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Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Integrated primary care settings serve an increasingly high volume of linguistically diverse patients. In English language-dominant countries, limited English proficiency (LEP) is associated with disparities in access and quality of behavioral health (BH) care. Interpretive services (IS) aim to address these disparities by assisting in the delivery of clinical care between patients and providers who speak different languages. Yet, there is a need for greater emphasis on the utilization of IS in clinical training for BH professionals (e.g., psychology, social work, counseling, and family therapy)., Method: In this conceptual article, we describe a BH practicum rotation for predoctoral psychology trainees in a free, student-run integrated primary care clinic that largely serves uninsured adults with LEP. First, we discuss our training model which includes a 90-min didactic lecture on IS for BH and supervised applied clinical experiences (e.g., psychotherapy, warm handoffs, and consultation). Then, we present vignettes prepared by trainees about the challenges and benefits associated with delivering BH care with IS at the predoctoral level of training., Results: From the practicum experience, clinical psychology trainees reported improved knowledge and competencies in utilizing IS as well as generalizable skills for delivering BH care with a focus on multicultural practice., Discussion: We recommend that other integrated primary care BH training sites consider emphasizing training in IS. This article concludes with recommendations for implementation and dissemination of our training model on other sites. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of diffuse large B-cell lymphoma that preferentially grows intravascularly within the capillaries and often has a fatal course. Most of the patients have advanced and disseminated disease at the time of presentation. It is often arduous to make the diagnosis during the antemortem period due to the multitude of presenting symptoms. We report a case of aggressive IVLBCL which presented with a myriad of complaints and acidosis and had a rapid clinical decline., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Deenadayalan et al.)

BCR-ABL1 -like B-acute lymphoblastic leukemia (B-ALL) is a genetically heterogeneous group of high-risk B-ALL that benefits from targeted tyrosine kinase inhibitor (TKI) therapy. The incidence of this high-risk B-ALL is relatively low and screening with surrogate markers will be useful to identify patients for further genetic testing. Here we demonstrate that widely available MUC4 protein immunohistochemistry (IHC) is predictive of a BCR-ABL1 -like genotype for a subset of patients. Overall, MUC4 expression was observed in 36% (9/25) BCR-ABL1 -like, 43% (3/7) BCR-ABL1 + and 9% (2/22) B-ALL other cases ( p =.019 for BCR-ABL1 like and BCR-ABL1 + versus B-ALL others). Furthermore, 83% (5/6) of patients with ABL class fusions showed MUC4 expression when compared to 25% (4/16, p =.006) patients with JAK class fusions. Overall, the study demonstrates that MUC4 expression is highly specific (90.9%) for BCR-ABL1 + and BCR-ABL1 -like B-ALL with high sensitivity for cases with ABL class fusions.

Background: Differential diagnosis of sellar masses includes adenoma, meningioma, craniopharyngioma, and metastasis. Primary paraganglioma is seldom considered. We present a case of this unique pathology, review the relevant literature, and compile a compendium of immunohistochemical characteristics for use as a resource., Case Description: A 73-year-old woman presented to the hospital with visual changes in her left hemifield. Noncontrast head computed tomography demonstrated a large sellar mass with suprasellar extension and displacement of the optic chiasm (diameter of 3.1 cm). Magnetic resonance imaging was unobtainable owing to an incompatible pacemaker. Computed tomography characterization was most consistent with a macroadenoma. Given the acute visual decline, surgical decompression via an endonasal transsphenoidal route was performed without complication. A diagnosis of paraganglioma was made based on histopathology. Following resection, the patient's visual field deficit improved. Computed tomography body imaging was negative for a metastatic origin., Conclusions: Paraganglioma is a rare but potential differential diagnosis to consider when evaluating sellar masses., (Copyright © 2019 Elsevier Inc. All rights reserved.)

One prominent class of cationic antibacterial peptides comprises the alpha-helical class, which is unstructured in free solution but folds into an amphipathic alpha-helix upon insertion into the membranes of target cells. To investigate the importance of alpha-helicity and its induction on interaction with membranes, a series of peptides was constructed based on a hybrid of moth cecropin (amino acids 1-8) and bee melittin (amino acids 1-18) peptides. The new peptides were predicted to have a high tendency to form alpha-helices or to have preformed alpha-helices by virtue of construction of a lactam bridge between glutamate and lysine side-chains at positions i and i + 4 at various locations along the primary sequence. In two examples where the use of lactam bridge constraints induced and stabilized alpha-helical structure in benign (aqueous buffer) and/or hydrophobic medium, there was a decrease in antibacterial activity relative to the linear counterparts. Thus the preformation of alpha-helix in solution was not necessarily beneficial to antimicrobial activity. In the one case where the lactam bridge did result in increased antibacterial activity (lower minimal inhibitory concentration values) it did not increase alpha-helical content in benign or hydrophobic medium. Broadly speaking, good activity of the peptides against Pseudomonas aeruginosa correlated best (r2 = 0.88) with a helican parameter which was calculated as the induction of alpha-helix in a membrane-mimicking environment divided by the alpha-helix formation under benign conditions. Interestingly, the activity of the lactam bridge peptide constructs correlated in part with alterations in bacterial outer or cytoplasmic membrane permeability.

Cationic peptides possessing antibacterial activity are virtually ubiquitous in nature, and offer exciting prospects as new therapeutic agents. We had previously demonstrated that such peptides could be produced by fusion protein technology in bacteria and several carrier proteins had been tested as fusion partners including glutathione-S-transferase, S. aureus protein A, IgG binding protein and P. aeruginosa outer membrane protein OprF. However these fusion partners, while successfully employed in peptide expression, were not optimized for high level production of cationic peptides (Piers, K., Brow, M. L., and Hancock, R. E. W. 1993, Gene 137, 7-13). In this paper we took advantage of a small replication protein RepA from E. coli and used its truncated version to construct fusion partners. The minimal elements required for high level expression of cationic peptide were defined as a DNA sequence encoding a fusion protein comprising, from the N-terminus, a 68 amino acid carrier region, an anionic prepro domain, a single methionine and the peptide of interest. The 68 amino acid carrier region was a block of three polypeptides consisting of a truncated RepA, a synthetic cellulose binding domain and a hexa histidine domain. The improved system showed high level expression and simplified downstream purification. The active peptide could be yielded by CNBr cleavage of the fusion protein. This novel vector was used to express three classes of cationic peptides including the alpha-helical peptide CEMA, the looped peptide bactenecin and the extended peptide indolicidin. In addition, mutagenesis of the peptide gene to produce peptide variants of CEMA and indolicidin using the improved vector system was shown to be successful.

The addition in trans of the pufQ gene to a strain of Rhodobacter capsulatus from which the entire puf operon had been deleted, increased its ability to synthesize coproporphyrinogen from both delta-aminolevulinic acid and porphobilinogen. Studies at the enzyme level indicated that the conversion of porphobilinogen to uroporphyrinogen III had about a 2-fold higher level of activity in the anaerobically-grown pufQ-containing strain. This increase in activity over the puf-deletion strain appeared to occur during transitions from aerobic to semiaerobic growth conditions. These results indicated that the PufQ protein may exert a stimulatory effect quite early in the pathway of bacteriochlorophyll biosynthesis.

The PufQ protein has been detected in vivo for the first time by Western blot (immunoblot) analyses of the chromatophore membranes of Rhodobacter capsulatus. The PufQ protein was not visible in Western blots of membranes of a mutant (delta RC6) lacking the puf operon but appeared in membranes of the same mutant to which the pufQ gene had been added in trans. It was also detected in elevated amounts in a mutant (CB1200) defective in two bch genes and unable, therefore, to make bacteriochlorophyll. The extremely hydrophobic nature of the PufQ protein was also apparent in these studies since it was not extracted from chromatophores by 3% (wt/vol) n-octyl-beta-D-glucopyranoside, a procedure which solubilized the reaction center and light-harvesting complexes. During adaptation of R. capsulatus from aerobic to semiaerobic growth conditions (during which time the synthesis of bacteriochlorophyll was induced), the PufQ protein was observed to increase to the level of detection in the developing chromatophore fraction approximately 3 h after the start of the adaptation. The enzyme, S-adenosyl-L-methionine:magnesium protoporphyrin methyltransferase, also increased in amount in the developing chromatophore fraction but was present in a cell membrane fraction at the start of the adaptation as well.

The PufQ protein, prepared by the recombinant expression of the pufQ gene of Rhodobacter capsulatus, has been reconstituted into liposomes in the presence of the bacteriochlorophyll precursor, protochlorophyllide. The liposomes were separated from liposomes free of the PufQ protein by sucrose density gradient ultracentrifugation and analyzed for their content of protochlorophyllide, protein, and phospholipid. The results indicated a 3.5 times higher level of association of protochlorophyllide with the PufQ protein-containing liposomes than with liposomes containing either the hydrophobic protein, apolipoprotein A-I, or the water-soluble maltose-binding protein. Only the association of the protochlorophyllide with the PufQ protein corresponded to a small but reproducible shift in its fluorescence emission maximum to a lower wavelength, consistent with a change in its environment.

Genetic studies have shown that the expression of the pufQ gene is required for normal levels of bacteriochlorophyll biosynthesis in Rhodobacter capsulatus. Yet, the exact function of the pufQ gene is unknown, and a pufQ gene product has never been isolated. We describe the recombinant overexpression of pufQ in Escherichia coli, as well as the purification and characterization of its gene product, the 74-amino-acid PufQ protein. Site-directed mutagenesis was used to facilitate the cloning of the pufQ gene into various expression vector systems of E. coli, including pKK223-3, pLcII-FX, and pMal-c. Although high levels of pufQ transcription were evident from constructs of all three vectors, high levels of protein expression were apparent only in the pMal-c system. In vector pMal-c, the recombinant PufQ protein is expressed as a fusion with an amino-terminal maltose-binding domain. After affinity purification on an amylose column, full-length PufQ protein was released from the fusion protein by limited proteolysis with the enzyme factor Xa. The PufQ protein demonstrated a strong tendency to associate with phospholipid vesicles, consistent with the view that it is an integral membrane protein. The PufQ protein was subsequently purified by high-performance liquid chromatography and identified by amino-terminal sequence analysis. A possible role for the PufQ protein in the transport of bacteriochlorophyll biosynthetic intermediates is discussed.