Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor is a polypeptide that stimulates proliferation and differentiation of a variety of cell types, including the developing intestinal epithelium; it is the agent in human milk that induces mitosis in human fibroblast culture. We systematically evaluated the EGF content of milk from 20 women delivering prematurely and from 11 women delivering at term. In preterm mothers, the concentration of EGF was 70 +/- 5 ng/ml (mean +/- SEM), with no significant change during seven weeks of lactation. EGF concentration in milk of term mothers was 68 +/- 19 ng/ml (mean +/- SEM). No diurnal variation in the concentration was found. Total EGF content was closely correlated with the volume of milk expressed, suggesting a passive transport from the circulation. These observations confirm that a substantial amount of EGF is present in human milk and that EGF concentrations are not affected by duration of gestation, time of day, or duration of lactation.
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PMID:Epidermal growth factor in human milk: daily production and diurnal variation during early lactation in mothers delivering at term and at premature gestation. 660 47

A polypeptide fraction isolated from the urine of normotensive subjects lowers the blood pressure (BP) in a rabbit bioassay (mean BP decrease 33.8% +/- 0.6%, SEM). Patients with primary hypertension exhibit reduced or no activity (mean BP decrease 8.8% +/- 1.2%). In contrast, patients with secondary forms of hypertension show activity like normotensives (mean BP decrease 33.4% +/- 1.0%). The results of the bioassay in the two patient groups correlate well with the family incidence of hypertension (68% and 37% for primary and secondary hypertension respectively). Cases with borderline hypertension fall into two groups; a larger one with vasoactivity inthe bioassay and lower family incidence of hypertension; and a smaller group reacting like patients with primary hypertension. Only the latter group may represent an initial stage of primary hypertension. In normotensive children and young men, an inactive fraction was found in 31% and 28% respectively. These inactive groups had twice the family incidence of hypertension compared to the groups with vasoactivity. These results suggest the existence of a possible genetic marker of primary hypertension and may offer the possibility to detect the disease before its manifestation.
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PMID:Defect in the excretion of a vasoactive polypeptide fraction A possible genetic marker of primary hypertension. 694 42

The possible involvement of nerves containing vasoactive intestinal polypeptide in Crohn's disease was investigated by immunocytochemistry and radioimmunoassay of specimens from 17 patients with well-defined clinical and histologic features of the disease. The characteristic pattern of slender fibers, evenly distributed across the gut wall, was seen in specimens taken from controls, which consisted of (a) specimens from uninvolved areas of gut from carcinoma resection (n = 17) and (b) jejunoileal specimens obtained during bypass operation for obesity (n = 8) as well as in four of the six specimens from patients with ulcerative colitis. In contrast, this characteristic pattern was lost in all 17 patients with Crohn's disease, the pattern being replaced by thickened and more intensely immunostained fibers. These changes were consistently found in the mucosa and submucosa, and in 13 of the Crohn's disease cases, the abnormal pattern was totally transmural, involving both the myenteric and submucous plexus as well as the muscle layers. There was a > 200% increase in VIP content, as determined by radioimmunoassay, in Crohn's disease (294 +/- 29 pmol/g wet wt, mean +/- SEM) in comparison with (a) ulcerative colitis (93 +/- 5 pmol/g [P < 0.001]), and (b) controls consisting of carcinoma resection (108 +/- 39) and bypassed gut from obese patients (86 +/- 27 [P < 0.001]). At least part of the previously documented autonomic nerve changes in Crohn's disease are, thus, due to an increase in vasoactive intestinal polypeptide innervation.
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PMID:Abnormalities of vasoactive intestinal polypeptide-containing nerves in Crohn's disease. 741 8

The nephric duct of the chick embryo starts to form at about stage 10 of Hamburger and Hamilton ([1951] J. Morphol. 88:49-92) and extends posteriorly, fusing with the cloaca at about the end of the third day of incubation (HH stage 17). Evidence from the literature suggests that the extension involves active migration of the posterior tip. This investigation concerned some molecules that might control this migration: fibronectin, vitronectin, the beta 1 integrin receptor, and NCAM polysialic acid. The concentration of fibronectin in the extracellular matrix was found by immunocytochemistry to be negligible at the posterior end of the duct; treatment of the living embryo with GRGDS failed to halt further extension of the duct; SEM examination of embryos treated with the synthetic peptides of fibronectin GRGDS, GRDGS, SDGR, and GRGES, or with vitronectin, revealed negligible morphological effects on the duct. It is concluded that there is yet no evidence that fibronectin is an important factor in duct migration. NCAM polysialic acid had a similar distribution to fibronectin, but treatment of the living embryo with Endo-N caused cessation of extension of the duct. Endo-N is an enzyme that specifically degrades PSA without affecting the NCAM polypeptide itself. It is suggested therefore that PSA may play an important role in duct extension. The synthetic peptides of fibronectin each produced distinctive patterns of blebbing on the surfaces of cells in trunk mesoderm, but the duct cells were unaffected. GRGES and SDGR caused blebbing on cells in the somites and the anterior segmental plate, though not on cells in the posterior segmental plate. This suggests that integrin receptors change in the anterior segmental plate as the mesoderm forms somites from somitomeres.
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PMID:Posterior extension of the chick nephric (Wolffian) duct: the role of fibronectin and NCAM polysialic acid. 754 37

The carcinoid neoplasm is marked by excessive serotonin, synthesized by the conversion of tryptophan (Trp) to 5-hydroxytryptophan by tryptophan hydroxylase (TPH) (EC 1.14.16.4) and decarboxylation of 5-hydroxytryptophan by aromatic-L-amino acid decarboxylase (AAAD) (EC 4.1.1.28). Because almost no biochemical data were available on human carcinoid TPH and AAAD, we have characterized these enzymes as a preliminary step to developing mechanism-based agents selective against carcinoid tumors. TPH was detected in all fourteen carcinoids analyzed [Km = 185 +/- 17 microM (mean +/- SEM); Vmax = 2.4 +/- 1.2 nmol/hr/mg protein]. AAAD was detected in thirteen tumors (Km = 45 +/- 6.7 microM; Vmax = 11 +/- 2.0 nmol/min/mg protein). In a subset of hepatic metastatic tumors obtained with adjacent normal liver, the Km and Vmax of TPH (N = 6) and the Km of AAAD (N = 7) were comparable in both tissues. However, the Vmax of carcinoid AAAD was 50-fold higher (P < 0.002) than that in normal liver (13 +/- 3.1 vs 0.26 +/- 0.04 nmol/min/mg protein). Western immunoblot analysis indicated that AAAD polypeptide content of carcinoid tumor was > 20-fold higher than in adjacent normal liver. These results suggest that AAAD might be an appropriate target for enzyme-activated cytotoxic agents for carcinoid tumors.
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PMID:Elevated aromatic-L-amino acid decarboxylase in human carcinoid tumors. 757 47

In primary cultures of rat pituitary cells, inhibin and follistatin reduce steady state levels of FSH beta mRNA to less than 10% of control within 4-6 h, while activin increases this mRNA 2- to 3-fold after 2-4 h of treatment. The effects of these three gonadal polypeptide hormones on the LH beta and common alpha-subunit mRNAs are more gradual and of lesser magnitude. The present study was designed to determine whether inhibin, activin, and/or follistatin act at the posttranscriptional level by altering the stability of the gonadotropin subunit mRNAs. To determine the decay rates of FSH beta, LH beta, and alpha-subunit mRNAs, primary pituitary cell cultures were treated for 1-24 h with either of two transcriptional inhibitors, actinomycin-D or 5,6-dichloro-1-beta-ribofuranosyl benzimidazole (DRB), in the presence or absence of recombinant human inhibin-A, recombinant human activin-A, or purified bovine follistatin. The decay of preexisting gonadotropin subunit mRNAs was followed by Northern blot analysis. Levels of LH beta and alpha-subunit mRNAs remained constant or increased during the 24-h exposure to transcriptional inhibitors; therefore, it was not possible to calculate their half-lives. The stability of these mRNAs was not altered by inhibin, activin, or follistatin. In contrast, FSH beta mRNA turned over rapidly: the estimated half-life was 2.6 +/- 0.19 h (mean +/- SEM of eight determinations) after actinomycin-D treatment and 1.9 +/- 0.14 h (mean +/- SEM of 12 determinations) after DRB treatment. When new RNA synthesis was blocked by either actinomycin-D or DRB, there were no significant effects of inhibin, activin, or follistatin on the stability of FSH beta mRNA (n = 2-4 for each hormone). The decay of FSH beta mRNA in the presence of inhibin or follistatin alone, however, was even more rapid than that determined after the administration of transcriptional inhibitors (P < 0.005). After an initial lag of 1-2 h, the half-life of FSH beta mRNA was 0.88 +/- 0.15 h (n = 4) or 0.62 +/- 0.11 h (n = 3), in the presence of inhibin or follistatin, respectively. The most likely interpretation of these results is that inhibin/follistatin reduces steady state levels of FSH beta mRNA by inducing a labile protein that accelerates the degradation of this mRNA species, and the synthesis of this protein is blocked by actinomycin-D or DRB treatment. It is not clear at present whether inhibin, follistatin, and activin have additional effects on transcription of the gonadotropin subunit genes.
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PMID:Decay of follicle-stimulating hormone-beta messenger RNA in the presence of transcriptional inhibitors and/or inhibin, activin, or follistatin. 768 52

Reperfusion of ischaemic intestine is characterised by an initial hyperaemia with ensuing mucosal repair. This study investigated possible roles for gut vasoactive neuropeptides and trophic peptides in these phenomena. Groups of rats were monitored during superior mesenteric artery occlusion for five or 20 minutes, with or without subsequent reperfusion for five minutes. Peptide concentrations (fmol/ml) in arterial blood, were measured using specific radioimmunoassays. Intestinal ischaemia alone did not cause haemodynamic disturbance or peptide release. Reperfusion, after five minutes of ischaemia, resulted in arterial hypotension and a rise in plasma vasoactive intestinal polypeptide (mean (SEM)) (37 (3), control 11 (4), p < 0.001). After 20 minutes of ischaemia, reperfusion resulted in greater hypotension (p < 0.05) and release of both vasoactive intestinal polypeptide (31 (3), p < 0.05 v control) and the more potent vasodilator beta-calcitonin gene related peptide (49 (3), control 23 (1), p < 0.001). By contrast, the vasodilators alpha-calcitonin gene related peptide and substance P and the vasoconstrictors neuropeptide Y, peptide YY, and somatostatin were not released. Bombesin, a stimulatory neuropeptide, was released after 20 minutes of ischaemia/reperfusion (13 (2), control 7 (3), p < 0.05). Plasma enteroglucagon rose from control (51 (4)) to 110 (16) (p < 0.001) and to 158 (27) (p < 0.005) after five and 20 minutes of ischaemia/reperfusion. The potent enteric vasodilators vasoactive intestinal polypeptide and beta-calcitonin gene related peptide, unopposed by vasoconstrictors, may promote post-ischaemic intestinal hyperaemia. The rise in plasma enteroglucagon may point to diffuse mucosal injury and is consistent with the putative trophic role of this peptide.
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PMID:Release of vasodilator, but not vasoconstrictor, neuropeptides and of enteroglucagon by intestinal ischaemia/reperfusion in the rat. 782 5

Fecal concentrations of total short-chain fatty acids were normal in 16 patients with ileorectal anastomoses (mean +/- SEM, 99.7 +/- 10.3 mmol/L) and 28 patients with ileal pouch-anal anastomoses (138.8 +/- 8.5 mmol/L) and did not differ from those in 14 healthy noncolectomized controls (130.7 +/- 12.6 mmol/L). Acetate:propionate:butyrate:isobutyrate+valerate+isovalerate ratios were similar in the ileorectum (71:12:12:5%) and in the colorectum (66:14:13:7%) of healthy noncolectomized controls, whereas the concentration of acetate was increased at the expense of the polypeptide-derived isobutyrate, valerate, and isovalerate in the ileal pouch (77:12:11:1%). Ammonia was accordingly significantly diminished in ileal pouch contents (28.8 +/- 3.2 mmol/L vs 45.2 +/- 4.1 mmol/L in controls) in contrast to concentrations in ileorectal contents (36.2 +/- 5.3 mmol/L). Concentrations of lactate were normal and low. Twenty-four-hour productions of total short-chain fatty acids in 16.6% fecal homogenates from both groups of patients were normal. Addition of saccharides (eg, glucose, starch, pectin, ispaghula husk) increased the production of acetate, propionate, and butyrate and decreased the production of ammonia and isobutyrate, valerate, and isovalerate, which was increased in homogenates with albumin added. This pattern of substrate fermentation was similar in homogenates from ileal pouch, ileorectum, and control colorectum. In conclusion, the concentrations of short-chain fatty acids, lactate, and ammonia indicate that ileorectal fermentation resembles normal colorectal fermentation in noncolectomized healthy individuals, whereas the fermentation in ileal pouch contents seems to be more carbohydrate predominated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Short-chain fatty acids, lactate, and ammonia in ileorectal and ileal pouch contents: a model of cecal fermentation. 827 56

Hyperglycemia is postulated to cause chronic changes in the vasculature of diabetic patients, suggesting structural or genetic alterations. We have characterized the glucose induced alterations of gene expression in cultured bovine aortic smooth muscle cells using the recently developed mRNA differential display method. After five days of incubation with either 5.5 or 22 mM glucose, RNA preparations were isolated from confluent cells and probed with 10 candidate clones identified after screening up to 3000 mRNA species. Among these, three clones (2A, 2C, 3) showed significant changes in expression by Northern blot analysis. Elevated glucose levels decreased the mRNA expression of clones 2A and 3 to 51 +/- 7% (P < .01) and 59 +/- 10% (P < .05) (mean% of control +/- SEM), respectively. Expression of clone 2C was increased in 22 mM glucose condition to 221 +/- 23% (P < .05). Nucleotide sequence analysis showed that clone 3 had 77% homology to the 3'-noncoding region of human elongation factor 2, a member of the GTPase family which is essential for polypeptide synthesis. Clones 2A and 2C do show no homology to known nucleotide sequences. These results indicate that physiologically attainable high glucose conditions can significantly effect gene expression in aortic smooth muscle cells. Furthermore, mRNA differential display can be used in metabolic studies to identify new genes regulated by nutrients such as glucose.
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PMID:Glucose induced genes in bovine aortic smooth muscle cells identified by mRNA differential display. 829 82

We used the whole cell patch clamp technique to investigate the characteristics of modification of cardiac Na+ channel gating by the sea anemone polypeptide toxin anthopleurin-A (AP-A). Guinea pig ventricular myocytes were isolated enzymatically using a retrograde perfusion apparatus. Holding potential was -140 mV and test potentials ranged from -100 to +40 mV (pulse duration 100 or 1000 ms). AP-A (50-100 nM) markedly slowed the rate of decay of Na+ current (INa) and increased peak INa conductance (gNa) by 38 +/- 5.5% (mean +/- SEM, P < 0.001, n = 12) with little change in slope factor (n = 12) or voltage midpoint of the gNa/V relationship after correction for spontaneous shifts. The voltage dependence of steady-state INa availability (h infinity) demonstrated an increase in slope factor from 5.9 +/- 0.8 mV in control to 8.0 +/- 0.7 mV after modification by AP-A (P < 0.01, n = 14) whereas any shift in the voltage midpoint of this relationship could be accounted for by a spontaneous time-dependent shift. AP-A-modified INa showed a use-dependent decrease in peak current amplitude (interpulse interval 500 ms) when pulse duration was 100 ms (-15 +/- 2%, P < 0.01, n = 17) but showed no decline when pulse duration was 100 ms (-3 +/- 1%). This use-dependent effect was probably the result of a decrease in the recovery from inactivation caused by AP-A which had a small effect on the fast time constant of recovery (from 4.1 +/- 0.3 ms in control to 6.0 +/- 1.1 ms after AP-A, P < 0.05) but increased the slow time constant from 66.2 +/- 6.5 ms in control to 188.9 +/- 36.4 ms (P < 0.002, n = 19) after exposure to AP-A. Increasing external divalent cation concentration (either Ca2+ or Mg2+) to 10 mM abolished the effects of AP-A on the rate of INa decay. These results demonstrate that modification of cardiac Na+ channels by AP-A markedly slowed INa inactivation and altered the voltage dependence of activation; these alterations in gating characteristics, in turn, caused an increase in gNa presumably by increasing the number of channels open at peak INa. AP-A slows the rate of recovery of INa from inactivation which is probably the basis for a use-dependent decrease in peak amplitude. Finally, AP-A binding is sensitive to external divalent cation concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modification of cardiac Na+ channels by anthopleurin-A: effects on gating and kinetics. 839 71


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