1,921 research outputs found
Management approach for recurrent spontaneous pneumothorax in consecutive pregnancies based on clinical and radiographic findings
OBJECTIVE: To describe management and clinical features observed in a patient's seven spontaneous pneumothoraces that developed during two consecutive pregnancies involving both hemithoraces. MATERIALS AND METHODS: A 21 year old former smoker developed three spontaneous left pneumothoraces in the index pregnancy, having already experienced four right pneumothorax events in a prior pregnancy at age 19. RESULTS: Chest tubes were required in several (but not all) hospitalizations during these two pregnancies. Following her fourth right pneumothorax, thoracoscopic excision of right apical lung blebs and mechanical pleurodesis was performed. The series of left pneumothoraces culminated in mini-thoracotomy and thoracoscopically directed mechanical pleurodesis. For both pregnancies unassisted vaginal delivery was performed with no adverse perinatal sequelae. With the exception of multiple pneumothoraces, there were no additional pregnancy complications. CONCLUSION: Spontaneous pneumothorax in pregnancy is believed to be a rare phenomenon, yet the exact incidence is unknown. Here we present the first known case of multiple spontaneous pneumothoraces in two consecutive pregnancies involving both hemithoraces. Clinical management coordinated with obstetrics and surgical teams facilitated a satisfactory outcome for both pregnancies. The diagnosis of pneumothorax should be contemplated in any pregnant patient with dyspnea and chest pain, followed by radiographic confirmation
Loss of expression of FANCD2 protein in sporadic and hereditary breast cancer
Fanconi anemia (FA) is a recessive disorder associated with progressive pancytopenia, multiple developmental defects, and marked predisposition to malignancies. FA is genetically heterogeneous, comprising at least 12 complementation groups (A–M). Activation of one of the FA proteins (FANCD2) by mono-ubiquitination is an essential step in DNA damage response. As FANCD2 interacts with BRCA1, is expressed in proliferating normal breast cells, and FANCD2 knockout mice develop breast tumors, we investigated the expression of FANCD2 in sporadic and hereditary invasive breast cancer patients to evaluate its possible role in breast carcinogenesis. Two tissue microarrays of 129 and 220 sporadic breast cancers and a tissue microarray containing 25 BRCA1 germline mutation-related invasive breast cancers were stained for FANCD2. Expression results were compared with several clinicopathological variables and tested for prognostic value. Eighteen of 96 (19%) sporadic breast cancers and two of 21 (10%) BRCA1-related breast cancers were completely FANCD2-negative, which, however, still showed proliferation. In the remaining cases, the percentage of FANCD2-expressing cells correlated strongly with mitotic index and percentage of cells positive for the proliferation markers Ki-67 and Cyclin A. In immunofluorescence double staining, coexpression of FANCD2 and Ki-67 was apparent. In survival analysis, high FANCD2 expression appeared to be prognostically unfavorable for overall survival (p = 0.03), independent from other major prognosticators (p = 0.026). In conclusion, FANCD2 expression is absent in 10–20% of sporadic and BRCA1-related breast cancers, indicating that somatic inactivating (epi)genetic events in FANCD2 may be important in both sporadic and hereditary breast carcinogenesis. FANCD2 is of independent prognostic value in sporadic breast cancer
Lorentz violating kinematics: Threshold theorems
Recent tentative experimental indications, and the subsequent theoretical
speculations, regarding possible violations of Lorentz invariance have
attracted a vast amount of attention. An important technical issue that
considerably complicates detailed calculations in any such scenario, is that
once one violates Lorentz invariance the analysis of thresholds in both
scattering and decay processes becomes extremely subtle, with many new and
naively unexpected effects. In the current article we develop several extremely
general threshold theorems that depend only on the existence of some energy
momentum relation E(p), eschewing even assumptions of isotropy or monotonicity.
We shall argue that there are physically interesting situations where such a
level of generality is called for, and that existing (partial) results in the
literature make unnecessary technical assumptions. Even in this most general of
settings, we show that at threshold all final state particles move with the
same 3-velocity, while initial state particles must have 3-velocities
parallel/anti-parallel to the final state particles. In contrast the various
3-momenta can behave in a complicated and counter-intuitive manner.Comment: V1: 32 pages, 6 figures, 3 tables. V2: 5 references adde
Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.
The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease
pp32 (ANP32A) Expression Inhibits Pancreatic Cancer Cell Growth and Induces Gemcitabine Resistance by Disrupting HuR Binding to mRNAs
The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy
Osseous erosion by herniated nucleus pulposus mimicking intraspinal tumor: a case report
Erosion of spinal osseous structure, so-called scalloping, has been rarely reported associated with herniated nucleus pulposus (HNP). We report a rare case of HNP causing erosion of the spinal osseous structure (including lamina). The patient was an 81-year-old woman with 3-year history of low-back pain and left leg radiating pain. Muscle weakness of the left leg was also apparent. Computed tomography following myelography showed severe compression of the dural sac at the level of L3–L4; furthermore, erosion of the lamina, pedicle, and vertebral body was noted, indicating that the space-occupying mass was most probably a tumorous lesion. The mass also showed calcification inside. During the surgery, the mass was confirmed to be an HNP with calcification. Following resection, the pain disappeared. Surgeons should be aware of the possibility of scalloping of the vertebrae caused by HNP mimicking a tumorous lesion
Potential antitumor effects of nitrogen-containing bisphosphonate in hormone receptor negative breast cancer patients with bone metastases
<p>Abstract</p> <p>Background</p> <p>This retrospective study evaluated, according to hormone receptor status, the antitumor effects of bisphosphonate especially on survival and disease progression in breast cancer patients with metastatic bone disease.</p> <p>Methods</p> <p>Of 317 patients with initial bone metastasis and known breast cancer subtypes, 230 patients (72.6%) had hormone receptor (HR) positive tumors, and 87 patients (27.4%) had HR negative tumors. We assessed the primary outcome of overall survival (OS), after adjusting for other factors, comparing a group that received bisphosphonates (BPs) with a group that did not receive it.</p> <p>Results</p> <p>87.8% of HR positive and 69.0% of HR negative patients received BPs with a median number of 17.7 cycles. Although BPs treatment made no survival benefit in HR positive group, HR negative patients showed a significant prolonged survival when they received BPs treatment (hazard ratio = 0.56 [95% CI 0.34 to 0.91], <it>P </it>= 0.019). In multivariate analysis, disease free interval > 2 years (<it>P </it>= 0.036), a sum of metastatic sites < 3 (<it>P </it>= 0.034), and BP treatments (<it>P </it>= 0.007) were significant factors for survival in HR negative patients.</p> <p>Conclusion</p> <p>Bisphosphonate treatment can result in a survival benefit in metastatic breast cancer patients with HR negative tumors.</p
A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry
We present here a review of the fundamental topics of Hartree-Fock theory in
Quantum Chemistry. From the molecular Hamiltonian, using and discussing the
Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock
equations for the electronic problem. Special emphasis is placed in the most
relevant mathematical aspects of the theoretical derivation of the final
equations, as well as in the results regarding the existence and uniqueness of
their solutions. All Hartree-Fock versions with different spin restrictions are
systematically extracted from the general case, thus providing a unifying
framework. Then, the discretization of the one-electron orbitals space is
reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition
of the basic underlying concepts related to the construction and selection of
Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we
close the review with a section in which the most relevant modern developments
(specially those related to the design of linear-scaling methods) are commented
and linked to the issues discussed. The whole work is intentionally
introductory and rather self-contained, so that it may be useful for non
experts that aim to use quantum chemical methods in interdisciplinary
applications. Moreover, much material that is found scattered in the literature
has been put together here to facilitate comprehension and to serve as a handy
reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and
subeqn package
YihQ is a sulfoquinovosidase that cleaves sulfoquinovosyl diacylglyceride sulfolipids
Sulfoquinovose is produced by photosynthetic organisms at a rate of 1010 tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studies unveiled the sequence signatures for binding the distinguishing sulfonate residue and revealed that sulfoquinovoside degradation is widespread across the tree of life
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