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Biomedical subjects

G C Harris

Publications and source records attributed to G C Harris.

At least 19 recordsLinked to original sources
PubMed2003

Expert opinion: Reporting needle core biopsies of breast carcinomas.

Many breast carcinomas are now diagnosed in needle core biopsies, after either mammographic detection or symptomatic presentation. There is dispute, however, about the range of information that should be included in the diagnostic report of these small and possibly unrepresentative samples. Is it sufficient to simply report the presence of carcinoma, in situ or invasive? Or should the histopathologist give a more detailed report including features of prognostic and predictive significance? If so, what is the evidence that the further information is, first, of clinical benefit and, second, not unreliable because of sampling variability? To address the question "What should be included in reports of needle core biopsies of breast carcinomas?" contributions were invited from authors in the USA and the UK.

Adenocarcinoma↗
PubMed2001

Preference for a cocaine-associated environment is attenuated by augmented accumbal serotonin in cocaine withdrawn rats.

RATIONALE: Recent studies have found decreased serotonin (5-HT) transmission within the nucleus accumbens following withdrawal from chronic cocaine. OBJECTIVE: We sought to investigate whether increasing brain 5-HT levels would decrease behavioral responses that occur following cocaine withdrawal, namely increased preference for a cocaine environment and anxiety. METHODS: The conditioned place preference and the defensive burying paradigms were used to measure the behavioral responses that occur 1 week following cocaine withdrawal. RESULTS: We show that pharmacological agents that increase 5-HT transmission (sertraline or 5-hydoxytryptophan, 5-HTP) abolish the preference of subchronically cocaine-treated, abstinent rats for a cocaine-associated environment. Similar results were seen when sertraline was microinjected into the nucleus accumbens. Conversely, rats acutely conditioned with cocaine showed an increased preference for a cocaine-associated environment when pretreated with these drugs. Sertraline also decreased the heightened anxiety-like behaviors found in subchronically treated cocaine rats. CONCLUSIONS: These results indicate that drugs that augment 5-HT function may reduce the desire for cocaine following cocaine withdrawal, and thus facilitate cocaine abstinence in dependent subjects.

5-Hydroxytryptophan↗
PubMed2001

Augmented accumbal serotonin levels decrease the preference for a morphine associated environment during withdrawal.

Recent studies have found that acute morphine administration increases serotonin (5-HT) transmission within the nucleus accumbens and other forebrain regions. In contrast, 5-HT transmission is depressed during withdrawal from chronic morphine. We show that pharmacological agents that increase brain 5-HT levels (fluoxetine or 5-hydoxytryptophan, 5-HTP) abolish the preference of chronically morphine-treated, withdrawn rats for a morphine-associated environment. Similar results were seen when fluoxetine was microinjected into the nucleus accumbens. Conversely, rats given morphine acutely showed an enhanced preference for a morphine-associated environment when pretreated with these agents. Fluoxetine also decreased the heightened anxiety found in morphine withdrawn rats. The results of our study indicate that drugs that augment 5-HT levels may reduce the desire for morphine during withdrawal.

5-Hydroxytryptophan↗
PubMed2001

Significance of the V-type ATPase for the adaptation to stressful growth conditions and its regulation on the molecular and biochemical level.

Two electrogenic H(+)-pumps, the vacuolar type H(+)-ATPase (V-ATPase) and the vacuolar pyrophosphatase, coexist at membranes of the secretory pathway of plants. The V-ATPase is the dominant H(+)-pump at endomembranes of most plant cells, both in terms of protein amount and, frequently, also in activity. The V-ATPase is indispensable for plant growth under normal conditions due to its role in energizing secondary transport, maintenance of solute homeostasis and, possibly, in facilitating vesicle fusion. Under stress conditions such as salinity, drought, cold, acid stress, anoxia, and excess heavy metals in the soil, survival of the cells depends strongly on maintaining or adjusting the activity of the V-ATPase. Regulation of gene expression and activity are involved in adapting the V-ATPase on long- and short-term bases. The mechanisms known to regulate the V-ATPase are summarized in this paper with an emphasis on their implications for growth and development under stress.

Adaptation, Physiological↗
PubMed1999

The dangerous patient exception to the psychotherapist-patient privilege: the Tarasoff duty and the Jaffee footnote.

With the U.S. Supreme Court's 1996 decision in Jaffee v. Redmond, all U.S. jurisdictions have now adopted some form of evidentiary privilege for confidential statements by patients to psychotherapists for the purpose of seeking treatment. The majority of states, following the decision of the Supreme Court of California in Tarasoff v. Regents of the University of California, have also adopted some form of duty by psychotherapists to breach confidentiality and warn potential victims against foreseeable violence by their patients. Largely unresolved is whether there should be a dangerous patient exception to the evidentiary privilege parallel to the Tarasoff exception to confidentiality. This Article argues that exception to the evidentiary privilege should be evaluated separately from the exception to confidentiality. Whether or not a Tarasoff duty to warn existed at an earlier time, exception to the evidentiary privilege should be made only where psychotherapists' testimony is necessary to prevent future harm to patients or identified potential victims. Applying this standard, the dangerous patient exception generally would not apply in criminal actions against patients, but would apply only in proceedings for the purpose of protecting patients or third parties, such as restraining order hearings or proceedings to hospitalize patients.

Confidentiality↗
PubMed1998

Characterisation of the biological effects of neurohypophysial peptides on seminiferous tubules.

Oxytocin (OT) is present in the mammalian testis and has been postulated to play a role in modulation of seminiferous tubule contractility. However, recent evidence suggests that the myoid cells responsible for such contractile activity do not express OT receptors. In this study computer-assisted analysis and time-lapse videomicrography were used to investigate the biological effects of neurohypophysial peptides and their analogues on seminiferous tubule contractility. Adult rat testes were placed in fresh oxygenated Dulbecco's modified Eagle's medium (DMEM) F12 medium, decapsulated and the tubules gently teased apart. A small section of tubule was placed in a microslide chamber and perifused with medium. Seminiferous tubules were treated with OT (2 nM), [Arg8]-vasopressin (AVP, 0.2 nM) or [Thr4,Gly7]-OT (TGOT, 2 nM, 8 nM and 0.2 microM). Specific antagonists were also given simultaneously with OT and AVP treatments. Data were analysed to give arbitrary units of contractility. Both OT and AVP increased tubule contractility, with AVP being at least 10 times more potent than OT. Treatment with the selective OT antagonist, desGly-NH2,d(CH2)5[d-Tyr2,Thr4]-ornithine vasotocin (OTA, 0.2 microM and 2 microM) significantly reduced OT-induced increases in seminiferous tubule contractility but had no effect on AVP-induced responses. In contrast, the AVP antagonist, Phaa-d-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH2 (AVPA) was more potent at reducing AVP-induced increases than OT-induced responses. The selective non-peptide AVPA SR 49059 blocked the response to both peptides in a similar manner, whilst the non-peptide OTA L367,773 did not block OT-induced increases in seminiferous tubule contractility at doses that were slightly inhibitory to AVP-induced responses. The specific OT agonist TGOT did not induce a contractile response. The data in this study demonstrate that in the testis AVP acts via V1a receptors to stimulate contractile activity and suggest that OT may act via a receptor which differs from the classical V1a and uterine-type OT receptor. These findings support a role for OT in the regulation of seminiferous tubule contractility and raise the possibility that AVP may also be important in this process.

Analysis of Variance↗
PubMed1998

Stage-related differences in rat seminiferous tubule contractility in vitro and their response to oxytocin.

Oxytocin (OT) is present in the mammalian testis and has been shown to play a role in the modulation of seminiferous tubule contractility and steroidogenesis. However, stage-specific effects of the peptide have not been previously investigated. In this study, computer-assisted analysis and time-lapse videomicrography were used to investigate basal contractility and the response to OT of seminiferous tubules at specific stages of the spermatogenic cycle. Adult rat testes were placed in fresh oxygenated DMEM F12 medium, decapsulated, and the tubules gently teased apart. Stages were identified by transillumination and a 10 mm section of tubule at each of stages IV-V, VII-VIII and XIII-I was placed in a microslide chamber and perifused with medium. After a control period of 3 h, OT (2 nM) was given for 1 h, followed by another control period of 1 h. The experiment was repeated using tubules from different rats and data were analysed to give arbitrary units of tubule contractility. Contractility was observed in all the tubules studied and the contractile activity was shown to vary depending on the stage of the spermatogenic cycle. Mean basal contractility at stages VII-VIII, the time when sperm are shed from the epithelium, was significantly lower than that at stages IV-V and XIII-I. The response of the tubules to OT was also stage-dependent, with the peptide producing the largest increases in contractile activity at stages VII-VIII and having no effect at stages IV-V. We postulate that these stage-specific differences in basal and OT-stimulated contractility may be important in co-ordinating the movement of developing germ cells towards the lumen of the seminiferous epithelium and in the process of spermiation.

Animals↗
PubMed1996

beta-adrenergic antagonism alters the behavioral and neurochemical responses to cocaine.

The effects of the beta-adrenergic antagonist propranolol on the locomotor stimulating, neurochemical, and reinforcing effects of cocaine were examined in rats. In Experiment 1, propranolol (1, 3 and 10 mg/kg, IP) produced a dose-dependent increase in the motor stimulant effects of cocaine without affecting basal motor activity. Atenolol, a peripherally restricted beta 1 antagonist, and (+) propranolol, the inactive isomer of propranolol, did not alter cocaine-induced locomotion. In Experiment 2, propranolol was shown to augment significantly the increase in extracellular dopamine content in the nucleus accumbens that accompanies a cocaine challenge. Experiment 3 demonstrated that propranolol produced a dose-dependent decrease in cocaine self-administration. Atenolol (10 mg/kg, IP) reduced cocaine self-administration but to a much lesser extent than propranolol. Experiment 4 demonstrated that coadministration of propranolol and cocaine did not alter the levels of cocaine in the brain and plasma achieved by cocaine administration alone. These data suggest that the blockade of beta-adrenergic receptors potentiates cocaine-induced elevation of dopamine transmission in the nucleus accumbens, which is associated with an increase in cocaine-induced motor activity and a decrease in cocaine self-administration.

Adrenergic beta-Antagonists↗
PubMed1996

Epididymal oxytocin in the rat: its origin and regulation.

Oxytocin is localized to the Leydig cells of the testis in the rat and several other species where it is postulated to play a role in steroidogenesis and seminiferous tubule contractility. Oxytocin has also been detected in the epididymis of the ram where active uptake of the peptide from luminal fluid has been demonstrated. This study was performed to investigate whether oxytocin is present in the rat epididymis, and the origin of the peptide. Immunoactive oxytocin was detected in the epididymis of all control animals examined (147.7 +/- 41.7 pg/g). Total epididymal oxytocin was reduced significantly following castration (p < 0.05). Testosterone treatment also reduced the epididymal concentration of the peptide in both intact and castrated rats. Efferent duct ligation (EDL) did not affect the presence of oxytocin in the epididymis. Immunoactive oxytocin was localized in discrete cells of the epithelium of the caput epididymis, with less staining apparent in the initial segment and cauda epididymis. Staining disappeared from the caput epididymis following castration, but reappeared following testosterone supplementation. No obvious alteration in staining was observed in the cauda epididymis after EDL. These data demonstrate for the first time the presence of oxytocin in the epididymis of the rat and that the peptide may be regulated by androgens. They further suggest an epididymal source of the peptide.

Animals↗
PubMed1995

Inhibitory effects of dopamine and methylenedioxymethamphetamine (MDMA) on glutamate-evoked firing of nucleus accumbens and caudate/putamen cells are enhanced following cocaine self-administration.

Rats were allowed to self-administer cocaine during a 3-h session for 15 days. One to 11 days after the last cocaine exposure, rats were anesthetized with urethane and effects of microiontophoretically-applied dopamine on glutamate-evoked firing of neurons in the nucleus accumbens and in the caudate/putamen were tested. Dopamine produced a dose-dependent inhibition of glutamate-evoked firing in both the nucleus accumbens and the caudate/putamen of rats that had been repeatedly exposed to self-administered cocaine and in control rats. However, the DA-induced inhibition was significantly greater in the group that had self-administered cocaine. The cocaine self-administration group was significantly sensitized to the inhibitory effects of dopamine in both early (1-3 day) and later (9-11 days) periods of cocaine abstinence. Following cessation of repeated cocaine self-administration sessions, nucleus accumbens cells were also sensitized to the inhibitory effects of methylenedioxymethamphetamine (MDMA), a drug that increases extracellular levels of DA and serotonin in the nucleus accumbens. This sensitization to DA- and MDMA-induced inhibition in the nucleus accumbens and in the striatum indicates that long-term neuroadaptations occur in these regions of the nervous system following repeated exposure to self-administered cocaine.

Animals↗
PubMed1994

Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome.

The nucleus accumbens is prominently implicated in the reinforcing effects of abused drugs, and is an important site for mediating aversive stimulus properties of opiate withdrawal. It is generally thought, however, that the role of the accumbens is negligible in the somatic signs of opiate withdrawal. Contrary to this assumption, we now report that D2 dopaminergic receptor activity in the accumbens area potently regulates somatic symptoms of opiate withdrawal. We find that activation of D2 receptors within the accumbens prevents somatic signs of naloxone-induced opiate withdrawal and, conversely, that blockade of accumbal D2 receptors in opiate-dependent animals elicits somatic withdrawal symptoms. These data indicate that dopamine in the accumbens not only is important in the rewarding effects of abused drugs, but also (via D2 receptors) plays a pivotal role in opiate withdrawal.

Animals↗
PubMed1994

Behavioral associations of neuronal activity in the ventral tegmental area of the rat.

The ventral tegmental area (VTA) is a central element in a system that mediates the reinforcing properties of natural stimuli (such as food), brain stimulation, and drugs of abuse. Although considerable effort has been applied to understanding how drugs of abuse influence this system, relatively little work has examined its function during conditioned reinforcement tasks in awake, behaving animals. In the present studies, bundles of four to eight microwire electrodes were chronically implanted in the VTA or prefrontal cortex (PFC) of male Wistar rats. Following recovery from surgery, simultaneous recordings from multiple single neurons and unit clusters were obtained in rats pressing a lever for a sucrose solution on a fixed-ratio schedule of reinforcement. Consistent with the hypothesis that these neurons encode information related to motivation, most of the neurons in both VTA and PFC showed significant modulation of firing rate associated with one or more events occurring within the response/reinforcement cycle. These events included lever presses, onset and end of a tone signaling sucrose delivery, and onset and end of sucrose consumption. Significant decreases in firing rate were observed, coincident with onset of the tone and sucrose delivery, or with consumption. These decreases were sustained through the end of sucrose consumption. A number of neurons also discharged bursts of activity associated with individual lever presses. These findings provide a clear demonstration that VTA neuronal activity is modulated during motivated behavior. Similar information about events within the ongoing response/reinforcement cycle appears to be distributed through many neurons within the VTA, and may be mirrored in target structures such as PFC.

Action Potentials↗
PubMed1993

Beta-adrenergic antagonists attenuate withdrawal anxiety in cocaine- and morphine-dependent rats.

Rats were treated chronically with either cocaine (20 mg/kg/day, 14 days), morphine (incrementing doses of 10 mg/kg/day to 80 mg/kg, 11 days) or saline. During morphine or cocaine abstinence (48 h), dependent rats showed increased anxiety-like behavior in a conditioned defensive burying paradigm as evidenced by significantly shorter latencies to begin burying as well as a 4-fold increase in burying duration relative to saline-treated animals. This withdrawal-induced increase in burying behavior was blocked by pretreatment with either the beta-adrenergic antagonist propranolol (5 mg/kg) or the lipophobic selective beta 1-antagonist, atenolol (5 mg/kg). These results are consistent with the possibility that activation of peripheral beta 1 receptors may substantially contribute to withdrawal-induced anxiety and that beta-adrenergic antagonists could be useful in treating in cocaine and morphine dependent addicts.

Adrenergic beta-Antagonists↗
PubMed1993

Beta-adrenergic antagonists attenuate somatic and aversive signs of opiate withdrawal.

The current studies were designed to evaluate the effectiveness of beta-adrenergic antagonists on opiate withdrawal symptoms utilizing a variety of paradigms. Male Sprague-Dawley rats were made moderately dependent on morphine with daily incremental injections. Both the nonselective beta-antagonist propranolol and the selective beta 1-antagonist atenolol, in the dose range of 5 to 20 mg/kg, were found to significantly reduce many of the somatic responses to either naloxone-precipitated or abstinence-induced withdrawal from morphine. In addition, propranolol (10 mg/kg) significantly reduced a withdrawal-induced conditioned place aversion, while atenolol was effective only at the highest dose tested (20 mg/kg). These data indicate that beta-adrenergic antagonists might be effective in the treatment of opiate addictions.

Adrenergic beta-Antagonists↗
PubMed1993

Selective inactivation of muscarinic M2 and M3 receptors in guinea-pig ileum and atria in vitro.

1. The role of muscarinic M2 and M3 receptors in ileal smooth muscle has been evaluated by use of selective receptor alkylation. The alkylating agents, 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMP mustard) was studied for effects against (+)-cis-dioxolane, at muscarinic M2 and M3 receptors in guinea-pig atria or ileum, respectively. 4-DAMP mustard (10 nM, 40 min exposure) did not discriminate between these muscarinic receptors. In ileum, 4-DAMP mustard, at 100 nM, resulted in a large dextral shift (197 fold) and depression in maxima. In atria there was a smaller dextral shift (14 fold) but no depression in maxima. 2. The muscarinic antagonists, atropine (non-selective), methoctramine (M2-selective) and para-fluorohexahydro-siladiphenidol (pFHHSiD; M3 selective) were studied in protection studies against alkylation by phenoxybenzamine. Washout studies following equilibration of the tissues with atropine (30 nM), methoctramine (0.3 microM) or pFHHSiD (3 microM), showed the compounds to be reversible. No temporal changes in sensitivity to (+)-cis-dioxolane were observed. 3. Exposure, for 20 min, of atria and ileum to phenoxybenzamine (3 and 10 microM respectively) caused dextral shifts and depressions in the maxima of the concentration-response curve to (+)-cis-dioxolane. These effects were inhibited by prior equilibration with atropine (30 nM) and methoctramine (0.1 microM) in atria or atropine (30 nM) and pFHHSiD (3 microM) in ileum. Similar results in ileum were obtained when pilocarpine was used as the agonist. 4. These data were consistent with muscarinic M2 receptors mediating responses in atria and M3 receptors mediating responses in ileum. No evidence was provided for a direct role of muscarinic M2 receptors in ileal contraction.5. It is concluded that receptor protection by reversible antagonists for muscarinic M2 or M3 receptors provides a means to isolate pharmacologically a single subtype in a tissue possessing heterogeneous populations. This technique may prove useful in defining the role of the respective subtypes in smooth muscle contraction.

Alkylating Agents↗
PubMed1992

Characterization of the interaction of the cervane alkaloid, imperialine, at muscarinic receptors in vitro.

The action of the cervane alkaloid, imperialine, has been assessed at M1, M2 and M3 receptors in functional assays and at M1, M2, M3 and putative M4 sites in binding studies. In functional studies, imperialine acted as a selective surmountable antagonist at M2 receptors in guinea-pig isolated atria and uterus (-log KB = 7.7 and 7.4, respectively), in comparison to M1 receptors in canine isolated saphenous vein (-log KB = 6.9) or M3 receptors in a range of guinea-pig isolated smooth muscles including ileum, trachea, fundus, seminal vesicle or oesophagus (-log KB = 6.6-6.8). In rat aorta, the -log KB value at the M3 receptor (5.9) was slightly, but significantly, lower. In competition radioligand binding studies, imperialine was also selective toward to M2 sites in rat myocardium (-log Ki = 7.2) with respect to M1 and M3 sites (rat cerebral cortex, rat submaxillary gland; -log Ki = 6.1 and 5.7, respectively). However, it did not significantly discriminate between rat cardiac M2 sites and putative M4 sites in rabbit lung (-log Ki = 6.9). Imperialine resembles the alkaloid himbacine in terms of its pharmacological profile at muscarinic receptor subtypes in that it acts as an M2 selective antagonist with respect to M1 or M3 sites. It may also provide a second, commercially available, antagonist with which to discriminate between M1 and M4 receptors.

Alkaloids↗