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Biomedical subjects

M Majewski

Publications and source records attributed to M Majewski.

At least 19 recordsLinked to original sources

The SH3 domain contributes to BCR/ABL-dependent leukemogenesis in vivo: role in adhesion, invasion, and homing.

To determine the possible role of the BCR/ABL oncoprotein SH3 domain in BCR/ABL-dependent leukemogenesis, we studied the biologic properties of a BCR/ABL SH3 deletion mutant (delta SH3 BCR/ABL) constitutively expressed in murine hematopoietic cells. delta SH3 BCR/ABL was able to activate known BCR/ABL-dependent downstream effector molecules such as RAS, PI-3kinase, MAPK, JNK, MYC, JUN, STATs, and BCL-2. Moreover, expression of delta SH3 BCR/ABL protected 32Dcl3 murine myeloid precursor cells from apoptosis, induced their growth factor-independent proliferation, and resulted in transformation of primary bone marrow cells in vitro. Unexpectedly, leukemic growth from cells expressing delta SH3 BCR/ABL was significantly retarded in SCID mice compared with that of cells expressing the wild-type protein. In vitro and in vivo studies to determine the adhesive and invasive properties of delta SH3 BCR/ABL-expressing cells showed their decreased interaction to collagen IV- and laminin-coated plates and their reduced capacity to invade the stroma and to seed the bone marrow and spleen. The decreased interaction with collagen type IV and laminin was consistent with a reduced expression of alpha 2 integrin by delta SH3 BCR/ABL-transfected 32Dcl3 cells. Moreover, as compared with wild-type BCR/ABL, which localizes primarily in the cytoskeletal/membrane fraction, delta SH3 BCR/ABL was more evenly distributed between the cytoskeleton/membrane and the cytosol compartments. Together, the data indicate that the SH3 domain of BCR/ABL is dispensable for in vitro transformation of hematopoietic cells but is essential for full leukemogenic potential in vivo.

Animals

Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway.

The BCR/ABL oncogenic tyrosine kinase activates phosphatidylinositol 3-kinase (PI-3k) by a mechanism that requires binding of BCR/ABL to p85, the regulatory subunit of PI-3k, and an intact BCR/ABL SH2 domain. SH2 domain BCR/ABL mutants deficient in PI-3k activation failed to stimulate Akt kinase, a recently identified PI-3k downstream effector with oncogenic potential, but did activate p21 RAS and p70 S6 kinase. The PI-3k/Akt pathway is essential for BCR/ABL leukemogenesis as indicated by experiments demonstrating that wortmannin, a PI-3k specific inhibitor at low concentrations, suppressed BCR/ABL-dependent colony formation of murine marrow cells, and that a kinase-deficient Akt mutant with dominant-negative activity inhibited BCR/ABL-dependent transformation of murine bone marrow cells in vitro and suppressed leukemia development in SCID mice. In complementation assays using mouse marrow progenitor cells, the ability of transformation-defective SH2 domain BCR/ABL mutants to induce growth factor-independent colony formation and leukemia in SCID mice was markedly enhanced by expression of constitutively active Akt. In retrovirally infected mouse marrow cells, the BCR/ABL mutant lacking the SH2 domain was unable to upregulate the expression of c-Myc and Bcl-2; in contrast, expression of a constitutively active Akt mutant induced Bcl-2 and c-Myc expression, and stimulated the transcription activation function of c-Myc. Together, these data demonstrate the requirement for the BCR/ABL SH2 domain in PI-3k activation and document the essential role of the PI-3k/Akt pathway in BCR/ABL leukemogenesis.

Animals

Treatment of Philadelphia leukemia in severe combined immunodeficient mice by combination of cyclophosphamide and bcr/abl antisense oligodeoxynucleotides.

BACKGROUND: Philadelphia cells are human chronic myelogenous leukemia (CML) cells that contain the BCR/ABL oncogene (a fusion of the BCR and ABL genes). Selective eradication of these cells in vitro can be achieved by combined treatment with antisense phosphorothioate oligodeoxynucleotides ([S]ODNs) specifically targeted to this oncogene (bcr/abl [S]ODNs) and a suboptimal (for use as a single agent) dose of mafosfamide (the in vitro active form of cyclophosphamide). PURPOSE: We evaluated the ability of bcr/abl antisense [S]ODNs, alone or subsequent to treatment with a single injection of cyclophosphamide, to suppress the leukemic process induced in severe combined immunodeficient (SCID) mice by Philadelphia cells (i.e., primary CML-blast crisis [CML-BC] cells). In addition, we studied potential mechanisms that might explain the efficacy of the bcr/abl antisense [S]ODN-mafosfamide combination against Philadelphia cells in vitro. METHODS: The effects of treating leukemic mice with cyclophosphamide (25 mg/kg body weight; 25% of the dose required to eradicate evidence of leukemia in SCID mice) and/or bcr/abl antisense [S]ODNs were assessed by analysis of survival, by examination of bone marrow for the presence of leukemia cells (using a colony formation assay or using coupled reverse transcription and the polymerase chain reaction to screen for bcr/abl messenger RNA), and by examination of a variety of tissues for the presence of infiltrating leukemia cells. The induction of apoptosis (a cell death program) in vitro in primary CML-BC cells following treatment with bcr/abl antisense [S]ODNs plus or minus prior treatment with mafosfamide was monitored by use of a commercial assay. Relative cellular uptake of [S]ODNs by CML-BC cells treated in vitro with or without prior treatment with mafosfamide was determined by use of confocal microscopy and flow cytometry (for fluorescent [S]ODNs) or by use of blotting techniques that employed radioactively labeled probes (for extracted, unlabeled [S]ODNs). Levels of specific proteins in treated and untreated cells were determined by use of western blotting methods. Reported P values are two-sided. RESULTS: The disease process in leukemic mice was retarded substantially by combination treatment with cyclophosphamide and specific bcr/abl antisense [S]ODNs (P < .001, relative to treatment with specific antisense [S]ODNs alone, cyclophosphamide alone, or cyclophosphamide plus nonspecific [i.e., control] antisense [S]ODNs); 50% of the mice treated with cyclophosphamide and specific antisense [S]ODNs appeared to be cured of leukemia. The combination treatment was associated with increased induction of apoptosis. In addition, cellular uptake of bcr/abl antisense [S]ODNs appeared to be increased twofold to sixfold by prior treatment with mafosfamide. This increased uptake of [S]ODNs was associated with enhanced suppression of p210bcr/abl protein levels. CONCLUSIONS AND IMPLICATIONS: Combination therapy with antisense [S]ODNs targeted to specific oncogenes and less toxic doses of anticancer drugs may represent a rational strategy to purpose for the treatment of human leukemias.

Animals

Immunohistochemical characteristics of nerve fibres supplying the porcine vas deferens. A colocalisation study.

Double-labelling immunofluorescence was used to investigate the coexistence of the catecholamine-synthesising enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase and several neuropeptides including neuropeptide Y, vasoactive intestinal polypeptide, Leu5-enkephalin, somatostatin, calcitonin gene-related peptide and substance P in nerve fibres supplying the vas deferens in juvenile and adult pigs. The study has revealed three major populations of nerve terminals innervating the organ: (1) noradrenergic fibres; (2) non-noradrenergic (putative cholinergic) fibres containing vasoactive intestinal polypeptide, neuropeptide Y and somatostatin, supplying almost exclusively the lamina propria; and (3) non-noradrenergic, presumably sensory fibres, containing calcitonin gene-related peptide and substance P. The population of noradrenergic nerves can be divided into three subpopulations: a somatostatin-containing, a Leu5-enkephalin-containing and a subpopulation immunonegative to the peptides investigated, in descending order of magnitude. Coexistence patterns of the substances existing within nerve fibres supplying the vas deferens blood vessels are clearly different from those found in nerve fibres innervating the organ wall. The majority of the noradrenergic fibres associated with blood vessels contain neuropeptide Y only, while non-noradrenergic perivascular nerves contain predominantly vasoactive intestinal polypeptide. The possibility of different sources of origin of the particular nerve fibre subpopulations supplying the porcine vas deferens and its blood vessels is discussed.

Animals

Noradrenergic and peptidergic innervation of the testis and epididymis in the male pig.

This study was designed to investigate the distribution of noradrenaline (NE)- and peptide-containing nerves in the testis of the boar. Testes, as well as caput and cauda epididymides from five 5 week-old and 3 adult boars were sectioned and immunostained with antisera to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), Leu-enkephalin (L-ENK) and somatostatin (SOM). In addition, double-labelling immunofluorescence method was used to disclose the pattern of co-existence of these substances in the nerve fibres. The most abundant innervation was found in the cauda epididymidis, and the density of the nerves distinctly decreased towards the caput epididymidis. The testicular parenchyma and caput epididymidis was supplied with very scattered TH-, D beta H-, NPY-, VIP-, SP-, CGRP-, L-ENK- and SOM-containing nerve fibres. The present study has demonstrated for the first time the existence of CGRP, L-ENK and SOM in nerve fibres innervating the testis of a vertebrate species. Different subpopulations of nerve fibres, including TH+/D beta H+, D beta H+/NPY+, D beta H-/NPY+, D beta H+/NPY-, D beta H+/VIP+, D beta H-/VIP+, D beta H+/SP+, D beta H-/SP+, D beta H+/L-ENK+ D beta H-/L-ENK+, D beta H+/SOM+ and D beta H-/SOM+, were localized and documented.

Animals

Increased expression of nitric oxide synthase in a subpopulation of rat sympathetic neurons after axotomy - correlation with vasoactive intestinal peptide.

Nitric oxide synthase (NOS) expression is increased in peripheral sensory and central motor neurons after axotomy. By applying double-labelling immunofluorescence and non-radioactive in situ hybridization, we have investigated the regulation of NOS in axotomized sympathetic rat superior cervical ganglia. Furthermore, co-localization of NOS with vasoactive intestinal peptide, which is also induced by axotomy, has been examined. Very few (<0.1%) NOS-expressing neurons are observed in control ganglia. Some large cell bodies located at the exit of the internal carotid nerve are additionally immunoreactive for vasoactive intestinal peptide. One week following postganglionic axotomy, the number of NOS-immunoreactive and NOS mRNA-expressing neurons increases but does not exceed 2% of the whole neuronal population. About 20% of these neurons are also immunoreactive for vasoactive intestinal peptide. Preganglionic nerve fibre meshworks that are immunoreactive for NOS in untreated ganglia disappear after ganglionic decentralization, whereas some presumably postganglionic fibres remain visible after combined axotomy and decentralization. The findings are indicative of an increased synthesis of NOS in a small subset of postganglionic neurons of the rat superior cervical ganglion, possibly because of the loss of target-derived factors that inhibit nitric oxide synthesis under normal conditions.

Adrenergic Fibers

Distribution of catecholamine-synthesizing enzymes and some neuropeptides in the median eminence-arcuate nucleus complex (MEARC) of the immature female pig.

The presence of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (D beta H) and some neuropeptides, including neuropeptide Y (NPY), Leu5-enkephalin (LENK), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL) and somatostatin (SOM) was investigated in nerve fibres and perikarya of the median eminence-arcuate nucleus complex (MEARC) of the sexually immature female pigs by means of the immunohistochemical avidin-biotin complex method. Although immunoreactivities to all the studied substances were found in nerve fibres of the porcine MEARC, there were differences in the distribution and density of particular subsets of nerve fibres within the complex. While loose D beta H-immunoreactive (D beta H-IR) and dense TH-, NPY- and VIP-IR nerve meshworks occurred predominantly in the internal layer of the MEARC, nerve fibres immunoreactive to TH, CGRP, SOM, SP and LENK were more numerous in the external than in the internal layer of the median eminence (ME). Numerous TH-, D beta H-, NPY-, VIP-, SP- and CGRP-IR perivascular nerve fibres were also observed within both layers of the median eminence. There were also differences in the distribution of a particular subset of neurons within the porcine MEARC: NPY-, VIP-, GAL-, SP- and TH-IR (but not D beta H-IR) perikarya were found in the arcuate nucleus, while in the median eminence only subpopulations of NPY-, VIP and GAL-IR neurons were observed.

Animals

Distribution of some neuropeptides in the porcine inferior mesenteric ganglion.

The occurrence and distribution of vasoactive intestinal polypeptide, substance P, and bombesin/gastrin-releasing peptide in neuronal cell bodies and nerve fibers of the porcine inferior mesenteric ganglion were studied with the indirect immunohistochemical technique. Of all substances studied only vasoactive intestinal polypeptide was found in principal ganglionic neurons. The presence of nerve fibers immunoreactive to vasoactive intestinal polypeptide, bombesin/gastrin-releasing peptide, and substance P was also found in the ganglion. There were differences in the pattern of distribution and density of the nerve fibers immunoreactive to the particular peptides. Fibers containing vasoactive intestinal polypeptide and bombesin/gastrin-releasing peptide were numerous, while fibers containing substance P were comparatively scarce. The present results revealed both similarities and specific differences in the occurrence and localisation of various neuropeptides in the porcine inferior mesenteric ganglion in comparison with that of other mammalian species.

Animals

Peptidergic innervation of the porcine oviduct studied by double-labelling immunohistochemistry.

Neurochemical coding of nerve fibres supplying the porcine oviduct was studied by means of double-labelling immunofluorescence. Immunoreactivities to rate-limiting enzymes of catecholamine synthesis, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DbetaH), were found in numerous oviductal nerve fibres. All TH-immunoreactive (TH-IR) nerve processes were simultaneously DbetaH-IR. This subset of nerves was considered to be sympathetic noradrenergic. In addition to noradrenaline, many axons additionally exhibited immunoreactivity to neuropeptide Y (NPY), or leu5-enkephalin (Leu-ENK). Small numbers of somatostatin- (SOM-) or vasoactive intestinal polypeptide-immunoreactive (VIP-IR) fibres, sometimes coexpressing TH/DbetaH-immunoreactivity, supplied the porcine oviduct. Substance P- (SP- ) and/or calcitonin gene-related peptide-immunoreactive (CGRP-IR) nerve fibres were only sporadically found. Although these nerves did not contain TH/DbetaH-immunoreactivity, they often ran in close vicinity to TH/DbetaH-IR axons, forming together thin nerve bundles. All the above mentioned subpopulations of nerve fibres were found throughout the entire length of the oviduct being mainly related to the vascular and non-vascular smooth myocytes. However, some of the putative afferent (i.e. SP- or CGRP-IR) or parasympathetic efferent (i.e. VIP- or NPY-IR but TH/DbetaH-immunonegative) axons were located beneath the epithelium. Such distribution implies these nerve fibres to be involved in the regulation of the oviductal blood flow, non-vascular smooth myocyte tonus, transmission of sensory information and control of the epithelial secretion.

Animals

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.

Animals

Distribution and immunohistochemical characteristics of neurons in the porcine caudal mesenteric ganglion projecting to the vas deferens and seminal vesicle.

Combined retrograde tracing (using fluorescent tracer Fast Blue) and double-labelling immunofluorescence were used to study the distribution and immunohistochemical characteristics of neurons in the porcine caudal mesenteric ganglion projecting to the vas deferens and seminal vesicle. The distribution and immunohistochemical properties of neurons projecting to both organs were similar. As revealed by retrograde tracing, Fast Blue-positive neurons were located within the left and right ganglia, with a distinct predominance in the ipsilateral one. In the ipsilateral ganglion, the majority of the neurons were located caudally, along the dorso-lateral ganglionic border, suggesting a somatotopic organization of the ganglion. Immunohistochemistry revealed four populations of retrogradely labelled neurons (from the largest to the smaller one): tyrosine hydroxylase-positive/neuropeptide Y-negative (TH+/NPY-), TH+/NPY+, TH-/NPY-, TH-/NPY+. With respect to their surrounding nerve fibres, two subpopulations of the dye-labelled neurons could be distinguished. The small one consisted of solitary neurons receiving a strong calcitonin gene-related peptide- and Leu5-enkephalin-, and a less intense vasoactive intestinal peptide-immunoreactive innervation. The remaining neurons were poorly supplied by singular nerve fibres containing some of the investigated peptides. We conclude that the caudal mesenteric ganglion should be considered as a prominent source of adrenergic and/or NPY-positive innervation for the porcine male reproductive tract.

Amidines

The distribution and co-localization of immunoreactivity to nitric oxide synthase, vasoactive intestinal polypeptide and substance P within nerve fibres supplying bovine and porcine female genital organs.

The distribution of nitric oxide synthase-immunoreactive (NOS-IR) axons and their relationship to structures immunoreactive to vasoactive intestinal polypeptide (VIP), substance P (SP) and tyrosine hydroxylase (TH) were studied by means of the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) technique or double-labelling immunofluorescence in the genital organs of cow and pig. Relevant neurons were also investigated in the pig. NOS-containing neural structures were TH-immunonegative in bovine or porcine genital organs, or in the studied ganglia. In the bovine ovary, NOS-IR nerves were neither VIP-IR nor SP-IR, whereas in the pig, most NOS-containing axons were also VIP-IR. The oviduct was supplied by single NOS/VIP- or NOS/SP-containing nerves, whereas in the uterus, NOS-IR axons were moderate in number, often being immunoreactive for VIP or SP. Numerous NOS/VIP-IR and NOS/SP-IR nerves were found in the vagina of both species. In all tissues studied, NOS-IR axons were mainly related to vascular smooth muscle. Most of the neurons of the paracervical ganglia and some neurons in dorsal root ganglia exhibited strong NOS activity. Only single neurons in sympathetic ganglia were NADPH-d-positive. Most nitrergic neurons in the autonomic ganglia were VIP-IR but SP-immunonegative. The sensory neurons were mostly NOS/SP-IR, whereas only single neurons co-expressed NOS and VIP immunoreactivity.

Animals

Existence and co-existence of vasoactive substances in nerve fibres supplying the abdomino-pelvic arterial tree of the female pig and cow.

The occurrence and co-localization of several presumed vasoactive neuropeptides, serotonin, and catecholamine-synthesising enzymes--tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H) and phenylethanolamine-N-methyltransferase (PNMT)--were investigated in perivascular nerves supplying the systemic and distributing arteries of the abdomino-pelvic arterial tree of the female pig and certain arteries supplying female reproductive organs in the cow. As revealed by single immunofluorescence, perivascular axons immunoreactive for TH, D beta H, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and Leu-enkephalin (LENK) occurred in both species examined, whereas galanin-immunoreactive (GAL-IR) nerve fibres were found exclusively in the pig. PNMT-, serotonin-, dynorphin A-, alpha-neoendorphin-, bombesin- or cholecystokinin-IR nerve terminals were not observed. The following classes of perivascular nerve fibres might be distinguished in the present study: 1) noradrenergic (i.e. TH/D beta H-IR), 2) NPY-, 3) GAL- (pig only), 4) LENK-, 5) VIP-, 6) SP-, 7) VIP/NPY-, 8) SP/CGRP-, 9) SP/GAL- (pig only), 10) SP/VIP- (cow only), 11) TH/D beta H/NPY- and 12) TH/D beta H/NPY/LENK-IR. Distinct differences in the distribution of LENK- and SP-IR axons around particular parts of the studied arterial tree in individual species were also observed. The present data indicate that the abdomino-pelvic arterial tree of the pig and cow receive perivascular nerve fibres that exhibit diverse chemical codes, and that different chemical coding of perivascular nerve fibres in individual species may depend on the target organ of the particular artery.

Abdomen

Peptidergic innervation of the bovine vagina and uterus.

The distribution of neuropeptide Y, substance P, vasoactive intestinal polypeptide, Leu5-enkephalin, bombesin/gastrin-releasing peptide, calcitonin gene-related peptide, somatostatin, cholecystokinin and catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase was studied immunohistochemically in nerve fibres supplying the bovine vagina and uterus. The nerves containing tyrosine hydroxylase or dopamine-beta-hydroxylase and neuropeptide Y-immunoreactivity were particularly numerous in both organs. Substance P, vasoactive intestinal polypeptide and Leu5-enkephalin-containing nerves were less numerous whereas somatostatin and calcitonin gene-related peptide-immunoreactive nerves occurred occasionally. Bombesin/gastrin-releasing peptide and cholecystokinin immunoreactivities were not present in nervous fibers of the bovine uterus and vagina. Generally, the immunoreactive nerve terminals, fibers, networks or nerve bundles were present below the serous membrane, between smooth muscle cells of muscular layers, around blood vessels, in the submucosal layer and below the luminal epithelium of the uterus and cervix.

Animals

Immunohistochemical localization of galanin in bovine reproductive organs.

The vagina, uterus and oviduct were shown to receive galanin immunoreactive (GAL-IR) nerve fibres, the number of which varied between particular organs. In the ovary, GAL-IR nerves were absent. A small number of these nerves were located in the layers of the oviduct. A moderate number of GAL-IR nerves were situated in the body and uterine horns, whereas the uterine cervix and vagina wall contained a large number of GAL-IR nerve fibres, evenly distributed throughout particular membranes of the organs. GAL-IR nerves were found to contain, simultaneously, either vasoactive intestinal polypeptide (VIP), substance P (SP) or Leu5-enkephalin (ENK). Many of the GAL-IR nerves contained tyrosine hydroxylase (TH). A group of GAL-IR nerves that did not possess immunoreactivity to VIP, SP, ENK or TH was also observed.

Animals

NADPH-diaphorase-containing cerebrovascular nerve fibres and their possible origin in the pig.

NADPH-diaphorase histochemical technique was applied to demonstrate the catalytic activity of nitric oxide synthase (NOS) in the nerve fibers supplying some porcine cerebral blood vessels, as well as in ganglia thought to be their possible sites of origin. Five sexually mature Large With Polish race sows were used. The following blood vessels and their branches were studied: the basal cerebral artery, medial cerebral artery, arteries of the circle of Wills as well as arteries located in the arachnoidea. The activity of NADPH-d was visualised in whole-mount preparations from the above listed blood vessels. The presence of NADPH-d was additionally studied in the ganglia of trigeminal nerves, the sensory ganglia of vagus nerves, the pterygopalatine and cranial cervical ganglia. NADPH-d activity was found in nerve fibres supplying all the studied arteries. Larger blood vessels, the basal cerebral artery, medial cerebral artery and arteries of the circle of Wills possessed very dense NADPH-d-positive nerve plexuses while arachnoidal arteries were poorly innervated by only single nerves. The vascular nerve fibers formed bundles varying in thickness, from very thick bundles often interchanging nerve fibers to quite thin fascicles. Thick bundles were absent from the walls of medium sized vessels and small meningeal arteries where only smaller fascicles or single fibres occurred. NADPH-d-positive neurons and nerve fibres were found in all the ganglia investigated. However, pronounced differences in the number of the positive nerve structures were observed between the ganglia. In the pterygopalatine, trigeminal and sensory ganglia of the vagal nerve the vast majority of neurons were NADPH-d-positive. Numerous NADPH-d-positive nerve fibers occurred within the pterygopalatine and trigeminal ganglion while sensory ganglia of the vagal nerve comprised smaller number of fibres. Small numbers of the neurons and moderate numbers of the nerve fibres occurred in the cranial cervical ganglion. The intensity of NADPH-d reaction in the endothelium was constant independent of the size of the vessels studied.

Animals