The tumor suppressor protein p53 has been well documented as a transcriptional activator involved in the regulation of a number
of critical genes involved in the cell cycle, response to DNA damage, ...and apoptosis. Activation by p53 requires the interaction
of the protein with a consensus binding site consisting of two half-sites, each comprising two copies of the sequence PuPuPuC(A/T)
arranged head-to-head and separated by 0â13 base pairs. In addition to activation, p53 has been shown to be a potent repressor
of transcription. However, the basis for p53-mediated repression is not well understood and has been proposed to occur indirectly
through interactions with other promoter-bound transcription factors. In the present study, we show that p53 can repress transcription
directly by binding to a novel head-to-tail (HT) site within the MDR1 promoter. A mutation that disrupted p53 binding to the MDR1 HT site blocked p53-mediated repression of the MDR1 promoter in transfection assays. Replacement of the HT site with a head-to-head (HH) site converted the activity of p53 from
repression to activation, indicating that simple recruitment of p53 to the promoter is not sufficient for repression and that
the orientation of the binding element determines the fate of p53-regulated promoters.
Discovery of somatically mutated cells in human tissues has been less frequent than would be predicted by in vitro mutational rates. We analyzed the PTEN tumor suppressor gene as an early marker for ...endometrial carcinogenesis, and we show that 43% of histologically normal premenopausal endometria contain rare glands that fail to express PTEN protein because of mutation and/or deletion. These persist between menstrual cycles. Histopathology of PTEN-null glands is initially unremarkable, but with progression, they form distinctive high-density clusters. These data are consistent with a progression model in which initial mutation is not rate limiting.
Intravesical administration of Bacillus Calmette-Guérin is used as a treatment method in superficial bladder cancer. While it is generally well tolerated, serious side effects may develop. ...Granulomatous hepatitis cases have been previously reported; however, only one case with tuberculous peritonitis exists in the current literature. We hereby present two cases, one of which is the second tubercular peritonitis case following Bacillus Calmette-Guérin treatment to be reported, and the other a case with granulomatous hepatitis. Complete cure was achieved in both cases with specific therapy. In the patient who developed peritonitis, intravesical Bacillus Calmette-Guérin therapy was recommenced after antituberculosis treatment, and completed without further complications.
The accurate diagnosis of abdominal tuberculosis usually takes a long time and requires a high index of suspicion in clinic practice. Eighty-eight immune-competent patients with abdominal ...tuberculosis were grouped according to symptoms at presentation and followed prospectively in order to investigate the effect of symptomatic presentation on clinical diagnosis and prognosis.
Based upon the clinical presentation, the patients were divided into groups such as non-specific abdominal pain & less prominent in bowel habit, ascites, alteration in bowel habit, acute abdomen and others. Demographic, clinical and laboratory features, coexistence of pulmonary tuberculosis, diagnostic procedures, definitive diagnostic tests, need for surgical therapy, and response to treatment were assessed in each group.
According to clinical presentation, five groups were constituted as non-specific abdominal pain (n = 24), ascites (n = 24), bowel habit alteration (n = 22), acute abdomen (n = 9) and others (n = 9). Patients presenting with acute abdomen had significantly higher white blood cell counts (p = 0.002) and abnormalities in abdominal plain radiographs (p = 0.014). Patients presenting with alteration in bowel habit were younger (p = 0.048). The frequency of colonoscopic abnormalities (7.5%), and need for therapeutic surgery (12.5%) were lower in patients with ascites, (p = 0.04) and (p = 0.001), respectively. There was no difference in gender, disease duration, diagnostic modalities, response to treatment, period to initial response, and mortality between groups (p > 0.05). Gastrointestinal tract alone was the most frequently involved part (38.5%), and this was associated with acid-fast bacteria in the sputum (p = 0.003).
Gastrointestinal tract involvement is frequent in patients with active pulmonary tuberculosis. Although different clinical presentations of patients with abdominal tuberculosis determine diagnostic work up and need for therapeutic surgery, evidence based diagnosis and consequences of the disease does not change.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUNDHypertriglyceridemia (HTG)-induced acute pancreatitis (AP) leads to higher morbidity and mortality compared with other etiologies. The role of plasma exchange (PE) in this context is still ...not well established. We aimed to assess the clinical outcomes of patients with HTG-induced AP who underwent PE and compare it with those who did not.
PATIENTS AND METHODSWe retrospectively evaluated the data of patients who were admitted with HTG-induced AP between January 2013 and May 2018. The endpoint of the study was to assess the clinical outcomes, which included complication rates, mortality, and pancreatitis recurrence rate.
RESULTSOverall, 41 patients were included in the final analysis. Of these, 12 (29.2%) underwent PE. Patients undergoing PE had more severe pancreatitis on the basis of the Japanese Severity Score 10 (83.3%) vs. 14 (48.3%), P=0.03, respectively). Although mortality was higher in patients who underwent PE three (25.0%) vs. zero, P<0.01, respectively, there was no difference in terms of complications and recurrence rates. Over a median 21 months of follow-up, 11 (26.8%) patients had recurrent AP.
CONCLUSIONAlthough PE effectively reduced plasma triglyceride levels, there was no decrease in mortality or recurrences.
The Temperature Laboratory at TUBITAK UME initiated a study which focused on the construction of freezing point cells of ITS-90 as primary temperature standards. The first cell constructed within the ...scope of this study was an open tin freezing point cell and the results were in good agreement with the reference tin fixed point cell of UME. The second set of cells constructed was two open zinc freezing point cells. The design of these cells is similar to the tin freezing point cell. After construction, all the home-made cells were evaluated by analyzing their melting and freezing curves. Finally comparison measurements were performed between the current laboratory reference zinc cell and all newly constructed cells.
Missense mutations in the gene TP53, which encodes p53, one of the most important tumor suppressors, are common in human cancers. Accumulated mutant p53 proteins are known to actively contribute to ...tumor development and metastasis. Thus, promoting the removal of mutant p53 proteins in cancer cells may have therapeutic significance. Here we investigated the mechanisms that govern the turnover of mutant p53 in nonproliferating tumor cells using a combination of pharmacological and genetic approaches. We show that suppression of macroautophagy by multiple means promotes the degradation of mutant p53 through chaperone-mediated autophagy in a lysosome-dependent fashion. In addition, depletion of mutant p53 expression due to macroautophagy inhibition sensitizes the death of dormant cancer cells under nonproliferating conditions. Taken together, our results delineate a novel strategy for killing tumor cells that depend on mutant p53 expression by the activation of chaperone-mediated autophagy and potential pharmacological means to reduce the levels of accumulated mutant p53 without the restriction of mutant p53 conformation in quiescent tumor cells.
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