts in newborn human melanocytes 8 h after treatment with UVB, TPA, and cycloheximide in all combinations, using RNA arbitrarily primed PCR for differential display. The relative abundances of 205 transcripts (11% of all transcripts surveyed) were altered by one or more of the treatment combinations. Fourteen of the 77 genes up-regulated by TPA were also up-regulated by UVB, but 60 of the TPA up-regulated genes were down-regulated by UVB, indicating both intersecting and independent signal transduction pathways for UVB and TPA. A number of UVB and TPA target genes were identified by cDNA cloning. Consistent with UVB induction of a partly transformed phenotype in mammalian cells, UVB antagonized the TPA-inducible expression of tumor-suppressive tropomyosin 3 mRNA. In addition, UVB may impair mitochondrial functioning and induce oxidative stress by strong down-regulation of mitochondrial transcription. Finally, increased expression of the dihydropteridine reductase gene, a major regulator of the cellular tetrahydrobiopterin pool, was linked to the UV pathway.

Carcinogens↗

Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose-response effect favoring preoperative treatment.

PURPOSE: This study explored the relationship between radiation dose and reduction in local recurrence rate after preoperative and postoperative radiotherapy in rectal cancer. METHODS AND MATERIALS: All randomized trials initiated prior to 1988 comparing preoperative and postoperative radiotherapy with surgery alone or with each other were included. Local failure rates were available in 5626 randomized patients. The linear quadratic formula was used to compensate for different radiotherapy schedules. RESULTS: For preoperative radiotherapy, a clear dose-response relationship could be established. For postoperative radiotherapy, the range of doses was narrow, and a dose-response relationship could not be demonstrated. At similar doses, preoperative radiotherapy appeared to be more efficient in reducing local failure rate than postoperative. The only trial comparing preoperative with postoperative radiotherapy confirms this notion. A 15-20 Gy higher dose may be required postoperatively than preoperatively to reach similar efficacy. Neither approach alone significantly influences survival, although it is likely that a small survival benefit may be seen after preoperative radiotherapy. CONCLUSIONS: The information from the entire randomized experience suggests that preoperative radiotherapy may be more dose efficient than postoperative radiotherapy.

Combined Modality Therapy↗

Potential advantages of protons over conventional radiation beams for paraspinal tumours.

BACKGROUND AND PURPOSE: Conformal treatment planning with megavoltage X-rays and protons was studied in an attempt to determine if there are advantage of boost therapy with protons instead of X-rays for a patient with a tumour growing around the cervical spinal cord. MATERIALS AND METHODS: A patient with a Ewing sarcoma was selected for the model study. The proton boost plan was realised with a six beam patched technique. Several X-ray boost techniques were planned, some not yet practically realisable. The techniques giving the best dose distributions and the best tumour control probabilities in the absence of significant late toxicity were looked for. The boost techniques were added to two large lateral X-ray beams covering the planning target volume (PTV) and the main risk organ, the spinal cord. The evaluation was made with two biological models, i.e. the tumour control probability (TCP) model, proposed by Webb and Nahum (Webb, S. and Nahum, A.E. A model for calculating tumour control probability in radiotherapy including the effect of inhomogeneous distributions of dose and clonogenic cell density. Phys. Med. Biol. 38: 653-666, 1993), and the normal tissue complication probability (NTCP) model, first derived by Lyman (Lyman, J.T. Complication probability as assessed from dose-volume histograms. Radiat. Res. 104: s13-s19, 1985). RESULTS: The comparison showed small but clear advantages of protons for the boost. At 1% NTCP in the spinal cord, the calculated TCP was on average 5% higher. However, depending on the values of the parameters chosen in the biological models, the gain for protons varied from 0-10%. The smallest gains were seen in radiosensitive tumours for which the TCP was close to 100% with any of the techniques and in radioresistant tumours for which neither technique resulted in any appreciable probability of local cure. CONCLUSION: Protons appear to have therapeutic advantages over conventional radiotherapy in tumours with relatively high radiosensitivity situated close to the spinal cord.

Adult↗

The conceptual design of a radiation oncology planning system.

The conceptual design of a three-dimensional, radiation oncology planning system is described. To assure that clinical needs were met, the working routines in two major Swedish radiation oncology departments were analysed in detail. Generic work flow was identified and mapped and compared to those in other institutions. The flow was partitioned into a number of nodes that together formed a basis for the design of the system handling logistics. The design criteria of this system emphasised accommodation of current clinical practice and traditional treatment modalities, and facilitated means to validate the computational techniques. The system should also allow for new procedures and was based on the analysis of current practice and a synthetic idea of how 3D treatment planning should be done. The final product supports the treatment planning work in its entirety. It is believed that the techniques followed are of interest to those engaged in computer systems of similar purposes and complexities.

Computer Systems↗

Preoperative radiotherapy in rectal carcinoma--aspects of acute adverse effects and radiation technique.

PURPOSE: To explain a possible association between treatment technique and postoperative mortality after preoperative radiotherapy of rectal carcinoma, the dose distributions were compared in model experiments. METHODS AND MATERIALS: Preoperative radiotherapy with a three-beam technique delivered in five fractions to 25 Gy (5 Gy/daily for 5 or 7 days) was given to patients with primary resectable rectal carcinoma. The adverse effects of this treatment, both acute and late, have been low. In a parallel trial using an identical fractionation schedule and total dose but with a two-beam technique, the postoperative mortality was higher. Two-, three-, and four-beam techniques were analyzed in 20 patients with computed tomography based, three-dimensional dose planning. Dose distributions and dose-volume histograms in the planning target volume (PTV) and in the organs at risk were considered. A numerical "biological" model was used to compare the techniques. RESULTS: The two-beam and the four-beam box techniques give the most homogeneous dose distributions in the PTV, although all techniques result in dose distributions that would be considered adequate, provided 16 MV or higher photon energies are used. Three- and four-beam techniques show advantages over the two-beam technique with respect to organs at risk, particularly the small bowel. With the two-beam technique and the upper beam limit at mid-L4, the volume of the bowel that receives > 95% of the prescribed dose, and hence, is included in the treated volume (TV), is more than twice as large as that with three- and four-beam techniques, and that of the total body between 1.5 and 2 times as large. The results of the analyses using the biological model indicate that the three- and four-beam techniques result in less small bowel complication rates than the two-beam technique. The integral energy to the total body is similar for all treatment modalities compared. CONCLUSIONS: The volume of bowel included in the TV, rather than the energy imparted to the body, influences postoperative mortality, and emphasizes the importance of precise radiotherapy planning to minimize normal tissue toxicity.

Aged↗

Acute lumbosacral plexopathy during and after preoperative radiotherapy of rectal adenocarcinoma.

The benefit of preoperative radiotherapy of adenocarcinoma of the rectum with respect to a reduced local recurrence rate and an improved survival should be weighed against adverse effects. For 14 years a three-beam, isocentric technique was employed at our hospital to deliver five fractions (5.0 or 5.1 Gy), over 5 or 7 days preoperatively, to patients with rectal cancer which was considered primarily resectable. The adverse effects of the radiotherapy were few, but acute pain and subacute neurological symptoms and signs did occur. An apparent increase in the frequency of these symptoms/signs was noted during 1993. The pain and neurological symptoms are described in case reports and the individual treatments are reviewed. The three-beam technique was analyzed in detail with individual, CT-based, three-dimensional dose-planning and dose distributions in the vicinity of the lumbar nerve plexus are presented. The major result of this analysis showed that technical errors could be excluded, that human errors were unlikely, and that the culprit probably was an unexpected sensitivity to marginal changes in the daily dose and unknown or unexpected radiosensitizing effects of concurrent diseases or medication.

Acute Disease↗

Comparative treatment planning between proton and X-ray therapy in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: Conformal treatment planning with megavoltage X-rays and protons for medically inoperable patients with a large rectal cancer has been studied in an attempt to determine if there are advantages of using protons instead of X-rays. MATERIAL AND METHODS: Three dose plans were made for each of the six patients: one proton plan, including three beams covering the primary tumour and adjacent lymph nodes and three boost beams covering the primary tumour: one X-ray plan, eight beams including a boost with four beams and one mixed plan with four X-ray beams and a boost with three proton beams. A three dimensional treatment-planning systems, TMS, was used. The evaluation of the different plans was made by applying the biological models TCP and NTCP on the dose distributions in terms of dose-volume histograms. RESULTS: The comparison shows advantages of using protons instead of X-rays for all six patients, but in three of them, the advantage is only marginal. The dose-limiting organ at risk is the small bowel, but the proton plan and the mixed plan also spare the bladder and the femoral heads better. At 5% NTCP in any risk organ, the calculated mean TCP value for the six patients is increased by 14%-units with the proton plan and 8%-units with the mixed plan compared to X-rays only. CONCLUSIONS: Proton beam therapy has potential advantages when treating medically inoperable patients with a large rectal cancer over conventional X-ray therapy. Since the benefits are comparatively small, although clinically worthwhile, large randomised studies are needed.

Aged↗

Resting energy expenditure, weight loss, and altered body composition in HIV infection.

Failure to downregulate resting energy expenditure (REE) as an adaption to anorexia or malabsorption is often stated as the major cause of weight loss in individuals with AIDS. In a prospective study, REE was compared with weight changes in HIV-infected patients. The impact of altered body composition on REE was reassessed by critical review of the literature. Patients were 65 male HIV-infected patients, 28 with recent weight loss (WL), and 37 who were weight stable (WS); 50/65 patients had AIDS, and 29/65 had acute infections; 29 male healthy persons served as controls. Indirect calorimetry, prospective intake protocol, and bioelectrical impedance analysis were performed. Absolute REE was lower in WL patients than in controls (1459 +/- 309 versus 1711 +/- 151 kcal/d, p < 0.001) and in WS patients (1625 +/- 402 kcal/d, p < 0.05). REE/kg body cell mass (BCM) was higher in WL and WS than in controls (both p < 0.01) due to lower BCM in both patient groups (p < 0.001). REE (%Harris-Benedict) was not different among the three groups. Weight changes around the measurement were not correlated to REE (r2 = 0.0008, p = 0.82). REE was independent of diarrhea, acute infection, fever, or caloric intake. REE had a stronger correlation to body weight and to Harris-Benedict's prediction than to fat-free mass or BCM. REE explains < 1% of weight changes. Many patients can downregulate REE as an adaption to anorexia and/or malabsorption. Higher REE/kg BCM does not signify hypermetabolism at the cellular level but can be explained by the maintenance of energy-consuming visceral tissue within the BCM during BCM loss.

Acquired Immunodeficiency Syndrome↗

How to manage patients with severe left ventricular dysfunction and valvular regurgitation.

BACKGROUND AND AIMS OF THE STUDY: The purpose of this study is to analyze treatment options for valvular regurgitation with severe left ventricular dysfunction. MATERIAL AND METHODS: Results of valvular surgery in 98 patients with mitral or aortic regurgitation and severe systolic left ventricular dysfunction (LVD) were analyzed. Selection criteria were the absence of significant coronary heart disease and a resting ejection fraction (EF) < 40% for aortic and < 50% for mitral regurgitation. RESULTS: In patients with aortic regurgitation (n = 46) operative mortality was higher but not significantly so than in a control group of 238 cases (6.5% vs. 3.4%). The actuarial survival rates at five and 10 years were 84% and 55% vs. 84% and 67%, respectively. Independent preoperative predictors of severe postoperative LVD were rheumatic etiology and increased left ventricular end-systolic diameter. In patients with mitral regurgitation (n = 52), operative mortality was not significantly different from that of a control group of 273 cases (3.8% vs. 2.6%), whether the surgical procedure was valve replacement or valve repair. Perioperative morbidity was frequent (30% of cases), mainly low cardiac output, after valve replacement. The actuarial survival rates at eight years were respectively for the groups with and without LVD: 81% and 89% after valve repair, 60% and 75% after valve replacement. Independent predictors of severe postoperative LVD were increased left ventricular end-systolic volume and the type of surgery. Better results were observed after valve repair. CONCLUSIONS: It is concluded that a low EF is not a predictive factor of operative mortality but it influences late survival as do the degree of left ventricular dilatation, etiology in aortic and type of surgery in mitral regurgitation. Alternatives to valvular surgery have been envisaged but information on vasodilators in these patients is scant and results of heart transplantation are known only from a few small series.

Adult↗

Interleukin-10 is an autocrine growth factor for acquired immunodeficiency syndrome-related B-cell lymphoma.

Interleukin-10 (IL-10) is an acid-sensitive protein of 35 kD that has pleiotropic effects including inhibition of cytotoxic T-cell response, induction of major histocompatibility complex type II in B lymphocytes, induction of B-cell growth and differentiation, and autocrine growth factor activity in monocytes. We and others have shown that IL-10 is produced spontaneously by blood mononuclear cells from human immunodeficiency virus-seropositive patients. In an attempt to ascertain the potential role of IL-10 in acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, we evaluated the expression of human IL-10 in both tumor-derived B-cell lines and primary tumor cells. Expression of human IL-10 (hIL-10) mRNA and protein was detected in four of five cell lines examined. An IL-10 antisense oligonucleotide inhibited IL-10 mRNA expression and IL-10 protein production. The proliferation of all B-cell lines was inhibited by an antisense oligonucleotide in a dose-dependent manner that was abrogated by the addition of recombinant hIL-10 protein. No effect of antisense oligonucleotide was observed in the B-cell line not producing hIL-10. Evaluation of primary tumor cells from patients with AIDS-lymphoma cells showed similar production and response to IL-10. These data suggest an autocrine growth mechanism for IL-10 in AIDS-related lymphoma cells and that IL-10 may be important in its pathogenesis.

B-Lymphocytes↗

Effects of interleukin-1 and interleukin-1 receptor antagonist in AIDS-Kaposi's sarcoma.

Kaposi's sarcoma (KS) is the most common tumor seen in patients with HIV-1 infection. HIV-1 may induce KS directly through viral protein(s) or indirectly through regulation of cytokines such as IL-1 and IL-6. We have shown that AIDS-KS spindle cells express IL-1 beta and that IL-1ra inhibits KS-spindle cell growth. IL-1ra had little effect on human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells (HASM), and human foreskin fibroblast (NN41). These findings support an autocrine activity for IL-1. Furthermore, exogenous IL-1 can enhance AIDS-KS cell growth, and this effect is completely blocked by IL-1ra. As expected, IL-1ra also blocks IL-1 mediated upregulation of IL-6 and bFGF, both of which are autocrine growth factors for KS. IL-1ra is thus a potential candidate for the treatment of AIDS-associated KS.

Acquired Immunodeficiency Syndrome↗

Immune response to Chlamydia trachomatis heat-shock protein in infertile female patients and influence of Chlamydia pneumoniae antibodies.

A total of 446 sera from 245 patients with primary or secondary infertility, all of whom were examined laparoscopically, 117 patients with Chlamydia trachomatis-positive cervical swabs, and 84 control persons (50 obstetric patients and 34 female blood donors) were tested for antibodies to Chlamydia trachomatis and to Chlamydia pneumoniae with the microimmunofluorescence (MIF) test. MIF test antibody rates were highest in patients with complete tubal occlusion (73%) and in patients with proven Chlamydia trachomatis infection (74%), whereas only 9 to 10% of the control group showed Chlamydia trachomatis antibodies. Reaction to the 60 kDa antigen of Chlamydia trachomatis, a heat-shock protein (hsp) analogue, has been suggested as a possible marker for the development of chronic sequelae after Chlamydia trachomatis infection. Immunoblot analysis of 222 sera (169 infertility patients, 20 antigen-positive patients, and 33 mothers) showed a significantly higher anti-hsp antibody rate in patients with complete tubal occlusion than in infertility patients with normal fallopian tubes (76% vs. 19%, p < 0.001). The presence of antibodies not only to Chlamydia trachomatis but also to Chlamydia pneumoniae in the MIF test was associated with a significantly higher rate of anti-hsp antibodies and with complete tubal occlusion. This association did not appear to be due to cross-reactivity between Chlamydia pneumoniae and Chlamydia trachomatis antibodies in the MIF test.

Adult↗

Radiotherapy in addition to radical surgery in rectal cancer.

In order to lower unacceptably high local failure rates after surgery reported as curative for rectal cancer, perioperative radiotherapy has been extensively investigated. The collected information from a number of controlled trials indicates that the proportion of local recurrences is reduced to less than half when radiotherapy at moderately high doses is given preoperatively. This reduction in local failure rates is not seen after postoperative radiotherapy, even if higher doses have been used. Possibly, there is also a slight positive influence on survival from preoperative radiotherapy. Improved survival has been seen also in trials using postoperative radiotherapy, but then only when combined with chemotherapy. With proper dose planning, sufficiently high doses can be given preoperatively with little if any increase in postoperative mortality. Thus, although published knowledge is still rather limited, a properly planned preoperative radiotherapy seems to inflict small bowel and other complication rates, that are less than when radiotherapy of similar efficacy against the tumour is given postoperatively.

Combined Modality Therapy↗