Biomedical subjects

G L Wright

Publications and source records attributed to G L Wright.

At least 127 records · Page 7Linked to original sources

PubMed1986

Effect of reduced food intake on blood levels of a hypertensive factor in spontaneously hypertensive rats.

We have previously demonstrated the existence of an active component(s) of extracts prepared from rat erythrocytes that stimulates the in vitro uptake of calcium in aortic rings and induces a sustained elevation in the blood pressure of normotensive rats. The apparent concentration of the calcium stimulatory component and the responsiveness of aortic rings to stimulation of calcium uptake by the compound is exaggerated in adult spontaneously hypertensive rats (SHR) compared with normotensive controls. Although no effect was observed on tissue responsiveness to the compound, a decrease in the concentration of the compound was observed in the blood of adult SHR subjected to dietary manipulation designed to blunt the elevation of blood pressure. These data suggest that blood concentration of the active compound may be influenced by external stimuli such as dietary manipulation.

Animals↗

PubMed1985

Monoclonal antibody (anti-Leu 7) directed against natural killer cells reacts with normal, benign and malignant prostate tissues.

The reactivity of monoclonal antibody (MAb) anti-leu 7 (HNK-1) on formalin-fixed sections of prostate tissues was determined by an immunoperoxidase assay. Anti-Leu 7 was found to react with both primary and metastatic tissues from 6/6 normal prostate, 15/15 benign prostatic hyperplasia, and 37/39 prostate carcinoma samples. Anti-Leu-7 reactivity was localized in the cytoplasm of the supranuclear region of prostatic epithelial cells and the fibromuscular stroma did not stain. Myelinated nerve fibers in the stroma were stained with anti-Leu 7 and this served as an internal control. Anti-Leu 7 did not bind to prostatic acid phosphatase (PAP) or prostate-specific antigen (PSA) in direct or competitive binding radioimmunoassays. Anti-Leu 7 was more effective (5/5) in the identification of metastatic tumors of prostate origin than an MAb to PSA (2/5). The differential pattern of reactivity of anti-Leu 7 compared to anti-PSA on serial sections of prostate tissues suggests that Leu 7 may be a useful diagnostic and prognostic marker of prostate cancer.

Acid Phosphatase↗

PubMed1985

Antiprostate carcinoma monoclonal antibody (D83.21) cross reacts with a membrane antigen expressed on cytomegalovirus-transformed human fibroblasts.

Virological and epidemiological studies have implicated human cytomegalovirus (HCMV) as a possible etiological agent of prostate cancer. Because of the suspected associations, this laboratory tested the reactivity of a prostate-associated monoclonal antibody with HCMV-transformed cells. This mouse monoclonal antibody, D83.21, reacts with a membrane antigen on prostate and bladder tumor cells and does not bind to a variety of other malignant or normal cells. The results of this study indicated that the prostate-associated antibody bound to a membrane antigen on HCMV-transformed cells as detected by radioimmunoassay, immunofluorescence, and complemented-dependent cytotoxicity. This cross-reactivity appeared to be specific for HCMV-transformed cells and did not react with HCMV-infected cells or those transformed by other viruses. Antibody affinity chromatography, used to isolate the D83.21-reactive protein, revealed two peptides of 60 and 28 kd on both prostate tumor and HCMV-transformed cells. The results suggest that D83.21 reacts with a common cell surface protein expressed on HCMV-transformed cells and urogenital tumors.

Animals↗

PubMed1985

Cancer serum index and prostatic acid phosphatase for detection of progressive prostatic cancer.

The ratio of alpha 1 acid glycoprotein/prealbumin, referred to as a cancer serum index, has been proposed as a marker for neoplastic disease. In a series of 130 patients with prostate cancer, the cancer serum index was measured along with serum prostatic acid phosphatase. A significant difference for both the cancer serum index and serum prostatic acid phosphatase was detected between those patients with no evidence of active disease after treatment and those with progressive disease after treatment.

Acid Phosphatase↗

PubMed1985

Partial purification of a hypertensive substance from rat erythrocytes.

A crude extract prepared from rat erythrocytes was previously shown to contain an active component (hypertensive factor, HF) that stimulates the in vitro uptake of calcium by aortic rings and causes a sustained and severe elevation in systolic blood pressure in normotensive rats. The present report demonstrates that the in vitro effects of HF on calcium uptake are concentration dependent and reversible, and that these effects on calcium uptake provide a convenient bioassay for monitoring the purification of HF. HF was prepared from a diffusate obtained by dialyzing hemolyzed rat erythrocytes. The diffusate was applied successively to molecular sieve and anion exchange columns resulting in a 1500-fold increase in specific activity relative to the starting hemolysate. The compound stimulating calcium uptake was found to be heat stable and resistant to digestion with trypsin and chymotrypsin. In contrast, treatment with pronase E, a nonspecific protease, markedly increased the calcium transport stimulatory activity. The administration of the purified preparation to normotensive rats having a systolic blood pressure of 118 +/- 2 Torr (1 Torr = 133.322 Pa) resulted in a significant elevation of blood pressure (171 +/- 11 Torr) by day 5. The severity of this increase further suggests that there is a marked enhancement in potency relative to earlier fractions that were examined. Perhaps most importantly, these results indicate that, at this stage of purification, the pressor component and the calcium-stimulatory component of HF appear to co-purify.

Animals↗

PubMed1985

An antihypertensive substance associated with erythrocytes.

An extract was prepared from hemolyzed erythrocytes of spontaneously hypertensive rats (SHR) which inhibits lanthanum-resistant calcium uptake by aortic segments and lowers blood pressure in several models of hypertension. Erythrocyte hemolysates were extracted with Triton X-100 and partially purified by boiling and Sephadex G-150 column chromatography. The effects of the extract on calcium uptake by aortic segments in vitro were reversible and dose dependent. The extract was administered by intraperitoneal injection to male and female SHR, deoxycorticosterone-NaCl hypertensive rats (DOCA-NaCl), one-kidney one-clip (1K,1C) and two-kidney, one-clip (2K,1C) renovascular hypertensive rats, and their appropriate control groups. At 24 h postinjection, the antihypertensive factor (AHF) lowered the systolic blood pressure (SBP) in the conscious SHR male (200 +/- 7 to 132 +/- 11 Torr), SHR female (172 +/- 4 to 117 +/- 11), DOCA-NaCl (187 +/- 6 to 121 +/- 8), 2K,1C (165 +/- 8 to 127 +/- 7), and 1K,1C (167 +/- 8 to 146 +/- 13) models of hypertension. The duration of the effect on the SBP was model dependent. The SBP was significantly decreased for 4-8 days in SHR, 4 days in 1K,1C and 2K,1C, and 2 days in DOCA-NaCl. In contrast to the results obtained in hypertensive rats, AHF had little effect on the SBP of normotensive animals. Both the blood pressure and calcium effects were abolished by digestion with phospholipase D, tentatively suggesting that the compound(s) inducing these effects may be a phospholipid or have a phospholipid moiety.

Animals↗

PubMed1985

Benign parotid diseases of childhood.

A 25-year retrospective study of 63 pediatric surgical cases of benign parotid disease was done. Inflammatory disorders accounted for 34 of the cases. The remaining 29 non-inflammatory conditions included vasoformative, solid, and cystic lesions and were nearly always asymptomatic.

Abscess↗

PubMed1985

Disulfide bonding of a human prostate tumor-associated membrane antigen recognized by monoclonal antibody D83.21.

Previous reports from our laboratory have described the binding specificity of a monoclonal antibody, D83.21, prepared by fusing P3X63/Ag8 mouse myeloma cells with mouse lymphocytes immunized against the DU145 human prostate adenocarcinoma cell line. The D83.21 monoclonal antibody displayed preferential binding to human prostate and bladder carcinoma cell lines and tissues. This antibody was not reactive with a variety of other normal and malignant human cell lines or tissues. Immunofluorescence analysis indicated that the D83.21 antigen was located on the plasma membrane. Biochemical characterization of the target antigen was performed by subjecting detergent-soluble extracts of [3H]glucosamine-labeled cells to D83.21 monoclonal antibody affinity chromatography. The radioactive material that was specifically bound and eluted from the affinity column was analyzed by sodium dodecyl sulfate:polyacrylamide gel electrophoresis and fluorography. In the absence of 2-mercaptoethanol, the antigen displayed two prominent bands with molecular weights of 180 and 110 kilodaltons. In the reduced form, the antigen is composed of an Mr 60,000 heavy chain and an Mr 28,000 light chain. The antigen was further resolved using two-dimensional (intact/reduced) sodium dodecyl sulfate: polyacrylamide gel electrophoresis. These analyses indicated that the Mr 180,000 chain was composed entirely of Mr 60,000 subunits, whereas the Mr 110,000 band consisted only of Mr 28,000 subunits. The antigen recognized by the D83.21 monoclonal antibody is therefore a membrane glycoprotein with a subunit structure cross-linked together through disulfide bonds.

Antigens, Neoplasm↗

PubMed1984

A hypertensive substance found in the blood of spontaneously hypertensive rats.

A substance has been obtained from the blood of spontaneously hypertensive rats which produces a hypertensive elevation of the blood pressure in normotensive rats. The substance is dialyzable and is associated with the erythrocyte membrane. It appears to be relatively long-lived in its effect on arterial pressure. The erythrocyte fractions that exhibit pressor activity also stimulate the in vitro uptake of calcium by aortas obtained from normotensive animals. This suggests that the hypertensive factor or related substances may influence the calcium metabolism of vascular tissue.

Animals↗

PubMed1983

Immunohistochemical localization of prostate carcinoma-associated antigens.

The immunoperoxidase technique was used to study the localization and distribution of antigens reactive with two monoclonal antibodies, D83.21 and P6.2, produced against cultured prostate tumor cells, in formalin-fixed, paraffin-embedded histological sections of human tissues. Monoclonal D83.21 reacted with 11 of 19 (58%) primary prostate carcinomas and 1 of 6 (17%) metastatic tumors, whereas monoclonal P6.2 reacted with 14 of 19 (68%) primary and 4 of 6 (67%) metastatic prostate tumors. Neither antibody reacted with five primary prostate tumors and one metastatic prostate tumor. In some tumor cells, the antigens recognized by these monoclonals were localized in either the cytoplasm or cell membrane, while in other tumor cells, both diffuse cytoplasmic and membrane or focal staining patterns were observed. In addition to the variable staining patterns, antigenic heterogeneity was also noted within most prostate tumors examined. Two types of staining variability were observed: (a) tumor cells in one area of the tissue section stained positive, but in another area they did not react with the antibody; and (b) both stained and unstained tumor cells were adjacent to each other. These results would suggest that a panel of monoclonals will be required to detect the different subpopulations of prostate tumor cells. Neither antibody reacted with 6 normal or 12 benign prostate tissues, nor any of a variety of other normal human tissues except for staining of the proximal tubules of normal kidneys. The antigen detected by P6.2 demonstrated a wider tissue distribution being found on bladder, breast, lung, and pancreatic tumors, whereas the antigen recognized by D83.21 was restricted to prostate and bladder carcinomas. These antibodies may have clinical applicability for the identification of prostate tumor cells in biopsy specimens and for immunohistopathological classification of prostate carcinomas.

Adenocarcinoma↗

PubMed1982

Radioimmunoassay versus counterimmune electrophoresis for measurement of serum prostatic acid phosphatase.

Radioimmunoassay (RIA) kits obtained from commercial sources were evaluated and compared with a standard counterimmunoelectrophoretic (CIE) assay for the measurement of prostatic acid phosphatase (PAP) in serum. None of the radioimmunoassays was found to be more sensitive than the CIE assay in detecting elevated serum PAP. Both immunoassays were somewhat more effective clinically in measuring prostatic specific acid phosphatase than an enzyme colorimetric assay. The results obtained by CIE agreed with the results obtained by RIA in 96 per cent of the tests. The number of positive results in patients with confirmed prostate adenocarcinoma increased with disease progression. The low number of positive tests in localized adenocarcinoma (Stages A and B) suggests that neither the CIE nor any RIA procedure is useful for screening unselected populations for adenocarcinoma of the prostate.

Acid Phosphatase↗

PubMed1982

Mechanisms of calcification in Peyronie's disease.

Scanning and transmission electron micrographs demonstrate a calcification process in the penile plaques of patients with Peyronie's disease. Osteoid formation originates from vascular lumina via osteoblast-like cells, which align the calcified plaque. These cells are surrounded gradually by calcified connective tissue. Collagen fibers demonstrate calcification and decreased periodicity.

Calcinosis↗

PubMed1982

Bone marrow and acid phosphatase by counterimmune electrophoresis: pre-treatment and post-treatment correlations.

The value of bone marrow acid phosphatase in the staging of prostatic cancer has been a controversial issue. A number of investigators have concluded that the enzymatic determinations of bone marrow acid phosphatase are inaccurate because of lack of specificity. The introduction of the immune methods for measuring acid phosphatase has revived interest in the role of immune bone marrow acid phosphatase in pre-treatment staging. Fifty-five patients underwent determination of simultaneous immune bone marrow and serum acid phosphatase before any treatment. While positive values did predict a risk for initial and subsequent metastasis they could not be used to dictate against definitive therapy. Positive bone marrow values were paralleled by positive serum values and provided no additional staging information.

Acid Phosphatase↗

PubMed1982

Cell culture of Peyronie's disease plaque and normal penile tissue.

Cell cultures derived from Peyronie's disease plaque and normal penile tissue were characterized morphologically and examined by immunofluorescence for actin cable formation, and their growth properties were compared. Relative to normal penile cell cultures which grew as contact inhibited, poorly refractile fibroblast-like cells, plaque derived cell cultures consisted of round and spindle shaped cells that were more refractile and exhibited random crisscross growth patterns. Scanning electron microscopy of plaque derived cell cultures revealed changes in cell surface topography characterized by the appearance of surface membrane blebs amd microvilli. Transmission electron microscopy demonstrated cells containing organized cytoplasmic microfilament bundles and nuclear indentations which resembled myofibroblasts. Such alterations were less extensive or absent in normal penile cell cultures. The amount and extent of actin cable formation was increased in plaque derived compared to normal penile cell cultures. Plaque derived cells also exhibited differences in growth properties and grew to higher saturation densities than their normal counterparts. These results demonstrate that cells derived from Peyronie's disease plaque can be grown in vitro and that these cells are morphologically altered and have an enhanced proliferative capacity. The availability of these cell cultures will permit studies directed at understanding the etiology and pathogenesis of Peyronie's disease.

Actins↗

PubMed1982

Isolation and partial characterization of the most immunologically reactive antigen from Mycobacterium tuberculosis H37Ra culture filtrate.

The culture filtrate of Mycobacterium tuberculosis H37Ra was fractionated by ammonium sulphate precipitation, diethyl aminoethyl (DEAE) cellulose-Sephadex A-50 column chromatography, preparative isoelectric focusing and polyacrylamide gel electrophoresis to isolate the most antigenic tuberculoprotein. One protein, designated P2, was isolated and determined by immunodiffusion to be the most immunologically reactive antigen present in H37Ra culture filtrate. This protein had a molecular weight of about 22 000, a sedimentation constant of 2.2S and was present in Seibert's A, B, and C proteins.

Antigens, Bacterial↗

PubMed1982

A hypertensive substance in erythrocytes of spontaneously hypertensive rats.

The effect of the subcutaneous injection of plasma or erythrocytes on the blood pressure of Sprague-Dawley (S-D), Wistar-Kyoto (WKy), and spontaneously hypertensive (SH) rats was examined over a 3-week period. The injection of plasma produced no detectable alteration in blood pressure in either the normotensive or hypertensive strains. The injection of red cells from WKy rats had no effect on the blood pressure of S-D rats, whereas a moderate (20%) elevation was noted in WKy and SH rats which received erythrocytes from S-D and WKy rats, respectively. The injection of red cells from SH rats produced no effect on S-D rats, a moderate (20%) elevation of the blood pressure of WKy rats, and a marked (42%) increase in the blood pressure of SH rats. Despite the lack of effect of erythrocytes on the resting blood pressure of S-D rats, it was found that these animals exhibit a transient increase in the blood pressure response to norepinephrine (NE) following a single injection of SH red cells. The results suggest the presence of a substance in SH erythrocytes which enhances the pressor response to NE and produces an elevation of resting blood pressure. This substance also appears to occur to some extent in the red cells of S-D and WKy animals; the manifestation of its action on blood pressure elevation is determined to a significant degree by the intrinsic resistance or susceptibility of the animal.

Animals↗

PubMed1982

Concentrations of ionic and total calcium in plasma of four models of hypertension.

The levels of ionic calcium in whole blood obtained from female Sprague-Dawley (SDR). Wistar-Kyoto (WKY), and spontaneously hypertensive (SHR) rate tended to decrease between 5 and 13 wk of age. During this interval the plasma total calcium levels of each strain remained stable, indicating an increase in the binding or complexing of endogenous calcium with maturation. The ionic calcium levels of WKY were lower than those of SDR, while SHR levels were below those of the WKY and SDR strains. Neither the one-kidney, one-clip (1KHT) nor the two-kidney one-clip (2KHT) renovascular models of hypertension showed evidence of an alteration in blood ionic or total calcium concentrations compared with sham-operated controls. The ionic calcium levels of blood from deoxycorticosterone-treated (DOCA/saline) hypertensive rats were significantly reduced from those of sham-operated controls but were similar to values recorded for normotensive uninephrectomized controls. Each of the four models of hypertension studied and the normotensive uninephrectomized control group demonstrated some degree of reduction in the in vitro binding or complexing of exogenous calcium. The results indicate that the spontaneous, renovascular, and mineralocorticoid forms of hypertension examined were accompanied by some disturbance in extracellular calcium homeostasis. It is unlikely, however, that the alterations observed are primary causal factors in the maintenance of high blood pressure.

Animals↗

PubMed1982

Monoclonal antibodies to human prostate and bladder tumor-associated antigens.

Monoclonal antibodies to human prostate adenocarcinoma membrane antigens were produced by fusion of P3X63/Ag8 mouse myeloma cells with spleen cells from BALB/c mice immunized against the prostate cancer cell line DU145. The hybrids were screened for antibody production using glutaraldehyde-fixed cells in a solid-phase radioimmunoassay. Antibody-binding specificity was also checked by quantitative adsorption, membrane immunofluorescence, and complement-dependent cytotoxicity assays. A hybridoma clone (83.21) was isolated that secreted antibodies which preferentially bound to several prostate and bladder cancer cell lines but did not bind to a variety of other normal and malignant human cell lines. This antibody also reacted with a cytomegalovirus-transformed human embryonic lung cell line but not to normal human embryonic lung cells. Quantitative adsorption studies demonstrated that the 83.21 monoclonal antibody was strongly reactive to membrane preparations from human prostate adenocarcinoma tissue and a liver metastasis of prostate carcinoma. Little or no binding activity was observed against two other prostate carcinomas, bening prostatic hyperplasia, normal prostate, or normal liver. Binding studies indicate that the 83.21 monoclonal antibody does not bind to alpha-fetoprotein, carcinoembryonic antigen, prostatic acid phosphatase, human leukocyte antigen, beta 2-microglobulin, HLA-Dr antigens, fibronectin, or prostate antigen. The data indicate that we have isolated a monoclonal antibody that binds to an antigen(s) expressed by several urogenital carcinoma cell lines as well as human prostate tumor tissue and that the antibody is not directed against well-known human tumor cell markers.

Animals↗