Modeling the effect of entrained sand particles on pressure transverse in a flowing gas well

Purpose The production of natural gas from the reservoir is always associated with entrained solid particle of different sizes mainly sand particles and crystalline salts. Entrained solid transport along the gas phase has been a great concern for gas production engineer, as the detrimental consequences are often associated to a desirable high operational parameters such rate and pressure transverse in producing well. Design/methodology/approach A variety of models for predicting pressure transverse in flowing gas wells have been reported in the literatures. Most of the models were based on steady state fluid flow equation that did not consider time factor which results in inaccurate at early production time. Some of the early investigators overlooked the effect of the entrained solid on the pressure transverse phenomena in a gas well. Hence, there is a need for developing a more realistic model for estimating pressure transverse at all times in flowing solid-gas vertical well. Findings This study presents equation for pressure drop in flowing vertical well without neglecting any term in the momentum equation by the inclusion of accumulation and kinetic term. The solution of the resulting differential equation gives functional relationship between solid-gas flow rates and pressure at any point in flowing well at any given production time

Human Solid Tumor Xenografts in Immunodeficient Mice Are Vulnerable to Lymphomagenesis Associated with Epstein-Barr Virus

Xenografting primary human solid tumor tissue into immunodeficient mice is a widely used tool in studies of human cancer biology; however, care must be taken to prove that the tumors obtained recapitulate parent tissue. We xenografted primary human hepatocellular carcinoma (HCC) tumor fragments or bulk tumor cell suspensions into immunodeficient mice. We unexpectedly observed that 11 of 21 xenografts generated from 16 independent patient samples resembled lymphoid neoplasms rather than HCC. Immunohistochemistry and flow cytometry analyses revealed that the lymphoid neoplasms were comprised of cells expressing human CD45 and CD19/20, consistent with human B lymphocytes. In situ hybridization was strongly positive for Epstein-Barr virus (EBV) encoded RNA. Genomic analysis revealed unique monoclonal or oligoclonal immunoglobulin heavy chain gene rearrangements in each B-cell neoplasm. These data demonstrate that the lymphoid neoplasms were EBV-associated human B-cell lymphomas. Analogous to EBV-associated lymphoproliferative disorders in immunocompromised humans, the human lymphomas in these HCC xenografts likely developed from reactivation of latent EBV in intratumoral passenger B lymphocytes following their xenotransplantation into immunodeficient recipient mice. Given the high prevalence of latent EBV infection in humans and the universal presence of B lymphocytes in solid tumors, this potentially confounding process represents an important pitfall of human solid tumor xenografting. This phenomenon can be recognized and avoided by routine phenotyping of primary tumors and xenografts with human leukocyte markers, and provides a compelling biological rationale for exclusion of these cells from human solid tumor xenotransplantation assays

Banff 2022 liver group meeting report: monitoring long term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participantsincluded hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists.Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimisation and long-term structural changes.Potential revision of the rejection classification scheme to better accommodate and communicate lateT cell-mediated rejection patterns and related structural changes, such as nodular regenerativehyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression tomatch the heterogeneity of patient settings will be central to improving long-term patient survival.Such personalised therapeutics are in turn contingent on better understanding and monitoring ofallograft status within a rational decision-making approach, likely to be facilitated in implementationwith emerging decision support tools. Proposed revisions to rejection classification emerging fromthe meeting include incorporation of interface hepatitis and fibrosis staging. These will be opened toonline testing, modified accordingly and subject to consensus discussion leading up to the next Banffconference

A Fatal Case of Diffuse Alveolar Hemorrhage in the Setting of Systemic Lupus Erythematosus: A Case Report and Review of Noninfectious Causes of Acute Pulmonary Hemorrhage in Adults

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease, characterized by autoantibody production and immune complex formation, that has the potential to affect virtually any organ. Pleuropulmonary involvement occurs in 50–70% and commonly manifests as pleuritis and pleural effusion. Diffuse alveolar hemorrhage (DAH) is a rare manifestation of SLE. Most cases of DAH occur in young adults with an underlying autoimmune disease such as systemic vasculitis or Goodpasture syndrome. SLE is typically lower on the list of initial differential diagnoses of DAH due to its rarity compared to other etiologies. We present a case of a patient with dyspnea on exertion, dry coughs, lower extremity edema, and intermittent periorbital edema who ultimately succumbed to respiratory failure secondary to DAH in the setting of SLE. The diagnosis of SLE was suspected clinically and confirmed at autopsy due to her rapid clinical deterioration. DAH requires prompt intervention, and management is guided by the underlying disease process. SLE is a potentially treatable disease; therefore, timely diagnosis is important in order to exclude other noninfectious causes of DAH (reviewed in this report) and to initiate appropriate therapy

Immunoglobulin heavy chain gene rearrangements in non-HCC-like xenografts.

<p>PCR amplification of the variable region of the human IgH gene demonstrating unique dominant rearrangements in all of the non-HCC-like xenografts, confirming clonal B-cell proliferation. Dominant rearrangements were not amplified in HCC-like xenografts. Successful amplification of the β-globin gene confirms integrity of the genomic DNA analyzed.</p

Expression of leukocyte markers and EBER in non-HCC-like xenografts.

<p>(A) Representative section (×200) from a parent HCC sample that gave rise to a non-HCC-like xenograft, demonstrating a typical distribution of CD45⁺ leukocytes along a portal tract invaded by the tumor, only a small fraction of which are CD20⁺ B lymphocytes; EBER ISH is negative. (B) Representative sections (×400) from three non-HCC-like xenografts demonstrating that a very high proportion of cells stain positively for human CD45 and human CD20 (brown), consistent with human B lymphocytes; EBER ISH is very strongly positive in the cells in these xenografts (dark blue). (C) Representative multiparameter flow cytometry analysis of freshly isolated cells from a non-HCC-like xenograft demonstrating that a large proportion of tumor cells are human CD45⁺ leukocytes (left plot), and that the majority of the gated CD45⁺ population also expresses human CD19⁺ (right plot), consistent with B lymphocytes.</p

Targeted deletion of FGL2 leads to increased early viral replication and enhanced adaptive immunity in a murine model of acute viral hepatitis caused by LCMV WE.

Mounting effective innate and adaptive immune responses are critical for viral clearance and the generation of long lasting immunity. It is known that production of inhibitory factors may result in the inability of the host to clear viruses, resulting in chronic viral persistence. Fibrinogen-like protein 2 (FGL2) has been identified as a novel effector molecule of CD4(+)CD25(+) Foxp3(+) regulatory T (Treg) cells that inhibits immune activity by binding to FCγRIIB expressed primarily on antigen presenting cells (APC). In this study, we show that infection of mice with Lymphocytic Choriomeningitis Virus WE (LCMV WE) leads to increased plasma levels of FGL2, which were detected as early as 2 days post-infection (pi) and persisted until day 50 pi. Mice deficient in FGL2 (fgl2(-/-)) had increased viral titers of LCMV WE in the liver early p.i but cleared the virus by day 12 similar to wild type mice. Dendritic cells (DC) isolated from the spleens of LCMV WE infected fgl2(-/-) had increased expression of the DC maturation markers CD80 and MHC Class II compared to wild type (fgl2(+/+)). Frequencies of CD8(+) and CD4(+) T cells producing IFNγ in response to ex vivo peptide re-stimulation isolated from the spleen and lymph nodes were also increased in LCMV WE infected fgl2(-/-) mice. Increased frequencies of CD8(+) T cells specific for LCMV tetramers GP33 and NP396 were detected within the liver of fgl2(-/-) mice. Plasma from fgl2(-/-) mice contained higher titers of total and neutralizing anti-LCMV antibody. Enhanced anti-viral immunity in fgl2(-/-) mice was associated with increased levels of serum alanine transaminase (ALT), hepatic necrosis and inflammation following LCMV WE infection. These data demonstrate that targeting FGL2 leads to early increased viral replication but enhanced anti-viral adaptive T & B cell responses. Targeting FGL2 may enhance the efficacy of current anti-viral therapies for hepatotropic viruses

IFNγ secretion and signalling and FasL expression enable B6.lpr DN T cells to inhibit alloreactive CD4⁺ T cells in vitro and in vivo.

<p><b>A.</b> Preactivated ³H-thymidine labelled CD4⁺ T cells were cultured for 18h with preactivated B6.<i>lpr</i>, B6.<i>lpr</i>.IFNγ^−/−, or B6.<i>lpr</i>.IFNγR^−/− DN T cells at indicated ratios. Specific cytotoxicty was determined based on retention of ³H-thymidine in viable targets. Data are compiled from 4 experiments in which, respectively, B6.<i>lpr</i> (circles), B6.<i>lpr</i>. IFNγ^−/− (squares), or B6.<i>lpr</i>.IFNγR^−/− (triangles) DN T cells were used in 4, 3, and 2 experiments. Compared with B6.<i>lpr</i> DN, *Two-way ANOVA p = 0.0009 and **p<0.0001. <b>B.</b> In varying ratios, B6.<i>lpr</i> DN T cells were cultured with CFSE-labelled B6. Thy1.1 (Fas^+/+) or B6.<i>lpr</i> (Fas<i>^lpr/lpr</i>) CD4⁺ T cells, irradiated CB6F1 splenocytes and IL-2. CFSE dilution in live (7-AAD⁻) cells was determined after 5 days. Data from 2 independent experiments are shown; two-way ANOVA p<0.0001. <b>C.</b> Lethally irradiated CB6F1 mice received BM only (n = 5), BM+CD4⁺ (n = 8), BM+CD4⁺+2.5×10⁶ B6.<i>lpr</i> DN (n = 10, FasL⁺) or 2.5×10⁶ B6.<i>gld</i> DN (n = 12, FasL⁻). Data are from 2 independent experiments, each with 2–6 mice per group. *Log rank p = 0.006 vs. B6.<i>gld</i> DN.</p