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Molecular structure of the mouse CCK-A receptor gene.

We have cloned the mouse CCK-A receptor gene (Cckar), determined its nucleotide sequence, and analyzed its expression. The receptor protein is encoded in five exons distributed over 9 kb of genomic DNA. Intron/exon borders were determined by comparing the genomic nucleotide sequence with the mouse cDNA sequence obtained by reverse transcriptase polymerase chain reaction. RNase protection analysis of Cckar transcripts revealed the presence of a splice acceptor site 200 bp upstream of the translational start codon, indicating that the promoter is associated with a non-translated exon at an upstream site. The second coding exon contains a rarely used alternative splice site that would result in the production of a truncated, 48 amino acid protein. Cckar is widely expressed in the gastrointestinal system (pancreas, gallbladder, intestine, colon and stomach), as well as in brain and kidney.

Alternative Splicing↗

Activation of protease-activated receptor-2 (PAR-2) triggers mucin secretion in the rat sublingual gland.

Protease-activated receptor-2 (PAR-2) is distributed throughout the gastrointestinal systems. The present study investigated the role for PAR-2 in the rat salivary glands. PAR-2 mRNA was detected in the sublingual, submaxillary, and parotid glands by a reverse-transcriptase polymerase chain reaction. In the isolated sublingual gland that exhibited the strongest signal for PAR-2, Ser-Leu-Ile-Gly-Arg-Leu-NH(2), a PAR-2-activating peptide, and trypsin, a PAR-2-activating enzyme, but not thrombin that can activate PARs 1, 3, and 4, triggered secretion of N-acetylneuraminic acid, an indicator of mucin, that was a unique major sialic acid detectable after hydrolysis of the sublingual mucin with 0.1 N HCl. The PAR-2-mediated secretion of mucin was attenuated by genistein, a tyrosine kinase inhibitor, but not by inhibitors of protein kinase C and phosphatidyl inositol 3'-kinase. Thus, PAR-2 is expressed by the three distinct salivary glands in the rat, and sublingual PAR-2 appears to play a role in triggering mucin secretion, at least in part, via activation of tyrosine kinase.

Animals↗

Effect of socioeconomic status on aphasia severity and recovery.

Low levels of educational attainment and low socioeconomic status have been significantly linked to poor health and increased incidence of disease, including Alzheimer's disease and diseases of the cardiovascular, pulmonary, renal, and gastrointestinal systems. Our goal in the present study was to determine the degree to which educational level and socioeconomic status influence initial severity of aphasia and subsequent recovery. We evaluated the records of 39 persons with aphasia twice: at about 4 months and 103 months postonset. We found early severity of aphasia to be significantly greater for subjects in the lower educational and occupational groups. However, rate of recovery (the slope of the recovery curve) was the same regardless of educational or occupational status.

Aphasia↗

Distribution of fibronectin in foetal tissues.

The distribution of fibronectin in tissues of four human foetuses (7-14 gestation weeks/GW) and twenty seven pig foetuses (25-114 days of gestation) was investigated using immunofluorescence and avidin/biotin methods. Fibronectin was abundant in the circulatory and gastrointestinal system and its derivates, in reticular stroma of immune organs, and in connective tissues and chorionic villi at all developmental stages.

Animals↗

Spontaneous reporting of adverse drug reactions in elderly patients in Sicily (Italy).

The aim of this study was to investigate the spontaneous reports of suspected adverse drug reactions, observed in elderly patients (over 65 years of age) in Sicily (Italy) during the period from 1 January 1995 to 31 December 1997. Of 1307 reports, the geriatric ADRs were 284 (21.7%); 92 (32.4%) of these were serious. There was a correlation between the reporting rates of ADRs and the increase of age. Similar trends are seen in the number of serious ADR reports. Old-older patients result most frequently affected by serious ADRs. The antimicrobial and musculo-skeletal drugs were responsible for 48. 3% of the whole suspected geriatric ADRs. The commonest ADRs reported for the elderly, affected skin and the gastrointestinal system. There was probably a correlation between multi-drug consumption, comorbidity and seriousness of ADRs. A higher percentage of serious ADRs originated from university hospitals (57. 1%).

Adverse Drug Reaction Reporting Systems↗

Trimetrexate: a new antifol entering clinical trials.

Trimetrexate, a 2,4-diaminoquinazoline derivative, is a new antifol recently introduced into clinical trials. It differs from methotrexate principally in its transport (not carrier-mediated), and its intracellular retention (not polyglutamylated). Trimetrexate is active against tumors which are methotrexate-resistant on the basis of impaired transport, and has a broader range of antitumor activity in preclinical models. Animal studies predict toxicity principally to the central nervous system, gastrointestinal tract and bone marrow.

Animals↗

Hepatic intra-arterial infusion of vincristine.

Currently the chemotherapeutic agents available for intra-arterial infusion in metastatic liver cancer are limited to only a few. The recent demonstration of the feasibility of prolonged IV infusion of vincristine led to exploration of hepatic intra-arterial infusion of this agent. A continuous infusion of 0.4 mg total dose was administered daily for 5 days via a hepatic artery catheter to each of six patients with metastatic liver cancer. Transient but life-threatening toxicity principally involving the nervous and gastrointestinal systems occurred in five of them. Future investigation of hepatic intra-arterial infusion of vincristine should be based on dose-schedules other than that employed in the current trial.

Adult↗

Comparison of two different biliary agents in healthy subjects and in patients with liver disease.

The kinetics of the iminodiacetic acids, dimethyl and diethyl IDA were studied in patients without and with liver disease. Diethyl IDA seems to be superior to dimethyl IDA in its diagnostic usefulness. It shows lower urinary excretion and a faster liver uptake, leading to more pronounced differences in liver peak time and in liver elimination half time and to faster visualisation of the gall bladder in patients with liver disease. The enterohepatic reabsorption is negligible as shown by enteral administration of the radiopharmaceutical and monitoring blood activity. Therefore it is not necessary to correct time activity curves of the liver for the IDA secreted into the gastrointestinal system. The most valuable diagnostic information with this substances may be gained in investigations on cholecystectomized patients with cholestasis.

Humans↗

Double-blind, placebo-controlled study of OM-8980 in rheumatoid arthritis.

A total of 95 patients suffering from active rheumatoid arthritis were included in this double-blind, placebo-controlled study of the immunomodulator OM-8980. Treatment was one capsule daily of OM-8980 or placebo for 6 months. A significant improvement was observed in the OM-8980 group in comparison with the placebo group as regards the Ritchie index (P = 0.002), grip strength (P = 0.02) and pain (P = 0.03). The number of swollen joints, duration of morning stiffness and erythrocyte sedimentation rate decreased more markedly under OM-8980 than under the placebo, without reaching the level of statistical significance. A significant difference in favour of OM-8980 was observed in the intake of non-steroidal anti-inflammatory drugs and oral corticosteroids. Clinical tolerance was on the whole good (10 cases with side effects out of 49 in the OM-8980 group and 7 out of 46 in the placebo group, ns), with the majority of the side effects concerning the gastrointestinal system. The global assessment of the therapeutic efficacy both by the physician and the patient showed a highly significant superiority of OM-8980 over the placebo (P = 0.001).

Adjuvants, Immunologic↗

Neuromedin U-like immunoreactivity in the thyroid gland of the rat.

Neuromedin U is a novel neuropeptide found to have a widespread distribution extending throughout the mammalian central nervous system, gastrointestinal tract and the endocrine cells of the pituitary gland. In order to investigate the possibility that neuromedin U-like immunoreactivity is also present in the thyroid gland of the adult rat we have examined its localisation and molecular nature by radioimmunoassay, immunocytochemistry and chromatographic analysis. The neuromedin U content of the whole thyroid gland was found to be 331 +/- 67 fmol/gland (mean +/- SEM), and this value significantly decreased (163 +/- 17 fmol/gland) as a result of 14 days of treatment with the anti-thyroid agent methimazole (10 mg/rat/day. Thyrotoxicosis induced by exogenous T4 (10 micrograms/rat/day) failed to alter the thyroid content of this peptide. Immunostaining studies localised neuromedin U to a minor population of parafollicular C-cells in untreated animals. Complementary chromatographic studies revealed a single molecular form of neuromedin U-like immunoreactivity in thyroid tissue extracts which was indistinguishable from synthetic rat neuromedin U standard.

Animals↗

Distribution of two forms of somatostatin in the brain, anterior intestine, and pancreas of adult lampreys (Petromyzon marinus).

The distribution of two major immunoreactive forms of somatostatin, somatostatin-14 and somatostatin-34, within the brain, pancreas and intestine of adult lampreys, Petromyzon marinus, was identified using antisera raised against these peptides. Immunostaining of the brain is similar in juveniles and upstream migrants, and somatostatin-14 is the major somatostatin form demonstrated. A few somatostatin-34-containing cells are localized within the olfactory bulbs, thalamus and hypothalamus, but cells immunoreactive to anti-somatostatin-34 in the hypothalamus and thalamus do not co-localize somatostatin-14. Immunostaining of pinealocytes within the pineal pellucida with anti-somatostatin-14 may infer a novel function for this structure. Somatostatin-14 and somatostatin-34 are co-localized within D-cells of the cranial pancreas and caudal pancreas of juveniles and upstream migrants. Numerous somatostatin-34-immunoreactive cells are distributed within the epithelial mucosa of the anterior intestine but not all of these cells cross-react with anti-somatostatin-14. It appears that somatostatin-34 is the major somatostatin in the pancreo-gastrointestinal system of adult lampreys.

Animals↗

[Multiorgan failure].

The diagnosis of multiple organ failure is based upon the sequential occurrence of failure of vital organ functions within a short period of time (lung, kidney, circulatory system, gastrointestinal tract, liver, metabolism, hemostasis). Underlying diseases are polytrauma, high risk surgical procedures, acute abdominal complications. Sepsis is the main pathogenetic factor. The mortality is 60-80% and in patients with abdominal sepsis plus acute renal failure and dialysis plus acute lung failure and artificial ventilation up to 100%. Intensive care is therefore focussed upon prophylaxis, predominantly shock therapy and surgical treatment of sepsis.

Abdomen↗

Ilio-psoas abscess: diagnosis and management.

The triad of fever, limp, and pain in the flank, pelvis or leg often leads to the evaluation of the hip, genitourinary or gastrointestinal system. In the past 6 years, at our hospital, five adolescents and one young adult with these symptoms have had an ilio-psoas abscess, all diagnosed by ultrasonography. Once the diagnosis was established, four patients were treated successfully by percutaneous retroperitoneal drainage guided by ultrasonography or computed tomography. Catheter drainage averaged 11 days accompanied by appropriate antibiotics. The remaining two patients had surgical transperitoneal drainage. Growth of Staphylococcus aureus, from an ilio-psoas abscess indicates that the process is primary in origin. Growth of fecal flora suggests an intra-abdominal process and warrants further investigation. Ilio-psoas abscess can be readily diagnosed by ultrasonography or computed tomography and treated by percutaneous retroperitoneal drainage.

Abscess↗

Fatal atheromatous embolization during coronary angiography.

Multiple fatal embolism following left heart catheterization is described in two patients. Postmortem examination showed friable atheromatous aortic plaques as the likely source of emboli that clinically involved the heart, peripheral blood vessels, brain, gastrointestinal system and solid organs. Histologic examination showed widespread arterial embolism by atheromatous material.

Angiography↗

Management of celiac disease in childhood and adolescence: unique challenges and strategies.

Celiac disease (CD) is a common condition that occurs in genetically predisposed individuals when they ingest products containing wheat, barley, or rye. It produces an autoimmune-mediated enteropathy with characteristic histologic features on small intestinal mucosal biopsy. The clinical manifestations of CD are highly variable and initially may be unrelated to the gastrointestinal system. The condition is also strongly associated with other autoimmune and nonautoimmune conditions. Physicians caring for children and adolescents are challenged with identifying those who might have CD and require referral for definitive testing, recognizing the potential pitfalls in the diagnostic work-up of the pediatric patient, and providing ongoing care for those with a positive diagnosis. Confirmation of the diagnosis mandates that the individual be placed on a strict gluten-free diet (GFD) for life, as this is the only treatment currently available for CD. This article will discuss the immunopathogenesis, epidemiology, and clinical manifestations of CD and will outline a strategy of active case-finding using serological tests to identify those who require an intestinal biopsy for definitive diagnosis. The need for lifelong treatment by means of a GFD and for continued follow-up of children and adolescents after diagnosis is emphasized.

Journal Article↗

Interleukin-6 and its receptor are expressed in human intestinal epithelial cells.

Recent studies have suggested that intestinal epithelial cells demonstrate some of the functions associated with immune competent cells. Based on these observations, we investigated whether gastrointestinal epithelial cells express Interleukin-6 (IL-6). The presence of this cytokine was tested in 53 normal and pathological tissue specimens of the human gastrointestinal tract using an immunohistochemical technique with anti-IL-6 monoclonal and polyclonal antibodies. Immunostaining shows that IL-6 is expressed in gastric and small intestinal epithelial cells. The tumor cells from a large subset (11 of 15) of colon cancer specimens were strongly immunostained. IL-6 immunostaining was less conspicuous and less frequent in the epithelial cells of normal colonic mucosa. Northern blot experiments indicated that the expression of IL-6 in colonic mucosa correlates quantitatively with the presence of its m-RNA. Furthermore, IL-6 receptor (IL-6R) m-RNA was also detected and was twice as abundant in colonic carcinoma as in normal colon. It is concluded that mucosal epithelial cells of the gastrointestinal system express IL-6 and that in the case of the colon, malignancy is accompanied by a higher expression. In addition, the presence of IL-6R transcript suggests that normal and neoplastic colonic epithelial cells might be autocrinally regulated by IL-6.

Antibodies, Monoclonal↗

Perspectives of CCK antagonists in pancreatic research. Part II. Experimental studies.

In this article, the effects of different classes of cholecystokinin (CCK) receptor antagonists in CCK-related physiological processes of the pancreas have been discussed. Both glutaramic acid derivatives and natural (benzodiazepine) analogs are potent, competitive antagonists of peripheral CCK receptors. These compounds thus provide a powerful tool for investigating the physiological and pharmacological actions of CCK in the gastrointestinal system, and have already clarified the role of CCK in pancreatic secretion and trophism or growth.

Animals↗