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Biomedical subjects

J H Rudolph

Publications and source records attributed to J H Rudolph.

15 recordsLinked to original sources

Live cell imaging of heavy-ion-induced radiation responses by beamline microscopy.

To study the dynamics of protein recruitment to DNA lesions, ion beams can be used to generate extremely localized DNA damage within restricted regions of the nuclei. This inhomogeneous spatial distribution of lesions can be visualized indirectly and rapidly in the form of radiation-induced foci using immunocytochemical detection or GFP-tagged DNA repair proteins. To analyze faster protein translocations and a possible contribution of radiation-induced chromatin movement in DNA damage recognition in live cells, we developed a remote-controlled system to obtain high-resolution fluorescence images of living cells during ion irradiation with a frame rate of the order of seconds. Using scratch replication labeling, only minor chromatin movement at sites of ion traversal was observed within the first few minutes of impact. Furthermore, time-lapse images of the GFP-coupled DNA repair protein aprataxin revealed accumulations within seconds at sites of ion hits, indicating a very fast recruitment to damaged sites. Repositioning of the irradiated cells after fixation allowed the comparison of live cell observation with immunocytochemical staining and retrospective etching of ion tracks. These results demonstrate that heavy-ion radiation-induced changes in subnuclear structures can be used to determine the kinetics of early protein recruitment in living cells and that the changes are not dependent on large-scale chromatin movement at short times postirradiation.

Cell Culture Techniques↗

The management of clinical stage I endometrial carcinoma.

A retrospective analyses of 307 cases with clinical Stage I endometrial carcinoma was done in an attempt to determine the role of radiation therapy in the optimal treatment of this disease. A review of the modern literature with over 9000 cases served as a useful tool to corroborate inferences and conclusions. The present series has 155 patients (51%) treated with preoperative megavoltage external pelvic radiation with a variation in doses of less than 6%. Five-year survival estimates (79%-83%) in clinical Stage I endometrial carcinoma are similar among the several main treatment combination that are employed; they become a useless parameter for any comparison. The pelvic failure rate constitutes a more useful guideline in assessing the most adequate therapy. The pathologic grade of the tumor is the main prognosticator in endometrial carcinoma. Intimately related to the tumor grade is the depth of myometrial invasion of the carcinoma. The size of the uterus and/or its cavity carry less prognostic significance than traditionally thought. For grade I lesions, there is little error in diagnosis, few pelvic failures and excellent survival (96%); they could be approached with initial surgery and postoperative radiation reserved for selected patients. For grade 2 tumors, the error in diagnosis and the failure rate increases with an overall survival of 87%. For grade 3 tumors, the error in diagnosis and failure rates are quite high with a 5 year survival of only 70%. Preoperative radiation, especially external beam therapy, is suggested for grades 2 and 3 Stage I tumors. The use of this treatment modality yields only 3% pelvic failure and an overall 5 year survival of almost 90%.

Carcinoma↗

Adenosquamous carcinoma of the endometrium. An entity with an inherent poor prognosis?

Mixed adenosquamous carcinoma of the endometrium have been reported in recent years to have a steady increase in incidence, extreme aggressiveness, poor responses to radiation therapy, and a low five-year survival (less than 20%). In the present report, 87 mixed carcinoma (MC) are compared with 260 pure adenocarcinomas (AC) and 29 adenoacanthomas (AA). There were no basic differences in incidence, clinical history, responses to radiation therapy, and prognosis for any of these three entities. Adenocarcinomas of the endometrium with and without squamous elements should be regarded and approached as any pure AC. There is an overall tendency for endometrial carcinomas to be at an early stage at diagnosis and the five-year survival regardless of pathologic type, stage, grade, myometrial invasion, and therapy is 80%.

Adenocarcinoma↗