Genetic evidence for different male and female roles during cultural transitions in the British Isles.

Human history is punctuated by periods of rapid cultural change. Although archeologists have developed a range of models to describe cultural transitions, in most real examples we do not know whether the processes involved the movement of people or the movement of culture only. With a series of relatively well defined cultural transitions, the British Isles present an ideal opportunity to assess the demographic context of cultural change. Important transitions after the first Paleolithic settlements include the Neolithic, the development of Iron Age cultures, and various historical invasions from continental Europe. Here we show that patterns of Y-chromosome variation indicate that the Neolithic and Iron Age transitions in the British Isles occurred without large-scale male movements. The more recent invasions from Scandinavia, on the other hand, appear to have left a significant paternal genetic legacy. In contrast, patterns of mtDNA and X-chromosome variation indicate that one or more of these pre-Anglo-Saxon cultural revolutions had a major effect on the maternal genetic heritage of the British Isles.

Effects of stretch-based progressive relaxation training on the secretion of salivary immunoglobulin A in orofacial pain patients.

There is a growing body of evidence that psychologic stressors can affect physical health and proneness to disease through depletion of the body's immune system. Relatively little research, however, has investigated the potential immunoenhancing effect of stress-relieving strategies such as progressive muscle relaxation. This study explored the relationship between immune functioning and relaxation training with persons experiencing persistent facial pain. In a single experimental session, 21 subjects either received relaxation training or rested for an equivalent time period. Salivary immunoglobulin A, mood, pain, and tension levels were measured before and after relaxation and rest periods. Results indicated that a greater proportion of those receiving relaxation training had increases in secretion of salivary immunoglobulin A. These findings suggest that immunoenhancement may be another potential benefit of progressive relaxation training for persons with chronic pain conditions.

Relaxation training and opioid inhibition of blood pressure response to stress.

The present study was designed to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training. Opioid mechanisms were assessed by examination of the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and after relaxation training. Thirty-two young men with mildly elevated casual arterial pressure were recruited for placebo-controlled naltrexone stress tests and relaxation training. The results indicated that relaxation training significantly reduced the diastolic pressure response to mental arithmetic stress. Opioid receptor blockade with naltrexone antagonized the effects of relaxation training. These findings suggest that some of the physiological effects of relaxation training are mediated by augmentation of inhibitory opioid mechanisms.

N-methyl-D-aspartate (NMDA) stimulates release of alpha-MSH from the rat hypothalamus through release of nitric oxide.

Superfusion of rat hypothalamic slices with 10(-4) M N-methyl-D-aspartic acid (NMDA) resulted in increased release of alpha-melanocyte-stimulating hormone (alpha-MSH). Peptide release was blocked by 10(-6) M NG-nitro-L-arginine methyl ester (L-NAME) a specific competitive inhibitor of nitric oxide synthase but not by the inactive enantiomer D-NAME at 10(-6) M. The inhibition by L-NAME was reversed by the addition of 10(-5) mM L-arginine, an excess of enzyme substrate. Release of nitric oxide products into tissue superfusates was stimulated by a 50 mM concentration of potassium ions and by 10(-4) M NMDA. Potassium-stimulated release was blocked by L-NAME. Basal, potassium-stimulated and NMDA-stimulated release of nitric oxide products were significantly inhibited by the NMDA-receptor antagonist D(-)-2-amino-5-phosphopentanoic acid (AP5) at 10(-4) M and by the NMDA-channel blocker ketamine at 10(-4) M. We conclude that nitric oxide mediates the stimulatory action of glutamic acid on the release of alpha-MSH from the rat hypothalamus.

Endogenous glutamate stimulates release of alpha-melanocyte-stimulating hormone from the rat hypothalamus.

Release of alpha-melanocyte-stimulating hormone (alpha-MSH) and glutamic acid was quantified from superfused slices of rat hypothalamus. Application of L-glutamic acid 10(-4) M failed to evoke release of alpha-MSH but, in the presence of 10(-4) M dihydrokainic acid (DHK) an inhibitor of glutamate uptake systems, caused significant stimulation of release. DHK caused gradual and sustained increases in both alpha-MSH and glutamate release. That in alpha-MSH was blocked by 10(-4) M DL-2-amino-5-phosphopentanoic acid, a competitive N-methyl-D-aspartic acid (NMDA)-type glutamate receptor antagonist. We conclude that hypothalamic glutamate is subject to rapid uptake through mechanisms blocked by DHK and that alpha-MSH release is stimulated by endogenous and exogenous glutamate through NMDA-type receptors.

Endogenous gamma-aminobutyric acid tonically inhibits release of alpha-melanocyte-stimulating hormone from rat hypothalamic slices.

Release of immunoreactive alpha-melanocyte-stimulating hormone (alpha-MSH) from superfused slices of rat hypothalamus was stimulated by the gamma-aminobutyric acid (GABA) receptor antagonist, bicuculline, and inhibited by the benzodiasepine, chlordiazepoxide, an allosteric GABA receptor modulator, demonstrating the presence of tonic inhibition of alpha-MSH release by endogenous GABA in hypothalamic tissue. Chlordiazepoxide increased the effect of exogenous GABA which by inhibiting basal release of alpha-MSH demonstrated that the tonic inhibition was not maximal in the resting state.

Characteristics of NMDA receptors that stimulate release of hypothalamic alpha-MSH.

N-methyl-D-aspartic acid (NMDA) 10(-4) M stimulated release of immunoreactive alpha-melanocyte-stimulating hormone (alpha-MSH) from superfused slices of rat hypothalamus through receptors which shared common features with other central NMDA-type glutamate receptors. The receptors possessed inhibitory sites for both Mg2+ and ketamine; basal and NMDA-stimulated alpha-MSH release was reduced by high (5 mM) Mg2+ ion concentrations and by 10(-4) M ketamine, whilst use of Mg(2+)-free media led to a prolongation of the NMDA-stimulated response. The receptors were also shown to possess an allosteric glycine site. The glycine site agonist D-serine 10(-4) M potentiated basal and NMDA-stimulated alpha-MSH release whilst the antagonist, 7-chlorokynurenic acid 10(-4) M, reduced NMDA-stimulated release, an effect which was partially reversed by 10(-4) M D-serine.

Ionic, neuronal and endocrine influences on the proopiomelanocortin system of the hypothalamus.

Increasing evidence supports a neurotransmitter or a neuromodulator action for peptides derived from proopiomelanocortin in the hypothalamus. Peptide release involves sodium, potassium and calcium ion channels and is dependent on the presence of extracellular calcium ions at the time of depolarisation of neuronal membranes. Dopaminergic and gamma-aminobutyric acid-containing neuronal systems inhibit POMC-derived peptide release from the hypothalamus through D2-dopamine and GABAA receptors, respectively. Serotoninergic mechanisms exert a biphasic effect on peptide release being directly stimulatory at low concentrations of serotonin and indirectly inhibitory at higher concentrations via interactions with the endogenous dopaminergic system. Cholinergic and glutamergic drugs stimulate peptide release through nicotinic and N-methyl-D-aspartate receptors, respectively. Finally, circulating steroids regulate the hypothalamic POMC system with testosterone stimulating POMC gene expression whilst oestradiol and glucocorticoids induce an inhibitory control.

Regulation of alpha-melanocyte-stimulating hormone release from superfused slices of rat hypothalamus by serotonin and the interaction of serotonin with the dopaminergic system inhibiting peptide release.

Release of alpha-melanocyte-stimulating hormone (alpha-MSH) from frontal slices of rat hypothalamus superfused with oxygenated artificial cerebrospinal fluid (ACSF) was quantified by radioimmunoassay. Control depolarisations with 50 mM KCl-containing ACSF produced significant increases in alpha-MSH release which were partially blocked by 10(-6) M cinanserin, a serotonin (5-HT) receptor antagonist. Superfusion of the tissues with varying concentrations of 5-HT (10(-7) M to 10(-4) M) resulted in an inverted U-shaped dose-response curve, maximum alpha-MSH release being obtained with 10(-6) M 5-HT. Addition of 10(-6) M cinanserin shifted the 5-HT dose-response curve to the right whilst the presence of 10(-8) M flupenthixol, a dopamine receptor antagonist, resulted in a sigmoidal 5-HT dose-response curve. Superfusion with ACSF containing either 10(-7) M fluoxetine, a 5-HT re-uptake inhibitor, or 10(-7) M p-chloroamphetamine, an agent releasing 5-HT, induced significant increases in alpha-MSH release which were abolished in the presence of 10(-6) M cinanserin. These data demonstrate the presence of an endogenous 5-HT system that exerts a biphasic effect on alpha-MSH release. A stimulatory effect caused by lower 5-HT concentrations appears to be a direct action whilst an inhibitory effect at higher concentrations is mediated through an inhibitory endogenous dopaminergic system. A significant proportion of K+-stimulated peptide release is 5-HT-mediated.

D2- but not D1-dopamine receptors are involved in the inhibitory control of alpha-melanocyte-stimulating hormone release from the rat hypothalamus.

Release of alpha-melanocyte-stimulating hormone (alpha-MSH) from slices of rat hypothalamus superfused with artificial cerebro-spinal fluid (ACSF) was quantified by radioimmunoassay. Addition of 10(-6) M quinpirole, a D2-dopamine receptor agonist, to the superfusion medium caused a significant (P less than 0.001) reduction in the amount of alpha-MSH released upon depolarisation with 50 mM potassium from 319 +/- 37% to 110 +/- 16% of basal release in normal ACSF (mean +/- S.E.M.). Basal peptide release in the presence of quinpirole was unaffected. Sulpiride, a D2-dopamine receptor antagonist, at a concentration of 10(-6) M, induced a significant (P less than 0.05) increase of both basal and potassium-stimulated alpha-MSH release to 203 +/- 21% and 447 +/- 88% of basal release in normal ACSF respectively. The latter increases were abolished when sulpiride and quinpirole were added in combination. SK&F 38393-A and SCH 23390, a D1-dopamine agonist and antagonist respectively, had no significant effect on either basal or potassium-stimulated alpha-MSH release. It is proposed that endogenous dopamine exerts an inhibitory control on alpha-MSH release from the rat hypothalamus via D2-dopamine receptors and that in isolated hypothalamic slices there is a tonic inhibition of peptide release due to the activity of this system.

Ion and ion channel involvement in alpha-melanocyte-stimulating hormone secretion from superfused slices of rat hypothalamus.

Release of alpha-melanocyte-stimulating hormone (alpha-MSH) from 250 micron frontal slices of rat hypothalamus superfused at 37 degrees C with oxygenated artificial cerebrospinal fluid (ACSF) was quantified in freeze-dried samples of ACSF by radioimmunoassay. Significant reproducible increases in alpha-MSH release were caused by 40-70 mM K+ in ACSF, maximum release being caused by 50 mM K+. Fifty mM K+-stimulated alpha-MSH release was abolished in the absence of Ca2+ from ACSF and by the presence of 10(-6) M tetrodotoxin. Tetrapentylammonium ions, 10(-4) M and 10(-3) M, stimulated dose-dependent increases in alpha-MSH release. The data support a putative neurotransmitter/neuromodulator role for alpha-MSH in the CNS.

Dopaminergic inhibition of alpha-melanocyte-stimulating hormone release from superfused slices of the rat hypothalamus.

The dopamine agonist apomorphine (10(-6) M) significantly reduced the 50 mM K+-stimulated, Ca2+-dependent release of immunoreactive alpha-melanocyte-stimulating hormone (alpha-MSH) from superfused slices of rat hypothalamus but did not alter baseline peptide release. Flupenthixol (10(-6) M), a dopamine receptor antagonist, significantly increased both basal and 50 mM K+-stimulated alpha-MSH release, possibly via blockade of inhibition caused by endogenous dopamine release. The latter increases were Ca2+-dependent and were inhibited by 10(-6) M apomorphine.

Internal mammary lymphoscintigraphy in patients with breast cancer. Correlation with computed tomography and impact on radiation therapy planning.

Twenty patients with Stage I or II breast cancer, all of whom had undergone radiation therapy planning, were examined with internal mammary lymphoscintigraphy (IMLS) and computed tomography (CT). Based on the results of IMLS, radiation fields were revised in 12 cases (60%). The mean number of nodes identified by IMLS in each patient was 7.8, which is in agreement with previously published autopsy and scintigraphic data. CT identified 243 possible nodes of normal size, but only 49 of them were within 10 mm of regions shown to be positive on the scintigram. The authors conclude that IMLS is the method of choice for defining parasternal lymphatic drainage and identifying those internal mammary nodes that are normal in both size and function.

Behavioral preparation of patients for gastrointestinal endoscopy: information, relaxation, and coping style.

The effectiveness of two techniques for preparing patients to undergo a stressful medical examination was assessed using observer self-report, and physiological measures of distress during gastrointestinal endoscopy. Patients were either informed about expected sensations, trained in systematic muscle relaxation, or received normal hospital procedures. The influence of coping styles on the effectiveness of information and relaxation techniques was examined for measures of fear, avoidance, emotional control, arousability, and independence. Information and relaxation interventions reduced heart rate increases and observer ratings of distress during tube insertion. Relaxation training also increased positive mood change following the procedure. Interactions between coping styles and recovery measures suggested patients benefited most from preparation that matched their preferred coping style, but were not harmed by preparation that did not match their preferred style. Discussion focuses on how coping styles may interact with preparation procedures and suggests that the use of coping styles as criteria for excluding patients from certain preparation techniques is inappropriate.

Behavioral preparation for surgery: benefit or harm?

Elective surgery patients were prepared for surgery with training in muscle relaxation or with information about sensations they would experience. Relaxation reduced hospital stay, pain, and medication for pain and increased strength, energy, and postoperative epinephrine levels. Information reduced hospital stay. Personality variables (denial, fear, aggressiveness) were associated with recovery and influenced patients' responses to preparation. Less frightened patients benefited more from relaxation than did very frightened patients. Nonaggressive patients reacted to information with decreased hospital stay along with increased pain, medication, and epinephrine. Aggressive patients responded to information with decreased hospital stay along with decreased pain, medication, and epinephrine. Patients using denial were not harmed by preparation. A catharsis/moderation model is proposed to explain the benefits of relaxation. This study suggests that behavioral preparation benefits even frightened, aggressive, or denying elective surgical patients.