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Biomedical subjects

R C Reba

Publications and source records attributed to R C Reba.

At least 109 records · Page 6Linked to original sources
PubMed1983

Insensitivity of the cold pressor stimulation test for the diagnosis of coronary artery disease.

Cold pressor stimulation (CPS) was compared with supine bicycle exercise during radionuclide ventriculography as a procedure for diagnosing coronary artery disease (CAD). Thirty patients were studied. In the 18 patients with angiographically proved CAD, left ventricular ejection fraction (LVEF) decreased a mean of 5.0 +/- 1.0 ejection fraction units (+/- SEM) in response to CPS. Only two patients developed a new wall motion abnormality. In response to maximal supine exercise, the CAD group showed a mean decrease in LVEF from rest of 1.9 +/- 1.1%. Nine patients developed an exercise-induced wall motion abnormality. In the 12 patients with angiographically proved normal coronary arteries, LVEF decreased a mean of 5.8 +/- 1.3 units in response to CPS and increased a mean of 9.2 +/- 1.2% in response to exercise. Thus, the LVEF response to CPS was not significantly different in the CAD and normal groups (5.0 +/- 1.0 vs 5.8 +/- 1.3, NS). These same patients demonstrated the expected difference in LVEF response to exercise. We conclude that CPS produces similar changes in LVEF in patients with and without CAD, and therefore is not useful in diagnosing ischemic heart disease.

Adult↗
PubMed1983

Optimization of the DTPA mixed-anhydride reaction with antibodies at low concentration.

Diethylenetriaminepentaacetic acid (DTPA) was conjugated with antibody to human serum albumin (Ab) at low concentration (300 micrograms/ml, 2.0 microM) via the DTPA carboxycarbonyl mixed-anhydride method. To study parameters determining the balance between the degree of conjugation and the antibody-binding activity of Ab, a known concentration of the anhydride prepared at isobutylchloroformate (IBC)-to-DTPA ratios of 1, 2.1, or 4.2 was reacted with Ab. The percentage yields of the anhydride were determined by spectrophotometric and gravimetric titration. By the former method the percentage yields, based on DTPA concentration, were 18, 24, and 220, respectively, when the IBC-to-DTPA ratios were 1, 2.1, and 4.2. The corresponding percentage yields were 17, 39, and 262 when determined by the latter method. When the anhydride was prepared at an IBC-to-DTPA ratio of 2.1, an optimum conjugation giving three indium atoms per Ab was obtained, with 64% retention of antibody-binding activity. For an IBC-to-DTPA ratio of 1, the antibody retained almost 100% binding activity but the number of indium atoms incorporated (0.2) was too small. For an IBC-to-DTPA ratio of 4.2, up to 22 indium atoms were incorporated but antibody-binding activity was completely destroyed.

Anhydrides↗
PubMed1983

Factors influencing DTPA conjugation with antibodies by cyclic DTPA anhydride.

Diethylenetriaminepentaacetic acid (DTPA) was conjugated with a practical concentration (300 micrograms/ml) of antibody to human albumin (Ab) and 1083 17-1A monoclonal colorectal antibody (MAb-17-1A) via an acylation reaction using cyclic DTPA anhydride (cDTPAA). The conjugation reaction was favored as pH increased. Bicarbonate buffer at pH 8.2 was chosen for studies of the effect of the cDTPAA-to-antibody ratio on DTPA conjugation with antibody because of its good buffer capacity at that pH. The reaction of cDTPAA with Ab at molar ratios of 2000, 1000, 500, and 100 in the bicarbonate buffer gave rise to 11, 9, 8, and 2 indium atoms incorporated per Ab with 47%, 55%, 59%, and 77% retention of the binding activity. For the conjugation reaction of MAb-17-1A, 29, 28, 31, 11, 4, and 1 indium atoms were incorporated, with the retention of less than 5%, less than 5%, less than 5%, 12%, 60%, and 93% of binding activity when the molar ratio was 5000, 2000, 1000, 500, 100, and 50.

Animals↗
PubMed1982

The use of tritium labeled compounds to develop gamma-emitting receptor-binding radiotracers.

In an effort to evaluate receptor binding drugs for their potential as gamma labeled radiopharmaceuticals suitable for clinical heart scanning, in vivo data were compared with the results obtained from a theoretical model. The distribution of selected tritium-labeled, receptor-binding radiotracers was studied in animals to determine if the heart to blood ratios agree with those obtained using a theoretical model of receptor binding. In general, the in vivo studies agree with the theoretical model when the concentration of the radiotracer in the heart is due to specific receptor binding. The use of the theoretical model for a first approximation followed by in vivo biodistribution studies is an efficient strategy to select those few from among the large number of receptor binding compounds that will ultimately yield an efficacious radiopharmaceutical to study receptor changes in the intact human heart.

Adrenergic alpha-Antagonists↗
PubMed1982

Analogues of 3-quinuclidinyl benzilate.

A number of analogues of 3-quinuclidinyl benzilate (QNB) have been synthesized and their affinities to muscarinic receptor from rat or dog ventricular muscle measured. We have determined that the muscarinic receptor can to a different degree accommodate either a halogen in the ortho, meta, or para position of one phenyl ring or the replacement of one phenyl ring with an alkyl group. Our in vitro competition studies show that the affinities lie within a 270-fold range, from the highest affinity compound, 3-quinuclidinyl alpha-hydroxy-alpha-cyclopentylphenylacetate (2), to the lowest affinity compound, 3-quinuclidinyl alpha-hydroxy-alpha-2-propargylphenylacetate (11).

Animals↗
PubMed1982

Three radioligands compared for determining cytoplasmic estrogen-receptor content of human breast carcinomas.

We compared three radioligands for use in a cytoplasmic estrogen-receptor assay, using pooled cytosol from human breast adenocarcinomas. The estrogen receptor content was determined in vitro by a dextran-coated charcoal method involving a 4-h incubation with and without diethylstilbestrol. Tritiated moxestrol failed to come to equilibrium in 4 h, thereby preventing the use of conventional one-component Scatchard analysis. The use of 125I-labeled estradiol resulted in a higher estimate of estrogen-receptor concentration than that obtained with use of tritiated estradiol. This overestimation was not corrected by Scatchard, double-reciprocal, or Woolf plots, or by two different methods of data analysis: least squared and "robust." An underestimation of the specific activity of iodoestradiol with respect to that of tritiated estradiol and an unrecognized second component of nonreceptor binding could explain this disparity.

Breast Neoplasms↗
PubMed1981

Effect of phenobarbital on 99mTc-IDA scintigraphy in the evaluation of neonatal jaundice.

Hepatobiliary scintigraphy with 99mTc-IDA derivatives was used to evaluate 40 neonates with mixed jaundice. Fourteen patients proved to have biliary atresia. The remaining 26 patients had intrahepatic cholestasis with patent extrahepatic ducts. Sixteen of the 40 patients underwent examinations without phenobarbital stimulation. Sixteen patients had two examinations, one before and one after 3-7 days of phenobarbital therapy. The remaining 8 patients had their initial examinations after phenobarbital therapy. The results of this study show that administration of phenobarbital in a dose of 5 mg/kg/day for at least 5 days prior to the examination enhances and accelerates biliary excretion of IDA compounds and thereby significantly increases the accuracy of 99mTc-IDA scintigraphy in differentiating extrahepatic biliary atresia from neonatal hepatitis. Its routine use in the evaluation of neonatal jaundice is therefore highly recommended.

Bile Ducts↗
PubMed1981

Hepatobiliary scintigraphy with 99mTc-PIPIDA in the evaluation of neonatal jaundice.

Hepatobiliary scintigraphy with technetium 99m-labeled p-isopropylacetanilido iminodiacetic acid (99mTc-PIPIDA) was used to evaluate 22 neonates with mixed jaundice. Ten patients were proved to have biliary atresia; ten others were diagnosed as having neonatal hepatitis. In the remaining two, jaundice was secondary to prolonged hyperalimentation. Initial studies in all ten patients with biliary atresia showed no evidence of excretion of the tracer into the intestinal tract. Following three to seven days of oral administration of phenobarbital, repeat studies were performed in six of the ten patients. None showed evidence of excretion. Initial studies of the 12 patients with intrahepatic cholestasis showed definite excretion in five, questionable evidence of excretion in two, and no demonstrable excretion in five. Studies after phenobarbital therapy in five of the seven patients with questionable or no excretion on the initial studies showed definite excretion in four. Only in one patient who had poor hepatic extraction did the phenobarbital therapy not change the scintigraphic pattern. The authors conclude that hepatobiliary scintigraphy with 99mTc-PIPIDA after three to seven days of phenobarbital therapy is a highly accurate test for differentiating biliary atresia from other causes of neonatal jaundice.

Bile Ducts↗
PubMed1980

In vivo receptor binding of iodinated beta-adrenoceptor blockers.

Six radiolabeled beta-adrenoceptor blocking agents with a range of affinity constants were evaluated as radioindicators for adrenoceptors in guinea-pig heart and lung. All concentrated in the heart and lung at levels in excess of 0.1% dose/g tissue. On the basis of displacement studies using propranolol, two of the six compounds showed beta-adrenoceptor binding in the lung, and one, H-3 carazolol, showed receptor binding in the heart. These results agree qualitatively with a bi-molecular reversible equilibrium model, and suggest that the beta-adrenoceptor blockers as a group will not be useful in vivo probes of receptor concentration in the heart because of the low affinity constants and high levels of nonreceptor binding associated with the present-day clinical beta blockers. Beta-adrenoceptor blocking agents with affinity constants in excess of 10(9) will be needed to give heart-to-blood ratios of 10.

Adrenergic beta-Antagonists↗
PubMed1980

Radioiodinated estrogen derivatives.

Monoiodohexestrol exhibits 10 to 15% specific binding to the 8S estrogen receptor while the remainder binds to nonreceptor 4S proteins. Reduction of nonreceptor binding with either thyroxine or 8-anilino-1-naphthalene sulfonic acid was not quantitative. Thus no accurate determination of the concentration of receptor sites in the radioreceptor assay was possible by graphical analysis. Two additional estrogens--17 alpha [125I]iodoethynylestradiol and 17 alpha-[125I]iodoethynyl-11 beta-methoxy estradiol--were synthesized at high specific activity. Although the iodoethynyl derivatives were stable under synthetic conditions, deiodination in the presence of proteins is too fast to allow either in vivo or in vitro use. To make these compounds clinically useful, therefore, chemical modification to reduce nonreceptor binding and the rate of dehalogenation must be undertaken.

Anilino Naphthalenesulfonates↗
PubMed1980

Radiolabeling of antibodies.

The radiolabeling of antibodies is considered in terms of the choice of radionuclide, the method of conjugation, and the effect of conjugation on plasma clearance. Iodination techniques are reviewed, but the major emphasis is placed on the methods of conjugating metallic radionuclides using bifunctional chelating agents. The technique of producing clinically useful radiolabeled antibodies by balancing altered substrate specificity caused by radiolabeling against accelerated plasma clearance is discussed.

Antibodies↗