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Biomedical subjects

R J Nelson

Publications and source records attributed to R J Nelson.

At least 181 records · Page 10Linked to original sources

Hormonal control of gene expression: interactions between two trans-acting regulators in Drosophila.

The steroid hormone 20-hydroxyecdysone (20HE) and the Broad-Complex locus (BRC) are involved in regulating developmental changes in gene expression around the time of metamorphosis in Drosophila. We have investigated the regulatory interactions between 20HE, BRC, and a set of genes expressed in the fat body of third-instar Drosophila larvae. RNA levels for two hormone-inducible genes, Larval Serum Protein-2 and P1, accumulate to normal levels in BRC-mutant larvae. In contrast, RNA levels for the P6 gene were affected by mutations at BRC. On the basis of the results of experiments in which hormone concentrations were varied in BRC-mutant or wild-type larvae, we conclude that 20HE can both increase and decrease P6 RNA levels in the absence of BRC product(s). BRC appears to be a trans-acting modulator of the response of P6 to the hormone. We propose that BRC attenuates the repressive effect of the hormone, expanding the range of hormone concentrations that induce the gene, thus allowing P6 RNA to reach high levels during the third larval instar. The results are discussed in relation to other genes that are regulated by the same two trans-acting factors. A model is presented that refines the model of Ashburner et al. (1974, Cold Spring Harbor Symp. Quant. Biol. 38: 655-662) for the hormonal regulation of gene activity.

Age Factors↗

Effects of photoperiod and 6-methoxy-2-benzoxazolinone on male-induced estrus in prairie voles.

Prairie voles (Microtus ochrogaster) are characterized as facultative breeders with higher rates of reproductive activities observed during spring and summer than autumn and winter. The environmental factors regulating seasonal breeding in this species remain unspecified. Short day lengths inhibit reproductive organ development in male prairie voles in the laboratory, but these males remain fertile and capable of siring offspring; female prairie voles have been reported to be reproductively unresponsive to day length in the laboratory. The organization of estrus in this species is unusual in that females never display the cyclic changes associated with estrus; rather, female prairie voles require chemosensory stimuli associated with fertile males in order to be induced into estrus. The plant compound, 6-methoxy-2-benzoxazolinone (6-MBOA), is present in vegetatively growing grasses and sedges and acts to trigger reproduction in other rodent species exposed to short days. It was suspected that 6-MBOA present in the laboratory diet may have overridden the effects of photoperiod on female prairie voles in previous laboratory studies. In the present study, the effects of 6-MBOA and photoperiod on estrus induction were examined. Beginning at Week 0, female prairie voles were housed in long (LD 16:8) or short (LD 8:16) photoperiods for 9 weeks, then implanted subcutaneously either with an empty Silastic capsule or one packed with 6-MBOA. A special diet, devoid of 6-MBOA, was available ad lib from Week 5 to the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Maternal diet influences reproductive development in male prairie vole offspring.

The plant compound, 6-methoxy-2-benzoxazolinone (6-MBOA), is found in the meristematic tissue of young, vegetatively growing grasses, and its ingestion stimulates the reproductive system of rodents in both short and long photoperiods. The present study demonstrates the existence of a novel mechanism whereby the presence of 6-MBOA in the diet of pregnant prairie voles (Microtus ochrogaster) enhances gonadal development in their male offspring. Female voles were fed specially milled food in which 6-MBOA was present (50 micrograms of 6-MBOA/g food) or absent (0 microgram of 6-MBOA/g food) prior to the birth of their young; all of these dams received a diet that lacked 6-MBOA/g after the pups were born. Other females were fed food without 6-MBOA throughout pregnancy, but received one of the two diets during lactation. The pups from all experimental groups were weaned at 3 weeks of age and fed thereafter one of the two diets for 3 additional weeks. Prenatal exposure to 6-MBOA enhanced male reproductive development. Maternal ingestion of 6-MBOA during lactation or postweaning intake of 6-MBOA by the young did not influence reproductive development of males. This mechanism may be involved in the rapid rate of sexual maturation observed prior to peak population densities of microtine rodents.

Animals↗

Sensory response enhancement and suppression of monkey primary somatosensory cortical neurons.

Vibratory stimulus-related responses were recorded from monkey primary somatosensory cortical (SI) neurons while animals performed two tasks. In the movement task, vibratory stimuli served as the go-cue for wrist flexion or extension. In the no-movement task, movements normally made in response to vibratory stimuli were extinguished. Area 3a, 3b, and 1 neurons with deep receptive fields (RFs) exhibited greater stimulus-related activity during the movement task than during the no-movement task. Area 3b neurons with cutaneous RFs were similarly enhanced during the movement task, whereas area 1 neurons with cutaneous RFs were less responsive to vibratory stimuli during the movement task. These results suggest that motor-set and/or selective attention may modulate the responsiveness of SI neurons to peripheral stimuli and that changes in sensory responsiveness in SI neurons differ as a function of their cortical location and RF type.

Animals↗

Nerve growth factor, nerve grafts and amniotic membrane grafts restore erectile function in rats.

In an effort to reduce complications arising from radical pelvic surgery, an improved technique for restoration of autonomic innervation has been developed. The ability of nerve growth factor (NGF) alone or in combination with interposition nerve grafts, as well as the use of fetal amniotic membrane as an alternative growth matrix to enhance regeneration of ablated cavernous nerves were investigated in rats. Rats with ablated cavernous nerve displayed little or no penile erection, either in response to direct electrical stimulation or to an estrous female rat. A step wise improvement in electrically induced erections was observed by NGF alone, nerve graft alone, and the combination of NGF and nerve graft. Restoration of sexual behavior followed the same pattern obtained with electrical stimulation. Furthermore, the use of neonatal amniotic membrane as an alternative nerve growth matrix enhanced both electrically stimulated erection and mating behavior. These results suggest that the use of NGF and appropriate grafting materials can facilitate autonomic nerve regrowth and potentially reduce the morbidity of surgically induced nerve injuries.

Amnion↗

Cavernous nerve grafts restore erectile function in denervated rats.

Although potency can be preserved in most men following radical prostatectomy, in some patients one or both cavernous nerves must be sacrificed in order to excise all tumor. For these patients we have considered nerve reconstruction at the time of surgery using an interposition nerve graft. This possibility has been tested in a rat model. Animals were divided into three groups. In the sham control group, a pelvic exploration was conducted without division of the cavernous nerves. In the nerve ablation group, a five mm. segment of cavernous nerve was excised. In the graft group, five mm. of cavernous nerve was excised bilaterally and replaced with an interposition graft of genito-femoral nerve. At one month intervals postoperatively animals from each group underwent mating tests to determine potency; the ratio of vaginal intromission to unsuccessful mounts (I/M ratio) was determined. Following the mating tests the animals were re-explored and attempts were made to stimulate erections electrically via the pelvic nerve. Results at two months show the I/M ratio of the rats with grafts (0.05) and the nerve ablations (0.14) are low compared with the sham operated animals (1.0). By month four the graft group (0.89) has approached the sham group (0.91) while the ablation group (0.18) remains unchanged (p less than .05). Electrical stimulation at month two produced no erections in the nerve ablated or the grafted rats and 100% erections in the sham-operated animals. At month four, 50% of the rats with grafts, 10% of the nerve ablated animals, and 100% of the intact animals produced erections upon electrical stimulation (p less than .05). These results suggest that cavernous nerve grafting in rats can be successful in restoring potency after surgical injury. Application of these techniques to man may be indicated.

Animals↗

The effects of hyponatraemia and subarachnoid haemorrhage on the cerebral vasomotor responses of the rabbit.

Impairment of cerebral autoregulation and development of hyponatraemia are both implicated in the pathogenesis of delayed cerebral ischaemia and infarction following subarachnoid haemorrhage (SAH) but the pathophysiology and interactions involved are not fully understood. We have studied the effects of hyponatraemia and SAH on the cerebral vasomotor responses of the rabbit. Cerebrovascular reactivity to hypercapnia and cerebral autoregulation to trimetaphan-induced hypotension were determined in normal and hyponatraemic rabbits before and 6 days after experimental SAH produced by two intracisternal injections of autologous blood. Hyponatraemia (mean plasma sodium of 119 mM) was induced gradually over 48 h by administration of Desmopressin and intraperitoneal 5% dextrose. Sham animals received normal saline. The cerebrovascular reactivity (% change +/- SD in cortical CBF/mm Hg PaCO2, measured by hydrogen clearance) of hyponatraemic (4.8 +/- 3.0%) and SAH (1.3 +/- 2.0%) animals was significantly less (p less than 0.05) than control (11.6 +/- 4.0%) and sham (8 +/- 2.0%) animals, whereas the reactivity of hyponatraemic-SAH animals was preserved (9.8 +/- 6.0%). Hyponatraemia and SAH alone each significantly impaired CBF autoregulation but their combined effects were not additive. Systemic hyponatraemia impairs normal cerebral vasomotor responses but does not augment the effects of experimental SAH in the rabbit.

Animals↗

The resolution of transcranial Doppler scanning: a method for in vitro evaluation.

The circle of Willis may be examined using low frequency pulsed Doppler ultrasound transmitted through the thin squamous temporal bone or 'acoustic windows' of the skull. The thickness and shape of these windows affect the characteristics of the ultrasound beam and partly determine the spatial resolution of transcranial Doppler scanning. We have studied the effects of temporal bone on the ultrasound beam and sample volume characteristics of the EME Transcan 2 MHz transducer using a stepper motor, computer-controlled ultrasound plotting system. The lateral and axial spatial dimensions of the sample volume, and a direct estimate of the lateral resolution of the system, were determined at various depths of interest using Doppler targets. The results in this initial study of a small number of specimens indicates a decrease in sample width, and hence an increase in lateral resolution, presumably due to the lensing effect of the skull cusping. The estimated lateral resolution of the system is of the order of 4 mm.

Aged↗

Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure.

Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia.

Adult↗

Cloning and characterization of repetitive DNA sequences from genomes of Oryza minuta and Oryza australiensis.

The value of genome-specific repetitive DNA sequences for use as molecular markers in studying genome differentiation was investigated. Five repetitive DNA sequences from wild species of rice were cloned. Four of the clones, pOm1, pOm4, pOmA536, and pOmPB10, were isolated from Oryza minuta accession 101141 (BBCC genomes), and one clone, pOa237, was isolated from Oryza australiensis accession 100882 (EE genome). Southern blot hybridization to different rice genomes showed strong hybridization of all five clones to O. minuta genomic DNA and no cross hybridization to genomic DNA from Oryza sativa (AA genome). The pOm1 and pOmA536 sequences showed cross hybridization only to all of the wild rice species containing the C genome. However, the pOm4, pOmPB10, and pOa237 sequences showed cross hybridization to O. australiensis genomic DNA in addition to showing hybridization to the O. minuta genomic DNA.

Base Sequence↗

Effect of right atrial appendectomy on the release of atrial natriuretic hormone.

Atrial natriuretic hormone is released from the right atrial appendage in response to atrial distention. During cardiac operations the right atrial appendage is usually partially removed or ligated for venous cannulation. To evaluate the effect of right atrial appendectomy on the release of atrial natriuretic hormone and its natriuretic and diuretic responses, we prospectively randomized into two groups 23 patients undergoing elective coronary artery bypass operations. There were 16 male and 7 female patients with a mean age of 62 +/- 7 years. Group A (n = 11) had the right atrial appendage removed, and group B (n = 12) had the right atrial appendage preserved and venous cannulation done lateral to the appendage. The two groups were comparable for sexual distribution, age, number of grafts, and extracorporeal bypass time. All patients had normal left ventricular and renal functions, and they did not receive any diuretics during the study period. The patients were studied both preoperatively and postoperatively whereby the atrial natriuretic hormone serum levels, urine volume per minute, fractional excretion of sodium, amount of sodium excreted, and central venous pressure were measured before and after volume expansion with 5% albumin, 7.5 ml/kg. There was no statistical difference in these parameters preoperatively. In the postoperative period, however, group B patients had higher atrial natriuretic hormone levels after volume expansion than group A patients (376 +/- 84 versus 184 +/- 31 pg/ml; p less than 0.05), higher urine volume per minute (4.4 +/- 1.0 versus 2.0 +/- 0.4 ml/min; p less than 0.05), higher fractional excretion of sodium (2.30 +/- 0.66 versus 0.64 +/- 0.19; p less than 0.02), and higher amount of sodium excreted (511.1 +/- 150.9 versus 83.9 +/- 22.8 mmol/min; p less than 0.02). The central venous pressure was similar both before (9 +/- 1 versus 9 +/- 1 mm Hg) and after (16 +/- 1 versus 15 +/- 1 mm Hg) volume expansion in both groups. We conclude that preserving the right atrial appendage during cardiac operations significantly increased the release of atrial natriuretic hormone, resulting in increased urinary sodium excretion and better diuresis in the postoperative period.

Aged↗

Fibrin glue inhibits intra-abdominal adhesion formation.

To determine the effect of fibrin glue on intra-abdominal adhesion formation, 45 rats were randomized to three groups. Each animal received two adhesion models. Group 1 received no further treatment. Groups 2 and 3 had the adhesion models covered with fibrinogen from fresh frozen plasma (1.77 g/L) and cryoprecipitate (23.6 g/L), respectively. In group 1, 13 of 15 rats had high-grade adhesions in both models. In group 2, high-grade adhesions were noted in nine of 15 rats in model 1 and in 12 of 15 rats in model 2. In group 3, however, high-grade adhesions were seen in only three of 15 rats in model 1, with 11 rats having no adhesions, and in only two of 15 rats in model 2. Histologic analysis suggested accelerated healing in group 3. We conclude that (1) fibrin glue inhibits intra-abdominal adhesion formation in rats, (2) the inhibitory action is dependent on the fibrinogen concentration of the fibrin glue, and (3) adhesions are reduced by fibrin glue regardless of whether the peritoneal defect is closed.

Abdominal Muscles↗

Prolactin counteracts effects of short day lengths on pelage growth in the meadow vole, Microtus pennsylvanicus.

To test whether growth of the winter coat in short day lengths is contingent on suppression of plasma prolactin (Prl) levels, female meadow voles (Microtus pennsylvanicus) were kept in short day lengths for 12 weeks and were injected daily with saline or Prl; long-day animals were treated with either the dopamine agonist, bromocryptine (bromo), bromo plus Prl, or saline. Prl treatment prevented the growth of the winter coat normally observed after 12 weeks in short day lengths, but bromocryptine did not stimulate pelage growth in long-day voles. Pelage growth in short day lengths appears contingent upon decreased plasma prolactin levels.

Analysis of Variance↗

Fatal left ventricular perforation during mitral balloon valvoplasty.

Percutaneous balloon dilation of left-sided cardiac valves is being performed with increasing frequency. We describe and document the mechanism of injury of left ventricular perforation during mitral balloon valvoplasty. Despite a technically successful surgical repair with hemodynamic restoration, the patient was brain dead. We emphasize (1) the risk and the potentially catastrophic nature of left ventricular perforation during mitral balloon valvoplasty and (2) the need for surgical standby and rapid operative decompression for this complication.

Aged↗

Tracheal and main bronchial disruptions after blunt chest trauma: presentation and management.

Tracheobronchial disruption is one of the less common injuries associated with blunt thoracic trauma. This injury can be life threatening, however, and failure to diagnose it early can lead to disastrous acute or delayed complications. Nine cases of tracheobronchial disruption in the setting of nonpenetrating thoracic trauma were seen at four Los Angeles trauma centers between 1980 and 1987. Mechanism of injury, presentation, diagnosis, and management of these patients were reviewed. Disruptions involved the trachea in 3 patients, the right bronchus in 5 patients, and the left bronchus in 2 patients. Tracheobronchial disruptions occurred in settings of high-energy impact-type injuries and were more likely to have associated injuries than they were to occur alone. Common presenting signs included subcutaneous emphysema, dyspnea, sternal tenderness, and hemoptysis. Radiographic findings were most commonly pneumothorax, pneumomediastinum, and clavicle or rib fractures. Rigid bronchoscopy and fiberoptic bronchoscopy were both highly accurate methods for diagnosis but only in the hands of trained cardiothoracic surgeons. Delay in diagnosis increased the likelihood of postoperative complications.

Accidents, Traffic↗

Ascending aortic dissection in weight lifters with cystic medial degeneration.

We report 4 cases of ascending aortic dissection in patients with long histories of weight lifting. In 2 of the patients, the initial symptoms of dissection developed while they were lifting weights. Two patients had a history of hypertension and 2 had previously used anabolic steroids. All 4 were successfully treated surgically. Histopathology showed aortic medial changes in all 4. We believe that the hemodynamic stresses of weight lifting, namely, a rapid increase in systemic arterial blood pressure without a decrease in total peripheral vascular resistance, in combination with aortic medial degeneration may have contributed to the development of the aortic dissection.

Adult↗

Photoperiodic responsiveness in house mice.

House mice (Mus musculus) and laboratory strains of rats (Rattus norvegicus) have been traditionally considered nonphotoperiodic because their reproductive systems are unaffected by day length (photoperiod). In rats, however, at least three experimental manipulations, perinatal testosterone injection, chronic peripubertal testosterone exposure, or peripubertal olfactory bulbectomy, have revealed latent reproductive photoperiodism. The effectiveness of these experimental treatments may be unique to albino rats. Alternatively, these experimental manipulations may unmask the ability to discriminate short from long days in several "nonphotoperiodic" species and, thus, reveal clues to common physiological mechanisms underlying reproductive responsiveness to photoperiod. In the present study, male house mice were 1) subjected to olfactory bulbectomy or a sham operation at 23 days of age, 2) injected with testosterone or the oil vehicle at 3 days of age, or 3) implanted subcutaneously with an empty Silastic capsule or one filled with testosterone at 22 days of age. All mice were subsequently housed either in LD 16:8 or LD 4:20 photoperiods. The physiological mechanisms necessary to discriminate long from short day lengths are extant in house mice. Testicular mass was significantly reduced in short-day bulbectomized males when assessed 6 weeks postoperatively, but not when measured 10 weeks after surgery. Similarly, mice injected with testosterone when 3 days old and reared in short days had smaller testes as compared to testosterone-treated males housed in long days. Mice implanted with testosterone capsules regressed their reproductive systems regardless of photoperiod. Other reproductive organ weights followed the same general pattern of results as for testicular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗