2‐deoxy D‐glucose treatment does not elicit a hair growth response in alopecia areata

2‐deoxy D‐glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T‐cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell‐mediated autoimmune mouse disease, alopecia areata.     

Ibuprofen overdose in adults.

A prospective study of 63 ibuprofen overdose cases in adults (14 years or older) reported to the Rocky Mountain Poison and Drug Center between March 1987 and February 1988 was done to determine the incidence of renal injury and utility of timed plasma levels. No serious toxicity was noted. No CNS or other significant toxicity was seen with ingestion of less than 3 g. Two patients with normal serum creatinines had minor elevations of the blood urea nitrogen after ingesting 4 and 4.8 g. Timed plasma levels (125 total) from patients without coingestants from this study (48) and previously published reports (77) were compared with a previously described nomogram. The resulting nomogram revision may be useful in determining which initially asymptomatic patients are likely to remain so. Renal function tests are not routinely required for patients ingesting less than 6 g. Four h of observation is sufficient for asymptomatic patients not requiring psychiatric admission. Plasma ibuprofen levels are not required for proper patient management.     

Convergence of Genetic, Nutritional and Inflammatory Factors in Gastrointestinal Cancers

Gastrointestinal cancers account for 20% of all cancer incidences worldwide. Colorectal cancer is the second most common cause of all cancer-related mortality and is increasing in Western societies. Infection and inflammation contribute to 15–20% of all malignancies, and are predisposing risk factors for gastrointestinal cancers. Helicobacter pylori infection is commonly associated with gastric cancers, and chronic inflammation increases the risk of colorectal cancer by 1% per year. Micronutrient status and common genetic variations in human populations modify risk for gastrointestinal cancer. Chronic inflammation promotes carcinogenesis by inducing gene mutations, inhibiting apoptosis, and stimulating an-giogenesis and cell proliferation. Inflammation also induces epigenetic alterations that are associated with cancer development. Two key genes in the inflammatory process, cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-kB), provide a mechanistic link between inflammation and cancer and are targets for chemoprevention. Dietary components, and human genetic variation that affects nutrient utilization, can directly modify inflammatory processes and/or suppress genomic alterations that are the molecular antecedents of cancers. The present report focuses on the convergence of genetic, nutritional, and inflammatory factors in the initiation and progression of gastrointestinal cancers, and the emerging dietary strategies for cancer prevention.     

Novel chondroitin sulfate-modified ligands for L-selectin on lymph node high endothelial venules

The migration of lymphocytes into lymph nodes via high endothelial venules (HEV) is dependent on the expression of L-selectin on the lymphocyte cell surface. HEV express several L-selectin ligands including CD34, GlyCAM-1, MAdCAM-1 and two sulfated glycoproteins (Sgp) of 200 kDa and 170 kDa which remain to be identified. In this investigation, labeling with sodium [35S]sulfate, which is incorporated into and forms part of the functional carbohydrate ligand, has been used to isolate and characterize macromolecular L-selectin ligands. High endothelial cells (HEC) cultured from rat lymph node HEV were shown to express ligands for L-selectin. HEC synthesized two groups of sulfated glycoproteins of 150 kDa and > 200 kDa, which were present in conditioned medium. These coeluted on anion exchange chromatography at 1.0-1.2 M NaCl and supported calcium-dependent L-selectin-mediated cell adhesion. In common with known L-selectin ligands, Sgp 150/> 200 were shown to be O-sialoglycoproteins; however, in contrast to other ligands, Sgp 150/> 200 contained chondroitin sulfate glycosaminoglycan modifications which were required for L-selectin recognition. Chondroitin sulfate-modified ligands for L-selectin were expressed at the HEC surface and by HEV in lymph nodes, suggesting that they may participate in lymphocyte interactions with HEV in vivo.     

Spectral karyotyping combined with locus-specific FISH simultaneously defines genes and chromosomes involved in chromosomal translocations

Genes that play roles in malignant transformation have often been found proximate to cancer-associated chromosomal breakpoints. Identifying genes that flank chromosomal reconfigurations is thus essential for cancer cytogenetics. To simplify and expedite this identification, we have developed a novel approach, based on simultaneous spectral karyotyping and fluorescence in situ hybridization (FISH) which, in a single step, can identify gross chromosomal aberrations as well as detect the involvement of specific loci in these rearrangements. Signals for specifically queried genes (FISH probe) were easily detectable in metaphase cells, together with the signals from painted chromosomes (spectral karyotyping probes). The concentration and size of the FISH probes could cover a wide range and still be used successfully. Some of the nucleotide-bound dyes used for the labeling, as Cy3, Spectrum Orange, Alexa 594, Texas Red, and Rhodamine 110, were particularly efficient. More than one gene can be queried in the same metaphase, because multiple FISH probes could be hybridized simultaneously. To demonstrate this technique, we applied it to the myeloma cell line Karpas 620, which has numerous chromosomal rearrangements. The approach that we present here will be particularly useful for the analysis of complex karyotypes and for testing hypotheses arising from cancer gene expression studies. Published 2000 Wiley-Liss, Inc.     

Use of VSV-G pseudotyped retroviral vectors to target murine osteoprogenitor cells

Marrow stromal cells (MSC) and neonatal calvarial cells have the potential to differentiate and express markers of mature osteoblasts. Furthermore, MSCs can generate multiple differentiated connective tissue phenotypes. These properties and their ability to be expanded ex vivo make them good models for ex vivo gene therapy. In this study we examined the ability of vesicular stomatitis virus (VSV-G) pseudotyped retroviral vectors to transduce osteoprogenitor cells derived from bone marrow and from neonatal calvaria. Retrovectors encoding either beta-galactosidase or green fluorescent protein (eGFP) were used for transduction of primary murine marrow stromal and primary neonatal calvarial cell cultures. High infection efficiency was demonstrated by fluorescence-activated cell analysis when GFP was used as a marker or by estimating the number of beta-galactosidase-positive cells. Expression of markers of differentiated bone cells, including Col1a1, bone sialoprotein, and osteocalcin mRNA and alkaline phosphatase activity was not impaired by retroviral transduction. Our data suggest that VSV-G pseudotypes retroviral vectors are suitable for introducing genes into osteoprogenitor cells without affecting osteoprogenitor lineage progression.     

Assessment of Psychological Factors in Short-Stay Total Hip Arthroplasty Protocol

BackgroundSeveral variables are known to correlate with the successful completion of short-stay total hip arthroplasty (THA) protocols. The role of psychological factors remains unclear. We investigated the interaction between patient-reported measures of psychological fitness and successful completion of a short-stay THA protocol.MethodsWe performed a prospective cohort study of patients undergoing elective anterior total hip arthroplasty enrolled in a short-stay protocol (success defined as LOS ≤1 midnight versus failed, LOS >1 midnight). Psychological fitness was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) domains for self-efficacy, depression, anxiety, emotional support, and the ability to participate in social roles. PROMIS scores, patient demographics, and surgical factors were assessed for a relationship with failure to complete short-stay protocol.ResultsPatients that failed to complete the short-stay protocol had higher mean pre-operative PROMIS depression scores (50.8 vs 47.1, P = .025) and anxiety scores (53.6 vs 49.2, P = .008) and higher postoperative PROMIS depression (48.19 vs 43.49, P = .003) and anxiety scores (51.7 vs 47.1, P = .01). Demographic and surgical variables did not correlate with the successful completion of the short-stay protocol. That seventy-six percent of the patients did not adhere to the short-stay protocol was due to the inability to complete a physical therapy standardized safety assessment.ConclusionHigher levels of preoperative and postoperative anxiety and depression in otherwise psychologically healthy patients, is associated with an increased risk of failure to complete a short-stay protocol following THA. Targeted interventions are needed to facilitate rapid recovery in patients with psychological barriers to early mobilization.     

The utility of the implementation science framework “Integrated Promoting Action on Research Implementation in Health Services” (i-PARIHS) and the facilitator role for introducing patient-reported outcome measures (PROMs) in a medical oncology outpatient department

Quality of Life Research - We evaluated the utility of the implementation science framework “Integrated Promoting Action on Research Implementation in Health Services” (i-PARIHS) for...     

Tissue-specific distribution of the Goodpasture antigen demonstrated by 2-D electrophoresis and Western blotting

The target of autoantibodies in Goodpasture's disease, the Goodpastureantigen has recently been characterized as the NC1 domain ofthe 3 chain of type IV collagen. In order to study the Goodpastureantigen in different organs, NC1 domains were isolated frombasement membranes (BM) of human glomeruli (GBM), tubules (TBM),alveoli (ABM), placenta (PBM) and aorta (VBM). NC1 preparationswere separated by 2-D electrophoresis, and silver stained orimmunoblotted to determine the subunit structure and antigenicityof different basement membranes. All basement membranes containedmonomeric components of MW 26 kDa and 24 kDa, and associateddimers, corresponding to the 2-D location of 1(IV) and cc2(IV)chains respectively. However, GBM, ABM, and to a lesser extentTBM possessed an extra set of monomeric components of MW 28kDa and associated dimers corresponding to the proposed locationof 3(IV) and 4(IV) chains. 2-D-separated polypeptides were Westernblotted with autoantibodies from patients with Goodpasture'sdisease, a monoclonal antibody to the Goodpasture antigen (P1)and a monoclonal antibody to the bovine 3(IV) chain. The predominantbinding of all these reagents was to cationic 28 kDa monomersof GBM, ABM and TBM, corresponding to the 3(IV) chain, althoughautoantibodies and P1 also bound to neutral 28 kDa monomers,corresponding to the 4(IV) chain. Autoantibodies bound weaklyto more neutral components of PBM and VBM, but neither monoclonalantibody bound to these basement membranes. This study suggeststhat there are two separate type IV collagen networks: one containingthe l(IV) and 2(IV) chains appears to be present in all basementmembranes, and the other containing the 3(IV) and 4(IV) chainshas a tissue specific distribution. The latter network bearingthe Goodpasture antigen is expressed in the basement membranesof both kidney and lung, the organs involved in Goodpasture'sdisease.     

Correction to: Treatment of adults with intracranial hemorrhage on apixaban or rivaroxaban with prothrombin complex concentrate products

Journal of Thrombosis and Thrombolysis - In the original publication of the article, unfortunately the given name and family name of the author’s in the author group were inadvertently...