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P Alm

Publications and source records attributed to P Alm.

At least 109 records · Page 6Linked to original sources
PubMed1995

Nitric oxide pathway in cat esophagus: localization of nitric oxide synthase and functional effects.

In the cat lower esophageal sphincter (LES) and esophageal body, nitric oxide synthase (NOS) immunoreactive nerves were abundant in the circular smooth muscle layer, especially in the LES region. NADPH diaphorase staining showed an identical pattern. The ability to form L-citrulline from L-arginine corresponded roughly to the distribution of NOS. Confocal microscopic analysis indicated colocalization within neurons of vasoactive intestinal peptide (VIP) in 65% of NOS-positive nerves. In LES circular smooth muscle preparations, electrically induced relaxations (single train stimuli) were generally abolished by NG-nitro-L-arginine (L-NNA). Continuous electrical stimulation for 2 min evoked a relaxation in the presence of L-NNA. This relaxation was inhibited by VIP antiserum and followed by a decrease in guanosine 3',5'-cyclic monophosphate, but not by any consistent change in adenosine 3',5'-cyclic monophosphate levels. K+ (124 mM) induced a biphasic relaxation, with L-NNA inhibiting the first phase but not the second. We conclude that nitric oxide (NO) has a major role as the mediator responsible for relaxation in the cat esophagus. NO seems also to initiate the release and enhance the effect of another transmitter.

Amino Acid Oxidoreductases↗
PubMed1995

The prognostic information of DNA ploidy and S-phase fraction may vary with histologic grade in endometrial carcinoma.

DNA ploidy and S-phase fraction (SPF) were determined by flow cytometry on paraffin-embedded tumor material from 243 patients treated during 1980-1985. Patients with well differentiated and moderately differentiated tumors without solid areas (n = 351) formed a low-risk group (corrected 5-year survival 90%). Twenty-four patients, dead of disease within 5 years, were compared with 52 survivors. The estimated death risk was higher for those with SPF > or = 8.0% compared with those with SPF < 8.0% (odds ratio = 18.2; p < 0.001). SPF was the only independent prognostic factor in a multivariate analysis also including age, clinical stage and grade of differentiation. Patients with moderately differentiated tumors with solid areas or poorly differentiated tumors (n = 208) were regarded as a high-risk group. There was a difference in survival according to ploidy; the corrected 5-year survival was 75% for 106 patients with diploid tumors compared with 44% for those with non-diploid tumors (p < 0.0001). In a multivariate analysis DNA ploidy, age and clinical stage were independent prognostic factors, whereas SPF was no longer significant. Thus, DNA ploidy and SPF have different prognostic values depending on histological grade of endometrial carcinoma.

Adult↗
PubMed1995

Nitric oxide synthase-containing neurons in rat parasympathetic, sympathetic and sensory ganglia: a comparative study.

In rats, the distribution of nerve structures staining for NADPH-diaphorase, and showing immunoreactivities for nitric oxide synthase (NOS), tyrosine hydroxylase and various neuropeptides was studied in sensory ganglia (dorsal root, nodose and trigeminal ganglia), in sympathetic ganglia (superior cervical, stellate, coeliac-superior and inferior mesenteric ganglia), parasympathetic ganglia (sphenopalatine, submandibular, sublingual and otic ganglia), and in the mixed parasympathetic/sympathetic ganglia (major pelvic ganglia). The coincidence of neuronal cell bodies with strong NOS-immunoreactivity and strong NADPH diaphorase reactivity was almost total. The relative proportions of NOS-immunoreactive nerve cell bodies were largest in parasympathetic ganglia and major pelvic ganglia followed by sensory ganglia. In sympathetic ganglia no NOS-immunoreactive neuronal cell bodies could be detected. In parasympathetic and major pelvic ganglia, there was a very significant neuronal co-localization of immunoreactivities for NOS and vasoactive intestinal polypeptide (VIP). This was almost total in major pelvic ganglia, in which NOS-/VIP-immunoreactive nerve cell bodies were separate from sympathetic (tyrosine hydroxylase-/neuropeptide Y-immunoreactive), suggesting that NOS-/VIP-immuno-reactive neurons might also be parasympathetic.

Animals↗
PubMed1994

Nitric oxide synthase in the brain of a teleost.

The presence and distribution of the nitric oxide (NO) converting enzyme, NO synthase (NOS), was investigated in the brain of a teleost, the Atlantic salmon. Both NOS immunoreactive and NADPH diaphorase positive, non-neuronal and neuronal cell bodies, fibers and putative nerve terminals were identified throughout the brain. Even so, the staining was not identical in all regions. NO, synthesized by NOS-like enzymes, may play an important role in a diversity of cellular mechanisms in the brain of the salmon, including in neural systems related to olfactory, visual, hypophysiotrophic, viscero-sensoric and motor functions.

Amino Acid Oxidoreductases↗
PubMed1994

Nitric oxide synthase in the CNS of the Atlantic salmon.

This study describes for the first time the presence and distribution of the nitric oxide (NO) synthesizing enzyme, NO synthase (NOS), in the retina of a teleost. NADPH diaphorase (NADPHd) histochemistry and NOS immunohistochemistry revealed both NOS immunoreactive and NADPHd positive structures in photoreceptor outer segments, amacrine cells, horizontal cells and ganglion cells. Since NO is known to stimulate the synthesis of cGMP, our results implicate an important role for NO in retinal function, especially in cGMP related events in the photoreceptors.

Amino Acid Oxidoreductases↗
PubMed1994

Nitric oxide synthase-containing, peptide-containing, and acetylcholinesterase-positive nerves in the cat lower oesophagus.

The innervation of the cat lower oesophagus, including the lower oesophageal sphincter, was studied by enzyme histochemistry, immunohistochemistry, and confocal microscopy. In the lower oesophageal sphincter, and at a level 2 cm above it, no apparent differences were seen in the nerve distribution pattern. Among the nerve populations studied, acetylcholinesterase (AChE)-positive nerves were the most abundant in both these regions. The density of AChE-positive nerves was particularly marked in the circular muscle layer. A rich supply of nitric oxide synthase (NOS)-containing nerves was identified by using an antiserum against neuronal NOS, or by enzyme histochemical staining for NADPH diaphorase activity. Vasoactive intestinal peptide (VIP)-immunoreactive nerves had a similar distribution pattern as NOS-immunoreactive nerves, and nerves displaying immunoreactivity for NOS and VIP often showed profiles coinciding with AChE-positive nerves. As judged by confocal microscopy, immunoreactivities for helospectin, pituitary adenylate cyclase-activating peptide (PACAP) and VIP, to a large extent were found in the same nerves. At a level 7 cm above the lower oesophageal sphincter, the total nerve supply was less than in the sphincter itself and 2 cm above it. Immunoreactivity towards VIP, PACAP and helospectin was also found to co-exist with NOS and neuropeptide Y within the same nerve structures. It is concluded that there is an intricate innervation pattern in the feline lower oesophagus reflecting the complexity in the regulation of its motility.

Acetylcholinesterase↗
PubMed1994

Distribution, origin and projections of nitric oxide synthase-containing neurons in gut and pancreas.

Nitric oxide has been put forward as an important inhibitory neurotransmitter in the gut. Nitric oxide synthase-containing neurons were visualized by immunocytochemistry using antibodies against neuronal nitric oxide synthase or by beta-nicotinamide adenine dinucleotide phosphate diaphorase staining in whole mounts and cryostat sections from the gastrointestinal tract and pancreas of several mammals (mouse, rat, hamster, guinea-pig, cat and man). Nitric oxide synthase-containing neuronal cell bodies were numerous in the myenteric but fewer in the submucous ganglia all along the gut of all species. Varicose nerve terminals formed extensive networks in the circular smooth muscle and the myenteric ganglia. Nitric oxide synthase-containing nerve terminals were frequently found around the Brunner glands in the duodenum; scattered nerve terminals were also found in the gastric and colonic mucosa and around blood vessels in the submucosa all along the gut. In the rat small and large intestine nitric oxide synthase-containing submucous neurons terminated within the mucosa/submucosa and nitric oxide synthase-containing myenteric neurons issued short descending projections, approximately 3 mm, to the smooth muscle and other myenteric ganglia. In the pancreas of all species nitric oxide synthase-containing nerve cell bodies were regularly seen in intrapancreatic ganglia. Positive nerve fibers were mainly found within nerve trunks in interlobular spaces and as delicate fibers within the islets. Double staining for nitric oxide synthase and neuropeptides in intestine and pancreas of rat, guinea-pig and man revealed that only occasionally the nitric oxide synthase-containing nerve cell bodies stored in addition vasoactive intestinal peptide and neuropeptide Y, or enkephalin. However, nitric oxide synthase-containing nerve terminals, particularly those in the circular muscle of the gut, frequently contained vasoactive intestinal peptide/neuropeptide Y (rat and man) or vasoactive intestinal peptide/enkephalin (guinea-pig). In intrapancreatic ganglia few nitric oxide synthase-containing nerve cell bodies were also vasoactive intestinal peptide-immunoreactive. Coexistence of nitric oxide synthase and vasoactive intestinal peptide in nerve terminals could here be detected around blood vessels and interlobular ducts. The distribution of nitric oxide synthase indicates a major role of nitric oxide in the regulation of gut motility; a role in the regulation of blood flow and secretion in both gut and pancreas is also likely.

Amino Acid Oxidoreductases↗
PubMed1994

Renal and bladder functions in patients after spinal cord injuries.

Thirty-eight patients with spinal cord lesions, 22 recent and 16 sustained more than three years previously, were investigated with intravenous pyelography, chrome EDTA clearance, cystoscopy and urodynamic studies. Analyses of bladder biopsies for tissue concentrations of nor-adrenaline and occurrence of acetylcholinesterase staining of nerves were also performed. Despite high incidence of fairly mild infections and trabeculation of the bladder, renal function was normal in most patients. Apart from incontinence, stone formation and recurrent urinary tract infections were the most common complications. The concentrations of noradrenaline and the numbers of acetylcholinesterase-stained nerves in bladder tissue specimens did not differ from control findings. The organization of the nerve structures did not vary with time after the injury, suggesting unchanged adrenergic and cholinergic innervation.

Acetylcholinesterase↗
PubMed1993

Endothelin-1: immunocytochemistry, localization of binding sites, and contractile effects in human uteroplacental smooth muscle.

OBJECTIVE: Our purpose was to study the localization, distribution of binding sites, and contractile effects of endothelin-1 in human uteroplacental smooth muscle. STUDY DESIGN: The tissue localization of endothelin-1, the distribution of iodine 125-labeled endothelin-1 binding sites, and the mechanical effects of endothelin-1 were studied in isolated tissues from the human uterus and placenta by immunocytochemistry, autoradiography, and organ bath experiments. RESULTS: No specific endothelin-1 immunoreactivity could be detected in fetal placental tissues or in myometrium or intramyometrial arteries from term pregnant and nonpregnant women. In placental tissues a high density of iodine 125-labeled endothelin-1 binding sites was found in vessels of various sizes and in the chorionic villi, whereas the density in the jelly of Wharton was low. In myometrial tissue from pregnant and nonpregnant women a high density of iodine 125-labeled endothelin-1 binding sites was found, which in myometrium from pregnant women was mainly located to the myometrium and vascular smooth muscle. Endothelin-1 produced marked contractile responses in maternal and fetal uteroplacental vessels and in myometrial preparations. CONCLUSION: Endothelin-1 may be involved in the endogenous control of uteroplacental vascular and visceral smooth muscle.

Arteries↗
PubMed1993

Nitric oxide synthase in pig lower urinary tract: immunohistochemistry, NADPH diaphorase histochemistry and functional effects.

1. The distribution and colocalization of nitric oxide synthase (NOS)-like immunoreactivity and NADPH diaphorase activity in the pig lower urinary tract were investigated by immunohistochemical and histochemical staining techniques. Functional in vitro studies were performed to correlate the presence of NOS-immunoreactivity/NADPH diaphorase staining with smooth muscle responses involving the L-arginine/nitric oxide (NO) pathway. 2. NOS-immunoreactivity and NADPH diaphorase activity were expressed in nerve trunks and fine nerve fibres in and/or around muscular bundles in the detrusor, trigone and urethra. Thin nerve fibres that dispersed within the muscle bundles were mainly found in the urethral/trigonal area, whereas such fibres were less common in the detrusor. 3. Almost all neuronal structures that were NOS-immunolabeled were also stained for NADPH diaphorase. In contrast, the urothelium, which was intensively stained by the NADPH diaphorase technique, remained unstained by immunohistochemistry. 4. Electrical field stimulation of pig isolated trigonal and urethral preparations induced relaxations, which were inhibited by tetrodotoxin (1 microM) and NG-nitro-L-arginine (L-NOARG, 10 microM). 5. L-Arginine (1 mM), but not D-arginine, inhibited (25-30%) electrically evoked detrusor contractions. This inhibition was reversed by L-NOARG (0.1 mM). L-Arginine did not inhibit detrusor contractions in the presence of scopolamine (1 microM) and had no direct smooth muscle effects per se. 6. Acetylcholine (1 nM-10 microM) caused concentration-dependent relaxations of noradrenaline-induced contractions in pig vesical arteries. Removal of the endothelium practically abolished the acetylcholine-induced relaxation. Pretreatment with L-NOARG (0.1 mM and 0.3 mM) caused a rightward shift of the concentration-response curves to acetylcholine, but the maximal relaxation obtained was significantly reduced (to 65 +/- 12%; n = 6; P < 0.05) only at 0.3 mM L-NOARG. 7. In vessel segments contracted with K+ (60 mM), acetylcholine induced concentration-dependent relaxations. When the vessels were incubated with 0.3 mM L-NOARG and then contracted with K+ (60 mM) all relaxant responses to acetylcholine were abolished. 8. The presence of NO synthesizing enzyme in nerve fibres and the pharmacological evidence for NO-mediated relaxation of the trigone and urethra suggest that NO or a NO-related substance may have a role in inhibitory neurotransmission in these regions. In the detrusor, the presence of NO-synthesizing enzyme in nerves can be demonstrated, but its functional importance is unclear. NO, as well as other endothelium-derived factors seem to be involved in the endothelium-dependent acetylcholine-induced relaxation of pig vesical arteries.

Acetylcholine↗
PubMed1993

Immunohistochemical localization of peripheral nitric oxide synthase-containing nerves using antibodies raised against synthesized C- and N-terminal fragments of a cloned enzyme from rat brain.

Antibodies were raised in rabbits against C- or N-terminal fragments of a cloned nitric oxide synthase (NOS) enzyme from rat cerebellum, and used for demonstration of NOS-immunoreactive (NOS-IR) nerves in different tissues from the rat (colon, duodenum, adrenal gland, aorta, caval vein, penis and urethra). Both antisera demonstrated the same neuronal elements, although with differences in intensity in the immunoreaction in some tissues. Sections incubated with antisera preabsorbed with excess of the antigens showed no NOS immunoreactivity. In duodenum and colon, NOS-immunoreactivity was found in the cytoplasm of numerous cell bodies in myenteric ganglia and in some nerve cell bodies in the submucosa. NOS-IR nerve fibres were numerous in the circular muscle layer, while few were found in the longitudinal layer or the mucosa and submucosa. In the penis, strong NOS immunoreactivity was found in nerves surrounding the deep penile and dorsal arteries, and in nerves in the stroma of the cavernous tissue. In the urethra, NOS immunoreactivity was found in nerves in the mucosa. No NOS immunoreactivity was found in the urothelium. The adrenal medulla, and occasionally the cortex, contained nerve cell bodies with strong cytoplasmic NOS immunoreactivity as well as scattered nerve fibres. No NOS immunoreactivity was found in the abdominal aorta or inferior caval vein. Combined NOS immunostaining and NADPH diaphorase staining showed that virtually all NOS-IR nerve structures were also NADPH diaphorase-positive. However, thin nerve fibres and cell linings were sometimes better visualized by NOS-immunohistochemistry. Furthermore, the adrenal cortex, which only occasionally showed NOS immunoreactivity, was strongly NADPH diaphorase-positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

The L-arginine/nitric oxide pathway in the rabbit urethral lamina propria.

A non-adrenergic, non-cholinergic (NANC)-mediated relaxation has been demonstrated in the female rabbit urethral lamina propria, both in response to electrical stimulation and after administration of acetylcholine. The present study was performed to investigate if these relaxations are mediated via the L-arginine/nitric oxide (NO) pathway. In the lamina propria of the female rabbit urethra, numerous NADPH diaphorase-positive, fine varicose nerve fibres were observed both around arteries, in and around smooth muscle bundles, and in arterial endothelium. Since NADPH diaphorase histochemistry may be a marker of NO synthase-containing neurons, this finding suggests the occurrence of NO synthase in this tissue. Isolated preparations of the rabbit urethral lamina propria, contracted by noradrenaline, produced frequency-dependent NANC relaxations in response to electrical field stimulation, and concentration-dependent NANC relaxations in response to acetylcholine. Electrically induced relaxations were possible to evoke even in preparations where acetylcholine-induced relaxation was poor or absent. Pretreatment with the NO synthase inhibitor, NG-nitro-L-arginine (L-NOARG) reduced the maximum relaxation obtained at 30 Hz to 12% of the control response. NG-nitro-D-arginine (D-NOARG) had no effect. The effects of L-NOARG were antagonized by the addition of L-arginine. Acetylcholine relaxed noradrenaline-precontracted strips by 36%; vasoactive intestinal polypeptide (VIP) reduced the contraction by 95%. L-NOARG, but not D-NOARG, abolished or reversed acetylcholine-induced relaxations, but failed to reduce the relaxations produced by VIP. The results demonstrate the occurrence of NADPH diaphorase-positive nerve fibres in the lamina propria of the female rabbit urethra.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

The role of the L-arginine/nitric oxide pathway for relaxation of the human lower oesophageal sphincter.

Smooth muscle specimens were taken from the oesophagogastric junction (OGJ) in patients operated on for gastrointestinal malignancies not involving the OGJ. The smooth muscle bundles of the inner, circular layer of the OGJ were richly innervated by fine nerve fibres staining positively for NADPH diaphorase. The outer longitudinal layer had a markedly lower number of NADPH-diaphorase positive nerve fibres. When the preparations were suspended in organ baths for recording of isometric tension, they developed active tension. Transmural field stimulation (TMS) induced frequency-dependent relaxations, which were abolished by NG-nitro-L-arginine (L-NNA; 10(-4) M), and were often converted to atropine-sensitive contractions. The effect of L-NNA was concentration-dependent, and the concentration-response curve for L-NNA was shifted to the right by L-arginine pre-incubation. The enantiomer NG-nitro-D-arginine (10(-4) M) also showed inhibitory actions on the responses to TMS, but significantly less than L-NNA. Relaxant responses to vasoactive intestinal polypeptide (VIP), forskolin, and sodium nitroprusside were unaffected by L-NNA pre-incubation. Exposure to a 124 mM K+ solution resulted in a biphasic relaxation of the preparations. This relaxation was not seen in preparations treated with scorpion venom (20 micrograms ml-1) or L-NNA (10(-4) M). Instead, a contractile response to 124 mM K+ solution was found. The results suggest that NANC responses to electrical stimulation of nerves in the human OGJ are mediated by a product generated from L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1993

Peptide-containing nerve fibers in human airways: distribution and coexistence pattern.

The occurrence, distribution and coexistence pattern of an array of neuropeptides and tyrosine hydroxylase in the human larynx, trachea, bronchi and lungs were studied by immunocytochemistry. A rich supply of nerve fibers containing vasoactive intestinal peptide (VIP) was seen close to blood vessels, glands and nonvascular smooth muscle. Pituitary adenylate cyclase-activating peptide (PACAP)-containing fibers were numerous among bundles of smooth muscle. Moderate numbers of helospectin-containing nerve fibers were seen in the nonvascular smooth muscle. The majority of neuropeptide Y (NPY)-containing fibers were located in the nonvascular smooth muscle; some fibers also occurred around blood vessels and glands. Substance P (SP) and calcitonin gene-related peptide (CGRP)-containing fibers were generally few and distributed beneath the epithelium, among bundles of smooth muscle, around blood vessels and glands. A conspicuous finding was the lack of SP- and CGRP-containing fibers within the respiratory epithelium. Galanin-containing nerve fibers were moderate in number among bundles of smooth muscle. Tyrosine hydroxylase-containing fibers were numerous around blood vessels and glands. The majority of the VIP-containing nerve fibers present in nonvascular smooth muscle also stored PACAP and helospectin. A subpopulation of VIP-containing fibers in both vascular and nonvascular smooth muscle and around glands stored NPY. Additionally, galanin was found to occur in many VIP-containing fibers located among bundles of smooth muscle.

Adrenergic Fibers↗
PubMed1993

Prognostic significance of a formalin-resistant nuclear proliferation antigen in mammary carcinomas as determined by the monoclonal antibody Ki-S1.

Proliferative activity is a potential prognostic indicator of neoplastic cell growth. Usually the assessment of the tumor growth fraction requires specially processed or frozen tissue. We have raised a monoclonal antibody, Ki-S1, suitable for the detection of proliferating cells in routinely processed and paraffin-embedded tissue specimens. A retrospective study was conducted on 83 mammary carcinoma patients with a median follow-up of 45.6 months. Ki-S1 positivity was significantly (P < 0.0001) correlated with the S-phase fraction. A high proliferative activity of more than 30% of tumor cells being Ki-S1-positive was significantly correlated with recurrence (P < 0.001). Cumulative survival was significantly reduced in the high Ki-S1 expressing subgroup. In a multivariate model including Ki-S1, lymph node metastases, tumor size, and progesterone receptor positivity, independent significant information was provided by Ki-S1. We conclude that in mammary carcinomas, Ki-S1-determined growth fraction represents a significant and independent prognostic predictor.

Adult↗
PubMed1993

Characterization of a non-Goodpasture autoantibody to type IV collagen.

Goodpasture's syndrome is a very severe and aggressive autoimmune kidney disease. The patients' autoantibodies, which are pathogenic, are restricted to the C-terminal region of the alpha 3-chain of type IV collagen. In this paper we characterize an anti-type IV collagen antibody from a patient with a non-progressive form of glomerulonephritis. ELISA and immunoblotting were used to study the specificity of this patient's antibodies. The patient had high titres of antibodies restricted to the C-terminal region of the alpha 1-chain of type IV collagen. The antibody recognized an epitope hidden in the NC1 molecule which was fully exposed after denaturation or reduction. It was an IgG3 antibody composed of only lambda light chains, indicating that it has a potential to induce inflammatory damage and that it is probably monoclonal. This patient also had MPO-ANCA which were of IgG1 subclass. Our patient had no disease progression during the 5 years of treatment. Even though the anti-alpha 1 (IV) antibodies react with the same domain, but of a different chain of type IV collagen compared to the Goodpasture's antibodies, they do not induce any severe damage. It is thus uncertain if the anti-alpha 1 (IV) antibodies have any pathogenic role; the kidney damage might have been caused by the MPO-ANCA. The findings support the theory that the anti-alpha 3 (IV) antibody causes disease in Goodpasture's syndrome and that antibodies restricted to other subunits of the C-terminal region of type IV collagen are less harmful.

Animals↗