Prevalence of mycosis fungoides and its association with EBV and HTLV-1 in Pakistanian patients

Mycosis fungoides (MF) is an indolent T cell lymphoma that is distinguished from other lymphomas by its initial appearance on the skin. The histologic diagnosis of MF may be difficult because there is significant overlap in the histologic features of neoplastic T-cell infiltrates and inflammatory dermatoses. This T-cell neoplasm commonly occurs in a mixed, reactive background and can show only a subtle degree of cytologic atypia, rendering histologic diagnosis difficult. In this study MF constituted 0.86% of all non-Hodgkin s lymphoma (NHL) both T and B, as compared to the Western studies which have reported 0.5% prevalence for MF of all NHL. Polymerase chain reaction (PCR) technique was used to assess T-cell clonality in paraffin-embedded skin biopsies clinically and pathologically suspicious for early MF. Out of the 14 cases diagnosed as MF, amplifiable DNA was isolated from 6 cases, which were further studied for T-cell receptor (TcR) beta, gamma, and delta chain gene rearrangements. Clonal product was seen in 4 out of 6 cases for beta, gamma, and delta TcR chain genes. Association for Epstein Barr virus (EBV) was observed in 3 out of 6 cases (50%) of MF. Although these 3 cases were positive for EBV by PCR, but were negative by in-situ hybridization (ISH). No heterogeneity was noted in these 3 cases of MF for BamHI E, K, N, and Z regions of EBV. All six cases were negative for HTLV-1 (tax region) by PCR. It was concluded that the prevalence of MF in Pakistani population is comparable to the Western data, and that EBV association to MF cases was higher than in Western studies.     

The Replacement of Monocytes and Interleukin-1 by Phorbol Ester in Lectin-Induced Proliferation of Human Thymocytes and T Cells

Small human thymocytes isolated by counterflow centrifugal elutriation (CCE) failed to respond to lectins, and therefore they were considered to represent the immature thymocyte (IT) population. In addition, these IT also failed to respond to the tumor promotor 12-0-tetradecanoyl-13 acetate (TPA). Proliferation of the IT was induced if in addition to lectins irradiated allogeneic monocytes, crude interleukin-1 (IL-1) preparations or TPA at concentrations of 1–10^?3 µg/ml were added. Allogeneic monocytes, IL-1 or TPA also acted similarly in their synergistic effects with lectins (at concentrations that induced optimal proliferation) in the proliferative responses of unfractionated thymocytes (UT) and the medium sized to large thymocytes (MLT) which represent the mature thymocyte compartment. Irradiated autologous monocytes or TPA were also found to act in a similar synergistic way with lectins at suboptimal concentrations in the proliferation of mature T cells. These results indicate that TPA mimics the signal provided by monocytes or IL-1 in the mitogenesis of human thymocytes and mature T cells. However, at optimal lectin concentrations autologous monocytes were found to restore the reduced mature T-cell responses, whereas in contrast TPA caused strong reductions in the ³H-thymidine (³H-TdR) uptake of these cells. The mechanism of this depressed ³H-TdR uptake remains unclear, but our data so far indicate that metabolites of TPA are toxic for those T cells that have relatively large quantities of lectins bound to their membranes, since the same metabolites had no toxic effects on mature T cells activated with suboptimal lectin concentrations.     

The fine topography of climbing fiber projections to the paramedian lobule of the cerebellum in the cat

Motor cortex and somatosensory afferents of climbing fibers (CFs) which terminate in the two rostral folia of the paramedian lobule of the cerebellum were studied in pentobarbital-anesthetized cats. CF responses were elicited in all but one Purkinje cell recorded within the paramedian lobule by stimulation of one or more pericruciate sites; 67% of these also had a peripheral receptive field or were excited by stimulation of the superior radial, sciatic, or infraorbital nerve. CFs responded to stimulation of peripheral nerves at either short latency (14 to 34 ms) or long latency (<120 ms), or gave a mixture of both responses. Those responding at long latency generally did not have peripheral receptive fields. The forelimb was predominantly represented in folia a and b, although it was noted that the relationship between bodily representation and surface landmarks was variable between cats. The proximal portion of the limb was represented medially and the distal part laterally. A clear relation was established between the location of the lowest-threshold cortical site and the peripheral afferents which evoked a CF response in any given cell. The cortical site was generally in a region controlling movements of the body parts on which the peripheral receptive field was found. Two populations of CFs exist in this region, one receiving convergent and complementary cortical and peripheral information and another which, under the present experimental conditions, is excited only from the cortex. It is suggested that these two populations may project as interdigitating bands which run across the long axis of the folia.     

非何杰金氏皮肤淋巴瘤的免疫组织化学表现型鉴定

2例蕈样霉菌病(MF)和1例弥漫性大细胞性淋巴瘤(DLCL)的皮损中细胞浸润为不同的抗T淋巴细胞和它的亚型,B淋巴细胞和单核细胞的单克隆和多克隆抗体。皮损的冰冻切片应用间接免疫氧化酶技术进行检查,显示MF主要由Leu_4 Leu_3细胞浸润,具有Ia抗原阳性,而1例MF则为Leu_2~+型;DLCL病人皮损则为Lyt_2 Lyt_3 Leu_4 Leu_3 Ia~+细胞浸润。     

Primary cutaneous peripheral T-cell lymphoma with a late relapse solely in the ileum mimicking monomorphic epitheliotropic intestinal T-cell lymphoma

Background

Primary cutaneous peripheral T-cell lymphomas (PC-PTCLs) are classified into mycosis fungoides (MF) and other rare specific types; and those do not fit into any specific entities are designated as PTCL, not otherwise specified (NOS), an aggressive neoplasm. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an aggressive primary intestinal T-cell lymphoma with enteropathy in the non-neoplastic mucosa. We report a rare case of PC-PTCL-NOS with a late relapse solely in the ileum after complete remission. We discuss the importance of evaluating enteropathy, megakaryocyte-associated tyrosine kinase (MATK) immunostaining, and the implication of clonal relationship of metachronous lymphomas.

Acrolein induces selective protein carbonylation in synaptosomes

Acrolein, the most reactive of the alpha,beta-unsaturated aldehydes, is endogenously produced by lipid peroxidation, and has been found increased in the brain of patients with Alzheimer's disease. Although it is known that acrolein increases total protein carbonylation and impairs the function of selected proteins, no study has addressed which proteins are selectively carbonylated by this aldehyde. In this study we investigated the effect of increasing concentrations of acrolein (0, 0.005, 0.05, 0.5, 5, 50 microM) on protein carbonylation in gerbil synaptosomes. In addition, we applied proteomics to identify synaptosomal proteins that were selectively carbonylated by 0.5 microM acrolein. Acrolein increased total protein carbonylation in a dose-dependent manner. Proteomic analysis (two-dimensional electrophoresis followed by mass spectrometry) revealed that tropomyosin-3-gamma isoform 2, tropomyosin-5, beta-actin, mitochondrial Tu translation elongation factor (EF-Tu(mt)) and voltage-dependent anion channel (VDAC) were significantly carbonylated by acrolein. Consistent with the proteomics studies that have identified specifically oxidized proteins in Alzheimer's disease (AD) brain, the proteins identified in this study are involved in a wide variety of cellular functions including energy metabolism, neurotransmission, protein synthesis, and cytoskeletal integrity. Our results suggest that acrolein may significantly contribute to oxidative damage in AD brain.     

The role of high fat diet in the regulation of MAP kinases activity in left ventricular fibrosis

It is well known that obesity contributes to the development of systemic inflammatory responses, which in turn may be involved in the process of interstitial fibrosis and left ventricular (LV) remodelling. Activation of pro-inflammatory factors such as transforming growth factor β (TGF-β) can directly stimulate mitogen-activated protein kinase (MAPK) p38 and JNK. The aim of the study was to evaluate the level of TGF-β and MAPK p38 and JNK in the LV in Sprague Dawley (SPRD) rats maintained on a high fat diet (HFD).The SPRD rats from 4 weeks of age were on a normal fat diet (NFD) or a HFD for 12 weeks (NFD-16-week-old rats, NFD 16-wk; or HFD-16-week-old rats, HFD 16-wk) or 16 weeks (NFD-20-week-old rats, NFD 20-wk; or HFD-20-week-old rats, HFD 20-wk). At the end of the experiment, blood and LV were collected from all rats for further analysis (biochemical, Real Time PCR and immunohistochemical analysis). TGF-β mRNA expression did not differ between the study groups of rats. However, p38 MAPK mRNA expression was significantly lower in the HFD 20-wk rats than in both the HFD 16-wk rats and the NFD 20-wk rats. c-jun mRNA expression was significantly higher in the HFD 16-wk rats than in the NFD 16-wk rats. There was significantly lower expression of c-jun mRNA in the HFD 20-wk rats and in the NFD 20-wk rats than in the HFD 16-wk rats and in the NFD 16-wk rats, respectively. TGF-β type II receptor (TβRII) protein demonstrated only cytoplasmic reactivity, while p38 MAPK protein and c-jun protein showed both nuclear and cytoplasmic reactivity. The results suggest that a high fat diet and in two time intervals significantly influence the expression of p38 MAPK and JNK in the LV. However, demonstrating their potential involvement in the processes of interstitial myocardial fibrosis and left ventricular remodeling requires further research.     

Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.     

Antidepressant-like effects of Tagetes lucida Cav. in the forced swimming test

Aim of the Study

Tagetes lucida (Asteraceae), has been referred in Mexican traditional medicine for the treatment of different central nervous system (CNS) diseases, mainly depression. Nevertheless, the available scientific information about this species is scarce and there are no reports related to its possible effect on the CNS. In this work, the antidepressant-like effect of extract of Tagetes lucida was evaluated in rats, as well as its potential adverse effects on male sexual behavior (MSB).

Materials and methods

Antidepressant activity was studied using forced swimming test (FST), motor activity in the open-field test and on MSB in sexually experienced male. The aqueous extract of Tagetes lucida in doses of 5, 10, 50, 100 and 200 mg/(kg day)⁻¹ were administered orally for 14 consecutive days and evaluated on day 14, 2 h after the last dose treatment. Fluoxetine (10 mg/(kg day)⁻¹, p.o.) was used as the control positive.

Results

The aqueous extract (10, 50, 100 mg/(kg day)⁻¹) significantly reduced immobility and increased swimming without affecting climbing behavior in the FST. These same doses were not able to modify neither the motor activity nor the MSB.

Conclusion

These data indicate that the extract of Tagetes lucida possesses antidepressant-like properties in rats.