Suppression of humoral antibody formation against HSV is not only induced by replicating Herpes simplex virus type 2 (HSV-2) but also by the defective strain ANG and the deletion mutant 1301 of Herpes simplex virus type 1 (HSV-1). Moreover, ts-mutants A, H, K, S, 1201 and 1208 of HSV-1 as well as some ts-mutants of HSV-2 and "defective-interfering" particles of HSV-1 after high multiplicity of infection-passages induced suppression. Treatment of infected mice with ACG reduced antibody-formation but did not result in suppression. UV-irradiation of the antibody producing strain Len of HSV-1 strongly reduces antibody formation and induces suppression. Experiments using a series of intertypic recombinants showed the suppressing activity to be spread over the whole genome of HSV-2. It is concluded that suppression is induced by more than one region of the genome of HSV-2 and by incomplete replication of HSV-1 and 2.

We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.

Annals of the New York Academy of SciencesVolume 632, Issue 1 p. 283-295 The Tachykinin Neuroimmune Connection in Inflammatory Pain EBERHARD WEIHE, EBERHARD WEIHE Anatomical Institute, Johannes Gutenberg University, D-6500 Mainz, Federal Republic of GermanySearch for more papers by this authorDONATUS NOHR, DONATUS NOHR Anatomical Institute, Johannes Gutenberg University, D-6500 Mainz, Federal Republic of GermanySearch for more papers by this authorSABINE MÜLLER, SABINE MÜLLER Anatomical Institute, Johannes Gutenberg University, D-6500 Mainz, Federal Republic of GermanySearch for more papers by this authorMARKUS BÜCHLER, MARKUS BÜCHLER Department of General Surgery, University Clinics Ulm, D-7900 Ulm, Federal Republic of GermanySearch for more papers by this authorHELMUT FRIESS, HELMUT FRIESS Department of General Surgery, University Clinics Ulm, D-7900 Ulm, Federal Republic of GermanySearch for more papers by this authorHANS-JOACHIM ZENTEL, HANS-JOACHIM ZENTEL Anatomical Institute, Johannes Gutenberg University, D-6500 Mainz, Federal Republic of GermanySearch for more papers by this author EBERHARD WEIHE, EBERHARD WEIHE Anatomical Institute, Johannes Gutenberg University, D-6500 Mainz, Federal Republic of GermanySearch for more papers by this authorDONATUS NOHR, DONATUS NOHR Anatomical Institute, Johannes Gutenberg University, D-6500 Mainz, Federal Republic of GermanySearch for more papers by this authorSABINE MÜLLER, SABINE MÜLLER Anatomical Institute, Johannes Gutenberg University, D-6500 Mainz, Federal Republic of GermanySearch for more papers by this authorMARKUS BÜCHLER, MARKUS BÜCHLER Department of General Surgery, University Clinics Ulm, D-7900 Ulm, Federal Republic of GermanySearch for more papers by this authorHELMUT FRIESS, HELMUT FRIESS Department of General Surgery, University Clinics Ulm, D-7900 Ulm, Federal Republic of GermanySearch for more papers by this authorHANS-JOACHIM ZENTEL, HANS-JOACHIM ZENTEL Anatomical Institute, Johannes Gutenberg University, D-6500 Mainz, Federal Republic of GermanySearch for more papers by this author First published: September 1991 https://doi.org/10.1111/j.1749-6632.1991.tb33116.xCitations: 36AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Neuropeptides as growth factors: possible roles in human diseases. Regulat. Peptides 25: 1– 9. 32 Bishop, A. E., J. M. Polak, M. G. Bryant, S. R. Bloom and S. Hamilton. 1980. Abnormalities of vasoactive intestinal peptide-containing nerves in Crohn's disease. Gastroenterology 79: 853– 860. 33 Maggi, C. A.. 1990. Capsaicin and primary afferent neurons: from basic science to human therapy?. J. Auton. Nerv. Syst. In press. Citing Literature Volume632, Issue1Substance P and Related Peptides: Cellular and Molecular PhysiologySeptember 1991Pages 283-295 ReferencesRelatedInformation

The peptidergic innervation of rat thymus has been investigated by immunohistochemical methods, focusing on the spatial interrelationship of peptidergic nerve fibers with mast cells and macrophages in the rat. An antiserum directed against the protein gene product 9.5 (PGP 9.5) regarded as a pan-neuronal marker revealed a rich innervation, especially in the subcapsular cortex, in interlobular septa, and of the vasculature in the cortex and the corticomedullary boundary. A minor proportion of PGP 9.5-immunoreactive (ir) fibers supplied the thymic parenchyma. The main component of peptidergic innervation consisted of fibers costaining for tachykinins (TKs) and calcitonin gene-related peptide (CGRP), but considerable amounts of neuropeptide Y (NPY)/tyrosine hydroxylase (TH)-positive fibers and vasoactive intestinal polypeptide/peptide histidine isoleucine-positive fibers also were present. There were sparse Leu-enkephalin and galanin immunoreactivities in thymic nerve fibers, while neurotensin was absent from nerve fibers. Close associations of TKCGRP-ir and NPY-ir fibers with mast cells were frequently detected in the connective tissue areas of the thymus, often adjacent to the vasculature. TKCGRP-ir fibers and some rare NPY-ir fibers were found adjacent to ED1-positive macrophages and less frequently to mast cells. TKCGRP-ir and NPY-ir fibers were mainly detected in relation to the vasculature of the cortex and the corticomedullary boundary, but also were found in capsular and subcapsular regions of the thymic cortex. The possible importance of the close spatial relationship between the various peptide-containing nerve fibers and mast cells and ED1-positive macrophages in neuroimmune integration is discussed.

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.

The presence and distribution of galanin (GAL) in adrenal glands of rodent and avian species was investigated by light microscopic immunohistochemistry. GAL immunoreactivity was found in all medullary cells of guinea pig, duck and chicken adrenals. In contrast, only a subpopulation of medullary cells stained for GAL in Phodopus (Djungarian hamster) while the neuropeptide was completely missing in chromaffin cells of rat and pigeon. In rat, guinea pig and pigeon, GAL-immunoreactive nerve fibres were frequent in subcapsular regions and sparse in deeper cortical layers and in the chromaffin tissue. In contrast, only very few GAL fibres were found in Phodopus and no GAL fibres were observed in the adrenal glands of duck. In the chicken adrenal gland, fibres containing GAL were numerous throughout the organ and occurred in close vicinity to both steroidogenic as well as catecholaminogenic cells. The striking differences in the presence of GAL-positive cells and fibres are more pronounced between species within the rodent or avian group, respectively, than between the different vertebrate orders. The hitherto unknown and surprising variability of GAL expression and distribution in adrenal glands of various species suggests species-dependent functional (autocrine, paracrine and/or endocrine) roles of GAL in the neuroadrenal axis.

Injection of Complete Freund's adjuvant (CFA) into the hindpaw produces inflammation and alterations in nociceptive sensitivity. The present study was designed to compare the effects of CFA injection into the dorsal and plantar surfaces of the hindpaw on nociceptive sensitivity of the hindpaw to mechanical pressure, warm-water and a hotplate stimulus in male and female rats. CFA or vehicle (VEH) was injected into the dorsal or plantar surface of the right hindpaw on day 0 and tests were conducted on days 4, 6, 8, 10, 11 and 18. Up until day 11 the inflammation was confined to the injected hindpaw (monoarthritic state), whereas by day 18 both hindpaws were inflamed (polyarthritic state). The site of the CFA injection had minimal effects on thermal or mechanical sensitivity with the following exceptions. On days 11 and 18 males had higher hotplate latencies when injected in the dorsal as compared to the plantar surface. For both males and females, warm-water paw withdrawal latencies were longer in those rats injected in the dorsal versus the plantar surface on day 18. No sex differences in paw pressure thresholds were observed on days 11 and 18 in CFA-treated rats. In the warm-water paw withdrawal test CFA-treated males exhibited longer latencies than CFA-treated females on day 11, but similar latencies on day 18. In the hotplate test CFA-treated females exhibited shorter latencies than CFA-treated males on days 11 and 18. The present results demonstrate that nociceptive sensitivity is the result of the interplay among sex, CFA injection site (plantar vs. dorsal), arthritic state (mono- vs. polyarthritic) and stimulus modality (mechanical vs. thermal).

Bei einem 26jährigen Patienten fand sich als Ursache einer intermittierencien asymptomatischen Makrohämaturie eine lokalisierte Amyloidose der penilen und bulbären Harnröhre. Für den behandelnden Urologen stellt die Amyloidose in diagnostischer Hinsicht eine Herausforderung dar: Neben der fast ausnahmslos nachweisbaren Hämaturie finden sich häufig pseudotumoröse Veränderungen, die eine Abgrenzung gegenüber Malignomen, wie z.B. dem Urethrakarzinom schwierig machen.

By the use of light microscopic (LM) immunohistochemistry the distribution of tachykinin (TK)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity in nerves supplying the mammalian (rat, mouse, guinea-pig, cat) thymus gland has been determined. There were no interspecies variations. Fibres staining for TK and CGRP completely overlapped indicating coexistence. They were present in the capsule, in interlobular septa and in the corticomedullary boundary and occurred in perivascular and paravascular plexus supplying arteries, veins and the microvasculature. Some TK/CGRP-immunoreactive (ir) fibres travelled between lymphoid cells and close contacts with mast cells were frequent. NPY-ir fibres were different from those staining for TK/CGRP and predominated in the perivascular plexus of arterial blood vessels. Only very rarely they coursed in the lymphoid parenchyma. Intimate contacts of NPY-ir fibres with mast cells were less frequent than those of TK/CGRP-ir fibres. We conclude that the NPY innervation is mainly sympathetic noradrenergic while thymic nerves coding for TK and CGRP are most likely of sensory origin. These pathways may play a differential neuroimmunomodulatory role in the thymus, possibly via interaction with mast cells.

The influence of adjuvant-induced arthritis of the rat on central and peripheral peptide neuroanatomy was investigated by immunohistochemistry. The most striking feature of arthritic rats was the differential intensification of neuronal proenkephalin- and prodynorphin-related staining in dorsal horn. Changes were ipsilateral in monoarthritic and bilateral in polyarthritic rats as compared to controls. Opioid responsive neurons were target of substance P (SP) and calcitonin gene-related peptide (CGRP) fibers. Changes of SP and CGRP predominated in peripheral inflamed tissue and consisted of intensified immunostaining and an apparent sprouting of sensory fibers particularly around venules, in the epidermis and in areas infiltrated by immunocompetent cells. Opioid staining was absent from primary afferents but present in some immune cells of inflamed tissue. Endogenous antinociceptive opioids and pro-nociceptive/pro-inflammatory SP and CGRP may be crucial in the concerted response of the neuroimmune system to chronic inflammatory pain.

The fate of microtubules and of vimentin or keratin containing intermediate filaments during infection with fusion or rounding producing strains of herpes simplex virus (HSV) was investigated. Microtubules polymerize early after fusion of cells. However, they do not reconstitute 6–7 hours post infection (p.i.) after release of a colcemid block.

The mechanism of herpes simplex virus (HSV)-2-induced immunosuppression was analysed by determination of the number of IgM and IgG antibody-secreting B cells in female BALB/c mice using an immunospot assay. Primary HSV-1 or -2 as well as homologous or heterologous booster infections at different times were performed. In accordance with earlier results on humoral antibody generation, in contrast to HSV-1, HSV-2 induced only very low numbers of antibody-producing B cells in dose-response experiments. They appeared late after infection compared to HSV-1. Despite a homologous humoral booster reaction against HSV-1 at day 8 no IgM- or IgG-secreting cells in the spleen could be detected. This non-reactivity of the spleen had vanished 10 days later, when secondary reactions of B cells could be observed. Secondary infections with a high homologous dose of HSV-2 after a low primary dose produced only a low booster response of IgG-secreting B cells. Suppression of humoral antibody production induced by HSV-2 (high dose) waned after more than 50 days, indicating that the HSV-2-induced suppression did not impair antigen presentation or memory cell generation.

Strains ANG and ANG path of herpes simplex virus type 1 (HSV1) produced fusion from without (FFWO) of cells in culture. FFWO required 45 min to become complete. In contrast, fusion from within (FFWI) was not detected until 3-4 h after infection, depending on the cell type. FFWO was temperature dependent: at 0 degrees no fusion could be observed, but increase of temperature increased the degree of fusion. The pH optimum for FFWO was 7.8-8.5. The FFWO activity of the virus was found to be slightly more heat stable at 46 degrees than was infectivity. FFWO was produced in Vero, CV-1 and BSC1 cells, but not in BHK clone 13 or in primary or secondary rabbit kidney cells. FFWO was linked to the presence of virus particles and perhaps to other sedimentable, infected-cell material but not to soluble factors. Actinomycin D, cycloheximide, and UV irradiation did not block this activity, indicating no direct activity of the HSV1 genome for FFWO.