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Biomedical subjects

A J Pesce

Publications and source records attributed to A J Pesce.

At least 91 records · Page 5Linked to original sources

Immune complexes in transitional cell carcinoma.

Bladder cancer patients from 2 different medical centers were examined to establish whether such patients have circulating immune complexes. Four methods of analysis were used: 1) polyethylene glycol precipitation, 2) double crossed immunoelectrophoresis, 3) Raji cell and 4) Clq binding assays. In the first group of 24 patients 17 had positive results on cystoscopy for pathologically defined tumors at the time of the serum sample. Two tested positive for the presence of circulating immune complexes by all 4 techniques and an additional 1 tested positive by 3 of the 4 techniques. In the second group of 54 patients (41 of whom had pathologically definable tumors at sample date) 9 were judged possibly positive by the Raji cell assay, the polyethylene glycol and double crossed immunoelectrophoresis techniques. When tested by the Clq binding assay 8 of the 9 patients were positive, most being in the range of 260 to 320 microgram/ml. immune complex. Combining all data from the 78 patients with bladder cancer the results in 10 cases definitely were positive by all 4 techniques and an additional 2 were positive by 3 techniques. Our data indicate that a low percentage (13 to 15 per cent) of patients with bladder cancer has circulating immune complexes. Of interest is that the complexes, as judged by our assay procedures, bind Clq, contain aggregated IgG and can be dissociated into antigen and antibody. Thus, the immune complexes are similar to those found in immune complex diseases.

Aged

Occupational exposure to lead: effects on renal function.

Although nephrotoxicity is common following exposure to lead, the dose-response relationship in adults with occupational exposure is not well understood because information is lacking on early nephrotoxic effects. By the time serum urea nitrogen and creatinine levels are elevated, renal damage may be advanced and not fully reversible. Detailed investigations of renal glomerular and tubular function were performed in six adults with occupational exposure to lead. In all patients, the serum creatinine and urea nitrogen concentrations were within the normal range. GFR was decreased in all but two. Glucose reabsorptive capacity (TmG) was decreased in all, and this decrease was disproportionately greater than expected from the reduced GFR in all but one. Normal values for renal plasma flow (RFP) were observed in four of the six, and for rho-aminohippurate (PAH) secretory capacity (TmPAh) in all but one. Bicarbonate reabsorptive capacity (TmHCO3) and urinary excretion of beta2-microglobulin were normal in all. Routine clinical laboratory tests are insensitive for the detection of early renal effects of heavy metal exposure. Measurements of renal tubular reabsorptive capacity for glucose appears to be a sensitive method for the early detection of renal effect of lead.

Adult

ELISA assay for measurement of human hemoglobin A and hemoglobin F.

An enzyme-linked immunosorbent assay (ELISA) for the measurement of nanogram quantities of hemoglobin A and hemoglobin F is described. The assay employs hemoglobin bound to polystyrene test tubes. The antigen is quantitated by the addition of rabbit antibody specific for the hemoglobin type, followed by a second antibody of goat antirabbit gamma globulin coupled to alkaline phosphatase. Quantitation of the reaction is achieved by incubating the coated tubes with p-nitrophenyl phosphate. The binding characteristics, the linearity, the ability of the assay to discriminate between hemoglobin A and hemoglobin F, the ability to discriminate between native and denatured gamma globin, and the comparison of this assay with a previously described immunoradiometric (IRMA) assay are discussed.

Adult

beta 2-microglobulin in human tumors heterografted into athymic mice.

Beta 2-microglobulin (beta 2m) content of several human tumor lines implanted into athymic mice was investigated. The concentration of this protein was found to vary greatly from tumor to tumor. The growth rate of the tumors was inversely related to the amount of the extractable beta 2m. The fastest growing, undifferentiated tumors contained the least amount of beta 2m.

Animals

Release of beta 2-microglobulin by human tumors grown in nude mice.

Human tumors implanted subcutaneously into athymic mice produced human beta 2-microglobulin which was readily identified and quantified in mouse plasma. Implanted solid tumors of the lines Clouser, SW480, Hep-2, Capan-1, and HT-29 released amounts of beta 2-microglobulin directly related to tumor mass. The extractable beta 2-microglobulin per gram of tumor was constant for each cell line, but there was a 100-fold variation between the lines. In general, the plasma level of beta 2-microglobulin correlated with the amount of free beta 2-microglobulin extracted from each tumor. From these observations it can be concluded that the variablility observed in the circulating levels of beta 2-microglobulin among cancer patients is related to the beta 2-microglobulin content of the tumor and the total tumor mass.

Animals

The relationship of biological indices of lead exposure to the health status of workers in a secondary lead smelter.

The fidelity with which common indices of lead exposure correlate with renal and hematopoietic function and with frequency of symptoms was studied. The subjects were men working in a secondary lead smelter. Among several indices of renal function, only serum urea nitrogen (SUN) was consistently correlated with any of the indices of lead exposure. The concentration of lead in blood(PbB), the rate of urinary excretion of lead (PbU) and of alpha aminolevulinic acid in the urine (ALAU) correlated with SUN. By contrast, erythrocytic porphyrin concentration (EP) did not correlate with SUN. Similarly, the frequency of occurrence of symptoms correlated well with PbB and ALAU but did not correlate with EP. All of the above indices of lead exposure, with the exception of PbU, correlated well with hemoglobin (Hb) status. In summary, these results suggest that PbB rather than EP is the best single exposure index for biological monitoring of lead workers. This measurement should be supplemented by peiodic determination of SUN and Hb.

Adult

Influence of the mouse hepatitis virus (MHV) infection on the growth of human tumors in the athymic mouse.

The growth characteristics and histological appearance of tumors resulting from transplantation of the tumor lines HEp-2 and SW480 into pathogen-free and mouse hepatitis virus infected athymic mice were studied. Subcutaneous or intraperitoneal implantation 1 x 10(6) neoplastic cells into pathogen-free animals resulted in tumor growth. Subcutaneous transplants grew locally, surrounded by a capsule of connective tissue. The fibrovascular stroma supporting the neoplastic tissue was minimal and infiltration of tumor capsule was observed. Intraperitoneal tumors grew in a multifocal pattern, were not encapsulated, showed marked invasiveness and metastasized. The same number of neoplastic cells (1 x 10(6)) transplanted into hepatitis-positive animals failed to develop into grossly visible tumors. When the number of transplanted cells was increased to 2 x 10(7), tumors appeared in a few animals. All tumors, regardless of the site of transplantation, were characterized by the presence of severe fibrohistiocytic reaction at the site of implantation that possibily influenced the tumor growth. No evidence supporting T-cell-mediated tumor rejection was observed. It is concluded that the state of health of the athymic mice is critical for the growth of human tumors and may account for the variations in reporting successful transplantation of such tumors in nude mice.

Animals

Nephrotoxicity of Bence Jones proteins in the rat: importance of protein isoelectric point.

Bence Jones proteins (BJP) were isolated from the urine of 12 patients with multiple myeloma and various degrees of renal dysfunction. Proteins were characterized as to type (six type lambda and five type kappa), isoelectric point (pI), and secondary structure by circular dichroism (CD). Clinical renal function was more impaired with type-lambda proteins and with proteins of pI greater than 5.7. CD studies distinguished kappa from lambda proteins in most cases but did not correlate with nephrotoxicity. Protein dimer preparations were tested for nephrotoxicity in aciduric, hydropenic, female, Sprague Dawley rats by following renal function and morphology over 6 hours after injection i.p. of 300 mg of protein. Twelve rats of urine pH less than 5.5 injected with four BJP of pI less than 5.7 showed a mean rise in SUN of 5.3 mg/dl and in creatinine of 0.06 mg/dl, compared with a mean rise of 28.0 mg/dl (SUN) and 0.75 mg/dl (creatinine) in 21 rats injected with seven BJP of pI greater than 5.7 (P less than 0.01). Seven sodium-bicarbonate-fed rats of urine pH greater than 8 injected with a BJP of pI 6.2 showed mean rise in SUN of 1.8 mg/dl and in creatinine of 0.01 mg/dl, compared with 19.3 mg/dl (SUN) and 0.55 mg/dl (creatinine) in 7 aciduric rats injected with the same BJP (P = 0.009). Morphologic and immunohistologic studies showed distal cast formation in 9 rats with acute deterioration in renal function. It is concluded that BJP of pI greater than urine pH are acutely nephrotoxic in the rat by a mechanism that may involve a charge interaction in the distal nephron.

Animals

Monitoring the therapy of human tumor xenografts in nude mice by the use of lactate dehydrogenase.

With the use of circulating human lactate dehydrogenase (LDH) as a tumor marker, growth and remission of human tumor lines SW480, HEp-2, and Clouser, implanted into female BALB/c athymic nude mice, were followed during therapy. Three types of therapy were used: X-radiation, cyclophosphamide, and diphtheria toxin. After therapy tumor sizes were measured with calipers and compared to changes in the levels of circulating human LDH. Changes in LDH levels paralleled changes in tumor size, but the enzyme fluctuations were more pronounced. Mice bearing intraperitoneally growing SW480 and HEp-2 tumors were effectively treated with diphtheria toxin, and the measurement of circulating LDH was examined as a parameter for gauging the effectiveness of chemotherapy on tumors that could not be visualized. Circulating human LDH can be used to detect intraperitoneal tumor growth and/or remission and to predict death of the animal due to the tumor.

Animals

Nephrotoxicity of low molecular weight serum proteins: physicochemical interactions between myoglobin, hemoglobin, bence-jones proteins and tamm-horsfall mucoprotein.

Three types of low molecular weight serum proteins, myoglobin, hemoglobin and BENCE-JONES proteins, are associated clinically with acute renal failure. All have isoelectric points which render them anionic at blood pH but cationic in the distal nephron under conditions of aciduria. Experiments in which these proteins were mixed with TAMM-HORSFALL mucoprotein in vitro and the pH lowered with lN HCl showed co-precipitation of proteins at pH levels of 5.5 and below. In vivo experiments in which 11 different BENCE-JONES proteins of pl ranging from 5.2 to 6.6 were injected into aciduric, hydropenic rats showed an acute rise in serum urea nitrogen and creatinine concentrations with BENCE-JONES proteins of pl greater than 5.7 compared with little change in rats injected with BENCE-JONES proteins of pl less than 5.7. These data suggest that protein pl and urine pH are important in determining nephrotoxicity; a mechanism by which these low molecular weight serum proteins and TAMM-HORSFALL proteins interact in the distal nephron to initiate acute renal failure in postulated.

Acute Kidney Injury

Immunological properties of peptic fragments of bovine serum albumin.

The effect of peptic degradation on the immunological and antigenic properties of bovine serum albumin (BSA) was investigated. Molecular fragments obtained after various times of digestion (3-360 min) were studied. Enzymatic digestion resulted in a rapid loss of serologically defined antigenic determinants. The immunogenicity of the fragments as measured by the level of reaginic and total anti-BSA antibody response in BDF1 mice was also diminished. Pre-treatment of mice with fragments exhibiting a low density of B-cell interacting determinants before immunization with BSA, resulted in significant suppression of both the primary and secondary antibody response. The most effective immunosuppressive fragments were obtained following removal of peptides which bound to anti-BSA antibodies. The suppression was shown to be antigen specific. It was concluded that separate determinants on the BSA molecule were responsible for the immunogenic and suppressive properties of the antigen.

Animals

Albumin excretion by the kidney: the effects of osmotic diuresis.

Urine albumin excretion rate in female Sprague-Dawley rats was measured duing a stable period of normal hydration and following mannitol-induced osmotic diuresis. Mannitol infusion resulted in a significant increase in urine volume and fractional excretion of sodium, but glomerular filtration rate, albumin excretion rate, and the sieving coefficient for albumin remained stable. The results suggest that under physiological conditions, changes in albumin excretion are dependent upon changes in glomerular filtration rather than urine flow.

Albuminuria

Growth patterns and metastatic behavior of human tumors growing in athymic mice.

The growth characteristics and metastatic behavior of human tumors growing in athymic nude mice were studied. Human tumor cell lines HEp-2 (carcinoma or larynx) and SW480 (colon carcinoma) were transplanted into athymic nude mice of BALB/c origin. Tumor cells (1 x 10(6) and 2 x 10(7)) were given either s.c. or i.p. Following s.c. injection tumors developed rapidly to become easily palpable with 2 weeks forming a s.c. tumor focus surrounded by a thick fibrous capsule. Animals with s.c. transplants were little affected by the growing tumor. At the time they were sacrificed at Day 34 (HEp-2) and 62 (SW480), a large part of the tumor was necrotic. Capsular infiltration and invasion of lymphatic vessels and perineural and perivascular lymphatic spaces were observed. Metastases to regional lymph nodes were seen in animals kept alive for up to 6 months. Following i.p. transplantation, tumors spread widely in the peritoneal cavity, invaded intraabdominal organs, and metastasized to mediastinal lymph nodes and lungs. Fifteen of 26 animals (60%) developed metastases. Necrosis of the i.p. growing tumors was minimal. All animals in this group died as a result of tumor growth.

Animals