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Biomedical subjects

D Rudman

Publications and source records attributed to D Rudman.

At least 163 records · Page 9Linked to original sources
PubMed1977

A system of cancer-related urinary glycoproteins: biochemical properties and clinical applications.

UNLABELLED: Gel-filtration and immunodiffusion reveal most patients with disseminated cancer excrete 100 to 1000 mg/day of urine proteins, mol wt 10,000-60,000, which are distinct from known plasma proteins and cancer-related antigens. By gel-filtration and ion-exchange chromatography, 5 novel urinary glycoproteins have been isolated which are responsible for about 1/2 the mass of the "low molecular weight proteinuria" of patients with advanced cancer: BJC1 and BJC2 (patient B.J., chronic myelocytic leukemia); JBB5 (J.B., metastatic pancreatic carcinoma); EDC1 (E.D., acute myelocytic leukemia); HNC1beta (H.N., acute monocytic leukemia). Mol wts respectively are 29,000, 22,000, 55,000, 27,000 and 33,000, and carbohydrate contents respectively 61%, 23%, 23%, 27% and 40%. Attention to date has focussed on EDC1 and HNC1beta, because their urinary excretion directly reflects the course of the neoplastic disease. EDC1 and HNC1beta possess the same protein but different carbohydrate moieties. They are antigenically related to inter-alpha trypsin inhibitor, mol wt 160,000, which is one of the 6 antiproteolytic proteins in normal human plasma. EDC1 and HNC1beta both possess antitryptic activity. Specific radioimmunoassays (RIA) to these 2 glycoproteins were developed. Normal individuals (n = 210) excreted 0.3 +/- .02 (ave. +/- SE) mg EDC1 per g creatinine. In 18 non-neoplastic diseases (n = 75), urinary EDC1 was .5 +/- .06 mg/g creatinine. In disseminated cancer of 7 types (n = 81) (breast, ovary, colon, squamous of head-neck and lung; melanoma; acute myelocytic leukemia), ave. EDC1 excretion ranged from 10 to 190 mg/g creatinine. A significant increase (P less than .05) was found in the localized stage of squamous cancer of head-neck-lung, but only after regional or distant spread in the other types. Similar results were found with HNC1beta, urinary excretion of which averaged 1/10 that of EDC1. Effective chemotherapy in 5 patients with leukemia or solid tumors caused prompt disappearance of urinary EDC1; the glyco-protein reappeared in the urine several weeks before clinical relapse. CONCLUSIONS: (i) EDC1- and HNC1beta-proteinuria is a useful indicator of some types of localized and most types of disseminated cancer; (ii) the degree of this proteinuria reflects the effectiveness of chemotherapy; (iii) the antiproteolytic property of EDC1 and HNC1beta suggests a relation between proteolysis and tumorigenesis.

Carcinoma↗
PubMed1976

Selective and total shunts in the treatment of bleeding varices. A randomized controlled trial.

Two types of surgical therapy of bleeding esophageal varices were evaluated in 48 patients by a randomized controlled trial: 24 were randomized for a total shunt and 24 for the selective shunt. In two of the latter, a total shunt had to be performed for technical reasons. The fatality rates (six in the 24 total, and six in 22 selective [performed], and seven in 24 selective [randomized]), the frequency of shunt occlusion (two in each group), and of recurrent gastronintestinal bleeding (three in each group) were similar. Encephalopathy developed more often after a total shunt -- 10 of 24, or one per 58 patient-months -- than after selective (performed) -- one of 22, or one per 593 patient-months (P less than 0.005). Total shunts consistently diverted the hepatopetal mesenteric-portal flow from the liver. Deterioration of hepatic function (maximum rate of urea synthesis) was greater after total than selective shunt (P less than 0.05).

Adult↗
PubMed1976

Concentration of 3', 5' cyclic adenosine monophosphate in ventricular cerebrospinal fluid of patients with prolonged coma after head trauma or intracranial hemorrhage.

A previous study showed that cerebrospinal fluid from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure contains 15 to 30 nm 3', 5' cyclic adenosine monophosphate. We measured the concentration of this cyclic nucleotide by radioimmunoassay in cerebrospinal fluid from the lateral ventricle of six patients with prolonged coma (20 days or longer) after head trauma (four), or spontaneous intracranial hemorrhage (two). Coma was graded IV to I in order of decreasing severity. Fluid was removed at intervals of six to 72 hours from a Rickham reservoir placed in the lateral ventricle. Concentration of the cyclic nucleotide (mean +/- S.E.M.) in coma of Grades IV, III, II and I was 2.1 +/- 0.3, 4.6 +/- 0.5, 6.3 +/- 1.4 and 12.5 +/- 2.4 nM respectively. After sensorium became normal, cAMP was 21.0 +/- 1.4 nM. Correlation between grade of coma and concentration was -0.89 (P less than 0.01). Thus, prolonged coma appears to be associated with a disturbance of cyclic AMP metabolism within the central nervous system.

Adult↗
PubMed1976

Hypertyraminemia in cirrhotic patients.

To evaluate the role of tyramine in hepatic disorders, we used a radioimmunoassay to study plasma concentration of tyramine in eight healthy subjects, 20 hospitalized patients without liver disease, and 13 cirrhotic patients of whom seven had hepatic encephalopathy. The effect of increasing dietary protein on tyramine level of cirrhotic patients was also assessed. No significant difference in plasma tyramine concentration was seen between normal subjects, 1.3 +/- 0.1 ng per milliliter (average +/- S.E.), hospitalized patients without hepatic disease (1.4 +/- 0.1 ng per milliliter) and cirrhotic patients without encephalopathy (2.7 +/- 0.5 ng per milliliter). However, the tyramine level in cirrhotic patients with encephalopathy, 6.4 +/- 0.1 ng per milliliter, was significantly (P less than 0.001) higher than in normal subjects or in cirrhotic patients without encephalopathy. Increasing dietary protein from 40 to 80 g per day raised fasting tyramine concentration by 30 to 70 per cent within three days in both encephalopathic and non-encephalopathic cirrhotic patients. Concentration of plasma tyramine in cirrhotic subjects was significantly correlated with that of plasma tyrosine (P less than 0.001).

Adult↗
PubMed1976

Portal hypertension. A new beginning for an old problem.

There are two types of shunts for the treatment of esophageal varices: total shunts or selective shunts. The various total shunts are designed to "decompress" both the portal and the variceal venous systems. In contrast, a selective shunt decompresses the varices only, and the portal pressure and presumably portal flow are not affected. The very purpose of the total shunt is the total or partial diversion of portal flow. This is the case no matter which branches of the portal and systemic venous systems are connected and whether the anastomosis is a direct one or is through a graft. In an ongoing prospective, randomized clinical trial, which now includes 46 patients, a total shunt (mesorenal H graft) and the selective distal splenorenal (Warren) shunt are compared. The operative mortality rate and the frequency of postoperative bleeding are the same. However, encephalopathy is more frequent after the total shunt (P less than 0.05), and a trend is developing which suggests a better long-term survival rate after the Warren shunt. If these trends continue, then the superiority of the Warren shunt is established in a selected group of patients who have bled at least once from their varices. If these patients continue to remain free of encephalopathy and hemorrhage will not recur, then it is probable that the Warren shunt could improve the chances of survival of cirrhotic patients with esophageal varices who did not bleed yet. The "prophylactic" value of the Warren shunt will require a multicenter, cooperative, controlled clinical trial.

Esophageal and Gastric Varices↗
PubMed1976

Effect of antibiotics on growth of the immature rat.

The purpose of this study was to quantify the growth promoting effect of a mixture of antibiotics for rats eating diets deficient in protein or an essential amino acid. Male albino weanling rats (70 to 80 g weight, 4 weeks old) were fed (a) a control diet containing all other required nutrients and varying amounts of casein (0 to 27%), or (b) a purified amino acid diet containing all other required nutrients and varying amounts of valine (0 to 70 mumoles/g diet), threonine (0 to 69 mumoles/g diet) or tryptophan (0 to 8.6 mumoles/g diet), with and without an oral antibiotic supplement consisting of neomycin sulfate (10 mg/100 g body weight/day), bacitracin (500 units/100 g body weight/day), and polymyxin B sulfate (1 mg/100 g body weight/day). At suboptimal intake of casein, valine, tryptophan or threonine, rats eating antibiotic-enriched diet showed up to 3 times greater daily body weight gain (deltaBW) than rats eating a similar diet without antibiotics. The growth-promoting effect of antibiotics can be expressed as percent sparing of specified nutrient (casein or individual amino acid), defined as below: (see journal) where nutrient intakeO ab or nutrient intakeab represents that intake of casein or of a particular amino acid which is required to produce a specific deltaBW in antibiotic-free or antibiotic-supplemented group, respectively. The percent sparing was inversely proportional to the dietary content of casein or limiting amino acid. For diets containing 10% to 25%, 25% to 50%, 50% to 75%, and 75% to 100% of the daily requirement of the limiting nitrogenous nutrient, sparing on the average was greater than 80%, 60%, 20%, and less than 10%, respectively. Data on daily food intake of ad libitum fed rats, and data from an experiment with tube-fed rats, showed that the growth-enhancing effect of antibiotics was independent of changes in food intake.

Amino Acids, Essential↗
PubMed1976

Antidiuretic peptide in mammalian choroid plexus.

Lyophilized bovine, porcine, and human choroid plexuses contain .02-.09 U of antidiuretic activity per milligram. The antidiuretic factor in bovine choroid plexus was concentrated 100 times by extraction with acetic acid, fractional precipitation with acetone and ethyl ether, gel filtration, and paper chromatography. Resulting choroid plexus fraction IIgammaB2 was eluted from Sephadex G-25 in position corresponding to molecular weight between 750 and 3,500; its antidiuretic activity was destroyed by trypsin, performic acid, and thioglycollic acid, but was not affected by leucine aminopeptidase, carboxypeptidase A or B, or cyanogen bromide. HgammaB2 possesses antidiuretic, pressor, and oxytocic potencies (measured in anesthetized-hydrated rat, anesthetized rat, and isolated rat uterus, respectively) of 1.9, 0.5, and 0.1 U/mg, respectively.

Aminopeptidases↗
PubMed1976

Injection of melatonin into cisterna magna increases concentration of 3', 5' cyclic guanosine monophosphate in cerebrospinal fluid.

Rabbits were anesthetized with urethane and were given intracisternal injections of the following substances: adrenocorticotropin, beta-melanocyte stimulating hormone, choroid plexus peptide IIF, epinephrine, serotonin, histamine, oxytocin, lysine and a arginine vasopressins, acetylcholine and melatonin. The effects on the concentration of 3', 5' cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid were then measured. Only melatonin and acetylcholine caused a significant (p less than 0.05) effect on cGMP concentration. Both agents increased the nucleotide's concentration within 30 min. Melatonin was about 1,000 times more potent than acetylcholine; the mininal effective doses were 1 mug and 1,000 mug, respectively.

Animals↗
PubMed1976

Observations on the cyclic nucleotide concentrations in human cerebrospinal fluid.

Previous studies have shown that the concentrations of 3', 5' cyclic adenosine monophosphate (cAMP) and 3', 5' cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF), brain, or both, are increased by melanotropic peptides and catechol amines, and by cholinergic agents. The present study measured the concentrations of cAMP, cGMP, and melanotropic activity in the CSF of normal patients and in 136 subjects with various neurologic diseases. In normal lumbar CSF, concentrations (ave +/- SD) were: cAMP, 21 +/- 8 mM; cGMP, 2.4 +/- 0.5 mM; melanotropic activity, 17 +/- 6 units/100 ml. Concentrations of cAMP, cGMP, and melanotropic activity did not differ significantly (P is less than .05) from normal in the following categories of adult and pediatric patients: back pain due to vertigo of unknown cause; cerebral atrophy; cerebral vascular disease; and brain tumor subdural hematoma not causing increased ventricular pressure. Nine children with retarded psychomotor development caused by diffuse brain disease (infection, trauma, hemorrhage, degenerative process, long-standing hydrocephalus with thinning of the cerebral mantle) had subnormal levels of cAMP and melanotropic activity. These two variables were significantly correlated in the entire series of CSF samples (r=+0.55, P is less than .005). cGMP was elevated in the ventricular fluid of adult and pediatric patients when the ventricular pressure was abnormally elevated. The nucleotide's level rose as high as 50 X normal when ventricular pressure exceeded 300 mm H2O. The concentration of ventricular cGMP was proportional to that of ventricular pressure (r=+0.76, P is less than .005). The correlation was similar regardless of the type of hydrocephalus (congenital or acquired, communicating or obstructive), the age of the patient, or the nature of the underlying disease.

Adult↗
PubMed1976

Assay of pig growth hormone preparations for metabolic activities in the rat and in man.

The possible somatotropic effect in man of porcine growth hormone (pGH) and its plasmin digest has not been comprehensively studied before. For this purpose, pGH was digested with rat or human plasmin; acrylamide gel electrophoresis showed less than 10% native pGH remaining in the digests. Native pGH and the 2 types of plasmin digest possessed similar GH potency, as measured by the weight gain assay in the hypophysectomized rat: 1-2 IU/mg. In 7 GH-deficient children and 3 adults with myotonic dystrophy, we measured the capacity of human GH (hGH), pGH, and pGH plasmin digests to cause: a) the retention of N, P, K, Na, and Cl; b) a rise in plasma free fatty acids; c) a fall in plasma alpha-amino NL d) impaired glucose tolerance; and e) hyperinsulinemia. Human GH was active in all respects at minimal effective dosages of .0168 to 0.168 IU/kg BW(3/4) per day. The pGH preparations had no detectable effect at 0.532 I.U./kg BW(3/4)/day. The data show that in man pGH and its plasmin digests possess less than 1/30, less than 1/10, and less than 1/3 the anabolic, adipokinetic, and diabetogenic potencies of hGH, respectively.

Adolescent↗
PubMed1976

Technical pitfalls in measurement of venous plasma NH3 concentration.

Measurement of venous plasma NH3 in normal subjects by the ion-exchange method of Forman [Clin. Chem. 10, 497 (1964)] in a hospital clinical laboratory gave a mean value of 640 mug/liter (range, 300-1320 mug/liter; intraassay, intra-individual, and inter-individual coefficients of variation, 8, 47, and 47%, respectively). The following conditions adversely affect the reproducibility of the test: pollution of laboratory atmosphere and glassware by NH3-containing detergents; smoking by patient or analyst; delay, turbulence, or use of heparin lock in venipuncture; delay or warming of plasma above degrees C before mixing it with resin; and delay in colorimetric analysis of resin eluate. When these sources of error were eliminated, the mean value for normals was reduced to 330 mug/liter, the range was narrowed to 220-470 mug/liter, and the above-mentioned CV's were 5, 16, and 17%, respectively. With the precautions cited, furthermore, the intra-assay and intra-individual CV's for fasting NH3 concentration in cirrhotic patients were similarly reduced. An NH3 tolerance test was done by administering a standard dose of NH4Cl to patients and measuring venous plasma NH3 at 0, 15, 30, 60, and 90 min; the NH3 tolerance was quantified from the area under the curve relating concentration to time (mug - min/liter). As measured in the clinical laboratory, NH3 tolerance of cirrhotic patients showed intra-assay and intra-individual CV's of 50 to 90%. When the tolerance tests were repeated in the same subjects with the laboratory precautions listed above, these CV's were reduced to 8-15%.

Adolescent↗
PubMed1976

Cation-binding property of choroid plexus peptide IIF.

Preparations of the melanotropic-lipolytic peptide IIF from bovine choroid plexus contain 3% Ca, 1% Mg and less than 0.1% Na and K. Ca and Mg were removed by gel filtration on Sephadex G-10 in 1 N acetic acid. Capacity of the resulting cation-free peptide to bind Ca++, Mg++, Na+ and K+ was examined with the method of Hummel and Dreyer (Biochim. Biophys. Acta 63: 530-532, 1962). Peptide IIF bound a maximum of 3.7 to 4.4 mEq of Ca++, Mg++, Na+ or K+ per g of peptide. For each cation, linear Scatchard plot indicated one class of binding site. Association constants (liters per mole) were Ca++, 4.3 X 10(4); Mg++, 3.6 X 10(4); Na+, 4.8 X 10(2), K+, 1.9 X 10(2). Competitive binding experiments showed that all four cations occupied the same class of binding site.

Animals↗
PubMed1976

Isolation of a novel glycoprotein (EDC1) from the urine of a patient with acute myelocytic leukemia.

Gel filtration of urine from Patient ED with acute myelocytic leukemia showed a prominent protein peak with elution position corresponding to molecular weights of 20,000 to 35,000. The protein (EDC1) was isolated in pure form by sequential gel filtration and ion-exchange chromatography. Molecular weight of purified EDC1 was 27,000; it contained 27% carbohydrate and was rich in half-cystine (5% of residues). EDC1 was antigenically and chemically distinct from the recognized glycoproteins of normal plasma. With a specific rabbit antiserum and 125l-labeled EDC1, a radioimmunoassay for the glycoprotein was developed. Both noncancer and cancer plasmas contained immunoreactive material. In noncancer plasma, all the immunoreactivity was eluted from Sephadex G-75 and G-200 in position corresponding to molecular weights of 60,000 to 100,000 (Peak 1). In cancer plasma, an additional peak of immunoreactivity was eluted in the position corresponding to EDC1 (M.W., 20,000 to 30,000; Peak 2). Eighty-six % of urines from patients without clinical cancer were nonreactive in radioimmunoassay (less than 0.1 microgram immunoreactive EDC1 per ml); 11 and 3%, respectively, contained immunoreactivity equivalent to 0.1 to 0.9 and 1 to 9 microgram EDC1 per mi, entirely of Peak 1 type. Ninety-one % of urines from patients with disseminated cancer contained immunoreactivity equivalent to 10 to 9,999 microgram EDC1 per ml, primarily of Peak 2 type.

Amino Acids↗
PubMed1975

Observations on the lipolytic and melanotropic properties of neurophysin proteins.

Previous work indicated that brain contains 3 types of lipolytic-melanotropic peptide: (1) in adenohypophysis: ACTH, alpha-MSH, beta-MSH, peptide I, peptide L', beta-lipotropin and gamma-lipotropin; (2) in neurohypophysis: peptide 7D6, also termed neurophysin I, peptide II or Wuu-Saffran peptide; (3) in extrahypophyseal regions: peptide IIF. Bovine and human neurophysin I prepared by R. Walter has now been found devoid of lipolytic and melanotropic activities. Porcine and bovine peptide 7D6, closely similar or identical to bovine neurophysin I in electrophoretic mobility and amino acid composition, were therefore reexamined to determine whether their lipolytic-melanotropic property resided in a contaminating factor. When peptide 7D6 was analyzed in 100 transfer counter current distribution (1 butanol/0.1M NH4 HCO3), the neurophysin was recovered in tubes 1-9 (7D6-alpha) representing 95% of 7D6. 7D6-alpha was inactive in lipolytic and melanotropic assays. The biologic activities of 7D6 were recovered instead in tubes 50-70 (labeled 7D6-beta), representing 5% of 7D6. 7D6-beta proved to be a peptide with MW 1000-3000, closely similar to peptide IIF in amino acid composition, MW, and Rf values in 4 systems of paper chromatography.

Amino Acids↗
PubMed1975

Hyperdibasicaminoaciduria, hyperammonemia, and growth retardation: Treatment with arginine, lysine, and citrulline.

A 9-year-old girl with hereditary dibasicaminoaciduria has been studied for three years. Initially, clinical features were: growth failure; anorexia and aversion to protein, spontaneous daily protein intake averaging only 10 gm; fasting and postprandial venous hyperammonemia; subnormal plasma concentrations of lysine, arginine, ornithine, and citrulline, with generalized hypermonobasicaminoacidemia; abnormally high renal clearances of lysine, arginine, and ornithine; and intestinal malabsorption of lysine and arginine. Intestinal absorption of citrulline, a precursor of arginine and ornithine, was normal. The patient was observed during four sequential 6-month periods as follows: no treatment (Period I); dietary supplement of arginine and lysine (Period II); dietary supplement of citrulline and lysine (Period III); no treatment (Period IV). During Periods II and III growth rate increased 3- to 4-fold, spontaneous protein intake increased 2- to 3-fold, and abnormalities in blood NH3 and the plasma aminogram were partially corrected. In most respects the citrulline plus lysine supplement was more beneficial than that of arginine plus lysine.

Amino Acid Metabolism, Inborn Errors↗
PubMed1975

Plasma amino acid patterns during supplemental intravenous nutrition of low-birth-weight infants.

In 42 low-birth-weight infants (smaller than 1,200 gm), we have compared the effects of intravenous nutrition supplement versus conventional feedings on growth, morbidity, mortality, and plasma amino acid patterns. Despite similar total caloric intake in INS and control groups, weight gain was greater in the INS infants. The overall mortality rate did not differ in the two groups. Nonsurviving infants receiving INS lived longer (mean equal to 30 days) than nonsurviving CON infants (mean equal to 5 days). Complications were equally frequent in both groups except that hyperglycemia occurred more often in infants receiving INS. The plasma aminogram of the LBW infant is described and compared to those of the full-term infant and adult. Hypoaminoacidemia was present at birth in the LBW infants, concentrations of glutamine, alamine, glycine, histidine, and ornithine being significantly (P smaller than 0.05) below FT values. During INS, elevations of threonine, serine, and methionine above FT values occurred. Glutamine remained subnormal despite INS. Recommendations for an INS solution more suitable for use in LBW infants are presented.

Amino Acids↗
PubMed1975

Melanotropic activity in extrahypophyseal regions of rodent brain: effect of age, hormones, and drugs.

Two or more melanotropic peptides are present in extrahypophyseal regions of mammalian brain. Previous studies showed that extrahypophyseal melanotropic activity is not influenced by hypophysectomy, adrenalectomy, or exogenous glucocorticoid. The present study investigated the possible influence of the following factors on the level of melanotropic activity in whole brain, cerebral cortex, cerebellum, midbrain, and brainstem of mouse and rat: age, sex, starvation; and of the following hormones or drugs administered by the intraperitoneal or intracerebral route: norepinephrine, dihydroxyphenylalanine, pargyline, 6-hydroxy-dopamine, alpha-methyltyrosine methyl ester, reserpine, acetylcholine, pilocarpine, atropine, serotonin, p-chlorophenylalanine, pentobarbital, pentylenetetrazol, insulin, melatonin, and cycloheximide. Only age influenced extrahypophyseal melanotropic activity. The activity per unit of tissue wet weight or of tissue protein increased in all regions progressively from birth to 1 yr of age. Extrahypophyseal melanotropic activities perunit wet weight of tissue at 50 wk averaged 4.3 times those at birth. When brain of adult rodents was fractionated by differential centrifugation, the major proportion of melanotropic activity was recovered in myelin (27-35 percent), nerve endings (20-22 percent), and mitochondria (25-30 percent). The lower activity in newborn brain resulted not onlyfrom absence of a myelin fraction, but also from lower activity at birth in nerve endings and mitochondria.

Acetylcholine↗