Pathobiology of human papillomaviruses in human immunodeficiency virus – Infected persons

There is a complex interrelationship between human papillomaviruses (HPV) and human immunodeficiency viruses (HIV) that has been recognized from the start of the HIV epidemic. Cervical cancer was used as a surveillance indicator for acquired immunodeficiency syndrome (AIDS) before definitive identification of the viral etiology of either condition were known. Careful epidemiologic studies combined with clinical and laboratory measures of HPV, HPV-associated disease, and HIV have helped us understand many aspects of the relationship between these two virus groups; however, questions remain. The histopathology associated with HPV is identical in HIV-positive and negative patients though the lesions are more frequent, with higher frequency of multiple HPV types, and persistent in HIV infected individuals. In this review we will briefly explain the pathobiology of HPV in HIV-infected persons and the potential impact of secondary (screening) and primary (vaccination) prevention to reduce HPV-associated disease in those infected with HIV.     

Construction of human–rodent hybrid cells containing single transferable fragments of human chromosome 10p

The introduction of chromosome 10p into human glioblastoma or prostate cancer cells has been demonstrated to suppress their malignant phenotype, suggesting the presence of glioma or prostate tumor suppressor genes on 10p. As a resource for the fine mapping of these genes, a series of human-rodent hybrid cell lines containing single transferable fragments (STFs) of 10p were constructed. Normal chromosome 10 tagged with a neomycin-resistance gene on its short arm was fragmented by gamma-irradiation of 5–10 krad, transferred into mouse L cells or Chinese hamster ovary cells by microcell-mediated chromosome transfer (MMCT), and then selected against G418. Thirty-three independent rodent-human hybrids carrying various-sized STFs were obtained. Polymerase chain reaction (PCR)-based genotyping revealed that these STFs contained the whole, or portions, of a 43-cM region on 10p14-pter and could be defined by 19 sequence-tagged-site (STS) markers. Using this panel of hybrids as donors for further MMCT, genes on the refined fragments could be transferred into other cells. This hybrid panel would therefore be a useful resource for the fine mapping of the genes on 10p14-pter to segments of about 2.4 cM by functional complementation. Received: July 28, 2000 / Accepted: September 6, 2000     

Induction of TNF-α in human macrophages by avian and human influenza viruses

The highly pathogenic avian influenza virus H5N1 is known to induce high level of tumor necrosis factor α (TNF-α) from primary macrophages. However, it is still unclear whether current H5N1 strains also induce high TNF-α production, as most of the data were derived from extinct clade 0 H5N1 strain. Here, we show that current clade 1 and 2 H5N1 strains induce variable levels of TNF-α that are not necessarily higher than those induced by seasonal influenza viruses. The result suggests that hyper-induction of TNF-α in human macrophages is not always associated with a highly pathogenic phenotype. We further tested the contribution of the NS gene segment from H5N1 isolates to TNF-α induction by using reverse genetics. While NS conferred some variation in TNF-α induction when incorporated into an H1N1 virus genetic background, it did not affect TNF-α induction in an H5N1 virus genetic background, suggesting that other viral genes are involved.     

Effect of defensin HNP-1 of human neutrophils on production of tumor necrosis factor α by human blood monocytes in vitro

Research Institute of Hematology and Blood Transfusion, Ministry of Health of Belarus', Minsk. Institute of Experimental Hematology and Biotechnology, Moscow. University of California, Los Angeles. (Presented by Academician of the Academy of Medical Sciences B. F. Semenov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 5, pp. 524–527, May, 1992.     

Mutational pressure in genomes of human α-herpesviruses

Genomes of herpes simplex viruses (HSV1 and HSV2) possess highly GC-rich DNA (their G + C content is 0.68 and 0.70, respectively). This suggests a strong mutational GC pressure. The genome of varicella zoster virus (VZV) has a GC content of 0.46, which suggests a weak AT pressure. We have calculated the frequencies of nucleotide substitutions directed by mutational pressure for the genes encoding a major capsid protein (MCP) of human α-herpes viruses capable of infecting humans. For HSV1 the substitution frequencies were calculated from the MCP gene of HSV1 (G + C = 0.68, 3 GC = 0.89) to MCP gene of HSV2 (G + C = 0.70, 3 GC = 0.91) and to the homologous gene (G + C = 0.73, 3 GC = 0.99), which is phylogenetically related to HSV, i.e., primate herpes virus 16. In these two pairs of genes, transversions C → G and G → C were the most frequently observed. Less frequent were transitions in the direction of mutation GC pressure (T → C and A → G). Even less frequently, the transversions A → C and T → G were seen. For VZV, the substitution frequencies were calculated from an MCP gene of VZV (G + C = 0.47, 3GC = 0.41) to an MCP gene (G + C = 0.41, 3GC = 0.28) of the primate herpes virus 9 related to VZV. In this pair of genes, the most frequent transitions were seen in the direction of mutation AT pressure (C → T and G → A). The transversion frequencies of A → T and T → A were fairly lower; however, they exceeded the transversion frequencies of C → A and G → T. For the MCP gene of VZV, the probability of transition frequency induced by mutational pressure in the third codon positions (where the majority of transitions are synonymous) was 2.36-fold higher than in the MCP gene of HSV1 and 3-fold higher than in HSV2. These results tend to explain the rarity of recurrent zoster compared to herpes infection.     

β-Mannosidase of human trophoblast and skin fibroblasts

Institute of Biological and Medical Chemistry, Academy of Medical Sciences, Moscow. (Presented by Academician A. I. Archakov, Academy of Medical Sciences.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 4, pp. 371–372, April, 1992.     

Role of leptin in human visceral leishmaniasis?

Human visceral leishmaniasis (VL) is frequently found in poor population who are suffering from malnutrition in endemic areas. Therefore, obviously they may have reduced levels of leptin due to reduction in number of adipocytes which are major source of leptin production. Human pathogenesis of VL and reduced levels of leptin both are associated with increase in Th2 type immune response, characterized by secretion of cytokines such as IL-4 and IL-10. Whereas, the protective immune response during visceral leishmaniasis is associated with effective Th1 type immune response characterized by secretion of IFN-γ, IL-2 and IL-12, which correlates with leptin induction of T cells polarizing to Th1 population and secretion of proinflammatory cytokines, and also inhibition of Th2 type response. Therefore, we hypothesized that leptin might be effective in treatment of visceral leishmaniasis alone or VL patients who have co-infection with other immune deficiency syndromes such as AIDS/diabetes/autoimmune disorders by regulation of Th1/Th2 homeostasis.     

Ex vivo perfusion of human lymph nodes†

In a recent study published in The Journal of Pathology, Barrow-McGee et al described a feasibility study of a real-time ex vivo perfusion model of the axillary lymph nodes (ALNs) from breast cancer patients for immune-oncological investigations. The study showed that perfused ALNs remain viable for up to 24 h, and perfusion of therapeutic antibodies confirmed the ability to reach ALN-resident cells. This work is a highly encouraging demonstration of feasibility for further research into lymphatic system function, with applications to immune function, vaccinations, and cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

A metastasis map of human cancer cell lines

Here we introduce an in vivo barcoding strategy that is capable of determining the metastatic potential of human cancer cell lines in mouse xenografts at scale.We validated the robustness,scalability and reproducibility of the method and applied it to 500 cell lines1,2 spanning 21 types of solid tumour.We created a first-generation metastasis map(MetMap)that reveals organ-specific patterns of metastasis,enabling these patterns to be associated with clinical and genomic features.We demonstrate the utility of MetMap by investigating the molecular basis of breast cancers capable of metastasizing to the brain-a principal cause of death in patients with this type of cancer.     

Modulation of α-rhythm and autonomic status of human by color photostimulation

The effects of photostimulation with different colors on α-rhythm amplitude and parameters of variation pulsometry were studied. Green color stimulation modulates human functions: α-rhythm amplitude increases by 1.06 μV/√Hz (p<0.05) and the index of regulatory systems strain decreases significantly (p<0.05).     

The effect of ε-aminocaproyl-S-benzyl-L-cysteine on the t-PA activity of human saliva

PurposeThe aim of this work was to study the effect of the synthetic antifibrinolytics:ε-aminocaproic acid (EACA), tranexamic acid (AMCHA) and ε-aminocaproyl-S-benzyl-L-cysteine (H-EACA-S-Bzl-L-Cys-OH) on the fibrinolytic activity of saliva in order to obtain new data on the activity of saliva tissue plasminogen activator (t-PA).Material and MethodsSaliva samples were obtained from healthy volunteers. Saliva, precipitate and supernatant were tested 1hr, 4 hrs and 6hrs after collection. The effect of the synthetic antifibrinolytics was examined with the use of the clot lysis time determination.ResultsAll examined compounds inhibited the fibrinolytic activity of saliva 1hr after collection. H-EACA-S-Bzl-L-Cys-OH was the most active inhibitor. After 6 hours in room temperature only this compound showed a certain possibility to prolong the clot lysis time.ConclusionsThe obtained results may indicate the possibility of the difference in specificity between the activities of t-PA of saliva and recombinant tissue plasminogen activator activities. It may explain the unexpected high inhibitory activity of H-EACA-S-Bzl-L-Cys-OH in our study.     

Binding of zinc cations to human serum γ-globulin

Binding of zinc cations to human serum γ-globulin was studied by molecular ultrafiltration. The content of free metal in the filtrate was evaluated by reaction with o-phenanthroline. Conformation characteristics of the protein were determined by UV spectrophotometry. Our findings suggest that γ-globulin molecule contains several zinc binding sites differing by corresponding constants and successively occupied with increase in the content of bound metal. The parameters of zinc binding correspond to those obtained in experiments with copper. Conformation status of protein with bound zinc differs significantly from that of protein with bound copper cations. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 141, No. 5, pp. 540–543, May, 2006     

Increased expression of αA-crystallin in human diabetic eye

We recently demonstrated that αA-crystallin, a molecular chaperone, protected photoreceptors from apoptotic signals in intraocular inflammation. Advanced glycation end product (AGE) plays an important role in the progression of diabetic retinopathy. The aim of this study was to examine the expression of α-crystallins and apoptosis in human diabetic retina, and to analyze α-crystallin up-regulation in murine eyes after AGE stimulation. Eight eye globes were obtained from postmortem donors. Six out of the eight had a medical history of diabetes mellitus, while two were without diabetes. Formalin-fixed, paraffin-embedded tissue sections were subjected to H&E staining and immunohistochemistry with anti-αA and αB-crystallins, anti-AGE and receptor for AGE (RAGE) antibodies. Apoptotic cells were detected by the TUNEL assay. Recombinant AGE protein was injected into the vitreous of adult murine eyes, and the posterior eyecups were excised 4 days after the administration. Western blot analyses and quantitative real-time PCR were performed to evaluate the alteration of α-crystallin expression. Histopathology revealed no remarkable differences between diabetic and non-diabetic retinas. Immunoreactivity for αA-crystallin was predominantly detected in the diabetic retina, whereas αB-crystallin expression was relatively low. AGE immunoreactivity was highly detected in diabetic retina and the vitreous, whilst immunoreactivity for RAGE was less marked. TUNEL-positive apoptotic cells were occasionally observed in photoreceptors of the diabetic retina, whereas cytoplasmic immunoreactivity for αA-crystallin was relatively low. αA-crystallin expression was up-regulated, and αB-crystallin was down-regulated in murine posterior eyecups exposed to AGE protein. The mRNA levels of αA-crystallin were significantly up-regulated, whereas those of αB-crystallin remained unchanged after AGE stimulation. Thus, αA-crystallin and AGE were highly expressed in human diabetic retina. αA-crystallin responded to AGE accumulation, which may contribute to the protection of photoreceptors against AGE-related retinal tissue injury.     

Effect of recombinant human thrombopoietin on exsanguine thrombocytopenia mice

Effect of recombinant human thrombopoietin on exsanguine thrombocytopenia mice