Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the era of successful total hip replacement, hip arthrodesis has become an infrequent surgical procedure. Current indications are severe deterioration of the hip joint with a painful, reduced range of motion in young patients, such as disorders subsequent to sepsis of the hip joint, slipped capital epiphysis, Perthes' disease and trauma with contraindications for a total joint replacement. Another important indication is paralysis or musculature loss. From 1980 to 1990, 20 consecutive patients underwent a hip arthrodesis with a cobra plate and were evaluated. None of the patients was lost for follow-up; complications occurred in 5 out of 25 cases (20%). All patients had radiographic evidence of union, 2 patients required re-osteosynthesis and bone grafting. In two cases infection occurred. In one case the position of the fused join went into abduction. Thirteen patients were able to walk free of pain; however, 5 patients were disappointed with the arthrodesis result because of the handicap involved with a fused hip. Hip arthrodesis using the cobra plate is a technically demanding operation, but immediate mobilization and partial weight bearing are facilitated. There is little risk of non-union compared to other surgical procedures. If the technique is correct functional problems will be rare.
 ...
PMID:[Hip joint arthrodesis using the cobra plate. Indication, technique, outcome]. 869 66

Seventeen cases of knee fusion takedown with follow-up periods of 1 to 10 years have been reviewed. Two patients were re-fused for patellar tendon loss and sepsis. One had a chronic low-grade infection but refused re-fusion. Two patients who required immobilization for the first 10 days following total knee arthroplasty had a range of flexion of 35 degrees only. The mean range of flexion in the other patients in 84 degrees. Using The Hospital for Special Surgery rating, 29.4% scored excellent, 29.4% good, 17.6% fair, and 17.6% poor, including the two patients refused. Complications were found in nine patients (53%), six of which were resolved with further surgery. All patients preferred the mobile knee, but the complication rate is so high that the authors remain ambivalent about this procedure.
 ...
PMID:Results of total knee arthroplasty following takedown of formal knee fusion. 888 50

Three pairs of female conjoined twins--a xiphoomphalopagus, a pygopagus, and a thoracopagus--were encountered during the past 10 years. Surgical separation was successful in the xiphopagus, and both twins survived. Separation was also successful in the pygopagus, but only one of the twins survived; the twin that died had sustained cerebral hemorrhage before the operation. Both of the twins in the thoracopagus died before surgery could be performed, due to sepsis and heart failure, 44 days after birth. Separation surgery of conjoined twins is often successful with a high survival rate of both twins unless vital organs such as the brain or the heart are fused. However, unlike other operations, separation surgery entails ethical considerations pertaining to matters such as the distribution of organs in addition to surgical considerations. Furthermore, separation of conjoined twins is certain to cause various degrees of anatomical as well as functional disorders associated with the surgical procedure, and provision for the postoperative care for these disorders is indispensable.
 ...
PMID:Experience with treatment of three pairs of conjoined twins. 925 92

We studied the role of inducible nitric oxide synthase (iNOS) in septic lung injury using a novel and selective iNOS inhibitor (a fused piperidine derivative; ONO-1714) following a cecal ligation and puncture (CLP) procedure. All rats that received CLP died within 48 h after the intervention. The subcutaneous injection of ONO-1714 at 0.03 mg/kg every 12 h resulted in a significantly longer survival time than the saline control only when administration was started 12 h after the CLP procedure. The other administration schedules, which started immediately or 6 h after the intervention, did not show any improvement in the survival rates in comparison with the saline control. The administration of ONO-1714 at higher (0.1 mg/ kg) or lower (0.01 mg/kg) doses when given anytime after the intervention did not improve the survival rates. The NO(x) (NO(2)(-) + NO(3)(-)) levels in the plasma significantly increased 12 h after intervention in comparison with NO(x) at 0 h and thereafter further increased in parallel with the time elapsed. The CLP rats that were initially treated with ONO-1714 (0.03 mg/kg subcutaneously every 12 h) 12 h after intervention showed significantly reduced NO(x) levels in the plasma in comparison with the saline control. The NO synthase activity in lung homogenates increased from 6 to 24 h after the CLP and thereafter decreased to 42 h. The administration of ONO-1714 inhibited iNOS activity (under calcium-free conditions) in preference to total iNOS activity (under calcium-dependent conditions) in lung homogenates, which thus suggested that this compound selectively inhibited iNOS in lung tissue. The iNOS protein expression in the lung and liver homogenates showed a similar time course with alterations of NOS activity, namely a maximum level at 24 h after the intervention followed by decreasing levels to 42 h. On the other hand, other isozymes of NOS, eNOS, and nNOS in lung homogenates, were constantly expressed over the time course after the CLP. Since the iNOS mRNA expression in lung homogenates continued to elevate until 42 h, the decrease in iNOS activity and protein expression later than 24 h after the CLP was thus considered to be due to some posttranscriptional mechanism during the late phase of sepsis. In conclusion, intervention with a potent and selective iNOS inhibitor seemed to improve survival in CLP rats when used at the appropriate doses and time points. However, the self-limited mechanism of iNOS regulation in the lungs may also indicate that iNOS plays only a limited role in sepsis and septic shock.
 ...
PMID:Evaluating the role of inducible nitric oxide synthase using a novel and selective inducible nitric oxide synthase inhibitor in septic lung injury produced by cecal ligation and puncture. 1093 11

Tumor necrosis factor-alpha (TNF-alpha) is a key mediator of inflammatory responses and gram-negative bacterial sepsis, but the role that it plays during Salmonella enterica species bacterial infections in swine has not yet been elucidated. To facilitate studies on the role of TNF-alpha on the pathology associated with Salmonella infections in pigs, recombinant soluble porcine TNF receptor type I (rspTNF-RI) and soluble TNF receptor type I fused to the Fc region of porcine IgG1 (rspTNF-RI-IgG) were expressed in insect cells using a baculovirus expression system. The proteins were secreted into the cell culture media and purified by anti-soluble porcine TNF-RI antibody and protein G affinity chromatography, respectively. The yield of protein using this method was approximately 1.5mg rspTNF-RI and 4mg rspTNF-RI-IgG/L of cell culture medium. In in vitro assays, rspTNF-RI-IgG was approximately 10-fold (0.97 vs. 10.00pmol/ml) more effective than rspTNF-RI at completely inhibiting the cytotoxic activity of 500U of recombinant porcine TNF-alpha on 3 x 10(4) WEHI 164 murine fibrosarcoma, clone 13, cells. Compared to previously described methods, this method yields significantly more biologically active rspTNF-RI.
 ...
PMID:Development of a baculovirus expression system for soluble porcine tumor necrosis factor receptor type I and soluble porcine tumor necrosis factor receptor type I-IgG fusion protein. 1200 91

The MLL gene at chromosome band 11q23 is frequently rearranged and fused to partner genes in acute leukemias. Previously, the MSF gene, also called AF17q25, has been cloned as a fusion partner of the MLL gene in therapy-related or infant acute myelogenous leukemias with t(11;17)(q23;q25). MSF belongs to the septin family of proteins, which includes other MLL fusion partners, hCDCrel1 and Septin 6, and has also been implicated in the pathogenesis of human ovarian tumor and murine T-cell lymphoma. We describe here a 64-year-old man with de novo acute myelomonocytic leukemia (French-American-British subtype M4) with t(11;17)(q23;q25). His leukemia was successfully induced into a first remission, which, however, lasted only briefly. A second remission was never attained, and the patient died of sepsis 16 months after the diagnosis of leukemia. Examination of his leukemic cells at diagnosis revealed an MLL gene rearrangement, by Southern blotting, and an MLL-MSF fusion transcript, by the reverse transcriptase polymerase chain reaction (RT-PCR) method. Sequence analysis of the RT-PCR product further revealed that MLL exon 5 was fused in-frame to MSF exon 3. Further clinical and molecular analyses of acute leukemias with the MLL-MSF transcript may shed more light on the clinical characteristics and molecular mechanisms of the MLL-septin type leukemias.
 ...
PMID:Fusion of MLL and MSF in adult de novo acute myelomonocytic leukemia (M4) with t(11;17)(q23;q25). 1209 51

We present two patients with Ph-negative chronic myeloid leukemia (CML) and fusion signal BCR/ABL on both chromosomes 9, located in region 9q34. The first case was a 27 years old man with CML. Molecular studies (RT-PCR) revealed the rearrangement in the major-BCR region and expression of chimeric BCR/ABL mRNA of b3a2 configuration. By classical cytogenetic studies (G-banding) karyotype 46,XY was found in short-term cultivated bone marrow cells and phytohemagglutinin (PHA) stimulated peripheral lymphocytes. FISH studies revealed the BCR/ABL fusion signals on both chromosomes 9 and green BCR signals on both chromosomes 22 in all mitoses studied. Detection of the alleles of ABL1 intragenic STR locus by fluorescence PCR followed by fragmentation analysis in the patient and his parents provided no information about transmission of the ABL gene. Quantitative assessment of BCR/ABL transcript level by RT-PCR showed 60 and 70% BCR/ABL positivity in two peripheral blood samples at 6,5 and 10,5 months after diagnosis, respectively, which does not correspond to the expression from two identical BCR/ABL hybrid genes. Therefore, the possible mechanism of the origin of two BCR/ABL fusion signals present on both chromosomes 9 could not be resolved and remains speculative. The second case was a 53 years old male with diagnosis of chronic phase of CML, with first sign of acceleration one month after diagnosis and death because of sepsis in blastic phase within four months. The cytogenetic findings were identical to those in case No. 1., i.e. karyotype 46, XY by G-banding, two BCR/ABL fusion signals on both chromosomes 9 and RT-PCR molecular studies proved b3a2 breakpoints. It is generally accepted that prognosis of the patients with fused BCR/ABL gene located on chromosome 9 is poor. The presence of two fused genes could be anticipated as two Ph chromosomes in accelerated and blastic phases of the disease. However, in our study, quantitative findings of BCR/ABL transcripts did not corresponded to the expression of two BCR/ABL genes originating from duplication. If this assumption is correct then the expression of both fused genes BCR/ABL was in case No. 1 equally suppressed and total expression reached about the level of one BCR/ABL gene.
 ...
PMID:Location of the BCR/ABL fusion genes on both chromosomes 9q34 in Ph negative chronic myeloid leukemia. 1240 Jun 16

Streptococcus agalactiae is the leading cause of bacterial sepsis and meningitis in neonates and also the causative agent of different serious infections in immunocompromised adults. The wide range of diseases that are caused by S. agalactiae suggests regulatory mechanisms that control the formation of specific virulence factors in these bacteria. The present study describes a gene from S. agalactiae, designated rogB, encoding a protein with significant similarity to members of the RofA-like protein (RALP) family of transcriptional regulators. Disruption of the rogB gene in the genome of S. agalactiae resulted in mutant strain RGB1, which was impaired in its ability to bind to fibrinogen and fibronectin. Mutant RGB1 also exhibited a reduced adherence to human epithelial cells but did not show an altered invasion of eukaryotic cells. By real-time PCR analysis, mutant RGB1 revealed an increased expression of the cpsA gene, encoding a regulator of capsule gene expression. However, strain RGB1 exhibited a reduced expression of the rogB gene and of two adjacent genes, encoding putative virulence factors in S. agalactiae. Furthermore, mutant RGB1 was impaired in the expression of the fbsA gene, coding for a fibrinogen receptor from S. agalactiae. The altered gene expression in mutant RGB1 could be restored by plasmid-mediated expression of rogB, confirming a RogB deficiency as the cause for the observed changes in virulence gene expression in S. agalactiae. Reporter gene studies with a promotorless luciferase gene fused to fbsA allowed a growth-dependent analysis of fbsA expression in S. agalactiae. These reporter gene studies also suggest that RogB exerts a positive effect on fbsA expression in S. agalactiae.
 ...
PMID:Analysis of RogB-controlled virulence mechanisms and gene repression in Streptococcus agalactiae. 1293 48

Slide-based cytometry (SBC) and related techniques offer unique tools to perform complex diagnostic procedures at very early disease stages. Multicolor or polychromatic analysis of cells by SBC is of special importance, not only as a cytomics technology platform, but for patients with low blood volume such as neonates. The exact knowledge of the location of each cell on the slide allows the specimen to be restained and subsequently reanalyzed. These separate measurements can be fused to one data file (merging), increasing the information obtained per cell. Relocalization and optical evaluation of the cells, a typical feature of SBC, can be of integral importance for cytometric analysis. Predictive medicine is aimed at the detection of changes in the patient's state prior to the manifestation of deterioration or improvement. Such instances are concerned with multiorgan failure in sepsis or noninfectious posttraumatic shock in intensive care patients, or the pretherapeutic identification of high risk patients in cancer cytostatic therapy. Early anti-infectious or anti-shock therapy, as well as curative chemotherapy in combination with stem cell transplantation, may provide better survival chances for the patient as well as concomitant cost containment. Predictive medicine-guided, individualized, early reduction or cessation of therapy may lower or abrogate potential therapeutic side effects (individualized medicine). With the 8th Leipziger Workshop and the 1st International Workshop on Slide-Based Cytometry, cytomics technologies moved to more practical applications in the clinics and the clinical laboratory. This development will be continued in 2004, at the upcoming Leipziger Workshop and the International Workshop on Slide-Based Cytometry.
 ...
PMID:Slide-based cytometry and predictive medicine: the 8th Leipziger workshop and the 1st international workshop on slide-based cytometry. 1529 Jul 20

Although tightly regulated programmed cell death (apoptosis) possesses great importance for tissue homeostasis, several pathologic processes are associated with organ failure due to adversely activated cell apoptosis. Transient increase in apoptosis has been shown to cause organ damage during fulminant hepatitis B, autoimmune diseases, ischemia-reperfusion injury, sepsis, or allograft rejection. A defined and temporary inhibition of cell apoptosis may therefore be of high clinical relevance. Activation of death receptors results in caspase-8 recruitment to the death-inducing signaling complex, which initiates the apoptotic process through cleavage of caspase-8 and downstream substrates. This initial step may be inhibited by the caspase-8 inhibitor FLIP (FLICE inhibitory protein). To specifically inhibit the initiation of death receptor-mediated apoptosis we constructed a fusion protein containing FLIP fused N-terminally to the human immunodeficiency virus TAT domain. This TAT domain allows the fusion protein to cross the cell membrane and thus makes the FLIP domain able to interfere with the death-inducing signaling complex inside of the cell. We observed that incubation of lymphocytic Jurkat or BJAB cells with TAT-FLIPS proteins significantly inhibits Fas-induced activation of procaspase-8 and downstream caspases, preventing cells from undergoing apoptosis. Systemic application of TAT-FLIPS prolongs survival and reduces multi-organ failure due to Fas-receptor-mediated lethal apoptosis in mice. Therefore, application of cellular FLIPS in the form of a TAT fusion protein may open a promising, easily applicable new tool for providing protection against transient, pathologically increased apoptosis in various diseases.
 ...
PMID:Transduction of the TAT-FLIP fusion protein results in transient resistance to Fas-induced apoptosis in vivo. 1530 99


<< Previous 1 2 3 4 5 Next >>