Lymphocytic ganglionitis leading to megacolon in lymphocyte-rich glioblastoma.

T-cell immune attack of cancer cells underlies the efficacy of immune checkpoint inhibitors in many cancer subtypes, but is not yet well established in the primary brain cancer glioblastoma. Immune checkpoint inhibitor treatments that disinhibit the immune system to enhance immune clearance of cancer have in rare cases resulted in T-cell attack of peripheral ganglia causing lymphocytic ganglionitis. In glioblastoma, lymphocytic ganglionitis has not been reported and checkpoint inhibitors are not routinely used. Here we report a case of glioblastoma not treated with checkpoint inhibitors in which the primary tumor and peripheral ganglia of the celiac and sympathetic chains, as well as myenteric plexus, are infiltrated by CD8+ cytotoxic T-cells. In addition to the marked lymphocytic infiltrates, this case is also notable for an unusually long survival (8 years) after diagnosis with glioblastoma, but an ultimately fatal outcome due to ileus. The findings suggest T-cell immune attack of glioblastoma may prolong survival, but also suggest T-cell autoimmune diseases such as lymphocytic ganglionitis could become a risk with the future use of immune-targeted therapies for glioblastoma.

A monoclonal antibody that defines rostrocaudal gradients in the mammalian nervous system.

Spinal cord axons display a rostrocaudal, positional bias in their innervation of sympathetic ganglia and intercostal skeletal muscles. In an effort to examine the molecular basis of this positional specificity, we used the cyclophosphamide immunosuppression method to produce monoclonal antibodies that bind preferentially to rostral ganglia. The staining distribution of one of these antibodies, ROCA1, has been analyzed using a novel histological method. A graded decline in binding is observed along the chain of adult rat sympathetic ganglia, as well as in the nerves innervating intercostal muscles. The antigen is identified on immunoblots as a 65 kd protein, whose distribution corresponds to the pattern found histologically. Surprisingly, ROCA1 appears to bind to glial cells, implying rostrocaudal, molecular differences in their surfaces.

Autoantibodies to sympathetic ganglia, GAD, or tyrosine phosphatase in long-term IDDM with and without ECG-based cardiac autonomic neuropathy.

OBJECTIVE: To evaluate the association of autoantibodies to complement-fixing sympathetic ganglia (CF-SG), and tyrosine phosphatase (IA-2) with electrocardiogram (ECG)-based cardiac autonomic neuropathy (CAN) in long-term IDDM. RESEARCH DESIGN AND METHODS: We examined the prevalence of autoantibodies to CF-SG (by complement-fixing indirect immunoflourescence), GAD, and IA-2 (by radioligand assay) and islet cells (by indirect immunofluorescence) in 96 long-term IDDM patients (41 with ECG-based CAN, > or = 2 of 5 cardiac reflex tests abnormal; 55 without ECG-based CAN). As a control group, 89 healthy nondiabetic subjects were investigated. RESULTS: CF-SG autoantibodies were observed more frequently in long-term IDDM patients than in the control group (25 vs. 4%, P = 0.0001). Of the IDDM patients, 14 (34%) with CAN and 10 (18%) without CAN presented with CF-SG autoantibodies (P = 0.06). GAD or IA-2 autoantibodies were detected in 14 (34%) and 17 (41%) IDDM patients with CAN, compared with 24 (44%) and 29 (53%) IDDM patients without CAN (P = 0.2, P = 0.2). Islet cell antibodies were observed in 6 (15%) IDDM patients with and in 9 (16%) IDDM patients without CAN (P = 0.5). CONCLUSIONS: In long-term IDDM, the role of CF-SG autoantibodies, which tend to be more frequent in patients with ECG-based CAN, requires further investigations. The persistence of GAD and IA-2 autoantibodies is not related to ECG-based CAN.

Anti-sympathetic ganglia antibodies and postural blood pressure in IDDM subjects of varying duration and patients at high risk of developing IDDM.

We examined the sera of 94 subjects with insulin-dependent diabetes mellitus (IDDM) for the presence of complement-fixing sympathetic ganglia (CF-SG) antibodies. In a cross-sectional analysis (duration 0-43 yr), 22% had detectable CF-SG antibodies. Subjects at high risk for IDDM were also studied. Four groups were studied: group 1 (aged 4-64 yr) islet cell antibody-positive (ICA+) prediabetic subjects, 10 of 19 (53%) were CF-SG+; group 2 (aged 6-14 yr) ICA- prediabetic subjects (first-degree relatives of IDDM subjects with either transient hyperglycemia, impaired oral glucose tolerance, and/or first-phase insulin release after intravenous glucose tolerance testing), 4 of 9 (44%) were CF-SG+ (2 of the 4 ICA- CF-SG+ subjects have progressed to IDDM); group 3 (aged 1.5-43 yr) ICA+ IDDM subjects (less than or equal to 1 yr duration) 6 of 10 (60%) were CF-SG+; and group 4 (aged 8-59 yr) ICA- IDDM subjects (less than or equal to 1 yr duration), 2 of 11 (18%) were CF-SG+. All groups had increased CF-SG compared with controls. Postural blood pressure and simultaneous CF-SG antibody measurements were performed in 28 IDDM subjects. The drop in systolic blood pressure was greater in the CF-SG+ subjects (P less than .05), and the frequency of CF-SG was greater in the mean to -2SD group (P less than .03) when data were analyzed within mean +/- 2SD of the normal blood pressure response.

Complement-fixing antibodies to sympathetic and parasympathetic tissues in IDDM. Autonomic brake index and heart-rate variation.

We describe herein complement-fixing anti-adrenal medullary (CF-ADM) and anti-sympathetic ganglia (CF-SG) antibodies in insulin-dependent diabetes mellitus (IDDM). This study describes complement-fixing anti-vagus (CF-V) nerve antibodies and their relationship to the cardiovascular autonomic brake index (a measure of transient decrease in heart rate during the 1st min after a tilt), and R-R interval variation with deep breathing. CF-V was detectable in 7 of 83 (8.4%) subjects with IDDM aged 1.5-65.5 yr (mean +/- SE 28.7 +/- 1.8 yr) and duration of diabetes 0-47 yr (11.8 +/- 1.4 yr). Seventy-six nondiabetic subjects (aged 10-65 yr) all had negative CF-V scores. CF-V scores correlated with CF-ADM (0-16 yr of IDDM, r = 0.61, P less than 0.0001) and CF-SG (r = 0.39, P less than 0.05). Seventy IDDM subjects (aged 28 +/- 5 yr, duration of diabetes 17 +/- 3 yr) without proteinuria or proliferative retinopathy were screened for CF-ADM, CF-SG, and CF-V antibodies. Five of 70 (7.1%) had CF-SG only (negative for CF-ADM and CF-V). Brake indices ranged from 14.7 to 51.3 (37.3 +/- 6.9). Three of 70 (4.2%) had CF-ADM only, with brake indices from 26.9 to 45.1 (32.9 +/- 6.1). Four of 70 (5.7%) had CF-V antibodies only, with brake indices of 12.7-17.3 (15.1 +/- 1.1). Subjects with CF-SG or CF-ADM (anti-sympathetic) had higher brake indices than subjects with CF-V (anti-parasympathetic) antibodies (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in expression of a synaptic vesicle antigen in aging sympathetic neurons.

The effects of altering synaptic activity of sympathetic neurons on the expression of a synaptic vesicle protein (p65) were studied by deafferentation of the superior cervical ganglion (SCG) in adult and aged Fischer-344 rats. Levels of p65, an integral membrane protein of synaptic vesicles, were assayed by radioimmunoassay. After deafferentation, a transient increase in p65 levels is observed in the SCG of adult rats. In aged animals, the response to deafferentation is delayed and enhanced, and levels do not drop to values observed in operated adults. After SCG deafferentation, p65 levels in the iris, an SCG target, initially are depressed below control levels; p65 levels return to control values in adult animals after 14 days, but remain depressed in aged animals. In contrast, a transient increase in p65 levels is observed in the pineal of both adult and aged animals. These results suggest that while the aged sympathetic nervous system retains the ability to respond to alterations in synaptic activity, it is unable to reregulate once a response is initiated.

Separate origins for the dynorphin and enkephalin immunoreactive fibers in the inferior mesenteric ganglion of the guinea pig.

By different denervation procedures the origin of dynorphin-(1-17) and enkephalin immunoreactive fibers in the guinea pig inferior mesenteric ganglion was investigated. It was found that the dynorphin-(1-17)-positive fibers reached the ganglion predominantly via the colonic nerves and to a lesser extent via the hypogastric and intermesenteric nerves whereas the enkephalin-positive fibers reached the ganglion via the lumbar splanchnic nerves. These findings show that the dynorphin-(1-17) and enkephalin systems are separate in this ganglion.

Lymphocyte-mediated regulation of neurotransmitter gene expression in rat sympathetic ganglia.

It has been previously shown that sympathetic noradrenergic nerve fibers, in addition to supplying the smooth muscle of the splenic capsule, trabeculae and blood vessels, also form very tight appositions with lymphocytes of the periarteriolar lymphatic sheath. To determine whether there is a direct communication between the sympathetic neurons and the immune cells we have grown dissociated superior cervical ganglion (SCG) neurons together with splenic lymphocytes. Sympathetic neurons were grown both as mixed preparations (neurons and non-neuronal ganglion cells) and neuron-enriched preparations. These systems were used to investigate whether coculture with splenocytes alters neurotransmitter gene expression in SCG cultures. Northern blot analysis was used to measure changes in neurotransmitter mRNA expression. The results showed that expression of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, was significantly decreased when SCG cultures were grown in the presence of spleen cells compared to control SCGs grown either alone or in the presence of erythrocytes. When the mitogen concanavalin A (ConA) was used to stimulate the spleen cells in the cocultures the decrease in TH was more pronounced. In contrast, preprotachykinin-A (PPT-A) mRNA expression in cultured SCGs increased in the cocultures. Another neuropeptide, neuropeptide Y (NPY), showed different responses in the presence of stimulated vs. unstimulated splenocytes. NPY mRNA was slightly increased in the presence of resting spleen cells, but showed a 70% decrease when ConA was added to the cocultures. Thus, our results suggest that lymphocytes can differentially regulate neurotransmitter gene expression in sympathetic ganglia.

Macrophages, lymphocytes and major histocompatibility complex (HLA) class II antigens in adult human sensory and sympathetic ganglia.

We report an immunocytochemical study of sensory and autonomic ganglia from ten adult human subjects aged 18-83 years without peripheral nerve disease using monoclonal antibodies to macrophages, lymphocytes and human leukocyte (HLA) class II antigens. All ganglia and their associated nerve roots were found to contain a population of resident macrophages which accounted for 5-20% of the cells present. These macrophages and, in addition, many Schwann cells and satellite cells, gave reactions for HLA class II antigens in all cases. Very low numbers of CD3 and CD8 lymphocytes were also regularly detectable in sensory and autonomic ganglia. The resident macrophages may have important immunological and trophic functions. Their possible role in the development of immune-mediated peripheral nerve disease deserves further study.

Autonomic function and autoantibodies to autonomic nervous tissues at follow-up in a cohort of young patients with type 1 diabetes. Effects of serum from diabetic patients on human adrenergic cells.

Recent studies have linked autoimmunity to nervous tissue structures and diabetic autonomic neuropathy. To evaluate prospectively the early stage of type 1 diabetes and the natural history of this association, we monitored the autonomic function and the presence of autoantibodies (Ab) to sympathetic and parasympathetic nervous structures in a cohort of 92 diabetic adolescent patients, recruited and followed-up after 40+/-3 months. The presence of circulating Ab and their ability to activate complement was also assessed using a human adrenergic neuroblastoma cell line, and the effect of patients' sera on these cells was evaluated by different methods assessing cytotoxic effects and apoptosis. Thirty-nine percent of the Ab-positive patients had one abnormal test (p=0.07 vs. Ab-negative patients). Serum from four patients positive for anti-cervical ganglia Ab showed positive staining of neuroblastoma cells and displayed ability to activate complement. Serum from two adolescent patients with anti-cervical ganglia and anti-neuroblastoma cells Ab, induced cytotoxic effects and damaged the plasma membrane of the neuroblastoma cells. Moreover, sera from two adult patients with overt autonomic neuropathy, used as positive controls, induced apoptosis of these cells, assessed by TUNEL. Our data indicate that symptomatic autonomic neuropathy is not characteristic of young diabetic patients, but that autoantibodies to autonomic structures are present and persist in the first 20 years of disease, possibly associated with subtle autonomic dysfunction and cytotoxic effect on sympathetic cells.

Complement regulatory proteins and selective vulnerability of neurons to lysis on exposure to acetylcholinesterase antibody.

Systemic injection of antibodies against acetylcholinesterase (AChE) induces complement-mediated destruction of preganglionic nerve terminals in paravertebral sympathetic ganglia, but spares other AChE-rich structures, such as nerve terminals in prevertebral sympathetic ganglia, parasympathetic ganglia, and the neuromuscular junction. This pattern of differing sensitivity to "AChE immunolesion" might be explained by a differing expression of proteins that serve to protect host cells from complement activation. Two major complement regulatory proteins in rats are Crry, which interferes with the assembly of C3 convertase, and CD59, which blocks formation of the terminal cytolytic membrane attack complex. The present study used immunohistochemistry to demonstrate an inverse relation between levels of CD59 and Crry expression and sensitivity to AChE immunolesion in several AChE-rich targets. Thus, the most sensitive structures, i.e., preganglionic nerve terminals in the adrenal gland and superior cervical ganglion (SCG), expressed undetectable levels of CD59 and Crry immunoreactivities. By contrast, AChE-rich, but antibody-resistant, cholinergic nerve terminals in the inferior mesenteric ganglia (IMG) and diaphragm muscle expressed significant amounts of CD59 and Crry. Such expression was functionally important because, after membrane-anchored CD59 was removed from explanted IMG with phosphatidylinositol phospholipase C, exposure to AChE antibody and complement caused greater immunolesion. It was concluded that differential expression of regulatory proteins in different parts of the nervous system influences regional vulnerability to complement mediated damage.

Bombesin/gastrin-releasing peptide (GRP)- and Met5-enkephalin-Arg6-Gly7-Leu8-like immunoreactivities in small intensely fluorescent (SIF) cells and nerve fibers of rat sympathetic ganglia.

Superior cervical and hypogastric ganglia were removed from rats that had been perfused with a mixture of 4% paraformaldehyde and 0.25% glutaraldehyde. Specific antisera against Met5-enkephalin-Arg6-Gly7-Leu8 (MEAGL) and bombesin/gastrin-releasing peptide (BN/GRP) were used in the immunofluorescence procedure. In hypogastric ganglia, a subpopulation of small intensely fluorescent (SIF) cells, as identified by their aqueous aldehyde (Faglu)-induced fluorescence, showed MEAGL- and BN/GRP-like immunolabeling. SIF cells in the superior cervical ganglia were unlabeled. In both ganglia, varicose nerve fiber networks and nerve terminals surrounding principal ganglion cells showed MEAGL- and BN/GRP-like immunoreactivities. Unlabeled SIF cells often were in close contact with nerve fibers that had MEAGL-like immunolabeling. Immunoreactivities against MEAGL- and BN/GRP-like neuropeptides in nerve fibers and terminals suggest a neurotransmitter or neuromodulator role for these peptides. In addition, labeling in SIF cells implies their possible endocrine function.

Experimental murine schistosomiasis mansoni: modulation of the B-1 lymphocyte distribution and phenotype expression.

We studied the B-1 lymphocyte involvement in host reactions to parasites in the murine model of schistosomiasis. No modifications were observed in the prepostural phase of the disease. From the acute phase on, we observed sequentially an increase of Mac1- B-1 cells in the spleen, followed by their appearance in Peyer's patches and in mesenteric ganglia, suggesting that a fraction of splenic B-1 cells might follow this pathway of migration, acquiring progressively the Mac1 expression. These results are consistent with a primary activation of the splenic B cell compartment, with the subsequent mobilization of B-1 cells into the tissue involved by parasites. Conversely, we found no evidence of an increase of B-1 cells in the peritoneum, nor a mobilization of B-1 cells expressing the peritoneal phenotype (CD5lo, IgMhi) into the tissues involved by infection, despite the general inflammatory reactivity of peritoneal cells. In schistosomiasis, the peritoneal cavity B-1 cells on one side, and those involved in inflammatory reactions to parasites in the spleen, Peyer's patches, and mesenteric ganglia on the other, represent two distinct B-1 lymphocyte pools.

Neuropeptides in the human celiac/superior mesenteric ganglionic complex: an immunohistochemical study.

The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine (PHI), calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), galanin (GAL) and enkephalins (ENK) is studied in the human celiac/superior mesenteric ganglionic complex of pre- and full-term newborns, and adult subjects by means of immunohistochemistry. The antisera used labelled nerve fibres and terminal-like networks for each examined peptide, as well as VIP- and SOM-positive postganglionic neurons. Differences in the relative amount and density of the structures immunoreactive to the various peptides were observed. Moreover, variations in the amount and type of labelled elements were appreciable for each peptide when specimens from subjects at perinatal and adult ages were compared. Double-labelling immunofluorescence for SP and each other peptide showed that co-localization with SP is very frequent for CGRP, moderate to scarce for GAL and SOM, and rare to absent for PHI, VIP and ENK. VIP-, ENK- and CGRP-immunolabeled perikarya bearing the morphological features of the small intensely fluorescent (SIF) cells occurred in the organ. The presence of a paraganglion in one of the specimens examined allowed the detection of VIP- and ENK-positive cell bodies and VIP-, ENK-, SP- and GAL-like immunoreactive varicose nerve fibres in it. The results obtained provide substantial morphological data in support of the involvement of the examined peptides in the chemical interneuronal signalling in the human celiac/superior mesenteric ganglia.

Analysis of antibodies against components of the autonomic nervous system in diabetes mellitus.

Antibodies to autonomic nervous system structures have previously been detected using a complement fixation immunofluorescence test in the sera of patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM). These antibodies might play a role in the aetiology of autonomic neuropathy. Sera from 45 IDDM, 40 NIDDM and 52 control subjects were tested by immunofluorescence for antibodies to human sympathetic ganglia, human adrenal medulla and rabbit vagus nerve. The use of human sympathetic ganglia was compared with rabbit tissue for the detection of sympathetic ganglia antibodies; the results for these autonomic nervous system antibodies were also compared with results using an ELISA. There was no relationship between the presence of antibodies detected by ELISA and those detected by immunofluorescence, but of 14 IDDM patients with thyroid antibodies, 12 had autonomic nervous system antibodies detected by either immunofluorescence or ELISA (p < 0.005 compared to patients without thyroid antibodies). To further characterize the autoantigen(s), immunoblotting was performed. An adrenal antigen corresponding to 74 kDa was detected in sera from three patients, only one of whom had antibodies detectable by ELISA and immunofluorescence. One IDDM serum showed specific binding to a vagus nerve antigen corresponding to 33 kDa. No specific binding to sympathetic ganglia antigen was demonstrated. Antibodies against autonomic nervous system antigens are an inconsistent feature of diabetes, and appear more associated with coincidental autoimmunity against other organs such as the thyroid.

Effect of preganglionic stimulation on neuropeptide-like immunoreactivity in the stellate ganglion of the cat.

In pentobarbital-anesthetized cats, treated with hexamethonium and atropine, 40 Hz stimulation of the preganglionic input to the decentralized right stellate ganglion caused cardioacceleration. When the 40-Hz stimulation is maintained for 2 h, this cardioacceleration was progressively attenuated and eventually irreversibly lost. At this time, neurotensin-like and leucine-enkephalin-like immunoreactivity associated with intraganglionic fibers and presumptive axon terminals was also lost. Preganglionic 40 Hz stimulation for 2 h did not change substance P-like, somatostatin-like, vasoactive intestinal peptide-like and corticotropin-releasing factor-like immunoreactivity in the stellate ganglion. A 40-Hz 2-h stimulation of the intact stellate ganglion output caused no change of the neuropeptide immunoreactivity pattern. These findings suggest that neurotensin and leucine-enkephalin are released by sympathetic preganglionic axon terminals and that the releasable pool of these peptides is depleted by prolonged preganglionic stimulation. The association of peptide depletion with loss of the cardioacceleration, evoked by stimulation of the input to the stellate ganglion in the presence of cholinergic antagonists, suggests the possibility that peptides are involved in the non-cholinergic mechanism of ganglionic transmission mediating the cardioacceleration.

Secretoneurin-like immunoreactivity in rat sympathetic, enteric and sensory ganglia.

Distribution of secretoneurin-like immunoreactivity (SN-LI) was studied in the rat sympathetic ganglia/adrenal gland, enteric and sensory ganglia by immunohistochemical methods. SN-LI nerve fibers formed basket-like terminals surrounding many of the postganglionic neurons of the superior cervical, stellate, paravertebral chain ganglia, coeliac/superior mesenteric and inferior mesenteric ganglia. Postganglionic neurons of the superior cervical and other sympathetic ganglia exhibited low-to-moderate levels of SN-LI. In all these sympathetic ganglia, clusters of small diameter (< 10 microm) cells, which may correspond to the small intensely fluorescent (SIF) cells, were found to be intensely labeled. Surgical sectioning or ligation of the cervical sympathetic trunk for 7-10 days resulted in a nearly total loss of SN-LI fibers in the superior cervical ganglia, whereas immunoreactivity in the postganglionic neurons and small diameter cells remained essentially unchanged. In the thoracolumbar and sacral segments of the spinal cord, SN-LI nerve fibers were detected in the superficial layers of the dorsal horn as well as in the intermediolateral cell column (ILp). Occasionally, SN-LI somata were noted in the ILp. SN-LI nerve fibers formed a delicate plexus underneath the capsule of the adrenal gland, some of which traversed the adrenal cortex and reached the adrenal medulla. While heavily invested with SN-LI nerve terminals, chromaffin cells seemed to express a low level of SN-LI. In the enteric plexus, varicose SN-LI nerve fibers and terminals formed a pericellular network around many myenteric and submucous ganglion cells; the ganglionic neurons were lightly to moderately labeled. A population of ganglion cells in the dorsal root, nodose and trigeminal ganglia exhibited moderate-to-strong SN-LI. The detection of SN-LI in nerve fibers and somata of various sympathetic ganglia, enteric plexus and adrenal medulla and in somata of the sensory ganglia implies an extensive involvement of this peptide in sympathetic, enteric and sensory signal processing.

Expression of glial antigens C1 and M1 in the peripheral nervous system during development and regeneration.

The expression of C1 and M1 antigens was studied by indirect immunofluorescence methods in histological sections of peripheral nerves and ganglia of C57BL/6J mice during development and regeneration. In sciatic nerves of adult mice, C1 but not M1 antigen is found in vimentin- and glial fibrillary acidic protein (GFAP)-positive Schwann cells. A similar distribution is also seen in trigeminal nerve, dorsal root and superior cervical ganglia, and olfactory nerve. In all cases vimentin-positive structures outnumber GFAP- or C1 antigen-positive ones. At birth, C1 antigen and vimentin are expressed in sciatic nerves, but GFAP is not yet detectable. M1 antigen cannot be detected in Schwann cells. In monolayer cultures of neonatal mouse dorsal root ganglia, C1 antigen is expressed in a fibrillary staining pattern in some, but not all morphologically identified Schwann cells. In vitro, M1 antigen is not detectable in Schwann cells. After lesioning sciatic nerves of adult mice by cut or crush, detectable levels of C1 antigen rise after 4-6 days: The number of immunofluorescently labeled structures and their relative intensities are drastically augmented, first distally more so than proximally, over control values from non-lesioned, i.e. contralateral nerves. A similar augmentation is also observed for vimentin and GFAP. M1 antigen expression does not reach detectable levels in Schwann cells under these conditions. The increased detectability of C1 antigen persists up to 150 days after lesioning, the longest time period tested.

5-Hydroxytryptamine-immunoreactive nerve fibers in the rat and porcine prevertebral sympathetic ganglia: effect of precursor loading and relation to catecholaminergic neurons.

Localization of 5-hydroxytryptamine immunoreactivity was studied in the rat coeliac-superior mesenteric ganglion complex and in the porcine superior and inferior mesenteric ganglia by the indirect immunofluorescence technique. In normal rats, only 5-hydroxytryptamine immunoreactive SIF cells were seen in the coeliac-superior mesenteric ganglion complex. In the rats, pretreated with a 5-hydroxytryptamine precursor, L-tryptophan, and with a monoamine oxidase inhibitor, nialamide, a large number of 5-hydroxytryptamine-immunoreactive nerve fiber terminals were detected. In normal porcine superior and inferior mesenteric ganglia, intense 5-hydroxytryptamine immunoreactivity was found in numerous nerve fibers which were located around tyrosine hydroxylase-immunoreactive principal neurons. The origin and function of these fibers are discussed.

Cytochemical relationships in the paracervical ganglion (Frankenhäuser) of rat studied by immunocytochemistry.

Vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactivities have been demonstrated in the paracervical ganglion of the rat using immunocytochemistry. Dopamine beta-hydroxylase (D beta H) and neurofilament protein triplet immunoreactivities have also been demonstrated in this region. The VIP, NPY, D beta H and neurofilament immunoreactivities were located in ganglion cells and nerve fibres, while CGRP immunoreactivity was localized only in nerve fibres. Many cells immunoreactive with D beta H antiserum were also immunoreactive with NPY antiserum. A small number of cells immunoreactive with VIP antiserum were also immunoreactive with NPY antiserum. CGRP-immunoreactive nerve fibres were distributed in certain regions of the ganglion only.