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Biomedical subjects

M Kirschner

Publications and source records attributed to M Kirschner.

At least 19 recordsLinked to original sources
PubMed2004

[Diagnosis and therapy of acute complaints after "whiplash injury" in Germany. Results of a representative survey at surgical and trauma departments in Germany].

Whiplash injury of the cervical spine is a relevant medical and socioeconomic problem, which is still the subject of controversy. We performed a survey to evaluate the current status of diagnostics, classification, treatment, and doctors' subjective opinions at surgical and trauma departments in Germany. A total of 1568 hospitals were addressed to answer a standardized questionnaire on their proceedings and opinions concerning whiplash injury. We received 540 (34.44%) completed questionnaires. There was overall agreement concerning the need for physical examination. The radiological assessment included an a.p. and a lateral plain X-ray of the cervical spine in 82.6%. The indication for functional X-rays in flexion/extension was inconsistent. On average they were performed in 39.1% of all patients. In most cases (68.9%) whiplash injury was not classified; 13.2% of doctors used the classification according to the Quebec Task Force and 13.9% according to Erdmann. A cervical collar was prescribed in 85%. While 30% of patients received only a cervical collar, 55.6% underwent additional physiotherapy. Only 8.3% were treated by physiotherapy without immobilization. The doctors' subjective opinions indicated psychological factors to be important for long-lasting problems, but not for the acute period of complaints. There is no homogeneous concept for diagnostics, classification, and treatment of patients who suffered a whiplash injury in Germany. This situation reflects the current problems in management of this condition. Scientific evidence for functional treatment to avoid adverse influence of immobilization by cervical collars has not yet been transferred to our daily routine in Germany.

Germany↗
PubMed2001

Treatment of morbid obesity in inner-city women.

OBJECTIVE: To explore the use of the very-low-calorie formula diet (VLCD) in the indigent population of Newark, NJ, with the goal of achieving 10% weight loss within a relatively short period of 10 weeks. RESEARCH METHODS AND PROCEDURES: We accepted 131 morbidly obese indigent women into our study program. The study was limited to women only and the average starting weight was 292.3 +/- 5.9 lbs (+/- SE; 50.3 +/- 0.9 body mass index [kg/m(2)]). We used three treatment paradigms: total cost-free program for 10 weeks; cost-free, but compliance requirements; and a weekly charge of $25. The results obtained were compared with two control populations: women enrolled during the same recruitment period in a comparable suburban VLCD program and a historical control population of suburban women treated from 1985 through 1995. RESULTS: In group A (total cost-free), 79% of patients completed the 10-week program, but only 18% of patients achieved the goal of 10% weight loss. In group B when attendance and weight loss requirements were imposed, the dropout rate accelerated such that only 37% of patients completed the 10-week course, and 16% of the women were successful with their weight loss. In group C, imposing $25/wk financial outlay also accelerated dropouts but had little effect on weight loss success, which was 10% of the starting group. By comparison, the suburban patients and the historical control group exhibited 67% and 76% attendance rates after 10 weeks, and 33% and 55% success rates, respectively, in achieving the weight loss goal. DISCUSSION: We conclude that inner-city patients exhibit great interest in weight loss when financial barriers are removed. Successful weight loss was achieved in 10% to 18% of patients using the VLCD approach, approximately one-half of that obtained in affluent suburban women. Imposing financial or compliance restrictions to the inner-city patients served only to enhance dropouts.

Adult↗
PubMed2000

Transient expression and heat-stress-induced co-aggregation of endogenous and heterologous small heat-stress proteins in tobacco protoplasts.

Heat-stress granules (HSG) are highly ordered, cytoplasmic chaperone complexes found in all heat-stressed plant cells. We have developed an experimental system involving expression of cytosolic class I and class II small heat-stress proteins (Hsps) of pea, Arabidopsis and tomato in tobacco protoplasts to study the structural prerequisites for the assembly of HSG or HSG-like complexes. Class I and class II small Hsps formed class-specific dodecamers of 210-280 kDa, which, upon heat stress, were incorporated into HSG complexes. Interestingly, class II dodecamers alone could form HSG-like complexes (auto-aggregation), whereas class I dodecamers could do so only in the presence of class II proteins (recruitment). By analysing C-terminal deletion forms of Hsp17 class II, we obtained evidence that the intact C-terminus is critical for the oligomerization state, for the heat-stress-induced auto-aggregation and for recruitment of class I proteins. The class-specific formation of dimers as a prerequisite for oligomerization was analysed by the yeast two-hybrid system. In the presence of the endogenous (tobacco) set of heat-stress-induced proteins, all heterologous class I and class II proteins were incorporated into HSG complexes, whose ultrastructure was different from that of complexes formed by class I and class II proteins alone. Although other, more distantly related, members of the Hsp20 family, i.e. the plastidic pea Hsp21, the Drosophila Hsp23 and the mouse Hsp25, were well expressed in tobacco protoplasts and formed homo-oligomers of 200-700 kDa, none of them could be recruited to HSG complexes.

Amino Acid Sequence↗
PubMed1999

Intracellular proteolysis.

Our present understanding of intracellular protein degradation developed from an attempt to understand the metabolic stability of proteins in cells. With the unravelling of its complex biochemical machinery has come a realization that protein degradation plays an important role in the most crucial events in the cell cycle, in signal transduction and in maintaining the integrity of the proper folded state of proteins. In this review, I attempt to trace the curious history of intracellular protein degradation, its novel and elegant biochemistry and to extract the features that might be important for the next era of studies in cell physiology.

Animals↗
PubMed1998

Evolvability.

Evolvability is an organism's capacity to generate heritable phenotypic variation. Metazoan evolution is marked by great morphological and physiological diversification, although the core genetic, cell biological, and developmental processes are largely conserved. Metazoan diversification has entailed the evolution of various regulatory processes controlling the time, place, and conditions of use of the conserved core processes. These regulatory processes, and certain of the core processes, have special properties relevant to evolutionary change. The properties of versatile protein elements, weak linkage, compartmentation, redundancy, and exploratory behavior reduce the interdependence of components and confer robustness and flexibility on processes during embryonic development and in adult physiology. They also confer evolvability on the organism by reducing constraints on change and allowing the accumulation of nonlethal variation. Evolvability may have been generally selected in the course of selection for robust, flexible processes suitable for complex development and physiology and specifically selected in lineages undergoing repeated radiations.

Animals↗
PubMed1997

Workshop on schizophrenia.

On November 29-30, 1995, the National Academy of Sciences and the Institute of Medicine brought together experts in schizophrenia and specialists in other areas of the biological sciences in a workshop aimed at promoting the application of the latest biological information to this clinical problem. The workshop paid particular attention to evidence of pathology in the brains of people with schizophrenia, and to the possibility that this reflects an abnormality in brain development that eventually leads to the appearance of symptoms. The participants were impressed with the complexity of the problem, and felt that multiple approaches would be required to understand this disease. They recommended that a major focus should be on the search for predisposing genes, but that there should be parallel research in many other areas.

Brain↗
PubMed1997

[Regression of Yoshida sarcoma during normoxia and hypoxia after fractionated irradiation].

PURPOSE: Tumor regression is one of the most important factors determinating the tumor control probability after radiotherapy. The changes in the regression of tumors during fractionated radiotherapy and the application of different radioprotectors or radiosensitizers make render to assess their effectivity. MATERIAL AND METHOD: The effect of hypoxic breathing (8.1% O2) on the tumor regression of Yoshida sarcoma was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: No significant changes in the tumor regression after radiotherapy in any group in any time independent from respiratoric hypoxia were recorded. The tumor regression rate was significantly influenced by treatment schedule (p < 0.0005). CONCLUSIONS: Our results support the hypothesis of hypoxy-radiotherapy: The acute hypoxic hypoxia, caused due the breathing of hypoxic gas mixture with 8 to 10% oxygen, did not influence the radiation induced tumor regression in animal experiment. For this criterium no protection can be shown. The influence of hypoxy-radiotherapy on the local tumor control is necessary to evaluate in further experiments.

Acute Disease↗
PubMed1997

[Oxygen pressure distribution in lymph node metastases and the changes during acute respiratory hypoxia].

PURPOSE: The radiosensitivity of tissues is essentially influenced by hypoxia. Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while hypoxic breathing during irradiation. PATIENTS AND METHOD: The effect of hypoxic breathing (8.1% O2) on the pO2 in metastatic lymph nodes was studied in 14 patients. Tissue oxygenation was assessed using a polarographic electrode system. RESULTS: The median pO2 was 19.6 mm Hg prior to hypoxic breathing with a great intra- and intertumoral variability. The relative frequency of pO2-values < 5 mm Hg was between 0 and 88%. During hypoxic breathing we registered no significant changes in the mean, the median or the pO2 values < 5 mm Hg. CONCLUSIONS: In metastatic lymph nodes can be found chronic hypoxia with great inter- and intratumoral pO2 variability. The hypoxic breathing (8.1% O2) shows no significant modifications of the tumor oxygenation with increased pO2 variability. This fact explains the experimental and clinical experience, that the hypoxic breathing (8 to 10% O2) protects the healthy tissue without changes in the radiosensitivity of chronic hypoxic tumor tissue.

Acute Disease↗
PubMed1997

Stable transformation of an Arabidopsis cell suspension culture with firefly luciferase providing a cellular system for analysis of chaperone activity in vivo.

Using Agrobacterium, we developed a method to transform an Arabidopsis cell suspension culture. A stably transformed cell line expressing high levels of firefly luciferase (Luc) was used for in vivo studies of thermal denaturation and renaturation of the enzyme and the protective role of different chaperones. Luc activity was monitored under heat stress and recovery conditions in control, thermotolerant cells and cells expressing plant chaperones after transient cotransformation with plasmids encoding proteins of the heat shock protein Hsp90, Hsp70, or Hsp20 family. The effects of the expressed proteins were specific. The Hsp17.6 class I protein maintained Luc activity on a level comparable with that observed in thermotolerant cells and improved Luc renaturation. Although transient expression of Hsp90 did not protect Luc from thermal denaturation, it accelerated Luc renaturation during recovery. In contrast to the other chaperones tested, overexpression of Hsp70 alone had no effect on denaturation and renaturation of Luc but enhanced Luc renaturation if coexpressed with Hsp17.6.

Animals↗
PubMed1996

[Hypoxyradiotherapy: changes in the oxygen partial pressure distribution in the tumor and in the healthy tissue under acute respiratory hypoxia].

PURPOSE: Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while breathing hypoxic gas mixture during irradiation. MATERIAL AND METHODS: The effect of breathing hypoxic gas mixture (8.1% O2) on pO2 in Yoshida sarcoma and muscle was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. Tissue oxygenation was assessed with a polarographic electrode system. RESULTS: The median pO2 in Yoshida sarcoma was 10 mm Hg. 21% of pO2-values were lower than 5 mm Hg. During breathing of hypoxic gas mixture no significant changes in median tumor pO2 or radiobiologic hypoxic values (< or = 5 mm Hg) were recorded. The median pO2 in muscle was 30 mm Hg. During breathing of gas hypoxic mixture a significant decrease of the median to the value 12 mm Hg and an increase of the radiobiologic hypoxic values (p < 0.00001) were observed. The changes of pO2-values were constant independent from fractionation. CONCLUSIONS: Between tumor and healthy tissue exists a significant difference regarding changes in the radiobiologic fraction during breathing of hypoxic gas mixture. This fact explains the experimental and clinical experience, that the breathing hypoxic gas mixture protects the healthy tissue without changes in the radiosensibility of chronic hypoxic tumor tissue.

Acute Disease↗
PubMed1996

Concurrent Taxol and split-course accelerated radiotherapy for advanced head and neck cancer.

AIM: The aim of this study was to investigate feasibility and toxicity of fractionated paclitaxel administration concurrently with accelerated radiotherapy in the treatment of advanced head and neck cancer. PATIENTS AND METHODS: Patients with a proven histology of inoperable head and neck carcinoma were eligible for this study. Between July 1994 and August 1995, 12 patients with stage IV (UICC) tumors were treated. Patients were required to have normal end-organ function. Exclusion criteria included: age > 70 years, metastatic disease, performance status (Karnofsky < 70), major intercurrent medical disorders, and previous chemotherapy. External radiation was delivered twice a day at 1.5 Gy per fraction, specified to the reference point (ICRU 50), with a minimum interfraction interval of 6 hours. The accelerated scheme was split into 2 courses by a rest period of 9 days (including weekends) after administration of 30 Gy within 2 weeks. After 39 days a total dose of 72 Gy was reached. Paclitaxel (30 mg/m2/d) was administered as a continuous intravenous infusion over a period of 3 hours on days 1 to 5 and 29 to 33 of radiation therapy. All patients received premedication to avoid allergic reactions and circulatory monitoring was used routinely. RESULTS: Radiochemotherapy was completed in 10 patients with 8 complete and 2 partial remissions. Most important toxicity was a short period of neutropenia, which occurred 3 to 6 days after chemotherapy and was associated with fever in 9 cases. During paclitaxel infusion there was a significant but clinically not relevant increase in blood pressure and a decrease in heart rate. No acute cardiac effects occurred and no hypersensitivity reaction was seen. CONCLUSIONS: This regimen demonstrates a high activity in locally advanced head and neck cancer. Neutropenia associated with fever was the major dose limiting toxicity.

Aged↗
PubMed1996

[Reoxygenation in Yoshida sarcoma during different fractionated radiotherapy].

PURPOSE: Tumor reoxygenation is one of the most important factors determining the tumor control probability after radiotherapy. In experimental studies reoxygenation has been measured preferably after single dose irradiation. Only few data exist about changes in the hypoxic tumor fraction during fractionated radiotherapy. MATERIAL AND METHODS: The changes in the pO2 during fractionated radiotherapy were studied in Yoshida sarcoma transplanted to Wistar rats. Tissue oxygenation was assessed using a polarographic electrode system at the beginning, in the middle and at the end of radiation therapy. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: In the statistical analysis significant changes emerged in the mean, median, 10%-percentile and 0 to 2.5 mm Hg and 0 to 5.0 mm Hg values dependent on time. The tumors were significantly more hypoxic at the end of therapy. This trend became more pronounced with decreasing dose per fraction. CONCLUSIONS: The Yoshida sarcoma has no effective reoxygenation during fractionated radiotherapy.

Animals↗
PubMed1995

G1 cyclin-dependent activation of p34CDC28 (Cdc28p) in vitro.

In Saccharomyces cerevisiae, transient accumulation of G1 cyclin/p34CDC28 (Cdc28p) complexes induces cells to traverse the cell cycle Start checkpoint and commit to a round of cell division. To investigate posttranslational controls that modulate Cdc28p activity during the G1 phase, we have reconstituted cyclin-dependent activation of Cdc28p in a cyclin-depleted G1 extract. A glutathione S-transferase-G1 cyclin chimera (GST-Cln2p) efficiently binds to and activates Cdc28p as a histone H1 kinase. Activation of Cdc28p by GST-Cln2p requires ATP, crude yeast cytosol, and the conserved Thr-169 residue that serves in other organisms as a substrate for phosphorylation by cyclin-dependent protein kinase-activating kinase. This assay may be useful for distinguishing genes that promote directly the posttranslational assembly of active Cln2p/Cdc28p kinase complexes from those that stimulate the accumulation of active complexes via a positive-feedback loop that governs synthesis of G1 cyclins.

Amino Acid Sequence↗
PubMed1995

Ubiquitination of the G1 cyclin Cln2p by a Cdc34p-dependent pathway.

Recombinant G1 cyclin Cln2p can bind to and stimulate the protein kinase activity of p34CDC28 (Cdc28p) in an extract derived from cyclin-depleted and G1-arrested Saccharomyces cerevisiae cells. Upon activating Cdc28p, Cln2p is extensively phosphorylated and conjugated with multiubiquitin chains. Ubiquitination of Cln2p in vitro requires the Cdc34p ubiquitin-conjugating enzyme, Cdc28p, protein phosphorylation and unidentified factors in yeast extract. Ubiquitination of Cln2p by Cdc34p contributes to the instability of Cln2p in vivo, as the rate of Cln2p degradation is reduced in cdc34ts cells. These results provide a molecular framework for G1 cyclin instability and suggest that a multicomponent, regulated pathway specifies the selective ubiquitination of G1 cyclins.

Anaphase-Promoting Complex-Cyclosome↗