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Biomedical subjects

T M Chu

Publications and source records attributed to T M Chu.

At least 163 records · Page 9Linked to original sources

Carcinoembryonic antigen-binding immunoglobulin isolated from normal human serum by affinity chromatography.

A human immunoglobulin that binds carcinoembryonic antigen (CEA) was isolated from four individual normal human sera by affinity chromatography with the use of a CEA-Sepharose solid adsorbent. The yield of isolated protein, termed human CEA-binding protein (HCBP), ranged from 1.8 to 10 microgram/ml serum. HCBP is a gamma-globulin of restricted electrophoretic heterogeneity as shown by immunoelectrophoresis. HCBP was shown to bind radioiodine-labeled CEA both by a radioimmune precipitation assay and by a radioimmunoelectrophoresis assay. This protein was of practical interest because of its potential usefulness as a carrier of radioactivity or therapeutic agents to a CEA-producing tumor for therapeutic or diagnostic purposes.

Antibodies, Neoplasm↗

Human tissue polypeptide antigen in breast cancer.

Serum tissue polypeptide antigen (TPA) and plasma carcinoembryonic antigen (CEA) were simultaneously measured in 108 patients with breast cancer, in 40 healthy women, and in 26 women with benign breast disease. TPA levels were elevated (0.09 microgram/ml or higher) in 53% of 19 patients with primary breast cancer, and CEA levels were elevated (2.5 ng/ml) in 21%. Among 67 patients with metastatic breast cancer, TPA and CEA levels were increased in 70% and 61%, respectively. TPA was positive in 13% and CEA in 8% of the healthy women. CEA levels were not elevated in patients with benign breast disease, but levels of TPA were elevated in 27% of those studied. Elevation of TPA levels was more frequent in patients with visceral metastasis having higher values of the test results. Among 22 women with breast cancer who had no apparent cancer recurrence, TPA levels were elevated in 12 and CEA levels in 6. In another group of 39 patients with metastatic breast cancer who received palliative therapy, a limited correlation was noted between the clinical course of the disease and changes in TPA and CEA values measured in linear fashion. Thus TPA appeared to be equal to CEA as a tumor marker in most areas analyzed.

Antigens, Neoplasm↗

Purification of a human prostate specific antigen.

Rabbit antiserum raised against the crude extract of normal human prostatic tissue contained antibodies to a prostatic tissue-specific antigen as shown by immunoprecipitation techniques. Using this antiserum a prostate antigen was detected in normal, benign hypertrophic, and malignant prostatic tissues, but not in other human tissues. The prostate antigen was purified to homogeneity from prostatic tissues and showed a single protein band on analytical polyacrylamide gel electrophoresis and isoelectric focusing. This report thus presents the first demonstration of the purification of a prostate-specific antigen that does not represent prostatic acid phosphatase.

Antigens↗

Xanthine nephropathy during chemotherapy in deficiency of hypoxanthine-guanine phosphoribosyltransferase.

We describe an episode of obstructive uropathy produced by xanthine precipitation in the tubules of the kidney of a patient with histiocytic lymphoma during intensive chemotherapy, despite allopurinol therapy. Urinary oxypurine-uric acid ratio suggested a subclinical deficiency of hypoxanthine-guanine phosphoribosyltransferase. Results of an assay of this enzyme confirmed the abnormality. Both parents and three brothers of the patient had normal enzyme activity. The continued importance of adequate hydration for patients who receive allopurinol during initial periods of cancer therapy is emphasized.

Acute Kidney Injury↗

Clinical significance of serum alkaline phosphatase isoenzyme levels in advanced prostatic carcinoma.

The alkaline phosphatase isoenzymes in 105 patients with stage D carcinoma of the prostate who entered the National Prostatic Cancer Study were analyzed and these values were correlated to clinical response. Only patients with at least 3 measurements of alkaline phosphatase were evaluated. In 91% of patients with metastatic bone disease, bone alkaline phosphatase was elevated. Those patients with higher pre-treatment levels of alkaline phosphatase generally showed a poorer response to therapy. The results of alkaline phosphatase isoenzyme estimation indicate that these biological markers may be used in the evaluation of patients with metastatic prostatic cancer to predict and monitor their response to chemotherapy. The evaluation of bone and liver alkaline phosphatase isoenzymes in earlier stages also may be valuable.

Alkaline Phosphatase↗

Identification of a macromolecule containing an anticarcinoembryonic antigen-reactive substance and immunoglobulin M in human pancreatic cancer.

Ascitic fluid from a patient with carcinoma of the pancreas was fractionated by ammonium sulfate precipitation. The fraction precipitated between 25 and 50% saturation of ammonium sulfate was sequentially chromatographed on Sephadex G-200 and Sepharose 6B. A macromolecular fraction (greater than 10(6) daltons) obtained was found to react with both antihuman IgM and antiserum to carcinoembryonic antigen (CEA). This fraction was further purified by adsorption with protein A-Sepharose CL-4B and chromatography on DEAE-Sephacel. The purified macromolecular fraction had a sedimentation value of 28S as determined by ultracentrifugation. Upon dissociation of the purified macromolecule at pH 2.3 and purification of the dissociated components on Sepharose CL-2B and BioGel A 1.5M, a 19S protein and a 5S protein were recovered. The 19S protein showed a complete line of identity with a reference human IgM when reacted with antihuman IgM in gel diffusion, whereas the 5S protein showed a partial immunologic identity with colon CEA against anti-CEA. These results indicated the existence of an IgM-containing macromolecular complex with an anti-CEA cross-reactive substance in the extracellular fluid of human pancreatic cancer.

Ammonium Sulfate↗

Isoenzymes of human prostate acid phosphatase.

The isoenzymes of human prostatic acid phosphatase have been studied by an isoelectric focusing technique. Purified acid phosphatase from malignant prostates contained eight isoenzymes with pI 4.4--5.3. The sera from patients with prostate cancer were shown to have similar acid phosphatase isoenzyme patterns at pI 4.0--5.5; as the serum enzyme activities increased, the pI of isoenzymes shifted to more acidic pH. These isoenzyme patterns of sera from patients with prostate cancer were different from those of patients with Gaucher's disease or from acid phosphatase of human erythrocytes, both of which exhibited only one enzyme band around pI 5.0 and 6.0, respectively. Treatment of serum sample of prostate cancer with neuraminidase did not result in a single enzyme band but alter the pI of isoenzymes, which shifted to a higher pH region. The significance of acid phosphatase activities and its isoenzyme patterns in prostate cancer merits further investigation.

Acid Phosphatase↗

Identification of a breast tumor-associated orosomucoid by concanavalin A affinity chromatography.

Con A-Sepharose affinity chromatography was utilized to examine the glycoproteins in phosphosaline extracts of normal and breast tumor tissues and breast patient sera. In extracts of normal breast tissue, normal sera and patient sera, all glycoproteins were eluted from the Con A-Sepharose with a linear gradient of 0.0-0.5 M alpha-methylmannose. Using breast tumor extracts, a glycoprotein peak which could not be eluted as with normal tissue extracts was observed. This tightly-binding peak could be eluted from the Con A-Sepharose with acetate buffer containing 1.0 M KCl. Polyacrylamide electrophoresis of this tightly-binding glycoprotein peak revealed one major glycoprotein and four minor glycoproteins. The major glycoprotein obtained from electrophoresis represented about 60% of the Con A-Sepharose tightly-binding protein and reacted with antiserum to human orosomucoid (alpha 1-acid glycoprotein). All glycoproteins isolated from tumor tissue extracts appeared to represent normal serum constituents as they were retained on an immunoadsorbent containing antibodies to normal serum proteins. The possible significance of the isolated tumor-associated orosomucoid is discussed.

Adenocarcinoma↗

Biochemical and immunologic techniques for acid phosphatase measurement in the diagnosis of prostate cancer.

A counter immunoelectrophoresis procedure for the measurement of acid phosphatase is described. Acid phosphatase was purified from human prostate. A monospecific antiserum to the purified enzyme was produced in rabbits. With the specific antiserum and a sensitive chemical staining technique, a counter immunoelectrophoresis assay was developed for detection of serum prostate acid phosphatase. The isoenzymes of serum prostate acid phosphatase were also studied by an isoelectric focusing technique.

Acid Phosphatase↗

Immunochemical detection of serum prostatic acid phosphatase. Methodology and clinical evaluation.

An immunochemical method for detection of prostatic acid prosphatase is described. Purified acid phosphatase was isolated from cancerous human prostate. A specific antiserum to the purified enzyme was produced in rabbits. The antiserum to postatic acid phosphatase did not react with acid phosphatase originating from other tissues. A counter immunolectrophoresis, utilizing the specific antibodies and a chemical staining technique, has been developed and clinically evaluated. Sera from patients with prostatic carcinoma (6/20 of stage B, 27/49 of stage C, and 98/125 of stage D) gave positive results. Sera from 19 patients with benign prostatic hypertrophy, from 89 patients with other tumors, from 12 patients with Gaucher's disease, from 107 healthy volunteers, and from 50 normal age-matched men all gave negative results. The sensitivity of this method was 0.4 IU of enzyme activity or 20 ng per ml of prostatic acid phosphatase protein. Further clinical evaluation of patients in the early stage of prostatic cancer and of patients undergoing chemotherapy is in progress.

Acid Phosphatase↗