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Biomedical subjects

J A Vanderhoof

Publications and source records attributed to J A Vanderhoof.

At least 91 records · Page 5Linked to original sources
PubMed1990

Characterization of type I and type II insulin-like growth factor receptors in an intestinal epithelial cell line.

Insulin-like growth factors (IGFs) and insulin stimulate DNA and protein synthesis in IEC-6 cells (an intestinal epithelial cell line) grown in a chemically defined medium. IGF-I stimulates proliferation of IEC-6 cells at a lower concentration (ED50 = 1.6 nM) than either insulin or IGF-II. To gain insight into the mechanisms by which IGFs stimulate IEC-6 cell growth, we have examined the characteristics of specific IGF receptors on IEC-6 cells. Binding of 125I-IGF-I and 125I-IGF-II to IEC-6 monolayers was analyzed by incubation with various concentrations (0.2 nM to 0.5 microM) of radiolabeled IGFs for 16 h at 3 C. Scatchard plots of 125I-IGF-I binding were linear, suggesting a single class of binding sites with KD = 3.1 +/- 0.35 nM and Bmax = 50.7 +/- 6 fmol/10(6) cells. IGF-II was potent in displacing 125I-IGF-I (KI = 8.1 +/- 0.85 nM), but insulin had little effect. Affinity cross-linking with 125I-IGF-I followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed three bands with Mr of 270,000, 245,000, and 133,000, and the major band was the 133,000 species. Labeling of the 133,000 and 270,000 bands was greater than or equal to 80% inhibited by 10(-7) M unlabeled IGF-I, less potently inhibited by IGF-II and not at all by insulin. These results suggest that the 133,000 band represents the alpha-subunit of the type I IGF receptor. Scatchard plots of 125I-IGF-II binding to IEC-6 cell monolayers were curvilinear, suggesting two classes of binding sites: high affinity, low capacity sites, KD = 0.87 +/- 0.08 nM and Bmax = 28 +/- 2.5 fmol/10(6) cells; low affinity, high capacity sites, KD = 60 = +/- 8.8 nM and Bmax = 1780 +/- 230 fmol/10(6) cells. Neither IGF-I nor insulin was effective in inhibiting 125I-IGF-II binding. Affinity cross-linking with 125I-IGF-II labeled predominantly a 245,000 band, suggesting that this species is the type II receptor. A band with Mr 131,000 was barely detectable with 125I-insulin. These results indicate that IEC-6 cells have abundant quantities of the type I and II IGF receptors and few insulin receptors, suggesting that the mitogenic effect of IGFs is mediated through the type I IGF receptor.

Binding, Competitive↗
PubMed1989

Suppression of diamine oxidase activity enhances postresection ileal proliferation in the rat.

To assess the influence of diamine oxidase activity on the adaptive process of the small bowel after resection, we administered aminoguanidine, a potent diamine oxidase inhibitor, to rats for 10 days after either small bowel transection (n = 5) or 80% jejunoileal resection (n = 7). Five or more additional animals from each group received saline as controls. Ileal mucosal homogenates from the resection group receiving aminoguanidine, when compared with those from resection controls, showed no diamine oxidase activity with increased putrescine content and ornithine decarboxylase activity. Mucosal proliferation, as measured by mucosal mass, protein content, and deoxyribonucleic acid content, was greater in the resected animals receiving aminoguanidine when compared with that of resection controls. Sucrase activity per gram of mucosa was almost identical in both resection groups. These results show that the suppression of diamine oxidase during the postresection adaptive period results in enhanced mucosal proliferation with no effect on mucosal functional differentiation. Diamine oxidase may play a regulatory role in adaptive intestinal proliferation.

Adaptation, Physiological↗
PubMed1989

Effects of dietary linoleic acid on mucosal adaptation after small bowel resection.

We have shown that dietary long-chain triglycerides and 16,16-dimethyl prostaglandin E2 enhance and aspirin impairs postresection mucosal adaptation in rats. The present studies examined the hypothesis that supplemental linoleic acid (LA) above the minimum requirement may enhance postresection mucosal adaptation through altered prostaglandin (PG) synthesis. Forty male Sprague-Dawley rats (105 +/- 5 g) were fed purified diet containing either 5% LA or 4% palmitic acid and 1% LA. After 2 weeks, 12 rats from each dietary group underwent 70% proximal jejunoileal resection and the remainder were sham-operated. Dietary regimens were continued for an additional 13 days. Mucosal fatty acid analysis of 1% LA group revealed a ratio of 20:3 n-9/20:4 n-6 lower than 0.2, indicating normal essential fatty acid status. Mucosal protein per centimeter bowel was higher in the 5% LA group compared to the 1% group, but mucosal DNA, maltase, and ex vivo PG synthesis were not affected. These results indicate that LA stimulates postresection mucosal hypertrophy, which does not appear to be related to PG synthesis.

Adaptation, Physiological↗
PubMed1988

Nitrogen balance in adult hospitalized patients with the use of a pediatric amino acid model.

Normalization of plasma amino acid patterns and that relationship to improved nitrogen balance was studied using a pediatric-specific amino acid solution in 21 adults requiring total parenteral nutrition therapy. There was a significantly positive correlation between improved nitrogen balance and the amino acids cystine, tyrosine, total cysteine/cystine, and ornithine. When additional cysteine was added to the solution of 11 subjects, taurine also correlated with nitrogen balance. Despite higher amounts of histidine in solution, plasma amino acid levels were not normalized. These amino acids, heretofore considered nonessential, may be required in specific molar ratios in stress. The use of a 30% branched-chain pediatric-balanced amino acid solution resulted in near normalization of plasma amino acid levels and group mean positive nitrogen balance.

Adult↗
PubMed1988

Essential fatty acid deficiency and postresection mucosal adaptation in the rat.

The effect of short-term (biochemical) and long-term (clinical) essential fatty acid (EFA) deficiency on mucosal adaptation was studied in a surgical model of short bowel syndrome. Rats fed an EFA-deficient diet for 4 wk had biochemical evidence of EFA deficiency (hepatic and red blood cell triene to tetraene ratios greater than 0.4). Resected animals (70% proximal jejunoileal resection) receiving an EFA-deficient diet had a significantly impaired intestinal mucosal hyperplasia response in all remaining small bowel segments compared with resected controls. The effect of refeeding a control diet to clinically EFA-deficient resected rats was also evaluated. Short-term refeeding (2 wk) of a control diet resulted in a significant return toward normal tissue triene to tetraene ratios. Concomitantly, refed animals had significantly greater mucosal adaptation in the remaining duodenal/jejunal segment compared with resected animals maintained on an EFA-deficient diet postoperatively. These experiments underscore the dynamic nature of tissue EFA status and the importance of fatty acids in the normal compensatory mechanisms of mucosal adaptation after resection.

Adaptation, Physiological↗
PubMed1988

Morphological and functional effects of 16,16-dimethyl-prostaglandin-E2 on mucosal adaptation after massive distal small bowel resection in the rat.

The ability of 16,16-dimethyl-prostaglandin-E2 (PGE) to augment mucosal adaptation 14 days after a 70% distal small bowel resection in the rat was evaluated. In resected (R) and sham operated (S) animals, subcutaneous PGE 75 mg/kg, 2 X/day, induced significant (p less than 0.05) increases in mucosal protein, DNA, and disaccharidase concentrations per centimetre of bowel. The respective per cent increases in the residual proximal small intestine compared with their respective untreated controls were: protein, R = 60%, S = 66%; DNA, R = 69%, S = 29%; maltase, R = 57%, S = 5%. The uptake of leucine by intestinal rings was significantly higher (50%) in the PGE treated group at a concentration of 2 mmol/l of substrate, while the uptake of glucose was similar in all groups. The drug appears to be an effective agent in stimulating morphological and functional adaptation after massive distal small bowel resection.

Adaptation, Physiological↗
PubMed1988

Reduced mucosal prostaglandin synthesis after massive small bowel resection.

Exogenous 16,16-di-methyl-prostaglandin (PG) E2 administration augments mucosal hyperplasia after massive small bowel resection in the rat. We, therefore, evaluated the ability of aspirin to inhibit mucosal PG synthesis in the small intestine and further evaluated the effects of reduced PG synthesis on mucosal adaptation after a 70% jejunoileal resection in male Sprague-Dawley rats. Sixteen of 27 resected and 8 of 16 sham-operated rats were given aspirin 20 mg/kg body wt subcutaneously every 8 h for 12 days; the remainder were given vehicle only. Although mucosal PGE2, PGF2 alpha, and thromboxane B2 synthesis were all reduced by aspirin administration to 20-40% of the control values, mucosal adaptation in resected animals as measured by mucosal weight, DNA, protein, and maltase levels was only inhibited in the distal ileum. Aspirin did not affect these values in the duodenum, the upper jejunum, and the midileum. This study provides evidence for some involvement of endogenous PGs in regulation of the mucosal adaptation process in the distal ileum after massive small bowel resection in the rat. However, lack of inhibition more proximally suggests that factors other than PGs are more important.

Animals↗
PubMed1987

Hepatocarcinoma in a child with the Alagille syndrome.

A child with the Alagille syndrome of intrahepatic bile duct paucity developed hepatocarcinoma. Disabling cirrhosis had rendered this child a suitable candidate for transplantation before the discovery of carcinoma. However, the extension of the tumor outside the liver precluded the performance of this potentially life-saving operation. Serial monitoring of the serum alpha-fetoprotein concentration may be of value in the early identification of tumors in pediatric candidates for transplantation.

Abnormalities, Multiple↗
PubMed1987

Augmentation of postresection mucosal hyperplasia by plerocercoid growth factor (PGF). Analog of human growth hormone.

Postresection villus hyperplasia is a major compensatory mechanism in the short-bowel patient. Substances capable of augmenting postresection mucosal hyperplasia could have therapeutic implications. Human growth hormone (hGH) and human growth hormone releasing factor (hGHRF) stimulate growth of the gastrointestinal tract; however, the diabetogenic actions of growth hormone limit its usefulness in clinical practice. Plerocercoid larvae of the tapeworm Spirometra mansonoides produce an analog of hGH void of diabetogenic side effects. We assessed effects of plerocercoid growth factor (PGF) on mucosal adaptation following 70% proximal jejunoileal resection in young rats. Mucosal weight, DNA, protein, and total sucrase activity per centimeter of bowel were increased in resected PGF-treated animals compared to resected controls. We conclude PGF augments intrinsic postresection mucosal hyperplasia following extensive intestinal resection.

Animals↗
PubMed1987

Nutritional support for the infant with extrahepatic biliary atresia.

Some infants with biliary atresia obtain dramatic improvement for prolonged periods after the performance of hepatic portoenterostomy. Such infants may have life styles not substantially different from those of normal children. In others, the benefit from this operation, if any, is short lived. These infants are very vulnerable to the debilitating effects of severe, prolonged malabsorption and ultimately require orthotopic liver transplantation to sustain life. The physician caring for infants awaiting liver transplantation can do much, not only to prolong survival but to maintain satisfactory growth and development. The key consideration is to provide adequate nitrogen and nonnitrogen calories, liberally utilizing modern methods of enteral alimentation when necessary. In addition, attention must be directed toward several vitamin and mineral deficiencies, particularly those of the fat-soluble vitamins, that inevitably accompany severe malabsorption in children. Management of extrahepatic biliary atresia in infants is difficult and requires meticulous attention to details. Nevertheless, the long-term cure of this disorder provided by liver transplantation makes their care a rewarding experience.

Biliary Atresia↗
PubMed1987

Augmentation of mucosal adaptation following massive small-bowel resection by 16,16-dimethyl-prostaglandin E2 in the rat.

Survival following massive resection of the small intestine is often possible due to substantial hyperplasia of the mucosal surface in the remaining small intestine. While nutrients provide the major stimulus for hyperplasia in the clinical setting, the availability of drugs to augment this process would have obvious therapeutic implications. We evaluated the ability of 16,16-dimethyl-prostaglandin E2 (PGE2 to augment mucosal hyperplasia following massive small bowel resection in the rat. Three groups of 7 Sprague-Dawley rats, 160 g body weight, were subjected to 70% jejunoileal resection. One group was given 150 micrograms/kg of 16,16-dimethyl-PGE2 intragastrically twice daily, a second group 75 micrograms/kg subcutaneously, and a third group was untreated. After 17 days, segmental evaluation of mucosal mass in the remaining small intestine was determined by measuring mucosal protein, DNA, and disaccharidase levels. A significantly greater increase in mucosal mass was developed in the duodenum proximal to the anastomosis in both treatment groups, but neither the proximal nor distal ileum demonstrated significantly more adaptation. Histological examination in the duodenum confirmed the presence of a greater adaptive response in both the intragastrically and subcutaneously treated animals. 16,16-dimethyl-PGE2 appears to augment mucosal adaptation following massive small bowel resection in the rat, primarily in the very proximal small intestine.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Juvenile polysaccharidosis with cardioskeletal myopathy.

Polysaccharidoses with ultrastructural features reminiscent of glycogenosis type IV, but without enzymatic correlation, have been observed in several adolescent and adult patients. Little is known of the clinical, pathologic, or biochemical nature of these disorders. We describe a patient with ultrastructural characteristics consistent with glycogenosis type IV, but with normal brancher enzyme activity in dermal fibroblasts and cardiac muscle. During life and at autopsy, electron microscopy revealed amylopectin-like polysaccharide deposits present in a wide variety of tissues. The polysaccharidosis of our patient and similar patients may be a variant of glycogenosis type IV with a yet to be defined enzymatic defect.

Biopsy↗
PubMed1986

Lack of correlation of small bowel biopsy and clinical course of patients with intractable diarrhea of infancy.

To assess the value of small bowel biopsy in determining the prognosis of intractable diarrhea of infancy, small bowel biopsy specimens of 19 infants with this disorder were examined blindly, and a score reflective of the severity of injury for each biopsy specimen was derived. Biopsy scores were correlated with the duration of nutrition support required in the treatment of each patient. No correlation could be found between the severity of the small bowel mucosal injury on biopsy and the clinical course of the patient. Small bowel biopsies are not likely to be of assistance in determining the prognosis of this disorder and should not be used to determine therapy or to advise parents concerning the likely duration of intractable diarrhea of infancy.

Biopsy↗
PubMed1986

The importance of luminal factors in neomucosal growth.

Growing neomucosa on patched intestinal defects has been investigated as a method of expanding the intestinal absorptive area. The purpose of this study was to determine the effect of luminal factors on the rate of growth and function of neomucosa in rabbit ileum. A 2 X 5-cm distal ileal defect was patched with adjacent colon serosa in 10 New Zealand white male rabbits. A similar defect was patched in a bypassed ileal segment in an additional 10 rabbits. Five animals in each group were sacrificed at 4 and 8 weeks for determination of the gross and microscopic growth of neomucosa, glucose uptake, and disaccharidase activity. In addition, tritiated thymidine uptake was measured in neomucosa and incontinuity ileum at the 4-week sacrifice. Grossly, the patched defects were covered in nearly all animals by 4 weeks and coverage was complete at 8 weeks. Microscopically, the mucosa was less well developed in the bypassed group with a mean villous height significantly less than the incontinuity group (139.9 +/- 13.9 microns vs 212.33 +/- 30.3 microns, P less than 0.0005). In vitro uptake of [3H]thymidine was significantly higher in neomucosa in bypassed segments when compared with neomucosa in incontinuity segments (692.5 +/- 347.8 vs 278.0 +/- 134.8, P less than .05, expressed as percentage of normal incontinuity ileum). Glucose uptake was similar in both groups but disaccharidase activity was significantly less in the bypassed group. The increased uptake of [3H]thymidine in neomucosa in the bypassed segment may reflect the histologic immaturity of this tissue with a greater proportion of DNA synthesizing cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Growth of intestinal neomucosa on prosthetic materials.

The short bowel syndrome is a potential complication of the surgical management of diseases of the large and small intestine. Recently methods have been examined for expanding the small bowel absorptive area using prosthetic materials. We investigated the feasibility of growing intestinal mucosa on prosthetic patches and tubes. Ileal defects were patched with a 2 X 5-cm patch of either Dacron (n = 15), polyglycolic acid mesh (PGA) (n = 9), or polytetrafluroethylene (PTFE) (n = 5) prosthesis in New Zealand white male rabbits. Gross and microscopic analysis at 2, 4, and 8 weeks revealed that the serosal surface was covered with neomucosa by 4 weeks. Dacron and PTFE grafts were either minimally attached or extruded and PGA grafts had dissolved. At 8 weeks, none of the patches were present but with all three materials the resultant area of neomucosa was only 15% of the original defect. The neomucosa was functional as determined by glucose uptake and disaccharidase activity. Three centimeter Dacron tubes were interposed in the distal ileum of 10 rabbits and in a bypassed ileal segment in 11 rabbits. There was an 80% mortality within 2 weeks, and no evidence of neomucosal growth. Although prosthetic patches support the growth of functional neomucosa, there is a minimal increase in the final surface area. The type of prosthesis did not influence the outcome. The use of Dacron tubes is associated with high mortality and no neomucosal growth. The use of prosthetic materials is not likely to be useful in the clinical management of the short bowel syndrome.

Animals↗
PubMed1986

Reduced effect of taxol on plasma protein secretion by developing rat liver.

The effect of taxol, a potent stabilizer of microtubules, on plasma protein secretion by slices prepared from mature and developing rat liver was determined. After 4 hr of incubation, taxol (50 microM) inhibited albumin secretion by only 10% on gestation Day 19, by 16% 4 days after birth, but by 40% in the adult. Inhibition of glycoprotein secretion by taxol was similar to that of albumin secretion at all ages studied. Combined with information obtained from previous investigations, the present study indicates that agents that either inhibit microtubular assembly or that stabilize microtubules both have a reduced capacity to inhibit hepatic protein secretion during development. These findings suggest that a reduced requirement for microtubular participation in protein secretion is present in developing liver.

Alkaloids↗