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Biomedical subjects

D Rudman

Publications and source records attributed to D Rudman.

At least 145 records · Page 8Linked to original sources
PubMed1978

Antitryptic property of cancer-related glycoprotein EDC1.

Cancer-related urinary glycoprotein EDC1 inhibits the action of trypsin and chymotrypsin on casein and synthetic substrates. The amino acid and carbohydrate compositions of EDC1 are different from those reported for pregnancy-related urinary trypsin inhibitors.

Carboxypeptidases↗
PubMed1978

The specific proteinuria of cancer patients.

UNLABELLED: Most patients with disseminated cancer have proteinuria. Twenty-four hour urine protein averaged less than 80 mg in normals; 223 mg in patients with acute myelocytic leukemia; 177 mg in subjects with stage IV Hodgkin's; 215, 229, 233, and 280 mg in patients with metastatic cancer of colon, breast, ovary, and pancreas respectively. We recently purified the novel glycoprotein EDC1 (mol wt 27,000) from the urine of patients with several types of cancer and found it to be a fragment of plasma inter-alpha-trypsin inhibitor (IATI) (mol wt 170,000). Both EDC1 and IATI are antiproteolytic. By radial immunodiffusion and radioimmunoassay of the 41 recognized plasma proteins and of EDC1, we have now analyzed the composition of urine protein in: (i) five nephrotics ("glomerular proteinuria"), (ii) four patients with cystinosis and four with hereditary renal tubular acidosis ("tubular proteinuria"), and (iii) 26 proteinuria (200-800 mg/day) patients with the six types of disseminated cancer listed above. In (i), (ii) and (iii) the 41 plasma proteins accounted for 100%, greater than 95%, and 33-60% of the urine protein, respectively, while EDC1 accounted for less than 1%, less than 1%, and 40-63% respectively. In normals, (i), (ii) and (iii), plasma EDC1 averaged less than 1, less than 1, less than 1 and 65 micrograms/ml respectively. Renal clearance of EDC1 in (iii) averaged 3% of creatinine clearance. In three cancer patients with EDC1-proteinuria, postmortem renal histology was normal. CONCLUSION: most types of cancer cell interact with plasma IATI to generate plasma EDC1 which is rapidly filtered by the glomeruli, with a resultant "overflow" or "prerenal" proteinuria which is unique to disseminated neoplastic disease.

Adolescent↗
PubMed1977

Parenteral nutrition of adults with a 900 milliosmolar solution via peripheral veins.

UNLABELLED: The objective of this study was to compare the nutritional value of three parenteral fluids: a conventional solution (400 milliosmoles/liter, containing Na, K, and Cl in 5% glucose); the concentrated hyperalimentation solution of Dudrick (1,800 milliosmoles/liter, containing Na, K, Cl, Mg, Ca, P, and amino acids in 20% glucose); and an experimental solution (900 millisomoles/liter, containing Na, K, Cl, Mg, Ca, P, and amino acids in 6.5% glucose). These three solutions are termed P400, C1,800, and P900, respectively. Preliminary studies showed that when 5 mg of cortisol/liter were added to P900, this fluid could be infused through peripheral veins for as long a time (average 114 hr) as P400 before local reaction necessitated changing the site. When P400 was infused in undernourished subjects without oral intake, balances of N, P, Mg, and Ca/70 kg of body weight per day were strongly negative (-4 g, -0.4 g, -6 mEq, and -0.2 g, respectively), whereas balances of K were about zero and those of Na and Cl were positive. Weight loss occurred. In the same patients, P900 containing 5 mg of cortisol/liter converted balances of N, P, Mg, and K to positive, and stimulated weight gain. Comparison of P900 (containing cortisol) and C1,800 in three emaciated subjects showed that the latter fluid caused a 2 to 4 times greater degree of positive balance in N, P, K, and Mg than the former. Comparison of P900 (containing cortisol) + 670-1700 cal by mouth with C1,800 in four undernourished subjects showed no statistically significant difference between these two programs. CONCLUSIONS: by adding 5 mg of cortisol/liter to P900, the fluid can be infused through peripheral veins. P900 is intermediate in nutritional value between P400 and C1,800. P900 without oral supplement prevents negative balance of all elements except Ca. P900 + daily oral intake of 670-1700 cal is nutritionally equivalent to C1,800.

Adult↗
PubMed1977

Role of diet in the management of vasopressin-responsive and -resistant diabetes insipidus.

Dietary protein and NaCl are the precursors of about 60% of the urinary osmoles (urea and NaCl). This investigation tested the hypothesis that in patients with dieabetes insipidus, intake of dietary protein and salt will directly influence the degree of polyuria. Four subjects with pituitary and one with nephrogenic diabetes insipidus were studied. All medications were discontinued. To provide diets ranging between "low-solute" and "high-solute," protein was varied in increments from 40 to 130 g/day and NaCl was varied simultaneously from 0.5 to 10 g/day. In all patients, each increment in protein and salt caused a prompt increase in 24-hr urinary osmoles in the form of urea, Na+, and Cl-. The 24-hr urine volume likewise increased progressively. Average increase in urine osmoles and volume from low- to high-solute diet was +224% and +127%, respectively. In four of the five patients, Reduction of protein/salt intake from habitual dietary at home to the recommedded daily allowance caused a 50 to 100% reduction in the magnitude of polyuria.

Adolescent↗
PubMed1977

Effects of hormones on 3', 5' -cyclic adenosine monophosphate in choroid plexus.

Choroid plexus of rabbit and rat was incubated for 2-30 min at 37 degrees C under 95% O2-5% CO2 in Tyrode solution containing 10 mM glucose and 1 mM theophylline with these agents: epinephrine, norepinephrine, isoproterenol, dopamine, histamine, serotonin, arginine, and lysine vasopressins, oxytocin, angiotensin, adrenocorticotropin (ACTH), beta-melanocyte-stimulating hormone, and choroid plexus peptide IIF. After incubation, tissue and medium were analyzed for 3', 5' -cyclic adenosine monophosphate (cAMP) content. Each amine or peptide was tested initially at 1,000 microng/ml. Only ACTH and serotonin affected cAMP content of rabbit choroid plexus. At 1,000 microng/ml, these agents caused a 10 and 4 times (respectively) increase in cAMP content of tissue + medium at 2-10 min with decline in content at 10-30 min. More than 90% of the increment was located in tissue, less than 10% in medium. Minimal effective dose (MED) to cause a significant (P less than .05) accumulation of cAMP was 0.1 microng/ml (2.2 x 10(-8) M) for ACTH and 10 microng/ml (5.7 x10(-3) M) for serotonin. Only isoproterenol, epinephrine, and norepinephrine influenced cAMP content of rat choroid plexus. MED's for this effect by isoproterenol, epinephrine, and norepinephrine were .001, .01, and 10 microng/ml (4.7 x 10(-9), 5.5 x 10(-8), and 5.9 x 10(-5) M), respectively.

Adrenocorticotropic Hormone↗
PubMed1977

Distribution of branched-chain alpha-keto acid dehydrogenases in primate tissues.

The specific activity of the branched-chain alpha-keto acid (BCKA) dehydrogenases was measured in normal tissues of the rat, monkey, and man, and in cirrhotic human liver. In the rat, specific activity of the dehydrogenases in liver, kidney, and muscle averaged 33, 26, and 0.4 U/g wet tissue, respectively; proportion of the body's content of the enzyme located in these three organs was 70, 12, and 10%. In the monkey, specific activities in liver and kidney were only one-half to one-third as great as in the rat, whereas activity in muscle was the same; the monkey's body content of dehydrogenase was distributed 50% in liver, 13% in kidney, and 20% in muscle. In man, specific activities in liver and kidney were only 1/15th to 1/25th as great as in the rat, but activity in skeletal muscle was the same. Distribution of the dehydrogenases in man was 30% in liver, 2% in kidneys, and 60% in muscle. In six patients with alcoholic cirrhosis, specific activity of the dehydrogenase in liver was reduced to 20-50% of normal (average, 32%). This reduction may alter the efficiency of BCKA as substitutes for branched-chain amino acids when BCKA are administered orally, but will have little influence on efficiency when they are given intravenously.

Animals↗
PubMed1977

Anabolic actions of reduced and S-carbamidomethylated human growth hormone and its plasmin digest in man.

Six children aged 12-15 yr, deficient in endogenous growth hormone, were each treated, after a 7-day control period, for 7 days with 0.0168, 0.052, and 0.168 U/kg body wt3/4 human growth (hGH) (doses A, B, and C, respectively) in separate metabolic balance studies. Doses B and C caused a dose-related retention of N, P, K, Na, and Cl in ratios of 1/0.069/4.5/7.5/5.6. These ratios indicate increments in masses of protoplasm/extracellular fluid (ECF)/bone in ratios of 1/2.0/ less than 0.001. Three of the children were also treated with doses A, B, and C of reduced and carbamidomethylated hGH (RCAM-hGH). Doses B and C caused 1.2-2.8 times as much retention of N, P, and K, and 0.3-0.5 times as much retention of Na and Cl, as did the corresponding doses of hGH. The plasmin digest of RCAM-hGH gave results generally similar to RCAM-hGH. For RCAM-hGH and its plasmin digest, N, P, K, Na, and Cl were retained in ratios of about 1/0.14/5.4/2.2/2.1, indicating increments of protoplasm/ECF/bone of about 1/0.8/0.05. These findings indicate that reduction and carbamidomethylation alter the anabolic actions of hGH in man in both quantitative and qualitative manner. RCAM-hGH is more potent in stimulating enlargement of protoplasm and bone, and less potent in stimulating expansion of ECF, than is the native hormone. The profile of anabolic actions of RCAM-hGH in man does not appear to be further altered by digestion with plasmin.

Adolescent↗
PubMed1977

Deficiency of carnitine in cachectic cirrhotic patients.

Carnitine is synthesized from lysine and methionine. In the rat, inadequate intake of either of these essential amino acids causes carnitine depletion. Inasmuch as protein deficiency is common in the hospital population, we have investigated the possible occurrence of nosocomial carnitine deficiency. Fasting serum carnitine concentration was measured in 16 normal and 247 patients in 16 disease groups. Normal range of carnitine was 55-103 muM. Only the cirrhotic group showed significant (P < 0.05) hypocarnitinemia. 14 of 36 hospitalized cirrhotics had subnormal values for serum carnitine. The creatinine/height index, midarm muscle circumference, and triceps skin-fold thickness indicated protein-calorie starvation in the 14 hypocarnitinemic liver patients. In six of the hypocarnitinemic cirrhotics (average serum level 50% of normal), spontaneous dietary intakes of carnitine, lysine, and methionine were measured and found to be only 5-15% as great as in six normocarnitinemic, healthy controls. When these six cirrhotic and six normal subjects were given the same lysine-rich, methionine-rich, and carnitine-free nutritional intake, the normals maintained normal serum carnitine levels and excreted 100 mumol/day, whereas the cirrhotics' serum level fell to 25% of normal, and urinary excretion declined to 15 mumol/day. Seven hypocarnitinemic cirrhotics died. Postmortem concentrations of carnitine in liver, muscle, heart, kidney, and brain averaged only one-fourth to one-third those in corresponding tissues of eight normally nourished nonhepatic patients who died after an acute illness of a 1-3-day duration. THESE DATA SHOW THAT CARNITINE DEPLETION IS COMMON IN PATIENTS HOSPITALIZED FOR ADVANCED CIRRHOSIS, AND THAT IT RESULTS FROM THREE FACTORS: substandard intake of dietary carnitine; substandard intake of lysine and methionine, the precursors for endogenous carnitine synthesis; and loss of capacity to synthesize carnitine from lysine and methionine.

Adult↗
PubMed1977

Urinary excretion of the cancer-related glycoprotein EDCl: effect of chemotherapy.

The effect of chemotherapy on the urinary excretion of a cancer-related glycoprotein labeled EDCl, recently isolated from the urine of a patient with acute myelocytic leukemia, has been studied by radioimmunoassay in eight cancer patients who were excreting 200 to 500 mg/day before treatment. In five patients, chemotherapy caused marked clinical improvement, and the glycoprotein disappeared from the urine within 10 days after chemotherapy began. In the two patients with solid tumor who responded to chemotherapy, disappearance of glycoprotein EDCl from the urine preceded clinical improvement by 1 to 2 months. Four of the five responsive patients relapsed within 6 months; in each instance, the glycoprotein reappeared in the urine (greater than 100 mg/day) 2 to 5 weeks before clinical relapse. Three patients were resistant to chemotherapy, and their urinary glycoprotein did not decline during chemotherapy. Measurement of urinary glycoprotein EDCl will be useful in rapidly ascertaining which drug will be effective in a cancer patient and in predicting relapse.

Adolescent↗
PubMed1977

Isolation and characterization of the glycoprotein (JBB5) in the urine of a patient with carcinoma of the colon.

Patient J. B. with metastatic carcinoma of the colon excreted 0.5 to 1.0 g protein daily, about one-third of which was in Molecular Weight Class 30,000 to 60,000. The major component of this class was isolated by gel filtration and ion-exchange chromatography. The purified protein, labeled JBB5, contained about 11% sialic acid, 8% hexose, and 4% hexosamine. Its molecular weight was between 51,000 and 59,000. It did not react detectably with antisera to any of the recognized normal human plasma proteins. A specific antiserum to JBB5 was raised in the rabbit. Urine from 4% of subjects with nonneoplastic illnesses reacted in double immunodiffusion with anti-JBB5. Thirty-three % positive reactions were obtained with urines from patients with advanced neoplastic disease, the percentage varying from 64% in metastatic cancer of the pancreas to 15% in chronic lymphocytic leukemia.

Adenocarcinoma↗