Enteric nervous system and endocrine cells demonstrated in the gut in teratomas

A case of retroperitoneal teratoma, showing considerable morphological development presented as an encapsulated and pedunculated tumour with a seemingly mature intestinal loop. Markedly complex intramural nerve plexuses and numerous epithelial endocrine cells were revealed immunohistochemically in the gut tissue. Ten other mature teratomas containing gastrointestinal tissues were examined for comparison, but neither intramural ganglia nor nervous networks were found in the gut components, despite the presence of amine- and/or peptide-containing endocrine cells in all intestinal mucosa linings. Enteric endocrine cells were found to occur irrespective of the differentiation of intestinal layers or the occurrence of neural elements. These findings suggest that the epithelial endocrine cells of intestinal mucosa do not have the same origin as enteric neurons, but are rather of endodermal origin. This invertebrate well-formed teratoma, containing a highly organized enteric nervous system, suggests that teratoma and fetus in fetus are related entities distinguished by the presence of a vertebral axis.     

Effect of aging on gastrin receptor gene expression in rat stomach

Broiler chickens were raised in separate rooms kept at temperatures of either 27 C or 16 C from 28 through 39 days of age. At the high temperature mouth breathing was recorded, but it was absent at the lower temperature. The number of dust particles in the air was greater in the warm rooms. More than 50% of the chickens in warm rooms had microscopic lesions in the bronchi of their lungs, whereas fewer than 5% of chickens in cold rooms had such lesions. Large dust particles were visible in some of the lesions. It was postulated that the increased incidence of lung lesions in chickens from warm rooms was due to mouth breathing rather than the higher dust levels in the air of these rooms.     

Effect of multidrug-resistant P-glycoprotein gene expression on chloroaluminum tetrasulfonate phthalocyanine concentration

The effect of multidrug-resistant P-glycoprotein gene expression (MDR1) in 3T3 cells on cellular concentrations and cytotoxicity induced by the photodynamic agent chloroaluminum tetrasulfonate phthalocyanine (AlSPc) was evaluated. 3T3 cells transfected with a retroviral vector expressing human MDR1 cDNA were resistant to colchicine. Resistant cells incubated with daunomycin accumulated only 40-50% of the quantity of daunomycin accumulated in control cells. Resistant cells incubated with daunomycin in the presence of verapamil had intracellular daunomycin concentrations approximately equal to control cells without verapamil. When these MDR1 3T3 cells were incubated with AlSPc, cellular concentrations of AlSPc did not differ between cells resistant to colchicine and those that were not. Similarly, there was little difference in cytotoxicity demonstrated by 51Cromium release in the two cell lines exposed to AlSPc and light (675 nm; 6 J/cm2). This study suggests photodynamic therapy using AlSPc may be a useful treatment modality for tumors in which the MDR1 P-glycoprotein confers resistance to cancer chemotherapeutics.     

Effect of hepatitis B virus X protein on the expression of retinoblastoma gene product

Consistent reports from several recent studies suggest that users of third generation oral contraceptives (OCs) containing gestodene and desogestrel may be at increased risk of venous thromboembolic disease (VTE). Paradoxically, other reports indicate that these users may be at decreased risk of acute myocardial infarction (MI) compared with users of second generation OCs. To determine whether the potentially increased risk of VTE would outweigh the potentially reduced risk of MI in users of third generation OCs, we conducted an analysis to quantify the trade-offs providers and users may be faced to make between these formulations. The baseline rates of VTE and MI among non-users were calculated using US data on incidence and mortality of these conditions and estimates of the proportion of women exposed to these formulations in the US. These were multiplied by relative risks published in recent studies on third generation progestins to produce age- and formulation-specific risks. Results indicate that there would be small differences in disease burden between users of second and third generation OCs under the model assumptions at younger ages. However, among women 35-44 years of age, modeling results indicate that the potentially decreased incidence of MI among users of third generation OCs more than offsets the potentially increased risk of VTE at this age.     

Effect of short-term administration of dexamethasone on canine antral gastrin gene expression

In a two-part study of the circumcision status of boys with urinary tract infections (UTIs), we reviewed the occurrence of UTIs in 209,399 infants born in US Army hospitals worldwide from 1985 to 1990. During the first year of life, 1,046 (0.5%: 550 girls and 496 boys) were hospitalized for UTIs. Noncircumcised male infants had a 10-fold greater incidence of infection than did circumcised male infants. The frequency rate of circumcision rose significantly, from 70.3% to 80.2%, during the study period. Among uncircumcised boys younger than 3 months with UTIs, 23% had concomitant bacteremia involving the same organism. The second part of the study consisted of a meta-analysis of all nine previous reports on the circumcision status of boys with UTIs. These studies revealed a fivefold to 89-fold increased risk of infection in uncircumcised boys; the combined data yielded a 12-fold increase in UTIs in this population. Parents should be told of the lower risk of UTIs for circumcised boys during informed-consent counseling.     

Effect of propofol infusion on the endocrine response to cardiac surgery

PURPOSE: Bilateral lower extremity venous duplex scanning for acute deep venous thrombosis (DVT) has been advocated because of the high incidence of occult contralateral leg involvement. We investigated the clinical necessity of such a policy. METHODS: The results from 2996 venous duplex studies performed during the past 2 years were retrospectively reviewed. A total of 1694 of these scans were performed on patients with symptoms, of whom 248 (15%) were found to have an acute DVT. Symptoms were limited to one side in 198 patients, whereas bilateral complaints were noted in 50 patients. RESULTS: Among the patients with symptoms of acute DVT, 72 (29%) had bilateral involvement. Bilaterality was more likely in patients with bilateral symptoms than in those with only unilateral symptoms (56% vs 22%; p < 0.005). Of the patients with unilateral symptoms and bilateral DVT, all of them had either acute (80%) or acute and chronic (20%) thrombosis in the symptomatic leg. The contralateral asymptomatic limb had fewer acute and more chronic DVT (41% and 55%, respectively). No patient from the entire group admitted with symptoms had an acute DVT in the asymptomatic limb without a concomitant acute DVT in the symptomatic leg. Unilateral scanning would decrease the examination time by 21% and potentially increase total reimbursement for symptomatic venous scans by 9% compared with routine bilateral duplex scanning. CONCLUSIONS: Although bilateral involvement is frequent in patients with symptoms of acute DVT, treatment in these patients is not altered by this finding. We conclude that contralateral venous scanning in patients with unilateral symptoms is not clinically indicated and that unilateral scanning would result in improved cost-efficiency for vascular laboratories.     

Widespread expression in adult rat forebrain of mRNA encoding high-affinity neurotensin receptor

The peptides neurotensin (NT) and neuromedin N exert effects on neurons by means of a high-affinity NT receptor (NTRH) belonging to the superfamily of G-protein-coupled receptors. In the present study, we used in situ hybridization histochemistry with sensitive riboprobe methodology to investigate the distribution of NTRH mRNA in the forebrain of adult rats. Labeled cells were abundant in the hypothalamus, epithalamus, ventral thalamus, septum, amygdala, and pallidum, including many regions where NTRH mRNA had not been detected previously. In the hypothalamus, novel sites of NTRH mRNA expression included the arcuate, periventricular, paraventricular, supraoptic, medial preoptic, anterior, ventromedial, and posterior nuclei, as well as the lateral hypothalamic area. In the thalamus, novel sites of expression included the anterodorsal nucleus, lateral habenula, and zona incerta, where labeling was much more extensive than previously reported. Novel telencephalic sites of expression included most bed nuclei of the stria terminalis, most divisions of the amygdala, the main olfactory bulb, the endopiriform nucleus, the claustrum, many parts of retrohippocampal allocortex, and limited parts of most isocortical areas. Novel sites of expression were also observed in the midbrain and pons. Taking into account expected differences in the subcellular locations of receptor mRNA and protein, the regional distribution of NTRH mRNA agrees well with that of NTRH determined previously. Our results identify many novel sites of NTRH mRNA expression in adult brain and provide a basis for investigating involvement of NT and related peptides in regulating the activity of these diverse cells, whose phenotypes remain largely undetermined.     

Effect of electroacupuncture on gastric acid secretion and gut hormones

21 patients with mild type of chronic superficial gastritis were selected in this study. The effect of electroacupuncture in Zhongwan (RM12), Neiguan (P6) and Sanyinjiao (Sp6) on gastric acid secretion, serum gastrin, plasma somatostatin, plasma motilin concentration and erythrocyte acetylcholinesterase (AchE) activity were observed. The results were as follows: There were significant decreases in gastric acid output, serum gastrin concentration and AchE activity (P < 0.05), but no significant changes in plasma somatostatin and motilin concentration (P > 0.05) after simultaneous electroacupuncture in Zhongwan, Neiguan and Sanyinjiao.     

Effect of adrenal steroids on preproneurokinin-A gene expression in discrete regions of the rat brain

Glycogen phosphorylase b has been purified to homogeneity from the fat body of larval Manduca sexta. The purification procedure involved ammonium sulfate precipitation, and chromatography of DEAE-cellulose, 5'-AMP-Sepharose and Q-Sepharose. The final product, which showed a single band on SDS-PAGE with a M(r) = 92,500, was purified 50-fold from the original homogenate in a yield of about 3%. The molecular mass of the native purified phosphorylase b was estimated to be 186,000 Da from gel filtration, suggesting that the native enzyme is a dimer. The apparent Km values for glycogen, phosphate and 5'-AMP were 1.4 mM, 82 mM and 1.1 mM, respectively. The enzyme had a pH optimum of 7.05, and was inhibited by ATP, ADP and glucose, but not by trehalose, even at high concentration. Conversion of phosphorylase b into the a form was achieved by incubation with rabbit phosphorylase kinase and Mg(2+)-ATP. The molecular mass of phosphorylase a was estimated to be 250,000 Da by gel filtration chromatography. The specific activity of the a form in the presence of 5'-AMP was 1.6-1.7-fold higher than the specific activity of the b form under the same conditions. Thus, 5'-AMP activates the a form by about 20%, whereas ATP has no effect on the phosphorylase a activity.     

Mutation of the MENIN gene in sporadic pancreatic endocrine tumors

Pancreatic endocrine tumors occur both sporadically and as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome. MEN1 is an autosomal dominant disease characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and pituitary adenomas. The MEN1 gene called MENIN maps to chromosome 11q13 and is thought to function as a tumor suppressor gene. We previously demonstrated loss of heterozygosity (LOH) at 11q13 in approximately 40% of sporadic pancreatic endocrine tumors and hypothesize that MENIN is involved in the development of these tumors. Thirty-one sporadic pancreatic endocrine tumors were analyzed for mutation of MENIN by nonradioactive single-stranded conformation polymorphism. Twelve mutations were detected in 31 sporadic pancreatic endocrine tumors (34%). Twelve of these 31 tumors previously demonstrated loss of heterozygosity at 11q13. Of the tumors with LOH, seven contained mutations of the MENIN gene (58%). The majority of the MENIN mutations occurred within exon 2. Two independent mutations in MENIN were detected in a gastrinoma that also revealed LOH, leading to the possibility of another tumor suppressor gene locus at 11q13. Mutations were present in both benign and malignant pancreatic endocrine tumors, suggesting that a MENIN gene mutation is a frequent and early event in the tumorigenesis. The high incidence of truncating mutations in tumors with LOH at 11q13 support the hypothesis that MENIN is a tumor suppressor gene.     

Identification in the rat neurotensin receptor of amino-acid residues critical for the binding of neurotensin

In order to identify charged amino-acid residues of the cloned rat brain neurotensin (NT) receptor (NTR) that are critical for NT binding, we performed site-directed mutagenesis on the cDNA encoding this protein, followed by transient expression into mammalian COS-7 cells and in Xenopus laevis oocytes. Point substitutions of charged residues in the N-terminal part and in the 2nd and 3rd extracellular loop of the receptor either did not affect (125)I-Tyr3-NT binding or resulted in a decrease in binding affinity by a factor of 2-3. Mutations of amino acids Asp113 in the second transmembrane domain (TM) and of Arg149 or Asp150 in TM III yielded receptors that bound NT as efficiently as the native receptor. By contrast, replacement of the Asp139 residue in the 1st extracellular loop, or of Arg143 or Arg327-Arg328 residues at the top of TM III and in TM VI, respectively, completely abolished ligand binding. Confocal and EM immunocytochemical studies of the expression of these affected receptors, tagged with the C-terminal sequence of the vesicular stomatitis virus glycoprotein (VSV-G), indicated that this loss of binding was not due to altered receptor expression or to their improper insertion into the plasma membrane. When these mutated forms of neurotensin receptor were expressed into Xenopus oocytes, Asp139-Gly- and Arg143-Gly-modified receptors remained functional in spite of a lowered response to NT whereas the Arg327-Arg328 mutant form was totally insensitive to NT at concentrations up to 10 microM. In the case of the Arg327-Arg328 mutation, the observed insensibility to NT could be the result of a drastic conformational alteration of this mutant protein. By contrast, it would appear that Asp139 and Arg143 residues located in the first extracellular loop of the receptor may be directly involved in the interaction of the receptor with neurotensin.     

Effect of heparin on mesangial cell growth and gene expression of matrix proteins

BACKGROUND: Mesangial cell (MC) proliferation and matrix expansion are characteristics of many glomerulopathies. Heparin has been shown to inhibit MC proliferation in vitro and mitigate cell proliferation, matrix expansion, proteinuria, renal insufficiency, and hypertension in experimental glomerulonephritis and subtotal renal ablation. We examined the effect of standard heparin on MC proliferation and matrix protein expression in vitro which necessarily excludes the confounding influences of haemodynamic, inflammatory, haemostatic, and various other processes that are present in vivo. METHODS: Gene expression and release of fibronectin (FN), collagen IV and laminin by cultured rat MC were tested in the presence and absence of heparin. In addition the effect of transforming growth factor-beta1 (TGF-beta1) on the gene expression of those matrix proteins was assessed. RESULTS: Within a 3-1000 microg/ml concentration range, heparin inhibited gene expression and release of FN by 10% fetal calf serum (FCS)-stimulated MC in a concentration-dependent manner. At concentrations of 300 and 1000 microg/ml, heparin inhibited fibronectin mRNA levels in TGF-beta1 (6 ng/ml) stimulated cells. However, heparin had no effect on gene expression or release of collagen IV or laminin under these conditions. Heparin markedly inhibited 10% FCS-stimulated MC proliferation in a concentration-dependent manner. CONCLUSIONS: Heparin inhibited MC growth and fibronectin production. These effects may, in part, account for the reported beneficial effects of heparin on the course of renal disease in experimental animals.     

Segi's cap: group formation of gut endocrine cells at the tip of the villi in human embryonal intestine

Large groups of basal-granulated (entero-endocrine) cells occur on the top of villi in the duodenum and upper jejunum of the human fetus older than five months of gestation. This structure was discovered and described by Segi(1935), hence named Segi's cap. By the immunocytochemical technique, somatostatin-, gastrin- and motilin-producing cells were demonstrated. By electron microscopy, EC, D and S cells were identified in the cap. There were autonomic nerves in the lamina propria adjacent to Segi's cap. No intraepithelial lymphocytes were found in the villi with Segi's cap.     

Effect of aeration and unsaturated fatty acids on expression of the Saccharomyces cerevisiae alcohol acetyltransferase gene

The reduction of acetate ester synthesis by aeration and the addition of unsaturated fatty acids to the medium has been reported to be the result of the reduction in alcohol acetyltransferase (AATase) activity induced by inhibition of this enzyme. However, regulation of the AATase gene ATF1 has not been reported. In this study, ATF1 gene expression was studied by Northern analysis, and the results showed that the ATF1 gene was repressed both by aeration and by unsaturated fatty acids. The results also showed that the reduction of AATase activity is closely related to the degree of repression of ATF1 mRNA, which suggested that the gene repression is the primary means of reducing AATase activity in vivo. Using the Escherichia coli lacZ gene as a reporter gene, it was shown that a 150-bp fragment of the 5' flanking sequence played a major role in the repression by aeration and unsaturated fatty acid addition.     

Neurochemical and behavioural effects of neurotensin vs [D-Tyr11]neurotensin on mesolimbic dopaminergic function

Changes in bronchoalveolar lavage fluid (BALF) and blood were examined to assess the toxic effects of diborane (B2H6, CAS: 19287-45-7) on the lung. Male Wistar rats were exposed to diborane at 20 ppm (intended concentration) for 4 h (phase I study) to evaluate time-course changes up to 14 days, and at 10 or 1 ppm (intended concentrations) to assess the dose-effect relationship after 3 days (phase II study). BALF parameters [leukocyte counts, alpha 1-antitrypsin (alpha 1-AT), superoxide dismutase (SOD), total protein, phospholipids etc.] were examined and biochemical and histopathological studies were also carried out. In the phase I study, neutrophils (%) in BALF increased on the day of exposure and then decreased gradually for 3 days. Rapid and marked increases in alpha 1-AT and SOD activity in BALF were detected on the day of exposure, and phospholipids had sharply increased on day 3. After 14 days, these parameters in the exposed rats had returned to their background level and alpha 1-AT decreased significantly. In the phase II study, total protein, alpha 1-AT activity and phospholipids in BALF showed dose-dependent increases, and serum alpha 1-AT activity increased significantly. Alveolar capillary and alveolar cell damage were confirmed in rats exposed to 20 ppm, 10 ppm or 1 ppm diborane for 4 h by evaluating the parameters examined. The protection system appeared to start operating immediately after exposure, and the recovery mechanism seemed to start operating 1 day after exposure and cease by day 14. The no-observed-effect level could not be observed.     

Effect of electroacupuncture on cholecystokinin gene expression in rat hippocampus during penicillin-induced epileptic seizure

Implantable left-ventricular assist devices (LVAD) are successfully used as a bridge to transplant if the patient's condition is worsening and no donor organ is available. They allow recovery of compromised organ function. However, postoperative bleeding, thrombemboelism, and right-heart failure may jeopardize the important improvement of organ function and may even lead to death. We introduce our strategy for implantation of the Novacor LVAD system, which aims at minimal bleeding and maintained right-heart function. The Novacor LVAD was implanted with the heart beating during extracorporeal circulation in 8 patients, 3 of whom had previous cardiac surgery. Postoperatively, no patient developed right heart failure or had to undergo redo thoracotomy.     

Immunoreactivity and expression of amylin in gastroenteropancreatic endocrine tumors

Amylin was isolated from human insulinomas, but there has been only preliminary data regarding whether this peptide can also be detected in other types of gastroenteropancreatic endocrine tumors. In the present study, immunohistochemical staining of 87 gastroenteropancreatic endocrine tumors demonstrated amylin immunoreactivity in 21.8% of the neoplasmas. Thirteen of 15 insulinomas, three of 21 gastrinomas, two of 29 nonfunctioning tumors, and one of 18 carcinoids were amylin-immunoreactive. Seventeen of the 19 amylin-immunoreactive tumors were primarily located in the pancreas, but two tumors were found in the intestine. Measurements of amylin messenger RNA expression in a few tumors revealed amylin synthesis in these tumors. Amylin immunoreactivity did not correlate with invasion and metastasis. However, the rate of curative resections was significantly higher in amylin-immunoreactive tumors. These results demonstrate for the first time that amylin immunoreactivity is not restricted to insulinomas and can also occur rarely in endocrine tumors of the intestine.