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1.
Dermatol Online J ; 21(8)2015 Aug 15.
Article in English | MEDLINE | ID: mdl-26437163

ABSTRACT

The side effects of propylthiouracil, including cytopenia and vasculitis, are well established.  We present an interesting case in which cytopenia and cutaneous vasculopathy occurred concomitantly in a critically ill patient.  The patient was initially treated for suspected infection until dermatologic and rheumatologic workup revealed ANCA-positivity and vasculopathy on histopathology, most consistent with an atypical presentation of ANCA-positive vasculitis.  Upon initiation of immunosuppressive therapy, the patient's condition rapidly improved emphasizing the importance of early recognition of this condition.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/chemically induced , Antithyroid Agents/adverse effects , Propylthiouracil/adverse effects , Adult , Anorexia/etiology , Anti-Inflammatory Agents/therapeutic use , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Antithyroid Agents/therapeutic use , Blister/etiology , Eyelid Diseases/etiology , Fatigue/etiology , Female , Graves Disease/complications , Graves Disease/drug therapy , Hemorrhage/etiology , Humans , Immunosuppressive Agents/therapeutic use , Methylprednisolone/therapeutic use , Pancytopenia/chemically induced , Pharyngitis/etiology , Prednisone/therapeutic use , Propylthiouracil/therapeutic use , Respiratory Insufficiency/etiology
3.
Semin Cutan Med Surg ; 30(2): 107-12, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21767772

ABSTRACT

Itch represents a common and significant source of morbidity in the oncological setting. Itch sometimes can be associated with an underlying malignancy, most commonly leukemia or lymphoma. Alternatively, itch may present secondary to malignant invasion causing hepatic or renal dysfunction. Finally, itch may be related to therapeutic regimens for the underlying malignancy. This article seeks to review the clinical scenarios in which itch affects the oncological patient, to briefly present the latest understanding of the molecular and cellular mechanisms of malignancy-related itch, and to review currently available therapeutic options.


Subject(s)
Neoplasms/complications , Pruritus/complications , Antidepressive Agents/therapeutic use , Antineoplastic Agents/adverse effects , Antipruritics/therapeutic use , Antipsychotic Agents/therapeutic use , Humans , Neoplasms/drug therapy , Pruritus/diagnosis , Pruritus/drug therapy , Pruritus/etiology , Pruritus/physiopathology
4.
Cell Host Microbe ; 4(5): 447-57, 2008 Nov 13.
Article in English | MEDLINE | ID: mdl-18996345

ABSTRACT

The distal human gut is a microbial bioreactor that digests complex carbohydrates. The strategies evolved by gut microbes to sense and process diverse glycans have important implications for the assembly and operation of this ecosystem. The human gut-derived bacterium Bacteroides thetaiotaomicron forages on both host and dietary glycans. Its ability to target these substrates resides in 88 polysaccharide utilization loci (PULs), encompassing 18% of its genome. Whole genome transcriptional profiling and genetic tests were used to define the mechanisms underlying host glycan foraging in vivo and in vitro. PULs that target all major classes of host glycans were identified. However, mucin O-glycans are the principal host substrate foraged in vivo. Simultaneous deletion of five genes encoding ECF-sigma transcription factors, which activate mucin O-glycan utilization, produces defects in bacterial persistence in the gut and in mother-to-offspring transmission. Thus, PUL-mediated glycan catabolism is an important component in gut colonization and may impact microbiota ecology.


Subject(s)
Bacteroides/physiology , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/microbiology , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Polysaccharides/metabolism , Symbiosis , Animals , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacteroides/genetics , Female , Humans , Male , Mice , Models, Biological , Swine
5.
Proc Natl Acad Sci U S A ; 103(23): 8834-9, 2006 Jun 06.
Article in English | MEDLINE | ID: mdl-16735464

ABSTRACT

Bacteroides thetaiotaomicron is a prominent member of our normal adult intestinal microbial community and a useful model for studying the foundations of human-bacterial mutualism in our densely populated distal gut microbiota. A central question is how members of this microbiota sense nutrients and implement an appropriate metabolic response. B. thetaiotaomicron contains a large number of glycoside hydrolases not represented in our own proteome, plus a markedly expanded collection of hybrid two-component system (HTCS) proteins that incorporate all domains found in classical two-component environmental sensors into one polypeptide. To understand the role of HTCS in nutrient sensing, we used B. thetaiotaomicron GeneChips to characterize their expression in gnotobiotic mice consuming polysaccharide-rich or -deficient diets. One HTCS, BT3172, was selected for further analysis because it is induced in vivo by polysaccharides, and its absence reduces B. thetaiotaomicron fitness in polysaccharide-rich diet-fed mice. Functional genomic and biochemical analyses of WT and BT3172-deficient strains in vivo and in vitro disclosed that alpha-mannosides induce BT3172 expression, which in turn induces expression of secreted alpha-mannosidases. Yeast two-hybrid screens revealed that the cytoplasmic portion of BT3172's sensor domain serves as a scaffold for recruiting glucose-6-phosphate isomerase and dehydrogenase. These interactions are a unique feature of BT3172 and specific for the cytoplasmic face of its sensor domain. Loss of BT3172 reduces glycolytic pathway activity in vitro and in vivo. Thus, this HTCS functions as a metabolic reaction center, coupling nutrient sensing to dynamic regulation of monosaccharide metabolism. An expanded repertoire of HTCS proteins with diversified sensor domains may be one reason for B. thetaiotaomicron's success in our intestinal ecosystem.


Subject(s)
Bacterial Proteins/metabolism , Carbohydrate Metabolism , Intestines/microbiology , Polysaccharides/metabolism , Symbiosis , Animals , Bacteroides/metabolism , Cecum/microbiology , Cytoplasm/metabolism , Gene Expression Regulation, Bacterial , Germ-Free Life , Humans , Mannose/metabolism , Mice , Models, Biological , Oligonucleotide Array Sequence Analysis , Polysaccharides, Bacterial/genetics , Protein Binding , Protein Structure, Tertiary , alpha-Mannosidase/metabolism
6.
Trends Microbiol ; 12(1): 21-8, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14700548

ABSTRACT

Microbial genome sequencing projects are beginning to provide insights about the molecular foundations of human-bacterial symbioses. The intestine contains our largest collection of symbionts, where members of Bacteroides comprise approximately 25% of the microbiota in adults. The recently defined proteome of a prominent human intestinal symbiont, Bacteroides thetaiotaomicron, contains an elaborate environmental-sensing apparatus. This apparatus includes an unprecedented number of extracytoplasmic function (ECF) sigma-factors, and a large collection of novel hybrid two-component systems composed of membrane-spanning periplasmic proteins with histidine kinase, phosphoacceptor, response regulator receiver and DNA-binding domains. These sensors are linked to the organism's large repertoire of genes involved in acquiring and processing dietary polysaccharides ('the glycobiome'). This arrangement illustrates how a successful symbiont has evolved strategies for detecting and responding to conditions in its niche so that it can sustain beneficial relationships with its microbial and human partners.


Subject(s)
Bacteroides/physiology , Intestines/microbiology , Symbiosis , Amino Acid Sequence , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacteroides/genetics , Gene Expression Regulation, Bacterial , Humans , Models, Molecular , Molecular Sequence Data , Sigma Factor/metabolism , Signal Transduction
7.
Science ; 299(5615): 2074-6, 2003 Mar 28.
Article in English | MEDLINE | ID: mdl-12663928

ABSTRACT

The human gut is colonized with a vast community of indigenous microorganisms that help shape our biology. Here, we present the complete genome sequence of the Gram-negative anaerobe Bacteroides thetaiotaomicron, a dominant member of our normal distal intestinal microbiota. Its 4779-member proteome includes an elaborate apparatus for acquiring and hydrolyzing otherwise indigestible dietary polysaccharides and an associated environment-sensing system consisting of a large repertoire of extracytoplasmic function sigma factors and one- and two-component signal transduction systems. These and other expanded paralogous groups shed light on the molecular mechanisms underlying symbiotic host-bacterial relationships in our intestine.


Subject(s)
Bacteroides/genetics , Genome, Bacterial , Intestines/microbiology , Sequence Analysis, DNA , Symbiosis , Adult , Bacterial Outer Membrane Proteins/genetics , Bacterial Outer Membrane Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/physiology , Bacteroides/physiology , Biological Evolution , Carbohydrate Metabolism , Chromosomes, Bacterial/genetics , Gene Expression Regulation, Bacterial , Genes, Bacterial , Humans , Interspersed Repetitive Sequences , Physical Chromosome Mapping , Polysaccharides/metabolism , Proteome , Sigma Factor/genetics , Sigma Factor/physiology , Signal Transduction
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