RESUMO
We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (â ¢A). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.
Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Neoplasias Torácicas , Humanos , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia , Neoplasias Pulmonares/genética , Neoplasias Torácicas/diagnóstico , Neoplasias Torácicas/genética , Neoplasias Torácicas/patologia , DNA Helicases , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
Objective: To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment. Methods: A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained. Results: Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval (HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment (HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status (HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval (HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment (HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence (HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status (HR=1.69, 95% CI: 1.02-2.81), the recurrence interval (HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence (HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions: Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.
Assuntos
Neoplasias da Mama , Parede Torácica , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Mastectomia , Recidiva Local de Neoplasia , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To evaluate the effect of nutritional status on clinical and pathological data for stage â -â £ gastric cancer patients from the cancer survival investigation information. Methods: A database of 302 consecutive gastric cancer patients underwent radical gastrectomy was enrolled in this study. The clinical and pathological information of them were corrected and the relationship between the nutritional index and the patients survival time were analyzed by a Cox regression model. Results: The clinical data analysis of 302 patients with gastric cancer who received total gastric resection indicated that the nutritional status was related to the stage of tumor patients, suggesting that the later the stage was, the more necessary the nutritional therapy intervention was. Univariate analysis showed that â ¢+â £ of TNM staging (HR=4.417, 95%CI:2.483-6.351; P =0.029), patient age of 65 and above (HR=2.217, 95%CI:0.522-3.912; P =0.038), lymph node metastasis positive (HR=2.517, 95%CI:0.516-4.518; P=0.036), poor tumor differentiation (HR=3.626, 95%CI:0.721-6.531; P =0.021) and low PNI (HR=2.612, 95%CI: 0.712-4.512; P =0.029) is an important risk factor for poor prognosis. In the multivariate analysis, â ¢+â £ of TNM staging (HR=3.821, 95%CI:1.923-5.719; P =0.014), patient age of 65 and above (HR=1.168, 95%CI:0.321-2.015; P =0.036) and low PNI (HR=2.435, 95%CI:1.024-3.846; P =0.039) was independently correlated with poor survival time; When age was used as a stratification factor, the correlation between CONUT recurrence and survival in patients with gastric cancer ≥65 years old after total gastric resection was analyzed and compared. For disease-free survival, the CONUT high group (>3) was 25.2 months, while the CONUT low group (≤3) was 30.9 months, (χ2=3.763,P=0.029), showing a significant difference. For the overall survival, the CONUT high(>3) group was 30.3 months, compared with the CONUT low(≤3) group at 34.5 months, (χ2=4.924,P=0.042), and the difference was also statistically significant. Conclusions: High controlling nutritional status is an independent risk factor associated with poor gastric cancer survival and it is an independent risk factor in predicting overall survival (OS) in elderly (≥65) gastric cancer after radical gastrectomy.
Assuntos
Neoplasias Gástricas , Idoso , Gastrectomia , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estado Nutricional , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
Gibson (The ecological approach to visual perception, Houghton Mifflin, Boston, 1979/1986) defined affordances as opportunities for motor behaviors, and highly emphasized the interaction between perception and action. Research on children with developmental coordination disorder commonly reports difficulties in judgments of affordances (perception) and in postural control (action). However, how perception and action are coupled has not been studied yet. The present study sought to evaluate the relationship between control of postural sway and perception of affordances in children at risk for developmental coordination disorder (RDCD) and typically developing children (TDC). We hypothesized that the relationship between perception and action would differ between groups. Participants made a series of judgments about their maximum sitting height (SHmax) while standing with and without wearing 10 cm blocks on feet. Postural sway and the judgment accuracy were recorded. Our findings showed that RDCD swayed more during judgment sessions and made less accurate judgments compared to TDC. In addition, TDC reduced postural sway from inter-judgment to judgment sessions, whereas the postural sway of RDCD remained identical between sessions. Last, while TDC reduced postural sway across judgment trials and revealed a learning effect of the judgments about SHmax in the block condition, RDCD never modulated postural sway and did not learn their SHmax in both non-block and block conditions. Overall, modulation of postural sway differed between groups during judgment sessions and between inter-judgment and judgment sessions, whereby their perceptual judgments about SHmax were differentially influenced. To summarize, this study demonstrated a difference in perception and action coupling between RDCD and TDC.
Assuntos
Deficiências do Desenvolvimento/fisiopatologia , Julgamento/fisiologia , Transtornos das Habilidades Motoras/fisiopatologia , Equilíbrio Postural/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia , Análise de Variância , Criança , Feminino , Humanos , Masculino , Estatística como AssuntoRESUMO
AIM: To describe the clinical manifestations and radiological features contributing to the early diagnosis of radiation-induced sarcoma (RIS) after radiotherapy for breast cancer. MATERIALS AND METHODS: This retrospective analysis included four typical cases of RIS diagnosed at Affiliated Hospital of Academy of Military Medical Sciences between 1980 and 2013. Patient and imaging characteristics, treatment modalities, and outcomes were extracted from patients' medical records. Two pathologists reviewed all histological slides. RESULTS: All four cases were misdiagnosed and treated for several months as cases of breast cancer relapse. CT using the bone-window setting and three-dimensional reconstructions clearly displayed bone tumours of RIS in three cases. Skin alterations were observed in all cases. At the time of RIS diagnosis, three patients were free of breast cancer. In one patient with bilateral breast cancer and lung metastasis, chemotherapy resulted in complete remission of the metastasis, but RIS progression. No RIS in this series responded to chemotherapy or endocrine therapy. CONCLUSIONS: Abnormalities appearing in the radiation field long after RT should alert clinicians to the potential development of RIS. Careful physical examination and follow-up imaging studies are necessary. The presence of skin alterations, bone tumours at CT or radiography, and poor response to anti-cancer drugs may contribute to the early detection of RIS. Biopsy should be performed immediately when RIS is suspected.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Neoplasias Induzidas por Radiação/diagnóstico por imagem , Segunda Neoplasia Primária/diagnóstico por imagem , Sarcoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Erros de Diagnóstico , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos RetrospectivosRESUMO
Rab GDP-dissociation inhibitors (GDI) are evolutionarily conserved proteins that play an essential role in the recycling of Rab GTPases required for vesicular transport through the secretory pathway. We have found mutations in the GDI1 gene (which encodes uGDI) in two families affected with X-linked non-specific mental retardation. One of the mutations caused a non-conservative substitution (L92P) which reduced binding and recycling of RAB3A, the second was a null mutation. Our results show that both functional and developmental alterations in the neuron may account for the severe impairment of learning abilities as a consequence of mutations in GDI1, emphasizing its critical role in development of human intellectual and learning abilities.
Assuntos
Proteínas de Ligação ao GTP/genética , Inibidores de Dissociação do Nucleotídeo Guanina , Deficiência Intelectual/genética , Mutação , Encéfalo/embriologia , Cristalografia por Raios X , Desenvolvimento Embrionário e Fetal/genética , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/fisiologia , Ligação Genética , Humanos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Proteínas do Tecido Nervoso/metabolismo , Polimorfismo Conformacional de Fita Simples , Conformação Proteica , Proteínas Proto-Oncogênicas/metabolismo , Cromossomo X , Proteínas rab3 de Ligação ao GTPRESUMO
Objective: To grasp the epidemiological characteristics of influenza outbreaks in Guangdong Province by analyzing the outbreaks of influenza-like cases reported in Guangdong Province from January 2015 to the end of August 2022. Methods: In response to the outbreak of epidemics in Guangdong Province from 2015 to 2022, information on on-site epidemic control was collected, and epidemiological analysis was conducted to describe the characteristics of the epidemics. The factors that influence the intensity and duration of the outbreak were determined through a logistic regression model. Results: A total of 1 901 influenza outbreaks were reported in Guangdong Province, with an overall incidence of 2.05%. Most outbreak reports occurred from November to January of the following year (50.24%, 955/1 901) and from April to June (29.88%, 568/1 901). A total of 59.23% (1 126/1 901) of the outbreaks were reported in the Pearl River Delta region, and primary and secondary schools were the main places where outbreaks occurred (88.01%, 1 673/1 901). Outbreaks with 10-29 cases were the most common (66.18%, 1 258/1 901), and most outbreaks lasted less than seven days (50.93%,906/1 779). The size of the outbreak was related to the nursery school (aOR=0.38, 95%CI:0.15-0.93), the Pearl River Delta region (aOR=0.60, 95%CI:0.44-0.83), the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=3.01, 95%CI:1.84-4.90), the influenza A(H1N1) (aOR=2.02, 95%CI:1.15-3.55) and the influenza B (Yamagata) (aOR=2.94, 95%CI: 1.50-5.76). The duration of outbreaks was related to school closures (aOR=0.65, 95%CI: 0.47-0.89), the Pearl River Delta region (aOR=0.65, 95%CI: 0.50-0.83) and the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=13.33, 95%CI: 8.80-20.19; 4-7 days compared with ≤3 days: aOR=2.56, 95%CI: 1.81-3.61). Conclusions: An influenza outbreak in Guangdong Province exhibits two peaks, one in the winter and spring seasons and the other in the summer. Primary and secondary schools are high-risk areas, and early reporting of outbreaks is critical for controlling influenza outbreaks in schools. Furthermore, comprehensive measures should be taken to prevent the spread of the epidemic.
Assuntos
Epidemias , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Humanos , Influenza Humana/epidemiologia , Surtos de Doenças , China/epidemiologiaRESUMO
Medicinal plants are the primary sources of healthcare among the people of developing countries in villages and local towns. Documenting and reporting the traditional knowledge of medicinal plants may contribute to pharmaceutical research development. For this reason, we present our findings on ethnomedicinal plants from Lingchuan County, Shanxi, China, an unexplored area rich in medicinal plant resources. Information of ethnomedicinal plants were collected through questionnaire/semi-structured interviews from 180 informants, including traditional healers. Field surveys were conducted in 53 villages of Lingchuan County from 2017 to 2018. Informed consent was obtained from each participant before conducting the interview process. Quantitative analysis was performed for each recorded species, such as Relative Frequency Citation (RFC), Use Value (UV), and Factor of Informant Consensus (FIC). Diseases were categorized into twelve groups. A total 138 species of medicinal plants were recorded, belonging to 123 genera of 58 families. Asteraceae was the dominant plant family with 19 species, followed by Rosaceae and Fabaceae. Herbs were dominant among plant life-forms with 96 species, followed by shrubs and trees (15 species each). Roots were the most commonly used plant parts with 58 species, followed by whole plants and fruits (28 species each). Most plant species were reported non-toxic (84, 60%), followed by unknown toxicity (35, 25%), poisonous, and less toxic (19, 14%). Quantitative analysis revealed that Forsythia suspensa was with higher (0.33) RFC value, and Scutellaria baicalensis was recorded with a higher (0.91) UV. Treated diseases were categorized in 12 groups and evaluated by their FIC value, in which gynecological diseases have higher (0.93) FIC value followed by urinary system diseases. Most medicinal plants are used to clear away heat and relieve the surface. The present study revealed that local people of Lingchuan County confidently use ethnomedicinal plants for their healthcare needs. The higher indices value of a plant species resulted from quantitative analysis warrants further investigation, which may possess valuable phytochemical compounds that may result in new drugs for treating various human disorders.
Assuntos
Plantas Medicinais , China , Etnobotânica , Humanos , Medicina Tradicional/métodos , Fitoterapia , Plantas Medicinais/química , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The purpose of this study was to investigate whether children with developmental co-ordination disorder and balance problem (DCD-BP) had greater problems than controls in performing a primary balance task while concurrently completing different cognitive tasks varying in oral or listening cognitive complexity, as well as to investigate the automatization deficit hypothesis of DCD-BP. METHODS: Children with DCD-BP (n= 39), along with age-matched control counterparts (n= 39), were placed on automatic processing situation under dual-task conditions. All children were required to perform a primary task, five dual-task paradigms (oral counting task, auditory-verbal reaction task, auditory-choice reaction task, auditory-memory task and articulation alone) and an eyes-closed balancing task. RESULTS: In the primary task condition, the differences were not statistically significant (P= 0.393) between children with and without DCD-BP. However, children with DCD-BP were significantly more impaired on three of five dual-task conditions (oral counting task: P= 0.003; auditory-verbal reaction task: P= 0.011; auditory-memory task: P= 0.041) compared with the single-task situation, with the exception of the auditory-choice reaction task (P= 0.471) and articulation alone (P= 0.067). CONCLUSIONS: These results suggest that children with DCD-BP were more cognitively dependant and may have an automatization deficit.
Assuntos
Cognição/fisiologia , Transtornos das Habilidades Motoras/fisiopatologia , Equilíbrio Postural , Desempenho Psicomotor , Percepção Visual/fisiologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , PropriocepçãoRESUMO
The 1.81 A crystal structure of Rab GDP-dissociation inhibitor (GDI), a protein that plays a critical role in the recycling of Rab GTPases involved in membrane vesicular transport, has been recently determined. Biochemical studies implicate a highly conserved region involved in Rab binding, which is common to both GDI and the evolutionarily-related choroideremia gene product (CHM/REP) required for Rab prenylation. Here, we summarize the mechanisms by which members of the GDI superfamily might function to coordinate events leading to membrane fusion, and we discuss the unexpected, yet striking structural homology of GDI to FAD-binding proteins.
Assuntos
Alquil e Aril Transferases , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/metabolismo , Inibidores de Dissociação do Nucleotídeo Guanina , Proteínas rab de Ligação ao GTP , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Aminoácidos , Animais , Sítios de Ligação , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Coroideremia/genética , Sequência Conservada , Flavoproteínas/química , Flavoproteínas/metabolismo , Proteínas de Ligação ao GTP/fisiologia , Guanosina Difosfato/metabolismo , Humanos , Modelos Moleculares , Conformação ProteicaRESUMO
Mss4 and its yeast homologue, Dss4, have been proposed to function as guanine nucleotide exchange factors (GEFs) for a subset of Rab proteins in the secretory pathway. We have previously shown that Rab1A mutants defective in GTP-binding potently inhibit endoplasmic reticulum to Golgi transport, presumably by sequestering an unknown GEF regulating its function. We now demonstrate that these mutants stably associate with Mss4 both in vivo and in vitro and that Mss4 effectively neutralizes the inhibitory activity of the Rab1A mutants. An equivalent Rab3A mutant (Rab3A[N135I]), a Rab protein specifically involved in regulated secretion at the cell surface, associates with Mss4 as efficiently as the Rab1A[N124I] mutant. Although Rab3A[N135I] prevents the ability of Mss4 to neutralize the inhibitory effects of Rab1A mutants on transport, it has no effect on Rab1 function or endoplasmic reticulum to Golgi transport. Furthermore, quantitative immunodepletion of Mss4 fails to inhibit transport in vitro. We conclude that Mss4 and its yeast homologue, Dss4, are not GEFs mediating activation of Rab, but rather, they interact with the transient guanine nucleotide-free state, defining a new class of Ras-superfamily GTPase effectors that function as guanine nucleotide-free chaperones (GFCs).
Assuntos
Retículo Endoplasmático/metabolismo , Proteínas de Ligação ao GTP/fisiologia , Complexo de Golgi/metabolismo , Fosfotransferases , Proteínas/fisiologia , Proteínas de Saccharomyces cerevisiae , Transporte Biológico , Citosol/metabolismo , Retículo Endoplasmático/fisiologia , Proteínas de Ligação ao GTP/genética , Complexo de Golgi/fisiologia , Guanosina Difosfato/química , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Mutação , Fosfotransferases (Aceptor do Grupo Álcool) , Biossíntese de Proteínas , Saccharomyces cerevisiae , Proteínas rab1 de Ligação ao GTP , Proteínas rab3 de Ligação ao GTPRESUMO
Insulin-dependent diabetes (IDD) is positively associated with HLA-D proteins. A critical question is whether or not sequence differences within the HLA-D coding region are the same or different in diabetics and normal individuals of the same haplotype. We have isolated both DR beta 1 alleles from a Dw4/LD MN2 cDNA library and compared them to DR beta 1 genes isolated from normal individuals of the same Dw phenotype. We found no nucleotide differences in the coding region between the normal and diabetic alleles of DR beta 1 suggesting to us that DNA differences other than the DR beta 1 coding region may account for the observed association of HLA-D and diabetes.
Assuntos
Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA-D/genética , Antígenos HLA-DR/genética , Alelos , Sequência de Aminoácidos , Sequência de Bases , DNA/genética , Diabetes Mellitus Tipo 1/genética , Humanos , Polimorfismo de Fragmento de RestriçãoRESUMO
Two-dimensional gel electrophoresis of DQ molecules from three different Dw subtypes (Dw2, Dw12, and Dw21/FJO) of the HLA-DR2/DQw1 haplotype reveals that one alpha beta heterodimer of DQ molecule is expressed by each subtype and the DQ beta chain is electrophoretically variable among the three DR2/DQw1 subtypes. We have constructed cDNA libraries from the same homozygous typing cells used in the two-dimensional polyacrylamide gel electrophoresis analyses (HTC VYT for Dw2, HTC DHO for Dw12, and HTC FJO for Dw21/FJO) and isolated DQ beta cDNA clones with full-length coding sequences for each subtype. The deduced amino acid sequences show that the DQ beta chains of these three DR2/DQw1 subtypes are highly polymorphic and confirm their electrophoretic heterogeneity: for a mature protein of 229 amino acids, they differ with each other by 10-17 amino acids in the first domain and by 3-7 residues in the C-terminal sequence. Comparison among the available DQ beta sequences representing the four major DQ specificities (DQw1, DQw2, DQw3, and DQw4) in the DQ subregion as defined by serologic method suggests that (1) DR2,Dw2,DQw1 and DR3,DQw2 haplotypes probably interact with each other to generate the DQw3 and DQw4 beta alleles and (2) an evolutionary scheme may be proposed to relate the various beta alleles of the four major DQ specificities.
Assuntos
Antígenos HLA-DQ/genética , Antígeno HLA-DR2/genética , Alelos , Sequência de Aminoácidos , Sequência de Bases , Evolução Biológica , Linhagem Celular , Clonagem Molecular , Eletroforese em Gel Bidimensional , Cadeias beta de HLA-DQ , Humanos , Dados de Sequência Molecular , Polimorfismo Genético , Homologia de Sequência do Ácido NucleicoRESUMO
Non-invasive delivery of peptide and protein drugs will soon become a reality. This is due partly to a better understanding of the endogenous transport mechanisms, including paracellular transport, endocytosis, and carrier-mediated transport of mucosal routes of peptide and protein drug administration. This paper focuses on work related to the elucidation of structure-function, intracellular trafficking, and regulation of the intestinal dipeptide transporter, PepT1.
Assuntos
Biofarmácia , Proteínas de Transporte/farmacocinética , Dipeptídeos/farmacocinética , Oligopeptídeos/farmacocinética , Proteínas/farmacocinética , Simportadores , Transporte Biológico , Mucosa/metabolismo , Transportador 1 de Peptídeos , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: This exploratory study examined the relationships between pre- and post-injury sport participation among active individuals with spinal cord injury (SCI) in the United Kingdom. In particular, factors that influence individuals with SCI into sport were identified. METHODS: A total of 143 British individuals with SCI currently participating in wheelchair basketball, wheelchair rugby, wheelchair tennis, and wheelchair athletics were recruited. A total of 112 subjects were active prelesion, and 31 subjects were inactive preinjury. A Disability Sport Participation questionnaire developed by the authors was used for data collection. The questionnaire was distributed through the British Wheelchair Sport Associations. Personal, impairment, health and fitness, socialization, and participation data of athletes with SCI were collected. Groups of active preinjury and inactive preinjury were compared. RESULTS: For athletes who had been active pre-SCI, the in-hospital rehabilitation program and specialized sport club for people with disabilities were more important contexts for introducing the sport after injury to individuals. Friends and peers with disabilities were much more influential as initial and continuing socialization agents than rehabilitation therapists. The main reasons for athletes with SCI who participated in sports after injury were for fitness, fun, health, and competition, although many athletes noted that social aspects and rehabilitation also influenced their sport participation. CONCLUSION: This study identified social contexts, social agents, difficulties, sources of information, and reasons for sport participation of athletes with SCI. The results may offer some directions for the improvement of rehabilitation programs for people with SCI and also help the development of appropriate strategies to encourage people with SCI to participate in sports and leisure activities.
Assuntos
Apoio Social , Traumatismos da Medula Espinal/reabilitação , Esportes , Cadeiras de Rodas , Adulto , Atitude , Tomada de Decisões , Pessoas com Deficiência , Feminino , Humanos , Masculino , Grupo Associado , AutoimagemRESUMO
This report presents a rare case of odontogenic cutaneous sinus tract caused by a vertical root fracture. The root-fractured molar was probably caused by an accidental blow by a cow 3 years ago. Despite all treatments by physicians and surgeons for nearly 1 year, the sinus tract recurred repeatedly. After diagnosis and extraction of the fractured molar by the dentist, the sinus tract healed uneventfully in a month.
Assuntos
Fístula Cutânea/etiologia , Fístula Dentária/etiologia , Fraturas dos Dentes/complicações , Raiz Dentária/lesões , Adulto , Doença Crônica , Fístula Cutânea/diagnóstico , Fístula Cutânea/terapia , Fístula Dentária/diagnóstico , Fístula Dentária/terapia , Humanos , Masculino , Mandíbula , Dente Molar/diagnóstico por imagem , Dente Molar/lesões , Dente Molar/cirurgia , Radiografia , Recidiva , Extração Dentária , Fraturas dos Dentes/diagnóstico por imagem , Fraturas dos Dentes/cirurgia , Raiz Dentária/diagnóstico por imagem , Raiz Dentária/cirurgiaRESUMO
To determine whether lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) are involved in the induction of superoxide dismutase (SOD) in gingival tissue, we examined their effect on induction of SOD isozymes in cultured normal (NGF) and phenytoin-induced hyperplastic (PHF) gingival fibroblasts. Treatment of both NGFs and PHFs with 10 to 50 ng/mL TNF-alpha for 24 hours increased the level of manganese SOD (MnSOD) to as much as four times the level of untreated cultures. PHFs, but not NGFs, were shown to be responsive to TNF-alpha in eliciting a significant increase in copper-zinc SOD (Cu/ZnSOD), albeit in a lesser amount than MnSOD. Additionally, treatment of both types of cells with 5 to 50 mg/mL of LPS for 24 hours also elicited an increase in the levels of MnSOD. Again, an LPS-induced increase in Cu/ZnSOD levels could only be demonstrated in PHFs, but not in NGFs. These observations were further confirmed by comparing the achromatic bands associated with SOD isozymes exhibited in the electrophoretogram using a nondenaturing polyacrylamide electrophoresis technique. These results indicate that TNF-alpha and LPS were capable of inducing both MnSOD and Cu/ZnSOD simultaneously in PHF fibroblasts. PHFs may be inherently more capable than NGFs in combating oxidative stress.
Assuntos
Anticonvulsivantes/efeitos adversos , Hiperplasia Gengival/induzido quimicamente , Isoenzimas/metabolismo , Lipopolissacarídeos/farmacologia , Fenitoína/efeitos adversos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Indução Enzimática , Fibroblastos/enzimologia , Hiperplasia Gengival/enzimologia , Humanos , Técnicas In Vitro , TaiwanRESUMO
Post-exercise serum creatine kinase (CK) has been frequently used to evaluate muscle damage. The purpose of present study was to examine the effects of 45 eccentric contraction on serum creatine kinase levels during laboratory tests. Using a Lido isokinetic dynamometer, thirteen subjects (five distance runners and eight PE students), average age = 24.0 (yrs), height = 172.5 (cm), weight = 66.5 (kg), and percent body fat = 15.3 (%), completed 5 and 40 eccentric contractions at speed of 60 degrees C/s and 120 degrees/s, respectively. Blood sample was drawn before and 18, 42, 66, 90 hours after exercise protocol. Result indicated that PE students have a significant increase in serum CK levels post-exercise 18 hours (p less than 0.05) only. Both groups in absolute muscular strength or corrected strength have found non-significant difference (p greater than 0.05). Resulting findings showed that training effect may be an important factor for CK leakage rather than lean body mass. In the light of results, it is seem safe to say that the exercise protocol for distance runners using by this study would not contribute to severe CK elevations in blood. This testing protocol can be recommended as an appropriate test for students and distance runners with similar fitness level. Due to large variations occurred during CK testing, follow-up study should try to establish baseline serum CK level by repeated enzyme tests.
Assuntos
Creatina Quinase/sangue , Exercício Físico , Adulto , Humanos , Educação Física e Treinamento , CorridaRESUMO
STUDY DESIGN: A mixed design for kinetic comparison of 2 types of one-handed backhand strokes and 2 skill levels in tennis. OBJECTIVES: To develop and evaluate a model to estimate the impact force on the racquet during tennis stroke, and to compare the peak impact force between one-handed backhand stroke with a long backswing and one-handed backhand stroke with a short backswing and between the beginning and advanced players. BACKGROUND: A one-handed backhand stroke is commonly used in tennis and may be associated with many upper extremity over-use injuries. An understanding of kinetics of the backhand stroke is essential for understanding injury mechanisms and prevention. METHODS AND MEASURES: Five male advanced tennis players and 4 male and 1 female beginning tennis players participated. Mean age was 32.2 +/- 7.0 years. Each subject was instructed to use the 2 types of one-handed backhand strokes to hit balls from a tennis ball machine. Three-dimensional coordinates of critical body and racquet landmarks were obtained. A mathematical model was developed to estimate the contact duration and the peak impact force during a stroke. RESULTS: The estimated peak impact forces were reproducible and comparable to those reported in the literature from direct measurements. A one-handed backhand stroke with a short backswing had a significantly shorter contact duration (0.008 +/- 0.003 seconds) and a greater peak resultant impact force (330.0 +/- 140.7) than that with a long backswing (0.016 +/- 0.004 seconds and 180.8 +/- 49.1 N). Skill level did not significantly affect the peak resultant impact force. CONCLUSION: A long backswing in a one-handed backhand stroke may reduce the load on the upper extremity and may assist in reducing the risks of tennis-related upper extremity over-use injuries.