A neural interface for a cortical vision prosthesis. (73/4345)

The development of a cortically based vision prosthesis has been hampered by a lack of basic experiments on phosphene psychophysics. This basic research has been hampered by the lack of a means to safely stimulate large numbers of cortical neurons. Recently, a number of laboratories have developed arrays of silicon microelectrodes that could enable such basic studies on phosphene psychophysics. This paper describes one such array, the Utah electrode array, and summarizes neurosurgical, physiological and histological experiments that suggest that such an array could be implanted safely in visual cortex. We also summarize a series of chronic behavioral experiments that show that modest levels of electrical currents passed into cortex via this array can evoke sensory percepts. Pending the successful outcome of biocompatibility studies using such arrays, high count arrays of penetrating microelectrodes similar to this design could provide a useful tool for studies of the psychophysics of phosphene perception in human volunteers. Such studies could provide a proof-of-concept for cortically based artificial vision.  (+info)

[18F]-labeled 3-deoxy-3-fluoro-D-glucose: synthesis and preliminary biodistribution data. (74/4345)

A cyclotron target system for the production of anhydrous [18F] fluoride ion has been developed and used for the synthesis of carrier-free [18F]-3-deoxy-3fluoro-D-glucose (3-FDG). The synthesis is sufficiently rapid and efficient to allow production of usable amounts of 3-FDG with a 6-MeV cyclotron. Preliminary animal studies show that 3-FDG is in fact a glucose analog.  (+info)

Characterization of a variant of human adenovirus type 2 which multiples efficiently in simian cells. (75/4345)

In a previous report (Klessig, J. Virol. 21:1243--1246, 1977), the isolation of a variant (H2hr400) of adenovirus serotype 2 (Ad2) that overcomes the block to multiplication of wild-type Ad2 in simian cells was described. H2hr400 replicates efficiently on both human and simian cells, resulting in virus yields that are comparable to those found when wild-type Ad2 infects permissive, human cells. An extensive comparison of the genome of H2hr400 with that of its parent by restriction endonuclease, electron microscopic, and hybridization analyses failed to detect any differences and excludes the possibility that simian virus 40 sequences, which in certain Ad2-simian virus 40 hybrid viruses (e.g., Ad2+ND1) allow adenovirus to multiply efficiently in simian cells, are present in H2hr400. In contrast to Ad2, H2hr400 can fully express its late genes in both simian and human cells. The mutation has been mapped by a modified marker rescue technique to the segment of the viral genome located between coordinates 59 and 80.  (+info)

Supplement to the Carcinogenic Potency Database (CPDB): results of animal bioassays published in the general literature in 1993 to 1994 and by the National Toxicology Program in 1995 to 1996. (76/4345)

The Carcinogenic Potency Database (CPDB) is a systematic and unifying analysis of results of chronic, long-term cancer tests. This paper presents a supplemental plot of the CPDB, including 513 experiments on 157 test compounds published in the general literature in 1993 and 1994 and in Technical Reports of the National Toxicology Program in 1995 and 1996. The plot standardizes the experimental results (whether positive or negative for carcinogenicity), including qualitative data on strain, sex, route of compound administration, target organ, histopathology, and author's opinion and reference to the published paper, as well as quantitative data on carcinogenic potency, statistical significance, tumor incidence, dose-response curve shape, length of experiment, duration of dosing, and dose rate. A numerical description of carcinogenic potency, the TD(subscript)50(/subscript), is estimated for each set of tumor incidence data reported. When added to the data published earlier, the CPDB now includes results of 5,620 experiments on 1,372 chemicals that have been reported in 1,250 published papers and 414 National Cancer Institute/National Toxicology Program Technical Reports. The plot presented here includes detailed analyses of 25 chemicals tested in monkeys for up to 32 years by the National Cancer Institute. Half the rodent carcinogens that were tested in monkeys were not carcinogenic, despite usually strong evidence of carcinogenicity in rodents and/or humans. Our analysis of possible explanatory factors indicates that this result is due in part to the fact that the monkey studies lacked power to detect an effect compared to standard rodent bioassays. Factors that contributed to the lack of power are the small number of animals on test; a stop-exposure protocol for model rodent carcinogens; in a few cases, toxic doses that resulted in stoppage of dosing or termination of the experiment; and in a few cases, low doses administered to monkeys or early termination of the experiment even though the doses were not toxic. Among chemicals carcinogenic in both monkeys and rodents, there is some support for target site concordance, but it is primarily restricted to liver tumors. Potency values are highly correlated between rodents and monkeys. The plot in this paper can be used in conjunction with the earlier results published in the CRC Handbook of Carcinogenic Potency and Genotoxicity Databases [Gold LS, Zeiger E, eds. Boca Raton FL:CRC Press, 1997] and with our web site (http://potency.berkeley.edu), which includes a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency (TD50), and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Two summary tables permit easy access to the literature of animal cancer tests by target organ and by chemical. For readers using the CPDB extensively, a combined plot on diskette or other format is available from the first author. It includes all results published earlier and in this paper, ordered alphabetically by chemical. A SAS database is also available.  (+info)

Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs. (77/4345)

This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from (italic)in vivo(/italic) models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included.  (+info)

Parenteral administration of progestin Nestorone to lactating cynomolgus monkeys: an ideal hormonal contraceptive at lactation? (78/4345)

Nestorone (NES) progestin is highly effective for contraception following parenteral administration, but ineffective after oral ingestion due to rapid first-pass metabolism. Thus, NES might be ideal for lactational contraception; possible NES in milk should be metabolized by the nursing infant. We evaluated the distribution of NES, its endocrine effects and infant weight gain in five cynomolgus monkeys and their nursing infants. Nestorone implants, releasing approximately 40 microg NES/day in vitro, were placed s.c. in the mothers 3-4 months following delivery, where they remained in situ for 4 weeks. Sampling (blood daily from the mother; milk and blood from the infant at 3 day intervals) was initiated at 2 weeks prior to insertion, and continued for 2 weeks following removal of the implant. NES, oestradiol, progesterone and prolactin were measured by radioimmunoassays and the infants were weighed weekly. The (mean +/- SD) maternal serum and milk concentrations of NES were 337 +/- 90 and 586 +/- 301 pmol/l during the use of the implants. The ratio of milk/serum NES was 1.68 +/- 0.12 (mean +/- SE), and the serum and milk concentrations were significantly correlated (r = 0. 75, P < 0.001). NES was not detectable (<13 pmol/l) in any infant serum samples. Concentrations of prolactin (mean +/- SD) were 41.1 +/- 32, 26.7 +/- 7.6 and 26.3 +/- 9.5 ng/ml before, during and after the use of the implants respectively. The (mean +/- SE) infant weight increased from 643 +/- 54 g 1 week prior to insertion to 713 +/- 54 g 1 week following removal. These data confirm that NES in milk is rapidly metabolized by the suckling infant. Therefore, NES appears to be an ideal hormonal contraceptive for use during lactation.  (+info)

theta, a novel gamma-aminobutyric acid type A receptor subunit. (79/4345)

gamma-Aminobutyric acid type A (GABA-A) receptors are a major mediator of inhibitory neurotransmission in the mammalian central nervous system, and the site of action of a number of clinically important drugs. These receptors exist as a family of subtypes with distinct temporal and spatial patterns of expression and distinct properties that presumably underlie a precise role for each subtype. The newest member of this gene family is the theta subunit. The deduced polypeptide sequence is 627 amino acids long and has highest sequence identity (50.5%) with the beta1 subunit. Within the rat striatum, this subunit coassembles with alpha2, beta1, and gamma1, suggesting that gamma-aminobutyric acid type A receptors consisting of arrangements other than alpha beta + gamma, delta, or epsilon do exist. Expression of alpha2beta1gamma1theta in transfected mammalian cells leads to the formation of receptors with a 4-fold decrease in the affinity for gamma-aminobutyric acid compared with alpha2beta1gamma1. This subunit has a unique distribution, with studies so far suggesting significant expression within monoaminergic neurons of both human and monkey brain.  (+info)

Electrophysiological studies of human face perception. II: Response properties of face-specific potentials generated in occipitotemporal cortex. (80/4345)

In the previous paper the locations and basic response properties of N200 and other face-specific event-related potentials (ERPs) were described. In this paper responsiveness of N200 and related ERPs to the perceptual features of faces and other images was assessed. N200 amplitude did not vary substantially, whether evoked by colored or grayscale faces; normal, blurred or line-drawing faces; or by faces of different sizes. Human hands evoked small N200s at face-specific sites, but evoked hand-specific ERPs at other sites. Cat and dog faces evoked N200s that were 73% as large as to human faces. Hemifield stimulation demonstrated that the right hemisphere is better at processing information about upright faces and transferring it to the left hemisphere, whereas the left hemisphere is better at processing information about inverted faces and transferring it to the right hemisphere. N200 amplitude was largest to full faces and decreased progressively to eyes, face contours, lips and noses viewed in isolation. A region just lateral to face-specific N200 sites was more responsive to internal face parts than to faces, and some sites in ventral occipitotemporal cortex were face-part-specific. Faces with eyes averted or closed evoked larger N200s than those evoked by faces with eyes forward. N200 amplitude and latency were affected by the joint effects of eye and head position in the right but not in the left hemisphere. Full and three-quarter views of faces evoked larger N200s than did profile views. The results are discussed in relation to behavioral studies in humans and single-cell recordings in monkeys.  (+info)