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Biomedical subjects

H C Hughes

Publications and source records attributed to H C Hughes.

At least 19 recordsLinked to original sources

Bidirectional control of saccadic eye movements by the disconnected cerebral hemispheres.

The present investigation demonstrates that callosotomy patient J.W. can generate either leftward or rightward saccades in response to color cues presented unilaterally. When asked to name the colors, performance was at chance for left visual field presentations, demonstrating a disability in interhemispheric transfer of chromatic information. The successful control of saccadic direction based on discriminative color cues that appear confined to a single hemisphere may suggest a capacity for bidirectional control of saccadic eye movements in the disconnected cerebral hemispheres.

Brain

The perceived duration of gratings.

Since visible persistence of grating patterns increases with spatial frequency, it is often inferred that the perceived duration of a grating is also longer at higher spatial frequencies. However, other work has demonstrated that the perceived onset of a grating is also delayed at higher spatial frequencies. Thus it is impossible to infer the subjective duration from the results of visible persistence studies alone. In order to estimate perceived duration in the present study, reaction times (RTs) to grating onsets and offsets were measured for a range of spatial frequencies. The results indicate that although the perceived duration (ie the difference between offset and onset RTs) was consistently longer than the physical duration, the estimates of perceived duration did not vary with changes in spatial frequency. Differences between the present results and earlier findings are interpreted in the context of the different methods used to measure perceived offset.

Attention

Fixation-point offsets reduce the latency of saccades to acoustic targets.

If an observer's fixation point is extinguished just prior to the onset of a peripheral target, the latency to saccade to that target is reduced. We show that this "gap effect" is not specific to visual targets. Observers made saccades to a light flash or to a white-noise burst. A warning tone was presented on every trial to control for the possible warning effect of the fixation-point offset. For both target modalities, saccade latencies were significantly reduced when the fixation point was extinguished 200 msec prior to the target onset. Implications of this outcome for interpretations of the gap effect are considered. It is argued that the presence of a gap effect for tones, in conjunction with previous findings, is consistent with the hypothesis that the gap effect is produced by a facilitation of premotor processes in the superior colliculus.

Attention

Comparison of antibody response by use of synthetic adjuvant system and Freund complete adjuvant in rabbits.

Two commercially available synthetic adjuvant systems, trehalose dimycolate (TDM) and TDM + monophosphoryl lipid A (MPL), were compared with Freund complete adjuvant (FCA) for the ability to stimulate antibody production in New Zealand White rabbits (Oryctolagus cuniculus). In addition, each animal was evaluated for adverse reactions. The antigen, rat liver microsomal epoxide hydrolase, was administered SC emulsified with FCA, TDM, or TDM + MPL. Serum antibody titers were stimulated with all 3 adjuvant-antigen combinations. The highest titer was produced by use of FCA; TDM + MPL produced an intermediate response, and TDM produced the lowest titer. All of the rabbits immunized with FCA developed sterile subcutaneous abscesses. Rabbits immunized with TDM or TDM + MPL developed no abscesses, and only slight reactions at the injection site. The synthetic adjuvant system TDM + MPL is recommended for use in rabbits, considering its adequate stimulation of antibody production with minimal adverse reactions.

Adjuvants, Immunologic

Myocardial stimulation impedance: the effects of electrode, physiological, and stimulus variables.

With exposed metal at the electrode tissue interface (8 mm2, 28 mm2, 57 mm2), myocardial threshold stimulation impedance increased as pulse duration was lengthened, with left ventricular intramyocardial stimulation, and with the smaller surface area electrode. An 0.5 mm2 differential-current-density electrode, which eliminated direct metal-to-tissue contact at the electrode-myocardial interface, was associated with notably higher impedances than each of the three metal tip electrodes and did not show increasing impedance levels with changes in pulse duration, confirming the minimization of polarization energy losses with this device. The majority of electrode, electrode tissue interface, and myocardial variables that are characterized by high threshold stimulation impedance are associated with low threshold energy requirements for pacing and reduced pacemaker power source drain. No accurate information about sensing impedances can be derived from current knowledge of pacing impedance.

Acid-Base Imbalance

Effects of chronic parenteral carbohydrate administration on hepatic drug metabolism in the rat.

Effects of chronic parenteral carbohydrate administration on hepatic microsomal enzyme activity were studied in the rat. Intraperitoneal injections of either glucose or fructose (2.88 g daily for 7 days) significantly decreased hepatic cytochrome P-450 content and ethylmorphine N-demethylase and aniline hydroxylase activities. By the 5th day, cytochrome P-450 content decreased to 70-76% and ethylmorphine N-demethylase activity to 66-69% of control values. Aniline hydroxylase activity was not significantly altered until the 7th day, by which time it was 77-79% of control values. In vivo assessment of hepatic drug-metabolizing capacity using antipyrine as a test drug confirmed these decreases observed in vitro. Two major conclusions of these experiments are that such variables as time and dose of carbohydrate administration can affect the magnitude of the changes produced and that each parameter measured exhibited a distinctive pattern of change with time. Chronic carbohydrate administration produced hepatic fatty infiltration and glycogen depletion. Since all groups received identical amounts of specific nutrients, fatty infiltration was probably due to increased lipogenesis with decreased hepatic oxidative metabolism of fat. During these experiments neither hypoinsulinemia nor increased levels of cyclic AMP were observed. The molecular mechanisms responsible for hepatic glycogen depletion and decreased MFO activities remain to be established.

Aniline Hydroxylase

Ischemic injury to the conducting system of the heart. Involvement of myocardial lysosomes.

The conducting system was studied in an in situ perfused swine heart preparation with reduced coronary flow (ischemia) using perfusate containing high and low levels of glucose (26.6 versus 8.6mM) with and without insulin. Coronary flow was maintained at normal levels for 60 minutes in control hearts. In ischemic hearts flow was reduced to about 50 percent of control levels for 30 minutes. Ultrastructural studies documented only subtle modifications of Purkinje fibers in ischemic hearts. Glycogen depletion and disruption of cell junctions were observed in some fibers. One consistent finding was the activation of the lysosomal system. The outer membranes of primary lysosomes appeared herniated and in some cases disrupted, and small vesicles containing hydrolytic enzymes were seen in association with the Golgi apparatus and larger primary lysosomes. Specimens prepared for the demonstration of acid phosphatase indicated a redistribution of hydrolytic enzymes in Purkinje fibers with a depostion of acid hydrolases in smaller lysosomal vesicles, the transverse and side-to-side junctions between cells, and occasionally in the sarcoplasmic reticulum. Enriched perfusate containing high levels of glucose with insulin appeared to have no therapeutic effects in terms of the structure of the Purkinje fibers. The results suggest that alterations in the lysosomal system may be one of the earliest structural changes which occur in oxygen-deficient hearts.

Acid Phosphatase

True pregnancy toxemia (preeclampsia) in the guinea pig (Cavia porcellus).

In this study, normal nonpregnant, normal full-term pregnant, fasting ketotic and spontaneous pregnancy toxemic guinea pigs were compared to define the mechanism of this disease. In addition to conventional clinical, laboratory and pathologic studies, arterial blood pressure (thoracic and abdominal aortic) measurements and angiography were used. The results showed that in spontaneous cases of pregnancy toxemia, there is an aortic compression just caudal to the renal arteries. This compression reduced the aortic diameter by 22% of prerenal level as compared to 10% for fasting ketotic and normal pregnant guinea pigs. The aortic compression also resulted in a 30% postcompression reduction in blood pressure. No pressure differences were seen in the other groups. The postulated etiology for true toxemia of pregnancy in guinea pigs is, therefore, similar to that of man where aortic compression produces uterine ischemia and the resultant syndrome.

Alkaline Phosphatase

Visual acuity functions and pattern discrimination in the destriate cat.

The study provides evidence that the cat is capable of processing visual information of some detail after removal of area 17 and most of area 18. This postoperative discrimination of complex spatial stimuli is not based on the use of such cues as luminance differences or local flux cues. From the deficits which follow extensive lesions of areas 17-18, it appears as though these cortices participate in the detection of fine details. We found a modest increase in the threshold of grating acuity, moderate loss in orientation acuity and extensive deficit in a task requiring topographic alignment of contours (vernier offset). Further evidence for the substantial preservation of spatial vision in the destriate cat is provided by experiments which show that perceptual grouping of rectilinear arrays of figural elements (dots or line segments) into obliquely oriented rows is largely unaffected by the lesion, even when the grouping is initiated by near-threshold proximity cues. Since grouping effects are felt to be involved in the organization of the visual field into the figure-ground dichotomy, these results indicate that the neural mechanisms subserving the initial stage of form perception lie outside of areas 17 and 18. Consistent with the increased acuity thresholds of destriate cats, these animals have deficits in several pattern discriminations that require fine-grained spatial analysis The results suggest that areas 17-18 serve as a high-spatial frequency analyzer, but are not essential to pattern and form recognition.

Animals

Basic principles in selecting animal species for research projects.

One of the most important facets of biomedical research is selecting the species of laboratory animal best suited for a particular purpose. The four major categories of animal models are experimental, spontaneous, negative, and orphan. The experimental model is the one most frequently used, but each category has a place in medical research. Once the investigator has decided which type of model the project calls for, numerous other factors must be considered: ease of handling and surgical manipulation; size, docility, and body conformation; cost of the animal and its related supplies (food, bedding, and caging); the accessibility of superficial blood vessels; and the investigator's familiarity with the various species which are available. Among the biologic factors which should be considered are resistance to natural diseases, nutritional requirements, genotype, anatomy, physiology, and biochemistry.

Animals

Placenta extrachorialis in the stumptailed macaque (Macaca arctoides).

Placenta extrachorialis was diagnosed in two of 56 placentas obtained from stumtailed macaques (Macaca arctoides) after elective cesarean section. The condition was characterized by the presence of an annular ring of necrotic tissue and fibrin at the margin of the villous chorion. Because these cases occurred in two of six known primiparous females, it was suggested that thte condition may account, at least in part, for the high incidence of pregnancy-related problems observed in primiparous stumptailed macaques.

Animals

The organization of reticulo-olivo-cerebellar circuits in the North American opossum.

By employing the autoradiographic method we have determined that the inferior olivary nucleus receives input from the reticular formation of the midbrain, pons and, probably, the medulla. The remarkable thing about such connections is that they are not diffuse, but targeted in large part on restricted portions of the caudal acessory nuclei. From our previous studies it is clear that some of the olivary regions receiving reticular input also receive projections from the cerebral cortex, the spinal cord and the dorsal column nuclei. In addition, the HRP technique reveals that these same olivary regions relay to parts of the spinal cerebellum, i.e. to restricted zones of the anterior lobe (present study). Taken together these observations suggest that some reticulo-olivo-cerebellar connections provide indirect routes through which cortical and spinal information gains access to the spinal cerebellum. Such circuits have also been suggested by the physiological literature. Of particular interest, however, was our finding that several reticular areas of the midbrain and pons project to the portion of the medial acessory nucleus which relays in turn to auditory-visual areas of the cerebellar vermis (declive, folium and tuber). It would appear that at least some reticulo-olivo-cerebellar circuits are significant in the organization of motor responses to visual and/or auditory stimuli.

Afferent Pathways

Anatomical and neurobehavioral investigations concerning the thalamo-cortical organization of the rat's visual system.

The organization of thalamic afferents to the rat's visual cortex was investigated autoradiographically and through the retrograde transport of horseradish peroxidase (HRP) following infections into striate and peristriate cortex. The results revealed that Nucleus lateralis posterior (NLP) projects to a large peristriate cortical field that includes areas 18A, 7, and the anterior portion of area 18, and to a circumscribed temporal area corresponding to Krieg's ('46a,b) area 20. The dorsal lateral geniculate nucleus (LGNd) was shown to project to two spatially discontinuous cortical areas. The largest geniculate receiving area is partially coextensive with Krieg's area 17, but an extension of this projection posterior and medial to the striate cortex was found. In addition, a geniculate projection to a restricted field located in the lateral peristriate cortex was identified. Concurrent investigations were designed to assess the pattern discrimination abilities of rats prepared with striate cortical ablations, lesions in NLP and combined striate-cortical and thalamic ablations. Comparison of these animals with normal control subjects revealed that the striate cortex in the rat (as in the cat [Doty, '71; Sprague et al., '77] and the tree shrew [Killackey and Diamond, '71; Ware et al., '74]) is not necessary for successful pattern discrimination, and that the geniculo-striate and NLP-extra-striate projection systems are both involved in mediating the visual discriminative abilities of the rat. The results add species generality to the concept that the central connections to the visual cortex are characterized by parallel-conducting thalamic channels and contribute to the growing number of demonstrations that the extra-striate cortex and associated thalamic cell groups contribute significantly to the process of visual-pattern recognition.

Afferent Pathways

An inexpensive microphotometer system for measuring silver grain densities in autoradiographs.

An inexpensive microphotometric system is described which will facilitate reading grain-dense areas in autoradiographic material. It is reliable, easy to operate and adaptable to most light microscopes with a dark field condenser. In addition to the microscope, the components include a photodiode, an operational amplifier and a digital mV meter. Data are presented to demonstrate the sensitivity of the system and to illustrate the differential variability between the microphotometer and the counting of grains by eye.

Animals