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Biomedical subjects

J A Carr

Publications and source records attributed to J A Carr.

At least 37 records · Page 2Linked to original sources

Characterization of [125I]beta-endorphin binding sites in the rat caudal dorsomedial medulla.

[125I]beta-endorphin bound to high affinity (Kd = 0.25 nM) receptors in the caudal dorsomedial medulla of rats with a Bmax of 97 fmol/mg protein. The relative potency for displacement of [125I]beta-endorphin binding was: beta-endorphin(1-31) > beta-endorphin(1-27) > DAMGO > naloxone > N-acetyl-beta-endorphin(1-31) > U50488 > DPDPE. The Bmax for [3H]DAMGO binding was 81 fmol/mg protein, indicating that most [125I]beta-endorphin binding corresponds to mu-opioid receptors. [3H]DAMGO binding was not influenced by lesioning noradrenergic nerve terminals in the caudal dorsomedial medulla. Our findings indicate that beta-endorphin interacts primarily with mu-opioid receptors in the caudal dorsomedial medulla. These receptors are not affected by noradrenergic denervation.

Animals↗

Alterations in brain and pituitary beta-endorphin content in genetically epilepsy-prone rats.

We measured beta-endorphin concentrations in the anterior and neurointermediate lobes of the pituitary gland and in microdissected brain regions of moderate-seizure genetically epilepsy-prone rats (GEPR-3), severe-seizure GEPR-9s and Sprague-Dawley non-epileptic control rats. Plasma concentrations of beta-endorphin and beta-melanocyte-stimulating hormone (alpha-MSH) were also measured as indicators of pituitary POMC-peptide secretion. Concentrations of beta-endorphin in the anterior lobe of GEPR-3s were 53% higher compared to controls and 57% higher compared to GEPR-9s. There were no differences in neurointermediate lobe beta-endorphin concentrations between control and either GEPR strain. Plasma beta-endorphin concentrations were significantly lower in GEPR-9s than controls. Plasma levels of alpha-MSH did not differ between control and GEPRs. In the hypothalamus of GEPR-9s beta-endorphin concentrations in the arcuate nucleus were significantly greater than in GEPR-3s. Concentrations of beta-endorphin in the central amygdala of GEPR-9s were two- to threefold greater than in control or GEPR-3s. Beta-Endorphin concentrations in the central gray of GEPR-3s were 58% lower than control or GEPR-9s. These data suggest that anterior lobe beta-endorphin secretion is reduced in GEPR-9s. Furthermore, brain endorphinergic pathways appear to be differentially altered in GEPR-3s and GEPR-9s. Alterations in pituitary beta-endorphin secretion and brain endorphinergic systems may contribute to seizure susceptibility in GEPRs and to differences in seizure severity between GEPR-3s and GEPR-9s.

Animals↗

Spigelian hernia with Crohn's appendicitis.

We present a case report of a young man found to have Crohn's appendicitis in an incarcerated spigelian hernia, initially diagnosed via laparoscopy. We have found two published cases of incarcerated appendicitis in spigelian hernias; however, only one of them also showed histologic evidence of Crohn's disease, and neither was discovered during laparoscopy. Therefore, we submit this rare case presentation and discuss the advantages of laparoscopy as an aid in diagnosing the cause of chronic abdominal pain.

Adult↗

Interactions of androgens and estradiol on sex accessory ducts of larval tiger salamanders, Ambystoma tigrinum.

Immature tiger salamander larvae were treated with 12.5 or 25 micrograms of estradiol, testosterone, or dihydrotestosterone (DHT), or 12.5 micrograms of estradiol combined with 12.5 micrograms of either testosterone or DHT. Müllerian duct epithelium was more stimulated by combined steroid treatment than by any steroid alone. Estradiol antagonized the action of DHT in the Wolffian duct. Both of the androgens and estradiol when administered alone at the higher dose stimulated enlargement of connective tissue surrounding the ducts, but the combined 12.5 micrograms androgen/12.5 micrograms estrogen treatment was more effective even though the total steroid administered was the same. The effectiveness of DHT on müllerian cells of this species is evidence against a required aromatization of androgens to explain paradoxical steroid effects and suggests that fundamental differences may exist in steroid receptors of müllerian ducts, connective tissue, and Wolffian ducts. A possible role for the urodele duct system for assessing estrogenic activity of environmental contaminants is discussed.

Ambystoma↗

Beta-endorphin inhibition of endogenous norepinephrine release from the A2 noradrenergic nucleus in vitro: role of mu opiate receptors and Na+ ion permeability.

An in vitro approach was used to determine the opioid receptor subtype mediating beta-endorphin inhibition of endogenous norepinephrine release from the A2 nucleus in the caudal dorsomedial medulla of rats. The voltage-sensitive Na+ channel blocker tetrodotoxin was used to investigate the role of Na+-dependent action potentials in beta-endorphin inhibition of K+-evoked norepinephrine release. Human beta-endorphin(1-31) inhibited K+-evoked norepinephrine release in a concentration-dependent fashion. Activation of delta- and kappa-opioid receptors had no effect on endogenous norepinephrine release. The inhibitory effect of beta-endorphin was blocked in a concentration-dependent manner by the mu-opioid receptor antagonist CTOP (Cys2, Tyr3, Orn5, Pen7 amide). Tetrodotoxin (TTX) inhibited norepinephrine release evoked by 25 mM K+ in a concentration-dependent manner and blocked the inhibitory effects of beta-endorphin. These results indicate that beta-endorphin acts on mu-opioid receptors to inhibit K+-evoked norepinephrine release from A2 neurons and suggest that the receptors involved are not located on noradrenergic nerve terminals.

Adrenergic Fibers↗

Rats use an ordinal timer in a daily time-place learning task.

Rats received 2 daily sessions in a large clear chamber. A lever was mounted on each of the 4 chamber walls. For each rat, a different lever provided food during 0930 and 1530 sessions. The rats learned which lever would provide food at 0930 and 1530. Probe tests suggested that the rats learned to press 1 lever during their 1st session of each day and to then press a 2nd lever during their 2nd session of each day. We propose that this knowledge of the order of a set of events within a period of time constitutes ordinal timing. We contrast the temporal information provided by ordinal, phase, and interval timing and consider why multiple timing systems have evolved in animals.

Animals↗

Interleukin-12 exhibits potent antiviral activity in experimental herpesvirus infections.

The prophylactic and therapeutic efficacy of interleukin-12 was studied by using murine models of herpes simplex virus infection. Prophylactic administration consisted of two intraperitoneal doses of interleukin-12 given 48 and 24 h prior to infection. Therapeutic intraperitoneal administration of interleukin-12 commenced 6 h after the mice were infected with herpes simplex virus and was continued daily for a total of 5 days. Interleukin-12 therapy improved the survival rates of mice with systemic herpes simplex virus infection compared with those of placebo-treated infected mice. Subcutaneous administration of interleukin-12 also improved the rate of survival of mice after systemic herpes simplex virus infection, although higher doses were required to give comparable effects. Combined prophylactic and therapeutic administration of interleukin-12 produced the greatest effect on survival after an otherwise lethal systemic infection. Intraperitoneal administration of interleukin-12 for 2 days before and 3 days after systemic infection with herpes simplex virus resulted in survival of 80% of the mice. These surviving mice were resistant to subsequent reinfection with herpes simplex virus. Such resistance was apparently specific for herpes simplex virus infection, since a second group of survivors succumbed to a lethal infection with murine cytomegalovirus. Infectious virus was recovered from lumbar ganglia explants dissected from survivors of prophylactic interleukin-12 therapy and cultured for 5 days in vitro, suggesting that interleukin-12 treatment did not prevent the establishment of latent herpes simplex virus infection. One action of interleukin-12 may be to enhance natural killer cell-mediated clearance of the virus. However, interleukin-12 therapy was also effective in mice carrying the beige mutation, which reduces natural killer cell lytic activity, suggesting that interleukin-12 has additional activities in vivo.

Acyclovir↗

Alterations in brain and plasma concentrations of alpha-melanocyte-stimulating hormone during habituation of prey-catching behavior in toads.

Alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH) promote habituation of prey-catching behavior in toads. We tested the hypothesis that habituation is associated with alterations in the activity of alpha-MSH neurons in a toad, Bufo cognatus. We used immunocytochemistry and RIA to determine the organization and distribution of alpha-MSH neurons in the brain. In addition, we measured brain alpha-MSH and plasma concentrations in toads at different times before and during stimulus specific habituation of the turning response to a rotating prey dummy. Cell groups immunoreactive for alpha-MSH-/and ACTH were detected only in the infundibular hypothalamus. Projections from these cells innervated the olfactory nucleus, nucleus accumbens, septum, habenular nucleus, the preoptic area, the hypothalamus, the caudal thalamus, optic tectum and brain stem. The rank order of alpha-MSH concentrations in the brain of Bufo cognatus was caudal thalamus/hypothalamus (T/HT) > preoptic area (PO) > or = rostral telencephalon (Tel) > brain stem (BS) > optic tectum (OT). The only difference observed in tissue alpha-MSH levels between habituated and non-habituated toads was an elevation in T/HT alpha-MSH levels in control toads after 20 min in the testing apparatus. In contrast, many differences were observed in both groups as a function of time spent in the test apparatus. Concentrations of alpha-MSH in the T/HT and PO increased while concentrations in the Tel decreased over time for both control and habituated toads. Plasma alpha-MSH titers rose over time in control toads but not in habituated toads. Our findings suggest that habituation per se is not associated with dramatic alterations in brain or plasma alpha-MSH levels. On the other hand, prolonged confinement causes pronounced alterations in the activity of brain and pituitary proopiomelanocortin cells.

Animals↗

Interleukin-12 and infectious diseases: a potential novel therapy.

Interleukin-12 (IL-12) is emerging as a central component of both innate and acquired immunity. The multiplicity of biological activities associated with this cytokine, particularly the stimulation of cell-mediated immunity, suggests that it may be crucial in the control of extracellular and intracellular infections. In in vitro studies, IL-12 production is initiated rapidly after infection with a variety of viral, parasitic, fungal and bacterial agents. This induction correlates well with the reported resistance or susceptibility of animals to infection with these agents. Other factors may, however, influence responses in vivo, including host genetic make-up, microbial load and the induction of antagonistic cytokine pathways, notably IL-4 and IL-10. In some situations, IL-12 may direct immune responses to inappropriate pathways, and worsen disease, so that careful consideration of the type of required immune response is needed before IL-12 therapy is initiated. IL-12 treatment may also be useful in promoting protective immune responses to vaccines, allowing systemic immunisation with lower doses, or even normally non-immunogenic preparations, of antigen. Finally, IL-12 has been demonstrated to act in concert with standard antimicrobial chemotherapy in viral, parasitic, fungal and bacterial infections, allowing a reduction in the dose of the agent used and providing hope that such combination therapy may more effectively control drug-resistant strains of infectious agents.

Journal Article↗

An atypical recurrence of endometrial carcinoma following estrogen replacement therapy.

Following an abdominal hysterectomy and bilateral salpin-goophorectomy wherein a superficial (1.6 mm) well-differentiated endometrial cancer and bilateral ovarian serous cystadenomas were discovered, estrogen replacement was given. One year later the patient presented with a 9 x 7-cm left groin recurrence. Patients with endometrial carcinoma may request estrogen replacement. The benefits of such replacement are well recognized; however, these patients also need to be counselled that hormonal replacement may be complicated by recurrence. Physicians need to be cognizant of symptoms or signs which would suggest disease recurrence at unusual sites in these patients who are perceived as being at low risk for recurrent disease.

Adenocarcinoma↗

The effects of melanocortin peptides and corticosterone on habituation in the great plains toad, Bufo cognatus.

We investigated the ability of various melanocortin peptides and corticosterone to influence habituation of prey-catching behavior in the toad, Bufo cognatus. Male toads were injected with various melanocortin peptide fragments or corticosterone 30 min prior to acquisition. Adrenocorticotropin (ACTH[1-39]), ACTH[4-10], and N-acetyl ACTH[1-13] amide (alpha-MSH) significantly decreased the number of turning reactions during acquisition in relation to controls. The effects of the noncorticotropic ACTH fragments were rapid and transient, occurring within the first 20 min of acquisition. Corticosterone caused a slight but significant decrease in the number of turning reactions. Neither des-acetyl alpha-MSH nor (Nle4, D-Phe7) alpha-MSH had any effect on acquisition. ACTH[1-39] was the only peptide that delayed extinction. The ability of alpha-MSH to facilitate acquisition was not observed in the presence of the alpha-MSH antagonist U-76188E. These data suggest that the effects of ACTH on habituation are, in part, independent of effects on glucocorticoid secretion. Apparently, similar structural requirements are necessary for the behavioral effects of melanocortins in amphibians and mammals.

Adrenocorticotropic Hormone↗

Diurnal variation in alpha-melanocyte-stimulating hormone content of various brain regions and plasma of the Texas toad, Bufo speciosus.

We measured the concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH) in various brain regions as well as in the pituitary gland and plasma of the toad Bufo speciosus during a 24-hr light:dark cycle. There was significant diurnal variation of alpha-MSH concentrations in the hypothalamus and brainstem. In both areas alpha-MSH concentrations were highest during the scotophase. Peak alpha-MSH concentrations in the hypothalamus were observed at 21.00 and 05.00 hr, while a single peak in alpha-MSH concentrations was observed in the brainstem at 21.00 hr. In contrast, peak alpha-MSH concentrations in the plasma were observed during the photophase at 17.00 hr, when brain concentrations of alpha-MSH were low. There was no significant diurnal variation observed in the pituitary content of alpha-MSH throughout the 24-hr light:dark cycle. These data suggest that different mechanisms control hypothalamic and pituitary alpha-MSH cells in the toad during the 24-hr light:dark cycle. The fact that peak alpha-MSH concentrations were observed in the hypothalamus during the activity period of the toad is consistent with the proposed role of alpha-MSH peptides in learning and memory processes.

Animals↗

Opioid peptide inhibition of endogenous norepinephrine release from the A2 noradrenergic cell group in vitro.

We investigated the potential influence of opioid and melanotropic peptides on endogenous norepinephrine (NE) release from the A2 noradrenergic cell group of rats using a static, fixed-volume incubation procedure. Norepinephrine release from slices of caudal dorsomedial medulla (CDMM) was evoked by high potassium concentrations (20 and 60 mM) in a Ca(2+)-dependent and dose-related manner. Treatment with the potent melanotropin agonist [Nle4,D-Phe7] alpha-MSH(NDP-MSH) had no effect on K(+)-induced NE release. In contrast, human beta-endorphin1-31 significantly reduced K(+)-stimulated NE release, but not in the presence of naloxone. The highly-selective mu-opioid agonist [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) also significantly reduced evoked NE release. The inhibitory effect of DAMGO was completely blocked by naloxone. Naloxone alone did not alter evoked NE release. The inhibitory effect of DAMGO was not enhanced by reducing the stimulatory concentration of K+. None of the peptides tested influenced basal NE release. These data indicate that melanotropin receptors do not regulate NE release in CDMM. In contrast, the opioid peptides DAMGO and beta-endorphin inhibit K(+)-stimulated release of endogenous NE. These data suggest a role for mu-opioid receptors in controlling NE release from A2 noradrenergic neurons.

Animals↗

Hereditary sensory and autonomic neuropathy with cataracts, mental retardation, and skin lesions: five cases.

We report the clinical and electrophysiologic data on five subjects from two families with severe sensory and autonomic neuropathy who also exhibited peroneal muscular atrophy with the electrophysiologic features of an axonopathy, congenital cataracts, mental retardation, and skin lesions. One patient had hearing loss. Autosomal recessive inheritance was probable in both families.

Adult↗

Evaluation of a high-density polytetrafluoroethylene (n-PTFE) membrane as a barrier material to facilitate guided bone regeneration in the rat mandible.

The purpose of this investigation was to evaluate the use of high-density polytetrafluorethylene (n-PTFE) membranes to facilitate guided tissue regeneration (GTR) in the rat. The concept of guided tissue regeneration is based on the hypothesis that if the non-osteogenic connective tissue cells are mechanically blocked from entering a bone defect, selective re-population of the defect by osteoblasts will occur. Bilateral through-and-through defects of critical size were created in the mandibular angle of 12 rats. The experimental side was covered on both the medial and lateral aspects of the mandible with high-density n-PTFE membrane, with the opposite side serving as a control. Histological analysis revealed osteogenic tissue completely bridging the defect by two weeks. After six weeks of healing, osteogenic repair was observed at the margins of the defects, with islands of woven bone seen in the central areas. After 10 weeks of healing, complete ossification was observed on the n-PTFE-treated side. The control defects exhibited very little osseous regeneration, and rounding of the defect margins was observed after 10 weeks of healing. These results indicate that high-density n-PTFE can serve effectively as a guided tissue regeneration barrier in certain bone defects.

Animals↗

Effects of the enkephalin analog (D-Met2,Pro5)-enkephalinamide on alpha-melanocyte-stimulating hormone secretion.

We used the met-enkephalin analog (D-Met2,Pro5)-enkephalinamide (DMPEA) to investigate enkephalinergic control of alpha-melanocyte-stimulating hormone (alpha-MSH) secretion. Systemic (s.c.) administration of DMPEA elevated plasma titers of alpha-MSH in a dose- and time-related manner. Pretreatment with the opiate antagonist naltrexone had no effect on basal plasma levels of alpha-MSH but blocked DMPEA-induced alpha-MSH release. Treatment with a dose of naltrexone sufficient to block DMPEA-induced secretion of alpha-MSH had no effect on stress-induced secretion of alpha-MSH. Although pretreatment with the dopamine receptor agonist apomorphine prevented DMPEA-induced alpha-MSH secretion, DMPEA had no effect on the synthetic activity of tuberohypophysial dopamine neurons as gauged by measuring the accumulation of 3,4-dihydroxyphenylalanine in the neurointermediate lobe (NIL) following administration of NSD-1015. In vitro treatment of isolated NILs with DMPEA resulted in a significant increase in alpha-MSH release. Naltrexone completely blocked the stimulatory effects of DMPEA on alpha-MSH release in vitro. Our results indicate that DMPEA stimulates alpha-MSH secretion by acting directly through opiate receptors at the level of the NIL.

Animals↗

Alterations in spleen norepinephrine and lymphocyte [3H]dihydroalprenolol binding site number in genetically epilepsy-prone rats.

Noradrenergic neurotransmission plays an important role in normal immune reactivity. Genetically epilepsy-prone (GEPR-9) rats exhibit deficits in central noradrenergic systems and diminished plaque-forming cell responses following immunization in vivo. In the present study we examined the hypothesis that immunosuppression in GEPR-9 rats is associated with alterations in the splenic noradrenergic system. The content of norepinephrine (NE) in spleens of GEPR-9 age-matched nonepileptic Sprague-Dawley control rats was determined by high-performance liquid chromatography coupled with electrochemical detection (HPLC-EC). In addition, we measured the number of beta-adrenergic receptors on splenic lymphocyte membranes of GEPR-9 and control rats using the beta-adrenergic receptor antagonist dihydroalprenolol ([3H]DHA). HPLC-EC analysis revealed that splenic norepinephrine content was significantly greater in GEPR-9 rats than in controls. Results from receptor binding studies indicated a 33% reduction in specific binding of [3H]DHA to splenic lymphocyte membranes of GEPR-9 rats. Saturation of binding studies revealed a significant decrease in the maximum number of [3H]DHA binding sites on splenic lymphocyte membranes from GEPR-9 rats. These results indicate that the noradrenergic system in GEPR-9 rat spleen is altered. Whether either or both of these changes contribute to reduced immune reactivity in GEPR-9 rats remains to be determined.

Animals↗