Articles / Άρθρα

Primary cortisol resistance in man is a familial disease. It is characterized by increased plasma cortisol concentrations, high urinary free cortisol excretion, a normal circadian pattern of cortisol secretion, resistance to adrenal suppression by dexamethasone and absence of clinical stigmata of Cushing's syndrome. In its severe form, hypertension and hypokalemic alkalosis are present, owing to increased secretion of the sodium-retaining corticoids, corticosterone and deoxycorticosterone. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the disease is revealed only by detailed examination of several parameters of cortisol metabolism. In the whole-cell assay (peripheral mononuclear leukocytes or fibroblasts) the glucocorticoid receptor shows a low affinity for dexamethasone. The receptor may be unsaturable as suggested by decreased receptor concentrations in broken-cell systems. Thus, generalized target-tissue resistance to cortisol, including the pituitary gland and the hypothalamus, is accompanied by a decreased negative feedback of the cortisol-ACTH feedback system resulting in increased ACTH secretion. This causes higher plasma cortisol to compensate for the endorgan resistance and also increases the production of adrenal mineralocorticoids, as by-products. Thus hypertension and hypokalemic alkalosis depends on the degree of the resistance.Cortisol resistance in many New World primate species is characterized by greatly increased plasma cortisol concentrations, decreased cortisol binding globulin capacity and affinity, high levels of plasma and urinary free cortisol, marked resistance of ACTH suppression by dexamethasone, and no physiologic evidence of glucocorticoid hormone excess. Target tissues have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. The New World primates, unlike man, have compensated for this cortisol resistance with intra-adrenal adaptations over the 50 million years of their evolutionary development. These primates also have abnormalities of other steroid hormone-receptor systems such as progesterone, estrogen, androgen and mineralocorticoid. In contrast, the human syndrome appears to be a recent mutation with pathophysiologic consequences.

The squirrel monkey, a New World primate, has elevated plasma estradiol and progesterone concentrations compared to those in the cynomolgus macaque, an Old World primate. We previously reported that uterine progesterone receptor concentrations examined in ovariectomized squirrel monkeys 2 days after estrogen treatment were about one eighth those in identically treated cynomolgus macaques. To examine this in greater detail, we gave estradiol (10 μg/kgday) to ovariectomized squirrel and cynomolgus monkeys for various lengths of time (0,2,4,7, and 14 days), followed by measurement of uterine estrogen and progesterone receptors and assessment of endometrial histology (including glycogen and peroxidase stains), vaginal histology, and cytology. Endometrial and vaginal mor morphologies showed adequate estrogen effects, as did glycogen and peroxidase stains. Two days of treatment were sufficient to induce both estrogen and progesterone receptors to maximalbinding of [3H]moxestrol and [3H]R5020, respectively, in both species. Squirrel monkeys had about one third and one eighth the estrogen and progesterone uterine receptor concentrations, respectively, of cynomolgus monkeys. Receptor affinities in both species were similar.Neither [3H] moxestrol nor [3H]R5020 boundtouterine cytosols from untreated monkeys. We conclude that the increased plasma concentrations of estradiol and progesterone in the squirrel monkey compensate for the decreased estrogen and progesterone receptors in this species.

Several lines of experimental evidence suggest that acetylcholine and other cholinergic agonists are excitatory to the hypothalamic-pituitary-adrenal (HPA) axis. To examine the site on the HPA axis that is stimulated by cholinergic agents, we evaluated the in vivo and in vitro effects of the muscarinic cholinergic agonist arecoline in intact and pituitary stalk-transected rats as well as on isolated rat hypothalami, dispersed anterior pituicytes, and adrenocortical cells in culture. Arecoline, injected iv to catheterized, freely moving male Sprague-Dawley rats, stimulated plasma ACTH and corticosterone release in a dose-dependent fashion. The muscarinic cholinergic antagonist atropine significantly blunted the ACTH response to arecoline. Pituitary stalk transection led to diminished plasma ACTH and corticosterone responses to arecoline. Similarly, previous administration of anti-CRH serum significantly blunted these responses. These findings suggest that arecoline stimulates the HPA axis centrally, mainly via secretion of CRH. This hypothesis was confirmed by the dose-dependent ability of arecoline to cause hypothalamic CRH secretion in vitro, an effect antagonized by atropine, and its failure to elicit ACTH and corticosterone secretion by dispersed anterior pituicytes and adrenocortical cells in culture, respectively. These data suggest that the muscarinic cholinergic agonist arecoline stimulates the HPA axis in the rat and that this effect is mediated mainly by the release of endogenous CRH. Arecoline, therefore, appears to be a compound suitable to selectively evaluate the responsiveness of the central component of the HPA axis.

Stress-related activation of the hypothalamic-pituitary-adrenal axis (HPA) is associated with suppression of the reproductive axis. This effect has been explained by findings indicating that corticotropin-releasing hormone suppresses hypothalamic gonadotropin-releasing hormone (GnRH) secretion via an opioid peptide-mediated mechanism, and that glucocorticoids suppress both GnRH and gonadotropin secretion and inhibit testosterone and estradiol production by the testis and ovary, respectively. To evaluate whether glucocorticoids suppress the effects of estradiol on its target tissues, we examined the ability of dexamethasone to inhibit estradiol-stimulated uterine and thymic growth in ovariectomized rats. Estradiol alone, given daily for 5 days, caused dose-dependent uterine and thymic growth. Dexamethasone alone, given daily for 5 days, caused a dose-dependent decrease in body weight gain and in thymic growth. When estradiol and dexamethasone were administered simultaneously, however, body weight gain and thymic growth were also inhibited (p < 0.05). Dexamethasone decreased estradiol-induced uterine cytosolic and nuclear estrogen receptor concentrations (E2R0, p < 0.05; E2nR0, respectively), but had no effect on estradiol-induced progesterone receptor concentrations (P4R0, p > 0.05). Levels of uterine glucocorticoid receptors were not affected by estrogen and/or dexamethasone treatment. These findings suggest that stress levels of glucocorticoids, administered over a 5-day interval, block the estradiol-stimulated growth of female sex hormone target tissues. This effect may be partially mediated by a glucocorticoid-induced decrease of the estradiol receptor concentration. Thus, another mechanism by which the HPA may influence reproductive function during stress is by a direct effect of glucocorticoids on the target tissues of sex steroids.

We studied the effects of tumor necrosis factor-α (TNFα), a macrophage-derived pleiotropic cytokine produced during the inflammatory/immune response, on the function of the hypothalamic-pituitary-adrenal (HPA) axis of the rat. Intravenous injections of TNFα stimulated plasma ACTH and corticosterone secretion in a dose-dependent fashion. This effect was inhibited by a rat CRH antiserum that was administered to the rats 1 h before the TNFα injections. This suggested that CRH is a major mediator of the HPA axis response to TNFα. We subsequently evaluated the ability of TNFα to influence CRH and ACTH secretion in vitro by explanted rat hypothalami in organ culture and by dispersed rat anterior pituicytes in primary culture respectively. Hypothalami were incubated for 40 min with graded concentrations of TNFα (10 pM to 1 μM). This cytokine stimulated CRH secretion in a dose-dependent fashion, with an ECB0 of 6.7 x 10 pM (P < 0.05). Preincubation of hypothalamic expiants with dexamethasone, indomethacin (1 μM), eicosatetraynoic acid (10 μM), or nordihydroguaiaretic acid (30 μM) resulted in inhibition of TNFα-stimulated CRH secretion (P < 0.05). Interestingly, 4-h incubation with TNFα had no effect on ACTH secretion from rat anterior pituicytes at a concentration of 10 nM. Higher concentrations of TNFα (100 nM and 1 μM), however, elicited a dose-dependent increase in the ACTH concentration in the medium. Our results suggest that TNFα represents one of the immune response mediators that directly or via stimulation of other cytokines act as activators of the HPA axis during immune/inflammatory reactions. This effect appears to be glucocorticoid suppressible and eicos-anoid mediated. The primary site of action of TNFα appears to be the hypothalamic CRH-secreting neuron. Some pituitary and adrenal effects of TNFα, however, cannot be excluded.

High concentrations of the 'peripheral' benzodiazepine (pBZD) binding site ('receptor') have been described in the hypothalamus, the pituitary and the adrenal glands. This study was undertaken to examine the effects of ligands of this binding site on the hypothalamic-pituitary-adrenal axis (HPA). To accomplish this we administered graded doses of the pBZD receptor agonist 4-chloro-diazepam (Ro5-4864) i.v. to catheterized, freely moving adults male Sprague-Dawley rats. Serial blood samples for plasma adrenocorticotropin hormone (ACTH) and corticosterone determinations were drawn from the catheter before and after the injection of the drug. Ro5-4864 significantly stimulated ACTH and corticosterone secretion in a dose-dependent fashion. To examine whether this effect could be antagonized by the pBZD binding site antagonist PK 11195, we treated rats with PK 11195 at doses 10- and 50-times higher than Ro5-4864 before administration of a maximally effective dose of Ro5-4864. Neither dose of PK 11195 antagonized Ro5-4864-induced plasma ACTH or corticosterone elevations. However, this agent, given alone, stimulated ACTH and corticosterone release. Similarly, carbamazepine (CBZ), which binds to the pBZD binding site with low affinity, stimulated weakly the HPA in vivo, reaching statistical significance only at the highest dose tested. To examine the site(s) of action of these compounds on the HPA, we evaluated their effects on hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH secretion in vitro. Ro5-4864 stimulated hypothalamic CRH, but not pituitary ACTH secretion. Neither PK 11195 nor CBZ had any agonist effect on hypothalamic CRH secretion in vitro, whereas both antagonized Ro5-4864-induced CRH secretion. Both PK 11195 and CBZ, but not Ro5-4864, stimulated the in vitro activity of cultured pituitary corticotroph cells. These data suggest that benzodiazepine Ro5-4864 stimulates the HPA by acting mainly at the central component of this axis, whereas the isoquinolone derivative PK 11195 and the therapeutic agent CBZ may act mainly at the pituitary level.

To evaluate the recovery of the hypothalamicpituitary- adrenal (HPA) axis after discontinuation of prolonged exposure to glucocorticoids, we employed adult male Sprague- Dawley rats which were implanted sc with osmotic minipumps filled with saline (vehicle) or dexamethasone (DEX), 100 μg/ day, for 7 days. At the end of the glucocorticoid treatment period, the minipumps were removed and both saline- and DEX-treated rats were randomly assigned to five different groups tested at 1, 3, 7, 14, and 21 days after removal of the minipumps. Each group was divided into two subgroups receiving either arecoline (ARE), or ovine CRH (oCRH) stimulation tests. ARE was chosen because it has been shown to selectively stimulate the hypothalamic CRH neuron, whereas oCRH was selected as a probe of the pituitary component of the HPA axis. ARE (0.2 mg/kg) and oCRH (10 μg/kg) were injected iv to catheterized, freely moving rats and serial blood samples for plasma ACTH and corticosterone determinations were drawn from the catheter before, and 5, 15, 30, and 60 min after the injection. The day after the tests were performed, the rats were killed by decapitation, and body, adrenal and thymus weights, as well as hypothalamic CRH and pituitary ACTH content were determined. On the day of the stimulation tests, basal plasma levels of ACTH and corticosterone were not different between saline- and DEX-treated rats at any time-point after discontinuation of treatment. The ACTH response to ARE, on the other hand, was suppressed one day after, but became normal 3 days after discontinuation of DEX treatment. ACTH response to oCRH normalized later, after 7 days. Interestingly, corticosterone responses to both ARE and oCRH normalized 7 days after discontinuation of glucocorticoid administration. Body, adrenal and thymus weights were significantly reduced by DEX treatment. They recovered slowly and only after 22 days there was no difference between DEX- and saline-treated rats in body and adrenal weight. In contrast, thymus weight was still low on day 8, began to increase after 15 days, and by day 22 did not reach the values recorded in salinetreated rats. Hypothalamic immunoreactive CRH content was not different between DEX- and saline-treated rats, whereas the content of ACTH in the pituitary gland was lower in the DEXtreated rats the second day after discontinuation of GC treatment, normalized after 4 days and increased significantly after 8 days. These results suggest that in the rat, prolonged treatment with DEX reduces the ability of each component of the HPA axis to respond to an appropriate stimulus. This reduction is transient. Normalization of the hypothalamus occurs by the third day and of the pituitary gland and the adrenal cortex by the seventh day. This sequence of events is distinctly different from that which has been proposed in human beings.

High concentrations of ‘peripheral’ benzodiazepine binding sites have been described in the pituitary gland and in several other endocrine glands, such as the adrenal glands and the testes. The role played by these receptors on the regulation of the endocrine system is largely unknown. In this study, we report the effects of two ligands of the ‘peripheral’ benzodiazepine receptor, Ro5–4864 and PK 11195, on prolactin (PRL) release in the adult male rat. Ro5‐4864 stimulated PRL release with half maximal and maximal stimulatory doses of about 0.6 and 1.2 mg/kg, respectively. Pretreatment with the ‘peripheral’ benzodiazepine receptor antagonist PK 11195 did not have any effect on Ro5‐4864‐induced PRL release. Accordingly, PK 11195, given alone, stimulated PRL release in a dose‐dependent fashion. To examine whether the stimulatory effect of Ro5‐4864 and PK 11195 on PRL release was due to a direct effect of these compounds at the pituitary gland, we used primary cultures of anterior pituicytes. Neither Ro5‐4864 nor PK 11195 had an effect on basal PRL release nor were these agents capable of modulating thyrotropin‐releasing hormone‐stimulated or dopamine‐inhibited PRL release. These findings suggest that administration of agents that interact with the ‘peripheral’ benzodiazepine binding receptor cause PRL release without directly stimulating the pituitary gland. We speculate that Ro5–4864 and PK 11195 increase plasma PRL levels by modulating brain release of neurotransmitters and/or neuropeptides involved in the regulation of PRL release. Copyright

We report measurements of 11 hard X-ray selected active galaxies at 800 and 1100 μm made with the James Clerk Maxwell Telescope, and discuss these in the context of the continuum energy distribution from radio to X-ray wavelengths. Four other radio-loud AGN were also measured. Radio-loud objects show a spectrum which decreases smoothly in flux to higher frequencies, and supporting evidence strongly suggests a non-thermal origin. For radio-quiet objects we report only upper limits, but in all cases the fall from 100 μm to 1 mm is steep, strongly suggesting that thermal emission dominates the far-IR emission. Any underlying synchrotron components must become self-absorbed by a few tens of μm, implying that such non-thermal sources would have sizes of the order light hours (in conflict with the lack of far-IR variability) and should be heavily dominated by Compton scattering. We examine the alternative possibility that IR emission is entirely due to thermal dust re-emission of the observed UV continuum. Using a physical model in which we solve the radiative transfer through a spherical dust cloud, we find that to explain both the continuum shape over 5 μm to 1 mm, and the lack of silicate absorption, we require a region with τuv ∼ 10, and with density following r-1. To explain the continuum near 1 μm seems to need a strong stellar component, even in the unresolved nucleus, but we argue that such a nuclear star cluster may in fact be present. The strongest objections to such thermal models are the unexplained fine-tuning required, and a possible energy balance problem.

We present solutions of the axially symmetric radiative transfer problem in dust clouds, appropriate for modelling protostellar sources. In contrast to previous attempts to solve the axisymmetric problem, the method integrates the equation of radiative transfer exactly in the sense that it does not neglect any terms in the equation and treats multiple scattering from grains. The results of several computed models are presented showing the dependence of the emergent spectrum on model parameters and viewing angle.

The present report documents the breeding success of a new colony of common marmosets (Callithrix jacchus jacchus) and demonstrates a correlation between environmental stress and reproductive success. Environmental conditions ranged chronologically over 40 months, through four periods: I) the initial period, when the colony was formed; II) a phase of relative environmental stability; III) a stage of “environmental stress” (when the colony was disrupted by nearby construction); and IV) a return to a stable environment. Examination of reproductive status during each period indicated that the colony exhibited severe reproductive suppression during the time of the environmental disruption. Parity and the number of live births decreased and the number of spontaneous abortions increased during this period. Reproductive success remained low during period IV. More triplets than twins were born during the period of relative environmental stability.

We report here a study of the plasma ACTH and corticosterone responses to synthetic ovine CRH (oCRH) in hypothyroid and hyperthyroid rats studied 7, 15, and 60 days after either thyroidectomy or the administration of pharmaco-logical doses of T4. The purpose of this study was to further clarify the time-dependent effects of alterations in thyroid status on the functional integrity of the hypothalamic-pituitary-adrenal axis and to aid in the interpretation of the oCRH stimulation test in hypo- and hyperthyroid states. Our data demonstrate that hypothyroid rats have a significant reduction in the cere-brospinal fluid (CSF) levels of corticosterone and a significant decrease in adrenal weight in association with significant in-creases in the plasma ACTH response to oCRH. On the other hand, the corticosterone response to the ACTH released during the oCRH stimulation test was significantly reduced in hypo-thyroidism. With increasing duration of thyroidectomy-induced hypothyroidism, there was a progressive fall in CSF corticoster-one levels, a progressive increase in the plasma ACTH response to oCRH, and a gradual normalization of the corticosterone responses to the ACTH released during oCRH stimulation. Our findings in hyperthyroid rats were generally the converse of those seen in hypothyroidism. Hence, there was a significant increase in the CSF levels of corticosterone and a significant increase in adrenal weight in association with an initial slight decrease in the ACTH response to oCRH. On the other hand, the corticosterone response to the ACTH released during oCRH stimulation was significantly increased. There was a gradual increase in the magnitude of the rise in CSF corticosterone levels with time, as well as a gradual normalization of adrenocortical responses during oCRH stimulation. The ACTH plasma clear-ance rates were similar in hypo-, hyper-, and euthyroid rats. Our data do not permit definitive identification of the precise locus in the hypothalamic-pituitary-adrenal axis that is princi-pally affected by experimentally induced alterations in thyroid status. However, these data are most compatible with a subtle hypothyroid-induced centrally mediated adrenal insufficiency and a subtle hyperthyroid-induced centrally mediated hypercor- tisolism. These data also suggest that alterations in hypotha-lamic-pituitary-adrenal function in states of disturbed thyroid function become somewhat more pronounced as the duration of thyroid dysfunction increases. The fact that pituitary-adrenal responses to oCRH are consistently altered in states of thyroid dysfunction may be relevant to the clinical interpretation of oCRH stimulation tests. This is especially so because this test is commonly employed in clinical populations that show significant disturbances in thyroid function, including patients with major depression, Cushing’s disease, and anorexia nervosa.

1. 1. This study measured the changes in the auditory-evoked brainstem responses in the woodchuck (Marmota monax) during hibernation and arousal. 2. 2. The auditory brainstem response of the euthermic woodchuck consisted of four waves occurring in a 10 msec time window after stimulation. 3. 3. In the hibernating woodchuck, waves I and II could be traced down to the lowest body temperatures. 4. 4. As temperatures increased all the components of the ABR emerged. The latencies of all the waves showed systematic decrease with temperature increments, the effect being cumulative across the time window. 5. 5. These findings reflect activity in the VIIIth cranial nerve and the cochlear nuclei during hibernation and restoration of the functional integrity of the brainstem auditory pathway during arousal.

Peripherally-administered cholecystokinin (CCK) is a profound suppressor of food intake, can promote anxiety, and causes the acute release of ACTH into plasma. Centrally administered corticotropin-releasing hormone (CRH), on the other hand, not only represents the principal stimulus to the pituitary corticotroph cell, but also has been shown to suppress appetite and to be profoundly anxiogenic. Because of the overlap in the effects of peripherally administered CCK and of centrally administered CRH, we report here a study to determine whether sulphated CCK octapeptide (CCK-8) could induce the release of CRH within the central nervous system. To accomplish this task, we first assessed the dose-related effects of CCK8 on ACTH release. Graded doses of CCK8 (0.1-10 µg/kg BW) given in an iv bolus to freely moving male rats, resulted in a dose-dependent increase of plasma immunoreactive (IR)- ACTH (ED50: 1-10 µg/kg BW). The lowest maximal stimulatory dose of CCK-8 (5 µg/kg BW) was used in all subsequent experiments. To evaluate whether CCK-induced ACTH secretion was mediated by a peripheral CCK receptor, an iv bolus injection of vehicle or L-364, 718 (1 mg/kg BW), a specific, highly potent peripheral CCK receptor antagonist, was given before the iv administration of CCK-8 or vehicle. Plasma IR-ACTH response to CCK-8 was sianificantly attenuated bv L-364.718. A role for the vagal afferer & that contain CCK receptors in peripherally administered CCK-mediated hypothalamic-pituitary-adrenal (HPA) axis activation was examined in animals that had been pretreated with capsaicin, a potent neurotoxin that destroys vagal afferents. Plasma IR-ACTH and IR-corticosterone responses in capsaicin-treated animals were significantly lower than those in vehicle treated rate. In subsequent in vivo experiments, pituitary stalk-transected and sham-operated animals were used to evaluate whether CCK-8 stimulates the HPA axis via a centrally mediated mechanism. IR-ACTH and IR-corticosterone responses to iv CCKS were significantly reduced in the pituitary stalk-transected compared to sham-operated animals. In further effort to determine whether the central nervous system was involved in the plasma IR-ACTH response to the peripheral administration of iv CCK-8, we compared the effects of the iv administration of CRH antisera vs. normal rabbit serum on this parameter. IR-ACTH and IR-corticosterone responses to iv CCK-8 were significantly reduced in the context of pretreatment with CRH antisera compared to the administration of normal rabbit serum. We also showed that the intracerebroventricular administration of CCK-8 (250 ng) resulted in the significant stimulation of IR-ACTH release compared to vehicle, indicating a direct central effect of CCK. To further examine the locus-of the effects of CCK-8 on HPA axis stimulation, we also investigated the in vitro response of graded concentrations of CCK-8 on hypothalamic IR-CRH and pituitary IR-ACTH release. Although CCK-8 stimulates hypothalamic CRH secretion in a dose-dependent fashion, it had no effect, regardless of the dose, on IR-ACTH secretion by dispersed rat anterior pituicytes. We conclude that the HPA axis activation following the peripheral administration of CCK involves CCK-mediated CRH release occurring in part, via activation of CCK receptors on peripherally located vagal afferents. We also conclude that CCK in the central nervous system may cause the direct release of CRH from the paraventricular nucleus. These data suggest that CCK effects on pituitary-adrenal function, and perhaps food intake and anxiety, may be mediated, at least in part, via CRH. These data are of potential clinical relevance in the light of data linking both CCK and CRH to the pathogenesia and symptom complex of both eating and anxiety disorders.

Environmental events, both physical and emotional, can produce stress reactions to widely varying degrees. Stress can affect many aspects of physiology, and levels of stress, emotional status, and means of coping with stress can influence health and disease. The stress system consists of brain elements, of which the main components are the corticotropin-releasing homrone (CRH) and locus ceruleus (LC)-norepinephrine (NE)/autonomic systems, as well as their peripheral effectors, the pituitary-adrenal axis and the autonomic system, which function to coordinate the stress response. Activation of the stress system results in behavioral and physical changes which allow the organism to adapt. This system is closely integrated with other central nervous system elements involved in the regulation of behavior and emotion, in addition to the axes responsible for reproduction, growth and immunity. With current trends in stress research which focus on understanding the mechanisms through which the stress-response is adaptive or becomes maladaptive, there is a growing association of stress system dysfunction, characterized by hyperactivity and/or hypoactivity to various pathophysiological states. The purpose of this review is to 1) define the concepts of stress and the stress response from a historical perspective, 2) present a dynamic overview of the biobehavioral mechanisms that participate in the stress response, and 3) examine the consequences of stress on the physiologic and behavioral well-being of the organism by integrating knowledge from apparently disparate fields of science.

Binaural interaction in the auditory brainstem response: Multichannel recordings. Thodi, C. and Katbamna, B. (Department of Speech and Hearing, Cleveland State University, Cleveland, OH 44115, USA). Scand Audiol 1993; 22: 205-208 Binaural interaction (BI) waveforms were derived from multichannel recordings of auditory-evoked brainstem responses obtained at moderate and high intensity levels. The component latencies of all the BI responses derived from the contralateral channel were significantly prolonged compared with those derived from ipsilateral and non-cephalic channels. These channel differences were identified only at the moderate intensity level, indicating that BI cannot be isolated from the effects of stimulus interaction at higher intensities. The amplitudes were not significantly different across channels or intensities, indicating that ipsilateral, contralateral or non-cephalic recordings can be used to study BI. However, identification of channel differences on simultaneous multichannel recordings may provide an index of true neural interaction.

We present a generalization of the method of Efstathiou & Rowan-Robinson for the solution of the radiative transfer problem in dust clouds that takes into account a distribution of grain species and sizes. The method includes treatment of multiple scattering from grains and can be applied to axisymmetric density distributions. In this paper, however, we restrict our attention to the special case of spherical symmetry. We find that, in the parameter space we have explored, composite grains with 'average' absorption and scattering efficiencies approximate very well the emission from the grain mixture of Rowan-Robinson. We also re-examine the sample of compact H n regions of Crawford & Rowan-Robinson, and find that the combined effect of the multigrain calculations and a new model for interstellar grains by Rowan-Robinson is to improve considerably the agreement of models that assume high-optical-depth (Av ≈ 20-200) homogeneous clouds around hot stars with the IRAS data. For four objects we are able to compare our models with submillimetre data (350-1300 (xm). For W3(OH) the fit is good, but for the other three objects the models predict too much flux at long wavelengths. Possible reasons for this are discussed.

When mono-unsaturated fatty acids are heated in air, they form hemagglutinins. When the double bond is Δ-6,7 or Δ-9,10, the titer is higher than for Δ-11,12. Stearic acid does not become a hemagglutinin on heating. Hydroxy-monounsaturated fatty acids, ricinoleic (cis-12-OH-Δ-9) and ricinelaidic (trans-12-OH-Δ-9) are not hemagglutinins unless they are heated. Oleic acid (Δ-9-octadecenoic acid, OA) has a very low agglutination titer but lyses red cells at higher concentrations. Rabbit and rat erythrocytes (RBC) give the highest titers but RBCs of other species are also agglutinated. OA was chosen for further study. Its specific titer against rat RBCs increases with time of heating in air. Thin-layer chromatography (TLC) and mass spectroscopy (MS) show that higher molecular weight compounds are formed and that activity is associated with these materials. Synthetic (oxidation of oleic acid with tert-butyl peroxide) and commercial preparations of oleic acid dimers (Emery and Unichema) and a commercial preparation of oleic trimer mixed with polymer (Emery) have high hemagglutination titers against rat erythrocytes. A cyclic, long-chain dicarboxylic acid, 5(6)-carboxy-4-hexyl-2-cyclohexene-1-octanoic acid (Westvaco) gives a very low titer unless heated and no lysis. Sialidase treatment of the red cells increases the titer. Removal of cations does not alter the titer but addition of Ca2+ or Mg2+ lowers the titer. Light microscopy was used to characterize and visualize the agglutination process with rat RBCs. Agglutination without lysis or fusion is observed for low concentrations of heated oleic acid and C-18 dimers and trimer-polymer preparations, and no large vesicles are seen. We conclude that the oligomeric fatty acids with two or more hydrophobic chains of seven or more carbons are agglutinins at physiological pH. Agglutination by dimer may be the result of the its two hydrophobic side chains inserting into adjacent RBC membranes or the result of dimer inserting completely into RBC membranes and altering their properties. The carboxyl groups may also play a role in the process by interacting with polar headgroups in the RBC membrane.

We present a model for the nuclear infrared (IR) continuum spectrum of the Seyfert galaxy NGC 1068. The torus emission is modelled in terms of the tapered disc models of Efstathiou & Rowan-Robinson, which give a good fit to the global infrared properties of active galactic nuclei. The models include the effects of a distribution of grain species and sizes and multiple scattering from dust. Our analysis is constrained by the inclination of the torus predicted by optical spectropolarimetry. We assume in particular that our line of sight is inclined to the axis of symmetry by about 35°, and that the half-opening angle of the cone is 30°. We find that the torus emission alone cannot account for the whole of the IR continuum spectrum. While this is in agreement with recent mid-IR imaging observations, which show that up to 60 per cent of the flux is not originating from the torus, our model suggests that the difference between the observed and predicted torus emission is actually much greater at near-IR wavelengths. We attribute this excess IR emission to a component of optically thin dust [Av=0.1-0.5 mag) located in the ionization cone between the BLR and the NLR. This dust must be distributed as r-2 in order to produce the required spectrum. Flatter density distributions peak at longer density distributions peak at longer wavelengths and also produce a strong emission feature at 10 µm, contrary to observations. Even with an r-2 distribution, the grain mixture in the cone needs to be modified in order to suppress further the silicate emission feature. We suggest that this may be due to either destruction of silicate grains by shocks or the clumping of NLR dust. In addition, our model requires that the flux radiated by the central source towards the cone is at least a factor of 6 higher than that directed towards the bulk of the torus, which is naturally explained if the central source is an accretion disc. This conclusion depends mainly on the assumed inclination and opening angle of the torus, but is rather insensitive to other geometrical parameters.