Double rarity: malignant masquerade biliary stricture in a situs inversus totalis patient.

BACKGROUND: Situs inversus totalis is a rare anatomical variation of both the thoracic and the abdominal organs. Common bile duct strictures can be caused by malignant and benign diseases as well. 7-18% of the latter ones are 'malignant masquerade' cases, as pre-operative differentiation is difficult. CASE PRESENTATION: We present the case of a 68y male patient with known situs inversus totalis and a recent onset of obstructive jaundice caused by a malignant behaving common bile duct stricture. Technically difficult endoscopic retrograde cholangiopancreatography, brush cytology, magnetic resonance cholangiopancreatography, endoscopic ultrasound, and percutaneous transhepatic drainage with stent implantation were performed for proper diagnosis. Cholecystectomy, common bile duct resection with hilar lymphadenectomy, and hepatico-jejunostomy have been performed following multidisciplinary consultation. The final histology report did not confirm any clear malignancy, the patient is doing well. CONCLUSION: In situs inversus patients, both diagnostic and therapeutic procedures can lead to various difficulties. Benign biliary strictures are frequently misdiagnosed preoperatively as cholangiocellular carcinoma. Surgery is usually unavoidable, involving a significant risk of complications. The co-existence of these two difficult diagnostic and therapeutic features made our case challenging.

PULMONARY NODULE DETECTION IN CHEST CT USING A DEEP LEARNING-BASED RECONSTRUCTION ALGORITHM.

This study's aim was to assess whether deep learning image reconstruction (DLIR) techniques are non-inferior to ASIR-V for the clinical task of pulmonary nodule detection in chest computed tomography. Up to 6 (range 3-6, mean 4.2) artificial lung nodules (diameter: 3, 5, 8 mm; density: -800, -630, +100 HU) were inserted at different locations in the Kyoto Kagaku Lungman phantom. In total, 16 configurations (10 abnormal, 6 normal) were scanned at 7.6, 3, 1.6 and 0.38 mGy CTDIvol (respectively 0, 60, 80 and 95% dose reduction). Images were reconstructed using 50% ASIR-V and a deep learning-based algorithm with low (DL-L), medium (DL-M) and high (DL-H) strength. Four chest radiologists evaluated 256 series by locating and scoring nodules on a five-point scale. No statistically significant difference was found among the reconstruction algorithms (p = 0.987, average across readers AUC: 0.555, 0.561, 0.557, 0.558 for ASIR-V, DL-L, DL-M, DL-H).

mini spindles: A gene encoding a conserved microtubule-associated protein required for the integrity of the mitotic spindle in Drosophila.

We describe a new Drosophila gene, mini spindles (msps) identified in a cytological screen for mitotic mutant. Mutation in msps disrupts the structural integrity of the mitotic spindle, resulting in the formation of one or more small additional spindles in diploid cells. Nucleation of microtubules from centrosomes, metaphase alignment of chromosomes, or the focusing of spindle poles appears much less affected. The msps gene encodes a 227-kD protein with high similarity to the vertebrate microtubule-associated proteins (MAPs), human TOGp and Xenopus XMAP215, and with limited similarity to the Dis1 and STU2 proteins from fission yeast and budding yeast. Consistent with their sequence similarity, Msps protein also associates with microtubules in vitro. In the embryonic division cycles, Msps protein localizes to centrosomal regions at all mitotic stages, and spreads over the spindles during metaphase and anaphase. The absence of centrosomal staining in interphase of the cellularized embryos suggests that the interactions between Msps protein and microtubules or centrosomes may be regulated during the cell cycle.

Metaphase arrest with centromere separation in polo mutants of Drosophila.

The Drosophila gene polo encodes a conserved protein kinase known to be required to organize spindle poles and for cytokinesis. Here we report two strongly hypomorphic mutations of polo that arrest cells of the larval brain at a point in metaphase when the majority of sister kinetochores have separated by between 20-50% of the total spindle length in intact cells. In contrast, analysis of sister chromatid separation in squashed preparations of cells indicates that some 83% of sisters remain attached. This suggests the separation seen in intact cells requires the tension produced by a functional spindle. The point of arrest corresponds to the spindle integrity checkpoint; Bub1 protein and the 3F3/2 epitope are present on the separated kinetochores and the arrest is suppressed by a bub1 mutation. The mutant mitotic spindles are anastral and have assembled upon centrosomes that are associated with Centrosomin and the abnormal spindle protein (Asp), but neither with gamma-tubulin nor CP190. We discuss roles for Polo kinase in recruiting centrosomal proteins and in regulating progression through the metaphase-anaphase checkpoint.

Orbit, a novel microtubule-associated protein essential for mitosis in Drosophila melanogaster.

We describe a Drosophila gene, orbit, that encodes a conserved 165-kD microtubule-associated protein (MAP) with GTP binding motifs. Hypomorphic mutations in orbit lead to a maternal effect resulting in branched and bent mitotic spindles in the syncytial embryo. In the larval central nervous system, such mutants have an elevated mitotic index with some mitotic cells showing an increase in ploidy. Amorphic alleles show late lethality and greater frequencies of hyperploid mitotic cells. The presence of cells in the hypomorphic mutant in which the chromosomes can be arranged, either in a circular metaphase or an anaphase-like configuration on monopolar spindles, suggests that polyploidy arises through spindle and chromosome segregation defects rather than defects in cytokinesis. A role for the Orbit protein in regulating microtubule behavior in mitosis is suggested by its association with microtubules throughout the spindle at all mitotic stages, by its copurification with microtubules from embryonic extracts, and by the finding that the Orbit protein directly binds to MAP-free microtubules in a GTP-dependent manner.

Characterization of the Apc10/Doc1 subunit of the anaphase promoting complex in Drosophila melanogaster.

The anaphase promoting complex or cyclosome (APC/C) is a large protein complex with an ubiquitin ligase activity which specifically targets mitotic regulatory proteins for proteasomal degradation. The APC/C contains at least 11 subunits, most of which are evolutionarily conserved from yeasts to humans. We have isolated and characterized mutant alleles of the gene that codes for the APC10/Doc1 subunit of the Drosophila APC/C. Loss of function APC10/Doc1 mutants have rudimentary imaginal discs and arrest their development as prepupae. Larval neuroblasts from these mutants show gross mitotic defects including high mitotic index, chromosome overcondensation, metaphase-like arrest and frequent aneuploid and polyploid cells. Mitotically arrested cells accumulate one of the main substrates of APC/C, cyclin B, most likely due to disabled ubiquitination activity. Our results suggest that the Apc10/Doc1 subunit has an essential role in establishing E3 ubiquitin ligase activity of APC/C in Drosophila.

Management of Portal Hypertension After Liver Transplantation.

INTRODUCTION: Post-transplantation portal hypertension has severe complications, such as esophageal varix bleeding, therapy refractory ascites, extreme splenomegaly, and graft dysfunction. The aim of our study was to analyze the effectiveness of the therapeutic strategies and how to visualize the procedure. METHODS: A retrospective study involving liver transplantation patients from the Semmelweis University Department of Transplantation and Surgery was performed between 2005 and 2015. The prevalence, etiology, and leading complications of the condition were determined. The applied interventions' effects on the patients' ascites volume, splenic volume, and the occurrence of variceal bleeding were determined. Mean portal blood flow velocity and congestion index values were calculated using Doppler ultrasonography. RESULTS: The prevalence of post-transplantation portal hypertension requiring intervention was 2.8%. The most common etiology of the disease was portal anastomotic stenosis. The most common complications were esophageal varix bleeding and therapy refractory ascites. The patients' ascites volume decreased significantly (2923.3 ± 1893.2 mL vs. 423.3 ± 634.3 mL; P < .05), their splenic volume decreased markedly. After the interventions, only one case of recurrent variceal bleeding was reported. The calculated Doppler parameters were altered in the opposite direction in cases of pre-hepatic versus intra- or post-hepatic portal hypertension. After the interventions, these parameters shifted towards the physiologic ranges. CONCLUSION: The interventions performed in our clinic were effective in most cases. The patients' ascites volume, splenic volume, and the prevalence of variceal bleeding decreased after the treatment. Doppler ultrasonography has proved to be a valuable imaging modality in the diagnosis and the follow-up of post-transplantation portal hypertension.

Role of Contrast-Enhanced Ultrasound in the Follow-up of Kidney Transplant Patients.

BACKGROUND: Contrast-enhanced ultrasound combines the advantages of native ultrasound and other contrast-enhanced imaging modalities. In selected cases it can be preferable to computerized tomographic scan among kidney transplant recipients. METHODS: We performed a retrospective study involving patients of Semmelweis University Department of Transplantation and Surgery who underwent contrast-enhanced ultrasound examination from 2011 to 2015. During this period, 251 examinations were performed, including 45 on kidney transplant patients. A Toshiba Aplio XU ultrasound device was used, and 1-1.5 mL contrast agent (Sonovue) was administered intravenously for each patient. The indications of these evaluations can be divided into 3 groups: characterization of circumscribed kidney lesions, control after radiofrequency ablation therapy, and examination of graft perfusion. RESULTS: Fully 93% of the examinations were conclusive. In the 1st group of the 37 cases where tumor-suspect lesions were investigated, 13 examinations suggested the presence of a space-occupying lesion. Of those 13 cases, 2 patients had a negative biopsy, nephrectomy was performed in 11 cases, and histologic evaluation verified a tumor in 8 samples. In the 2nd group, the ablation control examination detected a residual tumor in none of the 6 cases. Finally, in 1 of the 2 grafts where the circulation was investigated, blood flow was satisfactory, and in the other it was low. CONCLUSIONS: The contrast-enhanced ultrasound examination was conclusive in most cases. The applied contrast material is not nephrotoxic, and the method uses nonionizing radiation. These features make contrast-enhanced ultrasound highly suitable for the examination of kidney transplant patients.

Cytogenetic and molecular localization of tipE: a gene affecting sodium channels in Drosophila melanogaster.

Voltage-sensitive sodium channels play a key role in nerve cells where they are responsible for the increase in sodium permeability during the rising phase of action potentials. In Drosophila melanogaster a subset of temperature-sensitive paralytic mutations affect sodium channel function. One such mutation is temperature-induced paralysis locus E (tipE), which has been shown by electrophysiology and ligand binding studies to reduce sodium channel numbers. Three new gamma-ray-induced tipE alleles associated with either visible deletions in 64AB or a translocation breakpoint within 64B2 provide landmarks for positional cloning of tipE. Beginning with the flanking cloned gene Ras2, a 140-kb walk across the translocation breakpoint was completed. Germline transformation using a 42-kb cosmid clone and successively smaller subclones localized the tipE gene within a 7.4-kb genomic DNA segment. Although this chromosome region is rich in transcripts, only three overlapping mRNAs (5.4, 4.4, and 1.7 kb) lie completely within the smallest rescuing construct. The small sizes of the rescuing construct and transcripts suggest that tipE does not encode a standard sodium channel alpha-subunit with four homologous repeats. Sequencing these transcripts will elucidate the role of the tipE gene product in sodium channel functional regulation.

P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: mutations affecting embryonic PNS development.

To identify novel genes and to isolate tagged mutations in known genes that are required for the development of the peripheral nervous system (PNS), we have screened a novel collection of 2460 strains carrying lethal or semilethal P element insertions on the third chromosome. Monoclonal antibody 22C10 was used as a marker to visualize the embryonic PNS. We identified 109 mutant strains that exhibited reproducible phenotypes in the PNS. Cytological and genetic analyses of these strains indicated that 87 mutations affect previously identified genes: tramtrack (n = 18 alleles), string (n = 15), cyclin A (n = 13), single-minded (n = 13), Delta (n = 9), neuralized (n = 4), pointed (n = 4), extra macrochaetae (n = 4), prospero (n = 3), tartan (n = 2), and pebble (n = 2). In addition, 13 mutations affect genes that we identified recently in a chemical mutagenesis screen designed to isolate similar mutants: hearty (n = 3), dorsotonals (n = 2), pavarotti (n = 2), sanpodo (n = 2), dalmatian (n = 1), missensed (n = 1), senseless (n = 1), and sticky ch1 (n = 1). The remaining nine mutations define seven novel complementation groups. The data presented here demonstrate that this collection of P elements will be useful for the identification and cloning of novel genes on the third chromosome, since >70% of mutations identified in the screen are caused by the insertion of a P element. A comparison between this screen and a chemical mutagenesis screen undertaken earlier highlights the complementarity of the two types of genetic screens.

P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E-87F.

We have established a collection of 2460 lethal or semi-lethal mutant lines using a procedure thought to insert single P elements into vital genes on the third chromosome of Drosophila melanogaster. More than 1200 randomly selected lines were examined by in situ hybridization and 90% found to contain single insertions at sites that mark 89% of all lettered subdivisions of the Bridges' map. A set of chromosomal deficiencies that collectively uncover approximately 25% of the euchromatin of chromosome 3 reveal lethal mutations in 468 lines corresponding to 145 complementation groups. We undertook a detailed analysis of the cytogenetic interval 86E-87F and identified 87 P-element-induced mutations falling into 38 complementation groups, 16 of which correspond to previously known genes. Twenty-one of these 38 complementation groups have at least one allele that has a P-element insertion at a position consistent with the cytogenetics of the locus. We have rescued P elements and flanking chromosomal sequences from the 86E-87F region in 35 lines with either lethal or genetically silent P insertions, and used these as probes to identify cosmids and P1 clones from the Drosophila genome projects. This has tied together the physical and genetic maps and has linked 44 previously identified cosmid contigs into seven "super-contigs" that span the interval. STS data for sequences flanking one side of the P-element insertions in 49 lines has identified insertions in the alphagamma element at 87C, two known transposable elements, and the open reading frames of seven putative single copy genes. These correspond to five known genes in this interval, and two genes identified by the homology of their predicted products to known proteins from other organisms.

One-hundred and five new potential Drosophila melanogaster genes revealed through STS analysis.

Complementation analysis had suggested that the Drosophila melanogaster genome contains approximately 5000 genes, but it is now generally accepted that the actual number is several times as high. We report here an analysis of 1788 anonymous sequence tagged sites (STSs) from the European Drosophila Genome Project (EDGP), totalling 463 kb. The data reveal a substantial number of previously undescribed potential genes, amounting to 6.1% of the number of Drosophila genes already in the sequence databases.

Re-entering the translocon from the lumenal side of the endoplasmic reticulum. Studies on mutated carboxypeptidase yscY species.

Misfolded or unassembled secretory proteins are retained in the endoplasmic reticulum (ER) and subsequently degraded by the cytosolic ubiquitin-proteasome system. This requires their retrograde transport from the ER lumen into the cytosol, which is mediated by the Sec61 translocon. It had remained a mystery whether ER-localised soluble proteins are at all capable of re-entering the Sec61 channel de novo or whether a permanent contact of the imported protein with the translocon is a prerequisite for retrograde transport. In this study we analysed two new variants of the mutated yeast carboxypeptidase yscY, CPY*: a carboxy-terminal fusion protein of CPY* and pig liver esterase and a CPY* species carrying an additional glycosylation site at its carboxy-terminus. With these constructs it can be demonstrated that the newly synthesised CPY* chain is not retained in the translocation channel but reaches its ER lumenal side completely. Our data indicate that the Sec61 channel provides the essential pore for protein transport through the ER membrane in either direction; persistent contact with the translocon after import seems not to be required for retrograde transport.

Overcoordinated hydrogens in the carbon vacancy: donor centers of SiC

Epitaxial silicon carbide is likely to contain hydrogen and vacancies ( V); therefore, V+nH complexes are likely to influence its electronic properties. Using ab initio calculations we show that neutral and positive H atoms are trapped by carbon vacancies ( V(C)) in three-center bonds with two Si neighbors. The double positive charge state of V(C)+H is not stable in equilibrium and in the triply positive state H binds only to one of the Si neighbors. At most two H atoms can be accommodated by a single V(C). The V(C)+nH complexes have donor character and exhibit rather atypical vibration modes for Si-H bonds. Occupation levels and spin distributions were calculated and compared for V(C)+H and V(C).

The antiallatal effects on locusts and lethal effects on nematodes of synthetic precocene-1 derivatives differing at the carbon 7 position.

Fourteen precocene-1 (P1) derivatives differing at C-7 were synthetized and tested for their antiallatal activities on Locusta migratoria (in vitro and in vivo) and nematocidal effects on Caenorhaditis elegans. An outstanding antiallatal effect was produced by 7-propargyloxy-P1 in vitro. It caused an elevated rate of mortality when applied in vivo to locusts or nematodes. The antiallatal effect of 7-cyclopentyloxy-P1 was not accompanied by toxicity. Aralkyloxy substitution at C-7 eliminated the precocene activity.

Deviceless low-pressure operation; a cost-effective way to reduce CO2-induced barotrauma during hand-assisted laparoscopic donor nephrectomy.

Between March 2008 and March 2011, hand-assisted laparoscopic donor nephrectomles were performed on 70 patients. Following the first 26 cases undertaken based on guidelines in the literature, we modified the procedure to avoid barotrauma to the kidney caused by the usual 12-13 mm Hg CO(2) pneumoperitoneum or pneumoretroperitoneum. The perirenal CO(2) pressure, therefore, was decreased to 8 mm Hg from the beginning of the surgery; the operation was performed without using a handport. Our early experience with the modified technique suggested that the safety and duration of the procedure were not affected but the incidence of delayed graft function due to barotrauma was decreased, a cost-effective improvement.

The significance of the circumaortic left renal vein and other venous variations in laparoscopic living donor nephrectomies.

Among the several vascular variation those concerning the venous system of the kidneys show the most significant variability. They often play an important role when it comes to choosing the kidney to be removed for transplantation. Based on our prior studies, we have surveyed these variations. When performing a laparoscopic living donor nephrectomy owing to the limited field of vision and the restricted possibilities for preparation, preoperative radiologic planning is of utmost importance. We evaluated 55 donors who underwent laparoscopic nephrectomies using the 16-section multidetector-row computed tomography angiography. Among the donors who underwent surgeries we observed circumaortic veins (CAV) in three cases, retroaortic veins in 6 cases, multiple renal veins in 10 cases, and a lumbar vein draining into the left renal vein (RV) in 30 cases. In the 2 cases wherein CAVs were discovered, the team decided to use the other kidney. In 1 case, due to a short right RV, we chose the left kidney. The complex development of the CAV that is sometimes difficult to reconstruct in 3D poses a challenge for both the radiologist and the surgeon.

Renal cell carcinoma of the native kidney: a frequent tumor after kidney transplantation with favorable prognosis in case of early diagnosis.

INTRODUCTION: The frequency of malignant tumors as a cause of death is increasing among kidney transplant patients. The aim of our study was to characterize kidney tumors occurring in the native kidneys of renal transplanted patients, and to determine their impact on recipient survival. METHODS: We retrospectively analyzed the 43/3003 (1.43%) renal cell carcinomas (RCC) in the native kidneys of patients transplanted between 1973 and 2010. RESULTS: During this period we diagnosed 293 posttransplant tumors, 14.6% of which were RCC. The male/female ratio was 2.1:1. The mean age of recipients at the time of tumor detection was 52.4 ± 12.1 years. The mean time from transplantation to diagnosis was 72.4 ± 61.6 months. RCC occurred on both sides in similar numbers. Tumors were multifocal in 8 cases. According to TNM staging, RCC was stage I in 38 cases. The histologic type was clear cell (n=27), papillary (n=13), chromophobe (n=2) or sarcomatoid (n=1). Radical nephrectomy was performed in 41 cases. Immunosuppressive management was converted to proliferation signal inhibitors in 27 patients (sirolimus n=19 or everolimus n=8). Fifteeen patients died at a mean survival time of 38.9 ± 62.4 months with 28 patients still alive at a mean follow-up 43.8 ± 35.6 months. Cumulative survival according to the Kaplan-Meier method was 79.2% at 1 year, 66.1% at 5 years, and 59.0% at 10 years. The patient survival rate was better among papillary than clear cell RCC (P=.038). CONCLUSION: RCC was the second most frequent tumor among kidney transplanted patients at our center. The diagnosis established at an early stage in the majority of cases, leading to favorable patient survivals. A regular yearly abdominal ultrasound screening is suggested for early tumor diagnosis.

Significance and imaging of lumbar veins and early-branching arteries in planning living-donor laparoscopic nephrectomy: two case reports from 21 months' experience.

A key aspect in planning laparoscopic living-donor nephrectomy is mapping of vascular variations. Lumbar veins and early-branching renal arteries are of utmost importance. To date, 43 candidates including 18 men and 25 women aged 25 to 67 years have been examined at our clinic using 16-section multidetector-row computed tomography angiography. Each examination was double-checked by an experienced radiologist. Of the 43 patients, 31 underwent surgery. In 29 of 31 patients (93.5%), the anatomy observed during surgery was identical to that demonstrated on the preoperative computed tomography scan. In 1 of 2 patients, 2 separate arteries were found at surgery, rather than the prognosticated early-branching arteries. In this patient, conversion to open surgery was necessary. In the other patient, a lumbar vein running into a retroaortic renal vein was discovered. In this patient, a 6-mm length of the joint stem contained the wall of the aorta and the periaortic tissue; thus, technically they were of separate origins. Careful mapping of the anatomy helps to prevent unexpected operative complications that are difficult to manage. Correct interpretation of the data must always be based on agreement between the radiologist and the surgeon.