Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antitumor effects of i.v. injected human recombinant tumor necrosis factor (rTNF) against solid Meth A tumors in mice appeared to be critically dependent on the dose and were limited by its toxicity. Extensive necrosis and complete cures were only induced by doses having untoward effects, such as diarrhea, hypothermia, ruffled fur, and lethargy. Murine tumor necrosis serum (TNS, 0.5 ml) had about the same antitumor potential and induced all side effects except diarrhea. More extensive necrosis and approximate doubling of the incidence of complete regression in the absence of gross side effects were observed upon administration of a low dose of rTNF combined with detoxified endotoxin, nontoxic poly A:U, or submicrogram doses of toxic endotoxin. The separate constituents had little antitumor effects, if any at all. Increasing the dose of toxic endotoxin resulted in a further potentiation of necrosis, overt toxicity, but no cures. Muramyl dipeptide and interferon alpha/beta did not potentiate effects of rTNF. In vitro growth of Meth A cells was not inhibited by toxic endotoxin, rTNF or the combination, although TNS was highly inhibitory. Data show that therapeutic effects of rTNF and its synergy with endotoxin are not due to direct effects on the tumor cells and that the extent of prompt in vivo tumor necrosis does not predict the course of tumor growth. Therapeutic effects of both TNS and toxic endotoxin probably involve a synergy between low levels of TNF and other factors/effects induced by endotoxin. Detoxified endotoxin and poly A:U probably induce the latter effects and little or no TNF, so explaining the absence of side effects, their weak antitumor potential, and their powerful synergistic action with rTNF. A role for interferon alpha/beta as an induced synergistic factor is not likely. Muramyl dipeptide and TNF might share properties needed for synergy with endotoxins.
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PMID:Synergistic action of human recombinant tumor necrosis factor with endotoxins or nontoxic poly A:U against solid Meth A tumors in mice. 382 51

BALB/cGnDu lethargic mutant mice suffer from an age-related temporary defect in their cell-mediated immune response which is "spontaneously" corrected in animals 7 weeks of age or older. Thus, mutants of different ages (3 to 4 weeks old and 7 to 9 weeks old) were used to compare tumor incidence, tumor growth rate, and host survival time of Harding-Passey (HP) melanoma, mKSA, and GI110(BK)B6D2Tu tumors. Normal littermates were used as controls. Only the HP tumor was successfully transplanted in all recipients. In the 3- to 4-week-old lethargic mutants, the HP tumor had an increased growth rate and decreased the mean lifespan of the mice, when compared to normal littermates, but only one mKSA and no GI110(BK)B6D2Tu tumors proved transplantable. In contrast, lethargic mutants 7 to 9 weeks old injected with the HP tumor survived longer than their normal littermates, and they did not accept either of the other tumors tested. These results corroborate the notion that lethargic mutant mice have a partially impaired anti-tumor cell-mediated immune response at 3 to 4 weeks of age, but that their anti-tumor response is enhanced at the time of their "spontaneous" correction of the immune deficiency. The need for future studies on the possible use of this model to study various human immunological and adrenal disorders is discussed.
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PMID:Tumor growth rate varies with age in lethargic mutant BALB/cGnDu mice. 673 74

This 6-month-old Caucasian boy presented with a 10-day history of lethargy, obtundation, inability to hold his head up and mild torticollis. MRI and CT scans showed a large solid and cystic mass involving the right temporal, parietal and occipital lobes, pineal, superior pons, mesencephalon and posterior right thalamus. He underwent craniotomy initially for a partial tumor resection with an intraoperative diagnosis of desmoplastic astrocytoma. With immunohistochemistry and special stains the diagnosis of desmoplastic infantile ganglioglioma (DIG) was made. A near total resection was performed a week after initial resection.The patient then was treated with chemotherapy. Two months later an MRI showed tumor growth. Following additional aggressive chemotherapy, an MRI at 5 months post-resection indicated further tumor progression. This case illustrates that some DIGs may behave more aggressively than typical WHO grade I lesions.
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PMID:December 2000: 6 month old boy with 2 week history of progressive lethargy. 1130 3

A 64-year-old nondiabetic woman presented with spells of lightheadedness and diaphoresis associated with lethargy and hunger of 2 weeks' duration. Physical examination was unremarkable; however, her fasting plasma glucose was 66 mg/dl, with concurrent plasma insulin of 171 microIU/ml (normal, 5-27 microIU/ml). Her C-peptide and pro-insulin levels were elevated, with negative insulin antibody and negative urinary sulfonylurea levels. Abdominal computed tomographic scan demonstrated a 5 x 4-cm mass in the tail of the pancreas and many liver metastases. She underwent resection of the pancreatic mass, radiofrequency ablation, and cauterization of hepatic lesions. Histology confirmed pancreatic insulinoma. Ten months later, she was free of hypoglycemic symptoms, with normal plasma insulin C-peptide and significantly decreased proinsulin levels. Insulinomas are rare, predominantly benign tumors. Surgery is the only curative treatment. Octreotide can be used to control hormone secretion and tumor growth. Other treatments include hepatic embolization, radiotherapy, chemotherapy, and liver transplantation.
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PMID:Metastatic insulinoma: case report and review of the literature. 1498 75