Effect of intranasal fluticasone proprionate on the immediate and late allergic reaction and nasal hyperreactivity in patients with a house dust mite allergy

Background Patients with perennial allergic rhinitis develop nasal symptoms not only after allergen exposure, but generally also after non-specific stimuli. Objective To evaluate the effect of 2 week's treatment with fluticasone propionate aqueous nasal spray (FPANS) on the nasal clinical response, inflammatory mediators and nasal hyperreactivity. Methods Twenty-four rhinitis patients allergic to house dust mite (HDM). participated in a douhle-blind. placebo-controlled crossover study. After 2 week's treatment with placebo or 200 μg FPANS twice daily, patients were challenged with HDM extract. Symptoms were recorded and nasal lavages were collected for up to 9.5 h after challenge. Nasal hyperreaclivity was determined by histamine challenge 24 h later. Results Because of a carry-over effect for the immediate symptom score, for this variable only the data from the first treatment period were used. FPANS treatment resulted in a significant decrease of nasal symptoms with 70%. 69% and 63% after 100. 1000 and 10000 Biological Units (BU)/mL of HDM extract respectively. Active treatment resulted in a 76% decrease of the late-phase symptoms. FPANS treatment significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to reduce tryptase release after HDM 1000 BU ml. (P 0.0629). During the late phase FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS significantly decreased histamine-induced symptom score with 34%, secretion with 32%, and sneezes with 41%. Conclusion FPANS significantly inhibits the immediate and late allergic response, and nasal hyperreactivity, probably by suppressing mast cells and eosinophils in the nasal mucosa.     

Secretion of γ-Interferon at the Cellular Level

Using a haemolytic plaque assay for gamma-interferon (IFN-gamma) secretion we found that in vitro Epstein-Barr virus (EBV) exposure of peripheral blood mononuclear cells from EBV immune individuals led to IFN-gamma secretion, which was apparent within 6 h after virus contact and peaked 12-24 h after induction. Live, ultraviolet-light-irradiated and heat-inactivated virions all caused IFN-gamma secretion. In contrast, blood mononuclear cells from EBV non-immune adults or neonates could not be activated to IFN-gamma production by EBV.     

Analysis of the Expression of I-Ak-like Antigens in Murine Fetal and Adult Tissues with the Monoclonal Antibody 10–2.16

The expression of I-Ak antigens in normal C3H/FeJ adult and 15-day embryonic mice has been investigated by indirect immunofluorescence staining of tissue cryostat sections with the anti I-Ak antigen monoclonal antibody 10-2.16. In adult mice I-Ak antigens were expressed in Langerhans-like cells in the skin, epithelium of the gastrointestinal tract, endometrium, thymic reticuloepithelial cells, and several capillary endothelia. On the other hand, these antigens were not detected in Kupffer cells, alveolar macrophages, brain or mammary gland. In 15-day-old embryos the expression of Ia-like antigens was restricted to thymic reticuloepithelial cells, isolated spleen cells, and capillaries of the gastrointestinal tract.     

Nitric oxide synthase neurons in the rodent spinal cord: distribution, relation to Substance P fibers, and effects of dorsal rhizotomy

The indirect immunofluorescent method was employed to investigate the distribution of neuronal nitric oxide synthase-like immunoreactivity(nNOS-LI) in the spinal cord of the golden hamster and to compare it to data obtained from rats. Immunoreactive neurons were found throughout the cervico-sacral extent in the dorsal horn (mainly in laminae I-III) and in the preganglionic autonomic regions, i.e., the sympathetic intermediolateral nucleus (IML), lateral funicle (LF), intercalated region (IC), the area surrounding the central canal (CA), and the sacral preganglionic parasympathetic cell group. While the distribution of immunoreactive cells was generally similar in both species, some differences were observed. For example in the hamster LF, a higher percentage of stained neurons was seen than in the IML, while the situation was rather inverse in the rat. In order to study the coincidence of nNOS-LI in the population of preganglionic sympathetic neurons (PSN) that innervate the superior cervical ganglion (SCG), these were identified by retrograde axonal transport of fluoro-gold (FG) following unilateral injection into the SCG. PSN were localized ipsilateral to the injection site mainly in the IML and LF of spinal segments C7-Th4. The portion of double-labeled neurons of the IML were lower in hamster (17% in C7, 34% in C8) of FG-labeled cells) than in rat (47% in C8, 77% in Th2), while in the LF of segments C8-Th2 in both species the majority of FG-neurons contained nNOS. While only very few double-labeled neurons were detected in the IC in hamster and rat, a striking difference was observed in the CA, where no double-labeled neurons were found in hamster, but up to 50% in rat. Double immunofluorescence detection of nNOS and substance P (SP) showed that in both the autonomic regions and the dorsal horn, SP-LI fibers and puncta were present in close spatial relationship to nNOS-LI cell bodies. These results were basically identical in the hamster and rat. Unilateral transection of the dorsal roots of segments C6-Th2 in rats resulted in a clear reduction of SP-LI structures in the dorsal horn 5 days after rhizotomy, but not in the autonomic regions. Compared to the unlesioned side, the numbers of nNOS-LI neurons in the superficial laminae of the dorsal horn were reduced to 32-46% in the lesioned segments, and to 53% and 87%, respectively, in the two segments cranial to the rhizotomized segments but remained unchanged caudally to the lesion. Numbers of nNOS-LI cell bodies in the autonomic regions were not altered following dorsal root transection. The present study provides data on the widespread distribution of nNOS in the spinal cord of golden hamster and describes the partial coincidence of the enzyme in PSN. The effects of dorsal rhizotomy on nNOS-LI neurons in the dorsal horn reveal that primary-afferent fibers provide a stimulatory influence on neurons of the dorsal horn to generate the gaseous neuroactive substance, nitric oxide.     

The role of the hypothalamic paraventricular nuclei for the regulation of pineal melatonin synthesis: new aspects derived from the vasopressin-deficient Brattleboro rat

There is evidence for an involvement of the hypothalamic paraventricular nuclei (PVN) in the regulation of pineal melatonin synthesis in rats. Since electrical stimulation of the PVN or the systemic administration of arginine-vasopressin (AVP) result in a depression of the nocturnal melatonin surge, this neuropeptide appears to be pivotal for the transduction of PVN-efferent, pinealopetal signals. We therefore used an AVP-deficient animal model, the Brattleboro rat, to further investigate the mechanisms responsible for pineal regulation. Anesthetized adult male animals received 2 min of bilateral electrical stimulation of the PVN either during the day or at night. Thirty min later, pineal glands were removed and pineal N-acetyltransferase (NAT) activities and melatonin contents were determined. Stimulation resulted neither during the day nor at night in any significant alterations of pineal NAT activity or melatonin content when compared to control or sham-stimulated animals. These data further support the proposed modulatory role of AVP for the regulation of melatonin synthesis in the Epiphysis cerebri of genetically intact rats.     

CD8+ lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection

In most HIV-1-infected patients, clinical and immunological progression develops within a few years. Few infected people, termed long-term non-progressors (LTNP), remain healthy and immunologically stable for a long time. The factors governing the maintenance of this condition are not well known, but it is conceivable that CD8⁺ lymphocytes, cells that play a central role in controlling in vitro HIV replication, may have a part in vivo in this process. The aim of this study was to characterize the phenotypic profile and the cytokine production of CD8⁺ cells in a group of LTNP patients who had stable CD4⁺ cell counts (>500/mm³) for at least 7 years. Their CD8⁺ absolute numbers were similar to a control group composed of HIV-1⁺ patients who have a progressive decline of their CD4⁺ cell counts. However, our multiparameter immunofluorescence studies show that a clinical and immunologically stable condition is associated with the presence of a CD28⁺, CD95 strongly positive CD8⁺ population, while disease progression is marked by the CD28⁻CD95⁺CD8⁺ subset. Purified CD8⁺ cells from LTNP retain their ability to produce IL-2, interferon-gamma (IFN-γ) and, to a lesser degree, to produce IL-10 and IL-4. In contrast, CD8⁺ cells from progressors are unable to secrete IL-2 and IL-10. Although CD8⁺ cytokine profile does not fit with the proposed T helper (Th)1/Th2 switch in progressive HIV infection, LTNP CD8⁺ T cells maintain their capacity to produce IL-2 and IL-10 (Th0-like), a pattern very similar to that observed in normal HIV healthy controls. We suggest that CD8⁺ cells expressing CD28, CD95 and having a Th0-like profile may be considered to be associated with long-term survival.     

Ventricular tachycardia as a complication of annular subvalvular ventricular aneurysm in a Caucasian woman

A Caucasian female patient with repetitive attacks of ventriculartachycardia and fibrillation caused by annular submitral leftventricular aneurysm is reported. During a follow-up periodof six years after aneurysmectomy, the patient remained symptom-free.     

Electrophysiological investigations on the central innervation of the rat and guinea-pig pineal gland

Summary The possible influence of central nervous structures on the electrical activity of single pineal cells was investigated in rat and guinea-pig.In the rat electrical stimulation of the hippocampal formation elicited both single cell responses with different latencies and mostly long-term excitations in single pineal cells, while stimulation of the habenular nuclei caused clear orthodromical responses with different latencies, alterations in the rate of spontaneous electrical activity and evoked discharges of silent units.In the guinea-pig electrical stimulation of the paraventricular nucleus influenced predominantly cells in the deeper layers of the posterior part of the pineal gland. Electrical stimulation of both the superior and inferior colliculi elicited field potentials with a constant latency, indicating a functional relationship between the corpora quadrigemina and the pineal organ.Intrapineal stimulation and recording in the guinea-pig indicate functional connections between anterior and posterior parts of the pineal organ and that information can be conducted in both directions of the pineal axis.The data from the rat pineal gland are part of a thesis presented by St. Reuss in partial fulfillment for the degree of Dr. rer. nat. Preliminary data have been presented at the NATO Symposion The pineal gland and its endocrine role, Sicily 1982 (cf. Semm, 1983) and at the 6th European Neuroscience Congress, Malaga 1982 (cf. Reuss andSemm, 1982). — Financial support of the Stiftung Volkswagenwerk is gratefully acknowledged.     

In Situ Study of Haemopoiesis in Human Fetal Liver

The anatomy of haemopoietic cells in human fetal liver was examined using immunohistological techniques on frozen sections of 31 fetuses (10-28 weeks gestational age). The immunohistological findings were consistent with reported cell suspension data. With regard to the location of haemopoietic activity no particular relationship existed between the various haemopoietic cell lineages. A large number of proliferating cells was present; only a few of these were reactive with haemopoietic progenitor cell monoclonal antibodies (MoAb) CD34. A population of haemopoietic cells expressed CD43 antigen (MoAb MT1) alone or together with anti-vimentin MoAb reactivity; this population needs further delineation. Erythropoiesis and myelopoiesis occurred in clusters around sinusoids and portal triad vessels respectively. Lack of MoAb reacting exclusively with early developmental stages of erythropoiesis and myelopoiesis precluded dissection of these lineages. Lymphopoiesis occurred in a loosely scattered pattern without any sign of focal development. Pre-B and B-cell numbers increased with gestational age. Cells expressing markers of more mature B cells (surface IgD, CD35, and CD21) were rare. Also, few cells reacted with mature T-cell markers, but CD7+ cells were obviously present. This expression of CD7 on haemopoietic fetal liver cells suggests that T-cell precursors develop in fetal liver as well as B cells.