Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purposes of this work are to: review the biological activities of Interleukin-2 (IL-2); evaluate the reported therapeutic benefits and toxicity of IL-2/lymphokine activated killer (LAK) cells; and project the role of IL-2/LAK cells in cancer therapy. Interleukin-2 is a glycoprotein lymphokine (mw 15,000) produced naturally by mitogen or antigen stimulated T-lymphocytes. The activities of IL-2 include: enhancement of IL-2 receptor positive T-lymphocytes and a variety of other in vitro and in vivo alterations of T cell function. The IL-2 gene has been cloned from the Jurkat leukemia cell line and expressed by recombinant biotechnology in an E. coli vector. In vitro incubation of IL-2 with selected T-lymphocytes results in the formation of lymphocyte activated killer (LAK) cells. Rosenberg and colleagues, in 1983, demonstrated that both exogenous IL-2 and LAK cells were needed in order to get maximum tumor regression in a murine model and later humans. Patients selected for IL-2/LAK cell therapy have clinical metastases or advanced unresectable cancers. Almost all patients treated demonstrate some toxic effects, including chills, fever, nausea, vomiting, diarrhea and hepatic dysfunction. Approximately 75 percent of the patients have profound hypotension and require intensive nursing care. A review of the literature indicates that tumor responsiveness will range from negligible (adenocarcinoma of the lung with metastases) to a 30+ percent response in renal cell carcinoma when complete and partial responders are totalled. Interleukin-2/LAK cell therapy has promise for some wide spread tumors for which no other therapy is available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 and lymphokine activated killer cells: promises and cautions. 264 90

The association of vitamin A supplementation with concentrations of positive acute-phase proteins in the serum was investigated in the Child Health Study of the Ghana Vitamin A Supplementation Trials, a randomized, controlled trial of the effect of vitamin A on morbidity in children aged < 5 y. Mean serum concentrations of alpha 1-acid glycoprotein, serum amyloid A, and C-reactive protein did not differ overall between the vitamin A-supplemented and placebo-treated groups. Treatment groups were then subdivided according to what symptoms children had experienced in the week before blood sampling. Acute-phase-protein responses to fever and cough were not affected by vitamin A supplementation. There was a tendency for vitamin A-supplemented children, but not placebo children, to have elevated acute-phase proteins in association with reported vomiting or severe diarrhea. The failure of unsupplemented children to mount an acute-phase response may have contributed to their increased morbidity from gastrointestinal symptoms.
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PMID:Vitamin A supplementation, morbidity, and serum acute-phase proteins in young Ghanaian children. 754 31

Rotaviruses are the commonest cause of diarrhea and are responsible for more than 25% of all deaths from diarrhea worldwide. Children become infected early in life and most infections in infants older than 3 months are symptomatic. These viruses account for 18 million cases of moderate or severe disease and 900,000 deaths each year. The incidence of rotaviral disease is similar in developed and developing countries but the number of deaths is higher in developing countries. Infections occur throughout the year in developing countries but are seasonal in developed countries, occurring mainly between October and March. The mean age at first infection is 6 to 9 months in developing countries and 9 to 15 months in developed countries. The greater severity of infections in developing countries is associated with malnutrition, lower hygiene standards and the lactose malabsorption and deficiencies of zinc and vitamin A that accompany diarrhea. Many mixed infections also increase the severity of the rotavirus infection. The clinical symptoms of the disease in hospitalized patients are diarrhea, vomiting and dehydration. There is more vomiting than with bacterial infections. The severity of the clinical symptoms depends on the virulence of different strains. The disease is more severe and persistent in patients with reduced immunity. Age also has an effect. All children may have rotavirus in their feces but the percentage of children developing diarrhea is highest at an age of 3 to 6 months and decreases steadily thereafter. Rotaviruses can survive in air and may remain on surfaces for several hours. They are thus often responsible for nosocomial infections. Rotavirus was first identified in cattle in 1969. The virulence of the strain and the age of the calf at infection are important in the pathogenesis of rotaviral infection in cattle. Replacement of villous enterocytes is slow in newborn calves. This means that newborn calves are susceptible to disease caused by strains that are only moderately virulent. They are, however, protected during the first days of life by antibodies transmitted via the colostrum. There is competition between the rate of replication of rotavirus and replacement of enterocytes in older animals so only more virulent strains cause diarrhea in six-week-old calves. Adult animals become resistant to disease, but not to infection. The rotavirus genome consists of 11 segments of double-stranded RNA. Genetic recombination between these segments occurs naturally and can be reproduced in vitro. Recombinants between human and bovine strains have been identified but the epidemiological importance of this is unknown. The genomic segments encode 6 structural proteins (VP) and 5 non-structural proteins (NSP). VP6, the major capsid antigen, present can be used to identify groups of rotaviruses. The presence of VP7 indicates that the virus belongs to the G (glycoprotein) group of serotypes. There are 14 G serotypes, 10 of which can infect humans. The four main G serotypes are G1 to G4, with G1 accounting for 60% of human serotypes. The presence of VP4 identifies the P (protease-sensitive) serotype. The serotypes have different geographic distributions with G1P8 responsible for more than 50% of epidemics worldwide. The WHO project for the control of rotaviral infections focuses on avoiding fecal contamination. This is achieved by ensuring high standards of food hygiene, sewage treatment and chlorinated running water and by introducing vaccination when vaccines become available. Recombinant animal (bovine or simian) and human rotaviruses are currently being tested in phase III studies. Attenuated live human viruses, including cold-adapted strains are being tested in phase I trials. The quadrivalent recombinant rhesuslhuman vaccine had only mild side-effects in children and was effective, giving 82-92% protection against severe diarrhea over two years and 50% protection on average. (ABSTRACT TRUNCATED)
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PMID:[Rotaviruses in human and veterinary medicine]. 929 11

A 58-year-old man experienced episodes of fever, vomiting, and diarrhea over a 2-year period. The laboratory evaluation during these attacks consistently disclosed thrombocytopenia, leukopenia, and elevated liver enzymes. A liver biopsy performed at one of these attacks showed a typical picture of granulomatous hepatitis. In retrospect, all episodes seemed to be associated with the ingestion of quinine. Indeed, such a correlation was established by a challenge with quinine. By using flow cytometry, quinine-dependent IgG antibodies to platelets were detected in the patient serum. By a two-color flow cytometric assay, the patient serum was also found to hold quinine-dependent antibodies specific for neutrophils, T lymphocytes, and B lymphocytes. Moreover, serum absorbed with neutrophils in the presence of quinine continued to react with platelets, T lymphocytes, and B lymphocytes; serum that was absorbed with mononuclear cells continued to react with neutrophils and platelets. These experiments indicated that the antigen targets were different on platelets, neutrophils, and lymphocytes. Further, the patient serum in the presence of quinine immunoprecipitated surface-labeled platelet proteins with electrophoretic mobilities closely resembling those of glycoprotein (GP) Ib/IX and GPIIb/IIIa. By a modified monoclonal antibody-specific immobilization of platelet antigens assay, the patient serum in the presence of quinine reacted with platelet GPIb/IX and GPIIb/IIIa. Also, the patient serum in the presence of quinine immunoprecipitated an uncharacterized 15-kD double-band from surface-labeled granulocyte proteins. We conclude that our patient's thrombocytopenia, neutropenia, and lymphocytopenia were caused by quinine-dependent antibodies and that these antibodies recognized cell lineage-specific epitopes.
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PMID:Multiple quinine-dependent antibodies in a patient with episodic thrombocytopenia, neutropenia, lymphocytopenia, and granulomatous hepatitis. 938 97

Three siblings suffered from an unusual disorder of cyclic vomiting and congenital hepatic fibrosis. Serum transferrin isoelectric focusing showed increased asialo- and disialotransferrin isoforms as seen in the carbohydrate-deficient glycoprotein (CDG) syndrome type I. Phosphomannomutase, which is deficient in most patients with type I CDG syndrome, was found to be normal in all three patients. Structural analysis of serum transferrin revealed nonglycosylated, hypoglycosylated, and normoglycosylated transferrin molecules. These findings suggested a defect in the early glycosylation pathway. Phosphomannose isomerase was found to be deficient and the defect was present in leucocytes, fibroblasts, and liver tissue. Phosphomannose isomerase deficiency appears to be a novel glycosylation disorder, which is biochemically indistinguishable from CDG syndrome type I. However, the clinical presentation is entirely different.
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PMID:A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency. 953 79

We report the case of a patient with carbohydrate-deficient glycoprotein syndrome type Ib who developed normally until 3 months of age, when she was referred to the hospital for evaluation of hypoglycemia that was found to be related to hyperinsulinism. She also had vomiting episodes, hepatomegaly, and intractable diarrhea, which evoked the diagnosis of carbohydrate-deficient glycoprotein syndrome. Oral mannose treatment at a dose of 0.17 g/kg body weight 6 times/d was followed by a clinical improvement and normalization of blood glucose, aminotransferases, and coagulation factor levels. Hyperinsulinemic hypoglycemia should be considered as a leading sign of carbohydrate-deficient glycoprotein syndrome type Ib, especially when it is associated with enteropathy and abnormal liver tests.
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PMID:Hyperinsulinemic hypoglycemia as a presenting sign in phosphomannose isomerase deficiency: A new manifestation of carbohydrate-deficient glycoprotein syndrome treatable with mannose. 1048 8

There are several physiological and pathophysiological situations where there is an apparent fluid flux across plasma membranes at the time when human chorionic gonadotropin (hCG) levels are high. These fluxes may take the form of a fluid loss from gastrointestinal tract (e.g. emesis/hyperemesis gravidarum) or accumulations in enclosures (e.g. amniotic fluid or hydatidiform mole). What is not obvious though is whether hCG is the cause of these fluid fluxes. Although glycoprotein hormones like hCG are mainly hormonogenic, their action in the latter process involves the efflux or conductance of halide ions. Since the basis of fluid secretion is an active efflux of ions such as chloride stimulated by a humoral agent, accompanied by a passive diffusion of water across a cell wall, I hypothesize that hCG is also a secretory hormone and responsible for fluid fluxes in the above and other clinical situations.
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PMID:Human chorionic gonadotropin: a secretory hormone. 1053 8

Carbohydrate deficient glycoprotein syndromes (CDGS) are inherited disorders in glycosylation. Isoelectric focusing of serum transferrin is used as a biochemical indicator of CDGS; however, this technique cannot diagnose the molecular defect. Even though phosphomannomutase (PMM) deficiency accounts for the great majority of known CDGS cases (CDGS type Ia), newly discovered cases have significantly different clinical presentations than the PMM-deficient patients. These differences arise from other defects affecting the biosynthesis of N-linked oligosaccharides in the endoplasmic reticulum and in the Golgi compartment. The most notable is the loss of phosphomannose isomerase (PMI) (CDGS type Ib). It causes severe hypoglycemia, protein-losing enteropathy, vomiting, diarrhea, and congenital hepatic fibrosis. In contrast to PMM-deficiency, there is no developmental delay nor neuropathy. Most symptoms in the PMI-deficient patients can be successfully treated with dietary mannose supplements. Another defect is the lack of glucosylation of the lipid-linked oligosaccharide precursor. The clinical features of this form of CDGS are milder, but similar to, PMM-deficient patients. Yeast genetic and biochemical techniques were critical in unraveling these disorders since many of the defective genes were known in yeast and corresponding mutants were available for complementation. Yeast strains carrying mutations in the homologous genes are likely to provide conclusive identification of the primary defects in novel CDGS types that affect the synthesis and transfer of precursor oligosaccharides.
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PMID:Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity. 1057 Oct 10

Castor beans (Ricinus communis) contain ricin. Ricin is a glycoprotein reported to cause hypotension, gastroenteritis, depression, and death. However, few deaths are reported following castor bean ingestion in animals. From January 1987 to December 1998, the American Society for the Prevention of Cruelty to Animals-National Animal Poison Control Center received 98 incidents of castor bean ingestion in dogs. The most commonly reported clinical signs were vomiting, depression, and diarrhea. Death or euthanasia occurred in 9% of the cases. The severity of clinical signs following castor bean ingestion may depend on whether the beans were chewed or swallowed whole.
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PMID:Evaluation of castor bean toxicosis in dogs: 98 cases. 1082 94

The majority of hematopoietic malignancies have aberrancies in the retinoblastoma (Rb) pathway. Loss in Rb function is, in most cases, a result of the phosphorylation and inactivation of Rb by the cyclin-dependent kinases (cdks), main regulators of cell cycle progression. Flavopiridol, the first cdk modulator tested in clinical trials, is a flavonoid that inhibits several cdks with evidence of cell cycle block. Other interesting preclinical features are the induction of apoptosis, promotion of differentiation, inhibition of angiogenic processes and modulation of transcriptional events. Initial clinical trials with infusional flavopiridol demonstrated activity in some patients with non-Hodgkin's lymphoma, renal, prostate, colon and gastric carcinomas. Main side-effects were secretory diarrhea and a pro-inflammatory syndrome associated with hypotension. Phase 2 trials with infusional flavopiridol in CLL and mantle cell lymphoma, other schedules and combination with standard chemotherapies are ongoing. The second cdk modulator tested in clinical trials, UCN-01, is a potent protein kinase C inhibitor that inhibits cdk activity in vitro as well. UCN-01 blocks cell cycle progression and promotes apoptosis in hematopoietic models. Moreover, UCN-01 is able to abrogate checkpoints induced by genotoxic stress due to modulation in chk1 kinase. The first clinical trial of UCN-01 demonstrated very prolonged half-life (approximately 600 h), 100 times longer than the half-life observed in preclinical models. This effect is due to high binding affinity of UCN-01 to the human plasma protein alpha-1-acid glycoprotein. Main side-effects in this trial were headaches, nausea/vomiting, hypoxemia and hyperglycemia. Clinical activity was observed in patients with melanoma, non-Hodgkin's lymphoma and leiomyosarcoma. Of interest, a patient with anaplastic large cell lymphoma refractory to high-dose chemotherapy showed no evidence of disease after 3 years of UCN-01 therapy. Trials of infusional UCN-01 in combination with Ara-C or gemcitabine in patients with acute leukemia and CLL, respectively, have commenced. In conclusion, flavopiridol and UCN-01 are cdk modulators that reach biologically active concentrations effective in modulating CDK in vitro, and show encouraging results in early clinical trials in patients with refractory hematopoietic malignancies. Although important questions remain to be answered, these positive experiences will hopefully increase the therapeutic modalities in hematological malignancies.
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PMID:Development of cyclin-dependent kinase modulators as novel therapeutic approaches for hematological malignancies. 1124 75


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