Tula Virus as Causative Agent of Hantavirus Disease in Immunocompetent Person,Germany

We report molecular evidence of Tula virus infection in an immunocompetent patient from Germany who had typical signs of hantavirus disease. Accumulating evidence indicates that Tula virus infection, although often considered nonpathogenic, represents a threat to human health.     

Uptake of indium-111 in the liver of mice following administration of indium-111-DTPA-labeled monoclonal antibodies: influence of labeling parameters, physiologic parameters, and antibody dose

Liver uptake of indium-111 (111In) in mice was investigated following administration of 111In-DTPA murine monoclonal antibodies (111In-DTPA-MAbs) labeled by the cyclic anhydride method. Biodistribution of HPLC-purified 111In-DTPA-MAb preparations was checked with a low (0.2 micrograms) and a high (8.0 micrograms) MAb dose. Using Bio Gel P-30 for desalting the MAb-conjugates, 111In uptake in the liver amounted to 8%-9% of the injected dose (ID) and was independent from the MAb dose, the DTPA-to-MAb molar ratio, tumor growth and biologic variability (different MAbs and different strains of mice). Using Sephadex G-25 for desalting, 0.2 micrograms doses from 7 out of 26 preparations showed increased liver accumulation of 111In in non-tumor mice ranging from 15%-25% of ID. Corresponding high doses led to a "normal" value of 8%-9%. Increased liver uptake of the low dose could not be reduced by coadministration of the unconjugated MAb, but was normal after reinjection of "in vivo filtered" material. An inverse intracellular distribution of 111In activity between sediment and supernatant of liver homogenates, following the administration of the low and the high MAb dose, indicated an artifact of the labeling procedure rather than an inherent biological property of labeled MAbs.     

Therapy of primary breast cancer in the 21st century: A prediction

Biology

New treatment selection criteria will arise from molecular biology parameters of growth and treatment response, most probably coupled with the increasing use of initial chemotherapy and repeated minimally invasive surgery.

Prevention

Secondary and hopefully also primary prevention of breast cancer will become more and more successful in the era of molecular genetics, and such interventions will be more directed to individuals and groups at defined higher risk.

Surgery

Surgery will increasingly tend towards “minimally invasive surgery,” which favors not only cosmetics and quality of life, but also more appropriate imaging follow-up.

Chemotherapy

Primary (preoperative) chemo- and endocrine therapy will become the standard initial form of breast cancer treatment, with the intent of down-staging of the tumors to allow later breast-conserving procedures, but also to use the tumor as a biological response parameter and hopefully also for better clinical outcome.

Cost — Effectiveness

Economical parameters might become more and more decisive, as we will have to live with much more “evidence based medicine” and with much more restricted allocation of resources in the future. This might mean, that we will have to diligently develop more simple and cheaper, but not prognostically worse treatment strategies in years to come. More specifically: Do we still need all of the traditional steps in diagnosis and treatment of breast cancer in order to achieve the same results?

Gain of Life

Finally in all of this, we have to make clearcut assumptions, supported also by society and people involved: How do we value “gained years of life” in breast cancer adjuvant and prevention trials? This certainly is not predominantly a medical or economical, but rather an ethical, social and political problem, which has to be finally answered by our socio-cultural environment, and not by doctors alone.     

Pax-1 in the development of the cervico-occipital transitional zone

The Pax-1 gene has been found to play an important role in the development of the vertebral column. The cervico-occipital transitional zone is a specialized region of the vertebral column, and malformations of this region have frequently been described in humans. The exact embryonic border between head and trunk is a matter of controversy. In order to determine a possible role of Pax-1 in the development of the cervico-occipital transitional zone we studied the expression of this gene in a series of quail embryos and murine fetuses with in situ hybridization and immunohistochemistry. Pax-1 is expressed in all somites of the embryo, including the first five occipital ones. During embryonic days 3–5 the gene is down-regulated in the caudal direction within the first five somites, whereas more caudally Pax-1 is strongly expressed in the cells of the perinotochordal tube. In 5-day-old quail embryos, the cartilaginous anlage of the basioccipital bone has developed and there is no more expression of Pax-1 in this region. The fusion of the dens axis with the body of the axis also coincides with switching off of the Pax-1 gene. More caudally, the gene is continuously expressed in the intervertebral discs of murine embryos and therefore seems to be important for the process of resegmentation. Quail embryos do not possess permanent intervertebral discs. Hyper- or hyposegmentation defects may be explained by an over- or under-expression of Pax-1 during development. We also reinvestigated the border between the head and trunk in chick embryos by performing homotopical grafting experiments of the 5^th somite between chick and quail embryos. Grafted quail cells formed mainly the caudal end of the basioccipital bone. They were also located in the cranial half of the ventral atlantic arch, and only a few cells were found in the tip of the dens axis.     

Extracellular site of action of phenylalkylamines on L-type calcium current in rat ventricular myocytes

The effects of the phenylalkylamines verapamil, gallopamil, and devapamil on L-type calcium currents (I_Ca) were studied in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. In particular, the question was addressed, whether the pharmacological binding sites for these drugs were located at the inner and/or at the outer surface of the cell membrane. Therefore, tertiary verapamil, gallopamil, and devapamil and their corresponding quaternary derivatives were applied either from the outside or the inside of the cell membrane. Extracellular application of verapamil, gallopamil and devapamil (each at 3 M) reduced Ica to 16.1 ±8.6%, 11 ± 8.9 %, and 9.3 ± 6 % of control, respectively. Intracellular application of the same substances, via the patch pipette filled with 30 M of either verapamil, gallopamil, or devapamil, failed to depress I_Ca. The quaternary derivatives of the phenylalkylamines (30 M) were ineffective both when applied extracellularly or intracellularly. It is suggested that phenylalkylamines block I_Ca in ventricular myocytes by acting on a binding site of the calcium channel molecule located at the outer surface of the cell membrane.     

Velocity invariance of preferred axis of motion for single spot stimuli in simple cells of cat striate cortex

In slices from the visual cortex of kittens maintained in vitro, long-term potentiation of synaptic transmission following high frequency stimuli (10 Hz, 2 min) delivered at low to medium stimulus intensities (80 to 200 A), is accompanied by changes of certain electrophysiological measures recorded intracellularly, such as long-lasting depolarization of membrane potential and decreased threshold to elicitation of an action potential. These parameters have never before been shown to be altered following high frequency stimulation in other systems widely used in studying synaptic plasticity, such as in hippocampal neurons. Another important difference between results from these two systems is that the amplitude of the excitatory post-synaptic potential is enhanced after high frequency stimulation in hippocampal neurons, whereas in striate cortex from young kittens, we observed a decrease. We demonstrate here that this decrease can be reversed to show enhancement from the original amplitude, upon clamp of membrane potential back to the voltage observed prior to stimulation. Thus, what appears to be long-term depression of synaptic transmission, as recorded extracellularly and represented by diminished flow of synaptic current, can be reversed by stepping membrane voltage back to the pre-high frequency stimulation level, to produce responses that then become consistent with long-term potentiation.     

Screening methods for thyroid hormone disruptors

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.