Contribution of striate cortex and the superior colliculus to visual function in area MT, the superior temporal polysensory area and the inferior temporal cortex

We studied the visual responses of single neurons in three extra-striate visual areas of the macaque following lesions of striate cortex, lesions of the tecto-pulvinar system or both. After striate lesions, there was (a) considerable specific activity remaining in area MT including direction selectivity, (b) only non-specific activity in the superior temporal polysensory area (STP), and (c) no visual responsiveness at all in inferior temporal cortex (IT). In animals with striate lesions, interruption of the tecto-pulvinar pathway eliminated the residual visual activity in MT and STP that survived the striate lesions. Interruption of the tecto-pulvinar pathway alone had little or no effect on visual evoked activity in any of the three areas. These results are related to the relative dependence of visual responsiveness in MT, STP and IT on striate cortex and the superior colliculus, to differences between the dorsal and ventral cortical processing streams, and to neural mechanisms underlying blind sight.     

Membrane-coated fiber array approach for predicting skin permeability of chemical mixtures from different vehicles.

A membrane-coated fiber (MCF) array approach was developed for quantitative assessment of skin absorption from chemical mixtures, which was based on the similarity in the absorption mechanisms of the MCF membrane and the stratum corneum of the skin. A set of probe compounds were used to detect the relative molecular interaction strengths of chemicals with the vehicle and the membranes, which provided a linkage between the skin permeability (log k) and MCF partition coefficients (log KF). A predictive model was established via multiple linear regression analysis of the data matrix of experimentally measured log k value and log KFm values; log k=a0+a1 log KF1+a2 log KF2+...+an log KFm, where m is the number of diverse MCFs. Twenty-five probe compounds and three MCFs (polydimethylsiloxane for lipophilic, polyacrylate for polarizable, and CarboWax for polar interactions) were used to demonstrate the model development processes in the MCF array approach. The skin permeability of the probe compounds was measured with conventional diffusion cell experiments using dermatomed porcine skin. Three predictive models were established for skin permeability prediction from chemical mixtures in water, 50% ethanol, and 1% sodium lauryl sulfate (SLS) with R2 values of 93, 91, and 83, respectively. The log k and log KF values were considerably altered by the addition of ethanol or SLS into the dose vehicle; however, their correlations to skin permeability remained strong under various conditions. These results suggested that the experimentally based MCF array approach can be used to predict skin absorption from chemical mixtures in different vehicles or formulations.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Severe tubulopathy and kidney graft rupture after coadministration of mannitol and ciclosporin.

Spontaneous allograft rupture after kidney transplantation is a rare complication usually due to an acute rejection of the interstitial type. In a 32-year-old man kidney transplantation was performed under immunosuppression with prednisolone and ciclosporin (CS). The dose of CS was 5 mg/kg body weight intravenously for the first 24 h, on the 2nd day 10 mg/kg/day orally, with gradually decreasing doses thereafter. The patient remained oliguric in the postoperative period and received additionally 600 ml mannitol solution intravenously for osmodiuresis within a period of 6 days. On the 8th postoperative day, 48 h after the last intravenous infusion of mannitol, spontaneous renal rupture occurred. The CS concentrations in the blood during the days before the rupture were within the upper normal range for effective immunosuppression (300-600 ng/ml). Intraoperatively the kidney appeared enlarged due to edematous swelling of the graft, but it showed no signs of rejection. The histological finding was a toxic tubulopathy with extensive isometric vacuolization and peritubular congestion, a known side effect of both of CS and of mannitol. The rupture was successfully repaired. Thirty-four days after the transplantation diuresis increased and hemodialysis therapy could be discontinued. In a second biopsy of the kidney the signs of toxic tubulopathy with isometric vacuolization were reduced. On the following days the serum creatinine dropped below 160 mumol/l. It can be assumed that the combination of CS therapy and administration of massive and continued doses of mannitol in an oliguric patient with allograft kidney may potentiate severe tubulopathy with concomitant edematous swelling of the graft. This can result in an increasing danger of spontaneous renal rupture.     

Screening for glaucoma: age and sex of referrals and confirmed cases in England and Wales

This paper is based on a prospective survey covering 275,600 sight tests by optometrists in England and Wales. It analyses the age and sex distribution of 1402 referrals for suspected glaucoma and 456 confirmed cases of the disease. The proportion of sight tests which led to a confirmed case increased with age, for both sexes, to a maximum at approximately 70 years, and then tended to decline. Cases of glaucoma in people aged 36-51 years accounted for about a tenth of the total, which is more than is generally recognized. Wider adoption of routine tonometry for middle aged people would help to ensure that these cases are detected at an early stage. Confirmed cases of glaucoma in which raised intraocular pressure had not been given as a reason for referral, i.e. probable low tension glaucomas, increased from 5% of patients < 51 years old to 13% of patients > 75 years old. Glaucoma was found to be much more common in men.     

Binding characteristics of the new thromboxane A2/prostaglandin H2 receptor antagonist [3H]BAY U 3405 to washed human platelets and platelet membranes.

The new thromboxane A2 antagonist [3H]BAY U 3405 was characterized for its binding to washed human platelets and platelet membranes. In washed platelets the specific binding was reversible, selective and stereospecific, but not saturable. The dissociation constant (Kd) was 6 +/- 2.5 nM, the number of specific binding sites 1177 +/- 306 per platelet. Three structurally different thromboxane A2 (TXA2)/prostaglandin H2 (prostaglandin endoperoxide) (PGH2) receptor ligands completely inhibited the specific binding of [3H]BAY U 3405 in a concentration-dependent manner, indicating that the observed high affinity binding site is the TXA2/PGH2 receptor. In platelet membranes, however, specific [3H]BAY U 3405 binding showed saturability in addition to reversibility, selectivity, and stereospecifity. The Kd of the binding was 9.6 +/- 2.3 nM in kinetic studies and 8.7 +/- 3.7 nM in saturation studies, the inhibition constant (Ki) was 10 +/- 1.1 nM in displacement studies. The TXA2/PGH2 receptor agonists U 46619 and CTA2, and the antagonists Daltroban (BM 13505), I-PTA-OH and SQ 29548 all completely inhibited the specific binding of [3H]BAY U 3405 thus defining the observed binding site as the TXA2/PGH2 receptor. In conclusion, the data suggest that the previously reported TXA2 antagonism of BAY U 3405 is mediated by binding to a specific high affinity binding site of human platelets and platelet membranes that represents the TXA2/PGH2 receptor.