RESUMO
Objective: To explore the clinical characteristics and long-term outcomes of mechanically ventilated patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods: In this observational study, patients with anti-NMDAR encephalitis were enrolled, who were admitted into Xuanwu Hospital of Capital Medical University from Jan 2012 to Jun 2015.All patients accepted tumor screening, symptomatic therapy, and immunotherapy.Outcomes were assessed by modified Rankin Scale (mRS) after immunotherapy every 6 months, and mRS 0-2 was defined as favorable outcome.The differences of clinical manifestations, auxiliary examinations, and outcomes between mechanical ventilation (MV) group and no MV group were analyzed. Results: Fifty-six patients (mean age 28±12 years, range 12 to 58 years) were enrolled, and 28 were male.MV group included 16 (28.6%) patients.Five female patients were diagnosed with ovarian teratoma.After 6 months, 50 patients (89.3%) had favorable outcomes, mortality was 0.The proportions of patients being female, with ovarian teratoma, conscious disturbance, dysautonomia, accepting plasmapheresis, immunodepressant treatment, admitted into neuro-critical care unit in MV group were significant higher than those in no MV group.The duration of illness prior to MV was 10-73 days (mean 33±19 days). The period of MV was 3-154 days (mean 46±41 days). There was no significant difference in the period of using MV among different outcome groups.After 6-48 months' follow-up, 6 patients (10.7%) relapsed, with 1 patient in MV group (1/16, 6.3%), 5 patients in no MV group (5/40, 12.5%). The relapses and long-term outcomes were not significant different between MV group and no MV group. Conclusions: The condition of mechanically ventilated patients with Anti-NMDAR encephalitis is severe, and the treatment is difficult. However, after active combined immunotherapy and life support, majority of these patients could get good long-term outcomes.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Respiração Artificial , Adolescente , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/patologia , Anticorpos , Criança , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Receptores de N-Metil-D-Aspartato , Adulto JovemRESUMO
Objective: To evaluate the effect of intestinal carbapenem-resistant Enterobacteriaceae (CRE) active screening combined with enhanced intervention in the prevention and control of nosocomial infection in patients admitted to the hematological ward. Methods: Patients who were admitted to the Department of Hematology in a tertiary-care general hospital from March 1, 2017 to December 31, 2019 and underwent chemotherapy or immunosuppressive therapy comprised the intervention group. They were screened for intestinal CRE at least thrice. From December 1, 2016 to February 28, 2017, patients who underwent chemotherapy or immunosuppressive therapy without active intestinal CRE screening in the Department of Hematology formed the control group. Both the patient groups were monitored for CRE infection in real time. The χ(2) test was used to compare the changes in the CRE infection rate and mortality in high-risk patients before and after the active screening. Results: During the intervention period, the CRE colonization rate of patients was 16.46% (66/401) ; in terms of disease distribution, the colonization rate of acute leukemia was the highest 23.03% (26/113) . Of the 66 colonized patients, 27 (40.9%) patients were identified as positive for CRE at the first screening, 15 (22.7%) were identified at the time of the second screening, and the remaining 24 (36.4%) were identified at the third or subsequent screening; Carbapenem-resistant Klebsiella pneumoniae (CRPK) strains were dominant among the pathogens, accounting for 54.55% (36/66) . During the active screening period, the CRE infection rate (2.49%) and mortality rate (50.00%) of high-risk patients were significantly lower than those of the controls (11.30% and 69.23%, respectively) . The pathogens of 10 CRE infection patients during the intervention period were exactly the same as the previous active screening pathogens, and the coincidence rate was 100%. Conclusion: The CRE colonization rate was the highest in patients with acute leukemia who were admitted in the hematology wards. CRPK is the main pathogen of CRE colonization, infection, and death. Increasing the frequency of screening can significantly raise the positive rate of screening, Active screening can effectively reduce the incidence and subsequent mortality of CRE in high-risk patients admitted in the hematological wards. High coincidence rate between CRE screening positive pathogens and subsequent CRE infection pathogens. Intestinal CRE screening can serve as an indicator of CRE bloodstream infection in patients with hematological diseases as well as provide information for antibiotics therapy.
Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Hematologia , Antibacterianos/uso terapêutico , Infecção Hospitalar/epidemiologia , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , HumanosRESUMO
mdm2 is part of a complex mechanism that regulates the expression of p53 as well as the function of Rb, p19ARF, and other genes. In humans, mdm2 dysregulation is associated with gene amplification. This study was undertaken to characterize altered mdm2 expression in a cohort of 38 invasive breast cancers and 9 normal breast specimens. Reverse-transcription PCR with primers spanning the entire open reading frame of the mdm2 gene in breast tissue RNA samples generated PCR products of full-length mdm2 (1526 bp) as well as smaller products (653, 281, 254, and 219 bp). Sequence analysis demonstrated that the 653-bp product was an alternatively spliced product (defined as splicing at the exon/intron boundary consensus sites), whereas the 281, 254, and 219 bp mdm2 products were aberrantly spliced products (splicing at sites not considered to be exon/intron boundary sites). Reverse-transcription-PCR with normal breast tissue RNA samples yielded only the 1526-bp product in five samples and the 1526-bp product and the 653-bp product in four samples. The 653-bp alternatively spliced product was expressed in 21% of breast cancers, and the smaller, aberrantly spliced mRNA products (281 bp, 254 bp, and/or 219 bp) were expressed in 16% of breast cancers. The protein products predicted by the alternatively spliced mRNAs and the aberrantly spliced mRNAs lacked either the entire binding domain for p53 or the majority of the binding domain for p53. Immunohistochemical analysis of HER2/neu (c-erbB2), estrogen receptor, progesterone receptor, epidermal growth factor receptor, and p53 protein was performed. p53 sequence alterations were identified by mismatch detection and confirmed by p53 oligonucleotide microarray technology. An association was demonstrated between the expression of aberrantly and/or alternatively spliced mdm2 mRNAs and a lack of progesterone receptor. An association was also demonstrated between mdm2 aberrantly and/or alternatively expression products and the presence of p53 tumor suppressor gene mutations. mdm2 is transcribed from two different promoters: one, p53-dependent, and the other, p53-independent. The 5' untranslated region of the transcripts was evaluated to determine the promoter usage in each breast cancer specimen. No correlation was observed between mdm2 splice products and promoter usage. The presence of aberrant expression products of mdm2 in breast cancer specimens was correlated with a shortened overall patient survival. These observations suggest that mdm2 expression is altered in invasive breast cancer and is associated with more aggressive disease.
Assuntos
Processamento Alternativo , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Proteínas Nucleares , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , Regiões 5' não Traduzidas/genética , Animais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Mama/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Genes p53/genética , Humanos , Camundongos , Mutação , Prognóstico , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas c-mdm2 , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Hemolysin is an important pathogenic agent of Edwardsiella tarda (ET). A fragment containing hemolytic gene, of which sequence is 4,264 bp, was cloned from ET-12 chromosome by shutgun method. It has no similarity to the hemolysin genes reported, of which 424 bp of open read frame (ORF) 3 has 68% similarity to the hemolysin regulatory gene of S. typhi (slyA). The subclone which has complete ORF3 was hemolytic, and the other of which Kanamycin gene was inserted in Pvu I of ORF3 was no hemolytic. It proved the gene was in chromosomes of ET-12 and the other ET strains by hybridization in situ and Southern blot. As recombination plasmid with the gene entered nonhemolytic ET by electroporation, no hemolytic phenomenon was observed. Conclusion was that the gene wasn't the hemolysin gene and was hemolytic relative gene.
Assuntos
Edwardsiella tarda/genética , Genes Bacterianos , Hemólise , Sequência de Aminoácidos , Sequência de Bases , Proteínas Hemolisinas/genética , Dados de Sequência MolecularRESUMO
The use of liquid RPMI 1640 medium (added NaHCO3 and serum) in sealed ampoule for in vitro assessment of sensitivity of Plasmodium falciparum to chloroquine and meflopuine in the field was very successful. On chloroquine plates with WHO supplied medium, 9 of 13 isolates were interpretable (successful rate 69.2%), the maturation rate from ring-forms to schizonts was 53.3%, the average number of nuclei per schizont 5.1. With lyophilized medium the successful rate was 100%, the maturation rate 65.9%, the average number of nuclei per schizont 7.4, while with medium in sealed ampoule, the corresponding figures were 92.3%, 65.1% and 7.3 respectively. On mefloquine plates with WHO supplied medium, 7 of 11 isolates were interpretable (63.6%). In control wells, 52.3% of schizonts matured, the number of nuclei per schizont was 5.1. With lyophilized medium the successful rate was 100%, the maturation rate 61.9%, the number of nuclei was 8.1, while those with liquid medium in sealed ampoule were 100%, 59.8% and 7.5 respectively. The results showed that the liquid medium in sealed ampoules stored within 56 days at 4 degrees C could still support the growth of Plasmodium falciparum, its supporting effect being better than that of WHO standard medium, but similar to lyophilized medium. The liquid medium in sealed ampoule had the advantages of easy carrying time-saving and more applicability under field conditions.
Assuntos
Cloroquina/farmacologia , Mefloquina/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Meios de Cultura , Resistência a Medicamentos , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
In view of the fact the resistance of Plasmodium falciparum to chloroquine occurred extensively in Hainan, a decision was made in 1979 that the use of chloroquine should be quit in the whole province. A longitudinal survey on chloroquine-sensitivity of P. falciparum was carried out during 1981-1991 to observe the variation in resistance of the parasite after the cessation of the chloroquine medication for every 2-3 years. A tendency of progressive decline of resistance was revealed. By using in vitro test, the rate of chloroquine-resistant P. falciparum dropped from 97.9% in 1981 to 60.9% in 1991 (P < 0.001). The mean dosage of chloroquine for complete inhibition of schizont formation declined from 10.46 pmol/microliters in 1981 to 3.02 pmol/microliters in 1991 (P < 0.001). The percentage of population requiring larger dosage (6.4 pmol/microliters to completely inhibit schizont formation declined from 83.3% in 1981 to 17.4% in 1991 (P < 0.001); whereas those requiring small dosage (1.6 pmol/microliters), increased from 4.2% in 1981 to 60.8% in 1991 (P < 0.001). In in vivo test, the rate of chloroquine-resistant P. falciparum decreased from 84.2% in 1981 to 40% in 1991 (P < 0.001). The proportion of RII plus RIII cases of the total resistant cases dropped from 59.4% in 1981 to 37.5% in 1991 (0.02 > P > 0.01).
Assuntos
Cloroquina/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Cloroquina/uso terapêutico , Resistência a Medicamentos , Técnicas In Vitro , Estudos Longitudinais , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Fatores de TempoRESUMO
The ferromagnetism in many carbon nanostructures is attributed to carbon dangling bonds or vacancies. This provides opportunities to develop new functional materials, such as molecular and polymeric ferromagnets and organic spintronic materials, without magnetic elements (for example, 3d and 4f metals). Here we report the observation of room temperature ferromagnetism in Teflon tape (polytetrafluoroethylene) subjected to simple mechanical stretching, cutting or heating. First-principles calculations indicate that the room temperature ferromagnetism originates from carbon dangling bonds and strong ferromagnetic coupling between them. Room temperature ferromagnetism has also been successfully realized in another polymer, polyethylene, through cutting and stretching. Our findings suggest that ferromagnetism due to networks of carbon dangling bonds can arise in polymers and carbon-based molecular materials.
Assuntos
Fenômenos Magnéticos , Nanotubos de Carbono , Politetrafluoretileno/química , Estresse Mecânico , Carbono/química , Ferro , Magnetismo , Imãs , Nanoestruturas/química , Nanotecnologia , Polietileno/química , Polímeros , Propriedades de Superfície , TemperaturaRESUMO
The Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1) has been mapped to human chromosome 21q22.3, and the candidate region has been narrowed to a region of less than 300 kb. We now report the isolation of a novel gene, PWP2H, from this EPM1 candidate region. The putative protein encoded by this gene is a novel member of the beta transducin protein superfamily with high homology to the yeast periodic tryptophan protein 2 (PWP2). PWP2H cDNA was isolated from a 14 week human trisomy 21 fetal brain cDNA library by using a modification of a direct cDNA selection method. PFGE analysis showed that PWP2H is located proximal to D21S25 and distal to TMEM1. Northern analysis of the 3.1-kb PWP2H cDNA revealed that a 3.3-kb major transcript is ubiquitously expressed in human adult tissues. DNA sequence analysis reveals a complete coding region of 2,610 bp as well as 5'- and 3'-UTR. The structure of the putative PWP2H protein contains 6 WD40 repeats, 2 acidic regions and one leucine zipper domain, suggesting that the protein may form specific protein complexes in which the WD40 repeats and the leucine zipper represent protein-protein binding sites. In conclusion, the map location and the homology to a gene family involved in a large variety of biological processes including signal transduction and development make PWP2H an intriguing candidate for EPM1 as well as for APECED (autoimmune polyglandular disease) and HPE1 (holoprosencephaly-1) that also map in this region of chromosome 21.
Assuntos
Cromossomos Humanos Par 21 , Epilepsias Mioclônicas/genética , Proteínas/genética , Proteínas de Saccharomyces cerevisiae , Sequência de Aminoácidos , Northern Blotting , Southern Blotting , DNA Complementar/isolamento & purificação , Síndrome de Down , Feto , Humanos , Immunoblotting , Dados de Sequência Molecular , Mapeamento por Restrição , Proteínas Ribossômicas , Análise de Sequência de DNA , Leveduras/genéticaRESUMO
The D2, D3, and D4 dopamine receptors cloned from brain correspond to the classically described "D2" receptors. Although radioligand binding and biochemical and functional studies have demonstrated the presence of D2-like receptors in the kidney, the expression of D2, D3, or D4 receptor genes has not been conclusively demonstrated in the kidney. Since Northern blot analysis may have precluded demonstration of dopamine receptor mRNAs because of their relative low abundance, the expression of the D2long and D3 receptor genes was studied by reverse transcription-polymerase chain reaction (RT-PCR). We were able to amplify PCR products of the predicted size using mRNA from glomeruli, proximal tubules, outer medulla, inner medulla, and renal microvessels from normotensive Wistar-Kyoto rats (WKY). Specificities of the amplified products were confirmed by restriction analysis and by sequencing the D2long product and Southern blotting the D3 product. Because some studies have suggested that D2-like receptor actions may be different between WKY and spontaneously hypertensive rats (SHR), similar studies were performed in this rat strain. In the SHR, as in WKY, PCR products of the predicted size were amplified, and restriction enzyme digestion patterns were as predicted from the cDNA sequence. The PCR-generated cDNA from the glomeruli of SHR was subcloned and sequenced and was revealed to be identical to the D2long receptor cDNA from WKY. We conclude that the D2long and D3 receptor genes are expressed in specific regions of the kidney including the glomeruli. No differences in the sequence of the D2long receptor cDNA in part of the 3rd cytoplasmic loop were noted between WKY and SHR. These studies do not rule out the possibility that mutations in other segments of the receptor exist in the SHR.
Assuntos
Expressão Gênica , Rim/fisiologia , Receptores de Dopamina D2/genética , Animais , Sequência de Bases , Southern Blotting , Masculino , Sondas Moleculares/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
The effects of 14 days neuroleptic treatment on the expression of the D3 dopamine receptor gene was investigated in rats using a sensitive polymerase chain reaction assay. In olfactory tubercle, D3 mRNA levels increased following haloperidol (40%), pimozide (56%), and sulpiride (63%) administration, and in nucleus accumbens, levels increased after haloperidol (50%) and sulpiride (50%). D3 expression in the motor striatum did not change with any antagonist tested. Clozapine did not affect D3 expression in any brain region. These data suggest that dopamine antagonists can regulate the expression of the D3 receptor in a brain region selective manner. The findings also suggest that the motor complications of chronic antipsychotic therapy are not due to D3 receptor up-regulation in the striatum.
Assuntos
Antipsicóticos/farmacologia , RNA Mensageiro/biossíntese , Receptores de Dopamina D2/biossíntese , Regulação para Cima/efeitos dos fármacos , Animais , Química Encefálica/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Masculino , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/metabolismo , Sondas de Oligonucleotídeos , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D3RESUMO
The D(3) dopamine receptor has a restricted regional distribution in brain and is regulated by dopaminergic agents. Additionally, the D(3) gene is implicated in the pathogenesis of several neuropsychiatric disorders or in their response to pharmacological agents. Elucidating its transcription control mechanisms is therefore of interest in order to explain these biological features of the D(3) gene. In this study, the 5' flanking region of the rat D(3) gene was characterized by isolating the 5' end of its cDNA as well as 4.6 kb of genomic sequence. Analysis of this region revealed the presence of two new exons 196-bp and 120-bp long, separated by an 855-bp intron, located several kilobases upstream of the previously published coding exons. Thus, current evidence indicates that the rat D(3) gene is organized into eight exons. Transcription initiation site was determined by primer extension analysis and repeated rounds of 5' RACE and was found to localize at a pyrimidine-rich consensus 'initiator' sequence, similar to the rat D(2) gene. The D(3) promoter lacks TATA or CAAT boxes but unlike that of other dopamine receptor genes has only 52% GC content. Functional analysis of D(3) promoter deletion mutants fused to a reporter gene in TE671 cells, which endogenously express this gene, revealed strong transcriptional activity localized within 36 nucleotides upstream of transcription start site, and a potent silencer between bases --37 and --537. The D(3) promoter is inactive in C6 and COS7 cells. We conclude that the D(3) gene, similar to the closely related D(2) gene, is transcribed from a tissue specific promoter which is under intense negative control.
Assuntos
Regiões 5' não Traduzidas/genética , Bulbo Olfatório/metabolismo , Regiões Promotoras Genéticas , Receptores de Dopamina D2/genética , Animais , Composição de Bases , Sequência de Bases , Sítios de Ligação , Células COS , Chlorocebus aethiops , Passeio de Cromossomo , Clonagem Molecular , Códon/genética , DNA Complementar , Proteínas de Ligação a DNA/metabolismo , Éxons , Genes Reporter , Humanos , Íntrons , Dados de Sequência Molecular , Ratos , Receptores de Dopamina D3 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Deleção de Sequência , Transcrição Gênica , Células Tumorais CultivadasRESUMO
In 1979, in view of the widespread resistance of Plasmodium falciparum to chloroquine in the island of Hainan, China, it use as an antimalarial was suspended throughout the island. A longitudinal survey of the chloroquine-sensitivity of P. falciparum was carried out over the period 1981-91 to investigate whether its resistance had changed from the 1979 level. In-vitro assays were carried out every 2-3 years, while in-vivo tests were performed annually over the period 1981-83 and also in 1991. Resistance to chloroquine declined progressively after its use had stopped. The in-vitro tests indicated that the rate of chloroquine-resistant P. falciparum was 97.9% in 1981, but dropped to 60.9% in 1991 (P < 0.001). The mean concentration of chloroquine for complete inhibition of schizont formation was 10.4 pmol/microliters in 1981, but decreased to 3.0 pmol/microliters in 1991 (P < 0.001). The proportion of samples taken from malaria cases that required high concentrations ( > 6.4 pmol/microliters) of chloroquine for complete inhibition of schizont formation was 83.3% in 1981, but only 17.4% in 1991 (P < 0.001); at low concentrations ( > 1.6 pmol/microliters), the corresponding proportions increased from 4.2% in 1981 to 60.8% in 1991 (P < 0.001). In the 4-week in-vivo test, the rate of chloroquine-resistant P. falciparum decreased from 84.2% in 1981 to 40% in 1991 (P < 0.001). RII + RIII cases represented 59.4% of the total resistant cases in 1981, but decreased to 37.5% in 1991 (0.02 > P > 0.01).