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Biomedical subjects

D H Alpers

Publications and source records attributed to D H Alpers.

At least 199 records · Page 11Linked to original sources
PubMed1976

Hartnup disease. Clinical, pathological, and biochemical observations.

Hartnup disease is a rare genetic disorder of amino acid transport associated with variable and intermittent clinical abnormalities. A family is described in which three siblings had an intermittently progressive neurological disease and two of the affected siblings had the Hartnup-pattern aminoaciduria. Neuropathological examination of one case showed severe diffuse atrophy, generalized neuronal loss in the cortex, and Purkinje cell loss in the cerebellum. In vivo and in vitro studies of intestinal amino acid transport in the surviving sibling indicated a partial defect in the transport of several neutral amino acids (tryptophan, alanine, serine, and methionine) with normal transport of other neutral amino acids (threonine, phenylalanine, histidine, tyrosine, and isoleucine). Transport of glycine, proline, hydroxyproline, and the basic amino acids appeared normal.

Adolescent↗
PubMed1976

Psychiatric illness and the irritable bowel syndrome. Practical implications for the primary physician.

Twenty-nine consecutive outpatients with irritable bowel syndrome were given structured psychiatric interviews, as were 33 consecutive medical controls who did not have irritable bowel syndrome. All were from an internal medicine group practice. Seventy-two percent of irritable bowel syndrome subjects had psychiatric illness, with hysteria and depression the most prevalent syndromes. Only 18% of controls had psychiatric illness. The primary physician made an accurate psychiatric assessment in only 28% of the subjects. An awareness of his patient's psychiatric illness is necessary for the physician to provide effective treatment, as for depression, and to spare the patient needless medications, hospitalizations, and surgery, as with hysteria.

Colonic Diseases, Functional↗
PubMed1976

Serum amylase determinations and amylase to creatinine clearance ratios in patients with chronic renal insufficiency.

Patients with severe chronic renal failure may have significant hyperamylasemia in the absence of clinical symptoms or signs of acute pancreatitis. Amylase to creatinine clearance (CA/CC) ratios were usually elevated in patients with chronic renal failure and were not helpful in evaluating the possibility of acute pancreatitis. The mean amylase to creatinine clearance ratio for the controls with normal renal function was 1.24 +/- 0.13. In patients with chronic renal failure, it was 3.17 +/- 0.42 (P less than 0.001). Serum amylase isoenzyme patterns revealed no difference in salivary to pancreatic isoenzyme ratios between normals (1.04 +/- 0.12) and patients with severe renal insufficiency without evidence of pancreatic disease (1.07 +/- 0.13). The isoenzymes were helpful in excluding the diagnosis of pancreatic in 1 renal failure patient whose hyperamylasemia was primarily salivary in origin and in confirming the diagnosis in another who had only a pancreatic band.

Adult↗
PubMed1975

The possible role of pancreatic proteases in the turnover of intestinal brush border proteins.

1. Intestinal brush border enzymes have heterogeneous rates of turnover, the largest proteins having the fastest turnover. Since the membrane faces the intestinal lumen, the effects of pancreatic factors were examined in mediating this turnover. Surgical subtotal pancreatectomy was used as an experimental model to study the turnover of brush border proteins in the absence of most pancreatic secretions. 2. Subtotal (95%) pancreatectomy of rats was found to cause elevations by about 50% of total activity and specific activities of certain brush border enzymes (maltase, sucrase, lactase), but not of others (alkaline phosphatase, trehalase). Rats were judged to be functionally deficient in pancreatic proteolytic enzymes (a) by demonstration of vitamin B-12 malabsorption, which was corrected by trypsin, and (b) by the finding of only about 20% of proteolytic activity appearing in the lumen after a test meal when compared to control. 3. To measure protein turnover in vivo the method of double labelling was used, where [3H]- and [14C]valine were administered intraduodenally in sequence 10 h apart. With this technique, a high 3H/14C ratio is correlated with rapid turnover. Proteins with apparent molecular weights of about 200 000-270 000 were found to turn over more rapidly than smaller proteins. 3H/14C ranged from 4.7 to 6.2 in animals without pancreatic insufficiency. In the face of decreased pancreatic proteolysis, the 3H/14C ratio was 2.3-3.1, similar to that of proteins with a slow half life. 4. Estimates of relative synthetic rates of large brush border proteins were lower than normal in pancreatectomized animals, but were constant over the period of the labelling experiment. The high enzyme levels in the face of lower synthetic rates confirms that, at the new steady rate, degradation rates must be slower for large brush border proteins in pancreatic insufficiency. 5. In vitro, using purified brush borders, unfractionated pancreatic enzymes were found to remove sucrase, maltase and lactase, but not alkaline phosphatase and trehalase. The enzyme most potent in this respect was the pancreatic protease, elastase. Non-proteolytic enzymes (amylase, lipase, phospholipase A) were inactive in removing enzyme from the brush border. The addition of elastase to pancreatectomized animals in vivo restored the rapid turnover rate of large brush border proteins. 6. A model is thus proposed for the normal catabolism of some large intestinal brush border proteins. It is suggested that the surface of intestinal absorptive cells is being constantly remodelled, and that certain surface enzymes are in part removed from the membrane by the action of pancreatic proteases. A possible special role for elastase is suggested.

Alkaline Phosphatase↗
PubMed1975

Control of deoxyribonucleic acid synthesis in normal rabbit colonic mucosa.

Although cyclic adenosine 3':5'-monophosphate (cyclic AMP, cAMP) is known to suppress DNA synthesis is cultured cells and experimental tumors, its role in normal intact tissue has been little explored. This study helps to define the influence of modifiers of cyclic AMP levels on DNA synthesis in rabbit colonic mucosa maintained in short term organ culture system. Base line studies showed that incorporation of [3H]thymidine into DNA was linear for 24 hr and predominantly in mucosal cells, as shown by autoradiography. Colon from a normal fed rabbit showed a gradient of DNA synthesis, lowest in the cecum and increasing to a maximum, 3-fold greater, at the splenic flexure. This pattern was obliterated by fasting, at which time no formed stool remained in the colon, and all colon mucosa incorporated thymidine at the lower level of the right colon. Known modifiers of intracellular cAMP were found to depress colonic DNA synthesis. Theophylline inhibited DNA synthesis by 35% at 0.5 mM concentration and increased intracellular cAMP levels. This inhibition took 10 hr to be manifest and was at least partly reversible. It was by far the most active of the methylxanthines, consistent with its potency as a phosphodiesterase inhibitor. N6,02-dibutyryl cyclic AMP inhibited DNA synthesis at concentrations as low as 0.025 mM, whereas adenosine and sodium butyrate were ineffective up to 1.0 mM. 5'-AMP did inhibit DNA synthesis, but only at 0.1 mM or higher and did not elevate intracellular cAMP levels. Other modifiers of cAMP which were effective included prostaglandins E1, E2, and F2alpha (2 times 10(-6) M) and papaverine (1 muM). Thymidine uptake was not affected by any of these drugs. The intrinsic thymidine pool was estimated at 20 muM by isotope dilution, and was not altered by theophylline. DNA synthesis in rabbit colon can be suppressed by increased cAMP levels within the time period allowed by organ culture. Thus, these drugs that elevated cAMP levels did not seem to suppress DNA synthesis by decreasing intracellular thymidine concentrations.

Animals↗
PubMed1973

Characterization of ileal vitamin B12 Binding using homogeneous human and hog intrinsic factors.

Elucidation of the mechanism of intrinsic factor (IF)-mediated vitamin B(12) (B(12)) binding to ileal binding sites has been hampered by the use of crude or only partially purified preparations of IF in previous studies. We have used homogeneous human IF and hog IF isolated by affinity chromatography to study [(57)Co]B(12) binding to ileal mucosal homogenates. The following observations were made: (a) Human IF-B(12) and hog IF-B(12) were bound to human, monkey, hog, dog, rabbit, mouse, hamster, and guinea pig ileal, but not jejunal, homogenates in amounts significantly greater than free B(12) or B(12) bound to five other homogeneous B(12)-binding proteins; (b) only IF-mediated B(12) binding was localized to ileal homogenates and was inhibited by EDTA; (c) values for the association constant (K(a)) for the various ileal homogenates mentioned above and human IF-B(12) and hog IF-B(12) ranged from 0.3 x 10(9) M(-1) to 13.0 x 10(9) M(-1). Apparent differences in the K(a) for human IF-B(12) and hog IF-B(12) existed in most species; (d) the number of ileal IF-B(12) binding sites per gram (wet weight) of ileal mucosa ranged from 0.3 x 10(12) to 4.9 x 10(12). The same value was always obtained with human IF-B(12) and hog IF-B(12) for any given homogenate preparation; (c) 100-fold excesses of free B(12) or human IF and hog IF devoid of B(12) did not significantly inhibit human IF-B(12) and hog IF-B(12) binding to human and hog ileal homogenates. THESE EXPERIMENTS PERFORMED WITH HOMOGENEOUS IF INDICATE THAT: (a) gastric factors other than IF are not required for B(12) binding to ileal IF-B(12)-binding sites: (b) the mechanism of ileal IF-B(12) binding is different from that of free B(12) or of B(12) bound to non-IF-B(12)-binding proteins; (c) human IF and hog IF have different structures; (d) human IF-B(12) and hog IF-B(12) bind to the same ileal binding sites; and (c) human and hog ileal IF-B(12) binding sites bind free B(12) and human and hog IF devoid of B(12) poorly, if at all.

Animals↗
PubMed1972

Protein synthesis in intestinal mucosa: the effect of route of administration of precursor amino acids.

All cells in the intestinal villus of the rat are capable of synthesizing protein from amino acid precursors (l-leucine). Moreover, polyribosomes from both crypts and villi are equally able to incorporate l-leucine into protein. Unlike other tissues, e.g. liver, there is no diurnal variation of protein synthesis in the intestine of the unfed rat, whether leucine is administered intraluminally or intravenously. The route of administration of precursor (l-leucine) is important in determining which part of the villus incorporates the label into protein. After intravenous administration, protein from cells near the villus-crypt junction is most heavily labeled, whereas after intraluminal administration protein from cells near the villus tip is most heavily labeled. The pattern of proteins most heavily labeled by radioactive precursor is different in the villus when compared with proteins from the crypt cells. Smaller molecular weight membrane-bound proteins are preferentially labeled in the crypt cells, whereas on the villus the pattern of labeling is more evenly distributed among the various proteins. Moreover, intraluminal leucine is utilized for protein synthesis to a greater extent than that in the blood, when the concentration in both compartments is similar. Thus, intraluminal and intravenous injections of labeled precursor are not equivalent. Both routes should be considered in data for experiments measuring intestinal protein synthesis.

Animals↗