Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors.

A role for the membrane/cytoskeleton interface in the development and progression of cancer is established, yet poorly understood. The neurofibromatosis type II (NF2) tumor suppressor gene encodes a member of the ezrin/radixin/moesin (ERM) family of membrane/cytoskeleton linker proteins thought to be important for cell adhesion and motility. We report that in contrast to the narrow spectrum of benign tumors in human NF2 patients, Nf2 heterozygous mice develop a variety of malignant tumors.

The C. elegans spe-9 gene encodes a sperm transmembrane protein that contains EGF-like repeats and is required for fertilization.

In the nematode worm C. elegans, individuals with mutations in the spe-9 gene produce spermatozoa with wild-type morphology and motility that cannot fertilize oocytes even after contact between gametes. Therefore, disruption of spe-9 function affects either gamete recognition, adhesion, signaling, and/or fusion.

K-ras is an essential gene in the mouse with partial functional overlap with N-ras.

Mammalian ras genes are thought to be critical in the regulation of cellular proliferation and differentiation and are mutated in approximately 30% of all human tumors. However, N-ras and H-ras are nonessential for mouse development. To characterize the normal role of K-ras in growth and development, we have mutated it by gene targeting in the mouse.

The effects of lattice water on free radical yields in X-irradiated crystalline pyrimidines and purines: a low-temperature electron paramagnetic resonance investigation.

The hydration layer of DNA increases the target size of DNA with respect to the formation of direct-type damage by ionizing radiation. The mechanisms that give rise to this increase are being investigated by EPR spectroscopy. To determine these mechanisms, it is necessary to distinguish between the change in sample mass and changes in packing/conformation brought about by the change in the level of hydration.

Gastroenteritis causing critical limb ischaemia.

Six days after admission to hospital with Salmonella gastroenteritis, this patient presented with a critically ischaemic leg, having developed an iliac occlusion, and a subcutaneous Salmonella abscess in the anterior compartment of the leg. Critical limb ischaemia and abscess formation can be added to infective aortic aneurysm as vascular complications of Salmonella gastroenteritis.

The influence of packing on free radical yields in crystalline nucleic acids: the pyrimidine bases.

The total free radical yield has been measured for crystals of five pyrimidine derivatives: thymine (T), 1-methylthymine (1MeT), 1-methyluracil (1MeU), 1-methylcytosine (1MeC) and cytosine monohydrate (C:HOH). Q-band EPR measurements were made on samples X-irradiated between 4 and 12 K. The G values in units of 10(-7) mol/J are 1MeC < 0.

Ontogenesis of peripheral benzodiazepine receptors: demonstration of selective up-regulation in rat testis as a function of maturation.

Peripheral benzodiazepine receptors (PBR) have been localized to the outer mitochondrial membrane in a variety of organs, where they apparently play a role in steroidogenesis, oxidative processes, and/or growth and development. Previous studies have demonstrated ontogenetic changes in heart and lung PBR, with maximal PBR density at 31 days, as opposed to negligible changes in brain PBR during the prenatal through postnatal periods. The present study was designed to examine the influence of maturation and aging upon PBR binding characteristics.

Distribution of electron trapping in DNA: protonation of one-electron reduced cytosine.

Electron spin resonance was employed to study one-electron reduced cytosine stabilized in glasses at low temperatures. In a LiCl/H2O glass, deoxycytidine gives an extra approximately 1 mT splitting that is not observed in oligomers. To better understand the source of the extra splitting, 1-methylcytosine (1mC) and N,N-dimethyldeoxycytidine (dmC) were examined in an HCl/H2O glass.

Electrochemical detection of human brain transmitter amino acids by high-performance liquid chromatography of stable o-phthalaldehyde-sulphite derivatives.

A simple, sensitive, reliable and reproducible isocratic HPLC technique for the measurement of OPA/sulphite derivatives of human brain amino acid neurotransmitters is described. This employs a sample preparation that is also compatible with the concurrent determination of monoamines and their metabolites on a separate HPLC system. The method has been applied to the determination of GABA and glutamate in brain tissue taken post-mortem from patients with Huntington's disease and control subjects.

Three-dimensional structure of cholera toxin penetrating a lipid membrane.

Two-dimensional crystals of cholera toxin bound to receptors in a lipid membrane give diffraction extending to 15 A resolution. Three-dimensional structure determination reveals a ring of five B subunits on the membrane surface, with one-third of the A subunit occupying the center of the ring. The remaining mass of the A subunit appears to penetrate the hydrophobic interior of the membrane.

Free radicals trapped in methyl alpha-D-mannopyranoside X-irradiated at 77 K: an ESR/ENDOR study.

Four free radicals are trapped in methyl alpha-D-mannopyranoside X-irradiated and maintained at 77 K. All four have been identified, with high confidence levels, using ESR and ENDOR spectroscopy. One, an alkoxy radical located at O4, is characterized by a gmax of 2.

Synaptic development in the rabbit superior colliculus and visual cortex.

The development of synapses in the visual cortex (VC) and superior colliculus (SC) of the rabbit has been examined with the electron microscope. In both areas, the number of synapses reaches adult levels by 20--25 days of postnatal age, but the development in the visual cortex is delayed in comparison to that in the superior colliculus. When S synapses (spheroidal vesicles, asymmetric thickening) are compared with F synapses (flattened vesicles, symmetric thickening), even greater differences are seen.

Intraocular penetration of topical clindamycin in rabbits. II. Clindamycin phosphate.

We have obtained comparative data for the intraocular absorption of topically administered clindamycin hydrochloride hydrate and clindamycin phosphate, made feasible with a new gas chromatographic method of analysis. Results indicated that clindamycin phosphate underwent hydrolysis in the eye, liberating the biologically active clindamycin. However, topical clindamycin hydrochloride produced higher levels (two to six times more) of the antibiotic than those achievable with the phosphates ester in the uvea, aqueous humor, and cornea, presumably due to clindamycin hydrochloride's higher lipid solubility.

Intraocular penetration of topical clindamycin in rabbits.

Clindamycin is a recently developed, semisynthetic antibiotic whose spectrum of activity suggests a potential for the treatment of common ocular infections. The upake by various ocular tissues and serum in albino rabbits after topical administration of 0.2% clindamycin hydrochloride was studied.