PubMed Health⌕ Search

Biomedical subjects

W Holt

Publications and source records attributed to W Holt.

At least 19 recordsLinked to original sources
PubMed2000

The hippocampus and contextual memory retrieval in Pavlovian conditioning.

Several theories of hippocampal function have suggested a role for the hippocampus in contextual memory retrieval. However, these theories are based on studies using permanent pretraining lesions, which confound the role of the hippocampus in learning with its role in retrieval. We argue that an alternative methodology is required to assess the role of the hippocampus in memory retrieval processes. This alternative methodology involves temporary inactivation of the hippocampus in Pavlovian paradigms that lend themselves to an examination of retrieval. An example of this approach is considered in a Pavlovian fear-conditioning paradigm. We examined the influence of hippocampal inactivation on the context-specific expression of latent inhibition, a response decrement displayed when excitatory conditioning is preceded by non-reinforced presentations of a to-be-conditioned stimulus. Reversible inactivation of the dorsal hippocampus prior to retrieval testing eliminated the context-specific expression of latent inhibition. The nature of the hippocampal role in retrieval processes is discussed in the light of these data.

Animals↗
PubMed2000

A role for amygdaloid PKA and PKC in the acquisition of long-term conditional fear memories in rats.

Although there is great interest in the cellular mechanisms underlying Pavlovian conditioning, few studies have directly examined the contribution of intracellular signaling pathways in the amygdala to the acquisition and expression of conditional fear memories. In the present study, we examined this issue by infusing 1-(5'-isoquinolinesulfonyl)-2-methylpiperazine (H7), a potent inhibitor of both protein kinase C (PKC) and cAMP-dependent protein kinase (PKA), directly into the amygdala prior to fear conditioning or retention testing. We found that infusion of H7 prior to training attenuated long-term conditional fear in a dose-dependent manner (Experiment 1), but short-term fear memories were spared. The contribution of protein kinases to conditional fear was region-specific within the amygdala: infusion of H7 into the basolateral amygdala (BLA) but not the central nucleus of the amygdala (CEA) resulted in attenuated freezing (Experiment 2). Moreover, the deficits in fear conditioning produced by PKA/PKC inhibition were not modality-specific, insofar as intra-BLA H7 reduced both contextual and auditory fear. The effects of H7 on conditional freezing were not attributable to either state-dependency or performance deficits (Experiment 3). Together, these experiments suggest that amygdaloid PKA and PKC play an important role in the acquisition of fear memories.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Muscimol inactivation of the dorsal hippocampus impairs contextual retrieval of fear memory.

Some models of hippocampal function have suggested a role of the hippocampus in contextual memory retrieval. We have examined this hypothesis by assessing the impact of reversible inactivation of the dorsal hippocampus (DH) on the context-specific expression of latent inhibition, a decrement in conditional responding produced by preexposure to a to-be-conditional stimulus. In Experiment 1, rats received tone preexposure either in the context that would later be used for extinction testing (context A) or in a different context (context C); a third group of rats did not receive tone preexposure. All rats then received fear conditioning, which consisted of tone-footshock pairings, in a third distinct context (context B). The following day conditional fear to the tone was assessed in one of the preexposure contexts (context A) by measuring freezing during a tone extinction test. Rats preexposed and tested in the same context exhibited less freezing to the tone than either rats preexposed and tested in different contexts or non-preexposed rats. These results indicate that the expression of latent inhibition is context specific. In Experiment 2, DH inactivation eliminated the context-specific expression of latent inhibition. Compared with saline-infused rats, rats infused with muscimol into the DH exhibited low levels of tone freezing independent of whether they had received tone preexposure in the test context or in a different context. Experiment 3 revealed normal contextual discrimination in rats after DH inactivation. These results suggest the DH is required for contextual memory retrieval in a latent inhibition paradigm.

Animals↗
PubMed1999

Impairment of cingulothalamic learning-related neuronal coding in rabbits exposed to cocaine in utero: general and sex-specific effects.

Neuronal activity was recorded in the cingulate cortex and the limbic thalamus in Dutch-belted rabbits (Oryctolagus cuniculus) exposed to cocaine (8 mg/kg/day i.v.) or saline in utero during acquisition and reversal learning of a discriminative avoidance response. Anterior cingulate cortical excitatory training-induced activity (TIA) was attenuated in cocaine-exposed female rabbits during acquisition and reversal learning, but only during reversal learning in male rabbits. Posterior cingulate cortical excitatory TIA was lessened in cocaine-exposed rabbits during acquisition, whereas discrimination between the positive and negative cues was enhanced. Neuronal firing was attenuated in the anterior ventral thalamus in cocaine-exposed rabbits during acquisition and reversal learning. Behavioral learning was normal in cocaine-exposed rabbits. Other data suggest that rabbits exposed to cocaine in utero exhibit a learning deficit when trained with nonsalient cues.

Animals↗
PubMed1998

Artificial insemination in Callithrix jacchus using fresh or cryopreserved sperm.

Assisted reproductive techniques are needed urgently to facilitate the captive breeding of many New World primate species which are endangered in the wild and to assist the effective genetic management of small colonies. A protocol was devised for artificial insemination in the common marmoset, Callithrix jacchus, using ejaculated sperm obtained by vaginal washing after copulation. A double insemination protocol was employed, with the first insemination taking place the day before ovulation was expected to occur and the second 48 h later. All six females inseminated with fresh ejaculated sperm became pregnant, delivering a total of 16 offspring at term. The gestation lengths and litter sizes were not statistically different from those observed in pregnancies following natural mating. The insemination protocol was adapted for use with cryopreserved ejaculated sperm by including an additional insemination on the day of expected ovulation, to take into account differences in the capacitation time of frozen-thawed sperm compared to fresh sperm. Three out of six females inseminated according to this triple insemination schedule, conceived, although one female subsequently resorbed twin foetuses approximately 100 days later. The remaining two pregnant females delivered four babies at term, one singleton and one set of triplets. In the final group, six females were inseminated with low doses of cryopreserved epididymal sperm using the same triple insemination protocol used for frozen-thawed ejaculated sperm. One female conceived, delivering triplets.

Animals↗
PubMed1996

Effect of resistance training on strength, postural control, and gait velocity among older adults.

The purpose of this study was to examine the effects of a 14-week resistance training program on the ankle strength, training intensity, postural control, and gait velocity of older adults. Forty-two older adults (mean age = 72), 21 in the resistance and control groups, completed the 14-week project. The resistance training group participated in 14 weeks of resistance training three times per week using elastic bands (Theraband) for resistance. Isokinetic ankle strength, training intensity, postural stability, and gait velocity were measured prior to and following the 14-week intervention. Following the training, the resistance group exhibited improved ankle dorsiflexion, training resistances, and gait velocity, but showed no change in plantar flexion or postural control. The control group also exhibited improvements in dorsiflexion, but these gains were approximately one-half of the gains observed in the resistance training group. Finally, when adjusted for baseline differences, subjects in the resistance training group demonstrated no changes in the dependent measures over the control group.

Age Factors↗
PubMed1994

Reproducibility of computer-aided semen analysis: comparison of five different systems used in a practical workshop.

STUDY OBJECTIVES: To assess a single (donor) sample by the use of five computer-assisted semen analysis (CASA) systems. SETTING: British Andrology Society advanced course on computer-assisted semen analysis techniques, September 1992. PARTICIPANTS: Clinical, technical and scientific personnel with mixed experience of CASA techniques, but all interested in semen assessment technology. RESULTS: 22 sets of data, comprising 6 commonly derived parameters, from the same sample were obtained using five CASA systems. The coefficients of variation for sperm concentration (29%) and proportion motile (24%) were comparable to those previously reported for manual assessments. For all parameters, "within system" variability was considerably greater than "between system," indicating that differences in sample handling and operator expertise were more significant sources of variation than the CASA systems themselves. CONCLUSIONS: Emphasis on operator training and standardization of sample handling techniques would enhance the reproducibility of CASA measurements more than improvements in the CASA systems themselves. There was evidence, however, that the CASA measurements were more consistent than equivalent manual measures, and also provide information about the quality of sperm motility which cannot be obtained by alternative techniques.

Education, Medical, Continuing↗
PubMed1993

The effect of a 12-week dynamic resistance strength training program on gait velocity and balance of older adults.

This study tested whether a 12-week dynamic resistance strength training program can change gait velocity and improve measures of balance among adults age 65 and older. Fifty-five community-dwelling adults (mean age = 71.1) were randomized into an exercise (n = 25) or control (n = 30) group. The exercisers were requested to complete three bouts of strength training per week for 12 weeks using elastic tubing. At posttest the exercisers demonstrated slower gait velocity, enhanced balance, and an improved ability to walk backward, although none of these posttest measures was significantly different from the control group.

Age Factors↗
PubMed1991

Mechanism for depressed cardiac function in left ventricular volume overload.

To assess the effects of left ventricular chamber volume on the mechanism of changes in left ventricular developed pressure we performed phosphorous-31 nuclear magnetic resonance spectroscopy, hydrogen-1 nuclear magnetic resonance spectroscopy with a shift reagent, two-dimensional echocardiography, atomic absorption spectrophotometry, microsphere analysis, and surface fluorometry on isovolumic isolated perfused rat hearts with incremental intraventricular balloon volumes, while left ventricular pressure was concurrently monitored. A three-phasic response of developed pressure was noted: 0 to 100 microliters balloon volumes resulted in an increase in developed pressure, whereas developed pressure remained constant at 250 microliters and fell at 400 microliters. Oxygen consumption and [Ca2+]i transients followed the same pattern as developed pressure and coronary flow. Intraventricular volumes of 250 microliters or greater (a volume overload) caused endocardial ischemia, a greater decrease in extracellular versus intracellular water, thinning of the left ventricular free wall, and an increase in chamber size. Mechanical pressure on the tissue, induced by the volume overload, caused ischemia as further evidenced by (1) a negative effect on developed pressure, (2) a decrease in [Ca2+]i transients, (3) a [Ca2+]i overload, (4) a moderate decrease in the phosphorylation potential, and (5) an increase in the oxidation-reduction state (nicotinamide-adenine dinucleotide). The high intracellular calcium associated with volume overload may have been due to both compression and ischemia, which leads to an increased number of cross-bridges in rigor, a high end-diastolic pressure, and an increase in wall stress.

Animals↗
PubMed1990

Subcellular distribution of copper in the liver of fetal deer in the last month of gestation.

Fetal deer, in the last month of gestation, accumulate high concentrations of copper in the liver. Livers from fetal deer in late gestation were homogenised and fractionated by continuous sucrose density gradient centrifugation. The distribution of copper closely followed that of DNA; approximately two thirds of the metal was localised to the nuclear fractions with the remaining third in the cytosolic fractions. The fractionation procedure was repeated with digitonin, a lysosomal perturbant: lysosomes were disrupted and the marker enzyme, N-acetyl-beta-glucosaminidase, shifted from the particulate fractions to the cytosolic fractions; the distribution of copper was unaffected. Differential centrifugation of homogenate confirmed that approximately two thirds of the copper was associated with the nuclear fraction. Further confirmation of a nuclear localisation of copper was provided by X-ray microanalysis of purified nuclei.

Animals↗
PubMed1988

Functional evaluation of the heart with magnetic resonance imaging.

This review examines the capability of cine MRI for evaluation of cardiovascular function and shows early results in valvular, ischemic, and congenital heart disease. MR assessment of left and right ventricular volumes is independent of geometrical models; dimensional values have been defined for normal individuals. Noninvasive measurement of peak and end systolic pressure along with cine MR imaging can be used to calculate left ventricular meridional wall stress which can be used for monitoring of myocardial diseases and evaluation of therapeutic intervention. Cine MR may be more accurate than angiography for identifying regional LV dysfunction since it can measure wall thickening as well as inward wall motion. Regurgitant jets due to valvular lesions are readily seen and their characteristics may be used to define the severity of aortic or mitral regurgitation. Calculation of the regurgitant volume separates patients with mild, moderate, or severe disease. Likewise, the shunt flow across ventricular and atrial septal defects has been visualized in cine MR images and shunt flow calculated. Cine MRI serves as a three-dimensional imaging technique with high temporal resolution. It extends the capability of MRI in cardiac disease beyond the depiction of anatomy and renders a comprehensive cardiac imaging technique for quantitation of cardiac anatomy and function.

Aortic Valve Stenosis↗
PubMed1988

Mechanics and energetics of overstretch: the relationship of altered left ventricular volume to the Frank-Starling mechanism and phosphorylation potential.

Isovolumic perfused rat hearts containing an intraventricular balloon were used to assess the effects of incremental balloon volumes on developed pressure, oxygen consumption, coronary flow, phosphorylation potential obtained by P-31 nuclear magnetic resonance, wall thickness obtained by two-dimensional echocardiography, and diastolic wall stress. Three phases in developed pressure were noted: (1) volumes from 0 to 150 microliter resulted in a continuous increase in developed pressure; (2) with volumes from 150 to 250 microliter, developed pressure remained constant whereas developed (systolic) and diastolic wall stress rose sharply; and (3) with volumes from 250 to 400 microliter, developed pressure fell whereas developed (systolic) and diastolic wall stress continued to rise. The ln [(PCr)/(Pi)] was in synchrony with oxygen consumption at 0 and 50 microliter balloon volumes, and then diverged at volumes greater than 100 microliter. Oxygen consumption increased from 0 to 50 microliter, was constant from 50 to 250 microliter balloon volume, and then declined. The ln [(PCr)/(Pi)] fell precipitously at balloon volumes greater than 100 microliter, most likely limited by oxygen consumption. Coronary flow did not change significantly until 250 microliter or more of water was added to the balloon, and then it started to decline. Volumes greater than 100 microliter result in overstretch of myofibers, as observed by the precipitous decline in ln [(PCr)/(Pi)], and the steep increase in diastolic wall stress. With excessive volume loading, the drop in phosphorylation potential, ln [(PCr)/(Pi)], appears to contribute to the decrease in developed pressure.

Adenosine Triphosphate↗
PubMed1987

Cine MR imaging: potential for the evaluation of cardiovascular function.

MR imaging is valuable in defining cardiac anatomy in a variety of cardiac abnormalities. However, evaluation of cardiac function by this technique has been limited by long imaging times and low temporal resolution. New, recently described pulse sequences shorten imaging time considerably and improve temporal resolution. This paper reports our early experience with cine MR imaging of the heart, a technique of gradient-recalled acquisition in the steady state (GRASS) that uses low flip angles and gradient-recalled echoes. Images were obtained in 36 subjects (14 normal volunteers and 22 patients with coronary artery or valvular heart disease) and displayed in a cinegraphic mode for assessment of cardiac function. The acquisition of 10 to 12 levels, covering the whole heart with up to 24 time frames per level, required a maximum imaging time of only 30 min. Because systole and diastole were readily identified, and the contrast between blood and surrounding structures was excellent, systolic wall thickening, wall motion, and motion of the cardiac valves were visualized easily. Regions of myocardial infarcts were clearly visible and characterized by lack of systolic wall thickening and/or diastolic wall thinning. Turbulence caused signal loss within the flowing blood, which usually had higher signal intensity than myocardium. Therefore, turbulent blood flow in valvular regurgitation and in valvular and subvalvular stenosis could be detected. Cine MR imaging is a promising new technique for the evaluation of myocardial and valvular function.

Adult↗
PubMed1987

Ventricular septal defect: visualization of shunt flow and determination of shunt size by cine MR imaging.

Cine MR imaging is a new, fast technique that employs low flip angles, short repetition and echo times, and gradient-refocused echoes. This technique was used in three patients with documented ventricular septal defects (VSDs) to obtain transverse and oblique sections of the heart spanning the cardiac cycle. In all patients, cine MR imaging showed high-velocity turbulent blood flow across the defect as areas of low signal intensity extending from the left ventricle to the right ventricle. In the oblique sections oriented parallel to the interventricular septum it was possible to identify the cross-sectional area of the VSD. Quantification of the left-to-right shunt was performed by comparing left and right ventricular stroke volumes determined from end-diastolic and end-systolic volumes of both ventricles. Cine MR imaging provides important functional information and anatomic detail in patients with VSD and may be useful for diagnosis, determination of severity, and noninvasive monitoring of the disease.

Coronary Circulation↗