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1.
Microbiol Spectr ; 12(6): e0034624, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38709084

ABSTRACT

Across the Burkholderia genus O-linked protein glycosylation is highly conserved. While the inhibition of glycosylation has been shown to be detrimental for virulence in Burkholderia cepacia complex species, such as Burkholderia cenocepacia, little is known about how specific glycosylation sites impact protein functionality. Within this study, we sought to improve our understanding of the breadth, dynamics, and requirement for glycosylation across the B. cenocepacia O-glycoproteome. Assessing the B. cenocepacia glycoproteome across different culture media using complementary glycoproteomic approaches, we increase the known glycoproteome to 141 glycoproteins. Leveraging this repertoire of glycoproteins, we quantitively assessed the glycoproteome of B. cenocepacia using Data-Independent Acquisition (DIA) revealing the B. cenocepacia glycoproteome is largely stable across conditions with most glycoproteins constitutively expressed. Examination of how the absence of glycosylation impacts the glycoproteome reveals that the protein abundance of only five glycoproteins (BCAL1086, BCAL2974, BCAL0525, BCAM0505, and BCAL0127) are altered by the loss of glycosylation. Assessing ΔfliF (ΔBCAL0525), ΔmotB (ΔBCAL0127), and ΔBCAM0505 strains, we demonstrate the loss of FliF, and to a lesser extent MotB, mirror the proteomic effects observed in the absence of glycosylation in ΔpglL. While both MotB and FliF are essential for motility, we find loss of glycosylation sites in MotB or FliF does not impact motility supporting these sites are dispensable for function. Combined this work broadens our understanding of the B. cenocepacia glycoproteome supporting that the loss of glycoproteins in the absence of glycosylation is not an indicator of the requirement for glycosylation for protein function. IMPORTANCE: Burkholderia cenocepacia is an opportunistic pathogen of concern within the Cystic Fibrosis community. Despite a greater appreciation of the unique physiology of B. cenocepacia gained over the last 20 years a complete understanding of the proteome and especially the O-glycoproteome, is lacking. In this study, we utilize systems biology approaches to expand the known B. cenocepacia glycoproteome as well as track the dynamics of glycoproteins across growth phases, culturing media and in response to the loss of glycosylation. We show that the glycoproteome of B. cenocepacia is largely stable across conditions and that the loss of glycosylation only impacts five glycoproteins including the motility associated proteins FliF and MotB. Examination of MotB and FliF shows, while these proteins are essential for motility, glycosylation is dispensable. Combined this work supports that B. cenocepacia glycosylation can be dispensable for protein function and may influence protein properties beyond stability.


Subject(s)
Bacterial Proteins , Burkholderia cenocepacia , Glycoproteins , Proteomics , Glycosylation , Burkholderia cenocepacia/metabolism , Burkholderia cenocepacia/genetics , Burkholderia cenocepacia/growth & development , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Glycoproteins/metabolism , Glycoproteins/genetics , Proteome/metabolism
2.
Genes (Basel) ; 14(2)2023 01 24.
Article in English | MEDLINE | ID: mdl-36833231

ABSTRACT

How complex morphological patterns form is an intriguing question in developmental biology. However, the mechanisms that generate complex patterns remain largely unknown. Here, we sought to identify the genetic mechanisms that regulate the tan (t) gene in a multi-spotted pigmentation pattern on the abdomen and wings of Drosophila guttifera. Previously, we showed that yellow (y) gene expression completely prefigures the abdominal and wing pigment patterns of this species. In the current study, we demonstrate that the t gene is co-expressed with the y gene in nearly identical patterns, both transcripts foreshadowing the adult abdominal and wing melanin spot patterns. We identified cis-regulatory modules (CRMs) of t, one of which drives reporter expression in six longitudinal rows of spots on the developing pupal abdomen, while the second CRM activates the reporter gene in a spotted wing pattern. Comparing the abdominal spot CRMs of y and t, we found a similar composition of putative transcription factor binding sites that are thought to regulate the complex expression patterns of both terminal pigmentation genes y and t. In contrast, the y and t wing spots appear to be regulated by distinct upstream factors. Our results suggest that the D. guttifera abdominal and wing melanin spot patterns have been established through the co-regulation of y and t, shedding light on how complex morphological traits may be regulated through the parallel coordination of downstream target genes.


Subject(s)
Drosophila Proteins , Drosophila , Animals , Drosophila/genetics , Drosophila Proteins/genetics , Melanins/genetics , Enhancer Elements, Genetic , Abdomen
3.
Sci Rep ; 12(1): 14767, 2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36042264

ABSTRACT

Initially, vanadium dioxide seems to be an ideal first-order phase transition case study due to its deceptively simple structure and composition, but upon closer inspection there are nuances to the driving mechanism of the metal-insulator transition (MIT) that are still unexplained. In this study, a local structure analysis across a bulk powder tungsten-substitution series is utilized to tease out the nuances of this first-order phase transition. A comparison of the average structure to the local structure using synchrotron x-ray diffraction and total scattering pair-distribution function methods, respectively, is discussed as well as comparison to bright field transmission electron microscopy imaging through a similar temperature-series as the local structure characterization. Extended x-ray absorption fine structure fitting of thin film data across the substitution-series is also presented and compared to bulk. Machine learning technique, non-negative matrix factorization, is applied to analyze the total scattering data. The bulk MIT is probed through magnetic susceptibility as well as differential scanning calorimetry. The findings indicate the local transition temperature ([Formula: see text]) is less than the average [Formula: see text] supporting the Peierls-Mott MIT mechanism, and demonstrate that in bulk powder and thin-films, increasing tungsten-substitution instigates local V-oxidation through the phase pathway VO[Formula: see text] V[Formula: see text]O[Formula: see text] V[Formula: see text]O[Formula: see text].

4.
ACS Appl Mater Interfaces ; 13(48): 57567-57575, 2021 Dec 08.
Article in English | MEDLINE | ID: mdl-34841849

ABSTRACT

Many of the promising, high-performing solid electrolytes for lithium-ion batteries are amorphous or contain an amorphous component, particularly in the Li thiophosphate Li2S-P2S5 (LPS) compositional series. An explicit study of the local structure in four samples of ostensibly identically prepared 70Li2S-30P2S5 glass reveals substantial variation in the ratio between the two main local structural units in this system: PS43- tetrahedra and P2S74- corner-sharing tetrahedral pairs. Local structural and compositional probes including Raman spectroscopy, X-ray photoelectron spectroscopy, and X-ray pair distribution function analysis are employed here to arrive at a consistent description of the relative amounts of isolated tetrahedral units, which vary by 13% across the samples measured. This local structure variation translates to differences in the activation energies measured by electrochemical impedance spectroscopy in these samples, such that the higher concentration of isolated tetrahedra corresponds to a lower activation energy. The measured temperature-dependent ionic conductivity data are compared to conductivity results across the literature reported on the same compositions, highlighting the variation in the measured activation energy for nominally identical samples. These findings have implications for the critical need to play close attention to the local structure in solid electrolytes, particularly in systems that are glasses or glass ceramics, or those that comprise any amorphous contribution.

5.
J Feline Med Surg ; 23(4): 331-336, 2021 04.
Article in English | MEDLINE | ID: mdl-32840421

ABSTRACT

OBJECTIVES: The aims of this study were to report the postoperative incidence of subcutaneous ureteral bypass (SUB)-associated bacteriuria and risk factors in a large population of UK cats, to identify the commonly implicated isolates in these cases and to report associations of positive postoperative urine cultures with device occlusion or a need for further surgery. METHODS: Electronic clinical records were reviewed to identify cats with ureteral obstruction that underwent unilateral or bilateral SUB implantation between September 2011 and September 2019. In total, 118 client-owned cats were included in the study population. Information recorded included signalment, history, surgical and biochemical factors, urinalysis and culture results. Multivariable logistic regression was performed to identify variables associated with a positive postoperative culture. RESULTS: In total, 10 cats (8.5%) had a positive postoperative culture within 1 month postsurgery and 28 cats (23.7%) within 1 year postsurgery. Cats with a positive preoperative culture were significantly more likely to have a positive culture within 6 months postoperatively (odds ratio [OR] 4.09, 95% confidence interval [CI] 1.18-14.18; P = 0.026). Of the 14 cats with a positive preoperative culture, six (42.9%) returned a positive culture within 1 year postoperatively, and in four cases (66.7%) the same isolate was identified. Cats with a higher end-anaesthetic rectal temperature were significantly less likely to return a positive culture within 3 months (OR 0.398, 95% CI 0.205-0.772; P = 0.006) postsurgery. Cats culturing positive for Escherichia coli at any time point (OR 4.542, 95% CI 1.485-13.89; P = 0.008) were significantly more likely to have their implant removed or replaced. CONCLUSIONS AND RELEVANCE: Perioperative hypothermia and preoperative positive culture were independent predictors of a postoperative positive culture and this should be taken into consideration when managing these cases. Positive postoperative culture rates were higher than have previously been reported.


Subject(s)
Cat Diseases , Ureter , Ureteral Obstruction , Animals , Cat Diseases/surgery , Cats , Retrospective Studies , Stents , Ureteral Obstruction/surgery , Ureteral Obstruction/veterinary , Urinalysis/veterinary
6.
EMBO J ; 39(16): e105057, 2020 08 17.
Article in English | MEDLINE | ID: mdl-32643835

ABSTRACT

Alveolar macrophages (AMs) and epithelial cells (ECs) are the lone resident lung cells positioned to respond to pathogens at early stages of infection. Extracellular vesicles (EVs) are important vectors of paracrine signaling implicated in a range of (patho)physiologic contexts. Here we demonstrate that AMs, but not ECs, constitutively secrete paracrine activity localized to EVs which inhibits influenza infection of ECs in vitro and in vivo. AMs exposed to cigarette smoke extract lost the inhibitory activity of their secreted EVs. Influenza strains varied in their susceptibility to inhibition by AM-EVs. Only those exhibiting early endosomal escape and high pH of fusion were inhibited via a reduction in endosomal pH. By contrast, strains exhibiting later endosomal escape and lower fusion pH proved resistant to inhibition. These results extend our understanding of how resident AMs participate in host defense and have broader implications in the defense and treatment of pathogens internalized within endosomes.


Subject(s)
Endosomes , Extracellular Vesicles/immunology , Influenza A virus/immunology , Macrophages, Alveolar/immunology , Paracrine Communication/immunology , Virus Internalization , A549 Cells , Animals , Dogs , Endosomes/immunology , Endosomes/pathology , Endosomes/virology , HEK293 Cells , Humans , Macrophages, Alveolar/pathology , Madin Darby Canine Kidney Cells , Mice , Rats , Rats, Wistar , THP-1 Cells
7.
PLoS One ; 12(2): e0173162, 2017.
Article in English | MEDLINE | ID: mdl-28241077

ABSTRACT

We investigated the mechanisms of mushroom toxin resistance in the Drosophila Genetic Reference Panel (DGRP) fly lines, using genome-wide association studies (GWAS). While Drosophila melanogaster avoids mushrooms in nature, some lines are surprisingly resistant to α-amanitin-a toxin found solely in mushrooms. This resistance may represent a pre-adaptation, which might enable this species to invade the mushroom niche in the future. Although our previous microarray study had strongly suggested that pesticide-metabolizing detoxification genes confer α-amanitin resistance in a Taiwanese D. melanogaster line Ama-KTT, none of the traditional detoxification genes were among the top candidate genes resulting from the GWAS in the current study. Instead, we identified Megalin, Tequila, and widerborst as candidate genes underlying the α-amanitin resistance phenotype in the North American DGRP lines, all three of which are connected to the Target of Rapamycin (TOR) pathway. Both widerborst and Tequila are upstream regulators of TOR, and TOR is a key regulator of autophagy and Megalin-mediated endocytosis. We suggest that endocytosis and autophagy of α-amanitin, followed by lysosomal degradation of the toxin, is one of the mechanisms that confer α-amanitin resistance in the DGRP lines.


Subject(s)
Alpha-Amanitin/pharmacology , Drosophila melanogaster/drug effects , Drosophila melanogaster/genetics , Drug Resistance , Animals , Crosses, Genetic , Drosophila Proteins/metabolism , Endocytosis , Gene Expression Profiling , Gene Expression Regulation , Genetic Association Studies , Genetic Variation , Larva/drug effects , Low Density Lipoprotein Receptor-Related Protein-2/metabolism , Oligonucleotide Array Sequence Analysis , Pesticides/chemistry , Phenotype , RNA/analysis , TOR Serine-Threonine Kinases/metabolism , Taiwan
8.
J Med Life ; 9(3): 284-287, 2016.
Article in English | MEDLINE | ID: mdl-27974935

ABSTRACT

Peritonitis is the main complication of peritoneal dialysis (PD) and also an important factor for raising the cost of the method to the level of hemodialysis. Associated with PD, peritonitis is responsible for the increase of morbidity and mortality of the procedure and, at the same time, the main cause of the technique failure. Severe and prolonged peritonitis or repeated episodes of peritonitis lead to ultrafiltration failure. Peritonitis treatment should aim for a rapid remission of inflammation in order to preserve the peritoneal membrane functional integrity. The treatment of PD peritonitis consists mainly of antibiotic therapy, surgical intervention not being usually required. However, it is of outmost importance to differentiate the so-called "catheter related" peritonitis from secondary peritonitis due to visceral lesions, in which the surgical treatment comes first. The confusion between secondary and "catheter related" peritonitis may lead to serious errors in choosing the correct treatment, endangering the patient's life. The differential diagnosis between a refractory or secondary peritonitis in a peritoneal dialyzed patient may be very difficult. In front of a refractory PD peritonitis, surgical exploration must not be delayed. Also we have to keep in mind that the aim of peritonitis treatment is the saving of the peritoneal membrane and not the catheter.


Subject(s)
Peritoneal Dialysis/adverse effects , Peritonitis/surgery , Aged , Diagnosis, Differential , Female , Humans , Male , Peritonitis/diagnosis , Time Factors
9.
Clin Child Psychol Psychiatry ; 20(4): 570-84, 2015 Oct.
Article in English | MEDLINE | ID: mdl-24928278

ABSTRACT

'Disruptive behaviour disorders' are the most common reason for referral to Child and Adolescent Mental Health Services (CAMHS). Current treatment guidelines focus on parent-training programmes. Difficulties are often reported when engaging families, with parental attributions and attitudes towards help-seeking proposed as influential factors. Previous research has tended to privilege pre-existing frameworks; this study utilised qualitative methods to add to the current understanding of the ways in which parents make sense of their children's behaviour. Semi-structured interviews were carried out with six mothers, recruited through CAMHS. Interpretative Phenomenological Analysis (IPA) revealed four master themes: 'Understanding the Emotional Child', 'The Emotional Parent', 'Getting Help' and 'The Journey'. Participants used a variety of explanations in order to make sense of their children's behaviour, including the impact of loss and trauma. Help-seeking was associated with feelings of shame, and services were often viewed as inconsistent and stigmatising. In contrast, positive experiences were those which were characterised as being non-judgemental, normalising and took into account the wider family context, including mothers' own emotional needs. These findings were discussed in relation to existing research and implications for clinical practice.


Subject(s)
Adolescent Behavior/psychology , Child Behavior/psychology , Conduct Disorder/psychology , Emotions/physiology , Mothers/psychology , Adolescent , Child , Female , Humans , Male , Shame
10.
J Med Life ; 7 Spec No. 3: 8-12, 2014.
Article in English | MEDLINE | ID: mdl-25870687

ABSTRACT

INTRODUCTION: Encapsulating peritoneal sclerosis is a pathological entity mainly associated with peritoneal dialysis (PD). The clinical syndrome is characterized by various degrees of intestinal obstruction due to thickening, sclerosis and calcification of peritoneum resulting in the encapsulation and cocooning of the bowel. It is a rare but potentially devastating complication associated with a considerable morbidity and mortality. MATERIALS AND METHODS: Cases of encapsulating peritoneal sclerosis (EPS), diagnosed in the Surgical Clinic of "Cantacuzino" Hospital, between 2007 and 2014 were retrospectively reviewed. During this interval, 432 surgical interventions related to peritoneal dialysis were performed: 306 peritoneal access interventions and 124 complications, of which 15 patients with EPS. RESULTS: In all but two cases, the EPS diagnostic was established at the time of the surgical intervention addressed to other complication or pathology. Moreover, in 2 of the 15 patients the diagnostic was established approximately 5 months after PD was discontinued, and, in one of these patients at the time of the extraction of the dialysis catheter. 12 of 15 patients were diabetic. Most patients had a history of multiple peritonitis episodes. All the patients required the passing from peritoneal dialysis to hemodialysis. There were 4 deaths (26,6%) of which one was around two months from the diagnosis. CONCLUSIONS: The timely diagnosis of the condition and the appropriate phase-specific treatment is of utmost importance in EPS. In advanced stages, the surgical intervention performed by a well-trained team could achieve good long-term results.


Subject(s)
Peritoneal Dialysis/adverse effects , Peritoneal Fibrosis/etiology , Adult , Aged , Female , Humans , Intraoperative Care , Male , Middle Aged , Peritoneal Fibrosis/surgery , Retrospective Studies
11.
J Med Life ; 7 Spec No. 3: 13-9, 2014.
Article in English | MEDLINE | ID: mdl-25870688

ABSTRACT

UNLABELLED: HYPOTHESIS AND AIM: The large number of invalidating surgical interventions in patients suffering from lesions of the diabetic foot, the late recognition of the lesions and sometimes the wrongful interpretation of their severity, have made necessary a multi-parameter study of these types of patients and the elaboration of a therapeutic-prognostic index to guide the physician in adopting the adequate method of treatment. Starting with the therapeutic-prognostic index imagined by professor Traian Patrascu, we have elaborated a new therapeutic prognostic index, by adding new, statistically significant parameters, for the purpose of facilitating the surgical indication, depending on the lesion type. METHODS: A number of 929 patients who were admitted at the Surgery Clinic of the "Dr. I. Cantacuzino" Hospital, between January 2013 and June 2014, have been analyzed, of whom 450 were evaluated retrospectively and 479 prospectively. RESULTS: The new therapeutic prognostic index has been calculated for the retrospective lot, resulting into a concordance between the actual surgical intervention and the prognostic index of 79.4% and, for the patients evaluated prospectively, we have found a confirmation of the relation of 82.6% between the performed surgical intervention and the forecasted surgical intervention, by calculating the index. DISCUSSION: The new therapeutic-prognostic index represents an easy method of establishing the therapeutic conduct of the patient suffering from lesions of the diabetic foot. It is of major use in preventing the execution of such surgical interventions that may be disproportionate compared to the severity of the lesions, especially in facilities where the pathology of the diabetic foot is less known.


Subject(s)
Diabetic Foot/pathology , Diabetic Foot/surgery , Adult , Age Distribution , Aged , Diabetic Foot/diagnosis , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
12.
J Med Life ; 7 Spec No. 3: 103-6, 2014.
Article in English | MEDLINE | ID: mdl-25870705

ABSTRACT

INTRODUCTION: The infectious syndrome associated with peritoneal dialysis is the most important complication of this substitution method of the renal function, also being the main cause of method failure. Refractory peritonitis can cause real problems in the differential diagnosis with secondary peritonitis, which can delay the surgical intervention and endanger the patient's life. MATERIALS AND METHODS: The patients with an end stage renal disease under peritoneal dialysis, who were admitted to "I. Juvara" Surgical Clinic of "Dr. I. Cantacuzino" Clinical Hospital, between 2007 and 2011, were retrospectively analyzed for catheter removal/ replacement due to infectious complications or ultrafiltration failure. RESULTS: 55 patients were identified: 33 with infectious complications (exit-site, tunnel infections 4 and peritonitis 29) and 22 with loss of peritoneum ultrafiltration capacity. The patients with ultrafiltration failure had a longer duration of PD and a smaller number of peritonitic episodes (0.28 episodes/ year at risk in the ultrafiltration failure group vs. 0.98, in the group of infectious complications). The removal of the catheter was the only surgical procedure performed for the patients with ultrafiltration failure, while the patients with peritonitis needed additional gestures like an exploratory laparotomy with peritoneal lavage and drainage and adhesiolysis in the majority of cases. In the group with infectious complications, 4 patients died: 2 by multisystem organ failure due to prolonged sepsis, one developed an upper gastrointestinal bleeding followed by respiratory insufficiency and one had in cataclysmic gastrointestinal bleeding which rapidly led to death. CONCLUSIONS: The immediate operative approach for an infectious peritoneal syndrome under peritoneal dialysis is seldom necessary. The surgical observation is absolutely mandatory in every case. The absence of a response to the proper medical treatment is an indication of peritoneal cavity exploration including laparoscopy/ laparotomy. Any delay in the diagnosis and definitive treatment gives an extremely high mortality rate.


Subject(s)
Peritoneal Dialysis/adverse effects , Peritonitis/diagnosis , Adult , Aged , Female , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Peritonitis/therapy , Retrospective Studies
13.
Chirurgia (Bucur) ; 107(6): 715-21, 2012.
Article in English | MEDLINE | ID: mdl-23294948

ABSTRACT

Colonic diverticulosis is a benign disease whose incidence has been steadily increasing throughout the world, especially in the economically developed countries in Western Europe. This increase is connected to the population ageing process, the diverticulosis being characteristic in the elderly, and with nowadays' eating habits. Frequently, colonic diverticuli may cause complications, such as hemorrhage or diverticulitis, with pericolic abscesses or peritonitis. Consequently, efforts are being made to set up a therapeutic algorithm appropriate for the diverticular disease, the predominance of the conservative or surgical attitude being continuously adjusted. We have analyzed the therapeutic options, their advantages and their limitations, based on both the experience of the "Prof. I. Juvara" Surgical Department of the "Dr. I. Cantacuzino" Clinical Hospital and the latest data in medical literature.


Subject(s)
Colon, Sigmoid , Diverticulitis, Colonic/therapy , Aged , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Colon, Sigmoid/surgery , Diverticulitis, Colonic/complications , Diverticulitis, Colonic/diagnosis , Diverticulitis, Colonic/surgery , Drug Therapy, Combination , Elective Surgical Procedures , Female , Humans , Middle Aged , Therapeutic Irrigation , Treatment Outcome
14.
Cancer Res ; 71(12): 4260-8, 2011 Jun 15.
Article in English | MEDLINE | ID: mdl-21512136

ABSTRACT

LIN28B is a homologue of LIN28 that induces pluripotency when expressed in conjunction with OCT4, SOX2, and KLF4 in somatic fibroblasts. LIN28B represses biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Recently, we have determined that LIN28B overexpression occurs in colon tumors. We conducted a comprehensive analysis of LIN28B protein expression in human colon adenocarcinomas. We found that LIN28B overexpression correlates with reduced patient survival and increased probability of tumor recurrence. To elucidate tumorigenic functions of LIN28B, we constitutively expressed LIN28B in colon cancer cells and evaluated tumor formation in vivo. Tumors with constitutive LIN28B expression exhibit increased expression of colonic stem cell markers LGR5 and PROM1, mucinous differentiation, and metastasis. Together, our findings point to a function for LIN28B in promoting colon tumor pathogenesis, especially metastasis.


Subject(s)
Colonic Neoplasms/etiology , RNA-Binding Proteins/physiology , Adult , Aged , Aged, 80 and over , Animals , Cell Differentiation , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Disease Progression , Female , Gene Expression Profiling , Humans , Kruppel-Like Factor 4 , Male , Mice , Middle Aged , Neoplasm Metastasis , Neoplastic Stem Cells/physiology
15.
Cancer Res ; 71(6): 2172-82, 2011 Mar 15.
Article in English | MEDLINE | ID: mdl-21252116

ABSTRACT

Insulin-like growth factor 2 mRNA-binding protein-1 (IMP-1) is an oncofetal protein that binds directly to and stabilizes oncogenic c-Myc and regulates, in turn, its posttranscriptional expression and translation. In contrast to normal adult tissue, IMP-1 is reexpressed and/or overexpressed in human cancers. We show that knockdown of c-Myc in human colon cancer cell lines increases the expression of mature let-7 miRNA family members and downregulates several of its mRNA targets: IMP-1, Cdc34, and K-Ras. We further show that loss of IMP-1 inhibits Cdc34, Lin-28B, and K-Ras, suppresses SW-480 cell proliferation and anchorage-independent growth, and promotes caspase- and lamin-mediated cell death. We also found that IMP-1 binds to the coding region and 3'UTR of K-Ras mRNA. RNA microarray profiling and validation by reverse transcription PCR reveals that the p53-inducible proapoptotic protein CYFIP2 is upregulated in IMP-1 knockdown SW480 cells, a novel finding. We also show that overexpression of IMP-1 increases c-Myc and K-Ras expression and LIM2405 cell proliferation. Furthermore, we show that loss of IMP-1 induces Caspase-3- and PARP-mediated apoptosis, and inhibits K-Ras expression in SW480 cells, which is rescued by CYFIP2 knockdown. Importantly, analysis of 228 patients with colon cancers reveals that IMP-1 is significantly upregulated in differentiated colon tumors (P ≤ 0.0001) and correlates with K-Ras expression (r = 0.35, P ≤ 0.0001) relative to adjacent normal mucosa. These findings indicate that IMP-1, interrelated with c-Myc, acts upstream of K-Ras to promote survival through a novel mechanism that may be important in colon cancer pathogenesis.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Colonic Neoplasms/metabolism , RNA-Binding Proteins/metabolism , ras Proteins/metabolism , 3' Untranslated Regions/genetics , Adaptor Proteins, Signal Transducing/genetics , Apoptosis , Caco-2 Cells , Cell Line, Tumor , Cell Proliferation , Cell Survival , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Female , Humans , Immunoblotting , Male , Protein Binding , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA Interference , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tissue Array Analysis , Up-Regulation , ras Proteins/genetics
16.
Chirurgia (Bucur) ; 105(3): 355-9, 2010.
Article in English | MEDLINE | ID: mdl-20726301

ABSTRACT

OBJECTIVE: We hereby analyzed a series of gallstone ileus cases operated on in our department starting from a Bouveret syndrome case. METHOD: Retrospective analysis of all gallstone ileus cases who underwent surgery in our department during the last 26 years. We took into consideration diagnostic elements, time from admission to surgery, type of surgery and post-operative outcome. RESULTS: During this period 9,143 gallstones were deferred to surgery; 27 biliary-digestive fistulae were discovered during surgery; gallstone ileus complicated fistula in 8 patients. Gallstone ileus was exclusively present in elderly women with associated comorbidities. Diagnosis was suggested by clinical features of acute or incomplete intestinal obstruction; it was sustained by imagistic studies with different degrees of relevance. The average time from admission to surgery was 2.6 days. Surgical approach varied from simple enterolithotomy to additional fistula repair. The outcome was uneventful in most of the cases with only one exception. CONCLUSIONS: gallstone ileus is a rare condition, occurring in elders with important comorbidities. The choice for surgical procedure depends on the obstructive syndrome's gravity and associated comorbidities; the type of intervention does not significantly influence post-operative morbidity and mortality rates.


Subject(s)
Biliary Fistula/surgery , Cholecystectomy/methods , Gallstones/surgery , Ileus/surgery , Intestine, Small/surgery , Aged , Aged, 80 and over , Biliary Fistula/diagnosis , Biliary Fistula/etiology , Biliary Fistula/mortality , Cholecystectomy/mortality , Female , Gallstones/complications , Gallstones/diagnosis , Gallstones/mortality , Humans , Ileus/diagnosis , Ileus/etiology , Ileus/mortality , Middle Aged , Retrospective Studies , Treatment Outcome
17.
Chirurgia (Bucur) ; 105(1): 93-6, 2010.
Article in Romanian | MEDLINE | ID: mdl-20405687

ABSTRACT

The term "synchronous tumors" is reserved for simultaneous evolution of two or more tumors with distinct sites, in which the possibility that one tumor is a metastasis of the other has been excluded. In medical practice, the involvement of two different cavitary organs of the gastrointestinal tract is very rare. We present two clinical cases of synchronous tumors: one of a malignant degeneration of a colonic polyp, associated to a jejunal tumor; the other of a patient with a gastric adenocarcinoma, who also had a bulky rectal villous tumor. We tried to find out the etiology of the tumors and the frequency of these associations, mentioned in medical literature. Immunohistochemistry investigations, genetic analysis and familial screening must complete an individualized medical approach in which the surgical technique must be adequate for each case.


Subject(s)
Adenocarcinoma, Mucinous/surgery , Colonic Neoplasms/surgery , Colonic Polyps/surgery , Neoplasms, Multiple Primary/surgery , Stomach Neoplasms/surgery , Adenocarcinoma/surgery , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Colon, Descending/surgery , Colonic Neoplasms/pathology , Colonic Polyps/pathology , Colonoscopy , Diagnosis, Differential , Digestive System Surgical Procedures , Duodenal Neoplasms/surgery , Gastroscopy , Humans , Jejunal Neoplasms/surgery , Male , Neoplasms, Multiple Primary/pathology , Stomach Neoplasms/pathology , Treatment Outcome
18.
Chirurgia (Bucur) ; 105(1): 123-5, 2010.
Article in English | MEDLINE | ID: mdl-20405693

ABSTRACT

We hereby aim to account on a case of actinomycotic infection occurred in a female patient with an intrauterine contraceptive device (IUCD). The infection occurred as a pseudo-tumour which raised differential diagnosis issues with a malignant tumour. The diagnosis has been eventually established following the pathologic examination of paraffin-embedded tissues. Although the infection's gateway was the uterus, the subsequent invasion of the parietal, urinary bladder and lateral rectal walls did not seem to affect the fallopian tubes or the ovaries.


Subject(s)
Actinomycosis/diagnosis , Intrauterine Devices/adverse effects , Pelvic Infection/diagnosis , Rectus Abdominis , Uterine Diseases/diagnosis , Actinomycosis/drug therapy , Actinomycosis/microbiology , Actinomycosis/surgery , Adult , Ampicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Diagnosis, Differential , Female , Humans , Laparotomy , Pelvic Infection/drug therapy , Pelvic Infection/microbiology , Pelvic Infection/surgery , Pelvic Neoplasms/diagnosis , Rectus Abdominis/microbiology , Rectus Abdominis/surgery , Treatment Outcome , Uterine Diseases/drug therapy , Uterine Diseases/microbiology , Uterine Diseases/surgery
19.
Chirurgia (Bucur) ; 104(5): 641-4, 2009.
Article in Romanian | MEDLINE | ID: mdl-19943569

ABSTRACT

Malignant melanomas of the gastrointestinal tract and particulary of the stomach are very rare intra-operative findings. The majority of such melanomas are metastatic from a cutaneous primary. We present the clinical case of a 69-years-old woman with malignant melanoma of the left pectoral region resected in 1988, presented with epigastric pain, weight loss and anaemia. Endoscopy and CT-scan suggested the diagnosis of malignant tumor of the large curvature of the stomach. Explorative laparotomy revealed a large ulcerated tumor of the fornix, with spleno-pancreatic invasion. We also found several pigmented satellite nodules. The surgical solution consisted in a total gastrectomy and distal spleno-pancreatectomy. Histology revealed the tumor and the satellite nodules to be composed of nests of epithelioid cells with melanin pigment. After 3 months, the evolution was favorable. There are some articles in medical literature which present cases of primary gastric melanomas. According to these scientific criterias from the literature, we discussed the nature of this melanoma - a primary or a metastatic one.


Subject(s)
Melanoma/secondary , Skin Neoplasms/pathology , Stomach Neoplasms/secondary , Aged , Female , Gastrectomy , Gastrointestinal Neoplasms/secondary , Humans , Melanoma/surgery , Pancreatectomy , Skin Neoplasms/surgery , Splenectomy , Stomach Neoplasms/surgery , Treatment Outcome
20.
Chirurgia (Bucur) ; 104(2): 213-7, 2009.
Article in Romanian | MEDLINE | ID: mdl-19499666

ABSTRACT

The gastric plasmacytoma represents a rarely encountered, so that, the diagnosis criteria, the medical attitude and the evolution of this disease are less coded. It is known the fact that this tumours, extramedullary plasmacytomas with gastric localization, develop in soft submucous tissue, therefore it's very difficult or even impossible preoperative diagnosis through an upper endoscopy including biopsy. We present the case of a 54 years old patient, with no significant pathological personal record, that was admitted in our Clinic for having melenic dark stools which have repeated within a 6 months period prior to this hospitalisation. Repeated gastric mucosal samples taken in another medical unit shown normal aspects, contrary to all imaging testing (e.g. ultrasonography, upper endoscopy and barium swallow) which revealed a tumor mass of considerable extent at the level of the gastric corpus. First-line therapy was gastric resection followed by radiotherapy, because it is well known that the tumour is highly radiosensitive. The patient's postoperative course was satisfactory, showing no signs or recurrence 6 months after surgery at upper endoscopy and CT-scan.


Subject(s)
Plasmacytoma/diagnosis , Plasmacytoma/surgery , Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgery , Diagnosis, Differential , Gastrectomy/methods , Humans , Male , Melena/etiology , Middle Aged , Plasmacytoma/complications , Plasmacytoma/radiotherapy , Radiotherapy, Adjuvant , Stomach Neoplasms/complications , Stomach Neoplasms/radiotherapy , Treatment Outcome
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