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)

We administered doses of 5 to 180 x 10(6) IU of beta-serine-interferon (IFN-beta ser17) twice weekly to 20 patients with recurrent malignant gliomas in a Phase I study. Interferon was given through an Ommaya reservoir connected by a catheter to the tumor cavity. Side effects of interferon therapy occurred in only one patient and consisted of nausea, vomiting, fever, and chills after each treatment, presumably due to rapid diffusion of interferon into ventricular cerebrospinal fluid (CSF). Problems with the Ommaya reservoir (obstruction in two patients and infection in four patients) led to six patients being terminated from the study, and represent the major difficulty with this form of therapy. Although this was primarily a study of interferon toxicity, of 12 evaluable patients, 3 had stable disease for 148, 192, and 539 days; 9 had progressive disease. In addition, we tested the effect of IFN-beta ser17 on the growth of early passage in vitro cultures of malignant gliomas established from patients. Growth inhibition varied from 0% to more than 50%. In all cultures evaluated, the combination of recombinant gamma-interferon plus IFN-beta ser17 enhanced growth inhibition. Further clinical and laboratory study is necessary to better define the therapeutic efficacy of IFN-beta ser17 and the role of combinations of interferons in the treatment of malignant gliomas.
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PMID:Intratumor administration of beta-interferon in recurrent malignant gliomas. A phase I clinical and laboratory study. 229 73

The goal of this study was to investigate the role of the disulphide bond of staphylococcal enterotoxin C1 (SEC1) in the structure and activity of the toxin. Mutants unable to form a disulphide bond were generated by substituting alanine or serine for cysteine at positions 93 and/or 110. Although we did not directly investigate the residues between the disulphide linkage, tryptic lability showed that significant native structure in the cystine loop is preserved in the absence of covalent bonding between residues 93 and 110. Since no correlation was observed between the behaviour of these mutants with regard to toxin stability, emesis and T cell proliferation we conclude that SEC1-induced emesis and T cell proliferation are dependent on separate regions of the molecule. The disulphide bond itself is not an absolute requirement for either activity. However, conformation within or adjacent to the loop is important for emesis. Although mutants with alanine substitutions were not emetic, those with serine substitutions retained this activity, suggesting that the disulphide linkage stabilizes a crucial conformation but can be replaced by residues which hydrogen bond.
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PMID:Investigation of the role of the disulphide bond in the activity and structure of staphylococcal enterotoxin C1. 781 47

Diarrhetic shellfish poisoning (DSP) is a serious and globally widespread phytoplankton-related seafood illness. Although DSP is rarely life-threatening, it causes incapacitating diarrhea and vomiting with no known medical treatments. In addition, phytoplankton producing DSP toxins have been identified in temperate coastal waters worldwide, and their numbers may be increasing as a result of coastal eutrophication. The toxic effects of the major DSP toxins, okadaic acid and dinophysistoxin-1 (35-methylokadaic acid), appear to originate from their inhibitory activity against a family of structurally related serine/threonine protein phosphatases (PSPases). In particular, the inhibition of essential PSPases (e.g. PP1 and PP2A) has catastrophic consequences in most eukaryonic cells. Exploiting the potent inhibitory property of the DSP toxins, we have developed an enzyme-based assay (PP2A assay) capable of detecting both okadaic acid and dinophysistoxin-1 in nanogram amounts. The assay employs purified PP2A, which has an extremely high affinity for both DSP toxins. This provides the PP2A assay with a level of sensitivity comparable to, or surpassing, that of most monoclonal antibody probes. To evaluate the PP2A assay as a means of detecting contaminated shellfish, a series of spike recovery experiments was conducted. The findings from these studies suggest that the PP2A assay has the potential for development into a rapid and relatively simple method for detecting PSPase inhibitors in crude extracts produced from shellfish.
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PMID:Development of a protein phosphatase-based assay for the detection of phosphatase inhibitors in crude whole cell and animal extracts. 902 95

Staphylococcal enterotoxins (SEs) are superantigenic toxins. They are five major classical types, i.e., SEA, SEB, SEC, SED, SEE, and new SEs or SE-like superantigens, such as SEG to SEU. Only the staphylococcal superantigens (SAgs) that induce emesis following oral administration in a monkey model are designated as SEs while other related toxins are called SE-like (SEl) superantigens. To survey the enterotoxin genotypes for S. aureus strains isolated from food-poisoning cases in Taiwan, we developed PCR primers specific for SEN, SEO, SEP, SEQ, SER, and SEU genes. The complete SE sequences and their expression potential for strains positive to sen, seo, sep, seq, ser, and seu specific primers were also determined. These strains were used as reference strains. With the PCR primers specific for all SEs or SAgs, including toxic shock syndrome toxin I (TSST-1), we assayed the genotypes of 147 S. aureus strains isolated from patients associated with staphylococcal food-poisoning outbreaks occurred during 2001-2003. For these 147 strains, 135 (91.8%) were found positive for one or more SE or SAg genes. For classical enterotoxin and TSST-1 types, the major one was tsst-1 (59.1%) following by sea (29.2%), seb (19.7%), sec (6.8%), and sed (2.0%). For new SE and SAg types, the major one was sei (29.9%) and sep (27.9%) followed by, sek (16.3%), seo (14.3%), seu (14.2%), sem (11.6%), sen (10.9%), seq (10.9%), seh (8.2%), sel (6.8%), and ser (5.4%) etc. This report reveals the whole SE and SAg genotypes for S. aureus strains isolated from staphylococcal food-poisoning cases in Taiwan.
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PMID:PCR detection of Staphylococcal enterotoxins (SEs) N, O, P, Q, R, U, and survey of SE types in Staphylococcus aureus isolates from food-poisoning cases in Taiwan. 1806 43

In addition to two known staphylococcal enterotoxin-like genes (selj and selr), two novel genes coding for two superantigens, staphylococcal enterotoxins S and T (SES and SET), were identified in plasmid pF5, which is harbored by food poisoning-related Staphylococcus aureus strain Fukuoka 5. This strain was implicated in a food poisoning incident in Fukuoka City, Japan, in 1997. Recombinant SES (rSES) specifically stimulated human T cells in a T-cell receptor Vbeta9- and Vbeta16-specific manner in the presence of major histocompatibility complex (MHC) class II(+) antigen-presenting cells (APC). rSET also stimulated T cells in the presence of MHC class II(+) APC, although its Vbeta skewing was not found in reactive T cells. Subsequently, we examined the emetic activity of SES and SET. We also studied SElR to determine emetic activity in primates. This toxin was identified in previous studies but was not examined in terms of possession of emetic activity for primates. rSES induced emetic reactions in two of four monkeys at a dose of 100 microg/kg within 5 h of intragastric administration. In one monkey, rSET induced a delayed reaction (24 h postadministration) at a dose of 100 microg/kg, and in the other one, the reaction occurred 5 days postadministration. rSElR induced a reaction in two of six animals within 5 h at 100 microg/kg. On this basis, we speculate that the causative toxins of vomiting in the Fukuoka case are SES and SER. Additionally, SES, SER, and SET also induced emesis in house musk shrews as in the monkeys.
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PMID:Identification and characterization of two novel staphylococcal enterotoxins, types S and T. 1871 Aug 64

Several synthetic mixtures of natural and racemic crystalline amino acids suitable for the daily nitrogen requirement are tested in dogs for their tolerance upon intravenous injection. Certain mixtures of the ten essential amino acids plus non-essential amino acids exclusive of glutamic acid are accepted without any obvious sign of disturbance even at rates above 10 mg. nitrogen per kilo per minute for quantities greater than 300 mg. per kilo. One such mixture consists in parts per 100 of dl-threonine 7, dl-valine 15, l(-)-leucine 10.9, dl-isoleucine 9.9, l(+)-lysine. HCl.H(2)O 10.9, dl-tryptophane 3, dl-phenylalanine 9.9, dl-methionine 6, l(+)-histidine.HCl.H(2)O 5, l(+)-arginine-HCl 5, glycine 9.9, dl-alpha-alanine 4, dl-serine 2, l(-)-cystine 0.5, and l(-)-tyrosine 1. In addition other well tolerated mixtures included the prolines. When glutamic acid, natural or racemic, is included in similar mixtures vomiting reactions frequently occur at nitrogen rates above 4 mg. per kilo per minute. Vomiting almost always occurs on the first daily injection containing glutamic acid and usually on any subsequent injection containing more than 100 mg. glutamic acid per kilo unless given very slowly. Upon the addition of glycine certain mixtures of the ten essential amino acids show an improved tolerance. Two casein digests tested usually produced vomiting at injection rates above 2 mg. nitrogen per kilo per minute, probably because of their glutamic acid content. No serious reaction has ever occurrred to any mixture of amino acids or casein digest tested. Elimination of minor reactions such as vomiting appears possible and desirable for greater usefulness of these solutions in parenteral feeding.
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PMID:TOLERANCE TO AMINO ACID MIXTURES AND CASEIN DIGESTS GIVEN INTRAVENOUSLY : GLUTAMIC ACID RESPONSIBLE FOR REACTIONS. 1987 68

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and intoxication and probably to vitamin deficiency. When the diet nitrogen is provided by certain mixtures of the ten growth essential amino acids plus glycine, given intravenously at a rapid rate, plasma protein production is good. The same mixture absorbed subcutaneously at a slower rate may be slightly better utilized. Fed orally the same mixture is better utilized and associated with a lower urinary nitrogen excretion. An ample amino acid mixture for the daily intake of a 10 kilo dog may contain in grams dl-threonine 1.4, dl-valine 3, dl-leucine 3, dl-isoleucine 2, l(+)-lysine.HCl.H(2)O 2.2, dl-tryptophane 0.3, dl-phenylalanine 2, dl-methionine 1.2, l(+)-histidine.HCl.H(2)O 1, l(+)-arginine.HCl 1, and glycine 2. Half this quantity is inadequate and not improved by addition of a mixture of alanine, serine, norleucine, proline, hydroxyproline, and tyrosine totalling 1.4 gm. Aspartic acid appears to induce vomiting when added to a mixture of amino acids. The same response has been reported for glutamic acid (8). Omission from the intake of leucine or of leucine and isoleucine results in negative nitrogen balance and rapid weight loss but plasma protein production may be temporarily maintained. It is possible that leucine may be captured from red blood cell destruction. Tryptophane deficiency causes an abrupt decline in plasma protein production. No decline occurred during 2 weeks of histidine deficiency but the urinary nitrogen increased to negative balance. Plasma protein production may be impaired during conditions of dietary deficiency not related to the protein or amino acid intake. Skin lesions and liver function impairment are described. Unidentified factors present in liver and yeast appear to be involved.
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PMID:PLASMA PROTEIN PRODUCTION INFLUENCED BY AMINO ACID MIXTURES AND LACK OF ESSENTIAL AMINO ACIDS : A DEFICIENCY STATE RELATED TO UNKNOWN FACTORS. 1987 90

Hawkinsinuria is a severe inherited condition that has a significant impact on the health of infants. The disease manifests as metabolic acidosis that significantly slows the growth rate and induces persistent diarrhea and vomiting. Though other causes may exist, an autosomal dominant mutation that alters codon 241 of the 4-hydroxyphenylpyruvate dioxygenase (HPPD) gene from encoding an asparagine to encoding a serine gives rise to the symptoms of the disease. The observed pattern of dominance of this mutation belies the paucity of reports of this disease in the literature and suggests that it may be rarely diagnosed. Diagnosis is based on the presence of 2-amino-3-{[2-(carboxymethyl)-2,5-dihydroxy-1-cyclohex-3-enyl]sulfanyl}propanoic acid (hawkinsin) in the urine. We have made the structurally equivalent mutation in the Streptomyces avermitilis (N245S) and rat (N241S) genes and shown that in both cases the N to S variant enzyme forms quinolacetic acid in place of the native product 2,5-dihydroxyphenylacetic acid (homogentisate). Importantly, the variant enzyme is highly active, establishing the basis for dominant pedigree pattern. Quinolacetic acid reacts readily by Michael addition with cellular thiols to form a two-electron oxidized form of hawkinsin. The N to S variants are also susceptible to inhibition by 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), a known inhibitor of wild-type HPPD. NTBC has been approved for use in the treatment of type I tyrosinemia and as such has an extensive history of use with infants. The N to S variant undergoes an apparent three-step binding mechanism with NTBC that forms with rate constants similar to those observed for the wild-type enzyme. Moreover, the extreme stability of the HPPD.NTBC complex suggests that NTBC would be a potent therapeutic for Hawkinisinuria that would alleviate the extreme frailty experienced in the early life period.
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PMID:Product analysis and inhibition studies of a causative Asn to Ser variant of 4-hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of Hawkinsinuria. 2067 79

Motion sickness is caused by exposure to unfamiliar motions and typical symptoms of motion sickness include nausea and vomiting. To observe the metabolic and hormonal differences between nausea/vomiting (NAV) subjects and non-nausea/vomiting (NNV) ones, and to understand how the differences in metabolites and hormones affect the tolerance of organism to acceleration, 60 volunteers were exposed to repetitive acceleration using a 6-degree-of-freedom ship motion simulator. Meanwhile, 36 rats were randomly divided into three groups: an acceleration model group (n=14, exposed to acceleration), insulin group (n=14, intraperitoneal injection of insulin 30 min before exposure to acceleration), and control group (n=8). Gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF/MS) was applied to analyze the serum metabolites in human subjects. Serum glucocorticoid, insulin, and glucagon levels were determined by radioimmunoassay in the NAV and NNV subjects as well as in rats, and serum epinephrine level was determined by ELISA. After acceleration exposure, 9 metabolites, including L-histidine, L-ornithine, L-serine, L-tyrosine, pyroglutamic acid, fumaric acid, urea, n-dodecanoic acid and n-tetradecanoic acid, had different changes in the NAV and NNV groups. The serum levels of 4-hydroxy-L-proline, glucose, oleic acid and urea were significantly higher in the NAV group than in the NNV group after exposure; however, only the elevation degree of serum glucose was significantly greater in the NAV group than in the NNV group (P<0.05). Serum cortisol and epinephrine were increased in both groups. Before exposure, insulin level in the NAV group was significantly lower than that in the NNV group (P<0.05). After rotation exposure, rat serum glucose in the insulin group was significantly lower than that in the acceleration model group (P<0.001), and the motion sickness index was significantly lower than that in the acceleration model group (P<0.05). Our study provides the first evidence that stable glucose level can help to relieve gastrointestinal symptoms in motion sickness, and suggests that acute hyperglycemia is related to gastrointestinal symptoms in motion sickness.
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PMID:Acute hyperglycemia is related to gastrointestinal symptoms in motion sickness: an experimental study. 2190 24

Staphylococcus aureus produces a wide variety of toxins including staphylococcal enterotoxins (SEs; SEA to SEE, SEG to SEI, SER to SET) with demonstrated emetic activity, and staphylococcal-like (SEl) proteins, which are not emetic in a primate model (SElL and SElQ) or have yet to be tested (SElJ, SElK, SElM to SElP, SElU, SElU2 and SElV). SEs and SEls have been traditionally subdivided into classical (SEA to SEE) and new (SEG to SElU2) types. All possess superantigenic activity and are encoded by accessory genetic elements, including plasmids, prophages, pathogenicity islands, vSa genomic islands, or by genes located next to the staphylococcal cassette chromosome (SCC) implicated in methicillin resistance. SEs are a major cause of food poisoning, which typically occurs after ingestion of different foods, particularly processed meat and dairy products, contaminated with S. aureus by improper handling and subsequent storage at elevated temperatures. Symptoms are of rapid onset and include nausea and violent vomiting, with or without diarrhea. The illness is usually self-limiting and only occasionally it is severe enough to warrant hospitalization. SEA is the most common cause of staphylococcal food poisoning worldwide, but the involvement of other classical SEs has been also demonstrated. Of the new SE/SEls, only SEH have clearly been associated with food poisoning. However, genes encoding novel SEs as well as SEls with untested emetic activity are widely represented in S. aureus, and their role in pathogenesis may be underestimated.
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PMID:Food poisoning and Staphylococcus aureus enterotoxins. 2206 59


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