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Biomedical subjects

M J Kelly

Publications and source records attributed to M J Kelly.

At least 127 records · Page 7Linked to original sources
PubMed1990

Membrane properties and response to opioids of identified dopamine neurons in the guinea pig hypothalamus.

The electrophysiological properties and opioid responsiveness of the dopamine-containing neurons in the arcuate nucleus of the guinea pig hypothalamus were examined. Dopamine-containing neurons, identified immunocytochemically by the presence of tyrosine hydroxylase, had a mean length-to-width profile of 14.9 +/- 4.4 x 11.5 +/- 3.1 microns (N = 14). The Na+ action potential of these neurons was of short duration, and induction of repetitive firing (20-50 Hz) caused an afterhyperpolarization of 6-9 mV in amplitude, with a decay half-time of approximately 1.5 sec. Dopamine-containing cells exhibited a low threshold spike, which induced 1-4 Na+ action potentials. This potential had a threshold close to -65 mV, could not be induced without prior hyperpolarization and was not sensitive to TTX. Dopamine-containing neurons also exhibited a time- and voltage-dependent inward current at potentials negative to -70 mV, and Cs+ blocked this conductance. The mu-opioid agonist Tyr-D-Ala-Gly-mePhe-Gly-ol hyperpolarized (14 +/- 3 mV) dopamine neurons via induction of an outward current (93 +/- 44 pA near the resting membrane potential) which had a reversal potential similar to that expected for a selective potassium conductance. TTX (1 microM) did not block the opioid effects. These results show that dopamine neurons of the arcuate nucleus differ in their intrinsic conductances and their responsiveness to opioids from other CNS dopaminergic neurons. Furthermore, opioid activation of a potassium conductance resulted in a direct hyperpolarization of dopamine neurons of the arcuate nucleus, and we suggest that this mechanism may underlie the effects of opioids on dopamine-mediated prolactin release.

Action Potentials↗
PubMed1990

A method for immunocytochemical identification of biocytin-labeled neurons following intracellular recording.

Because of the large number of cell phenotypes in the nervous system, it has been difficult to characterize each as to specific electrophysiological properties. We have developed a technique that allows the identification of central and peripheral nervous system neurons following intracellular recording. We use electrodes that contain 2% biocytin to do current- and voltage-clamp recordings; the recorded neurons are revealed with streptavidin-fluorescein isothiocyanate labeling and identified through immunohistochemical staining for specific antigens. Presently, we report on the use of this technique to identify four cell types--dopamine, beta-endorphin, vasopressin and oxytocin--in the hypothalamus of the mammal. This technique should have widespread applicability for electrophysiologists.

Animals↗
PubMed1989

Opioid inhibition of spontaneously active neurons of the rat arcuate nucleus in vitro.

The effects of opioid agonists were determined on single-unit activity recorded from the arcuate nucleus (ARC) in perfused, coronal slices of hypothalamus taken from proestrous rats. The selective, mu-receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO) produced a concentration-dependent decrease in the firing rate of 70-78% of the units tested. The concentration of DAGO that induced maximal inhibition of firing was approximately 0.5 microM. This inhibition of firing frequency occurred irrespective of cell location, firing pattern or baseline firing frequency. The effect of DAGO was antagonized by the opioid antagonist naloxone (0.1 microM). The selective, kappa-receptor agonist, trans-(+)-3,4 dichloro-N-methyl-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide methane sulfonate (U50,488H) did not decrease the firing rate in cells which did respond to DAGO. Blockade of synaptic activity decreased the level of spontaneous activity but did not prevent the inhibitory action of DAGO. These data support the hypothesis that opioids, through activation of mu-receptors, inhibit neuronal activity in the arcuate nucleus. Furthermore, the opioid inhibition occurs, in part, via a direct postsynaptic action.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Transurethral incision of the prostate: a preoperative and postoperative analysis of symptoms and urodynamic findings.

The efficacy of transurethral incision of the prostate was evaluated prospectively in 26 men with urodynamic evidence of outlet obstruction secondary to small prostate glands (estimated size less than 30 gm). All men completed preoperative and postoperative symptom questionnaires and extensive urodynamic testing with a median postoperative followup of 16.25 months. There was a significant improvement in subjective symptom analysis and objective urodynamic parameters (peak and mean uroflow rates, maximal detrusor pressure at peak flow, volume at first urge and post-void residual volume) as a result of transurethral incision of the prostate with minimal postoperative morbidity. Antegrade ejaculation was preserved in 55% of the men with normal preoperative ejaculation. Based on subjective and objective criteria, transurethral incision of the prostate is an effective treatment option for selected men with outlet obstruction.

Aged↗
PubMed1989

The radionuclide assessment of a system for slow intrathecal infusion of drugs.

The authors describe a new radionuclide method for assessing the functional integrity of slow intrathecal infusion devices. Approximately 11 mCi (400 MBq) of Tc-99m DTPA is injected into the pump chamber. Early and delayed imaging of the pump, tubing, and spinal cerebrospinal fluid space is performed on a digital large-field-of-view gamma camera. The digitally displayed images are then reviewed by adjustment of the grey scale window. Four patients have had eight studies and in each case the result has been confirmed by surgical exploration or by clinical response to change in therapy.

Aged↗
PubMed1989

Computers: the best friends a human genome ever had.

Mapping and sequencing the human genome will generate large amounts of data, which must be sorted, analyzed, and stored for rapid retrieval to complete this enormous task. Computers and their software programs provide the most important tool to the molecular biologist today. A discussion of current capabilities and future needs in computer hardware and software for the human genome project is the topic of this paper. The use of computer programs to generate restriction maps, manage clone libraries, manage sequence projects, and generate consensus sequences is presented. The use of computers to communicate useful information rapidly to scientific colleagues is also mentioned. The role of both GenBank and BIONET is central to the dissemination and analysis of sequence information. The capabilities of electronic communication worldwide for assisting this project is available on the BIONET National Computer Resource, using existing networks.

Base Sequence↗
PubMed1989

Effects of ovariectomy on GnRH mRNA, proGnRH and GnRH levels in the preoptic hypothalamus of the female rat.

Experiments were carried out to investigate the effects of ovariectomy on gonadotropin-releasing hormone (GnRH) messenger RNA (mRNA), proGnRH and GnRH peptide levels in the hypothalamus of female rats. Intact proestrous female rats and female rats, which had been ovariectomized for 2 weeks, were sacrificed at 9.00 h and the preoptic area (POA) and basal hypothalamus (BH) were dissected out and frozen on dry ice. One group of tissues from proestrous control and ovariectomized females were extracted in acetic acid, centrifuged at 13,000 g and the supernatant purified on a C18 column. The purified extract was then radioimmunoassayed for proGnRH, using a specific antiserum to rat proGnRH (ARK-2), and for GnRH using the E1-14 antiserum. Total cellular RNA was isolated from another group of tissues and prepared as Northern blots. Hybridization with 32P-labeled GnRH cRNA was used to detect GnRH mRNA. A third group of proestrous and ovariectomized female rats were perfused, and 50 microns vibratome sections were cut. These were immunostained with proGnRH or GnRH antiserum, followed by in situ hybridization with 35S-labeled GnRH cRNA to detect GnRH mRNA. Based on the histochemical staining, mRNA was colocalized to the cell soma of neurons containing proGnRH and GnRH throughout the POA and BH. Based on the radioimmunoassay, proGnRH levels were 2 times higher in the POA versus the BH, but GnRH levels were 6-7 times higher in the BH. Ovariectomy significantly decreased proGnRH levels in both the POA and BH, while GnRH decreased in the BH. In contrast, quantitative Northern blot analysis demonstrated that ovariectomy had no effect on mRNA levels in the POA and BH. These data indicate that the effects of ovariectomy on proGnRH and GnRH levels are a result of altered translation, posttranslational processing and/or secretion of GnRH.

Animals↗
PubMed1989

Estrogen modulation of the alpha-1-adrenergic response of hypothalamic neurons.

Intracellular recordings were made from 106 arcuate and cell-poor zone (ARC-CPZ) neurons in sagittal slices prepared from intact, ovariectomized and ovariectomized plus estradiol-benzoate-treated female guinea pigs, and the effects of norepinephrine (NE), the alpha 1-agonist methoxamine (MX) and the beta-agonist isoproterenol were tested. Either bath application or pressure application of 2-100 microM NE reversibly hyperpolarized and inhibited the spontaneous firing of the majority (57%, n = 60) of ARC-CPZ neurons. Isoproterenol also inhibited the majority (75%) of the ARC-CPZ neurons which it was tested on. In addition, 2-100 microM NE depolarized and/or increased the spontaneous activity of 20% (n = 21) of ARC-CPZ neurons, and some of these (n = 8) exhibited bursting activity. Similar doses of MX mimicked the NE excitation (depolarization and/or increased firing) in 48% (n = 14) of the ARC-CPZ neurons tested. Based on the serum levels of 17 beta-estradiol, the three groups of females were divided into high ( greater than 30 pg/ml) and low (less than 30 pg/ml) estrogen groups, and it was found that endogenous or exogenous estrogen significantly increased the number of neurons responding to MX (from 29 to 75%). Using intracellular labeling with procion yellow and immunocytochemistry, we have identified that luteinizing-hormone-releasing hormone neurons respond to NE. Therefore, it is suggested that one mechanism for an increase in the noradrenergic excitatory drive at the time of the preovulatory surge of luteinizing hormone in the mammal is an increase in the neuronal response to alpha 1-adrenergic stimulation.

Animals↗
PubMed1989

Use of the urological resectoscope in benign and malignant rectal lesions--review of 12 cases.

The urological resectoscope was used over three years for 27 transanal operations in 12 patients. The procedure was quick, safe and effective. Haemorrhage was not a problem, and histology was obtained in every case. It seemed to be the treatment of choice for low anastomotic strictures in the rectum (two cases) and for palliation of inoperable low carcinomas (three cases). Its use for villous adenomas (six cases) both alone and as an adjunct to open surgery is discussed in detail.

Adenoma↗
PubMed1989

Effect of bicarbonate, acetate, and citrate on water and sodium movement in normal and cholera toxin-treated rat small intestine.

Bicarbonate, citrate, or acetate are commonly included in oral rehydration solutions to correct acidosis and possibly because of their ability to promote water and sodium absorption. We have investigated the effect of these anions on water and sodium transport in normal and also in secreting (cholera toxin-treated) rat small intestine using a single-pass perfusion technique. In normal jejunum bicarbonate and acetate produced net absorption, and citrate net secretion of both water and sodium. In normal ileum all anions produced net absorption of water and sodium. In the secreting jejunum, however, bicarbonate had no effect on water and sodium secretion, whereas acetate and citrate actually enhanced the secretory state for both water and sodium. None of these anions had any effect on water and sodium secretion in the ileum. These observations suggest that normal and secreting intestine are qualitatively different with regard to handling of these organic anions. The addition, therefore, of bicarbonate, acetate, or citrate to oral rehydration solutions may have no beneficial effect with regard to the promotion of water and sodium absorption in the secreting intestine during acute diarrhoeal states and could actually be deleterious.

Acetates↗
PubMed1989

Targeting the at-risk male: a strategy for adolescent pregnancy prevention.

This article reviews some current literature relative to adolescent pregnancy, specifically the male partner. An overview is given of a successful program in Norfolk, Virginia, that addresses the dilemmas that these teenagers face. The young men's sexuality awareness program, funded by a federal grant through Eastern Virginia Medical School Area Health Education Center, was started in September 1985 with the following specific goals: to heighten the level of sexuality awareness among young men, to increase levels of self-esteem, and to create an awareness of what it means to be an effective father. The components, successes of the program, and implications for the future are discussed.

Adolescent↗
PubMed1988

Metronidazole and gentamicin prophylaxis in synergistic aerobe-anaerobe infections in mice.

The efficacy of prophylaxis by intraperitoneal injection of gentamicin, metronidazole or both drugs combined was investigated in a mouse model of mixed infection with Escherichia coli and Bacteroides fragilis. A three dose prophylactic regimen given 12 hourly was studied starting simultaneously with bacterial challenge. Serum antibiotic concentrations lay within the human therapeutic ranges. Metronidazole alone eliminated B. fragilis from the developing infections, but at higher challenge doses the mice developed abscesses which contained E. coli, and mortality was no different from controls. Gentamicin alone eliminated both bacteria and deaths in all infections, but sterile abscesses occurred in two of five animals at the highest challenge dose. Mixed metronidazole + gentamicin abolished all effects of the challenge bacteria, aborting all infections for all challenge doses with no formation of sterile abscesses. It is proposed that, in abdominal surgery, although metronidazole or gentamicin may be effective given alone for low levels of contamination, for higher levels (e.g. colonic surgery) both drugs may be required.

Animals↗
PubMed1988

Episodic luteinizing-hormone release in the ovariectomized female guinea pig: rapid inhibition by estrogen.

Negative feedback of estrogen was investigated in ovariectomized female guinea pigs. Two weeks after ovariectomy, indwelling catheters were inserted into the jugular vein, and 3 days later, blood samples were taken every 10 min to determine the pattern of luteinizing hormone (LH) secretion. LH secretion in these guinea pigs was episodic, with a mean pulse period of 32 min. The mean pulse amplitude was 2.1 ng/ml, with mean plasma LH levels of 1.8 ng/ml. Twenty-five micrograms 17 beta-estradiol (E2), given i.v., caused a pronounced inhibition of pulsatile LH release. Twenty-five microliters of 100% ethanol (vehicle) had no effect on plasma LH values. In a second set of experiments, ovariectomized female guinea pigs were given two injections of luteinizing hormone-releasing hormone (LHRH) (1 microgram/kg BW, i.v.) separated by 30 min. Sharp rises in serum LH values were detected after each injection. A third injection of LHRH was administered after an injection of either 25 micrograms E2 or 25 microliters vehicle. In the presence of E2, the LH response was significantly (p less than 0.005) diminished, whereas the vehicle did not change the LH response to LHRH. These rapid effects of E2 on LH secretion and the pituitary responsiveness to LHRH infusion indicate that in the ovariectomized guinea pig E2 can directly block gonadotropin secretion. These findings are consistent with the hypothesis that negative feedback actions of E2 are directly on the membrane of the gonadotrope.

Animals↗
PubMed1988

Longitudinal study of ventricular function after the Mustard operation for transposition of the great arteries: a long term follow up.

An earlier study of 25 patients who were investigated by radionuclide angiography after a Mustard procedure showed that they had had evidence of right and left ventricular dysfunction at rest and with exercise. Twenty one (mean age 17.0 years (range 13.7-20.6) 11 female patients) of the original 25 patients were followed up a mean of 4.3 years later (mean 14.6 years (range 12.5-16.0) after the procedure). The group means for resting right and left ventricular ejection fraction and exercise response were not significantly different from those reported five years before. Individual changes in values were within the normal variation seen in serial studies. This long term longitudinal follow up of patients after the Mustard operation showed that although some patients still had right and left ventricular dysfunction, resting ventricular function and exercise response remained stable over a five year period. This preservation of cardiac function may contribute to the long term survival of patients after the Mustard procedure.

Adolescent↗
PubMed1988

Plasma prolactin and luteinizing hormone profiles during the estrous cycle of the female rat: effects of surgically induced persistent estrus.

Experiments were carried out to investigate the hypothalamic control mechanism for prolactin (PRL) and luteinizing hormone (LH) secretion in the female rat. Anterior medial preoptic nucleus (AMPO) or suprachiasmatic nucleus (SCN) lesions were produced by passing 5-10 microA of direct current (tip negative). Persistent estrus (PE) began as early as 6 days and as late as 30 days after electrolytic lesioning. Blood samples obtained during diestrus, proestrus and estrus revealed well-described profiles of plasma PRL and LH in sham-lesioned animals, indicating that our cannulation and blood sampling procedure had no adverse effects on the plasma hormone levels. Individual sham-operated animals sampled on successive or alternate proestrous afternoons showed precise timing of the PRL and LH surges. However, when a shift occurred in the PRL surge a comparable shift would also occur in the LH surge, indicating a coupling between the mechanisms regulating the PRL and the LH surge. The AMPO-, SCN- or combine-lesioned PE animals exhibited low basal levels of plasma PRL and LH. Small secretory bursts occurred one to three times during the 6-hour sampling periods. Animals with incomplete SCN lesions had plasma PRL titers significantly higher than the other 3 groups. Plasma progesterone levels were significantly lower in the PE animals (p less than 0.01), whereas plasma estrogen levels were not significantly different from proestrous controls. These experiments indicate that during the afternoon of proestrus, the surges of plasma PRL and LH are very precise in the time of onset. Moreover, the mechanisms controlling the surge of PRL and LH are temporally coupled.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The determination of cysteamine in physiological fluids by HPLC with electrochemical detection.

Cysteamine, an amino thiol, was separated by rapid isocratic cation exchange chromatography and detected by electrochemical oxidation at a platinum electrode maintained at +0.45 V relative to an Ag/AgCl reference electrode. Eluent pH and electrode working potentials were optimized and the effects of alternative buffers and organic modifiers have been examined. On column sensitivity for cysteamine was 1.5 pmol at a signal-to-noise ratio of 5. Although the specificity was good, plasma samples required maximal sensitivity whereas urine samples required greater selectivity, which was achieved by use of lower working potentials. Cysteamine concentrations were determined in serial samples of plasma and urine from volunteers who had received a single oral dose of 200 mg of the drug. Cysteamine was rapidly oxidized in vivo, and detection required prior reduction with dithiothreitol before analysis.

Chromatography, High Pressure Liquid↗