Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unlike what has been approved overseas, only a low dose is approved in Japan for the use of Gentamicin Sulfate Injection (hereinafter referred to as GM Injection). A change in dose and administration was requested to the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs. As a consequence, high-dose GM Injection began to be developed in Japan. In order to assess the current use of GM Injection, a questionnaire survey was conducted among infectious disease specialists certified by the Japanese Association for Infectious Diseases, and physicians certified as specialists/instructors of antibiotic chemical treatment by the Japanese Society of Chemotherapy. Valid responses were obtained from as many as 38.0% of questionnaire recipients (719/1891 physicians). About 30% of the respondents used GM Injection in the year 2011. Major indications for adult patients included sepsis and infective endocarditis, and bacterial strains mainly included Pseudomonas aeruginosa, Staphylococcus, Enterococcus and Streptococcus species. Some diseases and bacterial strains domestically unapproved as indications were also treated with GM Injection. GM Injection is administered mainly as an intravenous infusion, usually once daily, which is not approved in Japan. Some physicians administered a fixed dose of GM (120 mg/day or less), not more than the upper limit approved in Japan. The majority of physicians, however, adopted a dosage of 3-5 mg/kgy/day, the standard dosage approved overseas. Physicians who implemented TDM outnumbered those who did not. The target blood level when administering 2-3 times a day was mostly 2 microg/mL or less as the trough level, and 4-10 microg/mL as the peak level. In particular, GM Injection was concurrently administered with other injectable antimicrobial agents to treat sepsis or infective endocarditis mainly in the following combinations: with penicillins or carbapenems for sepsis: with penicillins for infective endocarditis. Renal impairment was the most common adverse reaction requiring special care to be reported by the respondents. The survey revealed the current status of use, which is that GM Injection is used at the dose and administration approved in Japan, and that high-dose GM Injection, equivalent to the dosage approved overseas, is also used by quite a few physicians. The current use supports the request submitted to the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs. Therefore, the same dosage that is approved overseas is recommended to be approved as soon as possible in Japan.
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PMID:[Results of a questionnaire survey on the use of gentamicin sulfate injection]. 2381 49

The musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) has been recently recognized as a clinical entity. MC-EDS represents a differential diagnosis within the congenital neuromuscular and connective tissue disorders spectrum. Thirty-one and three patients have been reported with MC-EDS so far with bi-allelic mutations identified in CHST14 and DSE, respectively, encoding two enzymes necessary for dermatan sulfate (DS) biosynthesis. We report seven additional patients with MC-EDS from four unrelated families, including the follow-up of a sib-pair originally reported with the kyphoscoliotic type of EDS in 1975. Brachycephaly, a characteristic facial appearance, an asthenic build, hyperextensible and bruisable skin, tapering fingers, instability of large joints, and recurrent formation of large subcutaneous hematomas are always present. Three of seven patients had mildly elevated serum creatine kinase. The oldest patient was blind due to retinal detachment at 45 years and died at 59 years from intracranial bleeding; her affected brother died at 28 years from fulminant endocarditis. All patients in this series harbored homozygous, predicted loss-of-function CHST14 mutations. Indeed, DS was not detectable in fibroblasts from two unrelated patients with homozygous mutations. Patient fibroblasts produced higher amounts of chondroitin sulfate, showed intracellular retention of collagen types I and III, and lacked decorin and thrombospondin fibrils compared with control. A great proportion of collagen fibrils were not integrated into fibers, and fiber bundles were dispersed into the ground substance in one patient, all of which is likely to contribute to the clinical phenotype. This report should increase awareness for MC-EDS.
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PMID:The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations. 2637 98

The interaction of microorganisms with fibronectin plays an important role in infective endocarditis. Characterization of fibronectin binding is not sufficient for nutritionally variant streptococci (NVS), which is an important pathogen associated with this disease. In this study, we identified and purified the novel fibronectin binding protein (FBP) by sonication and column chromatography from a ' Granulicatella para-adiacens' strain isolated from the oral cavity of a healthy donor. The purified molecule was located at the top of the gel in SDS-PAGE analysis, and heat treatment in the presence of sodium dodecyl sulfate resulted in its dissociation into smaller molecules. An anti-purified protein antibody was reacted with the topmost component of the sonic extract only from two ' G. para-adiacens' strains in Western blot analyses. Immunofluorescence staining indicated that the protein of interest was located on the cell surface of ' G. para-adiacens', but not on other NVS species. Bacterial adherence to fibronectin was inhibited by the purified FBP preparation. Optimum conditions for fibronectin binding of purified FBP were shown to be an NaCl concentration higher than 150 mM and a pH of c. 7.0. These results provide additional information for the elucidation of fibronectin binding by NVS.
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PMID:Purification of a novel fibronectin binding protein from 'Granulicatella para-adiacens'. 3097 36


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