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Biomedical subjects

J Shoemaker

Publications and source records attributed to J Shoemaker.

11 recordsLinked to original sources

Effects of pergolide on sensorimotor gating of the startle reflex in rats.

RATIONALE: Prepulse inhibition (PPI), a cross-species measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders, including schizophrenia. This study was designed to assess the effects of the D2-family agonist pergolide in rats, in anticipation of human studies of the dopaminergic regulation of PPI. METHODS: The effects of pergolide (0.0001-0.5 mg/kg) on PPI of the acoustic startle reflex were studied in rats using a wide range of prepulse intensities [1-15 dB(A) over background] and prepulse intervals (5-100 ms, onset to onset). Studies also examined the effects of the D2 antagonist haloperidol on pergolide-induced changes in PPI. RESULTS: Pergolide exhibited dose- and stimulus-dependent effects on PPI. Pergolide increased PPI when startle stimuli were preceded by weak prepulses [1-5 dB(A) over background] at the longest prepulse interval (100 ms), or intense prepulses [15 dB(A) over background] at short prepulse intervals (5-20 ms). Pergolide (0.5 mg/kg) also decreased PPI elicited by intense prepulses at long intervals (60-100 ms). Both PPI-enhancing and PPI-disruptive effects of pergolide were reversed by the D2 antagonist haloperidol. CONCLUSIONS: These effects of pergolide suggest that D2 substrates mediate opposing influences on PPI under different stimulus conditions. The dopaminergic regulation of sensorimotor gating appears to interact with stimulus characteristics such as relative intensity and temporal separation, allowing for dynamic shifts in both the quantity and quality of "gated" information.

Animals↗

Frequency of sustained glaucomatous-type visual field loss and associated optic nerve cupping in Beaver Dam, Wisconsin.

PURPOSE: To determine the prevalence of persisting glaucomatous-type visual field loss in a Midwestern American adult population, in association with four grades of disc cupping. METHODS: On two separate occasions (1988-1990 and 1993-1995) 2955 predominantly Caucasian adults aged 43-84 provided medical history, underwent applanation tonometry, slit-lamp examination, quantitative suprathreshold perimetry and stereoscopic disc analysis as part of the National Institutes of Health-sponsored Beaver Dam Eye Study. Those demonstrating evidence of glaucomatous-type visual field loss at both visits were the subject of the present analysis. Among these individuals, associations were determined for four categories of optic disc cupping (vertical cup/disc < 0.5, > 0.5, > 0.6, > 0.8), intraocular pressure, blood pressure, cardiovascular pathology and prior glaucoma diagnosis. RESULTS: Of the 2955 subjects assessed, 120 (4%; 57 women, 63 men) demonstrated glaucomatous-type visual field defects at each visit. Fifty-five of these 120 (2% of the tested population) also exhibited some degree of disc cupping in a related eye at both visits. Among these 2%, positive associations relating the extent of field loss, cupping and intraocular pressure were confirmed, but the majority in each cupping category had normal eye pressures. Only seven of the 120 were aware of the presence or suspicion of eye disease prior to the screening. CONCLUSIONS: A majority of those found to have visual field loss and optic nerve cupping persisting together in the same eye after 3-5 years had normal pressures in each eye at both visits. Despite good access to medical care, very few who demonstrated persisting cupping and field loss (even among those with elevated eye pressure) were aware of their ocular condition through prior contact with an eye care professional.

Aged↗

Preventing the misuse of microorganisms: the role of the American Society for Microbiology in protecting against biological weapons.

The American Society for Microbiology's (ASM) involvement with issues surrounding biological weapons began during World War II and continues to the present time. The Public and Scientific Affairs Board (PSAB) of the ASM has played an important role in monitoring and responding to legislative and regulatory issues involving biological weapons. As this review makes apparent, there is no consensus of opinion among scientists on their role in biological defense research, or is it likely that there will ever be complete agreement. There is consensus that steps should be taken to prevent biological warfare and that openness of scientific research and global surveillance of disease outbreaks can significantly increase transparency for detecting development of biological weapons. The ASM recommends increased attention to and efforts directed toward global surveillance of disease outbreaks, not only to aid public health organizations in improving human health, but also to establish baseline data against which unusual disease outbreaks can be assessed. Issues of how best to increase global security and to achieve a scientifically based verification protocol of the Biological Weapons Convention are important and continue to be addressed by the ASM.

Biological Warfare↗

A Bayesian characterization of Hardy-Weinberg disequilibrium.

A Bayesian method for determining if there are large departures from independence between pairs of alleles at a locus, Hardy-Weinberg equilibrium (HWE), is presented. We endorse the view that a population will never be exactly in HWE and that there will be occasions when there is a need for an alternative to the usual hypothesis-testing setting. Bayesian methods provide such an alternative, and our approach differs from previous Bayesian treatments in using the disequilibrium and inbreeding coefficient parameterizations. These are easily interpretable but may be less mathematically tractable than other parameterizations. We examined the posterior distributions of our parameters for evidence that departures from HWE were large. For either parameterization, when a conjugate prior was used, the prior probability for small departures was itself small, i.e., the prior was weighted against small departures from independence. We could avoid this uneven weighting by using a step prior which gave equal weighting to both small and large departures from HWE. In most cases, the Bayesian methodology makes it clear that there are not enough data to draw a conclusion.

Alleles↗

Dynamic testing of hypothalamic-pituitary function in abnormalities of ovulation.

A review of 26 unusual patients indicates that a combined luteinizing hormone-releasing hormone (LRH)-clomiphene test in conjunction with an estrogen provocation test not only was helpful in identifying underlying pathophysiology of anovulation but also proved useful in the clinical management of the patients. Dynamic testing per se does not establish a diagnosis but, in conjunction with history and other laboratory findings, it does make possible further subdivisions of groups of patients who otherwise appear similar, both clinically and from routine laboratory evaluations. It, therefore, tends to pinpoint a lesion and establish the area in which further tests should be made. It is concluded that the value of such investigations will be more evident as gynecologic endocrinology moves into investigation of the supratentorial control of hypothalamic function and as hypothalamic LRH becomes available as a therapeutic agent.

Amenorrhea↗

Sensitivity to the dopaminergic regulation of prepulse inhibition in rats: evidence for genetic, but not environmental determinants.

Prepulse inhibition (PPI), a measure of sensorimotor gating, is reduced in schizophrenia patients and in rats treated with dopamine (DA) agonists. Reported strain and supplier-based differences in sensitivity to PPI-disruptive effects of DA agonists presumably reflect the differential impact of genetics and/or environment on DAergic substrates regulating PPI. In 2000, Harlan Laboratories established a Texas Sprague-Dawley line (SDHt; facility 211) using breeders from Indianapolis (SDHi; facility 202A). SDHi rats had been used, approximately 11 years earlier, to establish a colony in San Diego (SDHsd; facility 235). SDHt and SDHi rats are thus genetically similar, but raised in distinct environments; approximately 11 years of genetic "drift" separates SDHsd rats from both SDHi and SDHt rats. Harlan Long-Evans hooded rats (LEH; Madison, WI; facility 207) are genetically distinct from albino SDH. All except SDHsd rats were shipped to our facility by air freight. We used SDHt, SDHi, SDHsd, and LEH rats to assess genetic and environmental contributions to the DAergic regulation of PPI. Acoustic startle/PPI were assessed in rats treated with the D1/D2 agonist apomorphine (APO), the D2 agonist quinpirole, or the D1 agonist SKF 82958. The relative sensitivities to the PPI-disruptive effects were: APO: SDHt=SDHsd=SDHi>>LEH; SKF 82958: SDHt=SDHsd=SDHi (LEH not sensitive); quinpirole: SDHt=SDHsd=SDHi; SDHi>LEH. Strain/supplier differences in sensitivity to drug effects on startle magnitude did not correspond to patterns of PPI sensitivity. In these rats, strain differences in the DAergic regulation of PPI are most easily explained by genetic, rather than environmental influences that differentially impact both D1 and D2 substrates. This finding is consistent with published reports in other strains. Pharmacogenetic studies of PPI in rats may identify a genetic basis for a model of deficient sensorimotor gating in schizophrenia.

Animals↗

Prospective comparison of the Heine retinometer with the Mentor Guyton-Minkowski potential acuity meter for the assessment of potential visual acuity before cataract surgery.

Various techniques and devices have been developed to aid in the assessment of potential visual acuity prior to cataract surgery. We report a prospective comparison of two such assessments, one made using a new instrument, the hand-held Heine retinometer (HR) (Heine Instruments, Germany), and the other using the Mentor Guyton-Minkowski potential acuity meter (PAM) (Mentor, Inc, Norwell, Mass). A total of 37 eyes were assessed using both instruments just before cataract surgery. Three eyes were excluded from analysis due to postoperative complications affecting visual acuity that could not have been predicted with either instrument. The false-negative rate was 44% for the PAM and 32% for the HR. There were no false-positive results with either instrument. Neither instrument was particularly accurate in predicting actual final visual acuity (r2 = 0.290 and 0.144 for the PAM and HR, respectively). The HR was deemed easier to use.

Cataract↗