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Biomedical subjects

R J Nelson

Publications and source records attributed to R J Nelson.

At least 163 records · Page 9Linked to original sources
PubMed1994

Photoperiodic effects on tumor development and immune function.

Seasonal changes in adaptations associated with winter coping strategies have been frequently studied. Central among the suite of energy-saving, winter-coping strategies is the suspension of reproductive activities. The inhibition of reproduction by nontropical rodents is mediated by daylength changes. Although balanced annual energy budgets are critical, survival and subsequent reproductive success also require avoiding predators, illness, and early death. Because the stressors of winter could lead to suppressed immune function, we hypothesized that animals should have evolved survival strategies involving immunoenhancement. Short daylengths provide a predictive cue to individuals that could be used to enhance immune function in advance of stress-induced immunosuppression. In Experiment 1, adult female deer mice (Peromyscus maniculatus) were housed in either long (LD 16:8) or short (LD 8:16) days for 8 weeks, then injected with the chemical carcinogen 9,10-dimethyl-1,2-benzanthracene (DMBA) dissolved in dimethyl sulfoxide (DMSO) or with the DMSO vehicle alone. Animals were evaluated weekly for 8 weeks after injection. None of the animals treated with DMSO developed tumors in any of the experiments. Nearly 90% of the long-day deer mice injected with DMBA developed squamous cell carcinoma. None of the short-day deer mice injected with DMBA developed tumors. Small lesions developed at the site of injection; short-day females had less severe lesions and healed faster than long-day females. Immunoglobulin G (IgG) response to i.p. injection of sheep red blood cells (SRBC) did not differ photoperiodic conditions. The role of estrogens in the photoperiodic responses was evaluated in Experiment 2: Ovariectomized or sham-ovariectomized deer mice received estradiol benzoate replacement therapy or a control procedure in long daylengths for 8 weeks prior to injection of DMBA or DMSO, then were monitored for 8 additional weeks. Females treated with DMBA developed tumors at the same rate, regardless of estrogen manipulation. Estrogen did not affect healing rates. In Experiment 3, female deer mice were injected with a slurry of microspheres that either contained bromocriptine or were empty. Suppression of prolactin with bromocriptine resulted in a decrease of tumor incidence from 55.6% to 24% in long-day females 8 weeks after injection with DMBA. Healing rates were not affected by prolactin manipulations. Silastic capsules that were filled with either melatonin or cholesterol were implanted into long-day female deer mice in Experiment 4; 8 weeks later, females received an injection of either DMBA or DMSO, then were monitored for 8 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Advances in image-directed neurosurgery: preliminary experience with the ISG Viewing Wand compared with the Leksell G frame.

Because of the limited application of frame-based stereotaxy to general neurosurgical procedures, we have carried out a preliminary evaluation of the ISG Viewing Wand, a frameless image-directed surgical system that is based on the rapid reformat and accurate three-dimensional reconstruction capability of parallel processor-based computer technology. We have compared the first 36 cases carried out with the system in the Frenchay Neurosurgery Department with a retrospective analysis of the previous 36 cases carried out using the Leksell G frame. The stereotactic cases were completed over a period of 15 months, representing 2.8% of intracranial procedures. The wand cases were completed in 3 months, 13% of the intracranial practice during that time. The wand was used for 28 supratentorial craniotomies (76%), four infratentorial procedures (11%) and five biopsy procedures (13%). Conventional stereotaxy was not used for posterior fossa or skull base procedures. Supratentorial craniotomy was carried out in nine cases (25%), while the remaining 27 cases involved point source localization within the cranium (75%). The mean preparation time prior to surgery was 65 min for the stereotactic cases and 37 min for the wand cases. We therefore conclude that the indications for frame-based stereotaxy and Viewing Wand use are mutually exclusive. Leksell stereotaxy remains the method of choice for point source localization deep within the cranium. All other procedures requiring an image-directed minimally invasive surgical approach are more appropriately carried out using the Viewing Wand. The system has potential immediate application in supratentorial, skull base and infratentorial tumour surgery, vascular surgery, epilepsy surgery and upper cervical spine surgery.

Brain Mapping↗
PubMed1993

Whiplash injury and surgically treated cervical disc disease.

The incidence of a previous whiplash injury in 215 unselected patients who underwent an anterior cervical discectomy and fusion between 1988 and 1991 was found to be twice that of a control population of 800 general orthopaedic outpatients (P < 0.05). The mean age at which the whiplash injury occurred in the surgical group was 37 years and in the control group 36 years. The mean age at operation of those patients with a previous whiplash injury (45 +/- 12 years) was significantly less than those patients without a previous whiplash injury (55 +/- 14 years, P < 0.001). This study provides further evidence that whiplash injury causes structural changes predisposing to premature degenerative disc disease.

Adult↗
PubMed1993

Heat shock proteins: molecular chaperones of protein biogenesis.

Heat shock proteins (Hsps) were first identified as proteins whose synthesis was enhanced by stresses such as an increase in temperature. Recently, several of the major Hsps have been shown to be intimately involved in protein biogenesis through a direct interaction with a wide variety of proteins. As a reflection of this role, these Hsps have been referred to as molecular chaperones. Hsp70s interact with incompletely folded proteins, such as nascent chains on ribosomes and proteins in the process of translocation from the cytosol into mitochondria and the endoplasmic reticulum. Hsp60 also binds to unfolded proteins, preventing aggregation and facilitating protein folding. Although less well defined, other Hsps such as Hsp90 also play important roles in modulating the activity of a number of proteins. The function of the proteolytic system is intertwined with that of molecular chaperones. Several components of this system, encoded by heat-inducible genes, are responsible for the degradation of abnormal or misfolded proteins. The budding yeast Saccharomyces cerevisiae has proven very useful in the analysis of the role of molecular chaperones in protein maturation, translocation, and degradation. In this review, results of experiments are discussed within the context of experiments with other organisms in an attempt to describe the current state of understanding of these ubiquitous and important proteins.

Cytosol↗
PubMed1993

Prolactin and testosterone inhibit torpor in Siberian hamsters.

Female Siberian hamsters maintained in a winter photoperiod (8 h light/day) ceased to undergo daily torpor during infusion of prolactin (PRL) from osmotic minipumps; winter torpor was reinstated within 3 days of discontinuation of treatment. By contrast, PRL infusion was ineffective in suppressing daily torpor elicited by restricting food intake in female hamsters housed in a summer photoperiod (16 h light/day). Summer daily torpor was, however, completely inhibited in long-day gonadectomized male hamsters treated with testosterone (T). We suggest that the hyperprolactinemia, which in previous studies is characteristic of hamsters that sustain ablation of the suprachiasmatic nucleus, is incompatible with winter torpor. Summer torpor may be controlled by a mechanism less responsive to variations in plasma PRL concentration. Both winter and summer torpor are inhibited by exogenous T; it remains uncertain, however, whether sustained decreases in endogenous T secretion are as essential for the expression of summer as they are for winter torpor.

Animals↗
PubMed1993

Winter adaptations of male deer mice (Peromyscus maniculatus) and prairie voles (Microtus ochrogaster) that vary in reproductive responsiveness to photoperiod.

Individuals of many nontropical rodent species restrict breeding to the spring and summer. Seasonal reproductive quiescence putatively reflects the energetic incompatibility of breeding and thermoregulatory activities. However, so-called "out-of-season" breeding occurs in virtually all rodent populations examined, suggesting that the incompatibility can be resolved. Both reproductive inhibition and development of energy-saving adaptations are mediated by environmental photoperiod, but some individuals do not inhibit reproduction in short days. In order to assess the costs and benefits of winter breeding, the present study examined the extent to which male prairie voles (Microtus ochrogaster) and deer mice (Peromyscus maniculatus) that maintained summer reproductive function in winter-simulated daylengths also maintained summer thermoregulatory adaptations. Circadian locomotor activity patterns, basal metabolic rate, capacity for nonshivering thermogenesis, nest building, body mass, and daily food consumption were compared among short-day (LD 8:16) regressed males, short-day (LD 8:16) nonregressed males, and long-day (LD 16:8) males. Short-day nonregressed deer mice resembled long-day conspecifics in terms of body mass and nest-building activities; however, the locomotor activity pattern of short-day nonregressed deer mice was similar to that of their short-day regressed conspecifics. Short-day nonregressed prairie voles had body masses similar to those of long-day conspecifics. Regardless of their reproductive response to photoperiod, short-day prairie voles reduced their daily food consumption and wheel-running activity, compared to long-day voles. These results suggest that winter breeding has energetic costs, most likely resulting from maintaining a "summer-like" body mass relative to that of reproductively regressed animals. These costs may be ameliorated to some extent by the reduction in locomotor activity and nest-building behavior emitted by short-day animals, regardless of reproductive response to short days. Thus, the occurrence of winter breeding may be the result of sufficient numbers of reproductively photoperiod-nonresponsive morphs in the population and sufficiently mild ambient conditions to permit survival of these larger animals.

Adaptation, Physiological↗
PubMed1992

The translation machinery and 70 kd heat shock protein cooperate in protein synthesis.

The function of the yeast SSB 70 kd heatshock proteins (hsp70s) was investigated by a variety of approaches. The SSB hsp70s (Ssb1/2p) are associated with translating ribosomes. This association is disrupted by puromycin, suggesting that Ssb1/2p may bind directly to the nascent polypeptide. Mutant ssb1 ssb2 strains grow slowly, contain a low number of translating ribosomes, and are hypersensitive to several inhibitors of protein synthesis. The slow growth phenotype of ssb1 ssb2 mutants is suppressed by increased copy number of a gene encoding a novel translation elongation factor 1 alpha (EF-1 alpha)-like protein. We suggest that cytosolic hsp70 aids in the passage of the nascent polypeptide chain through the ribosome in a manner analogous to the role played by organelle-localized hsp70 in the transport of proteins across membranes.

Amino Acid Sequence↗
PubMed1992

Prediction of migration behavior of oligonucleotides in capillary gel electrophoresis.

The influence of the primary structure (base composition) on the electrophoretic migration properties of single-stranded oligodeoxyribonucleotides in capillary polyacrylamide gel electrophoresis was investigated using homo- and heterooligomers under denaturing and non-denaturing conditions. Homooligodeoxyribonucleotides of equal chain lengths but of different base composition showed significant differences in mobility. In addition, the migration properties of heterooligomers were found to be highly dependent on their base composition. A simple equation is presented for predicting relative migration times using denaturing and non-denaturing polyacrylamide capillary gel electrophoresis. Orange-G was used as an internal standard and as the basis of the relative migration time calculations. Examples are presented using homo- and heterooligomers in the 10-20-mer range to show the correlation of the primary structure and their predicted and observed migration rates.

Base Sequence↗
PubMed1992

Striatal neuronal activity during the initiation and execution of hand movements made in response to visual and vibratory cues.

Recordings were obtained from 146 neurons in the neostriatum of rhesus monkeys while they performed wrist movements in response to visual and vibratory cues. Of these, 75 putamena nd 29 caudate neurons exhibited changes in firing rate that were temporally related to the onset of the wrist movements and that began prior to movement onset. This premovement activity (PMA) usually was directionally specific, in that the magnitude or direction of change in firing rates was different during flexion trials as compared to trials involving wrist extension. PMA onset usually preceded movement onset by more than 100 ms and in most instances preceded the average onset of task-related changes in electromyographic (EMG) activity in muscles of the wrist and forelimb. For most neurons, the changes in neuronal activity that began prior to movement were maintained during movement execution. However, approximately one-third of the neurons that exhibited PMA changed their firing rate in the opposite direction, relative to their PMA and to their baseline rate of activity, once the movement began. Several other neurons either exhibited PMA only or they altered their discharge rates during movement execution but did not exhibit PMA. These observations suggest that, despite the close temporal relationship between the onset of PMA and the onset of wrist movement, the neuronal mechanisms mediating the PMA may differ from those that occur during movement execution. The PMA onset of neostriatal neurons occurred earlier in visually cued than in vibratory cued trials. These differences were statistically significant only for flexion trials, however, in which movements were made against a load and in the same direction as the palmar vibratory stimulus. For trials involving wrist extension, PMA onsets for visually cued as compared with vibratory cued trials were not statistically different. These findings contrast with data obtained previously from somatosensory cortical neurons during performance of the same behavioral task. On average, PMA in the putamen began earlier, relative to movement onset, than it did in the somatosensory cortex. Moreover, in the somatosensory cortex, PMA onset occurred earlier in vibratory cued than in visually cued trials, irrespective of movement direction (Nelson 1988; Nelson and Douglas 1989). For putamen neurons, but not for caudate or cortical neurons, the onset of PMA also occurred significantly earlier during extension trials than flexion trials, irrespective of the modality of the "go-cue".(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Isolation and characterization of extragenic suppressors of mutations in the SSA hsp70 genes of Saccharomyces cerevisiae.

Saccharomyces cerevisiae strains that contain null alleles of two hsp70 genes, SSA1 and SSA2, are temperature sensitive for growth. In this study, extragenic suppressors of ssa1 ssa2 have been isolated. Suppression is due to mutations at nuclear loci designated EXA1, EXA2 and EXA3 for EXtragenic suppressor hsp70 subfamily A. Two of the four EXA1 alleles are dominant as is EXA3-1. The other two EXA1 alleles as well as the sole EXA2 allele are recessive. EXA1 mutations lead to accumulation of a previously uncharacterized form of hsp70. EXA2 and EXA3 mutations affect the regulation of the stress response. In exa2-1 ssa1 ssa2 strains the gene products of the remaining SSA hsp70 genes, SSA3 and SSA4 (Ssa3/4p), accumulate to higher levels. The EXA3-1 mutation results in increased accumulation of both Ssa3/4p and the hsp70s encoded by the SSB1 and SSB2 genes (Ssb1/2p), suggesting that the EXA3 gene product plays a central role in the yeast stress response. Consistent with this hypothesis, EXA3-1 is tightly linked to HSF1, the gene encoding the transcriptional regulatory protein known as "heat shock factor." All of the genes identified in this study seem to be involved in regulating the expression of SSA3 and SSA4 or the activity of their protein products.

Alleles↗
PubMed1992

Photoperiod influences the critical caloric intake necessary to maintain reproduction among male deer mice (Peromyscus maniculatus).

The concept of critical day length is well established among rodents; reproductive function is maintained when day lengths are greater than some specific threshold. In addition to day length cues, seasonal breeding in deer mice can also be regulated by food availability. The caloric threshold necessary to support reproduction remains unspecified for seasonally breeding rodents. The present study examined the interaction between photoperiod and food availability on reproductive function in adult male deer mice (Peromyscus maniculatus). A critical caloric intake profile was constructed in long (16L:8D) and short (8L:16D) photoperiods; groups of deer mice in both photoperiods either received food ad libitum or 90, 80, or 70% of their individual ad libitum food intake for 10 wk. At autopsy, paired testes, epididymides, and seminal vesicles were removed and weighed. Body mass, total body fat, and total body water contents were also obtained. Short, as compared to long, day lengths inhibited the reproductive systems of male deer mice. However, food consumption interacted with photoperiod to affect reproductive function. Significant reductions in reproductive organ size as well as spermatogenic activity were observed among short-day mice after a 10% reduction in ad libitum food intake. Long-day animals required a 20% reduction in caloric intake to depress reproductive function. Body mass and total body water content were generally unaffected by either photoperiod or food consumption. Total body fat content was reduced in short- as compared to long-day mice. Individual reproductive responsiveness to short days increased as food availability decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Experimental aspects of cerebrospinal hemodynamics: the relationship between blood flow velocity waveform and cerebral autoregulation.

The dynamic relationships among mean flow velocity, its pulsatile amplitude (FVa), cortical cerebral blood flow (CBF), and cerebral perfusion pressure (CPP) were studied in normal rabbits and rabbits with subarachnoid hemorrhage using 8-MHz pulsed transcranial Doppler ultrasound and hydrogen clearance under conditions of systemic hypotension and intracranial hypertension. A two-slope relationship was observed between FVa and CPP with a break point that correlated closely with the lower limit of CBF autoregulation in each animal. Below this CPP break point, FVa varied directly with CPP, and above the break point FVa varied inversely with CPP. In this experimental model, an inverse correlation between FVa and CPP indicates intact CBF autoregulation, whereas loss of that correlation implies exhaustion of autoregulatory reserve. Simultaneous recording and computation of FVa, CPP, and the correlation coefficient between FVa and CPP may be a means of monitoring CBF autoregulation in clinical practice.

Animals↗
PubMed1991

Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis.

Blood feeding by the sand fly Lutzomyia longipalpis is aided by the presence of a vasodilator in its salivary glands. This novel vasodilator has been isolated by reversed-phase high-performance liquid chromatography. Ten nanograms of the vasodilator are present in the extract of a pair of sand fly salivary glands. It has 500 times the vasodilatory activity of calcitonin gene-related peptide, previously the most potent vasodilator peptide known. This novel peptide is thus called maxadilan.

Amino Acids↗
PubMed1991

Relationships between sensory responsiveness and premovement activity of quickly adapting neurons in areas 3b and 1 of monkey primary somatosensory cortex.

When monkeys make wrist movements in response to vibration of their hands, primary somatosensory (SI) cortical neurons that adapt quickly to the vibratory stimulus often exhibit two temporally separate types of activity. Initially, these neurons respond to the stimulus. They then cease discharging, only to resume firing prior to the movement. This activation, cessation and reactivation occurs even though the sensory stimulus remains on until after the movement is begun. The first change in activity is most likely related to sensory input. The second, which has been called premovement activity, may have a sensory component as well as one related to the upcoming movement. We wanted to test the hypothesis that the premovement activity exhibited when vibration is present represents both a reactivation of a neuron's vibratory response and the premovement activity that normally occurs when vibration is absent. We also wanted to determine if area 3b and 1 quickly adapting (QA) neurons show similar or different activity patterns during the initiation and execution of sensory triggered wrist movements. Four monkeys were trained to make wrist flexion and extension movements in response to vibratory stimuli delivered to the handle which the animals used to control the behavioral paradigm. Two fo the four monkeys also made similar wrist movements following visual cues. We found that the premovement activity of QA neurons located in area 1 (but not area 3b) is comprised of a sensory-related component as well as a movement-related component. The magnitude of these individual components differs in relationship to a neuron's receptive field type, the movement direction and the external force imposed on the stimulated forelimb. Premovement activity of area 3b and area 1 QA neurons occurs at the same time prior to movement, regardless of whether visual or vibratory cues are used to trigger wrist movements. This activity occurs at about the same time as others have observed elevations in the threshold for tactile perception, suggesting that premovement activity and changes in sensory responsiveness before movement may be related. These and previous findings are used to construct a model which may predict the firing patterns of SI QA neurons during behavioral tasks. These findings also suggest that areas 3b and 1 may have different roles in processing task-related somatosensory information.

Animals↗
PubMed1991

Ultrasonic decalcification of the aortic annulus during aortic valve replacement.

Aortic valve replacement for calcifica aortic stenosis requires meticulous debridement of the aortic annulus to effect optimal valve seating. Since 1987, we have used ultrasonic energy to debride the aortic annulus during aortic valve replacement in 56 patients. In our experience, ultrasonic debridement of the annulus is superior to traditional methods of debridement, affords improved seating of the valve, and may allow placement of a larger valve. Our follow-up ranges from 2 to 32 months (mean follow-up, 13 +/- 9 months) with 0% incidence of paravalvular leak or valve failure. We advocate the use of ultrasonic debridement as an adjunctive tool in aortic valve replacement.

Adult↗