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Biomedical subjects

R F Johnson

Publications and source records attributed to R F Johnson.

At least 73 records · Page 4Linked to original sources

Regulation of cytochrome P-450 dependent steroid hydroxylase activity in Manduca sexta: evidence for the involvement of a neuroendocrine-endocrine axis during larval-pupal development.

Ecdysone 20-monooxygenase activity and the factors which may regulate this steroid hydroxylase were examined in the midgut of the tobacco hornworm, Manduca sexta, during the last larval stadium. Radioassay experiments revealed that midgut ecdysone 20-monooxygenase undergoes a single 50-fold increase in activity temporally coincident with the onset of the wandering stage. The increase in midgut monooxygenase activity was prevented by actinomycin D and cycloheximide, and could be elicited in head (but not thoracic) ligated animals by a brain-retrocerebral complex factor(s) released at the same time as prothoracicotropic hormone. In contrast, ecdysone or 20-hydroxyecdysone could elicit the increase in enzyme activity in both head and thoracic ligated animals. These data suggest the operation of a neuroendocrine-endocrine axis in the regulation of midgut ecdysone 20-monooxygenase activity.

Animals↗

Two brain nuclei controlling circadian rhythms are identified by GFAP immunoreactivity in hamsters and rats.

The intergeniculate leaflet (IGL) of the lateral geniculate complex is marked by the presence of neuro-peptide Y-containing neurons that project to the suprachiasmatic nuclei (SCN) of the hypothalamus. In the present study, we demonstrate that both the IGL and SCN in the hamster and rat are specifically delineated by the presence of glial fibrillary acidic protein-like immunoreactivity. This is significantly greater than in most other diencephalic regions and is particularly dense in the hamster brain. These observations suggest that glial-neuronal interactions may participate in circadian rhythm generation and regulation.

Animals↗

Paraventricular nucleus efferents mediating photoperiodism in male golden hamsters.

Knife cuts were placed around the paraventricular nucleus of the hypothalamus (PVN) in an effort to identify the pathways mediating gonadal regression in male golden hamsters housed in a short photoperiod. Horizontal cuts dorsal to the PVN only affected photoperiodic responsiveness if they actually damaged the PVN. Coronal cuts caudal to the PVN had no effect on testes regression. Parasagittal cuts adjacent to the medial PVN had little or no effect on gonadal regression induced by short photoperiod. We conclude that efferents of the PVN arising dorsally or medially are not necessary for photoperiodic control of testes function, whereas projections from or through the lateral PVN region descending towards the spinal cord are important.

Animals↗

Localization of spinal cord preganglionic neurons innervating the superior cervical ganglion in the golden hamster.

The retrograde neuronal tracer Fluoro-Gold (FG) was used to determine the location and distribution of preganglionic sympathetic neurons in the spinal cord of the golden hamster. FG was injected unilaterally into the superior cervical ganglia. Labeled neurons were found only ipsilateral to the injection site in segments C8 to T5 of which the segments T1 to T3 contained about 98% of the labeled cells. Neurons were found in four regions of the spinal cord: the intermediolateral nucleus (43%), the lateral funiculus (55%), the central autonomic area (1%) and the intercalated region (less than 1%). In the intermediolateral nucleus, cells often were arranged in clusters of which several were seen in each spinal segment.

Animals↗

Lateral geniculate lesions alter circadian activity rhythms in the hamster.

The suprachiasmatic nucleus (SCN) receives photic input via a direct retinohypothalamic tract (RHT) and an indirect geniculohypothalamic tract (GHT). The neurons giving rise to the GHT are in the intergeniculate leaflet (IGL) of the lateral geniculate nucleus (LGN) and contain neuropeptide-Y (NPY) immunoreactivity. The present study used the neurotoxin, N-methyl aspartate (NMA), to examine the effects of lesions of the LGN on circadian wheelrunning in the hamster. The results are compared to those from control lesioned animals and animals with parasigittal cuts through the hypothalamus. The effectiveness of the lesions was examined with NPY immunohistochemistry of the SCN and IGL. NMA injections destroyed the neurons of the IGL and the adjacent ventral and dorsal divisions of the LGN and greatly reduced NPY immunoreactivity in the SCN. The results of the rhythm studies were: 1) NMA injection into the LGN area produced phase advances if the injection occurred within the 12 hr preceding activity onset and delays or no effect if injected during the 12 hr after activity onset; 2) the NMA lesions reduced the rate of reentrainment to 6 hr shifts in the LD 14:10 photoperiod and advanced the entrained phase angles by about 10 min; 3) the knife cuts advanced the entrained phase angles by about 30 min; 4) neither NMA lesions nor knife cuts altered circadian period in constant dim light. Our results indicate that the GHT is not required for entrainment or normal expression of circadian rhythmicity, but that the GHT does exert an influence on entrainment.

Animals↗

Effect of ethanol on human placental transport of model amino acids and glucose.

Prior studies in rodents, sheep, and subhuman primates have shown that ethanol, especially after chronic exposure, inhibits the transport of amino acids by the placenta. A small decrease in glucose transport by rat placenta chronically exposed to ethanol has also been noted. With human placental slices, however, only pharmacological (high) concentrations of ethanol impaired uptake of amino acids, and there are no data on glucose transport. In the present study, the effect of brief exposure to ethanol on human placental transport of model amino acids and glucose was studied by two techniques not previously jointly employed for this--the perfused human placental cotyledon and human placental vesicle systems. The nonmetabolizable amino acids, alpha-aminoisobutyric (AIB) acid and cycloleucine (CLEU), as well as D-glucose, and nonmetabolized glucose (3-O-methyl-D-glucose), were used as probes. AIB and CLEU are transferred normally by active transport and D-glucose by facilitated transport from maternal to fetal compartments. The perfused placental system was exposed to ethanol (300-500 mg%) for 2-4 hr and the vesicles to 200-400 mg% ethanol for times varying from 10 min to 48 hr. There was no impairment of AIB, D-glucose, or 3-O-methyl-D-glucose transfer by ethanol using these techniques. Normally, about 60% of AIB transport by human placenta is sodium dependent. This component (using the vesicle system) was also not impaired by ethanol. Ethanol caused a very small decrease of CLEU clearance by the perfused human placenta (p = 0.05) but not using vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of attitude and expectation on moods and symptoms during cold weather military training.

The present study examined the influence of the following: 1) air temperature, 2) day into training, 3) self rating of life stress, 4) rating of relative warmth in cold weather, and 5) expectation for liking cold weather training, on 59 soldiers' self-reports of illness and mood during 3 days of training in the cold (-18 degrees to 0 degree C range). Mood was assessed on six domains of the Profile of Mood States rating scale, and symptoms of illness were assessed on 5 domains of the Environmental Symptoms Questionnaire. Multiple regression analyses showed that: 1) the more soldiers expected to dislike the cold weather training, the more tense, depressed, angry, fatigued, and physically uncomfortable they were during training; 2) the more stress they perceived in their everyday lives, the more fatigued, confused, and physically uncomfortable they were during training; 3) as days into training increased the more fatigued and physically uncomfortable they became; and 4) due to appropriate clothing and training, ambient temperature was found to have no significant influence on the soldiers' moods and symptoms.

Adult↗

Retinohypothalamic projections in the hamster and rat demonstrated using cholera toxin.

The organization of retinohypothalamic tract (RHT) projections in the rat and hamster was studied using anterograde transport of cholera toxin conjugated to HRP (CT-HRP). In both species the major RHT projections lead to the suprachiasmatic nuclei (SCN). This projection begins in the rostral SCN as a loose plexus in the hamster and a a dense aggregation of terminals along the chiasmal border in the rat. Through the remainder of the SCN there is a very dense terminal plexus in the ventral and lateral part of the nucleus with fewer terminals present medially. The RHT projection to the SCN is greater contralaterally in the rat whereas in the hamster the contralateral and ipsilateral projections are approximately equal. In addition to projections to the SCN, the RHT projects to the anterior hypothalamic area, the retrochiasmatic area and lateral hypothalamic area in both species. The anterior hypothalamic projections are more extensive in the hamster than in the rat and extend into the perifornical region, the dorsal hypothalamus and zona incerta. The SCN and anterior hypothalamic projections are continuous with a projection to the retrochiasmatic area and, in the hamster, with a projection extending into the subparaventricular zone with some axons and terminals continuing into the paraventricular nucleus. In contrast to these, the lateral hypothalamic projection in the rat is more extensive than in the hamster. Albino and pigmented rats show identical projections. In addition to the hypothalamic projections, there is in the hamster a small projection along the base of the telencephalon to the anterior amygdaloid area and cortical amygdaloid nucleus and a very sparse projection to the anterior thalamic nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Loss of entrainment and anatomical plasticity after lesions of the hamster retinohypothalamic tract.

The suprachiasmatic nuclei receive photic input information directly through a retinohypothalamic tract (RHT) and indirectly through a projection from the intergeniculate leaflet of the lateral geniculate complex, the geniculohypothalamic tract (GHT). Prior work has established that the RHT is sufficient for entrainment, but has not shown whether it is necessary because it has not been possible to transect that pathway. The present study addresses this problem by employing knife cuts to sever the RHT in male hamsters. Three knife cut procedures were used and one of these succeeded in separating the SCN from the optic chiasm in 8 animals with limited damage to the chiasm and the SCN. The effectiveness of the RHT lesion was confirmed by cholera toxin-HRP histochemistry which demonstrated that the knife cuts eliminate the normal retinal innervation of the SCN while sparing projections to thalamic and tectal visual centers. In a light-dark cycle, the lesioned animals exhibit free-running rhythms indicating that the RHT is necessary for entrainment. A surprising observation is the presence of extensive axonal sprouting of retinal fibers in brains of animals with RHT lesions. The newly-formed axons grow extensively into the SCN, anterior hypothalamus and basal forebrain, but form anomalous axonal plexuses which have no evident function.

Animals↗

Running wheel activity in hamsters with hypothalamic damage.

The amount of wheel running activity by hamsters sustaining damage to the suprachiasmatic nuclei, adjacent hypothalamic areas or lateral geniculate nuclei was examined with numerical and actogram methods. The various hypothalamic lesions reduced activity in a region-specific fashion. Damage to the suprachiasmatic nuclei was associated with the most profound decrease in activity. Reduced daily wheel running was not necessarily correlated with lower activity levels as estimated from the actogram. Some animals with greatly reduced activity had actogram records with apparent increases in activity. The inconsistency between the actogram and numerical analysis was the product of an interaction between changes in running rate and length of activity bouts after lesions. These data indicate a role for the suprachiasmatic region in the regulation of level of activity. The analyses also show that the standard actogram can be a very poor index of changes in activity.

Activity Cycles↗

Lateral geniculate lesions block circadian phase-shift responses to a benzodiazepine.

Several pharmacological treatments, including application of an excitatory neurotoxin to the lateral geniculate nucleus (LGN) and systemic administration of triazolam, a clinically effective benzodiazepine, can elicit large phase shifts in a circadian rhythm according to the time of administration. The hypothesis that the LGN might mediate the effect of triazolam on circadian clock function was tested. Bilateral lesions of the LGN, which destroyed the connection from the intergeniculate leaflet to the suprachiasmatic nucleus, blocked phase-shift responses to triazolam. The requirement of an intact LGN for triazolam to shift circadian phase suggests that the LGN may be a site through which stimuli gain access to the circadian clock to modulate rhythm phase and entrainment.

Animals↗

A comparative evaluation of the transport of H2-receptor antagonists by the human and baboon placenta.

Using a single cotyledon perfusion model, the placental transport of four H2-receptor antagonists, cimetidine, famotidine, nizatidine, and ranitidine, was determined and compared using normal term human and normal preterm baboon placentas. In both the human and baboon placentas, the transport of each agent was similar whether administered singly or in combination with the other drugs. Drug transport was the same in both directions, maternal-to-fetal and vice versa, indicating a lack of preferential transfer. The H2-receptor antagonists were transported at about 40% the rate of the freely diffusable reference compound, antipyrine. There were no significant differences between the human and baboon in any of the parameters of placental function evaluated. Placental glucose and oxygen consumptions, and lactate production were comparable in the human and baboon preparations. The transport and clearance of each of the H2-antagonists were similar in each species.

Adolescent↗

Renal transplant dysfunction: MR evaluation.

The results of 45 MR examinations were prospectively compared with the clinical course and biopsy results in 38 renal transplant patients to determine the role of MR in evaluating allograft dysfunction. Twenty-six patients underwent allograft biopsy. In eight patients in whom the biopsy was performed more than 48 hr after MR examination and in 19 patients who did not have a biopsy, the subsequent clinical course was sufficiently diagnostic to determine the specific cause of the transplant dysfunction. Corticomedullary differentiation, graded from 0 to 3, was not helpful in separating rejection (n = 20) from acute tubular necrosis (n = 9), drug toxicity (n = 7), pyelonephritis (n = 2), or normal grafts (n = 7) because of overlap between groups (sensitivity =; 60%, specificity = 60%). In the six patients with two or more MR studies, serial changes in corticomedullary differentiation were not consistent and could not be used to diagnose rejection. When any abnormality of allograft sinus fat, size or shape, or corticomedullary differentiation was considered, the sensitivity for the diagnosis of rejection approached 80%; however, specificity was low (48%). We conclude that MR imaging is not sufficiently accurate to replace transplant biopsy and therefore has a limited role in the evaluation of transplant dysfunction.

Cyclosporins↗

Left ventricular aneurysm in short axis: a comparison of magnetic resonance, ultrasound and thallium-201 SPECT images.

Short axis magnetic resonance images of a left ventricular aneurysm were compared to similar views obtained by echocardiography and by thallium-201 single photon emission computed tomography. Images of the dyskinetic left ventricular apex and the contractile left ventricular base were analyzed and compared. Unlike the previously reported orthogonal plane magnetic resonance images, short axis imaging provided representative and quantitative information in views comparable to those obtained by standard noninvasive imaging techniques. These data indicate that short axis magnetic resonance imaging is capable of identifying and sizing the aneurysmal and the residual segments of the left ventricle. The findings may be of prognostic value in patients with left ventricular aneurysm.

Coronary Aneurysm↗

Human placental transport of cimetidine.

This study addresses the mechanism of transport of the H2-receptor antagonist, cimetidine, by the human placenta. A 4-h recycling perfusion of a single placental cotyledon of normal, term, human placenta was used. At a maternal concentration of 1 microgram/ml, cimetidine clearance from the maternal circulation was 0.58 +/- 0.16 ml/min per g placenta, a rate about one third that of antipyrine. There was no evidence of cimetidine metabolism by the placenta. Transfer of cimetidine from maternal to fetal compartments showed no saturation kinetics and was not inhibited by putative carrier competitors. Cimetidine did not accumulate against a drug concentration gradient. Fetal clearance of cimetidine was similar to maternal clearance. Studies with placental apical vesicles confirmed lack of saturability of cimetidine transport and of its concentration within vesicles. Thus, (a) cimetidine is transported across the human placenta bidirectionally at a rate about one third that of antipyrine, (b) the drug is not metabolized by the placenta, and (c) the transport is a passive one.

Adolescent↗

Effect of H2-receptor antagonists on steady-state extraction of indocyanine green and lidocaine by the perfused rat liver.

Variable effects of cimetidine on the clearance in humans of the high-clearance compounds lidocaine and indocyanine green have been reported, some investigators finding a reduction and others no change. We measured the extraction of indocyanine green, which is not metabolized and of lidocaine, which is metabolized by the perfused rat liver, in an open system with a fixed flow rate. The extraction ratios of both indocyanine green (ERICG) and lidocaine (ERL) were determined under control conditions and during continuous infusion of cimetidine and other H2-receptor antagonists (ranitidine, nizatidine, and ICI 125,211) on separate occasions. The effects of increasing concentrations of cimetidine and ranitidine were measured, and single concentrations of nizatidine and ICI 125,211 were used. Indocyanine green was measured spectrophotometrically or by high-performance liquid chromatography (HPLC). Lidocaine concentrations in perfusate were measured by gas chromatography, and H2-receptor antagonist levels in perfusate and in liver by HPLC. The perfused rat liver extracted indocyanine green (ERICG = 0.43 +/- 0.04) and lidocaine (ERL = 0.78 +/- 0.01) with steady state being reached within 5 minutes. Neither cimetidine nor ranitidine altered steady-state indocyanine green extraction. In contrast, ERL was decreased by all four H2-receptor antagonists but with differing potencies. In this system, cimetidine was the most potent agent, reducing ERL by 28.5% at a cimetidine concentration of 56 mumol/L. The other H2-receptor antagonists also decreased ERL:ICI 125,211 by 20% (49 mumol/L), ranitidine by 13% (38 mumol/L), and nizatidine by 9% (43 mumol/L). A dose-response relationship for cimetidine and ranitidine was developed, confirming the greater potency of cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Grooming reflexes and Brown-Séquard epilepsy in cats with pontile lesions.

The literature on the relation between the scratch reflex and Brown-Séquard epilepsy in the guinea pig indicates that the scratch reflex is a stimulus-induced myoclonus that is the first component of a complete seizure. Cats with pontile lesions and cats with frontal neocortical lesions exhibit the scratch reflex and other grooming reflexes. The grooming reflexes in cats with pontile lesions develop over a period of a year or more into complete seizures that are similar to Brown-Séquard epilepsy as described for the guinea pig by Brown-Séquard and others. Cinematographic analyses revealed that the scratch reflex in cats with pontile lesions and in cats with frontal neocortical lesions has the same frequency and the same complex spatial and temporal pattern as normal scratching behavior. In addition, the myoclonus of the complete seizures is identified as the scratch reflex, representing a very vigorous and long-lasting afterdischarge. Reconstruction of the pontile lesions indicate that the lateral and rostral portions of the paralemniscal tegmental fields were destroyed along with portions of the pontile gray and pyramidal tract.

Animals↗