Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic hyperthermia in man may occur by accident, as in heat stroke or malignant hyperthermia during general anesthesia, or it may be therapeutically induced (fever therapy). The latter has been used infrequently since the advent of antibiotics, except recently for treatment of cancer. Local or regional heating combined with x irradiation for human cancer therapy has been sporadically reported for over 60 years, but has not found its place in clinical medicine possibly due to technical limitations in heat production and dosimetry. Preliminary results are reported for treatment of spontaneous animal tumors with radiofrequency current fields and x irradiation.
 ...
PMID:Prospects for hyperthermia in human cancer therapy. Part I: hyperthermic effects in man and spontaneous animal tumors. 32 7

Acute lymphatic leukemia (ALL) represents one of the most frequent malignancies in childhood. Central venous access ports or partly implanted silicone catheters are usually placed for high-dose chemotherapy in these children. We report two patients aged 7 and 3 years with acute lymphoblastic beta-cell leukemia (B-ALL), a less common subtype of ALL, which presented with hyperthermia (38.4 degrees C and 39 degrees C) during anesthesia with isoflurane for implantation of a central venous catheter. The hyperthermic reactions were accompanied by an increase in expired CO2 and acidosis as well as moderate elevation of heart rate and blood pressure. As in both patients the history and preoperative findings did not reveal signs of infection or other causes of fever, the observed alterations were interpreted as symptoms of malignant hyperthermia triggered either by succinylcholine or isoflurane, which were used in both children. In addition, the hyperthermia responded to administration of dantrolene sodium according to dose recommendations for treatment of malignant hyperthermia. In one of the patients, withdrawal of dantrolene during the initial postoperative hours was followed by a recurrent increase in body temperature, which once again could be suppressed by additional dantrolene infusion. According to the literature, malignant hyperthermia has occasionally been described in children with malignancies such as leukemia or Burkitt's lymphoma. Our observations indicate that children with B-ALL may be especially susceptible to malignant hyperthermia. Close monitoring of body temperature and expiratory CO2 are therefore indicated in these children, and dantrolene therapy should be started immediately in case of increased temperature during anesthesia.
 ...
PMID:[Hyperthermic reaction in the perioperative phase in 2 children with acute lymphoblastic leukemia of B-cell type]. 292 70

An adult patient with massive abdominal Burkitt's lymphoma developed malignant hyperthermia during exploratory laparotomy. Simultaneously, evidence of tumor lysis appeared. The lethal effect of heat on cancer cells has been amply demonstrated experimentally, and clinical trials of regional and whole-body hyperthermia in various human malignancies have appeared. Lymphomas have not been reported among those tumors studied. Burkitt's lymphoma, a rapidly growing tumor, is likely to respond to hyperthermia, and the evidence reported here should be pursued with controlled clinical trials involving induced hyperthermia in refractory malignant lymphomas.
Cancer Treat Rep
PMID:Burkitt's lymphoma: tumor lysis following malignant hyperthermia. 740 66

Pharmacogenetics of cytochromes P-450. Cytochromes P-450 are a large family of enzymes found in all living species whose function is the activation of molecular oxygen which, in turn, will oxidize an organic substrate. They are divided in two groups: one including the constitutive enzymes that intervene in vital processes such as cholesterol synthesis, cholesterol transfer into steroid and sex hormones, prostaglandin synthesis, etc.; the other group including the inducible enzymes, responsible of the metabolism of exogenous substances. Their concentration increases in the presence of specific substrates, like herbicides, cigarette smoke, hydrocarbons, insecticides, etc.. Of the latter group, the genetic polymorphism of two families is described. Family I is involved in the metabolism of polycyclic aromatic hydrocarbons: an allele codifying for a low activity cytoplasmic receptor (autosomic recessive inheritance) and a high affinity one (recessive inheritance) are present. The transformations carried out by the cytochromes P-450 give origin to intermediate reactive products, epoxides, that bonding to nucleoproteins or nucleic acids, can have either toxic or carcinogenic action. Therefore, the subjects with high affinity genes have an increased risk of cancer. This phenomenon, relating to pulmonary cancer, has been demonstrated in cigarette smokers. Family II is the group of greatest pharmacogenetic and clinical interest, since it is responsible of the polymorphism of the response to different drugs, such as halothane, (malignant hyperthermia), ethanol (alcohol intolerance), nitrosamine, (cancer), debrisoquine (hypotension), spartein (excessive uterine contractions). An increased or reduced ability to metabolize specific substances is the consequence: the pharmacological effects can therefore vary very much in the two classes of carriers of different alleles. Possible future applications of these polymorphisms in clinical practice are discussed.
 ...
PMID:[Pharmacokinetics of cytochrome P-450]. 823 56

The protease prostate-specific antigen (PSA) is a marker widely used clinically for monitoring prostatic malignancies. Under normal conditions, this enzyme is mainly involved in the post ejaculation degradation of the major human seminal protein, the seminal plasma motility inhibitor precursor/semenogelin I (SPMIP/SgI), which is the predominant protein component of human semen coagulum. PSA primary structure and activity on synthetic substrates predict a chymotrypsin-like activity whose specificity remains to be established. The present study was aimed at characterizing the proteolytic processing of the SPMIP/SgI by PSA. Purified SPMIP/SgI was incubated with PSA in the presence or absence of protease inhibitors. General serine protease inhibitors, heavy metal cations (Zn2+ and Hg2+), and the heavy metal chelator 1,10-phenanthroline partially or totally inhibited the proteolytic activity of PSA toward SPMIP/SgI. Under identical conditions, other proteins, such as bovine serum albumin, ovalbumin, and casein, were very poor substrates for PSA. Hydrolysis products were separated by reverse-phase high-performance liquid chromatography, assayed for sperm motility inhibitory activity, and analyzed by immunoblotting and mass spectrometry. The region responsible for the sperm motility inhibitory activity and containing an SPMI antiserum epitope was localized to the N-terminal portion of the molecule between residues 85 and 136. On the other hand, a monoclonal antibody against a seminal vesicle-specific antigen (MHS-5) recognized fragments derived from the central part of the SPMIP/SgI (residues 198-223). PSA hydrolysis occurred almost exclusively at either leucine or tyrosine residues, demonstrating directly for the first time a restricted chymotrypsin-like activity on a physiological substrate. The results suggest that PSA is the main enzyme responsible for the processing of SPMIP/SgI in human semen and that this protease manifests unusual specificity with respect to hydrolyzable substrates and sites of hydrolysis.
 ...
PMID:Characterization of prostate-specific antigen proteolytic activity on its major physiological substrate, the sperm motility inhibitor precursor/semenogelin I. 909 10

Oculopharyngodistal-myopathy (OPDM) is an autosomal dominant, heredofamilial myopathy accompanied with slowly progressive ptosis and extraocular palsy, and weakness of the masseter, facial, and bulbar muscles, as well as distal involvement of the limbs starting around 40 years of age or later. A 54-year-old female with OPDM underwent resection of the uterus for uterus body cancer. We speculated the patient might be at the risk of aspiration pneumonia, prolonged respiratory depression, and malignant hyperthermia, and chose spinal and epidural anesthesia. The operation was performed successfully and the patient was discharged uneventfully.
 ...
PMID:[Anesthetic management of a patient with oculopharyngodistal-myopathy]. 1264 70

The development of intraoperative hyperthermia has been reported in association with blood malignancies. This is case report of hyperthermia in a child with neuroblastoma, which was not an episode of malignant hyperthermia as determined by arterial blood cases and physiologic vital signs.
 ...
PMID:Intraoperative hyperthermia in a child with neuroblastoma. 1688 75

A 70-year-old man with lung cancer was scheduled for partial resection of the right lung. Preoperative serum creatine kinase was elevated (1808 IU x l(-1), CK-MM 97%). Acute coronary syndrome was denied by the absence of significant stenosis of coronary artery and the normal segmental wall motion in echocardiography. The other examinations did not reveal the cause of CK elevation. He did not receive dantlorene preoperatively, but the surgical procedure was performed uneventfully without the use of the triggering agents, such as volatile inhalational anesthetic gases and suxamethonium. Thoracic wall was not invaded by the tumor. After the operation, CK went down quickly. It decreased further after the postoperative chemotherapy. We concluded that CK elevation might have been produced by adenocarcinoma itself, judging from the rapid decrease after surgery and the absence of thoracic wall invasion. Though CK elevation may indicate the malignant hyperthermia, we should not delay the surgery too long when there is possibility of CK elevation derived from cancer itself.
 ...
PMID:[How should we manage patients with elevated preoperative creatine kinase? --A case of CK productive lung cancer]. 1757 18

Previous studies have shown that there are profuse lymphatic tissues under the intestinal mucous membrane. Moreover, vaccine administered orally can elicit both mucous membrane and system immune response simultaneously, accordingly induce tumor-specific cytotoxic T lymphocyte. As a result, the oral route is constituted the preferred immune route for vaccine delivery theoretically. However, numerous vaccines especially protein/peptide vaccines remain poorly available when administered by this route. Nanoemulsion has been shown as a useful vehicle can be developed to enhance the antitumor immune response against antigens encapsulated in it and it is good for the different administration routes. Of particular interest is whether the protein vaccine following peroral route using nanoemulsion as delivery carrier can induce the same, so much as stronger antitumor immune response to following conventional ways such as subcutaneous (sc.) or not. Hence, in the present study, we encapsulated the MAGE1-HSP70 and SEA complex protein in nanoemulsion as nanovaccine NE (MHS) using magnetic ultrasound method. We then immuned C57BL/6 mice with NE (MHS), MHS alone or NE (-) via po. or sc. route and detected the cellular immunocompetence by using ELISpot assay and LDH release assay. The therapeutic and tumor challenge assay were examined then. The results showed that compared with vaccination with MHS or NE (-), the cellular immune responses against MAGE-1 could be elicited fiercely by vaccination with NE (MHS) nanoemulsion. Furthermore, encapsulating MHS in nanoemulsion could delay tumor growth and defer tumor occurrence of mice challenged with B16-MAGE-1 tumor cells. Especially, the peroral administration of NE (MHS) could induce approximately similar antitumor immune responses to the sc. administration, but the MHS unencapsulated with nanoemulsion via po. could induce significantly weaker antitumor immune responses than that via sc., suggesting nanoemulsion as a promising carrier can exert potent antitumor immunity against antigen encapsulated in it and make the tumor protein vaccine immunizing via po. route feasible and effective. It may have a broad application in tumor protein vaccine.
Cancer Immunol Immunother 2009 Feb
PMID:The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following peroral administration route. 1852 70

Ryanodine receptors (RyRs) are high conductance intracellular cation channels that release calcium ions from stores such as the endoplasmic reticulum and sarcoplasmic reticulum. Although RyRs are expressed in many cell types, their roles have only been extensively characterised in tissues in which they are abundant: RyR1 is essential for excitation-contraction coupling in skeletal muscle; whereas RyR2 is required for the analogous signal transduction pathway in heart. Defects in RyR1 cause malignant hyperthermia and a spectrum of myopathies in skeletal muscle; whereas RyR2 dysregulation can result in fatal cardiac arrhythmias and is involved in heart failure. Altered RyR gating has been implicated in a range of other diseases, including epilepsy, neurodegeneration, pain and cancer. RyRs interact with a range of toxic substances, providing insights into their functional and structural properties. Consequently, these channel complexes represent potential therapeutic targets for treatment of numerous diseases. Furthermore, strategies for combating multicellular parasites and agricultural pests could exploit pharmacological differences between their RyRs and those of vertebrates. However, available pharmacological tools for manipulation of RyR gating are generally unsuitable for clinical, veterinary or agricultural use, owing to their lack of selectivity, inappropriate solubility in the aqueous or lipid environment, or generation of side-effects. The expression, subcellular distribution and gating of RyRs is modified by a wide variety of cellular proteins, some of which are expressed in a developmentally or tissue-restricted manner. This commentary examines the possibility of manipulating the expression and function of such proteins in order develop new drugs acting on RyR channel complexes.
 ...
PMID:Ryanodine receptor calcium channels and their partners as drug targets. 2009 79


1 2 Next >>