Rapid adaptation to internal states as a coding strategy in visual cortex?

Adaptation is a prominent feature of biological neuronal systems. A common interpretation of adaptation in terms of function is that it provides flexibility for a neuronal system to perform well under varying external conditions, for example by adjusting the input/output relation of a sensory system with reference to the ensemble of stimuli the organism currently perceives. This interpretation, however, only applies if the time-scale of adaptation is slower than the time-scale at which the environment changes. Experimentally it is observed, however, that adaptation can be very rapid. Spike-frequency adaptation of cortical neurons, for example, occurs on a time-scale of approximately 100 ms. Here we show that those rapid adaptation processes can also be understood within the framework of information theory. We start with the hypothesis that neuronal codes are designed to optimize the information a neuronal representation conveys about an input stimulus for any increasing time window beginning with stimulus onset, and we show that this implies a rapid adaptation of the neuronal code on the time-scale of stimulus presentation. Adaptation, however, does not occur because the state of the environment changes. Rather it is a reaction to changes of the organisms own internal state, e.g. the level of noise in the neuronal representation. We apply this approach to a model of an orientation hypercolumn in the primary visual cortex, and predict that inter-columnar interactions should adapt on the time-scale of a typical fixation period ( approximately 300 ms).     

Folate status in Germany 1997-2000

Data about folate intake and blood values of the German population, published between 1997 and 2000, have been reviewed. Median folate intake is about 250 micrograms/day in the adult population, which indicates a high likelihood of inadequate intake when compared to the Estimated Average Requirement (EAR) of 320 micrograms/day. Only a few studies have evaluated serum and erythrocyte folate or plasma homocysteine as a marker of folate status. The most representative data show that 25% of German women of childbearing age have an inadequate recent folate intake. Only 13.3% of the women have red blood cell folate values above the critical value of 400 micrograms/day established by Daly et al (1995). Folic acid fortification of food is shown to be responsible for about 25% of folate intake in the German child and adolescent population in one study. If we extrapolate these data to the general population, folic acid fortification could be the explanation for the differences observed between folate intake and blood values. The discrepancy might also be explained by slight inaccuracies in food composition tables. Folate intake from fortified food or from supplements is not taken into account in most of the studies, which is a variable that can lead to confusion. Nutrition surveys should adapt official composition tables for local food patterns, and include fortified commercial foods, in order to make folate intake data more accurate. However, representative serum and erythrocyte folate values are lacking for most age groups. Before taking public health measures concerning folate fortification of food, the real folate status of the German population should be established.     

Experiments on effects of an intermittent 16.7-Hz magnetic field on salivary melatonin concentrations, rectal temperature, and heart rate in humans

OBJECTIVES: The present experiments concerned the hypothesis that an intermittent, strong and extremely low frequency magnetic field reduces salivary melatonin levels and delays consecutively the nadirs of rectal temperature and heart rate. METHODS: Twelve healthy young men (18-25 years) participated in three randomly permuted sessions, which were performed as constant routines. The participants kept a strict bed rest over 26 h, air temperature was 20 degrees C, illumination < 30 lx, and sound level < 50 dBA. Salivary melatonin levels were determined hourly, rectal temperature and heart rate were registered continuously throughout. An intermittent magnetic field was administered in one session from 6 p.m. to 2 a.m. at 16.7 Hz, 0.2 mT and alternating on/off-periods of 15 s. This situation was compared with a control session without any additional stress. Another session was performed to determine the participants' ability to respond to a well-known melatonin-suppressing stress, namely bright light (1,500 lx, 10 p.m.-2 a.m.). RESULTS: Bright light inhibited melatonin synthesis in all 12 participants and delayed the nadirs of rectal temperature and heart rate. The only significant alteration that was associated with exposure to the magnetic field was a delay in the heart rate nadir, which was not mediated by an accordingly altered melatonin profile. CONCLUSION: The fact that the circadian rhythm of only the heart rate was altered indicates an internal dissociation which might constitute a health risk in the long run and needs to be investigated more extensively.     

Uranium mining in Germany: incidence of occupational diseases 1946–1999

OBJECTIVES: In East Germany, uranium mining was performed on a large scale for approximately 45 years (1946-1990). In particular, the poor working conditions during the post-war years until 1955 led to a high level of occupational diseases. The present study gives an overview of the occurrence of occupational diseases during the mining period as well as after uranium mining was stopped in 1990. METHODS: The number of occupational diseases which occurred during the mining period was calculated from the files of the former Wismut SDAG. Although exposure to uranium ceased after 1990, new cases of occupational diseases were recognized after that date. These were recorded by the German Federation Of Institutions For Statutory Accident Insurance And Prevention (HVBG). RESULTS AND CONCLUSIONS: Today, more than 35,000 cases of occupational diseases are known, and many more are expected. About two-thirds of them are lung diseases: 16,376 cases of silicosis/silicotuberculosis and 7,695 cases of bronchial carcinomas. The increase in the number of recognized occupational diseases is shown and discussed against the background of changes in criteria for recognition and in working conditions as well as the duration of the latency period.     

Bcl-X(L) is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy

Malignant melanoma is a tumor that responds poorly to a variety of apoptosis-inducing treatment modalities, such as chemotherapy. The expression of genes that regulate apoptotic cell death plays an important role in determining the sensitivity of tumor cells to chemotherapeutic intervention. Bcl-x(L) is an antiapoptotic member of the Bcl-2 family and is universally expressed in human melanoma. To evaluate the Bcl-x(L) protein as a potential therapeutic target in melanoma, the influence of Bcl-x(L) expression levels on the chemoresistance of human melanoma cells was investigated. Overexpression of Bcl-x(L) in stably transfected human melanoma Mel Juso cells significantly reduced sensitivity to cisplatin-induced apoptosis (p < or = 0.05). In a parallel approach, reduction of Bcl-x(L) protein by specific AS oligonucleotide (ISIS 16009) treatment enhanced the chemosensitivity of Mel Juso cells by 62% compared to cells treated with MM control oligonucleotide (ISIS 16967) as well as chemotherapy-induced apoptosis. These data suggest that Bcl-x(L) is an important factor contributing to the chemoresistance of human melanoma. Reduction of Bcl-x(L) expression by AS oligonucleotides provides a rational and promising approach that may help to overcome chemoresistance in this malignancy.     

Gemcitabine and Radiotherapy in the Treatment of Brain Metastases from Transitional Cell Carcinoma of the Bladder: A Case Report

Hematogenous metastases occur in over 50% of muscle-invasive transitional cell carcinomas (TCC) of the bladder. Despite treatment (mostly surgery and radiotherapy), patients with brain metastases have an especially poor prognosis (median survival 2–5 months), making palliative treatment an important consideration. We followed a 60-year-old man with multiple brain metastases who was ultimately treated with gemcitabine chemotherapy. He underwent a cystectomy in 1997 because of a T3a N0 M0 G3 TCC of the bladder. Two years later, he developed one brain metastasis and one lung metastasis. Both metastases were resected and adjuvant chemotherapy was planned. Before chemotherapy, the patient suffered from headaches and symptoms of hemiparesis. A magnetic resonance imaging (MRI) showed multiple brain metastases of up to 2cm, particularly in the brain stem. The patient underwent whole-brain radiotherapy with 30Gy, followed by four cycles of a 3-week gemcitabine (800mg/m² on days 1 and 8) schedule. Another MRI showed a nearly complete response after four cycles of chemotherapy, with only small residual tumors remaining in the brain stem. This impressive activity was accomplished without adverse side effects, suggesting that radiotherapy combined with gemcitabine monotherapy may be an excellent choice for palliative treatment of TCC of the bladder.     

Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: a comparative evaluation

Introduction The usefulness of routine axillary dissection (AD) at levels I–II in breast cancer patients has been questioned for years because of the high postoperative morbidity in the shoulder and arm region, and the increasing number of patients with negative nodes. Sentinel node biopsy (SNB) was hoped both to reduce morbidity and to improve the reliability of staging. This study was designed to provide more evidence in this matter by comparing the follow-up data of patients with AD and those with SNB only. Method One hundred forty patients who had undergone AD between 1993 and 1996 were questioned for their subjective and objective symptoms using a questionnaire and subsequently subjected to a clinical examination. Their data were compared with those of 57 patients who had undergone SNB only between 1998 and 2000. Results Local recurrences have not been seen to date. The difference between the two groups in terms of a loss of quality of life was negligible. The differences in overall complaints, number of symptoms, pain, limited range of motion of the operated upper extremity, numbness, paresthesias, and arm swelling as well as perceived disability in activities of daily living were significantly in favor of SNB. The length of hospital stay was significantly shorter for SNB patients. Conclusion SNB appears to be an accurate procedure for axillary nodal staging in breast cancer patients and is associated with reduced postoperative morbidity and length of hospital stay. But it is still investigational and should not be implemented as therapeutical standard before results of randomized trials are published.     

Tumor cell-targeting by phage-displayed peptides

We isolated cancer cell-specific phages by subtracting and selecting complex peptide display phage libraries on cultured human cancer cells. The best candidate was selected by performing three rounds of subtraction before each of five selections on the human colorectal WiDr cell line. The phage showed more than 1000-fold higher binding efficiency for WiDr cells when compared to five other human cancer cell lines, including two of colorectal origin, and when compared to wild-type M13 phage. Fifty-fold higher binding efficiency was also seen for a human breast cancer cell line. We show that the WiDr cell binding of the selected phage was efficiently competed by the synthetic peptide HEWSYLAPYPWF, predicted from the phage sequence. This confirms that the specificity of the peptide is independent of the display by the phage coat proteins. The identified peptide may target biomarkers linked to colorectal cancer, and thus be useful for designing gene transfer vectors as well as diagnostic and prognostic tools for this disease.     

Homogeneous Ir-192 afterloading-flab-irradiation of plane surfaces

Homogeneous irradiation of plane targets by Ir-192 afterloading flabs made by a parallel series of linear applicators can be time-consuming even with modern planning systems. The aim of the present study was to develop an algorithm that supplies homogeneous dose distributions in an arbitrary given plane in parallel to the equipped plane of a flab. The edge and corner positions of the flab are of particular importance. The identity of the dose in the optimisation distance above the flab centre, corners, and middle of the flab edges, leads to a strict relation of the respective dwell weights. Formulas can be derived that allow the calculation of the dwell times. The dimensioning of the flab can be rapidly adapted to new conditions. A comparison with the results of Nucletron PLATO-BPS for applicator-applicator distances and step sizes of 1 cm at optimisation distances of 10, 20, 30, and 40 mm and various flab sizes (3 x 3, 9 x 9, and 15 x 15 cm2) shows the following results: The standard deviation of the proposed algorithm is sometimes slightly higher than the results of the commercial planning system, whereas the underdosage at the flab edges is usually smaller. The effort for planning and preparation of the irradiation, for example using a Nucletron HDR, is below 5 minutes--a considerable reduction of planning time.