Lipid nanoparticles (LNPs) have been demonstrated to hold great promise for the clinical advancement of RNA therapeutics. Continued exploration of LNPs for application in new disease areas requires identification and optimization of leads in a high throughput way. Currently available high throughput in vivo screening platforms are well suited to screen for cellular uptake but less so for functional cargo delivery.
View Article and Find Full Text PDFBackground: The current FDA-approved time interval between plerixafor dosing and apheresis initiation is approximately 11 hours, but this time interval is impractical for most care providers. Few studies have examined mobilization kinetics beyond 11 hours in multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) patients. Therefore, this study's intent was to analyze an interval of 17 to 18 hours between plerixafor dosing and apheresis initiation.
View Article and Find Full Text PDFIntroduction: Prior in vivo murine studies suggest circadian oscillations for hematopoietic stem cell release, which are maintained following administration of granulocyte colony-stimulating factor (G-CSF) or plerixafor. Furthermore, retrospective data analysis of healthy donors who underwent G-CSF-induced mobilization demonstrated significantly increased CD34(+) cell yields when collected in the afternoon compared with the morning.
Methods: A prospective study was conducted to directly examine the number of peripheral blood CD34(+) and CD34(+)CD38- progenitor/stem cells at baseline and then every 6 hours for 24 hours on days 4 to 5 of G-CSF (10 μg/kg/day in the morning) mobilization in 11 allogeneic donors.
Context: Nephrogenic adenoma is a rare benign lesion of the urinary tract. Owing to its strong association with a history of urinary tract irritation, nephrogenic adenoma was initially thought to originate from urothelial metaplasia; however, no solid proof of this association has been found. More recent investigation has pointed to a renal tubular cause.
View Article and Find Full Text PDFThe pathologic distinction of small cell from non-small cell-lung carcinoma is of considerable therapeutic significance. In particular, the ability to distinguish poorly differentiated non-small-cell lung cancer from small-cell lung carcinoma (SCLC) is at times difficult based upon morphology alone; available immunohistochemical markers such as neuroendocrine markers are of limited utility. We have demonstrated the role of p63 and thyroid transcription factor-1 (TTF-1) in the differential diagnosis of poorly differentiated squamous-cell carcinoma (PDSCC) versus SCLC, mostly in biopsy samples (Wu et al.
View Article and Find Full Text PDFStudies from this laboratory have shown that obese men have elevated serum estrogen levels and diminished levels of follicle-stimulating hormone (FSH) and free and total testosterone, all in proportion to their degree of obesity. The decreases in testosterone and FSH constitute a state of hypogonadotropic hypogonadism (HHG), and we have hypothesized that it results from feedback suppression of the pituitary by the elevated estrogen levels. We tested this hypothesis by lowering the serum estrogens of 6 health obese men (body mass index [BMI], 38 to 73) by administering the aromatase inhibitor testolactone (1 g daily for 6 weeks).
View Article and Find Full Text PDFThe nested variant of urothelial carcinoma is a recently described bladder tumor entity with a rare incidence. Two cases of this disease are presented in this report; the patients in both cases were elderly men, with a predominant involvement of the trigone region. Histologically, the tumor cells were arranged in ill-defined nests and had low-grade nuclear features.
View Article and Find Full Text PDFWe studied the usefulness of p63 and thyroid transcription factor-1 (TTF-1) immunostains for differentiating poorly differentiated squamous cell carcinoma (PDSCC) from small cell lung carcinoma (SCLC). We used monoclonal antibodies reactive to p63 or TTF-1 to stain 4-microns-thick sections from 30 formalin-fixed, paraffin-embedded lung biopsy and resection specimens and 7 alcohol-fixed, formalin-postfixed, paraffin-embedded cell blocks from lung fine-needle aspirations (FNAs). For p63, we used a streptavidin-biotin kit, diaminobenzidine as the chromogen, and a hematoxylin counterstain.
View Article and Find Full Text PDFTo investigate the occurrence of lymphoid progenitor cells in human tonsils, we studied tonsils from children and adults by immunohistochemistry by using a panel of antibodies to antigens associated with lymphoid progenitor cells, including terminal deoxynucleotidyl transferase (TdT), CD10 (CALLA), CD34, CD99 (p30/32mic2), and CD117 (c-kit), and compared them to reactive lymph nodes. Lymphoid progenitor cells, positive for TdT, CD10, and CD99, but not CD34 or CD117, were readily identified in tonsils from children and adults (TdT, 14 of 15; CD10, 15 of 15; CD99, 11 of 15), but were rarely present in lymph nodes (TdT, 1 of 8; CD10, 1 of 8; CD99, 0 of 8). Lymphoid progenitor cells in tonsils were localized to discrete foci at the periphery of lymphoid lobules adjacent to fibrous septae.
View Article and Find Full Text PDFContext: The etiology of lymph node infarction may be difficult or impossible to determine by histologic examination. Lymph node infarction is followed by malignant lymphoma in some but not all patients. The role of immunohistochemistry in the evaluation of lymph node infarction is not well defined.
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