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Biomedical subjects

D Brune

Publications and source records attributed to D Brune.

At least 19 recordsLinked to original sources
PubMed1998

Chlorophyll alpha synthesis upon interruption and deletion of por coding for the light-dependent NADPH: protochlorophyllide oxidoreductase in a photosystem-I-less/chlL- strain of Synechocystis sp. PCC 6803.

The gene coding for the light-dependent NADPH:protochlorophyllide oxidoreductase (POR) was interrupted or deleted in a Synechocystis sp. PCC 6803 strain lacking photosystem I (PS I) as well as ChlL, which takes part in light-independent catalysis of protochlorophyllide reduction. Interruption of por by a kanamycin-resistance cartridge between the codons for M263 and V264 (about 83% into the coding region) did not abolish POR activity, but resulted in a decrease in the protochlorophyllide-(PChlide)-binding capacity of POR. Deletion of por in the PS I-less/chlL- strain generated a mutant [PS I-less/chlL-/por (del)] which accumulated both monovinyl-PChlide and divinyl-PChlide and excreted PChlides into the medium. This mutant also synthesized small amounts of protochlorophyllide dihydrogeranylgeraniol ester (protochlorophyll) when it was grown under light-activated heterotrophic growth conditions. However, the mutant was still able to synthesize small amounts of normal chlorophyll a under weak continuous illumination, even though the quantum yield of chlorophyll a formation was reduced. Either protochlorophyll or PChlide reduction by an unspecific reductase or by a ChlB/ChlN complex could account for chlorophyll a synthesis in the PS I-less/chlL-/por (del) strain. Functional photosystem II (PS II) was assembled in this mutant, but the PS II/chlorophyll ratio was fourfold lower than in the PS I-less strain with normal chlorophyll synthesis. The PS I-less/chlL-/por (del) mutant had a 77-K fluorescence emission maximum at 685 nm but no peak or shoulder at 695 nm when the cells were excited at 435 nm. Much of the chlorophyll in the PS I-less/chlL-/por (del) mutant therefore seems to be associated with components other than PS II.

Chlorophyll↗
PubMed1998

Liarozole--a novel treatment approach for advanced prostate cancer: results of a large randomized trial versus cyproterone acetate. Liarozole Study Group.

OBJECTIVES: To compare the efficacy of oral liarozole, the first retinoic acid metabolism-blocking agent (RAMBA) to be developed as differentiation therapy for human solid tumors, with that of cyproterone acetate (CPA), an antiandrogen for the treatment of metastatic prostate cancer. Liarozole promotes differentiation of cancer cells by increasing the intratumoral levels of retinoic acid. METHODS: A total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy entered a Phase III international multicenter study (recruitment from February 1992 to August 1994) comparing liarozole (300 mg two times daily) with CPA (100 mg two times daily). RESULTS: Accounting for differences in baseline prognostic factors, the adjusted hazard ratio for survival was 0.74 in favor of liarozole (P = 0.039), indicating a 26% lower risk of death than in patients treated with CPA. Median crude (unadjusted) survival time was the same in the liarozole group as in the CPA group (10.3 months). More patients showed a PSA response (at least 50% reduction in PSA from baseline) when treated with liarozole (20%) than with CPA (4%) (P < 0.001). Prostate-specific antigen (PSA) responders had a median survival benefit of 10 months over nonresponders, irrespective of treatment (hazard ratio 0.43; P = 0.0018). PSA response was apparent within 3 months in approximately 90% of patients who responded. Pain improved more in the liarozole group than in the CPA group (P = 0.03). PSA responders had lower median pain scores than nonresponders (1.7 versus 2.5) and better quality of life (median Functional Living Index-Cancer score 108 versus 98) at end point, ie, treatment discontinuation, as well as throughout the treatment period. Among the most frequently occurring adverse events in the liarozole group were dry skin (51% of patients), pruritus (25%), rash (16%), nail disorders (16%), and hair loss (15%). These adverse events were generally mild to moderate in severity and did not affect the overall quality of life score. There were no detectable effects of either treatment on vital signs such as blood pressure, heart rate, electrocardiogram, and body weight. CONCLUSIONS: Liarozole is superior to CPA in terms of PSA response, PSA progression, and survival, and is capable of maintaining patients' quality of life. The observed adverse events were mild to moderate in nature. These results show that liarozole is a possible treatment option after first-line endocrine therapy has failed.

Aged↗
PubMed1998

Health-related quality of life and sequelae in patients treated with brachytherapy and external beam irradiation for localized prostate cancer.

PURPOSE: To evaluate late physical and psychosocial sequelae in patients treated with an association of external beam irradiation (EBI) and brachytherapy (BT) for localized prostate cancer. PATIENTS AND METHODS: Seventy-one patients free of disease, treated at the Centre François Baclesse from 1988 to 1992, were enrolled in a case-control study. Seventy-one healthy controls, matched on age and residence, were selected at random from electoral rolls. Two self-administered questionnaires were mailed in January 1996. The French translation of the Nottingham Health Profile questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 core questionnaire were used to evaluate physical, role, emotional, cognitive and social functioning, global health status as well as energy and sleep disturbance. Specific problems related to prostate cancer were explored using the prostate specific module developed by the EORTC Genito-Urinary Tract Cancer Cooperative Group. Concordance between clinical complications reported by patients and those reported by physicians was also analyzed. RESULTS: General health quality of life scale scores did not significantly differ between patients and controls, nor did general symptom scale scores. Furthermore, no more late psychosocial sequelae were reported by patients than by controls. No major digestive complications were observed among patients. However, statistical differences were observed concerning interest in sex (P = 0.016) and sexual activity (P < 0.001), urinary incontinence (P < 0.001) and cystitis (P = 0.01). Late subjective morbidity (dysuria, nocturia, urinary incontinence, pelvic pain) appraisal differed slightly between patients and physicians who generally underestimate its severity. While nocturia was reported more often by physicians than by patients (P = 0.0016), patients reported urinary incontinence and pelvic pain more often than physicians (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: The study demonstrates that survivors from localized prostate cancer treated with an association of BT and EBI have good global health status. Major problems that persist are sexual disorders, urinary incontinence and cystitis while digestive disorders were rare. This association could be an alternative to standard EBI in patients with localized prostate cancer. Whatever the treatment choice, patients should be involved in the therapeutic decision which should consider not only expected survival rate but also quality of life.

Aged↗
PubMed1994

Hydrodynamic steering effects in protein association.

Protein-ligand reaction rates are often limited by the rate of diffusional encounter of the protein and ligand in solution. Reaction rates, however, can be much greater than expected, given the necessity for correct orientation before reaction. A number of forces can affect the orientation of the protein and ligand in solution, and thus increase the reaction rate. We have considered hydrodynamic forces, produced when water molecules between protein and ligand must be pushed out of the way to allow their encounter. We have used the cleft enzymes as a model system, as they could be expected to show strong hydrodynamic effects. One particular type of hydrodynamic interaction stands out: a steering torque which occurs when the enzyme and substrate move toward each other in solution. The magnitude of this steering torque is compared to the mutual torque experienced by interacting "protein-sized" dipoles in solution. A simple model is used to demonstrate that the hydrodynamic steering torque can be 2 orders of magnitude greater than the electrostatic torque.

Biophysical Phenomena↗
PubMed1994

Patient and staff needs drive changes on a postsurgical unit.

In response to a dynamic health care environment and influenced by fiscal pressures, "business as usual" on the postsurgical unit at University of Nebraska Medical Center required examination. Both internal and external factors prompted a staff-driven task force to plan and implement changes. The task force consisted of representatives from staff and management to redesign current practices collaboratively. Issues addressed were nursing workload, responsibilities, scheduling, patient satisfaction, job satisfaction, and professional development. Expected outcomes of changes in the work design on the unit centered on increased efficiency of nursing time, cost effectiveness, and increased satisfaction of patients and nursing staff. The task force proposed and implemented innovative changes in the report and documentation system, utilization of nonprofessional staff, and redesign of work hours. The article presents these changes in the work environment and focuses on a written report system and a clearly defined role for nonprofessional staff.

Academic Medical Centers↗
PubMed1993

Biological specimen bank for smelter workers.

The biological specimen bank was initiated by the department of Environmental Medicine and the department of Medicine at the University of Umeå in 1975. The aims of the bank are to collect information on trace elements in human organs. Special attention is focused on the influence of occupational exposure. Tissue samples are taken from deceased workers from a copper and lead smelter in northern Sweden. Control specimens have been collected from deceased normal individuals from four control areas. Lung, liver and kidney samples are collected with quartz instruments and stored in quartz ampoules to avoid contamination. Other samples, e.g. bone, brain, fat, hair, heart muscle, nails, skin and stomach are taken with common autopsy instruments and stored in acid-washed polyethene vessels. The samples are stored at -20 degrees C. The elements Sb, As, Cd, Cr, Co, La and Se are analyzed by neutron activation analysis, Pb and Zn by atomic absorption spectrophotometry. The findings over time can be related to a number of factors: normal values in tissues, airborne exposure and causes of death. Special attention is paid variation over time, reevaluation of threshold limit values and risk assessment.

Autopsy↗
PubMed1993

Predicting protein diffusion coefficients.

Diffusion coefficients for proteins in water are predicted. The numerical method developed is general enough to be applied to a wide range of protein surface shapes, from rodlike to globular. Results are presented for lysozyme and tobacco mosaic virus, and they are compared with actual data and with predictions made by less general methods.

Diffusion↗
PubMed1993

International project for producing reference values for concentrations of trace elements in human blood and urine--TRACY.

In assessing the concentrations of toxic metals, such as cadmium, chromium, and mercury, in human blood and urine samples to determine whether they are abnormal or not, reliable reference values are needed from populations of nonoccupationally exposed subjects. Numerous publications present concentrations claimed to be typical for the study populations, but they can differ by up to an order of magnitude for a particular element. This is the consequence of general problems that are related to the definition of the reference groups, and the sampling and analytical procedures used, and that make it difficult to define typical and unbiased values. An international group of experts now establishes criteria and procedures to evaluate publications containing information on the concentrations of metals in tissues and body fluids for reference populations. These evaluations have been compiled in a data base (TRACY).

Hazardous Substances↗
PubMed1993

Normal concentrations of chromium in serum and urine--a TRACY project.

The validity of "normal" concentrations for total chromium in serum and urine (S-Cr and U-Cr, respectively) in papers published mainly in the last decade were evaluated and graded by two investigators according to TRACY criteria. The results were in close agreement. Because of possible contamination during sampling from stainless steel needles, the description of the sample collection method was considered important. Documentation of analytical quality control was emphasized. The chromium concentrations were categorized according to nonoccupational conditions that could influence the levels. Eighty-seven publications reporting chromium concentrations in blood and 58 on U-Cr were evaluated, 53 dealing with S-Cr and 41 with U-Cr being found suitable for the TRACY project. In selected publications the arithmetic mean values presented for S-Cr and U-Cr in individuals with no known exposure were within the following ranges: 1-3 nmol.1-1 for S-Cr and 2-10 nmol.1-1 or 0.2-1 mumol.mol creatinine-1 for U-Cr.

Chromium↗
PubMed1992

The ICOH and IUPAC international programme for establishing reference values of metals.

In cooperation with the ICOH Scientific Committee on the Toxicology of metals and IUPAC Commission on Toxicology, we have developed evaluation criteria for derivation of reference values for metal concentrations in human tissues and fluids. In a first attempt to illustrate how these criteria may be used, tentative reference values for mercury in human blood were derived. For persons who do not eat fish, a mean value of 10 mumol/1 (2 micrograms/1) was suggested. It was pointed out, however, that this value was based on information that did not meet the desired quality requirements, which, unfortunately were not met by any of the published reports.

Animals↗
PubMed1992

Prostate cancer treated by radiotherapy: a multivariate study.

According to respective proportions of evolutive status groups, results of multivariate studies are difficult to interpret. Among the 1099 cases of local form of prostate cancer, treated by radiotherapy from 1975 to 1982 in 16 French Anticancer Institutes, we can observe two homogeneous status groups of patients: disease-free survivors (285 cases) and patients who died of prostate cancer (278 cases). These correspond to 51% of the whole population. Among other things, they are comparable in size, for age at the beginning of radiotherapy and for delay between histologic diagnostic and radiotherapy. We chose to analyse them using multivariate analysis. To take survival into account, we used a Cox model and Kaplan-Meier curves; the group deceased of prostate cancer was further analyzed by a tree-structured regression method. The Cox model and the Kaplan-Meier curves confirmed two main explicative factors: Stage (p < 0.0001) and tumor grade (p < 0.001). Poorer evolution occurs in extracapsular forms and grade I has better survival than others. The tree-structured regression method indicates two other pejorative factors: hormonotherapy prior to radiotherapy and the presence of cardiovascular pathology. Though the pelvic dose does not appear to be a main explicative factor, it seems to improve survival and delay between radiotherapy and recurrence or metastasis in some categories of cases. Other factors such as tumor dose, age and delay between diagnosis and radiotherapy were not found to be significant. These results cannot be extended to the whole population for which they do not constitute a predictive study. We consider them as "baseline data".(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

A review of normal concentrations of mercury in human blood.

The present survey is a critical review and quality grading of 98 publications in the international scientific literature presenting mercury concentrations in human whole blood, blood cells and plasma of individuals who have not been occupationally exposed to mercury ("normal values"). Most of the papers reviewed were published after 1976 and were found in the Medline database. Additional information has been obtained in response to requests addressed to scientists with high reputation from different parts of the world working in the field of trace element analysis. The evaluation system includes separate grade scales for sampling and chemical analysis. In no case were the requirements justifying the highest Grade 1 i.e. superior quality, fulfilled. Most reports suffered from various degrees of a lack of information concerning description of individuals, diet, experimental design or analytical and statistical treatment. Nineteen papers were rejected because of insufficient information or obvious erroneous sampling or analytical treatment (Part I). The influence on blood mercury level of various non-occupational exposures, particularly fish consumption, but also medication with mercury-containing drugs, presence of amalgam restorations, etc., has been surveyed. The levels have been systematized according to such parameters. The evaluated and systematized data have been stored in a PC database "Tracy", which includes information about concentrations of total, inorganic or organic mercury in whole blood, blood cells or plasma. Mercury in maternal-cord blood is also included. One hundred and thirty-two data sets from 79 reports were included in the database (Part II). Because of the shortcomings of the available information, only tentative reference values for mercury in whole blood, blood cells and plasma were established (Part III). There is an obvious need for additional high-quality data.

Humans↗
PubMed1988

Multielemental assay of tissues of deceased smelter workers and controls.

Concentrations of 23 elements in lung, liver and kidney from deceased smelter workers are compared with those from rural and urban controls. The analyses were made by neutron activation analysis and atomic absorption spectrophotometry. Significantly higher levels of antimony, arsenic, cadmium, chromium, cobalt, lanthanum, lead and selenium were found in the smelter workers lungs (n = 85) compared with the rural controls (n = 15). Significantly higher concentrations of antimony, arsenic and lead were observed among all smelter workers compared with urban controls (n = 10). The highest increase, about 11-fold, was found for antimony in smelter workers compared with non-exposed controls. A six-fold increase was noted for arsenic. Workers who died from lung cancer (n = 7) had the lowest lung selenium content relative to concentrations of other metals, both compared with other disease categories among the workers (GI-cancer, other cancers, cardiovascular diseases, cerebrovascular diseases, other causes) and with the two control groups. The low lung selenium concentrations may have influenced the development of lung cancer. The highest lung tissue levels of cadmium were found in the lung cancer group. Smokers and ex-smokers were over-represented in this group and tobacco is a known cadmium source. The highest, or one of the highest, lung values for some of the other metals (antimony, arsenic, cadmium, lanthanum and lead) were observed in one or several of the lung cancer cases. Metal concentrations in liver (metabolism) and kidney (excretion) reflect the systemic distribution. The highest cadmium levels in the liver and the lowest selenium content in the kidney were found among the lung cancer cases. A multifactorial genesis for the development of lung cancer is concluded from this study, which visualizes the need for systematic health surveillance and follow-ups both in active and retired workers.

Aged↗
PubMed1988

(3,6-Dimethyl-3,6-diazaoctan-1,8-dithiolato-S1,N3,N6,S8)oxotechnetium(V) pertechnetate.

[TcO(C8H18N2S2)]TcO4, Mr = 484.2, monoclinic, P2(1)/c, a = 7.447 (2), b = 16.952 (8), c = 12.236 (3) A, beta = 99.63 (2) degrees, V = 1523 (1) A3, Z = 4, D chi = 2.112, Dm = 2.09 (1) Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.06 mm-1, F(000) = 952, T = 295 (1) K, final R = 0.071 for 2496 significant reflections and 173 parameters. The Tc atom is bound to the oxo group and the N and S atoms of the complex ligand in a rough square pyramid. The Tc atom lies 0.770 (3) A out of the S,N,N',S' plane. This plane is significantly distorted such that N and N' lie nearly 0.25 A out of the plane on opposite sides. The Tc-S bonds [2.238 (3), 2.266 (3) A] are short but other bond lengths and angles are normal.

Models, Molecular↗
PubMed1988

Radiation therapy of carcinomas of the skin of nose and nasal vestibule: a report of 1676 cases by the Groupe Europeen de Curiethérapie.

A retrospective multicentric analysis of the results of irradiation of 1676 carcinomas of the skin of the nose and nasal vestibule was performed by the Groupe Européen de Curiethérapie (Tunis, May 1986). Overall local control was 93% with a minimum follow-up of 2 years. Local control is dependent on the tumor size (diameter less than 2 cm: 96%, 2-3.9 cm: 88%, greater than or equal to 4 cm: 81%), and tumor site (external surface of the nose: 94%, vestibule: 75%). Local control was independent of histology for smaller tumors, but for those larger than 4 cm, basal cell carcinomas were more frequently controlled than squamous cell carcinomas. Recurrent tumors are less frequently controlled than those being treated for the first time (88 vs. 95%). There were few complications and cosmetic results were generally satisfactory. The results of implantation, orthovoltage and megavoltage irradiation are compared with respect to local control, complication rate and cosmesis. Implantation is usually the treatment of choice for vestibular tumors but for those of the external surface the choice depends on the tumor diameter. Implantation and orthovoltage irradiation are equivalent for tumors less than 2 cm. For those from 2 to 3.9 cm, the results of orthovoltage irradiation may be satisfactory in a selected population but implantation is usually more suitable for tumors with rapidly changing contour.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Is prophylactic para-aortic irradiation worthwhile in the treatment of advanced cervical carcinoma? Results of a controlled clinical trial of the EORTC radiotherapy group.

From November 1977 to July 1981, 441 patients with cervical carcinoma were randomized between pelvic irradiation and pelvic and para-aortic irradiation. Included were patients with stage I and IIB with proximal vaginal and/or parametrial involvement with positive pelvic lymph nodes either on lymphangiogram or at surgery, and stage IIB with distal vaginal and/or parametrial involvement and III regardless of pelvic node status on lymphangiogram. Patients with clinically or surgically involved para-aortic nodes were not included. The external beam dose to the para-aortic area was fixed at 45 Gy. There was no statistically significant difference between the two treatment arms in terms of local control, overall distant metastases and survival with no evidence of disease (NED), although the incidence of para-aortic metastases and distant metastases without tumor at pelvic sites was significantly higher in patients receiving pelvic irradiation alone (pelvic group). The 4-year NED survival rate was 51%. The incidence of severe digestive complications was significantly higher in patients receiving para-aortic irradiation (para-aortic group). Routine para-aortic irradiation for all high risk patients with cervical carcinoma is of limited value, but patients with a high probability of local control can benefit from extended field irradiation, despite an increase in severe digestive complications.

Aorta↗