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D O'Donnell

Publications and source records attributed to D O'Donnell.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression of thyrotropin-releasing hormone receptor 2 (TRH-R2) in the central nervous system of rats.

The distribution of the recently discovered thyrotropin-releasing hormone (TRH) receptor subtype TRH-R2 was studied in rat brain, pituitary, and spinal cord by in situ hybridization histochemistry and compared with the distribution patterns of the other elements of TRH signaling, namely TRH, TRH-R1, and the TRH-degrading ectoenzyme (TRH-DE). In contrast to the very restricted mRNA expression of TRH-R1 in the central nervous system, TRH-R2 mRNA was widely distributed with highest transcript levels throughout the thalamus, in the cerebral and cerebellar cortex, medial habenulae, medial geniculate nucleus, pontine nuclei, and throughout the reticular formation. In accordance with the well-known endocrine function of TRH, TRH-R1 is found predominantly expressed in hypothalamic regions. Expression of TRH-R1 in various brainstem nuclei and spinal cord motoneurons seems to be associated with the described effects of TRH on the vegetative and autonomic system as well as on the somatomotor system. Furthermore, the fully complementary expression of both receptor subtypes, even in regions where transcripts for both receptors were found (e.g., medial septum, lateral hypothalamus superior colliculi, substantia nigra, etc.), indicates that in discrete neuroanatomical pathways the two receptors serve highly specific functions for the transmission of TRH signals. Together with TRH-DE, the putative terminator of TRH actions that shows in various, but not all, brain areas, an overlapping mRNA distribution pattern with both receptors, the distribution of TRH-R2 mRNA seems to provide the anatomical basis for the described effects of TRH on higher cognitive functions as well as its effect on arousal, locomotor activity, and pain perception.

Aminopeptidases↗
PubMed2000

Intradermal microdialysis: kinetics of iontophoretically delivered propranolol in forearm dermis.

Intradermal microdialysis permits us to measure the concentration in dermis of drugs applied to the skin. Microdialysis is especially efficient in sampling water-soluble molecules. Consequently, it appears particularly suitable to study current based delivery systems like iontophoresis that deliver ions or highly polar molecules. The purpose of this work was to evaluate the adequacy of a skin microdialysis technique to characterize and quantify the dermatopharmacokinetics of iontophoretically delivered propranolol in the dermis of healthy human volunteers. Linear microdialysis probes were inserted in the subject's forearm skin and an iontophoresis device was installed above them. Constant current was applied for two periods of 1 h each separated by a 1-h interval. Dialysate samples were collected every 6 min for 4.4 h and analyzed by HPLC. Probes were always placed in the dermis as measured by ultrasonography. Propranolol was detectable in the dialysate. It was possible to build detailed concentration vs. midtime profiles that mirrored the current applied. Elimination rate from the dermis had first-order kinetics and was similar in all subjects. Quantification of the absorption process, indexed by lag-time and area under the concentration curve showed a high inter- and intrasubject variability that did not correlate with probe depth.

Adult↗
PubMed2000

Pathways from emotional adjustment to glycemic control in youths with diabetes in Hong Kong.

OBJECTIVE: To examine factors that influence emotional adjustment, adherence to diabetic care, and glycemic control in Hong Kong youths with insulin-dependent diabetes mellitus (IDDM). METHODS: Seventy youths, their mothers, and matched controls provided information on health beliefs, authoritarian parenting style, parent-child conflict, emotional adjustment, and adherence to medical regimen. Glycosylated hemoglobin levels were obtained to measure glycemic control. RESULTS: Predictors explained 34% of the variance in emotional adjustment and 39% of the variance in glycemic control. The data supported a pathway from emotional adjustment to self-efficacy to adherence behaviors to glycemic control. In contrast to Western culture and consistent with prediction, parenting style did not associate with negative outcomes, and even relatively low levels of parent-child conflict correlated negatively with emotional adjustment in this culture. CONCLUSIONS: Management of conflict and self-efficacy enhancing interactions are suggested interventions to enhance adherence to diabetic care in Hong Kong youths with IDDM.

Adaptation, Psychological↗
PubMed1999

Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: distinct distribution from GALR1.

Recent molecular cloning studies by our laboratory and others have identified the existence of a novel rat galanin receptor subtype, GALR2. In the present study, we examined the regional and cellular distribution of GALR2 mRNA in the rat central nervous system (CNS) by in situ hybridization. For comparative purposes, adjacent sections were probed for GALR1 mRNA expression. Our findings indicate that dorsal root ganglia express by far the highest levels of GALR2 mRNA in the rat CNS. Hybridization signal is mainly concentrated over small and intermediate primary sensory neurons. In spinal cord, the large alpha motoneurons of the ventral horn are moderately labeled and several small, but less intensely labeled, cells are scattered throughout the gray matter. In brain sections, the highest levels of GALR2 mRNA are detected in granule cells of the dentate gyrus, in the mammillary nuclei, and in the cerebellar cortex. Moderate levels of GALR2 mRNA are observed in the olfactory bulb, olfactory tubercle, piriform and retrospinal cortices, hypothalamus (namely the preoptic area, arcuate nucleus, and dorsal hypothalamic area), substantia nigra pars compacta, and sensory trigeminal nucleus. Moderate to weak hybridization signal is also present in several other hypothalamic nuclei, specific layers of the neocortex, periaqueductal gray, and several nuclei within the pons and medulla, including locus coeruleus, lateral parabrachial, motor trigeminal, pontine reticular, hypoglossal, vestibular complex, ambiguus, and facial and lateral reticular nuclei. This novel pattern of GALR2 distribution within the rat CNS differs considerably from that of GALR1, suggesting that specific physiologic effects of galanin may be ascribed to the GALR2 galanin receptor subtype.

Age Factors↗
PubMed1999

Iontophoretic current and intradermal microdialysis recovery in humans.

When microdialysis (MD) is used to study dermal delivery by iontophoresis, the effects of current may alter MD recovery through an increase in temperature, a change of pH, hyperemia, and dermal hydration. The objective of this work is to assess whether these effects of current may cause a measurable change in the retrodialysis of a model compound (sodium fluorescein, Fl). Two linear MD-probes were inserted in the forearm dermis of healthy human volunteers and perfused with Ringer's solution containing Fl. Two identical iontophoresis chambers (IC, filled with NaCl in propylene glycol) were placed over the MD-probes. Each IC included a laser Doppler flowmetry probe to monitor skin blood flow. At one IC, current was applied for two periods of 30 min each, separated by 30 min of no current. No current was applied to the control site. Dialysate samples were collected every 5 min and analyzed for Fl by HPLC. Skin blood flow increased in response to iontophoresis, on average, 570% compared to the control site. However, there was no difference in the recovery of Fl between the current-active site versus the control site, and between the period with applied current versus the period with no current. In conclusion, iontophoretic current did not affect intradermal MD recovery.

Administration, Cutaneous↗
PubMed1999

The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor.

Gene-knockout studies of melanin-concentrating hormone (MCH) and its effect on feeding and energy balance have firmly established MCH as an orexigenic (appetite-stimulating) peptide hormone. Here we identify MCH as the ligand for the orphan receptor SLC-1. The rat SLC-1 is activated by nanomolar concentrations of MCH and is coupled to the G protein G alpha i/o. The pattern of SLC-1 messenger RNA expression coincides with the distribution of MCH-containing nerve terminals and is consistent with the known central effects of MCH. Our identification of an MCH receptor could have implications for the development of new anti-obesity therapies.

Animals↗
PubMed1999

Bcl-2 inhibits ischemia-reperfusion-induced apoptosis in the intestinal epithelium of transgenic mice.

Little is known about the effects of ischemia-reperfusion on the inductive, commitment, or execution phases of apoptosis. We have created a genetically defined model to study the response of small intestinal epithelial cells to ischemia-reperfusion injury as a function of their proliferative status and differentiation. Occlusion of the superior mesenteric artery for 20 min in adult FVB/N or C57BL/6 mice results in the appearance of TUNEL-positive apoptotic cells in the jejunal epithelium within 4 h, with a maximum response occurring at 24 h. Stimulation of apoptosis is greater in postmitotic, differentiated epithelial cells located in the upper portions of villi compared with undifferentiated, proliferating cells in the crypts of Lieberkühn (7-fold vs. 2-fold relative to sham-operated controls). Comparisons of p53(+/+) and p53(-/-) mice established that the apoptosis is p53 independent. To further characterize this response, we generated FVB/N transgenic mice that express human Bcl-2 in epithelial cells distributed from the base of crypts to the tips of their associated villi. The fivefold elevation in steady-state Bcl-2 concentration is not accompanied by detectable changes in the levels or cellular distributions of the related anti-apoptotic regulator Bcl-xL or of the proapoptotic regulators Bax and Bak and does not produce detectable effects on basal proliferation, differentiation, or death programs. The apoptotic response to ischemia-reperfusion is reduced twofold in the crypts and villi of transgenic mice compared with their normal littermates. These results suggest that both undifferentiated and differentiated cells undergo a commitment phase that is sensitive to Bcl-2. Forced expression of Bcl-2 also suppressed the p53-dependent death that occurs in proliferating crypt epithelial cells following gamma-irradiation. Thus suppressibility by Bcl-2 operationally defines a common feature of the apoptosis induced in the crypt epithelium by these two stimuli.

Animals↗
PubMed1999

Role of nitric oxide in the vascular effects of local warming of the skin in humans.

Local warming of skin induces vasodilation by unknown mechanisms. To test whether nitric oxide (NO) is involved, we examined effects of NO synthase (NOS) inhibition with NG-nitro-L-arginine methyl ester (L-NAME) on vasodilation induced by local warming of skin in six subjects. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for delivery of L-NAME and sodium nitroprusside. Skin blood flow was monitored by laser-Doppler flowmetry (LDF) at microdialysis sites. Local temperature (Tloc) of the skin at both sites was controlled with special LDF probe holders. Mean arterial pressure (MAP; Finapres) was measured and cutaneous vascular conductance calculated (CVC = LDF/MAP = mV/mmHg). Data collection began with a control period (Tloc at both sites = 34 degrees C). One site was then warmed to 41 degrees C while the second was maintained at 34 degrees C. Local warming increased CVC from 1.44 +/- 0.41 to 4.28 +/- 0.60 mV/mmHg (P < 0.05). Subsequent L-NAME administration reduced CVC to 2.28 +/- 0.47 mV/mmHg (P < 0.05 vs. heating), despite the continued elevation of Tloc. At a Tloc of 34 degrees C, L-NAME reduced CVC from 1.17 +/- 0.23 to 0.75 +/- 0.11 mV/mmHg (P < 0.05). Administration of sodium nitroprusside increased CVC to levels no different from those induced by local warming. Thus NOS inhibition attenuated, and sodium nitroprusside restored, the cutaneous vasodilation induced by elevation of Tloc; therefore, the mechanism of cutaneous vasodilation by local warming requires NOS generation of NO.

Adult↗
PubMed1998

Cloning and evaluation of the role of rat GALR-2, a novel subtype of galanin receptor, in the control of pain perception.

We have identified a novel subtype of galanin receptor (GALR-2) in rat dorsal root ganglia and spinal cord. The open reading frame of GALR-2 is 1116 nucleotides long, encoding a protein of 372 amino acids with a theoretical molecular mass of 40.7 kD. Membranes prepared from stable pools of 293 cells expressing GALR-2, but not wild-type 293 cells, demonstrated high affinity galanin binding sites. Rat galanin and galanin-related peptides M40, C7, M15, and galanin effectively competed for binding; peptide C7 demonstrated a lower affinity for rGALR-2, and all these peptides were agonists at rGALR-2 when assessed on a microphysiometer. Studies on the expression of GALR-2 in various tissues by Northern and in situ hybridization analyses suggest a low abundance but wide distribution of GALR-2 mRNA, including several discrete areas in brain and spinal cord and a high abundance in the dorsal root ganglia.

Amino Acid Sequence↗
PubMed1998

Cloning and characterization of a cDNA encoding a novel subtype of rat thyrotropin-releasing hormone receptor.

A cDNA encoding a thyrotropin-releasing hormone (TRH) receptor expressed in the pituitary was previously cloned (De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) Biochem. J. 284, 891-899; De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) J. Biol. Chem. 267, 25703-25708; Duthie, S. M., Taylor, P. L., Anderson, J., Cook, J., and Eidne, K. A. (1993) Mol. Cell Endocrinol. 95, R11-R15). We now describe the isolation of a rat cDNA encoding a novel subtype of TRH receptor (termed TRHR2) displaying an overall homology of 50% to the pituitary TRH receptor. Introduction of TRHR2 cDNA in HEK-293 cells resulted in expression of high affinity TRH binding with a different pharmacological profile than the pituitary TRH receptor. De novo expressed receptors were functional and resulted in stimulation of calcium transient as assessed by fluorometric imaging plate reader analysis. The message for TRHR2 was exclusive to central nervous system tissues as judged by Northern blot analysis. Studies of the expression of TRHR-2 message by in situ hybridization revealed a pattern of expression remarkably distinct (present in spinothalamic tract, spinal cord dorsal horn) from that of the pituitary TRH receptor (present in hypothalamus, and ventral horn of the spinal cord, anterior pituitary). Therefore, we have identified a novel, pharmacologically distinct receptor for thyrotropin-releasing hormone that appears to be more restricted to the central nervous system particularly to the sensory neurons of spinothalamic tract and spinal cord dorsal horn, which may account for the sensory antinociceptive actions of TRH.

Amino Acid Sequence↗
PubMed1998

Informativeness of child and parent reports on substance use disorders in a sample of ADHD probands, control probands, and their siblings.

OBJECTIVE: To evaluate parent-child agreement on psychoactive substance use disorder (PSUD) reporting among children with attention-deficit hyperactivity disorder (ADHD) and to test whether agreement level could be predicted from measures of parent and child psychopathology and substance use severity. METHOD: The authors examined 348 pairs of child and parent assessments in a sample of 108 ADHD and 68 normal control probands and their 172 siblings aged 12 and older. RESULTS: PSUD rates were higher when the child was the reporter than when the parent was. Agreement between parent and child reports was strongest for cigarette smoking, alcohol dependence, and any PSUD. Although parental reports were frequently endorsed by the child's report, the reverse was rarely true. Predictors of parental awareness of the child's PSUD included impaired social functioning, younger age of the child, presence of multiple substance use disorders in the child, and comorbid bipolar disorder. CONCLUSIONS: PSUD rates vary by informant and are higher when the child is the reporter. Because severity of PSUD and multiple substance use were the strongest predictors of parental awareness, more efforts are needed to identify the more covert and milder cases of PSUD that may not reach clinical attention.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Disentangling the overlap between Tourette's disorder and ADHD.

OBJECTIVE: To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. METHOD: The sample consisted of children with Tourette's syndrome with ADHD (N = 79), children with Tourette's syndrome without ADHD (N = 18), children with ADHD (N = 563), psychiatrically referred children (N = 212), and healthy controls (N = 140). RESULTS: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. CONCLUSIONS: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.

Adolescent↗
PubMed1997

Differential serological diagnosis of HTLV-I and HTLV-II infection by external membrane protein peptide-based enzyme immunoassays.

BACKGROUND: HTLV antibody screening assays detect both antibodies to the etiological agent of adult T-cell leukemia and tropical spastic paraparesis HTLV-I and to the less pathogenic HTLV-II. It is critical to make a differential diagnosis of the two viruses. OBJECTIVES: To design and evaluate synthetic core and envelope-derived peptide enzyme immunoassays (EIA) for serological differential diagnosis. STUDY DESIGN: Peptide EIAs were evaluated with a panel of 202 plasma samples comprised of HTLV antibody positive, serologically classified as confirmed, indeterminate, or non confirmed, characterized as HTLV-I, HTLV-II or neither by genomic amplification. The peptide EIA with the best performance was further used to differentiate between HTLV-I and HTLV-II antibodies in 807 samples from 18 countries in four continents and to provide ratios between the two infections. RESULTS: The gp46 peptide EIA correctly identified 96.5% of HTLV-I and 98.6% of HTLV-II antibody-confirmed samples. HTLV-I was found exclusively in Japan and Caribbean countries; almost exclusively in Africa. HTLV-II represented 10-25% of samples from Canada, Chile and Venezuela and was predominant in the US. CONCLUSIONS: Differential diagnosis between HTLV-I and HTLV-II can be reliably performed using specific peptides from the gp46 envelope protein of each virus.

Antigens, Viral↗
PubMed1997

Is comorbidity with ADHD a marker for juvenile-onset mania?

OBJECTIVE: To compare the characteristics and correlates of mania in referred adolescents and to determine whether attention-deficit hyperactivity disorder (ADHD) is a marker of very early onset mania. METHOD: From 637 consecutive admissions, 68 children (< or = 12 years) and 42 adolescents (> 13 years) who satisfied criteria for mania were recruited. These were compared with the 527 nonmanic referrals and 100 normal controls. RESULTS: With the exception of comorbidity with ADHD, there were more similarities than differences between the children and adolescents with mania in course and correlates. There was an inverse relationship between the rates of comorbid ADHD and age of onset of mania: higher in manic children intermediate in adolescents with childhood-onset mania, and lower in adolescents with adolescent-onset mania. CONCLUSIONS: ADHD is more common in childhood-onset compared with adolescent-onset cases of bipolar disorder, suggesting that in some cases, ADHD may signal a very early onset of bipolar disorder. Clinical similarities between the child- and adolescent-onset cases provide evidence for the clinical validity of childhood-onset mania.

Adolescent↗