Potent combinations of antiretroviral drugs diminish the turnover of CD4؉ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4؉ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4؉ T cell counts, the CD45RA؉ subset, and fractions of proliferating or apoptotic CD4؉ T cells. Compared with normal controls, we documented decreased numbers of CD4؉ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4؉ T and CD45RA؉ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA؉ CD4؉ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4؉ T cell populations can be partially restored by control of active replication without eradication of HIV-1.

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Context.-Distinction of medullary carcinoma of the large intestine from other cytokeratin (CK) 7 À /CK20 À carcinomas can be challenging when working on a tumor of unknown primary because the majority of medullary carcinomas are negative for CK7, CK20, and CDX2.Objective.-To investigate the expression of cadherin-17 and SATB-2 and other markers in medullary carcinomas of the large intestine and cadherin-17 and SATB2 in a large number of carcinomas and normal tissues from various organs to further test their diagnostic specificity.Design.-This study evaluated cadherin-17 and SATB2 expression in 18 medullary carcinoma cases and 1941 tumors and 358 normal tissues from various organs. Other immunomarkers, including MLH1, PMS2, MSH2, MSH6, CDX2, CK7, CK20, TFF3, MUC4, calretinin, p504S, villin, and synaptophysin, were also tested on the 18 medullary carcinoma cases.Results.-The results demonstrated (1) loss of MLH1 and PMS2 in more than 80% of medullary carcinomas; (2) expression of cadherin-17 and SATB2 in 89% of medullary carcinomas; (3) focal expression of TFF3, MUC4, calretinin, CDX2, CK20, and synaptophysin in 72%, 72%, 67%, 67%, 28%, and 17% of 18 medullary carcinoma cases, respectively; and (4) expression of SATB2 and cadherin-17 in 97% and 98% of the colorectal adenocarcinomas, respectively, whereas their expression was seen in 3.6% and 3.3% of nongastrointestinal tumors, respectively.Conclusions.-We concluded that SATB2 and cadherin-17 were highly sensitive and specific markers for colorectal carcinomas and propose including MLH1, cadherin-17, and SATB2 in a routine immunostaining panel when working on a tumor of unknown primary, especially in an elderly patient with a CK7 À /CK20À carcinoma.

This review article delineates some critical points in preanalytic, analytic, and postanalytic phases; reiterates some important questions, which may or may not have a consensus at this time; and updates the newly proposed guidelines on antibody validation from the College of American Pathologists Pathology and Laboratory Quality Center. Additionally, the article intends to share Geisinger's experience with (1) testing/optimizing a new antibody and troubleshooting; (2) interpreting and reporting immunohistochemistry assay results; (3) improving and implementing a total immunohistochemistry quality management program; and (4) developing best practices in immunohistochemistry.

Pyloric gland adenoma (PGA) is a rare neoplasm demonstrating gastric epithelial differentiation. In this series, we studied 41 PGAs from 36 patients. We compared them to 28 gastric foveolar type gastric adenomas (GTAs) from 25 patients. PGAs occurred in an older population with a mean age of 73 compared with 48 in GTAs (P<0.001). There was a significant female predominance, particularly for gastric PGAs. Morphologically, PGAs were characterized by closely packed pyloric gland-type tubules with a monolayer of cuboidal to low columnar epithelial cells containing round nuclei and pale to eosinophilic cytoplasm with a ground glass appearance. The cells lacked an apical mucin cap, a feature distinct from GTAs. An immunohistochemical panel of mucin core peptides (MUCs) and CDX2 was performed on a subset of the lesions. All PGAs expressed MUC6 with coexpression of MUC5AC, whereas GTAs expressed predominantly MUC5AC without MUC6. Both lesions lacked CDX2 and MUC2 except in areas of intestinal metaplasia (IM) found in some PGAs. Histologic features consistent with conventional dysplasia were found in 26 (63.4%) PGAs. Using a 2-tier grading system, 5 (12.2%) cases demonstrated low-grade dysplasia whereas 21 (51.2%) cases showed high-grade dysplasia including 5 (12.2%) cases with an associated intramucosal or more deeply invasive adenocarcinoma. This was significantly different from GTAs; all cases showed only low-grade dysplasia (P<0.001). In addition, 60% of gastric PGAs were associated with IM in the surrounding mucosa and 40% of lesions arose in a background of autoimmune gastritis, whereas these 2 conditions were only associated with 1 case (3%) of GTA. In summary, PGA is a distinct entity. Despite its bland histologic appearance, it is much more likely to be accompanied by background IM and autoimmune gastritis and can evolve into invasive adenocarcinoma displaying pyloric gland differentiation.

Sequential encoding of motor programs is essential for behavior generation. However, whether it is critical for instinctive behavior is still largely unknown. Mouse hunting behavior typically contains a sequential motor program, including the prey search, chase, attack, and consumption. Here, we reveal that the neuronal activity in the lateral periaqueductal gray (LPAG) follows a sequential pattern and is time-locked to different hunting actions. Optrode recordings and photoinhibition demonstrate that LPAGVgat neurons are required for the prey detection, chase and attack, while LPAGVglut2 neurons are selectively required for the attack. Ablation of inputs that could trigger hunting, including the central amygdala, the lateral hypothalamus, and the zona incerta, interrupts the activity sequence pattern and substantially impairs hunting actions. Therefore, our findings reveal that periaqueductal gray neuronal ensembles encode the sequential hunting motor program, which might provide a framework for decoding complex instinctive behaviors.

RNAscope for albumin is highly sensitive and specific for identifying HCCs and is highly specific and moderately sensitive for detection of ICCs; however, rare carcinomas (non-HCC, non-ICC, and those with no hepatoid histomorphology) can also have aberrant expression of albumin.

Since chondrocyte hypertrophy greatly limits the efficiency of cartilage defects repairing via cartilage tissue engineering (CTE), it is critical to develop a functional CTE scaffold able to inhibit chondrocyte hypertrophy during this period of cartilage regeneration. In this study, we tested the applicability of using decellularized sturgeon cartilage ECM (dSCECM) scaffold to cease chondrocyte hypertrophy during cartilage damage repair. The dSCECM scaffolds with interconnected porous structure and pore size of 114.1 ± 20.9 μm were successfully prepared with freeze‐dry method. Chondrocytes displayed a round shape and aggregated to form cellular spheroids within dSCECM scaffolds, which is similar to their chondrocytic phenotype within cartilage in vivo. Higher transcriptional level of chondrogenic related genes and integrin related genes was observed in chondrocytes incubated with dSCECM scaffolds instead of type I collagen (COL I) scaffolds, which were used as the control due to their widely usage in CTE and clinic applications. Furthermore, it confirmed that, compared with COL I scaffolds, dSCECM scaffolds significantly reduced the transcription of chondrocyte hypertrophy related genes in chondrocytes following the hypertrophic induction treatment. To test the ability of dSCECM scaffold to inhibit chondrocytes hypertrophy in vivo, chondrocytes with dSCECM scaffolds and COL I scaffolds were cultured with hypertrophic media and were implanted into nude mice respectively. Following 4 weeks implantation, interestingly, only the specimens derived from COL I scaffolds displayed consequences of chondrocyte hypertrophy like calcification deposition, demonstrating that chondrocyte hypertrophy is ceased by the dSCECM scaffold following hypertrophic induction. It suggests that the dSCECM scaffold can be potentially applied in clinical treating cartilage defects via the CTE approach to avoid the risk of chondrocyte hypertrophy.