Toxicity of 5-methoxymethyl-2'-deoxyuridine in hamsters and evaluation of its mutagenicity by sister chromatid exchanges and hypoxanthine guanine phosphoribosyl transferase assays.

Toxic effects of 5-methoxymethyl-2'-deoxyuridine (MMdUrd), a drug with antiviral activity against herpes simplex virus, were investigated in Chinese golden hamsters. Pathological, hematological, and clinical chemistry parameters were studied. Systemic toxicity was not observed in hamsters after intraperitoneal (ip) administration of MMdUrd in single doses up to 3000 mg/kg and in repeated dosages of 600 mg/kg daily for 15 days.

A semi-quantitative atlas of 5-hydroxytryptamine-1 receptors in the primate brain.

The regional distribution of 5-hydroxytryptamine-1 receptors in the primate brain was studied by semi-quantitative autoradiographic analysis of tritiated ligand binding. Areas showing the highest density of 5-hydroxytryptamine-1 receptors (greater than 200 fmol [3H]5-hydroxytryptamine bound per mg tissue), included the cerebral cortex (laminae I-II), claustrum, posterior cell group of the basal nucleus of Meynert, the infracommissural part of the globus pallidus, cortical amygdaloid nucleus, hippocampal formation (CA1-subiculum region, the anterior CA2, CA3 and CA4 regions and the molecular layer of the dentate gyrus), thalamic nuclei (parafascicular, parataenial, paraventricular and superior central lateral nuclei), substantia nigra pars reticulata, dorsal raphe nucleus and choroid plexus. The distribution of 5-hydroxytryptamine-1 receptors is compared to the distribution of both 5-hydroxytryptamine receptors and terminal fields of serotonergic projections as previously described in subprimates.

Pattern of convergence of the receptors of the barnacle's three ocelli onto second-order cells.

The giant barnacle, Balanus nubilus, has three simple eyes, two lateral and one median. We have studied the convergence of the receptors of these ocelli by recording from the second-order cell (I-cell) and from the receptors' terminals. The I-cell's responses to illumination of the median and lateral eyes are similar in shape, dynamic range, and reversal potential, but the response to lateral input has a longer latency, a slower rise time, and a smaller amplitude.

Adaptation in the input-output relation of the synapse made by the barnacle's photoreceptor.

A study was made of synaptic transmission between the four median photoreceptors of the giant barnacle (Balanus nubilus) and their post-synaptic cells (I-cells). Simultaneous intracellular recordings were made from the presynaptic terminal region of a photoreceptor and from the soma of an I-cell. The photoreceptor's membrane potential provided feed-back to bath electrodes that passed current into the receptors' axons, permitting the voltage to be controlled at the point of arborization of their presynaptic terminals.

Antiviral activity, antimetabolic activity, and cytotoxicity of 3'-substituted deoxypyrimidine nucleosides.

The antiviral activity, effect on cellular DNA and RNA synthesis, and cytotoxicity toward mammalian cells of 5-fluoro-2'-deoxyuridine, 5-methoxymethyl-2'-deoxyuridine, 2'-deoxythymidine, and their corresponding 3'-p-nitrophenylphosphate and 3'-p-aminophenylphosphate derivatives were determined. The 3'-p-aminophenylphosphate-2'-deoxy-5-methoxymethyluridine derivative was as potent as 5-methoxy-methyl-2'-deoxyuridine in inhibiting herpes simplex viruses; however, 3'-p-aminophenylphosphate-2'-deoxy-5-fluorouridine was less potent than 5-fluoro-2'-deoxyuridine in inhibiting viral replication. The results suggest that the deoxypyrimidine ribonucleoside kinase has bulk tolerance for substituents at the 3-position of the ribofuranose moiety.

Is gamma-aminobutyric acid the neurotransmitter of barnacle photoreceptors?

The hypothesis that gamma-aminobutyric acid (GABA) is the neurotransmitter of barnacle photoreceptors was tested by studying the effect of GABA on the membrane of the cell directly postsynaptic to the photoreceptor, by testing the ability of GABA antagonists to block transmission at this synapse, and by estimating the free GABA content of the photoreceptor. The results of these experiments suggest that GABA is not the photoreceptor's neurotransmitter.

Reed-Sternberg/lymphocyte rosette: lymphocyte subpopulations as defined by monoclonal antibodies.

The Reed-Sternberg cell/lymphocyte rosette characteristic of Hodgkin's disease tissue and cell suspensions was investigated with monoclonal antibodies on fresh viable cell suspensions prepared from nine cases of Hodgkin's disease. The biopsy material comprised six spleens and three lymph nodes. The majority of the rosetting lymphocytes were T cells, primarily of the helper subset.

Coupling between horizontal cells in the carp retina revealed by diffusion of Lucifer yellow.

Electrical coupling among 4 different types of horizontal cells in Cyprinus carpio was examined from the diffusion of the intracellularly injected Lucifer yellow. The type of horizontal cells was identified by a spectral response and by a distinct morphology when the retina was viewed in flat mounts under a fluorescence microscope. Lucifer yellow diffused from the injected cell into surrounding cells, and in all of these preparations, diffusion was limited to horizontal cells of the same morphological type.

Staining of human splenic sinusoids and demonstration of unusual banded structures by monoclonal antisera.

The monoclonal antiserum OKT8 is useful as a marker of splenic sinusoids. Banded and fibrillary structures are also delineated by this antiserum; these appear to be different from the ring fibres of the spleen and the tentative suggestion is made that these represent basal plates or endothelial striations. The reactivity of sinus lining cells with a number of antisera is noted and the conclusion is drawn that splenic sinal endothelium differs substantially from the endothelium of blood vessels.

The reactivity of Reed-Sternberg cells with monoclonal antisera at thin section and ultrastructural levels.

In an attempt to improve the morphology of Reed-Sternberg cells after immunochemical procedures, the biotin-avidin technique has been used. Satisfactory morphology was obtained at the level of both light and electron microscopy. Reed-Sternberg cells failed to react with a monoclonal antimonocyte serum but gave positive results with anti-1a and FMC7, a monoclonal anti-B cell serum.

Comparison of the antiviral effects of 5-methoxymethyldeoxyuridine-5'-monophosphate with adenine arabinoside-5'-monophosphate.

Methoxymethyldeoxyuridine-5'-monophosphate (MMUdR-MP) and arabinofuranosyladenine-5'-monophosphate (Ara-AMP) had significant antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in RK-13 and Vero cells. MMUdR-MP and Ara-AMP were more potent than methoxymethyldeoxyuridine (MMUdR) and arabinofuranosyladenine (Ara-A) against the MS strain of HSV-2. MMUdR-MP inhibited replication of HSV-1r (mutant resistant to MMUdR).

Restoration of functional continuity in dystrophic murine muscle after crushing.

The recovery of functional continuity after crush injury was measured by a simple electrophsiological technique in semitendinosus muscles of normal and dystrophic mice of the C57BL/6J(dy2Jdy2J) strain. In contrast to virtually complete restitution in normal muscles, only one-third of fibers regained continuity in dystrophic muscles. The study also confirmed the lower resting membrane potentials of dystrophic fibers and the presence of "functional" denervation in some of them.

Absence of fibrillation after muscle injury.

The possibility was examined that fibrillation potentials may occur in those parts of muscle fibers which become functionally denervated following segmental necrosis. Focal necrotic lesions were induced in rat semitendinosus muscles by crushing, ligating, or cutting muscle fibers. When the treated muscles were examined microscopically and recordings made with intracellular or extracellular electrodes, fibrillations were found to be either completely absent or extremely infrequent.

Zinc supplementation and its effect on taste acuity in children with chronic renal failure.

Diminished taste acuity (hypogeusia) and zinc deficiency have been reported in children on maintenance haemodialysis and with varying degrees of chronic renal failure. We have studied the effect of 6 weeks' zinc supplementation in 20 children with chronic renal impairment using a double-blind crossover trial. Although we achieved significant increases in serum zinc levels no significant improvement in taste acuity could be demonstrated.

2,4-diamino-5-benzylpyrimidines and analogues as antibacterial agents. 6. A one-step synthesis of new trimethoprim derivatives and activity analysis by molecular modeling.

A new route to 2,4-diamino-5-(4-hydroxybenzyl)pyrimidines has been developed that involves the condensation of 2,4-diamino-5-(hydroxymethyl)pyrimidine with phenols in acidic medium. The use of phenol and its 2,6-dialkyl derivatives produces 5-(4-hydroxybenzyl)pyrimidines exclusively. However, 2,6-dimethoxyphenol produces a mixture of 5-(3-hydroxy-2,4-dimethoxybenzyl)- and 5-(4-hydroxy-3,5-dimethoxybenzyl)pyrimidines.

Synaptic contacts between physiologically identified neurons in the visual system of the barnacle.

Neurons in the median visual system of the barnacle were injected with horseradish peroxidase (HRP) and their processes traced in serial thick (3 micrometers) and thin (100 nm) sections with light and electron microscopy. The anatomy confirms that the I-cells identified by Oertel and Stuart (Oertel, D., and A.

The lectin binding affinity of Reed-Sternberg cells.

Reed-Sternberg cells from ten cases of Hodgkin's disease were examined by the direct immunofluorescence technique, for their affinity for nine lectins. The surrounding lymphocytes and monocytes of HD tissue were also assessed for their ability to bind lectins. RS cells showed considerable heterogeneity of reaction.

Lateral visual pathway of giant barnacle.

1. We have studied the responses to light, conduction down the axons, and anatomical projections of the photoreceptors of the lateral eye in the giant barnacle, Balanus nubilus. By recording intracellularly from ganglion cells that respond to visual input, we have described convergence of the lateral and median visual pathways.

A new method of dosimetry-a study of comparative laser-induced tissue damage.

The use of lasers in medicine and surgery has increased slowly-its effectiveness based on trial-and-error clinical experience. Very little comprehensive data has been published that scientifically presents dosage, energy, absorption, and comparisons between types of lasers. Our laboratory has developed a method for taking the guesswork out of laser dosage using scientific data to optimize therapy and give reproducible responses.

The reaction of xenogeneic and monoclonal antisera with Reed-Sternberg cells.

Xenogeneic antisera have been prepared against human monocytes, B lymphocytes and T lymphocytes. The reactivity of these antisera against a variety of normal and neoplastic cells is described. Reed-Sternberg cells from three cases of Hodgkin's disease failed to react with xenogeneic anti-T and anti-monocyte sera, but reacted with an anti-B serum.