Biomedical subjects

D N Orth

Publications and source records attributed to D N Orth.

At least 73 records · Page 4Linked to original sources

PubMed1987

Characterization of a high-molecular-weight form of epidermal growth factor in an extract of human urine.

We purified from a side fraction of the commercial preparation of urokinase from large volumes of human urine a high-molecular-weight (HMW) form of human epidermal growth factor (hEGF). Sequence analysis of the amino terminus of the intact molecule and of two tryptic fragments and carboxypeptidase Y analysis revealed the molecule to correspond to residues 828-1023 of the hEGF precursor predicted by the nucleotide sequence of human renal hEGF mRNA, with hEGF forming its carboxyl terminus. HMW hEGF bound poorly to concanavalin A-agarose, quite avidly to wheat germ lectin-agarose, and completely to phenyl boronate-agarose, suggesting that it was O-glycosylated. Sephacryl S-200 chromatography of freshly-voided urine revealed mostly hEGF, with smaller amounts of a much higher molecular weight hEGF, but little material that was the size of the HMW hEGF we characterized. The large fragment we characterized presumably is cleaved from the larger form by enzyme(s) present in urine during the collection, storage, and processing of urine. We have confirmed that hEGF is synthesized as a large precursor molecule, as predicted by the nucleotide sequence of hEGF mRNA.

Adult↗

PubMed1987

Urinary TGFs1 in neoplasia: immunoreactive TGF-alpha in the urine of patients with disseminated breast carcinoma.

A tumor-associated growth factor was identified in a 22-liter pool of urine from patients with disseminated breast cancer using an isolation scheme which separates transforming growth factor-alpha (TGF-alpha) from the high level of human epidermal growth factor (hEGF) normally present in urine. Concentration of urinary proteins by adsorption onto methyl bonded microparticulate silica, selective elution by acetonitrile, and subsequent gel permeation, cation exchange, and high performance liquid chromatography, resolved an EGF-related growth factor which generated a competitive binding curve similar to that of synthetic rat TGF-alpha in radioimmunoassay. A 26-liter pool of urine from normal subjects, evaluated in the same manner as a part of another study, did not contain measureable quantities of this factor.

Adenocarcinoma↗

PubMed1987

Specific high-affinity binding protein for human corticotropin-releasing hormone in normal human plasma.

A protein of Mr 25-40 kilodaltons in normal human plasma binds human corticotropin-releasing hormone (hCRH), but not ovine CRH. Binding requires both N- and C-terminal hCRH sequences and has a Kd of 2 X 10(-10) M and a binding site concentration of 1.4 pmoles per ml of plasma. Its binding is not affected by heating to 56 degrees C for 1 h, but is abolished by exposure to 6 M guanidine-HCl, 10 mM dithiothreitol. Binding proceeds rapidly at 37 degrees C and is 75% complete within 4 min. Neither rat nor sheep plasma appears to contain a CRH-binding protein. CRH-binding protein may explain the brief biological action of hCRH as compared to ovine CRH in man and why high concentrations of plasma immunoreactive hCRH in women during third-trimester pregnancy do not cause increased ACTH secretion.

Antibody Specificity↗

PubMed1987

Human brain tumor-associated urinary high molecular weight transforming growth factor: a high molecular weight form of epidermal growth factor.

Urinary protein obtained from a patient with a highly malignant brain tumor (astrocytoma, grade IV) was adsorbed to trimethylsilyl controlled-pore glass beads and selectively eluted with acetonitrile to yield a high molecular weight (HMW) human transforming growth factor (hTGF). This HMW hTGF promoted clonogenic cell growth in soft agar and competed for membrane receptors with mouse epidermal growth factor. After surgical resection of the tumor, no HMW hTGF was found in urine. HMW hTGF generated a human EGF (hEGF) radioimmunoassay competitive binding curve similar to that of hEGF and parallel to that of a highly purified HMW form of hEGF previously reported to be present in trace concentrations in normal human urine. Both hEGF and HMW hEGF were clonogenic in soft agar, and their clonogenic activity as well as that of HMW hTGF was inhibited by anti-hEGF serum. Both HMW hTGF and HMW hEGF had 20 to 25% of the radioreceptor binding activity of hEGF. HMW hTGF purified from the pooled urine of several patients with malignant astrocytomas and HMW hEGF purified from normal control urine comigrated at Mr 33,000. Thus, HMW hTGF was indistinguishable from HMW hEGF in terms of apparent molecular size, epidermal growth factor receptor binding activity, epidermal growth factor immunoreactivity, and clonogenic activity. Urinary HMW hEGF/hTGF may be of tumor cell origin or may represent a response of normal host tissues to the tumor or its products.

Brain Neoplasms↗

PubMed1987

Plasma immunoreactive beta-melanocyte stimulating hormone (lipotropin) levels in individuals with Prader-Labhart-Willi syndrome.

Plasma immunoreactive beta-melanocyte-stimulating hormone (beta-MSH) levels, which actually represent the combined concentrations of beta-lipotropin (beta-LPH) and gamma-LPH in normal individuals, were measured in 12 patients (6 males and 6 females with an average age of 16.8 years, range 4 months to 27 years) with the Prader-Labhart-Willi syndrome (PLWS). Five patients were previously identified with high-resolution analysis as having the 15q chromosomal deletion, whereas 7 patients had normal chromosomes. Hypopigmentation was observed in all 5 patients with the 15q deletion. Of the 7 individuals with normal chromosomes, two were hypopigmented and 5 had normal pigmentation. Fasting (6 to 12 hours) plasma samples were analyzed for immunoreactive beta-MSH in the 12 PLWS individuals. Plasma immunoreactive beta-MSH (LPH) levels were within the normal range in all 12 individuals. There was no significant difference in the plasma immunoreactive beta-MSH concentrations between patients who did and did not have the chromosomal deletion or in those who were or were not hypopigmented. Thus, a decrease in circulating plasma immunoreactive beta-MSH (LPH) does not appear to be the cause of the hypopigmentation observed in some patients with PLWS.

Adolescent↗

PubMed1987

Intestinal glucose transport in suckling rats fed artificial milk with and without added epidermal growth factor.

Epidermal growth factor (EGF), a potent mitogen present in milk, is postulated to play an important physiologic role in the ontogeny of the intestine. An artificial rat milk, free of EGF, was developed and fed to newborn rats in an effort to evaluate the physiologic role of EGF on intestinal glucose transport. Comparisons were made between mother-fed (group 1) and artificially fed pups (group 2). Group 1 was divided into two subgroups to received either the EGF vehicle (group 1-A) or twice daily subcutaneous injections (0.1 micrograms/g body weight/day) of EGF (group 1-B). Group 2 was divided into four subgroups: formula without EGF (group 2-A), formula with 62 ng/ml of EGF (group 2-B), formula with 200 ng/ml EGF (group 2-C), and formula without EGF but added anti-EGF IgG (40 ng/ml) plus subcutaneous injections of 1 micrograms anti-EGF twice daily (group 2-D). Treatment regimens were initiated on day 3 and assays performed on day 11 of life. Glucose transport was measured using gut "sheet" preparations in all but group 2-C, which utilized brush border membrane preparations. Group 1-B showed a significant (p less than 0.03) increase in gut length (47.5 +/- 1.2 versus 42 +/- 0.9 cm) and an increase (p less than 0.03) in both Vmax (10.2 +/- 0.5 versus 7.2 +/- 0.3 nM/mg tissue) and Km (2.74 +/- 0.49 versus 1.20 +/- 0.19 mM) compared to group 1-A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Detailed kinetic analysis of adrenocorticotropin secretion by dispersed rat anterior pituitary cells in a microperifusion system: effects of ovine corticotropin-releasing factor and arginine vasopressin.

We have developed a microperifusion system in which we have examined the ACTH secretory responses of acutely dispersed normal rat anterior pituitary cells to ovine CRF (oCRF) and arginine vasopressin (AVP), alone and in combination. The system approached square-wave stimulus hydrodynamics. ACTH secretion was observed within 5 sec of exposure to either secretagogue and reached a maximum within 20-40 sec. ACTH secretion remained constant for as long as oCRF was perifused and then fell gradually toward the basal level. Persistent ACTH release after oCRF perifusion was stopped could not be explained by persistence of oCRF in the perifusion chamber. In contrast to the response to oCRF, ACTH secretion fell progressively toward basal despite continued AVP perifusion. AVP had a synergistic effect with oCRF only if it was perifused simultaneously with oCRF or within 30 sec after oCRF was stopped; it had no synergistic effect if perifused immediately before oCRF. Simultaneous perifusion of oCRF and AVP resulted in an oCRF-like response of greater magnitude, whereas sequential perifusion of oCRF followed by AVP resulted in the usual plateau response to oCRF followed by the initial spike response characteristic of very high concentrations of AVP alone and a subsequent rapid decrease in secretion despite continued perifusion of AVP. The different kinetic response profiles suggest that oCRF and AVP act via different intracellular signal transduction pathways, and the time and sequence dependency of their synergism suggests that the factors that mediate their interactions have different intracellular half-lives. The microperifusion system appears to be uniquely suited to detailed kinetic analysis of anterior pituitary hormone secretion and the intracellular pathways through which secretagogues act and interact.

Adrenocorticotropic Hormone↗

PubMed1987

Effect of ovine corticotropin-releasing hormone administered during insulin-induced hypoglycemia on plasma adrenocorticotropin and cortisol.

The factors that mediate the hypothalamic-pituitary response to hypoglycemia in man are unknown. To investigate the role of CRH in the plasma ACTH response to hypoglycemia, two different doses of ovine CRH (oCRH) were given to normal men during insulin-induced hypoglycemia. We hypothesized that if the endogenous CRH response to hypoglycemia were less than maximally stimulating, administration of oCRH during hypoglycemia would result in a greater peak plasma immunoreactive (IR) ACTH response. Six normal men were given 1) 0.15 U/kg regular insulin, iv; 2) insulin plus 1 microgram/kg oCRH, iv, 5 min after serum glucose fell to 40 mg/dL or less; and 3) oCRH alone. The degree and duration of hypoglycemia were the same when insulin was given alone or with oCRH. Plasma IR-ACTH after insulin alone and insulin plus oCRH rose at the same rate to similar peaks of 226 +/- 37 (mean +/- SEM) and 213 +/- 53 pg/mL, respectively, both of which were greater (P less than 0.05) than the peak plasma IR-ACTH after oCRH alone (61 +/- 19 pg/mL). The peak plasma IR-cortisol levels after insulin alone (24 +/- 4 micrograms/dL), insulin plus oCRH (27 +/- 3 micrograms/dL), and oCRH alone (18 +/- 2 micrograms/dL) were not significantly different. In a second study, six normal men were given 0.15 U/kg regular insulin, iv; insulin plus 10 micrograms/kg oCRH, iv; and 10 micrograms/kg oCRH alone. Administration of oCRH 5 min after serum glucose fell to 40 mg/dL or less did not affect the degree or duration of hypoglycemia. Plasma IR-ACTH after insulin alone and insulin plus oCRH rose at the same rate to similar peaks of 258 +/- 14 and 290 +/- 33 pg/mL, respectively, both of which were greater (P less than 0.01) than the peak (54 +/- 6 pg/mL) after oCRH alone. After insulin alone, plasma IR-ACTH declined to baseline by 3 h. However, after insulin plus oCRH, plasma IR-ACTH fell gradually until 2 h, rose to a second peak at 2.5-3 h, and remained greater (P less than 0.01) than after insulin or oCRH alone for the 4-h duration of the study. The mean peak plasma IR-cortisol level after insulin plus oCRH (33 +/- 4 micrograms/dL) was similar to that after insulin alone (28 +/- 3 micrograms/dL), but was greater (P less than 0.05) than that after oCRH alone (18 +/- 2 micrograms/dL).(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

PubMed1987

Pituitary response to intravenous hypothalamic releasing peptides in cynomolgus monkeys treated with contraceptive steroids.

The secretory response of the pituitary to an iv bolus dose of hypothalamic releasing peptides (HRP) was evaluated in male and cycling (CYC) or contraceptive-treated female cynomolgus monkeys. Parenteral delivery of levonorgestrel and 17 beta-estradiol by intravaginal ring (CVR) was compared with oral administration (OC) of norgestrel and ethinyl estradiol in the diet. LH secretion was suppressed in the CVR group compared to that in other groups, and the response in males was greater than that in either CYC or OC females (P less than 0.01). Elevated plasma PRL concentrations in the CVR group during the baseline period (P less than 0.05) together with their larger pituitary weights (P less than 0.01) suggested lactotroph hypertrophy or hyperplasia compared to other groups. The plasma GH response was similar in the male, CYC, and CVR groups, but plasma GH levels increased from -15 to 0 min before HRP injection in the OC group (P less than 0.001) and continued to be higher for 15 min after HRP compared to values in the other groups (P less than 0.001), suggesting a treatment effect. Neither plasma TSH nor T4 levels were different among the groups after HRP administration, but T4 was elevated (P less than 0.01) in the OC group due to increased T4-binding globulin. The greater ACTH response 15 min after HRP treatment (P less than 0.05) in the CVR group compared to that in the other groups was associated with greater adrenal weights of the CVR females (P less than 0.05), suggesting chronic tropic stimulation. However the adrenal steroid results did not support this interpretation. We conclude that the differences in pituitary hormone secretion during these studies could be attributed to the nature of the reproductive steroid environment.

Adrenocorticotropic Hormone↗

PubMed1987

Effect of altered thyroid hormone levels on hypothalamic-pituitary-adrenal function.

To determine whether alterations in serum thyroid hormone levels affect hypothalamic-pituitary-adrenal function, we measured the plasma immunoreactive (IR) ACTH and IR-cortisol responses to 1 microgram/kg BW ovine CRH (oCRH) given iv in the late afternoon and the plasma IR-ACTH, IR-cortisol, and IR-11-deoxycortisol responses to 2 g metyrapone given orally at midnight in 10 athyreotic patients during T4 treatment and 1 month after stopping T4 when they were biochemically, but not clinically, hypothyroid. Mean serum TSH increased from 0.7 +/- 0.9 (+/- SD) mU/L (normal range 0.5-4.9 mU/L) during T4 therapy to 107 +/- 82 mU/L after stopping T4. The serum total T4 level and free T4 index fell from 165 +/- 37 nmol/L and 1.9 +/- 0.4, respectively (normal range, 59-154 nmol/L and 0.9-2.5, respectively), to 19 +/- 9 and 0.2 +/- 0.1, respectively, after stopping T4. Basal plasma IR-ACTH and IR-cortisol levels at 0800 and 1630 h were similar during and after stopping T4 therapy. Peak plasma IR-ACTH and IR-cortisol levels after oCRH were significantly greater after stopping T4 (20 +/- 9.2 pmol/L and 880 +/- 260 nmol/L, respectively) than during T4 therapy (9.7 +/- 4.7 pmol/L and 720 +/- 190 nmol/L; P less than 0.01 and P less than 0.05, respectively). The mean integrated plasma IR-ACTH and IR-cortisol responses to oCRH were also significantly greater P less than 0.01 and P less than 0.05, respectively) after stopping T4 than during T4 therapy. Plasma IR-ACTH the morning after metyrapone was slightly (1.6-fold) but not significantly greater during therapy than after stopping T4 therapy (100 +/- 86 vs. 65 +/- 54 pmol/L, respectively). The plasma IR-11-deoxycortisol responses to metyrapone during and after stopping T4 therapy were similar (720 +/- 250 and 750 +/- 330 nmol/L, respectively), presumably because plasma IR-ACTH concentrations were maximally stimulating in both instances. These results indicate that thyroid hormone deficiency of short duration 1) increases corticotroph sensitivity to oCRH, 2) may diminish the plasma ACTH response to metyrapone-induced hypocortisolemia, and 3) has no apparent effect on the acute adrenal response to ACTH. These data together with those of previous studies that have shown reduced responses of the hypothalamic-pituitary-adrenal axis to metyrapone and hypoglycemia in hypothyroid patients suggest that the release of hypothalamic CRH and/or other ACTH secretagogues may be decreased in hypothyroidism.

Adult↗

PubMed1987

Corticotropin-releasing hormone: stimulation of ACTH secretion in normal man.

Synthetic ovine corticotropin-releasing hormone (oCRH) is a potent and specific ACTH secretagogue in man. Threshold and maximal i.v. doses are 0.01-0.03 and 3-10 micrograms/kg or less, but increase in frequency, severity, and duration at higher doses. oCRH produces a biphasic plasma immunoreactive (IR)-ACTH response and has a prolonged duration of action that is probably due to its long circulating half-life. Other pro-opiomelanocortin IR-peptide are secreted concomitantly in equimolar amounts. Plasma IR-cortisol concentration tends to follow that of ACTH, but also reflects cortisol's longer circulating half-life and the fact that acutely the maximally-stimulating plasma IR-ACTH level is about 45 pg/ml. oCRH is as effective given s.c. as i.v., but intranasal administration is only 1% as effective. Sex and age have no effect on the plasma IR-ACTH and IR-cortisol responses to oCRH. The time of day of oCRH administration has little influence on the plasma IR-ACTH response, but the plasma IR-cortisol response is much greater to oCRH given later in the day than early in the morning. Plasma IR-ACTH response to oCRH is more dependent on the basal plasma IR-cortisol level than the time of day. Arginine vasopressin given at the same time as oCRH potentiates 4-fold the plasma IR-ACTH response to oCRH alone, almost to levels obtained with insulin-induced hypoglycemia. However, oCRH administered at the onset of insulin-induced hypoglycemia does not cause higher plasma IR-ACTH levels, indicating that endogenous CRH levels are maximally-stimulating during the hypoglycemic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1986

Human A673 cells secrete high molecular weight EGF-receptor binding growth factors that appear to be immunologically unrelated to EGF or TGF-alpha.

Extracts of serum-free conditioned medium from human rhabdomyosarcoma A673 cells contain high molecular weight (HMW) transforming growth factors (TGFs) that can be partially purified by Bio-Gel P-100 and carboxymethyl (CM)-cellulose chromatography (Todaro et al: Proc Natl Acad Sci USA 77:5258, 1980). Reverse-phase high performance liquid chromatography (HPLC) revealed a principal peak of epidermal growth factor (EGF) radioreceptor assay (RRA) activity and anchorage-independent growth (AIG) activity that coeluted with 25-26% acetonitrile. If a trailing shoulder of EGF RRA activity from the CM-C chromatography was included in the material for HPLC analysis, additional active fractions were observed at 21-22% acetonitrile. Importantly, both active regions from HPLC failed to compete in radioimmunoassays under reduced and denatured conditions for human EGF (hEGF), human TGF-alpha (hTGF-alpha), or rat TGF-alpha (rTGF-alpha) and failed to give positive signals in Western blots under conditions in which TGF-alpha was readily detected when using an antisera raised against the 17 C-terminal amino acids of rTGF-alpha. Nonreducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed EGF RRA and AIG activities in gel slices corresponding to Mr 15,000 and 22,000 in the 25-26% acetonitrile eluate and Mr 15,000, 20,000, 27,000, and 48,000 in the 21-22% acetonitrile eluate. The presence of multiple forms of EGF-receptor-binding peptides produced in vitro suggest size heterogeneity and possible immunologic diversity among high molecular weight members of the EGF/TGF-alpha family of growth-promoting polypeptides.

Biological Assay↗

PubMed1986

Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture.

Bordetella pertussis synthesizes a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changed the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. We conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is this response that explains the subsequent acceleration of hormone release.

Adenylate Cyclase Toxin↗

PubMed1986

Effect of epidermal growth factor and artificial feeding in suckling rats.

To evaluate the effects of epidermal growth factor (EGF) in dietary milk, a new method of delivering an artificial (EGF-deficient) formula was developed using 42 rat pups, 1-14 days of age. In a second study the effect of EGF was evaluated in suckling rats from 3-11 days of age: group 1, mother-fed; group 2, mother-fed plus daily injections of EGF (0.1 micrograms/g body weight); group 3, artificial milk fed with added EGF (62 ng/ml); and group 4, artificial milk fed without EGF. Each group consists of nine rats. In group 2 there was premature eye opening and tooth eruption and a significant reduction in body weight and weight of liver, kidney, thyroid, and thymus but an increase in length of the intestine and weights of stomach, pancreas, lung, and adrenal (p less than 0.04), when compared to group 1. Both groups 3 and 4 showed premature tooth eruption and eye opening, and their body weights and most organ weights were similar to group 2; exceptions were a smaller stomach, thyroid, thymus, lung, and adrenal, which were similar to those in group 1. In addition, intestinal length in groups 3 and 4 were similar to the mother-fed EGF-treated pups (group 2). There was no difference in intestinal length between the artificially fed pups, whether or not they received oral EGF. These findings demonstrate a new and effective technique of artificial feeding and suggest that the increase in intestinal length caused by injections of EGF (0.1 micrograms/g body weight) can also be induced by feeding an artificial milk with or without physiologic levels of EGF.

Age Factors↗

PubMed1986

Plasma immunoreactive proopiomelanocortin peptides and cortisol in normal dogs and dogs with Addison's disease and Cushing's syndrome: basal concentrations.

We measured basal plasma concentrations of the immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides ACTH, beta-lipotropin (beta LPH), beta-endorphin (beta END), and alpha MSH in 160 normal dogs, 32 dogs with Addison's disease, 42 dogs with adrenocortical tumors causing Cushing's syndrome, and 169 dogs with pituitary-dependent Cushing's disease. In normal dogs, plasma IR-POMC peptide levels were similar to those in man, except that IR-alpha MSH, a pars intermedia POMC product, was readily detected. In Addisonian dogs, plasma cortisol was decreased, and the IR-POMC peptides were increased, except for IR-alpha MSH, which was normal. In 7 Addisonian dogs given dexamethasone, elevated plasma IR-ACTH, beta LPH, and beta END levels fell dramatically. In dogs with Cushing's syndrome due to adrenal tumors, plasma IR-ACTH, beta LPH, and beta END were decreased, and cortisol was increased, but IR-alpha MSH was normal. Dogs with Cushing's disease due to pars distalis tumors had elevated plasma IR-ACTH, beta LPH, beta END, and cortisol, but normal IR-alpha MSH; their plasma cortisol was suppressed by dexamethasone. There appeared to be 2 types of pars intermedia tumors causing Cushing's disease: 1 dexamethasone nonsuppressible and with disproportionately high plasma IR-alpha MSH levels, the other relatively dexamethasone suppressible and with normal to slightly elevated IR-alpha MSH levels. These 2 pars intermedia tumor types may arise from 2 distinct normal canine pars intermedia cell types. Canine Cushing's disease may provide a useful model for variants of the disorder in man.

Addison Disease↗

PubMed1986

Epidermal growth factor in human milk and the effects of systemic EGF injection on intestinal calcium transport in suckling rats.

Epidermal growth factor (EGF) is a polypeptide that stimulates proliferation and differentiation of a variety of cell types, including intestinal epithelium; it is the agent in human milk that induces mitosis in human fibroblast culture. It has been postulated that EGF in human milk may play an important role in the normal intestinal maturation since specific EGF receptors are present on the surface of intestinal cells. For this reason, human milk samples from mothers delivering prematurely, as well as at term gestation, were analyzed for their content of EGF. Samples from mothers delivering prematurely showed levels of 70 +/- 5 ng ml-1 and those delivering at term had levels of 68 +/- 19 ng ml-1. There was no diurnal variation and no change with length of lactation up to 50 days. Although previous studies demonstrated that subcutaneous injections of EGF given to suckling rats caused changes in morphology and enzyme activities, no studies had demonstrated that EGF caused changes in function. We injected two-week-old suckling rats and three-week-old weanling rats with 0.1 microgram of g-1 BW twice daily for three days. EGF treatment caused a decrease in somatic weight gain, an increase in weight per unit length of bowel, an increase in lactose specific activity and an increase in net calcium transport. In contrast to the two-week-old suckling rats, the EGF had no effect on intestinal function although somatic weight gain was also depressed in three-week-old animals. These findings demonstrate that human milk contains substantial amounts of EGF and that systemic injections of EGF can cause both morphological and functional changes in the intestinal tract of suckling rats.

Animals↗

PubMed1986

Cowden disease: gene marker studies and measurements of epidermal growth factor.

Cowden disease (CD) is a familial syndrome characterized by tumors of the skin, oral mucosa, breast, thyroid, and intestinal epithelium. Since the syndrome is inherited as an autosomal dominant, we examined a battery of gene markers in a family with CD to detect linkage between the CD gene and known marker genes. There was no positive evidence for linkage of a CD locus with any of the markers; other investigators can add to our data to confirm and extend these findings. Additionally, we measured epidermal growth factor (EGF) in body fluids from CD patients and controls to determine if elevated EGF levels might be responsible for the widespread epithelial proliferation in CD. EGF levels in saliva, serum, plasma, and urine were similar in CD patients and control subjects. Although alterations in growth factors or their receptors may play a role in CD, excess circulating EGF is not responsible for the manifestations of the syndrome.

Adult↗

PubMed1985

Two distinct insulin-related molecules in the guinea pig: immunological and biochemical characterization of insulin-like immunoactivity from extrapancreatic tissues of the guinea pig.

In this study we extracted guinea pig brain and testis with; the extract was adsorbed to and eluted from cartridges (the Sep-Pak C18 procedure). We found this procedure superior for recovering crystalline insulin added to buffers or tissues, and for recovering endogenous insulin from plasma, but inferior for recovery of insulin from tissues. However, we did find 'rat/pork' type-insulin in guinea pig brain and testis (5-50 pg/g wet weight tissue). Our results with the Sep-Pak C18 procedures were reproduced by four other laboratories (who found 4-60 pg/g wet weight of tissue) and similar findings were also obtained by an independent investigator. Thus, we conclude that extrapancreatic tissues of guinea pigs have a second type of insulin-related material that is more typical of other mammalian insulins, but that the amount recovered is dependent upon the extraction procedure utilized.

Animals↗