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Prion disease genetics.

Prion diseases have stimulated intense scientific scrutiny since it was proposed that the infectious agent was devoid of nucleic acid. Despite this finding, genetics has played a key role in understanding the pathobiology and clinical aspects of prion disease through the effects of a series of polymorphisms and mutations in the prion protein gene (PRNP). The advent of variant Creutzfeldt-Jakob disease has confirmed one of the most powerful human genetic susceptibility factors, as all tested patients have an identical genotype at polymorphic codon 129 of PRNP. This review will also consider the

Heterogeneity in telomere length of human chromosomes.

Vertebrate chromosomes terminate in variable numbers of T2AG3 nucleotide repeats. In order to study telomere repeats at individual chromosomes, we developed novel, quantitative fluorescence in situ hybridization procedures using labeled (C3TA2)3 peptide nucleic acid and digital imaging microscopy. Telomere fluorescence intensity values from metaphase chromosomes of cultured human hematopoietic cells decreased with the replication history of the cells, varied up to six-fold within a metaphase, and were similar between sister chromatid telomeres. Surprisingly, telomere fluorescence intensity val

Comparison of the Gen-Probe Group A streptococcus Direct Test with culture and a rapid streptococcal antigen detection assay for diagnosis of streptococcal pharyngitis.

The Gen-Probe Group A Streptococcus Direct Test (GP-ST) is a new assay which utilizes a nucleic acid probe to detect group A streptococci directly from pharyngeal swabs. In this study, 1,103 specimens were cultured and tested by GP-ST. The sensitivities and specificities were as follows: culture, 98.8 and 100%; GP-ST, 92.4 and 99.6%. Of the 1,103 specimens, 808 were also tested with the TestPack Strep A assay. For the specimens tested by all three methods, the sensitivities and specificities were as follows: culture, 99.5 and 100%; TestPack Strep A assay, 76.3 and 99.7%; GP-ST, 93.5 and 99.7%.

Detection of gene alteration for color vision defects by polymerase chain reaction.

According to the fact that the abnormalities of visual pigment genes were always involved in the changing of the exon 5, two oligonucleotide primers were designed to amplify the exon 5 of red pigment gene and green pigment gene. After electrophoresis of the PCR products digested with Rsal or Sau3A, the DNA fragments from the exon 5 of red pigment gene (RPG) and green pigment gene (GPG) were separated since there are different restriction endonuclease sites. On the other hand, we analyzed the exon 5 related fragment by Southern blot hybridization with probe out of the 3' end of the fourth intro

Teratogenicity testing based on the interaction with a mutant allele.

The system of congenic strains of the laboratory rat carrying the mutant allele lx which is determining the polydactyly-luxate syndrome (PLS) was used for testing teratogenicity of six compounds from different pharmacological groups (cyclophosphamide, cyadox, carbadox, imipramine, verapamil, TIA). The interaction of the mutant lx allele with cyclophosphamide was highly significant (P less than 0.001) involving both polydactyly and tibial hemimely. Significant interaction with the lx allele was also proved after cyadox and carbadox treatment when compared with lx allele penetrance in LEW/BN, +/

Chlamydial rRNA in the joints of patients with Chlamydia-induced arthritis and undifferentiated arthritis.

Synovial fluid and synovial membrane specimens of 11 patients with Chlamydia-induced arthritis (CIA), 24 patients with undifferentiated arthritis (UndA), 4 patients with post-enteritic reactive arthritis, 3 patients with Lyme arthritis and 9 patients with rheumatoid arthritis were investigated for the presence of Chlamydia trachomatis (C. trachomatis). A single stranded DNA-probe was used for nucleic acid hybridization with ribosomal RNA (rRNA) from C. trachomatis. In 4 patients (CIA = 1, UndA = 3) chlamydial rRNA was found in the synovial fluid. In one additional patient (CIA) the specimen of

Analysis of Creutzfeldt-Jakob disease infectious fractions by gel permeation chromatography and sedimentation field flow fractionation.

Gel permeation chromatography and sedimentation field flow fractionation (SF3) were used to further analyze highly infectious fractions from Creutzfeldt-Jakob disease (CJD) infected hamster brain. These analyses defined the relative molecular mass and physical size of the Creutzfeldt-Jakob disease (CJD) agent with greater precision than previously possible. Highly purified disaggregated fractions yielded single, homogeneous Gaussian peaks with both methods. The relevant analytical peaks contained protein-nucleic acid complexes with an M(r) of approximately 1.5 x 10(7) daltons and a mean radius

Молекулярный подход к интеровиральному диагнозу идиопатической кардиомиопатии и миокардита.

В некоторых случаях миокардит человека и расширенная кардиомиопатия считаются этиологическими агентами. Мюрин-модели острого коксакивируса B3 миокардита включают вирусы коксаки B в качестве возможных причин миокардита человека. Косвенные данные, свидетельствующие о том, что энтеровирусы в качестве причинно-следственных агентов являются сердечными заболеваниями человека, получены в результате сероологических исследований. В последнее время в результате анализа гибридизации нуклеиновой кислоты были получены прямые доказательства присутствия в организме сердечных тканей больного человека. Хотя да

Morphological demonstration of the first phase of polyomavirus replication in oligodendroglia cells of human brain in progressive multifocal leukoencephalopathy (PML).

Ultrastructural characteristics of adsorption, penetration and intracellular transport of polyomavirus is demonstrated in oligodendrocytes in PML. The findings are compared with those obtained by virological examinations of polyomavirus infections described in cell cultures. The morphology of the eclipse phase and the site of the beginning of virus assembly are also described. The vacuolization of the cytoplasm is considered to be the consequence of the production of viral protein and nucleic acid. The cytoplasmic virions surrounded by membrane in the early and late phases of replication are c

Isolation and characterization of subacute sclerosing panencephalitis virus nucleocapsids.

Nucleocapsids from subacute sclerosing panencephalitis (SSPE) virus-infected CV-1 cells were concentrated by differential centrifugation employing sucrose cushion techniques and further purified by centrifugation through a linear CsCl density gradient. The bouyant density of (3)H-uridine-labeled nucleocapsids in CsCl was found to be 1.31 g/cm(3). Ultraviolet absorption spectra of the purified SSPE nucleocapsid showed an absorption maximum at 260 to 265 nm and a 280/260 ratio that corresponded to a nucleic acid content of approximately 4.3%. Negatively stained preparations of SSPE nucleocapsids

Rapid Onset Fibrosing Cholestatic Hepatitis C Following Transplant of a Hepatitis C Infected Graft Into a Naïve Recipient.

Fibrosing cholestatic hepatitis (FCH) is a devastating complication that can occur when hepatitis C virus (HCV) recurs following liver transplantation. When it occurs, FCH typically develops between 1 and 6 months following transplant and is associated with markedly elevated HCV levels. With the advent of direct-acting antiviral therapy, FCH C is now a rare occurrence. Here, we describe a rare case of early-onset FCH that occurred when an HCV nucleic acid test (NAT) positive liver graft was transplanted into a hepatitis C naïve recipient. This case highlights the importance of initiation of an

Influence of protein aggregates, extracellular vesicles, and lipoprotein fusion on ionizable lipid nanoparticles protein corona analysis.

Since 2018, ionizable lipid nanoparticles (LNPs) have revolutionized nucleic acid therapeutics. However, achieving potent extrahepatic delivery remains a formidable challenge, primarily due to rapid hepatic uptake driven by apolipoprotein adsorption. While analyzing the LNP protein corona is essential for engineering organ-specific tropism, these soft materials present unique analytical hurdles. Co-isolation of blood-borne contaminants, such as extracellular vesicles and lipoproteins, often masks the true corona composition. This perspective examines the critical need for refined proteomic str

Multiple regulatory roles of UNC93B1 in innate immunity.

Uncoordinated 93 homolog B1 (UNC93B1) is a key innate immune regulator that affects the function of pattern recognition receptors. UNC93B1 is responsible for governing the intracellular trafficking and activation of nucleic acid-sensing TLRs. Recently, UNC93B1 was shown to regulate the cGAS/STING signaling pathway. As a result, UNC93B1 is a promising therapeutic target for various human diseases. In this review, we provide an update on new findings establishing the regulatory role of UNC93B1 in innate immunity, including the antibacterial activity of neutrophils, the PRR-mediated signaling pat

In Vivo Evaluation of Pam2Cys-Modified Cancer-Testis Antigens as Potential Self-Adjuvanting Cancer Vaccines.

Peptide-based vaccines, formulated with an appropriate adjuvant, offer a versatile platform for targeted cancer immunotherapy. While adjuvants are usually coadministered for nucleic acid and protein vaccines, synthetic peptide antigens afford a more effective opportunity to covalently and regioselectively graft immunostimulatory motifs directly onto the antigen scaffold to yield self-adjuvanting vaccines. Herein, we explore the synthesis of two tissue-restricted cancer-testis antigens (CTAs); New York oesophageal cell carcinoma 1 (NY-ESO-1) and B melanoma antigen 4 (BAGE4), both carrying the t

Biological Nanocarriers in Cancer Therapy: Cutting Edge Innovations in Precision Drug Delivery.

Cancer is a highly detrimental and fatal illness that poses a significant threat to human well-being. The pattern of cancer treatment is continuously being optimized by the advancement of old treatment approaches and the invention of novel treatment modes. Nanotechnology-based approaches are emerging as powerful candidates in the development of these advanced methods for treating tumors. This article provides a concise overview of nanotechnology for cancer or cancer nanomedicine and its applications. In light of prevalent issues, such as inadequate precision in targeting initial chemotherapy d

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… ASOs are short synthetic single-stranded nucleic acid sequences that can specifically bind to RNA target molecules in order to manipulate gene expression. … Furthermore, some researchers have developed polymers especially for the delivery of nucleic acids. …

Beyond anaphylaxis: a multidimensional exploration of sesame allergy in a globalized world.

Sesame (Sesamum indicum) seeds offers a varieties of health benefits, which include protection against hypertension, cognitive decline, diabetes, and anti-inflammatory properties. However, sesame allergy is becoming as a significant global health concern, primarily driven by IgE-mediated reactions that can ranges from mild symptoms to severe anaphylaxis. So far, seven sesame allergens have been officially recognized by the World Health Organization and the International Union of Immunological Societies. This article highlights the characteristics and universal prevalence of these allergens, th

Tissue distribution pharmacokinetics of intrathecal U1 adaptor oligonucleotide in mice.

U1 Adaptor is a novel gene-silencing technology, offering an innovative approach to target genes in the CNS for the treatment of diseases. Intrathecal delivery is a medically viable route of administration of CNS-bound nucleic acid drugs; therefore, it is important to investigate U1 Adaptor distribution after intrathecal drug delivery. We investigated the distribution patterns of U1 Adaptor upon intrathecal bolus administration in mice. It readily distributes to CNS tissues, including the lumbar and the cervical spinal cord, and the cerebellum. Over time, the U1 Adaptor also accumulates in the

[Parasitological examination of stools: french ANOFEL/LABAC recommendations].

Parasitological examination of stools is a challenging analysis due to the diversity of parasites to be screened for, depending on the exposure context and patient background. Parasite detection is traditionally performed using direct wet mount and various concentration methods followed by microscopic reading, which requires expertise. The quotation of this analysis in the nomenclature of medical biology procedures has become obsolete due to the development of molecular biology techniques and epidemiological changes. Currently commercialized nucleic acid detection techniques, often in multiple

Molecular and immunological diagnosis of Monkeypox virus in the clinical laboratory.

The 2022 monkeypox outbreak outside Africa is ongoing. Cases have been reported in Hong Kong and Chongqing, China. In order to better prevent and control the potential spread of monkeypox virus in China, the development of sensitive and reliable detection commercial kits is imminent. This correspondence reviews the existing laboratory assays and related technologies for nucleic acid (PCR) and serological assays for the diagnosis of monkeypox virus to provide reference for the management and decision-making departments. Due to the serological cross-reactivity of orthopoxviruses, PCR is the labo

Discovery of the First Druggable GPR52 Antagonist to Treat Huntington's Disease.

GPR52 is an orphan G protein-coupled receptor (GPCR) highly expressed in the brain, especially in the striatum, and represents an emerging therapeutic target for Huntington's disease (HD), an incurable monogenic neurodegenerative disorder caused by the mutation of the huntingtin (mHTT) gene. This Viewpoint discusses the discovery, published in this journal, that a highly potent and specific GPR52 antagonist was identified through high-throughput screening and structure-activity relationship study, which diminishes not only mHTT protein levels, but also ameliorates HD-like phenotypes in the ani