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Biomedical subjects

A Goldenberg

Publications and source records attributed to A Goldenberg.

At least 37 records · Page 2Linked to original sources

The effect of ERCP on circulating pancreatic enzymes and pancreatic protease inhibitors.

The pathogenesis of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis is poorly understood. To elucidate a role for pancreatic enzymes in ERCP-induced pancreatitis, we measured serum amylase, lipase, trypsin, and elastase in 25 patients undergoing ERCP. Serum alpha 1-antitrypsin and alpha 2-macroglobulin, two major pancreatic protease inhibitors, also were measured. All pancreatic enzymes measured rose significantly after ERCP. Pancreatic duct cannulation was associated with a greater elevation in serum amylase and lipase. Circulating alpha 2-macroglobulin was reduced by 7% (p = 0.04) 6 h after ERCP, whereas circulating alpha 1-antitrypsin increased over the same time period. Papillotomy, stent placement, or underlying disease did not influence changes any further. Three patients developed ERCP-induced pancreatitis. All three patients had circulating alpha 2-macroglobulin levels below 243 mg/dl (p = 0.03). The ERCP-induced alterations in circulating pancreatic enzymes and their inhibitors are similar to changes seen in clinical pancreatitis. Low circulating alpha 2-macroglobulin levels may predispose to ERCP-induced pancreatitis.

Acute Disease↗

Imaging of human tumor xenografts with an indium-111-labeled anti-epidermal growth factor receptor monoclonal antibody.

The mouse monoclonal antibody (mAb) 225 IgG1 against the epidermal growth factor (EGF) receptor has been investigated for its capacity to localize in human tumor xenografts. The EGF receptor is the product of the c-erb-B proto-oncogene (also known as EGFR). Elevated expression of EGF receptors has been demonstrated in many human tumors and tumor cell lines. We studied A431 human vulvar squamous cell carcinoma cells, with 2 X 10(6) receptors per cell; MDA-MB-468 (MDA 468) human breast adenocarcinoma cells, with 3 X 10(5) receptors per cell; and MCF-7 human breast adenocarcinoma cells, with 5 X 10(3) receptors per cell. The 111In-labeled pentetic acid (DTPA), derivative of mAb 225 (111In-DTPA-225) was injected intraperitoneally into nude mice bearing subcutaneous tumor xenografts. We measured uptake by quantifying radioactivity in tumor and normal tissues and by obtaining gamma camera images. Uptake in A431 xenografts was 28% +/- 2.4% of the injected dose per gram of tumor on day 3 and 12.4% +/- 3.0% on day 7. Distribution ratios comparing uptake in the tumor with that in normal tissues were consistently greater than 4. In contrast, there was far less uptake of the control mAb KS1/4S-1 labeled with 111In. This conjugate, 111In-DTPA-KS1/4S-1, has an IgG1 isotype but does not bind to human or murine cells. Imaging of the tumor with mAb 225 was excellent, especially on days 3-7. MDA 468 xenografts exhibited reduced localization of mAb 225 in the tumor. For MCF-7 xenografts, the tumor uptake of mAb 225 after 7 days was only 0.70% +/- 0.10% of the injected dose per gram of tumor, which was comparable to the uptake of the KS1/4S-1 control mAb. The ratio of the concentration of radioactivity in the tumor to that in normal tissue (distribution ratio) showed poor selectivity of uptake, and imaging was not obtained. These observations suggest that labeled mAb can target the product of a proto-oncogene, the EGF receptor, when it is expressed at high levels in human tumor xenografts.

Animals↗

Anti-epidermal growth factor receptor antibodies inhibit the autocrine-stimulated growth of MDA-468 human breast cancer cells.

The response of malignant and nonmalignant human breast cell lines to the growth inhibitory effects of monoclonal antibodies against the epidermal growth factor (EGF) receptor was studied. A series of human breast cell lines, which express EGF receptor, were used: MDA-468, MDA-231, and Hs578T human breast cancer cells and the transformed human mammary epithelial cell lines 184A1N4 and 184A1N4-T that have been benzo[a]pyrene immortalized and further transformed with SV40T, respectively. Four antibodies of two different classes were tested: 225 immunoglobulin G (IgG), 108.4 IgG, 96 immunoglobulin M (IgM), and 42 IgM. All four antibodies inhibited the anchorage-dependent and -independent, EGF-stimulated growth of 184A1N4 and 184A1N4-T cells, respectively, and this growth inhibition could be reversed by the addition of increasing concentrations of EGF. In contrast, the antibodies inhibited the anchorage-dependent and -independent growth of MDA-468 cells in the absence of exogenous EGF suggesting that the antibodies were acting to block access of an endogenously produced ligand to the EGF receptor. In the presence of antibody and increasing concentrations of EGF, MDA-468 cell growth was first stimulated then inhibited as the EGF concentration increased, thus, uncovering the growth stimulatory potential of low concentrations of EGF in these cells. Data is presented that indicates MDA-468 cells secrete a transforming growth factor with autocrine growth stimulatory capabilities. The growth of MDA-231 and Hs578T cells, which contain activated ras oncogenes, was not inhibited by the antibodies and the growth of these cell lines was not stimulated by EGF. Of the cell lines studied only MDA-468 cells appear to possess an autocrine growth stimulatory capacity.

Antibodies, Monoclonal↗

Phase II trial of mitoxantrone in advanced gastric cancer.

A Phase II trial of mitoxantrone was performed in patients with advanced adenocarcinoma of the stomach. All patients had measurable or evaluable disease, and none had received prior chemotherapy. Mitoxantrone was administered intravenously at a dose of 14 mg/m2 every 3 weeks. The major toxicity seen was myelosuppression. The drug was, in general, well tolerated. No major objective responses were seen. We conclude that mitoxantrone has less than 20% activity in this patient population. No further studies are planned.

Adult↗

Anti-epidermal growth factor receptor monoclonal antibodies may inhibit A431 tumor cell proliferation by blocking an autocrine pathway.

Monoclonal antibodies which bind to the EGF receptor have the capacity to inhibit EGF-induced effects upon proliferation and biochemical functions in cultured human cells. Some EGF receptor-bearing tumor cells are prevented from growth by treatment with antireceptor antibody. Evidence is presented which suggests that antibody-mediated antiproliferative activity may result from effects upon growth factor-dependent processes in the receptor-bearing cells.

Antibodies, Monoclonal↗

CO2 laser and suture in splenic parenchyma: an experimental study.

Hemisplenectomy was performed with the scalpel in 12 mongrel dogs. The blood vessels of the splenic pedicle were temporarily clamped. In a six-dog group, hemostasis was obtained by CO2 laser and residual bleeding was controlled by sutures. In the other six dogs, group hemostasis was performed only by sutures. The surgical procedure was free of mortality. No hematological changes were observed in both groups. Histological studies revealed a better hemostatic effect and intensive necrosis of the splenic parenchyma in the lasered group compared with the sutured group.

Animals↗

Membrane Development in the Cyanobacterium, Anacystis nidulans, during Recovery from Iron Starvation.

Deprivation of iron from the growth medium results in physiological as well as structural changes in the unicellular cyanobacterium Anacystis nidulans R2. Important among these changes are alterations in the composition and function of the photosynthetic membranes. Room-temperature absorption spectra of iron-starved cyanobacterial cells show a chlorophyll absorption peak at 672 nanometers, 7 nanometers blue-shifted from its normal position at 679 nanometers. Iron-starved cells have decreased amounts of chlorophyll and phycobilins. Their fluorescence spectra (77K) have one prominent chlorophyll emission peak at 684 nanometers as compared to three peaks at 687, 696, and 717 nanometers from normal cells. Chlorophyll-protein analysis of iron-deprived cells indicated the absence of high molecular weight bands. Addition of iron to iron-starved cells induced a restoration process in which new components were initially synthesized and integrated into preexisting membranes; at later times, new membranes were assembled and cell division commenced. Synthesis of chlorophyll and phycocyanins started almost immediately after the addition of iron. The absorption peak slowly returned to its normal wavelength within 24 to 28 hours. The fluorescence emission spectrum at 77K changed over a period of 14 to 24 hours during which the 696- and 717-nanometer peaks grew to their normal levels, and the 684 nanometer peak moved to 687 nanometers and its relative intensity decreased to its normal level. Analysis of chlorophyll-protein complexes on polyacrylamide gels showed that high molecular weight chlorophyll-protein bands were formed during this time, and that low molecular weight bands (related to photosystem II) disappeared. The origin of the fluorescence emission at 687 and 696 nanometers is discussed in relation to the specific chlorophyll-protein complexes formed during iron reconstitution.

Journal Article↗

Cyclic AMP response to prostaglandin E1 in mononuclear cells from peripheral blood and synovial fluid of patients with rheumatoid arthritis.

The cyclic AMP response to prostaglandin E1 (PGE1) was studied in peripheral blood (PB) and synovial fluid (SF) mononuclear cells from patients with rheumatoid arthritis (RA). The PGE1 induced accumulation of cyclic AMP was consistently (7 of 8 patients) less in cell suspensions derived from SF than in suspensions of equivalent numbers of mononuclear cells obtained simultaneously from PB. The high PB/SF cyclic AMP ratio was seen most clearly at the lowest concentration (10(-6)M) of PGE1 tested. There was no correlation between the patients' therapy and cyclic AMP response to PGE1. The high PB/SF cyclic AMP ratio was not accounted for by the presence of platelets in PB cell suspensions.

Arthritis, Rheumatoid↗