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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine if there is a difference in the biochemical composition of the edge of a tumor and the center of a tumor. There was a greater concentration of histamine in the edge (mean +/- SEM, 9.3 +/- 1.2 pmole/mg of wet weight) than in the center (3.6 +/- 0.4 pmole/mg of wet weight) of a transplantable golden hamster insulinoma. There was, however, no difference in the concentration of norepinephrine, protein, DNA, or phosphate, or in the activity of the enzymes, monoamine oxidase, catechol-O-methyltransferase, L-dopa decarboxylase, or 5'-nucleotidase in the edge or in the center of the tumor. Using chemical analysis and autoradiography, there was a comparable incorporation of tritiated thymidine in the edge and in the center of the tumor.
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PMID:Biochemical composition of edge and center of malignant hamster insulinoma. 609 91

The subunit structure of receptors for insulin and insulin-like growth factor-1 has been demonstrated on a rat insulinoma cell, RIN-m5F, grown in continuous culture. The specific binding of [125-I]-insulin-like growth factor-1 (2.9 +/- 0.42%; mean +/- SEM) to the RIN-m5F cell was significantly greater than of [125I]-insulin (0.7 +/- 0.2%). Immunoprecipitation of receptors from [125I]-surface labeled cells and analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography revealed reduced subunits of Mr 130,000 and 90,000, identical to those for both insulin and insulin-like growth factor-1 receptors on classic target tissues. An apparent abundance of insulin-like growth factor-1 over insulin receptors could be due to downregulation of the latter by secreted insulin. These findings support a role for insulin and insulin-like growth factor-1 receptors in regulating metabolic or growth functions in the beta cell.
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PMID:Structure of insulin/insulin-like growth factor-1 receptors on the insulinoma cell, RIN-m5F. 609 9

Pentamidine can cause hypoglycemia followed by hyperglycemia. The mechanism of this biphasic response is not known but has been reported to be similar to that of streptozotocin and N-3-pyridyl-N-p- nitrourea (Vacor). Pentamidine (4 mg/kg per day for 12 days) was used in a patient with malignant insulinoma after several unsuccessful debulking procedures and chlorozotocin therapy. Mean glucose and immunoreactive insulin levels (+/- SEM) before and after therapy were 80 +/- 40 mg/dl versus 70 +/- 50 mg/dl and 216 +/- 12 microU/ml versus 198 +/- 22 microU/ml, respectively. These were not significantly different. The patient's five-month-old malignant insulinoma monolayer cell culture was incubated with pentamidine (60 micrograms/ml) in the presence or absence of supplemented stimulatory medium consisting of glucose (300 mg/dl) and theophylline (20 micrograms/ml). Chloroquine (60 micrograms/ml) was added to inhibit lysosomal degradation of immunoreactive insulin. Aliquots of media for immunoreactive insulin determination were obtained at 30 minutes, 20 hours, 72 hours, and three weeks. The cells were examined by high-power light microscopy at each time interval. At 30 minutes, pentamidine alone caused passive release of immunoreactive insulin, 23 percent higher than control (p less than 0.01). Stimulatory medium increased immunoreactive insulin 45 percent greater than control (p less than 0.01). Pentamidine plus stimulatory medium had no additive effect on immunoreactive insulin released within 30 minutes. At the end of 20 hours, immunoreactive insulin was no different with pentamidine and/or stimulatory medium. However, the addition of chloroquine increased immunoreactive insulin by 35 percent above the medium with pentamidine and stimulatory medium (p less than 0.01). At 72 hours, pentamidine suppressed immunoreactive insulin by 100 percent in all the media, irrespective of the presence or absence of stimulatory medium and/or chloroquine. At the end of three weeks, there was 50 percent suppression of immunoreactive insulin in the control medium, but pentamidine again completely suppressed immunoreactive insulin. High-power microscopy demonstrated intact cells in the control medium, whereas no cell structure could be detected in the media containing pentamidine at three weeks. In summary, pentamidine had no acute in vivo effect in a patient with malignant insulinoma. However, when used in an in vitro monolayer system, pentamidine caused (1) acute immunoreactive insulin release followed by inhibition of immunoreactive insulin secretion and (2) cytolysis of human malignant insulinoma cells in vitro.
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PMID:Diabetogenic effect of pentamidine. In vitro and in vivo studies in a patient with malignant insulinoma. 633 Nov 62

The amounts of immunoreactive proinsulin (IRP), immunoreactive insulin (IRI), and C-peptidelike immunoreactivity (CPR) in six insulinomas and one nesidioblastosis lesion were determined together with those in the surrounding pancreatic tissue. Four non-insulinoma and nondiabetic human pancreases were used as the control. The IRP in the seven tumors ranged from 5.85 micrograms/g to 65.45 micrograms/g (mean +/- SEM, 28.70 +/- 8.01 micrograms/g), while the IRP in the surrounding pancreatic tissue ranged from 2.08 micrograms/g to 11.71 micrograms/g (5.32 +/- 1.76 micrograms/g). Control pancreases had an IRP content of 12.01 +/- 2.36 micrograms/g. The IRI in the seven tumors ranged from 4.02 U/g to 47.97 U/g (14.40 +/- 6.35 U/g), while that in the surrounding pancreatic tissue ranged from 0.28 U/g to 3.64 U/g (2.32 +/- 0.63 U/g). Mean tumor CPR was 206.84 +/- 81.6 micrograms/g and it was 29.16 +/- 9.15 micrograms/g in the surrounding pancreatic tissue. The molar ratio of the IRP to IRI content was 6.83 +/- 1.95% for tumor tissue and 6.24 +/- 2.18% for the surrounding pancreatic tissue. These levels were similar to the ratio in the control pancreases (7.67 +/- 1.88%), in contrast to the higher serum IRP/IRI ratio in the tumor patients.
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PMID:Tumor and serum levels of proinsulin and insulin in insulinoma patients. 795 10

The C-peptide suppression test employing the euglycemic hyperinsulinemic clamp technique has been proposed as a useful diagnostic measure for insulinoma. To examine the specificity of the C-peptide suppression, we applied this test to subjects with symptoms suggesting reactive hypoglycemia. Five subjects studied had never experienced fasting hypoglycemia, and were negative in ultrasound, CT and MRI of the pancreas. Plasma C-peptide was not suppressed by physiological (50-100 microU/ml) and supraphysiological (200-500 microU/ml) hyperinsulinemia (% of baseline: 97.3 +/- 8.6% and 90.6 +/- 10.4%, +/- SEM, respectively, both NS). Three subjects were re-examined one year later, when their hypoglycemic episodes were noticeably attenuated. No significant suppression was found. Significant suppression was observed when plasma glucose was clamped at 50-60 mg/dl in four of five subjects (61.7 +/- 11.5%, P < 0.05), but one subject responded to neither higher plasma insulin nor low-normal glucose. In contrast, normal glucose tolerance (n = 13), IGT (n = 12) and obese NIDDM (n = 31) subjects showed highly significant suppression during euglycemic and physiological hyperinsulinemia (37.1 +/- 3.8%, 46.3 +/- 5.6%, 39.9 +/- 2.6%, respectively, all P < 0.001). In conclusion, the results of the present study indicate that a failure of hyperinsulinemic suppression of C-peptide in euglycemia is not specific for insulinoma, and that suppression of C-peptide by insulin at lower plasma glucose levels (50-60 mg/dl) would be a better diagnostic test.
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PMID:Lack of C-peptide suppression by exogenous hyperinsulinemia in subjects with symptoms suggesting reactive hypoglycemia. 907 3

An oxygen microsensor with a < 3-micron tip diameter was developed for monitoring oxygen levels at single cells and mouse pancreatic islets. The sensor was fabricated by electrochemically recessing an etched Pt wire inside a pulled glass micropipet and then coating with cellulose acetate. This fabrication process was found to be simpler than previous oxygen electrode designs of comparable size. The microsensors had a average sensitivity of 0.59 +/- 0.29 pA/mmHg (mean +/- SD, n = 42), signals that were minimally perturbed by convection, and response times of < 1 s. The electrode was used to measure the oxygen gradient around and inside single mouse islets. The measurements demonstrate that oxygen levels within even the largest islets at maximal glucose stimulation are 67 +/- 1.6 mmHg (mean +/- SD, n = 5), indicating that islets have adequate oxygen supplies by diffusion under tissue culture conditions to support insulin secretion. The electrode was also used to record the dynamics of oxygen level at single islets as a function of glucose concentration. As glucose level was changed from 3 to 10 mM, oxygen level decreased by 15.8 +/- 2.3 mmHg (mean +/- SEM, n = 6) and oscillations with a period of 3.3 +/- 0.6 min (mean +/- SEM, n = 6) appeared in the oxygen level. In islets bathed in quiescent solutions containing 10 mM glucose, similar oscillations could be observed. In addition, in the quiet solutions it was possible to detect faster oscillations with a period of 12.1 +/- 1.7 s (mean +/- SEM, n = 6) superimposed on the slower oscillations. Oxygen consumption could also be observed at single insulinoma cells using the electrode. Individual cells also showed oscillations in oxygen consumption with a period of a few seconds. The results demonstrate that the electrode can be used for dynamic oxygen level recordings in biological microenvironments.
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PMID:Oxygen microsensor and its application to single cells and mouse pancreatic islets. 1048 19

In previous studies, we demonstrated that rat insulin promoter (RIP)-driven gene therapy successfully targeted human pancreatic tumor PANC-1 cells and mouse insulinoma NIT-1 cells, which are both pancreatic duodenal homeobox-1 (PDX-1)-positive. The purpose of this study was to perform a human tissue array analysis to determine potential targets for RIP-driven gene therapy. A custom-designed tissue MicroArray analysis of various human cancer specimens was performed using a PDX-1 polyclonal antibody generated in our laboratory. The custom-designed Tissue MicroArray of human tumor specimens consists of human cancer specimens from different origins, such as the pancreas, breast, colon, prostate, kidney, liver, lung, and ovary. A panel of normal human specimens from 20 organs or tissues was used as a control. All tissues were fixed in formalin and embedded in paraffin. The immunohistochemistry studies of the cytoplasm and the nuclear expression levels were compared using the Loda method and blind reviews. Data are presented as the mean +/- SEM (p < 0.05 was considered significant by the unpaired student t-test). PDX-1 expression intensity was elevated in both benign and malignant tissues from the same patient with pancreas, breast, colon, prostate, and kidney cancers, whereas normal human tissues from control subjects without cancer did not express PDX-1. These results suggest that PDX-1 is an early marker for these cancers and could be potentially used as a diagnostic parameter and perhaps could be targeted by PDX-1-activated gene therapies, such as RIP-TK.
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PMID:Tissue MicroArray analyses of pancreatic duodenal homeobox-1 in human cancers. 1570 33

A system for vascular hollow fiber bio-artificial pancreas development, optimization and in vitro testing was implemented and operated in a simple and fully described manner, allowing other researchers to test a variety of experimental conditions (different biomaterials, biologic tissue, addition of proteins or other adjuvants). In this work, a polysulfone hollow fiber was used as bioprotective material. Two different cell sources were co-immobilized with agarose microspheres in and experimented with the membrane device: rat islets of Langerhans and mouse beta-TC-3 insulinoma cells. The results obtained with islets of Langerhans were used as islet comparable insulin-release data. Beta-TC-3 cells were mainly used in these studies, due to higher control and reproducibility of cell number and behavior: addition of hemoglobin was beneficial for sustained cell viability, especially during cell insertion in the device (viability assessed by beta-TC-3 lactate dehydrogenase activity in the recirculating culture medium); cells did not adhere to the polysulfone membrane (assessed by SEM observation of membrane samples from dynamic cultures). Comparable device functionality and insulin-release results were attained with both cell types: device functionality was maintained for 7-9 days and maximum insulin-release during dynamic glucose challenges were 2.6 x 10(-3)+/-7 x 10(-5)microU/beta-cell x 8 h, with islets, and 9.3 x 10(-4)+/-2 x 10(-5)microU/beta-cell x 2 h, with beta-TC-3 cells.
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PMID:Development of a polysulfone hollow fiber vascular bio-artificial pancreas device for in vitro studies. 1912 45


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