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Biomedical subjects

D Rudman

Publications and source records attributed to D Rudman.

At least 181 records · Page 10Linked to original sources

Elemental balances during intravenous hyperalimentation of underweight adult subjects.

Intravenous hyperalimentation was done in 11 underweight adults whose body weight (body wt) was less than 85 percent of ideal. For the first 6 days, "complete formula" was infused furnishing per kilogram ideal body wt per day: 15 g glucose, 0.40 g N, 0.018 g P, 2.4 meq K, 3.0 meq Na, 2.3 meq C1, 0.5 meq Mg, 0.45 meq Ca, and 50 ml H20. Patients gained weight at an average rate of 9.0 g/kg ideal body wt/day and showed average balances/kilogram ideal body wt/day as follows: plus 0.14 g N; plus 0.012 g P; plus 0.43 meq K; plus 0.49 meq Na; plus 0.37 meq Cl; and plus 0.085 meq Ca. Application of standard equations to the elemental balances indicated weight gain consisted of 35-50 percent protoplasm, 35-50 percent extracellular fluid, 5-25 percent adipose tissus, and less than 1 percent bone. Withdrawas of N, P, Na, or K impaired or abolished retention of other elements. Removal of N halted retention P, K, Na and C1; withdrawal of K stopped retention of N and P; and removal of Na or P interrupted retention of all other elements. Weight gain continued at a rate of 1.4-3.1 g/kg ideal body wt/day despite zero or negative elemental balances of N, K, P, and sometimes Na and C1. Calculations showed that weight gain during infusion of fluids lacking N, P, K, or Na consisted largely of adipose tissue, with little or no contribution by protoplasm or extracellular fluid. Data show that repletion of protoplasm and extracellular fluid of wasted adults by intravenous hyperalimentation is retarded or abolished if N, P, Na, or K is lacking. Repletion of bone mineral does not occur in absence of Na or P but proceeds in absence of N, P, K, or Na. Thus, quality of weight gained by underfed adult patients during hyperalimentation depends on elemental composition of the infusate.

Adolescent↗

Effect of intrathecal injection of melanotropic-lipolytic peptides on the concentration of 3',5' cyclic adenosine monophosphate in cerebrospinal fluid.

Rabbits were anesthetized with urethane, and the concentration of 3',5' cyclic adenosine monophosphate (cAMP) in cerebrospinal fluid (CSF) was measured before and after injection into the cisterna magna of the following biologically active peptides and amines; adrenocorticotropin (ACTH), beta-melanocyte-stimulating hormone (beta-MSH), choroid plexus peptide IIF, arginine vasopressin, oxytocin, glucagon, epinephrine, serotonin, histamine, and acetylcholine. Only epinephrine and the lipolytic-melanotropic peptides ACTH, beta-MSH, and IIF influenced cAMP. Five to 500 mug ACTH caused a 3 to 10X increase in cAMP within 30 min; the concentration of nucleotide returned to baseline within 60-90 min after 5 or 50 mug, and remained elevated for at least 120 min after 500 mug. Effects of the same magnitude and tempo as those caused by 5 to 500 mug ACTH were produced by .1 to 10 mug beta-MSH and 5 to 500 mug IIF. Epinephrine at doses of 5 to 500 mug caused rises in cAMP of similar degree as the same dose of ACTH or peptide IIF, but the peak value was not reached until 60 to 90 min after injection.

Acetylcholine↗

Effects of choroid plexus peptide IIF on adenylate cyclase and 3',5'-cyclic adenosine monophosphate in adipose tissue.

Two hypophyseal lipolytic peptides, adrenocorticotropin (ACTH) and beta-melanocyte-stimulating hormone (beta-MSH), and the extrhypophyseal lipolytic peptide IIF, were compared with regard to their effects on free fatty acid production and 3',5'-cyclic adenosine monophosphate (cAMP) concentration in isolated rabbit and rat adipose tissue, and on adenylate cyclase activity in the tissue homogenates. ACTH at concentrations of 0.01 mug/ml or more increased lipolysis and cAMP levels in both tissues. beta-MSH at concentrations of 0.001 mug/ml or more increased lipolysis and cAMP in the rabbit tissue, but a concentration of 10 mug/ml did not stimulate lipolysis and did not alter nucleotide concentration in the rat tissue. Peptide IIF at 0.01 mug/ml or more stimulated lipolysis in rabbit adipose tissue and caused an accumulation of cAMP. A concentration of 100 mug/ml failed to stimulate free fatty acid production in the rat tissue and the cAMP level was also unaffected. In a medium containing 7.6 mEq/l of Mg++ and no Ca++, ACTH at 0.1 mug/ml or more stimulated adenylate cyclase activity in both rabbit and rat adipose homogenates by 6- to 12-fold. This effect was inhibited when Mg++ was replaced by Ca++, Na+ or K+. beta-MSH stimulated adenylate cyclase in rabbit, but not in rat, adipose homogenate in Mg++-containing incubation midium; again, the effect on rabbit adenylate cyclase was suppressed when Mg++ was replaced by Ca++, Na+ or K+. Peptide IIF failed to influence adenylate cyclase in the rabbit tissue homogenate in the Mg++-containing, Ca++-free medium; but when the medium contained 7.6 mEq/l of Ca++ in place of Mg++, 0.1 mug/ml or more of IIF caused a 4- to 15-fold increase in cyclase activity. IIF did not affect cyclase in the rat tissue homogenate in the presence or absence of Ca++. The data are consistent with the conclusion that extrahypophyseal lipolytic peptide IIF, as well as hypophyseal peptides ACTH and beta-MSH, accelerates lipolysis in susceptible adipocytes by stimulating adenylate cyclase to produce cAMP. The effect of IIF on cyclase requires the presence of exogenous Ca++; that of ACTH and beta-MSH requires exogenous Mg++.

Adenylyl Cyclases↗

The metabolic basis of portasystemic encephalopathy and the effect of selective vs nonselective shunts.

Portasystemic encephalopathy has been a major deterent to the utilization of total or non-selective shunts. A procedure to determine the maximum rate of urea synthesis (MRUS) has been developed and a depression in the ability to synthesize urea has been shown to correlate closely with the development of encephalopathy. Utilizing this procedure and a modified ammonium tolerance curve, a controlled comparison was instituted between selective and non-selective shunts. Following a non-selective or total shunt, there was a definite deterioration in both the MRUS and the ammonium chloride tolerance curve which was accompanied by a high rate of clinical encephalopathy. In marked contrast, the selective shunt, which maintains portal venous perfusion of the liver, showed little or no change in the MRUS and the ammonium chloride tolerance curve following the selective shunt and there was a very low incidence of encephalopathy. The difference between the non-selective and selective shunt in maintenance of urea synthesis, metabolism of ammonium chloride, and the development of clinical encephalopathy show the selective shunt procedure to be definitively superior in this regard.

Ammonium Chloride↗

Isolation of a novel glycoprotein from the urine of a patient with chronic myelocytic leukemia.

Patient B. J. with chronic myelocytic leukemia excreted 0.5-1.1 g protein per day in the urine. Gel filtration on Sephadex G-75 showed about one-third of this protein to be in molecular weight range 20,000-40,000 (fraction BJC). BJC, prepared from 9 liters of urine by gel filtration, was chromatographed on carboxymethylcellulose. Two proteins were eluted from the resin in pure form (as shown by zone and immunoelectrophoresis) in yields representing 8 and 3 mg/liter of urine: BJC1 and BJC2. Their amino acid compositions were identical. BJC1 contained 61% carbohydrate (33% hexose, 11% sialic acid, 13% glucosamine, 5% galactosamine). BJC2 contained one-fourth to one-half as much of each carbohydrate. Molecular weight of BJC1 was estimated at 29,000 by gel filtration. Neither glycoprotein reacted with rabbit antiserum to normal human serum.Antiserum to BJC1 was made in the rabbit. Immunoelectrophoresis with this antiserum showed a faint precipitin line, corresponding in mobility to BJC1, in normal human plasma, and a stronger line in most leukemic plasmas. By immunodiffusion, BJC1 was not detectable in normal human urine, but a positive reaction occurred in the following conditions: leukemia, 64-72%; other types of disseminated neoplastic disease, 36-78%; regional ileitis, 45%; ulcerative colitis, 38%; tuberculosis, 33%; during the 1st wk after major surgery, 33%.BJC2 was found in the urine by immunoelectrophoresis in 10% of patients with neoplastic disease and was not observed in urine of other patients or in human plasma. Amino acid composition, carbohydrate content, and antigenic specificity indicate BJC1 is a previously unrecognized member of the system of normal human plasma glycoproteins. Like certain other glycoproteins, its plasma concentration frequently increases in patients with neoplastic disease, chronic inflammatory disease, or tuberculosis and after surgery. Because molecular weight is 29,000, increased plasma concentration readily causes its appearance in the urine.

Aged↗

Orosomucoid content of pleural and peritoneal effusions.

22 nonneoplastic, noninflammatory effusions (cirrhosis and congestive heart failure), 12 non-neoplastic inflammatory effusions (tuberculosis, lupus erythematosus, rheumatoid arthritis, and idiopathic pleuropericarditis), and 58 neoplastic effusions (cancer of lung, breast, ovary, and pancreas, and lymphoma) were analyzed by radial immunodiffusion for orosomucoid concentration. The average concentration +/-SE was 35+/-4, 65+/-17, and 130+/-13 mg/100 ml in the three types of effusion, respectively. By gel filtration and ion exchange chromatography, orosomucoid was isolated from 12 nonmalignant and 14 malignant fluids. The orosomucoid preparations reacted as single components in acrylamide gel electrophoresis at pH 9.0, and in immunodiffusion and immunoelectrophoresis against antisera to human serum and to human plasma orosomucoid. In radial immunodiffusion, the slope of the line relating concentration to the square of the diameter of the precipitate area was identical for orosomucoid isolated from normal human plasma and from nonneoplastic effusions, but was subnormal for orosomucoid isolated from neoplastic fluids. All orosomucoid preparations had normal amino acid composition. Orosomucoid from the nonmalignant effusions had normal carbohydrate content. 11 of 14 samples of orosomucoid isolated from neoplastic fluids had abnormalities in carbohydrate composition, consisting of subnormal content of sialic acid (11 of 14), hexose (10 of 14), and hexosamine (3 of 14), and abnormally high content of hexosamine (4 of 14). Discriminant analysis showed that concentration of orosomucoid distinguished between neoplastic and nonneoplastic noninflammatory effusions more effectively than concentration of total protein, albumin, alpha(1), alpha(2), beta, or gamma-globulin.

Albumins↗

Utilization of alpha-keto and alpha-hydroxy analogues of valine by the growing rat.

When 70-80-g male albino rats eat a diet furnishing daily requirement of valine for optimal growth (70 mumol/g) and all other nutrients ("complete diet"), they gain weight at an average rate of 3.0 g/100 g body wt/day. When valine is removed, they lose weight at an average 2.1 g/100 g body wt/day. The growth retardation is improved or corrected by adding valine to the diet, daily weight gain being proportional to dietary valine content over a range of 0-70 mumol/g. Addition of alpha-ketoisovaleric acid instead of valine to the valine-free diet also improves or corrects the growth failure. Percent efficiency of alpha-ketoisovaleric acid as a substitute for valine was calculated as: 100 x (micromole valine per gram diet required to produce specified growth response)/(micromole alpha-ketoisovaleric acid per gram diet required to produce the same response). Efficiency of the substitution is inversely related to dietary content of the keto analogue, being 80% when diet contains 17.5 mumol/g (molar equivalent of (1/4) the daily requirement of valine), and 37% when diet provides 140 mumol/g (molar equivalent of twice the daily requirement of valine).alpha-Hydroxyisovaleric acid also substitutes for valine. Efficiency of the substitution at the single ration tested, 70 mumol/g diet, is 45%, similar to that for the keto analogue under the same conditions. When [1-(14)C]alpha-ketoisovaleric acid is injected intravenously, 30-80% of the administered radioactivity is exhaled as (14)CO(2) within 24 h. This finding suggests that inefficiency of alpha-ketoisovaleric acid as a substitute for valine results in part from degradation of the keto acid to isobutyric acid by branched chain dehydrogenase-decarboxylase. Oral administration of neomycin, polymyxin, and bacitracin reduces efficiency of alpha-ketoisovaleric acid as a substitute for valine by (1/4)-(1/2). This effect suggests that transamination of the keto acid may be performed in part by gastrointestinal microbes.

Animals↗

Diurnal variation in the responsiveness of human subjects to human growth hormone.

The objective of this study was to compare the responsiveness of human subjects to the anabolic effects of human growth hormone (HGH) administered at 8 a.m. or at 11 p.m. Three doses of HGH were used: A, 0.0168 U/kg body weight (BW)(3/4) per day; B, 0.0532 U/kg BW(3/4) per day; C, 0.168 U/kg BW(3/4) per day. The effect of each dose on daily balances of N, P, Na, and K and on BW was measured. The subjects were of two groups: (a) seven GH-deficient children, of whom three were deficient in ACTH; and (b) three patients with limb-girdle dystrophy. ACTH-deficient patients in group (a) received exogenous cortisol at 7 a.m. In all 10 subjects, the anabolic effects of dose C, and sometimes of B and A, administered at 11 p.m. were significantly (P < 0.05) greater than when administered at 8 a.m. In these experiments plasma cortisol concentration averaged 3 times greater at 8 a.m. than at 11 p.m. In the next experiments, exogenous cortisol was administered to the three ACTH-deficient patients at 10 p.m. and the responsiveness to HGH injected at 11 p.m. vs. 8 a.m. was again compared. Under these conditions, when plasma cortisol concentration averaged 3 times greater at 11 p.m. than at 8 a.m., HGH injected at 8 a.m. caused significantly greater anabolic responses than HGH injected at 11 p.m. These findings indicate that the magnitude of the anabolic response to exogenous HGH is inversely related to the plasma cortisol concentration at the time of HGH injection.

Adolescent↗

Responsiveness of growth hormone-deficient children to human growth hormone. Effect of replacement therapy for one year.

Previous studies have shown that growth hormone (GH)-deficient children are more responsive to exogenous human growth hormone (HGH) than non-GH-deficient children. In six GH-deficient children, velocity of linear growth was less than 2.5 cm/yr. By the metabolic balance study technique, anabolic responses (increments in elemental balances) were measured to a 7 day course of 0.0532 U HGH/kg body weight (BW)(3/4) per day (dose B) and to 0.168 U/kg BW(3/4) per day (dose C). They were then treated for 1 yr with HGH at a dose intermediate between B and C. Velocity of linear growth accelerated to 15-25 cm/yr for the first 4-7 mo, then declined to 0-8 cm/yr. At 12 mo, responsiveness to doses B and C was measured again; the responses were only 20-60% as great as before treatment. After 3 mo without HGH treatment, responsiveness to the anabolic effects of doses B and C returned to the magnitudes observed before treatment. A low titer of plasma antibodies to HGH was detected in two of the six children at the end of the year's treatment; these titers showed little change after 3 mo without HGH. Thus the hyperresponsiveness of GH-deficient subjects to exogenous HGH, compared to non-GH-deficient individuals, declines during long-term HGH treatment and is restored by 3 mo interruption of treatment. These changes in peripheral responsiveness may be related to the decline in velocity of linear growth which occurs after 4-7 mo of continuous treatment. When HGH was withdrawn after 12 mo, all six patients exhibited negative balances of N, P, Na, and K and loss of BW. Ratios of elemental balances showed about half the weight loss to represent protoplasm, and about half extracellular fluid. These observations indicate a role of GH in the continuing regulation of nitrogen and mineral metabolism in addition to its function as a growth-promoting hormone.

Adenoma, Chromophobe↗