Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017536 (giardiasis)
 1,714 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty patients with late-onset idiopathic immunoglobulin deficiency were studied and the frequency of various clinical associations and complications was observed. Men and women were equally affected, although the age at onset in men peaked in the third decade whereas it was more uniformly distributed in women. Sinobronchopulmonary infections were common and were caused by Haemophilus influenzae. Diplococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus: bronchiectasis occurred in 28 per cent. Thirty patients (60 per cent) had diarrhea, which was often associated with steatorrhea, giardiasis, achlorhydria, abnormal Schilling tests and morphologic abnormalities on small bowel biopsy specimens, including nodular lymphoid hyperplasia; three patients had pernicious anemia. In the 20 patients without diarrhea these abnormalities were not observed except for giardiasis in one patient and achlorhydria in two patients. Cholelithiasis occurred in both groups in about a third of the patients tested. A high degree of susceptibility to neoplasia was noted. Thyroid abnormalities, including primary hypothyroidism and Graves' disease, were observed in six patients. Additional occasional findings were vitiligo, keratoconjunctivitis sicca and arthritis. Splenomegaly occurred in 14 (28 per cent) patients. The percentage of B lymphocytes in the blood was determined in 10 patients; it was normal or slightly decreased in eight patients and low in two patients.
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PMID:Idiopathic late-onset immunoglobulin deficiency. Clinical observations in 50 patients. 78 41

A patient with common variable hypogammaglobulinemia (CVH) who presented with recurrent sinopulmonary infections, nodular lymphoid hyperplasia of the small bowel, and intestinal giardiasis was studied. A diffuse lymphocytic lymphoma with small bowel, skin, and hepatic involvement subsequently developed in the patient. Light microscopy of the tumor revealed tissue infiltration with mononuclear cells having the morphologic features of T-lymphocytes. The malignant lymphocytes had characteristics of T-suppressor/cytotoxic cells as established by the absence of surface immunoglobulin and Leu 3 surface markers, and the presence of OKT3 and OKT8 surface markers. Peripheral blood lymphocyte studies revealed an increased number of T-suppressor cells, a reversal of the helper-suppressor ratio, and a generalized state of hyporesponsiveness to mitogen and antigen stimulation. No evidence of retroviral reverse transcriptase activity was detected in cultures of peripheral blood lymphocytes. The association between CVH and a lymphoma composed of cells with T-suppressor/cytotoxic surface markers has not been previously reported. The postulated role of T-suppressor cells in the failure of immunoglobulin synthesis in some forms of CVH suggests that the finding of a T-suppressor/cytotoxic cell lymphoma complicating CVH may be more than fortuitous.
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PMID:Common variable hypogammaglobulinemia complicated by an unusual T-suppressor/cytotoxic cell lymphoma. 294 34

Although treatments have improved patient prognosis in surgically resectable colorectal cancer, new effective drugs with improved safety profiles are needed to improve the currently poor outcomes of patients with recurrent or metastatic colorectal cancer. Quinacrine, a small molecule anti-malarial agent that has activity in giardiasis, lupus, prion disease, and used as a means of non-surgical sterilization, has shown cytotoxic activity across a broad range of cancers. Here, we evaluate the potential of adding quinacrine to anticancer chemotherapeutics and targeted agents as a potential novel combinatorial therapy for advanced colon cancer. We show that quinacrine synergizes with 5-fluorouracil and significantly enhances the cytotoxicity of sorafenib in a panel of 10 human colorectal cancer cell lines, including those with KRAS mutations protein gel blot analysis confirmed that quinacrine's anticancer activity partially arises from its ability to stabilize p53 and lower anti-apoptotic protein levels. In a series of in vivo studies, quinacrine monotherapy lowered the tumor load of nu/nu mice bearing human colorectal cancer xenografts. In combination, quinacrine and 5-Fluorouracil significantly delayed tumor growth of a variety of different xenografts, as compared to each agent administered alone. Our results suggest that the administration of quinacrine in combination with chemotherapeutic agents and targeted agents should be further explored in patients with recurrent, locally advanced, or metastatic colorectal cancer.
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PMID:Quinacrine synergizes with 5-fluorouracil and other therapies in colorectal cancer. 2172 13

The flagellated protozoan Giardia duodenalis is a worldwide parasite causing giardiasis, an acute and chronic diarrheal disease. Metabolism in G. duodenalis has a limited complexity thus making metabolic enzymes ideal targets for drug development. However, only few metabolic pathways (i.e., carbohydrates) have been described so far. Recently, the parasite homolog of the mitochondrial-like glycerol-3-phosphate dehydrogenase (gG3PD) has been identified among the interactors of the g14-3-3 protein. G3PD is involved in glycolysis, electron transport, glycerophospholipids metabolism, and hyperosmotic stress response, and is emerging as promising target in tumor treatment. In this work, we demonstrate that gG3PD is a functional flavoenzyme able to convert glycerol-3-phosphate into dihydroxyacetone phosphate and that its activity and the intracellular glycerol level increase during encystation. Taking advantage of co-immunoprecipitation assays and deletion mutants, we provide evidence that gG3PD and g14-3-3 interact at the trophozoite stage, the intracellular localization of gG3PD is stage dependent and it partially co-localizes with mitosomes during cyst development. Finally, we demonstrate that the gG3PD activity is affected by the antitumoral compound 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol, that results more effective in vitro at killing G. duodenalis trophozoites than the reference drug metronidazole. Overall, our results highlight the involvement of gG3PD in processes crucial for the parasite survival thus proposing this enzyme as target for novel antigiardial interventions.
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PMID:The FAD-dependent glycerol-3-phosphate dehydrogenase of Giardia duodenalis: an unconventional enzyme that interacts with the g14-3-3 and it is a target of the antitumoral compound NBDHEX. 2608 64