Clinical Diagnosis and Prenatal Screening of Hb Lepore-BW Associated with IVS-II-654 Heterozygous Mutation / 中国实验血液学杂志

OBJECTIVE@#To identify one case of rare Hb Lepore-BW associated with IVS-II-654 heterozygous mutation in Sichuan area.@*METHODS@#The blood routine examination and hemoglobin electrophoresis methods were used to analyze the blood routine parameters, HbA2 and HbF in the samples of peripheral blood in proband and his parents, as well as the cord blood of pregnant woman. The detection of thalassemia gene and Sanger sequencing methods were used to detect the hemoglobin mutations.@*RESULTS@#The result showed that the Hb Lepore-BW heterozygous mutation was detected in the father of the proband, while a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation was detected in the proband, as well as his mother and cord blood were both detected as IVS-II-654 heterozygous mutation.@*CONCLUSION@#The study identified a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation, which was characterized by intermediate β-thalassemia. It is necessary to hemoglobin electrophoresis combined with routine blood testing in prenatal screening.

The poly(ADP-ribosyl)ation of BRD4 mediated by PARP1 promoted pathological cardiac hypertrophy

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.

Magnetic systems for cancer immunotherapy

Immunotherapy is a rapidly developing area of cancer treatment due to its higher specificity and potential for greater efficacy than traditional therapies. Immune cell modulation through the administration of drugs, proteins, and cells can enhance antitumoral responses through pathways that may be otherwise inhibited in the presence of immunosuppressive tumors. Magnetic systems offer several advantages for improving the performance of immunotherapies, including increased spatiotemporal control over transport, release, and dosing of immunomodulatory drugs within the body, resulting in reduced off-target effects and improved efficacy. Compared to alternative methods for stimulating drug release such as light and pH, magnetic systems enable several distinct methods for programming immune responses. First, we discuss how magnetic hyperthermia can stimulate immune cells and trigger thermoresponsive drug release. Second, we summarize how magnetically targeted delivery of drug carriers can increase the accumulation of drugs in target sites. Third, we review how biomaterials can undergo magnetically driven structural changes to enable remote release of encapsulated drugs. Fourth, we describe the use of magnetic particles for targeted interactions with cellular receptors for promoting antitumor activity. Finally, we discuss translational considerations of these systems, such as toxicity, clinical compatibility, and future opportunities for improving cancer treatment.

To Evaluate the Diagnostic Yield of Transbronchial Needle Aspiration in Cases of Lung Cancers and Mediastinal Masses or Adenopathy

Background: A great deal of interest in transbronchial needlespiration (TBNA) lies in its utility as a staging tool in patientswith bronchogenic carcinoma. The aim of this study toevaluated the diagnostic yield of TBNA in cases of lungcancers and mediastinal masses or adenopathy.Materials & Methods: The study was carried out and datawere gathered in a prospective fashion and all the data werereviewed retrospectively. Samples were collected from allpatients bronchial washings (BW), brush biopsy (BB), EBB,and TBNA. All TBNA specimens were sent for cytologicevaluation without ROSE as per recommended guidelines.Results: The mean age of studied cases was 58.07 years. Thecommon radiological presentation on x-ray chest was masslesions in 76.66%, mediastinal widening 60%, consolidation26.66% and SPN 3.33% of cases. The diagnostic yield ofvarious bronchoscopic procedure were 27% by BW, 47% byBB, 60% by EBB, 87% by TBNA.Conclusion: We conclude that the overall diagnostic yield offlexible bronchoscopy procedure is increased in patients withEML or SPD by the addition of TBNA. The TBNA is a safeprocedure that should be routinely used to increase diagnosticyield in patients with EML or SPD. In cases of SPD, TBNAshould be considered the procedure of choice.

Partial Purification and Antimycobacterial Screening of the Ethyl Acetate Extract of Alcaligenes faecalis BW1.

Aims: The focus of this study was to evaluate the antimycobacterial activity of Alcaligenes faecalis BW1 extract and to purify it partially. Study design: Partial purification of A. faecalis BW1 extract was performed by using thin layer chromatography and active substances responsible for the biological activity were localized. Place and Duration of Study: The study was carried out at laboratory of Microbial Biotechnology, Department of Biology, Faculty of Sciences and Technical, University Sidi Mohamed Ben Abdellah, BP 2202, Road of Immouzer, Fez, Morocco, during the period from January 2011 to July 2011. Methodology: Crude extract of A. faecalis BW1 was obtained by using ethyl acetate as an organic solvent and its antimycobacterial effect was investigated by agar discs diffusion method. The extract was then fractionated by thin layer chromatography and the bioactivity was assessed with a bioautography technique followed by spots elution tests. Results: The results showed that A. faecalis BW1 produced compounds with antimycobacterial activity. All the detected spots by thin layer chromatography inhibited the growth of M. smegamtis. Conclusion: Various metabolites of A. faecalis BW1 are responsible for the sought effect or they could act synergistically to inhibit mycobacterial growth. These compounds could be used after their total purification in further work against mycobacterial infections.

Tolerance Tests of Alcaligenes faecalis BW1 Extract.

Aims: To highlight whether metabolites of Alcaligenes faecalis BW1 extract can be administered orally for their possible antimycobacterial effects. Study Design: Study of the influence of certain parameters on the extract of Alcaligenes faecalis by using either discs or well diffusion methods against M. smegmatis. Place and duration of study: Laboratory of Microbial Biotechnology, Department of Biology, Faculty of Sciences and Technical, University Sidi Mohamed Ben Abdellah, BP 2202, Road of Immouzer, Fez, Morocco. From April to August, 2012. Methodology: The impact of acidic pH of gastric juice, bile, hydrogen peroxide, pancreatic enzymes and lysozyme on the antimycobacterial activity of Alcaligenes faecalis BW1 extract was evaluated by agar diffusion method. Detection whether or not antibacterial metabolites having a synergistic effect with rifampicin against M. smegmatis was also explored. Results: Antibacterial metabolites of Alcaligenes faecalis BW1 extract resist to the action of gastric pH, gallbladder bile and hydrogen peroxide. In addition, they are not affected by pancreatic enzymes and lysozyme. Moreover, they have a synergistic effect with rifampicin against M. smegmatis. Conclusion: Anti-mycobacterial metabolites of Alcaligenes faecalis BW1 extract are compatible with rifampicin and could be administered orally as antitubercular agents after their purification, identification in further work.

Normativas internacionais de proteção contra bioterrorismo e biocrimes: lacunas e vulnerabilidades no Brasil / International standards for protection against bioterrorism and biocrimes: gaps and vulnerabilities in Brazil

Saúde Global pode ser entendida como questões de saúde que transcendem fronteiras nacionais e demandam intervenções nos assuntos que determinam a saúde das populações. Atualmente, os Estados deparam-se seguidamente com problemas e crises relacionadas à área da saúde. Em relação à segurança nacional, essa preocupação se manifesta sob a forma de ameaças de proliferação de Armas Biológicas e de Bioterrorismo. A comunidade internacional tem se esforçado para propor normas que previnam tais atos. Os melhores exemplos são a Convenção para a Proibição de Armas Biológicas e suas Toxinas (CPAB), a Resolução 1540 do Conselho de Segurança das Nações Unidas (Res 1540/CSNU) e o Regulamento Sanitário Internacional (RSI). Contudo, existem várias lacunas e vulnerabilidades que podem ser exploradas nesses documentos. O escopo desse estudo é propor questionamentos a partir da Análise Documental desses tratados, ponderando a articulação entre os órgãos nacionais com a responsabilidade de prevenção, controle e resiliência contra ataques biológicos. O Brasil é signatário das principais normativas internacionais direcionadas à prevenção e controle de uso intencional de agentes biológicos e vem respondendo a contento à comunidade internacional. Ainda assim, é necessário mais que uma resposta formal a entidades supranacionais para prover, efetivamente, a devida proteção à população. O País possui capacidades técnicas estruturadas de forma isolada e fragmentada em diversos órgãos inexistindo um sistema formalmente instituído para a prevenção,resposta e controle de ataques bioterroristas...

Global Health can be understood as health issues that transcend national borders andrequire intervention in matters that determine the health of populations. Currently, States face crisis and problems related to health realm. Regarding national security, thisconcern is manifested in the form of threats of Biological Weapons proliferation and Bioterrorism. The international community has endeavored to propose regulations that prevent such acts. The best examples of it are the Convention for the Prohibition ofBiological Weapons and their Toxins (BWC), the United Nations Security Council Resolution 1540 (Res 1540/UNSC) and the International Health Regulations (IHR). However, there are several gaps and vulnerabilities that can be exploited in thesedocuments. The scope of this study is questioning these treaties using DocumentAnalysis, pondering the link between national entities responsible for prevention,control and resilience against biological attacks. Brazil is signatory of the major international instruments aimed at the prevention and control of biological agentsintentional use and has responded satisfactorily to the international community. Never theless, it takes more than a formal supranational response to provide effectivelyappropriate protection to population. The country owns technical capabilities not connected, distributed in several organs and lacks a system for the prevention, responseand control of bioterrorist attacks. Likewise, there is no national protocol established inorder to coordinate the activities of the bodies responsible for controlling the threat. Factors that determine individuals or groups to employ biological agents and toxins intheir violent attacks are not fully understood. Thus, more reckless than exacerbate therisk of intentional actions with biological agents is not being properly prepared toprevent and control such acts...

Bw4 motif expressed on HLA-B antigen affects HIV-1 specific T cell responses induced in patients with acute HIV-1 infection / 中华微生物学和免疫学杂志

Objective To investigate whether Bw4 motif expressed on HLA-B affects Gag-specific T cell responses in patients with acute HIV-1 infection.Methods Sequence specific primer polymerase chain reaction ( SSP-PCR) was performed for human leukocyte antigen ( HLA) typing.Peripheral blood mononuclear cells ( PBMCs) from 36 patients with six months of acute HIV-1 infection were stimulated with HIV-1 CRF01_A/E Gag peptides to detect the HIV-1 specific T cell responses by using ELISPOT assay. Results (1) The set point viral load of 18 patients carrying no Bw4 motif on HLA-B was 4.49±0.56 which was higher than that in other 18 patients carrying 1-2 Bw4 motif(s) on HLA-B (3.78±0.75) (P=0.005). (2) T cells from 26 out of 36 patients with acute HIV-1 infection responded to P24 peptides pool including 15 patients carrying no Bw4 motif on HLA-B and 11 patients carrying 1-2 Bw4 motif( s) on HLA-B, but no significant difference was observed between them (P>0.05).The magnitude of P24-specific T cell responses induced in patients carrying no Bw4 motif on HLA-B was (1317.8 ±1238.0) SFC/106 PBMCs which was greater than that induced in patients carrying 1-2 Bw4 motif(s) on HLA-B [(549.9±778.5) SFC/106 PBMCs] ( P=0.032) .The breadth of T cell responses to P24 peptides was 2(0-5) in patients carrying no Bw4 motif on HLA-B which was broader than that of patients carrying 1-2 Bw4 motif(s) on HLA-B [1(0-4)] (P=0.080).(3) The viral loads of HIV-1 infected patients carrying no Bw4 motif on HLA-B were negatively correlated with the magnitude of P24-specific T cell responses (rs=-0.482, P=0.043) and the breadth of responses to P24 peptides (rs=-0.496, P=0.036).No correlations were observed between viral loads and the magnitude or breadth of P24-specific T cell responses in HIV-1 infected patients carrying 1-2 Bw4 motif(s) on HLA-B.Conclusion Compared with HIV-1 infected patients carrying no Bw4 motif on HLA-B, the patients carrying 1-2 Bw4 motif( s) on HLA-B showed lower levels of set point viral load, weak-ened magnitude of P24-specific T cell responses and narrowed breadth of responses to P24 peptides.

Impact of broad antigen HLA-Bw4 on HIV-1 disease progression / 中华微生物学和免疫学杂志

Objective To explore the impact of broad antigen HLA-Bw4 on disease progression in HIV-1 infected subjects. Methods Three hundred and forty subjects chronically infected with HIV-1 and 69 HIV-1 negative subjects were recruited and HLA-B alleles were typed with sequence-based high resolution typing assay. HLA-Bw genotypes of these HIV-1 infected subjects were determined and their association with CD4+ T cell counts and viral loads were analyzed. Results Sixty-five HLA-B alleles were detected in HIV-1 positive subjects. Subjects with Bw4 (Bw4 homozygotes and Bw4Bw6 heterozygotes ) had higher CD4+ T cell counts ( P = 0. 004 ) and lower plasma viral load ( P = 0.003 ) than subjects without Bw4 ( Bw6 homozygotes). When compared with HIV-1 postive subjects with CD4+ T cell counts above 500 celis/μl, those with CD4+ T cell counts below 500 cells/μl were observed with decreased percentage of Bw4Bw6 heterozygote ( P =0.0002) and increased percentage of Bw6 homozygotes ( P < 0. 0001 ). There is no significant difference in CD4+ T cell counts between Bw4 homozygotes and Bw4Bw6 heterozygote, but lower viral loads were observed in Bw4Bw6 heterozygotes( P = 0. 037 ). Conclusion HLA-Bw4 can confer pretective effects on H1V-1 infected subjects by maintaining higher CD4+ T cell counts and lower viral load, the mechanism behind this effect need further exploration.

Measurement of bone mineral density in Korean newborns by dual photon absorptiometry

No abstract available.

Prognostic comparison of Behcet's disease with or without HLA-Bw 51 antigen

To know the prognosis of Behcet's disease with HLA-Bw 51 antigen, comparison studies of 24 cases of Behcet's disease were investigated. The sex distribution was 14 males (58%) and 10 females (42%). The patients were grouped into three clinical types: the complete type with 11 cases (45%), the incomplete type with eight cases (33%) and the suspect type with five cases (22%), according to the criteria established by the Behcet's Disease Research Committee in Japan (1982). They were also divided into three ocular types according to the location of the inflammation: the anterior segment type, the fundus type and the mixed type. They were divided into 10%, 10% and 60% in HLA-Bw 51 negative group and 14%, 22% and 64% in HLA-Bw 51 positive group, respectively. Skin lesions observed in 30% of the HLA-Bw 51 negative group and 70% of the HLA-Bw 51 positive group, which was statistically significant (p 0.1).

EFFECTS OF DIFFERENT DRUGS ON THE GENERATION OF ACTIVE OXYGEN IN POLYMORPHONEUCLEAR LEUKOCYTES ( PMN_s ) FROM RATS / 中国药理学通报

By the method of chemiluminescence, it was showed that BW-755C strongly inhibited the generation of active oxygen in PMNs stimulated by f-MLP, A23187 or opsonized zymosan A, while the inhibitory effect of indomethacin was quite weaker, Nifidipine, diltiazem and verapamil inhibited the generation of active oxygen in PMNs stimulated by A23187 at low concentration, but they did not block intracel-lular calcium ion increase stimulated by A23187. PGE1 was shown in to be a selective inhibitor of f-MLP-induced active oxygen production PMNs.