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Biomedical subjects

M Gallagher

Publications and source records attributed to M Gallagher.

At least 181 records · Page 10Linked to original sources

Effect of the bacterial DNA gyrase inhibitors, novobiocin, nalidixic acid, and oxolinic acid, on oxidative phosphorylation.

When incubated with isolated intact rat liver mitochondria, novobiocin and nalidixic acid act as uncouplers of oxidative phosphorylation; they stimulate oxygen uptake and inhibit ATP synthesis. Novobiocin is about as powerful an uncoupler as is 2,4-dinitrophenol, nalidixic acid is somewhat less powerful, and oxolinic acid exerts no inhibition whatsoever at the concentrations used. The three inhibitors are without effect on oxidative phosphorylation in Escherichia coli nor does novobiocin affect this process in a novobiocin-permeable mutant of yeast. While it would appear that oxolinic acid may be a relatively specific tool for the manipulation of the superhelicity of DNA in complex systems such as mammalian mitochondria and intact mammalian cells, the specificity of each of these inhibitors may depend upon the particular conditions and species used and such experiments require adequate controls on oxidative phosphorylation.

Animals↗

Opiate antagonist facilitation of time-dependent memory processes: dependence upon intact norepinephrine function.

Post-training administration of opiate antagonists improves retention of recent learning in laboratory animals tested on a variety of tasks. We examined the possibility that this effect of opiate antagonist treatment might be due to release of brain norepinephrine (NE) function from opioid peptide inhibition. The behavioral testing procedure in the experiments consisted of one-trial passive avoidance conditioning. Rats received post-training treatments immediately after the training trial and retention was tested 24 h later. Lesions of the dorsal noradrenergic bundle (DNB) that were induced by 6-hydroxydopamine (6-OHDA) were found to prevent the memory enhancing effect of post-training naloxone administration. The memory enhancing effect of naloxone was restored when NE neurons were protected from 6-OHDA by pretreatment with a NE uptake inhibitor. Earlier research indicated that the amygdala complex is one brain site that is sensitive to the effects of opiate manipulations on memory processes. In this study, lesions of the DNB were also found to prevent the memory enhancing effect of intracranial opiate antagonist administration into the amygdala complex.

Amygdala↗

Treatment of radiation-induced cystitis with hyperbaric oxygen.

The effects of hyperbaric oxygen on radiation cystitis have been documented in 3 patients with radiation-induced hemorrhagic cystitis refractory to conventional therapy. Cessation of gross hematuria and reversal of cystoscopic bladder changes were seen in response to a series of hyperbaric oxygen treatments of 2 atmosphere absolute pressure for 2 hours. To our knowledge this is the first report of cystoscopically documented healing of radiation-induced bladder injury.

Aged↗

Effects of opiate antagonists on spatial memory in young and aged rats.

The effects of post-training opiate antagonist administration on spatial memory were assessed in young and aged male Long Evans rats. In Experiment I rats were trained to visit each arm of an eight-arm radial maze once in a session to obtain a food reward placed at the end of each arm. During training aged rats required significantly more trials to achieve criterion performance when compared to young mature rats. However, administration of the opiate antagonist naloxone (2.0 mg/kg) immediately after each training trial did not significantly alter the rate of achieving accurate performance in either age group. In Experiment II young and aged rats that were previously trained to a comparable criterion on the radial maze were tested on the same maze apparatus in novel spatial environments. When animals were exposed to novel spatial information, the effects of post-trial opiate antagonists were examined using a within-subjects counter-balanced design. In Experiment IIa naloxone (2 mg/kg) enhanced the performance of both young and aged rats. In Experiment IIB naltrexone (1.0 mg/kg) was found to have a comparable effect of enhancing the performance of both age groups. In addition, in Experiment IIb a significant age-related deficit was found in rats tested in novel spatial environments. These results indicate that opiate antagonists are capable of improving memory for new spatial information in both young and aged rats on a task that is sensitive to behavioral deficits during normal aging.

Age Factors↗

Effect of beta-funaltrexamine on retention of passive-avoidance conditioning.

Rats received administration of an opiate antagonist immediately following single-trial passive-avoidance training. Retention of passive-avoidance conditioning was assessed 1 week after training. Compared to noninjected and vehicle-injected control groups, post-training naloxone (2.0 mg/kg) administration significantly increased retention. A comparable facilitation of retention was also observed when animals received post-training administration of beta-funaltrexamine (40 mg/kg). These data provide additional support for mu opiate receptor activity in the regulation of memory processes.

Animals↗

Role of noradrenergic function in the opiate antagonist facilitation of spatial memory.

Animals previously trained to criterion on an eight-arm radial maze task received either bilateral 6-hydroxydopamine lesions of the dorsal noradrenergic bundle (DNB) or control surgery. Following a 3-week recovery period, the animals were trained on the same radial maze in two novel environments. By a within-subjects design, in one of these environments animals received posttraining systemic treatment with the opiate antagonist naloxone; in the other novel environment, they received vehicle injection. In animals that received control surgery, opiate antagonist treatment produced a reliable enhancement of performance. Although the DNB-lesion animals did not differ from the control-surgery animals under the saline treatment condition, denervation of forebrain norepinephrine (NE) was found to prevent the memory enhancing effect of posttraining naloxone administration. These results provide further support that enhanced retention obtained with opiate antagonist administration is dependent upon intact NE function.

Animals↗

Isolation of immunogenic neuraminidases of human influenza viruses by a combination of genetic and biochemical procedures.

Neuraminidases were purified from reassortant viruses (H6N1 and H6N2) containing the two antigenic subtypes (N1 and N2) found in human influenza viruses. Surface glycoproteins were solubilized with octylglucoside, and the neuraminidase was isolated by chromatography on DEAE-Sephadex. Neuraminidase isolated by this technique coeluted with viral lipids and spontaneously formed liposomes on dialysis. The purified neuraminidase was immunogenic in rabbits, producing a significant antibody response at dose levels as low as 1 microgram.

Animals↗

Opiate antagonists improve spatial memory.

Rats trained on an eight-arm radial maze were challenged by placing the maze in new spatial environments. Administration of opiate antagonists, either naloxone or diprenorphine, after exposure to the new environments significantly improved subsequent performance. The effect of naloxone on spatial memory was attenuated when drug administration occurred 2 hours after maze exposure.

Animals↗

Benzodiazepine effects on heart rate conditioning in the rabbit.

The present experiment was undertaken to assess the ways in which benzodiazepine administration alters heart rate responding during Pavlovian aversive conditioning in the rabbit. Each of three benzodiazepine compounds (chlordiazepoxide, flurazepam, diazepam) reliably attenuated the magnitude of the conditioned bradycardia response as compared to vehicle controls. Lower doses of two of these compounds significantly potentiated the conditioned bradycardia response. Benzodiazepine treatment did not significantly alter baseline heart rate, the expression and habituation of the heart rate orienting response, or heart rate responding during unpaired stimulus presentations. The effects of benzodiazepines under these conditions therefore appeared to be selective to those heart rate responses that were conditioned. These results are consistent with evidence suggesting the involvement of benzodiazepine-sensitive processes in the expression of emotional responses, including concomitant cardiovascular alterations.

Animals↗

Multiple unit activity recorded from amygdala central nucleus during Pavlovian heart rate conditioning in rabbit.

Using a Pavlovian heart rate conditioning paradigm, a rapid development of short latency increases in the multiple unit activity of the amygdala central nucleus were observed in response to a tone conditioned stimulus. In some cases the increase in multiple unit response showed a parallel development with the conditioned decelerative heart rate response and were significantly correlated with it. These results suggest a direct role for the central nucleus in the expression of conditioned heart rate responding in rabbit.

Amygdala↗

Cardiovascular responses elicited by electrical stimulation of the amygdala central nucleus in the rabbit.

Recent behavioral and anatomical evidence suggests the involvement of the amygdala central nucleus projection to medullary cardioregulatory nuclei in the expression of conditioned bradycardia during aversive Pavlovian conditioning in the rabbit 6,7,11,15. The present study sought to determine the extent to which electrical stimulation of the central nucleus produces bradycardia in the rabbit, and the extent to which any bradycardia elicited varies with stimulation at sites within as opposed to adjacent to the medial component of the central nucleus, the component from which the projection to cardioregulatory nuclei originates. Over 900 sites in 30 rabbits anesthetized with alpha-chloralose were explored. Monopolar stimulation (30-100 Hz; 0.5 ms pulse duration; 5.0 s train duration; 100-500 microamperemeter) at sites within the central nucleus produced bradycardia and depressor responses. Maximum bradycardia was produced from sites within the anterior, medial component of the nucleus. This response usually began within one second of stimulus onset, reached peak magnitude within two seconds of stimulus onset and in many instances was followed by a slight tachycardia following stimulus termination. The accompanying depressor responses occurred at longer latencies than the bradycardia responses. The responses persisted following artificial ventilation and immobilization by Flaxedil and were attenuated by i.v. injections of atropine methylnitrate. While bradycardia and depressor responses were elicited from sites immediately dorsal, ventral and lateral to the medial central nucleus, component. The results are consistent with previous evidence which suggests a contribution for the central nucleus in the expression of cardiovascular responding during aversive Pavlovian conditioning in the rabbit.

Amygdala↗

Enkephalin analogue effects in the amygdala central nucleus on conditioned heart rate.

The experiment was conducted to assess the effects of enkephalin analogue administration into the amygdala central nucleus on the acquisition of classically conditioned heart rate responding in rabbits. Bilateral injections of either D-Ala2, Met5-enkephalinamide (DALA) or D-Ala2, D-Leu5-enkephalin (DADL) were administered in a 1.0 microliter volume into the central nucleus immediately prior to the conditioning session. Administration of DALA significantly attenuated the acquisition of conditioned heart rate responding whereas groups which received comparable doses of DADL exhibited conditioned responding which did not differ from the vehicle-injected control group. The effect on conditioned responding produced by DALA administration was blocked by concurrent administration of the opiate antagonist naloxone. These results provide some support for the involvement of mu receptor activity within the central nucleus region of the amygdala in conditioning processes.

Amygdala↗

Detection of influenza virus neuraminidase-specific antibodies by an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay was developed for the titration of antibodies in human sera to influenza virus neuraminidase, employing partially purified N1 neuraminidase. Specificity of the test was demonstrated, and the test was more sensitive than either the conventional neuraminidase inhibition or plaque size reduction tests in detecting anti-neuraminidase antibody.

Antibodies, Viral↗