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Biomedical subjects

H Harris

Publications and source records attributed to H Harris.

At least 145 records · Page 8Linked to original sources
PubMed1983

Structure and function of the Ca antigen.

The Ca antigen, which can be detected in a wide range of malignant human tumours by means of the Cal antibody, is a glycoprotein of the mucin type. At least 95% of the carbohydrate is 0-glycosidically linked to the polypeptide which contains high proportions of glycine, serine and glutamic acid. The carbohydrate has a very simple structure: it is composed almost entirely of tetra- tri- and disaccharides having the general formula (NeuNac)n leads to [Gal leads to GalNac] alpha leads to, where n = 0, 1 or 2. In many malignant cell lines, the antigen is produced constitutively in vitro; but in one that has been examined, its synthesis can be induced by high concentrations of lactate. Evidence is presented for the view that a primary function of this glycoprotein is to shield the cells that produce it from hydrogen ion concentrations outside of the physiological range. The presence of the Ca antigen in malignant tumours may thus be a reflection of metabolic conditions that are known to be characteristics of such tumours.

Amino Acids↗
PubMed1983

A controlled clinical trial of alprazolam for the treatment of anxiety.

The authors report the results of a large-scale double-blind study comparing the anxiolytic effects of alprazolam, a triazolobenzodiazepine; diazepam, a 1,4-benzodiazepine; and placebo in 151 anxious outpatients. Alprazolam and diazepam produced similar clinical improvement, which was significantly larger than improvement produced by placebo and was clearly evident after only 1 week of treatment. The incidence of sedation was lower with alprazolam than with diazepam.

Adult↗
PubMed1983

Kinetic parameters of hexose transport in hybrids between malignant and nonmalignant cells.

Matched pairs of isogeneic hybrid cells, in which one member of the pair was malignant and the other not, were used to examine the linkage between malignancy and functional alterations in hexose transport. The kinetic parameters of uptake of 2-deoxy-D-glucose were measured in a range of such hybrids, both human and murine. Some other malignant cell lines were also examined and were compared with non-tumorigenic derivatives of tumour cells selected by exposure to the lectin, wheat-germ agglutinin. In every case, malignancy, as defined by the ability of cells to grow progressively in vivo, was found to be linked to a decrease in the Michaelis constant of hexose uptake. Independent measurement of the transport and phosphorylation reactions involved in hexose uptake revealed that this decrease was determined by the membrane transport system. The difference in Michaelis constant between malignant and non-malignant cells was observed with 3-O-methylglucose, a hexose that is transported into the cell but not further metabolized. The activity of hexokinase in cell homogenates was higher than the level that would be required to cope with transport and showed no correlation with tumorigenicity. Measurement of the uptake of D-glucose itself, by a rapid filtration centrifugation method, gave results similar to those obtained with 2-deoxy-D-glucose.

3-O-Methylglucose↗
PubMed1983

Discrimination of human placental alkaline phosphatase allelic variants by monoclonal antibodies.

Eighteen monoclonal antibodies were produced by the mouse hybridoma method using purified placental alkaline phosphatase (ALP) as antigen. The ability of the various antibodies to discriminate among allelic variants of the enzyme was tested using a large panel of placental ALPs that had been typed electrophoretically. The panel included sets of samples of each of the six common polymorphic phenotypes as well as a series of rare variants. The reactivity of each antibody with each placental ALP (binding ratio) was determined relative to a single standard placental ALP (type 1) in a quantitative binding assay. The findings for six of the antibodies have already been reported. The results on the other 12 antibodies are presented here, and the combined data on the total series of 18 antibodies are analyzed and discussed. Six of the 18 antibodies showed significantly reduced binding to one or another of the products of the three common alleles. In three cases, the discrimination was reflected by essentially "all-or-none" binding reactions. In the other three cases, the binding differences were less marked but could be demonstrated by quantitative comparisons of the binding ratios. Quantitative binding ratio comparisons also enabled heterozygotes to be differentiated from homozygotes in each case. Some of the antibodies showed reduced binding with certain of the rare variant ALP electrophoretic phenotypes. It is estimated that at a minimum this unselected series of 18 antibodies is directed to at least nine different antigenic determinants on the surface of the placental ALP molecule. The results illustrate the power of monoclonal antibodies to discriminate among allelic variants of enzymes.

Alkaline Phosphatase↗
PubMed1983

Immunohistochemical localization of placental-like alkaline phosphatase in testis and germ-cell tumors using monoclonal antibodies.

Six monoclonal antibodies raised against the human placental alkaline phosphatase (ALP) recognizing distinct antigenic determinants on the surface of this isozyme were used for immunohistochemical studies of adult and fetal human testes and testicular germ-cell tumors. ALP reacting with all six antibodies was defined as placental, whereas ALP reacting with some but not all antibodies was labeled as placental-like. ALP reacting with one of the monoclonal antibodies that recognizes a determinant common to intestinal and placental ALP was tentatively considered probably intestinal, unless it reacted with any other monoclonal placental specific antibody. Using this approach, the authors have identified placental ALP in 4 of 7 seminomas, 3 of 7 tumors composed in part or fully of embryonal carcinoma, and 1 yolk sac carcinoma. Placental-like ALP was identified in 2 additional seminomas and 4 embryonal carcinoma-containing tumors, whereas 1 seminoma and 1 benign teratoma were devoid of either placental or placental-like ALP. Trophoblastic giant cells in 2 seminomas and 3 teratocarcinomas expressed only the antigenic determinant common to placental and intestinal ALP. The authors thus show that testicular tumor cells may express either placental or placental-like ALP and that in some instances, the tumor isozyme is antigenically different from ALP found on either fetal or adult testicular germ cells.

Adult↗
PubMed1983

Monoclonal antibodies to an ectopically expressed alkaline phosphatase in a human malignant cell line.

The D98/AH-2 cell line (a subline of HeLa) expresses a form of alkaline phosphatase (ALP) which closely resembles the adult and fetal intestinal forms of ALP. To characterize this ectopic form of ALP, four monoclonal antibodies were raised against D98/AH-2 ALP, and their binding with ALPs from D98/AH-2 cells, placenta, fetal intestine (meconium), adult intestine, and liver was compared using an electrophoretic titration procedure. The ALPs were either untreated or treated with neuraminidase. All four monoclonal antibodies bound desialated D98/AH-2 ALP most strongly. Adult intestinal ALP, which does not contain sialic acid residues, reacted much more strongly than either sialated or desialated fetal intestinal ALP. Two of the four monoclonal antibodies reacted very weakly or not at all with placental ALP, but two others reacted more strongly with placental ALP than with fetal intestinal ALP. None of the antibodies reacted with liver ALP. From these results, it appears that D98/AH-2 ALP may be a modified form of adult intestinal ALP.

Adult↗
PubMed1982

Production of a monoclonal antibody to human liver alkaline phosphatase.

A monoclonal antibody to human liver alkaline phosphatase (ALP) has been produced by the mouse-hybridoma method using a partially purified enzyme preparation as antigen. The particular hybridoma secreting the antibody was detected by a screening procedure based on the retention of enzyme activity by the enzyme/antibody complex. The antibody cross-reacts strongly with human kidney and bone ALPs but not with human placental or intestinal ALPs. It also cross-reacts with liver and kidney ALPs from gorilla, chimpanzee and orangutan. It shows no significant reaction, under the conditions used, with liver or kidney ALPs from several lower primates. An antibody affinity column was prepared and shown to be effective for the final stages of liver ALP purification.

Alkaline Phosphatase↗
PubMed1982

Demonstration using monoclonal antibodies of inter-locus heteromeric isozymes of human alkaline phosphatase.

Monoclonal antibodies were used to demonstrate hybrid forms of human alkaline phosphatase (ALP) composed of subunits from both placental and intestinal loci. Four main isozymes with alkaline phosphatase activity appear on polyacrylamide gels of the HeLa cell line, Hep 2/5 after electrophoresis. The mobilities of all 4 isozymes are retarded after incubating cellular extracts with a monoclonal antibody specific for placental ALP, while the mobilities of 2 isozymes are also affected by a monoclonal antibody which reacts specifically with intestinal ALP. These 2 isozymes, therefore represent interlocus heteromers (placental/intestinal ALP).

Adult↗
PubMed1982

A search for trace expression of placental-like alkaline phosphatase in non-malignant human tissues: demonstration of its occurrence in lung, cervix, testis and thymus.

A search for placental or placental-like human alkaline phosphatase (ALP) was made in human tissues. The tissue extracts were assayed for ALP before and after heating at 65 degrees C for 1 h. Trace amounts of heat-stable ALP activity (greater than 0.01 IU/g) were found in lung, testis, cervix and thymus. The heat-stable ALP in these four tissues gave in Ouchterlony double diffusion plates lines of apparent identity with placental ALP when a rabbit anti-human placental antiserum was used. Inhibition studies with L-phenyl-alanine (Phe), L-homoarginine (Har), L-phenylalanylglycylglycine (Pgg), L-leucine (Leu) and levamisole (Leva), were carried out on the heat-stable ALP and on the total ALP. The heat-stable ALPs from cervix and lung gave [I]50 values with each inhibitor comparable to those of placental ALP. The heat-stable ALPs froM testis and thymus gave [I]50 values for Leu and Pgg which were significantly different from the placental isoenzyme. Electrophoresis of heat-stable lung ALP from different individuals showed polymorphic differences similar to those seen with placental ALPs. Such differences were not seen with heat-stable testis ALP. We conclude that human non-malignant testis, cervix, lung and thymus tissues contain small amounts of placental or placental-like ALPs. The heat-stable ALPs in cervix and lung appear to have the same characteristics as placental ALP and are probably encoded by the same gene locus. The heat stable ALPs in testis and thymus, though immunologically very similar to placental ALP differ from it in inhibition profile and electrophoretically. The significance of the results in relation to the "ectopic' expression of placental and placental-like ALPs in malignancy is discussed.

Alkaline Phosphatase↗
PubMed1982

A new marker for human cancer cells. 3. Immunocytochemical detection of malignant cells in serous fluids with the Ca1 antibody.

The Ca1 antibody has been used in an immunocytochemical procedure on smears of cells recovered from 50 effusions from the pericardial, peritoneal, and pleural cavities. In 25 samples containing malignant cells, as assessed by conventional morphological criteria, this antibody distinguished malignant from non-malignant cells in 21 samples. The exceptions were 2 lymphomas and 2 out of 6 carcinomas of the lung. The Ca1 antibody also reacted with malignant mesothelial cells from 2 mesotheliomas, but not with reactive mesothelial cells. This antibody thus provides a new method for the identification of malignant cells in pericardial, peritoneal, and pleural effusions.

Antibodies, Neoplasm↗
PubMed1982

A new marker for human cancer cells. 1 The Ca antigen and the Ca1 antibody.

In a search for antibodies that might distinguish between malignant and non-malignant cells a panel of matched pairs of hybrid cells produced by fusion of diploid fibroblasts with malignant cells originating from a cervical carcinoma was used as a screen. Each pair consisted of a hybrid in which malignancy was suppressed and a malignant segregant derived from this hybrid. A monoclonal antibody, designated Ca1, was found that discriminated absolutely between the hybrids in which malignancy was suppressed and the malignant segregants. This antibody detected an antigen present in the cell membranes of a wide variety of malignant human cells lines but not of diploid human cell strains. The antigen was found in very low concentrations, if at all, in homogenates of normal adult or fetal tissues. It could be immunoprecipitated by the Ca1 antibody from extracts of malignant cells but not from extracts of non-malignant cells. After reduction, the immunoprecipitated antigen separated in sodium dodecyl sulphate acrylamide gels as two bands with proximate molecular masses of 390 000 and 350 000. These two components had a properties of glycoproteins with a high carbohydrate content; both bound the Ca1 antibody. The antigenic determinant resisted boiling at 100 degrees C and extraction by range of organic solvents. The binding of the Ca1 antibody to the antigen was substantially reduced by treatment of the antigen with neuraminidase, and the antigenic determinant was largely destroyed by certain endoglycosidases and by extensive proteolysis. Pending its further characterisation, this antigen had been called the Ca antigen.

Antibodies, Monoclonal↗
PubMed1982

A new marker for human cancer cells, 2 immunohistochemical detection of the Ca antigen in human tissues with the Ca1 antibody.

The Ca1 antibody has been used in an immunohistochemical procedure to detect the Ca antigen in sections of tissues routinely embedded in paraffin wax. A representative sample of benign and malignant tumours from all the systems of the human body has been examined. The majority of malignant tumors express the Ca antigen. The exceptions are: prostatic carcinomas, testicular teratocarcinomas and seminomas, some sarcomas, some lymphomas, malignant brain tumours, neuroblastomas, and melanomas. The antigen is least readily detected in epithelial malignancies of the alimentary system, particularly of the colon. The Ca1 antibody does not react with any benign tumour. The only normal tissues that react specificity with this antibody are the epithelium of the fallopian tube and the transitional epithelium of the urinary tract. The Ca1 antibody also readily distinguishes malignant cells in smears of malignant effusions. These findings indicate that the Ca1 antibody may be useful in the diagnosis of malignancy in routine clinical practice where the morphological interpretation of the biopsy or cytological smear is in doubt.

Antibodies, Monoclonal↗
PubMed1982

A monoclonal antibody that reacts with nonallelic enzyme glycoproteins.

One of six monoclonal antibodies raised against purified human placental alkaline phosphatase cross-reacts with the adult and fetal forms of intestinal alkaline phosphatase. The placental and intestinal enzymes are nonallelic. A new electrophoretic titration procedure was used to assess the relative reactivities of the different enzymes with the antibody. The placental enzyme was the most reactive. However, the adult intestinal enzyme showed greater reactivity than the fetal enzyme. The determinants to which the antibody binds on these three forms of alkaline phosphatase presumably differ in their detailed molecular configurations.

Alkaline Phosphatase↗