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F Merz

Publications and source records attributed to F Merz.

11 recordsLinked to original sources
PubMed2005

Low temperature of GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of deltatigdeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C deltatigdeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of deltatigdeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/= 60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Chaperonin 10↗
PubMed2004

Low temperature or GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor and DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of DeltatigDeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C DeltatigDeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of DeltatigDeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/=60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Chaperonin 10↗
PubMed2004

Functional dissection of Escherichia coli trigger factor: unraveling the function of individual domains.

In Escherichia coli, the ribosome-associated chaperone Trigger Factor (TF) promotes the folding of newly synthesized cytosolic proteins. TF is composed of three domains: an N-terminal domain (N), which mediates ribosome binding; a central domain (P), which has peptidyl-prolyl cis/trans isomerase activity and is involved in substrate binding in vitro; and a C-terminal domain (C) with unknown function. We investigated the contributions of individual domains (N, P, and C) or domain combinations (NP, PC, and NC) to the chaperone activity of TF in vivo and in vitro. All fragments comprising the N domain (N, NP, NC) complemented the synthetic lethality of Deltatig DeltadnaK in cells lacking TF and DnaK, prevented protein aggregation in these cells, and cross-linked to nascent polypeptides in vitro. However, DeltatigDeltadnaK cells expressing the N domain alone grew more slowly and showed less viability than DeltatigDeltadnaK cells synthesizing either NP, NC, or full-length TF, indicating beneficial contributions of the P and C domains to TF's chaperone activity. In an in vitro system with purified components, none of the TF fragments assisted the refolding of denatured d-glyceraldehyde-3-phosphate dehydrogenase in a manner comparable to that of wild-type TF, suggesting that the observed chaperone activity of TF fragments in vivo is dependent on their localization at the ribosome. These results indicate that the N domain, in addition to its function to promote binding to the ribosome, has a chaperone activity per se and is sufficient to substitute for TF in vivo.

Escherichia coli↗
PubMed2002

Intraoperative radiotherapy given as a boost after breast-conserving surgery in breast cancer patients.

Conventional radiotherapy after breast-conserving therapy is confined to 50-55 Gy external beam radiation therapy (EBRT) to the whole breast and 10-16 Gy external boost radiation to the tumour bed or brachytherapy to the tumour bed. Local recurrence rate after breast-conserving surgery varies between 5 and 18%. External boost radiation can partially miss the tumour bed and therefore can result in local failure. Intra-operative radiotherapy (IORT) as a high precision boost can prevent a 'geographical miss'. From October 1998 to December 2000, 156 patients with stage I and stage II breast cancer were operated upon in a dedicated IORT facility. After local excision of the tumour, the tumour bed was temporarily approximated by sutures to bring the tissue in the radiation planning target volume. A single dose of 9 Gy was applied to the 90% reference isodose with energies ranging from 4 to 15 MeV, using round applicator tubes 4-8 cm in diameter. After wound healing, the patients received additional 51-56 Gy EBRT to the whole breast. No acute complications associated with IORT were observed. In 5 patients, a secondary mastectomy had to be performed because of tumour multicentricity in the final pathological report or excessive intraductal component. 2 patients developed rib necroses. In 7 patients, wound healing problems occurred. After a mean follow-up of 18 months, no local recurrences were observed. Cosmesis of the breast was very good and comparable to patients without IORT. Preliminary data suggest that IORT given as a boost after breast-conserving surgery could be a reliable alternative to conventional postoperative fractionated boost radiation by accurate dose delivery and avoiding geographical misses, by enabling smaller treatment volumes and complete skin-sparing and by reducing postoperative radiation time by 7-14 days.

Adult↗
PubMed1999

Radiotherapy for lung cancer: target splitting by asymmetric collimation enables reduction of radiation doses to normal tissues and dose escalation.

PURPOSE: This study was performed to develop a method of reducing the radiation doses to normal thoracic tissues, increasing the target dose, especially in the primary radiotherapy of non-small cell lung cancer (NSCLC), and to evaluate acute/subacute toxicity of dose escalation. METHODS AND MATERIALS: From December 1195 to March 1998, the technique of target splitting has been applied to 58 patients. In this period, 30 patients were treated with doses > 80 Gy (ICRU-specification, mean 85.1 Gy, range 80. 1-90.2 Gy). The target volume is split into a cranial part (e.g., upper mediastinum) and a caudal part (e.g., primary tumor and middle mediastinum). Both volumes are planned and treated independently, using conformal irradiation techniques for both parts with half-collimated fields to prevent over- or underdosage in the junction plane. After fine-adjustment of the jaws, a verification film, exposed in a polymethylmethacrylate (PMMA) phantom, demonstrates the homogeneity of dose in the entire target volume. For comparison with conventional techniques, planning to identical doses is performed for 5 patients. Dose-volume histograms (DHVs) for normal lung tissue are presented for both methods. RESULTS: The irradiated volume of normal tissue of the ipsilateral lung can be lowered at dose levels > or = 65, > or =45 Gy, and > or = 20 Gy to values of 37% (range 25-54%), 49% (range 46-54%), and 86% (range 55-117%), respectively. Other organs at risk, such as heart or esophagus, can also be spared significantly. Only 1 patient showed a transient grade 3 toxicity (pneumonitis), and there where no grade 4 acute/subacute side-effects. Two patients with Stage III A central tumors in close proximity to the large vessels died due to a pulmonary hemorrhage 2 and 4 months after therapy, respectively. No patient developed esophagitis. Antimycotic prophylaxis for esophagitis and posttherapeutic steroid prophylaxis for pneumonitis for several weeks were routinely used. CONCLUSION: The technique of target splitting by asymmetric collimation helps to increase conformation, and thus enhances the sparing of normal tissues. It can be used whenever there is a marked difference in the shape of the planning target volume (PTV) in a cranio-caudal direction. This technique can principally be handled with 2D-planning systems, because it is coplanar. We consider target splitting as an important tool for dose escalation in the primary radiotherapy of NSCLC, that should also be used for other lung cancer patients necessitating moderate doses only.

Adenocarcinoma↗
PubMed1999

[Long-term tumor control and fertility after para-aortic limited radiotherapy of stage I seminoma].

PURPOSE: To review patterns of relapse in a long-term analysis of patients with Stage I seminoma treated by orchidectomy and radiotherapy to the paraaortic lymph nodes only and to follow follicle stimulating hormone (FSH) levels dependent on testicular scatter dose. PATIENTS AND METHODS: From 1980 to 1995, 58 patients with Stage I seminoma received elective radiotherapy to the paraaortic lymph nodes only (Th12 to L4), with a mean total dose of 28.07 Gy (+/- 2.2 SD), using fractional doses between 1.5 and 2 Gy (mean 1.62 Gy +/- 0.083 SD). Since 1989, testicular scatter doses were measured routinely by in-vivo thermoluminescent dosimetry (TLD) in 45 patients. In 26 patients with normal pre-treatment values of FSH, FSH-levels were repeatedly controlled after radiotherapy in order to evaluate any radiation-induced sequelae. RESULTS: During a mean observation period of 69.4 months (range 30 to 210), 2 out of 57 patients (3.5%) developed regional recurrences in the ipsilateral pelvic lymph nodes 14 months and 5 years after radiotherapy, respectively. One patient was lost to follow-up. The relapse-free survival rate at 5 years was 96.5% after radiotherapy alone. After salvage chemotherapy, both relapse-free survival and overall survival rates come to 100%. The mean testicular scatter dose in 45 patients was 0.22 Gy (+/- 0.087 SD). Seven out of 26 patients (26.9%) developed a transient increase of FSH-levels, reaching peak values at 4.2 months and returning to normal ranges within 18 months after radiotherapy. Below 0.2 Gy, no effect on FSH was observed. Testicular scatter doses showed no clear correlation to FSH risings (Figure 1). CONCLUSION: After exclusive paraaortic radiation of Stage I seminoma, even at follow-up periods in excess of 5 years the incidence of pelvic lymph node relapses remains below 4%. However, there seems to be a small potential for the development of late recurrences. With limited radiotherapy, permanent radiation-induced effects on the remaining testicle are very unlikely.

Adult↗
PubMed1996

Quality assurance in breast cancer brachytherapy: geographic miss in the interstitial boost treatment of the tumor bed.

PURPOSE: To assess the role of geographic misses in the interstitial boost treatment of breast cancer patients and to evaluate methods of optimizing breast implants in design, performance, and dosimetry. METHODS AND MATERIALS: During lumpectomy, the tumor excision sites of 89 patients were marked by five hemoclips. Postoperative radiographs demonstrated the clips' positions with respect to the extension of the surgical cavity, which was demarcated by air and hematoseroma. Twenty-seven selected patients received interstitial boosts to the tumor bed. The implant was first designed according to the clinical assumptions of the tumor bed's topography and then compared with the radiological findings. Prior to brachytherapy, the planning of the implant's dimension and the needle guidance was performed under simulator control. Dose distributions were first calculated following the Paris System and then electively optimized for the target volume by changing source positions and dwell times. RESULTS: Compared to clinical estimations, the radiological determination of the tumor bed's location revealed an overall potential of topographic errors of 51.8% (14 out of 27 patients), rising up to 78.5% in patients with large adipose breasts (11 out of 13 patients). This observation was due to a high mobility of the tissue, leading to varying tumor site projections at the time of mammography, surgery, and brachytherapy. In all patients, the presimulation of the implant resulted in an adequate coverage of the target volume. In 17 of the 27 treated patients, dose distributions were modified to achieve a higher dose delivery in zones where a higher residual tumor load was expected (boost-in-boost). CONCLUSION: Breast implants have a high potential of geographic misses that can be avoided by intraoperative clip demarcation. The delineation of the tumor bed allows for dose reports actually referring to the target volume and not to the implant system to be obtained. In addition, modern afterloading techniques offer possibilities of individual dose planning with regard to high risk subvolumes within the implanted tissue.

Brachytherapy↗