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At least 1,171 records · Page 65Linked to original sources
PubMed1990

hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma.

Approximately 50% of human breast tumors secrete a small cysteine-rich protein, pS2, of unknown function. pS2 protein was recently found to be homologous to a porcine protein with hormonogastric activity, pancreatic spasmolytic polypeptide (PSP), in which the 5-cysteine domain present in pS2 is tandemly duplicated. We have characterized cDNA species encoding PSP and its human and mouse counterparts, hSP and mSP. We show that hSP and pS2 are separately encoded in the genome, and that the two proteins are co-expressed in normal stomach epithelium. However, expression of hSP was not detected in breast tumors. Computer analysis revealed that the pattern of conserved cysteine residues in hSP and pS2, the P domain, is present at the N termini of two other mammalian proteins, intestinal sucrase-isomaltase and lysosomal alpha-glucosidase.

Amino Acid Sequence↗
PubMed2004

Migration of an intrauterine contraceptive device to the ovary.

We present the case of a 37-year-old woman with a history of 2 consecutive insertions of intrauterine contraceptive devices (IUDs) 3 years before she was referred to us for sonographic evaluation of lower abdominal pain. The first of the IUDs was presumed to have been expelled spontaneously, and 3 months after insertion of the second device, the patient had begun experiencing lower abdominal pain. Medical treatment with antibiotics and spasmolytics had been unsuccessful. We performed transvaginal sonography, which revealed the presence of an IUD in the uterus and a 2-cm linear metallic echogenic area in the left ovary, believed to represent another IUD. Anteroposterior radiography confirmed that there were 2 IUDs in the pelvis, and CT demonstrated 1 IUD in the uterus and another in the left ovary. The patient underwent laparoscopic removal of the ovarian IUD and was discharged in good condition. To our knowledge, this is the first report of migration of an IUD to the ovary detected on transvaginal sonography. We recommend consideration of this possibility during evaluation of women with unexplained chronic pelvic pain.

Abdominal Pain↗
PubMed2005

Small bowel motility assessment with magnetic resonance imaging.

PURPOSE: To assess primarily the feasibility of magnetic resonance imaging (MRI) as a tool to monitor small bowel peristaltic motion and secondarily to validate this technique by demonstrating drug-induced motility changes. MATERIALS AND METHODS: After a standardized oral preparation of Ispaghula husk (Metamucil) and meglumine gadoterate (Gd-DOTA; Dotarem), 10 volunteers underwent dynamic MRI using a two-dimensional turbofast field echo (TFE) sequence with a slice repetition time of 500 msec. Intraluminal cross-sectional caliber changes over time were assessed allowing quantification of the peristaltic frequencies and amplitudes of the small gut on various regions of interest. Pharmacologically induced alterations of the peristaltic motion after spasmolytics and gastrokinetic motion enhancers were investigated. RESULTS: Small bowel diameter measurement resulted in a peristalsis of 10.96 (SD = +/-2.51) waves per minute, oscillating regularly with mean amplitudes of 6.65 mm (SD = +/-1.15 mm). Peristaltic frequency in normal individuals is consistent with that observed with other techniques. Intravenous administration of scopolamine butylbromide (= hyoscine butylbromide/Buscopan) resulted in small bowel paralysis within 21.3 seconds (SD = +/-2.8 seconds). Prokinetic effect of intravenous metoclopramide (Paspertin) after Buscopan paralysis was tested in one volunteer, characterized by a slow recovery of peristalsis, which propagated from the proximal to the distal segments and enhanced contraction amplitudes. CONCLUSION: Dynamic MRI allows observing and quantifying small bowel peristalsis, characterizing motion patterns, and monitoring the effects of interfering factors such as drugs.

Adolescent↗
PubMed2005

MRI in Crohn's disease.

Technological developments have extended the role of MRI in the evaluation of the gastrointestinal tract. The potential of MRI to evaluate disease activity in Crohn's disease has been investigated extensively, as MRI has intrinsic advantages over other techniques, including noninvasiveness and the absence of ionizing radiation. For perianal fistulizing disease MRI has become a mainstay in evaluation of disease, as localization and extent of disease can be very well appreciated using both T2-weighted and T1-weighted sequences, fat suppression, and intravenous contrast medium. Imaging of the small bowel and colon in Crohn's disease is more complicated due to bowel peristalsis and respiratory movement. However, using fast breathhold sequences and intravenous spasmolytic medication, images of good diagnostic quality can be acquired. To obtain sufficiently distended bowel, which in our estimation is a prerequisite for evaluation of the bowel, MR enteroclysis can be performed. However, applicability of different oral contrast media has been studied, as a noninvasive method for bowel distension would be preferable. Abdominal MRI is a valuable imaging technique for evaluation of luminal, transmural, and extraintestinal manifestations of Crohn's disease as degree of disease activity, presence of luminal pathology (e.g., stenoses), and extraintestinal manifestations of disease (e.g., abscesses, fistulas) can be accurately assessed.

Crohn Disease↗
PubMed1994

Comparison of absorption of aqueous lidocaine and liposome lidocaine following topical application on rabbit vessels.

Liposomes are small particles that encapsulate lidocaine to form topical drug carriers. Forty rabbits were used to compare the absorption of aqueous lidocaine with that of liposome lidocaine after application of each on femoral and iliac vessels. Both agents entered the circulation rapidly. The serum levels of lidocaine were significantly lower and the peaks in concentration appeared later after the use of liposome lidocaine than after the use of aqueous lidocaine. This phenomenon was due to local accumulation of liposome lidocaine and slow release of lidocaine from the liposome. As a topical spasmolytic agent, liposome lidocaine may be superior to the aqueous form due to a lower serum concentration and less total absorption.

Absorption↗
PubMed1992

Determination of fenoverine, a modulator of smooth muscle motility, in capsules and in human plasma: application to dosage form stability and a pilot study in humans.

Fenoverine is a novel, potent, musculotropic, spasmolytic agent that affects primarily the gastrointestinal tract, bile duct, and female genital organs. A simple, specific, and accurate HPLC method was developed for the determination of fenoverine in capsules and plasma. This method has been successfully applied to stability studies of fenoverine capsules and to a pilot study in a normal, healthy volunteer following oral administration of fenoverine. For the determination of fenoverine in capsules, a Nucleosil 5-micron CN column, with acetonitrile:0.1 M ammonium acetate (60:40) as mobile phase and detection at 254 nm, was employed. The mean correlation coefficient of the calibration curve (n = 6) for the assay was 0.9999 over a concentration range of 24.6 to 147.6 micrograms/mL of fenoverine standard solutions. Fenoverine did not decompose significantly at 4, 45, 55, and 65 degrees C for 3 months. The mean correlation coefficients of within-day and between-day calibration curves were 0.9995 and 0.9999, respectively, over a range of 10 to 1000 ng/mL of fenoverine in plasma. The limit of detection was 10 ng in plasma.

Administration, Oral↗
PubMedDate not supplied

Calcium antagonism in heart and vascular smooth muscle.

Calcium antagonism is an unifying concept that offers a common denominator for a multitude of beneficial effects in cardiovascular therapy such as: direct reduction of myocardial energy expenditure and oxygen demand, improvement of myocardial oxygen supply resulting from spasmolytic and vasodilator effects on coronary trunk arteries (including collaterals and anastomoses), lowering of systemic arteriolar resistance (antihypertensive action), indirect diminition of cardiac oxygen requirement due to a fall in afterload, cardioprotection by prevention of excessive myocardial Ca uptake, damping effects on ectopic cardiac automaticity and on reentry pathways (not discussed in the present paper), and possibly anticalcinotic protection of the arterial walls at an advanced age or in cases of premature arterial senescence due to diabetes, hypertension, or nicotine intoxication.

Animals↗
PubMed1987

Experimental vasospasm.

Vasospasm is known to be present during most microvascular procedures. Not until recently has microsurgery made it possible to directly observe the dynamic nature of vascular spasm. This report reviews the physiologic events and the causes of vascular spasm during microsurgery. The current research models and the use of spasmolytic agents to relieve spasm are outlined. Future research in specific areas that pertain to the cremaster muscle model and the future direction and need for research in this area are discussed.

Animals↗
PubMed1995

Intravesical oxybutynin in patients with posterior rhizotomies and sacral anterior root stimulators.

This report investigates the use of intravesical oxybutynin in spinal injury patients, who have had dorsal rhizotomies to abolish reflex detrusor activity and void with S2, S3, and S4 stimulation, done with the Brindley anterior root stimulator. Six male patients (age range 27 to 56, mean 36 years) who have had Brindley anterior root stimulators implanted were included in this study. Video urodynamic assessment was done and 10 mg of oxybutynin hydrochloride was instilled through the urethral catheter. This was left in the bladder for 60 minutes and video urodynamics were repeated. Voiding, both pre and post oxybutynin, was achieved with sacral root stimulation. Peak detrusor pressure (Pves) during voiding in the 6 patients before oxybutynin instillation was 89, 154, 90, 60, 56, and 80 (mean 88.2) cm of water. Post oxybutynin the pressures were 83, 163, 95, 40, 30, and 68 (mean 79.8) cm of water. The peak flow rate (Qmax) pre oxybutynin was 32, 24, 20, 20, 12, and 28 (mean 22.7) ml per second and this changed to 28, 31, 18, 24, 10, and 32 (mean 23.8) ml per second. This shows no difference in the detrusor pressure (P = 0.2) and flow rate (P = 0.54) pre and post oxybutynin instillation into the bladder. Effectiveness of oxybutynin is attributed to a combination of M3 receptor antagonism in the smooth muscle and direct spasmolytic, local anaesthetic and calcium channel blocking action. Its therapeutic benefit is limited by the anti cholinergic side effects (40-80%) and recent studies have shown the intravesical route to be effective and better tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗
PubMed1990

Epidermal growth factor (EGF/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues.

The pS2 gene encodes for a small cysteine-rich protein, and was originally found by differential screening of a cDNA library from the human breast carcinoma cell line, MCF-7. The presence of pS2 is closely correlated with oestrogen dependence in breast carcinomas. While the function of pS2 is unknown, pS2 protein has been shown to be homologous with the gastrointestinal peptide hormone pancreatic spasmolytic polypeptide (PSP) and its human counterpart hSP, in which a 5-cysteine domain is tandemly repeated. The 5' flanking region of the pS2 gene contains an enhancer region responsive to oestrogens and to epidermal growth factor (EGF/URO). We now report that pS2 and hSP expression occurs in a wide range of endodermally-derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration. In each case, this expression was associated with secretion of immunoreactive EGF/URO. We further show that the co-expression of pS2 and hSP in gastric surface epithelial cells is also associated with the secretion of EGF/URO in the subjacent mucous neck cells. Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses. The finding of similar patterns of EGF/URO, hSP and pS2 expression in association with chronic damage suggests that this is a fundamental response in the healing of these tissues.

Cell Line↗
PubMed1994

The ulceration-associated cell lineage (UACL) reiterates the Brunner's gland differentiation programme but acquires the proliferative organization of the gastric gland.

The ulceration-associated cell lineage (UACL) develops in the human gastrointestinal mucosa after ulceration; it grows out from the bases of adjacent crypts and ramifies in the lamina propria to form a new gland, finally giving rise to a duct by which the glandular secretion and indeed cells are carried to the surface. Using immunocytochemistry and in situ hybridization with 35S-labelled riboprobes, we have defined the pattern of trefoil peptide gene expression (pS2; human spasmolytic polypeptide, hSP), epidermal growth factor/urogastrone (EGF/URO), and the distribution of cell proliferation during the development of the UACL, as indicated by immunostaining for proliferating cell nuclear antigen (PCNA). Our studies reveal that the morphogenesis of the UACL shows a marked morphological resemblance to developing Brunner's glands; the pattern of trefoil peptide gene expression during UACL development is also very similar. However, trefoil peptide gene expression in the mature UACL complex is unique amongst gastrointestinal cells. The mature UACL shows a distinctive proliferative organization: while the early buds and glands are non-proliferative, apparently being fed by cells from the parent crypts, a definitive proliferative zone develops within the duct. This, of course, corresponds to the location of the gastric gland proliferative zone. We propose that while the UACL shows novel features, it shares its differentiation programme with Brunner's glands, but its pattern of cell renewal eventually is that of the gastric gland.

Brunner Glands↗
PubMed2002

Selective serotonin reuptake inhibitor-induced urinary incontinence.

PURPOSE: Irrespective of its cause, urinary incontinence is a medical condition seriously affecting quality of life and is increasingly recognized. In this study, we examined the association between the use of selective serotonin reuptake inhibitors (SSRIs) and urinary incontinence. METHODS: A retrospective follow-up study among starters with an SSRI was performed to estimate the relative and absolute risk for urinary incontinence associated with SSRI use. Data came from the PHARMO database, which includes information on drug dispensing for approximately 450,000 residents living in eight Dutch cities. All patients initially using an SSRI between 1994 and 1998 were selected. The frequency measures for urinary incontinence were estimated by using prescription sequence analysis, where initiation of spasmolytic drugs or absorbent products was used as a measure for urinary incontinence. Besides crude incidence density calculations, Andersen-Gill's model was used in order to control for possible confounding factors and time varying covariates. RESULTS: A total of 13,531 were identified as first time users of an SSRI. Compared to non-exposure, the incidence density ratio for urinary incontinence during SSRI exposure was 1.75 (95% CI 1.56-1.97). Overall, compared to baseline, SSRI use caused 14 extra cases of urinary incontinence per 1000 patients treated per year; the elderly were more at risk resulting in 60 extra cases per 1000 patients per year. The adjusted relative risk for urinary incontinence due to SSRI use was 1.61 (95% CI 1.42-1.82); the risk for sertraline users was 2.76; 95% CI 1.47-5.21). CONCLUSIONS: Exposure to SSRIs is associated with an increased risk for developing urinary incontinence, which can be explained pharmacologically. Approximately 15 out of 1000 patients treated per year with an SSRI developed urinary incontinence. The elderly and users of sertraline are at the highest risk.

Adult↗
PubMed2005

Saturation labeling with cysteine-reactive cyanine fluorescent dyes provides increased sensitivity for protein expression profiling of laser-microdissected clinical specimens.

Laser capture microdissection (LCM) provides the capability to isolate and analyze small numbers of cells from a specific area of a histologic section. LCM has particular value for analysis of early stage tumors, which are often small and intermixed with non-tumor tissue. It has previously been shown that a new generation of cysteine-reactive cyanine dyes can, in principle, provide increased sensitivity for two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) profiling when sample quantitities are limiting. However, the comparative advantage of the new dyes in a clinical setting has not been established. Here, we report that cysteine-reactive dyes allowed the identification of more features than established, lysine-reactive dyes with a given number of cells. This was true both with extracts prepared from human papillomavirus E6 and E7-transduced human keratinocytes, a model for early-stage cervical cancer, and with LCM samples. In an experiment comparing LCM clinical samples of gastric adenocarcinoma versus precancerous, spasmolytic polypeptide expressing metaplasia (SPEM) from the same patient, cysteine labeling allowed the identification of more than 1000 discrete protein spots in samples containing 5000 cells. This is a 5- to 50-fold smaller sample than used in previous studies. Both labeling methods had a comparable success rate for protein identification by mass spectrometry (MS). The proteins associated with more than 40 differentially abundant spots in the clinical samples were identified by MS. In this exploratory analysis, changes in expression levels of cytoskeletal proteins, molecular chaperones, and cell-signaling proteins were seen. The identification of a number of proteins that are potentially relevant to tumor progression suggests that the method holds promise for biomarker discovery.

Adenocarcinoma↗
PubMed2001

Trefoil peptides promote restitution of wounded corneal epithelial cells.

The ocular surface shares many characteristics with mucosal surfaces. In both, healing is regulated by peptide growth factors, cytokines, and extracellular matrix proteins. However, these factors are not sufficient to ensure most rapid healing. Trefoil peptides are abundantly expressed epithelial cell products which exert protective effects and are key regulators of gastrointestinal epithelial restitution, the critical early phase of cell migration after mucosal injury. To assess the role of trefoil peptides in corneal epithelial wound healing, the effects of intestinal trefoil factor (ITF/TFF3) and spasmolytic polypeptide (SP/TFF2) on migration and proliferation of corneal epithelial cells were analyzed. Both ITF and SP enhanced restitution of primary rabbit corneal epithelial cells in vitro. While the restitution-enhancing effects of TGF-alpha and TGF-beta were both inhibited by neutralizing anti-TGF-beta-antibodies, trefoil peptide stimulation of restitution was not. Neither trefoil peptide significantly affected proliferation of primary corneal epithelial cells. ITF but not SP or pS2 mRNA was present in rabbit corneal and conjunctival tissues. In summary, the data indicate an unanticipated role of trefoil peptides in healing of ocular surface and demand rating their functional actions beyond the gastrointestinal tract.

Animals↗
PubMed1996

The gene encoding human intestinal trefoil factor (TFF3) is located on chromosome 21q22.3 clustered with other members of the trefoil peptide family.

The gene coding for human intestinal trefoil factor (hITF), a recently described cellular motogen produced by gastrointestinal goblet cells and epithelia elsewhere, is a member of the rapidly growing trefoil peptide family. In a rodent-human somatic cell hybrid panel, the hITF (HGMW-approved symbol TFF3) genomic locus segregated with human chromosome 21q. Fluorescence in situ hybridization with a 2.1-kb genomic probe of the hITF gene mapped this locus more precisely to the q22.3 region. Triple fluorescence in situ hybridization, together with physical mapping of human genomic DNA using pulsed-field gel electrophoresis, revealed that the hITF gene is tightly linked to those encoding the other known human trefoil peptides, namely the breast cancer estrogen-inducable gene pS2 (BCEI) and human spasmolytic polypeptide (hSP/SML1). This gene family could become a useful marker for the genetic and physical mapping of chromosome 21 and for a better definition of the region involved in the clinical phenotype of several genetic diseases.

Chromosome Mapping↗
PubMed1997

High-resolution solution structure of human pNR-2/pS2: a single trefoil motif protein.

pNR-2/pS2 is a 60 residue extracellular protein, which was originally discovered in human breast cancer cells, and subsequently found in other tumours and normal gastric epithelial cells. We have determined the three-dimensional solution structure of a C58S mutant of human pNR-2/pS2 using 639 distance and 137 torsion angle constraints obtained from analysis of multidimensional NMR spectra. A series of simulated annealing calculations resulted in the unambiguous determination of the protein's disulphide bonding pattern and produced a family of 19 structures consistent with the constraints. The peptide contains a single "trefoil" sequence motif, a region of about 40 residues with a characteristic sequence pattern, which has been found, either singly or as a repeat, in about a dozen extracellular proteins. The trefoil domain contains three disulphide bonds, whose 1-5, 2-4 and 3-6 cysteine pairings form the structure into three closely packed loops with only a small amount of secondary structure, which consists of a short alpha-helix packed against a two-stranded antiparallel beta-sheet. The structure of the domain is very similar to those of the two trefoil domains that occur in porcine spasmolytic polypeptide (PSP), the only member of the trefoil family whose three-dimensional structure has been previously determined. Outside the trefoil domain, which forms the compact "head" of the molecule, the N and C-terminal strands are closely associated, forming an extended "tail", which has some beta-sheet character for part of its length and which becomes more disordered towards the termini as indicated by (15)N{(1)H} NOEs. We have considered the structural implications of the possible formation of a native C58-C58 disulphide-bonded homodimer. Comparison of the surface features of pNR-2/pS2 and PSP, and consideration of the sequences of the other human trefoil domains in the light of these structures, illuminates the possible role of specific residues in ligand/receptor binding.

Amino Acid Sequence↗
PubMed1998

Receptor binding profile of Otilonium bromide.

The interaction of Otilonium bromide (OB) with binding sites for 63 different receptors and ion channels in appropriate preparations has been investigated. Experiments were also performed in rat colon, the preferred tissue for OB 'in vivo' uptake after oral administration. Among the receptors investigated OB binds with sub microM affinity to muscarinic M1, M2, M4, M5 and PAF receptors and with microM affinity to the diltiazem binding site on L type Ca2+ channels. In the rat colon OB shows competitive interaction with the verapamil binding site on L type Ca2+ channels and with muscarinic M2 receptors with IC50 of 1020 and 1220 nM, respectively. These findings provide a molecular rationale to explain the spasmolytic action exerted by OB on intestinal smooth muscle. In particular, a combination of antimuscarinic and Ca2+ channel blocker properties seems to best account for the action of this compound.

Animals↗
PubMed1990

Effect of L-arginine on haemoglobin-induced inhibition of endothelium-dependent relaxation of isolated cerebral arteries.

The effects of Oxy-haemoglobin were investigated in the rat isolated basilar artery and compared to Methylene blue and NG-Nitro-L-Arginine (NOLAG), as these compounds interfere with the relaxation induced by the endothelium-derived relaxing factor. Acetylcholine induced a concentration-related relaxation of serotonin-precontracted arteries which was further enhanced by the application of L-arginine. Similarly, the spasmolytic activity of L-arginine was enhanced by acetylcholine. Oxy-haemoglobin, Methylene blue and NOLAG induced an increase of resting tension and inhibited acetylcholine-induced relaxation. Furthermore, inhibition of acetylcholine-induced relaxation by Oxy-haemoglobin and NOLAG but not that by Methylene blue was partially reversed by L-arginine.

Acetylcholine↗