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1.
Artigo em Inglês | MEDLINE | ID: mdl-36338797

RESUMO

The purpose of this study was to evaluate the impact of an 8-week remote summer program in supporting underrepresented students interested in orthopaedic surgery. Methods: We received 115 applications, and a total of 17 students participated in the program (14.8%). Nine faculty mentors were matched with 1 or 2 students each. The program delivered a curriculum from June-August 2021 consisting of (1) weekly instructional courses on research-related topics led by a content expert; (2) weekly faculty lectures discussing topics including orthopaedic topics, diversity in medicine, leadership, and work-life balance; and (3) a research experience paired with a faculty mentor and peer mentor. We surveyed students to measure skill progression, satisfaction, and overall program evaluation. Preprogram/postprogram evaluation, midprogram check-in, and student feedback surveys were collected. Results: Program participants represented a range of race and ethnic backgrounds, research experience levels, and various geographic locations across the United States. The cohort included a high rate of female (42%) and Black (35%) participants. On average, postprogram survey scores indicated that participants believed that the summer program improved their research skills (9.6 of 10), improved their orthopaedic interest (8.9 of 10), and improved mentorship and networking (9.1 of 10). For feedback surveys, 14 respondents of 15 total responses (93%) felt they were adequately matched to their faculty mentor. Twelve (80%) felt they had realistic deliverables for research projects within the 8-week program. Thirteen (87%) indicated they contributed to an abstract or manuscript as a coauthor. Conclusion: Our findings indicate that students improved their research skills, interest, and confidence to pursue orthopaedic residency and mentorship/networks in the field. The long-term goal is to improve the accessibility and quality of mentorship for underrepresented students in order to foster an equitable pathway into the field of orthopaedic surgery.

2.
JBJS Rev ; 10(2)2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35180146

RESUMO

¼: Idiopathic toe-walking is a diagnosis of exclusion. ¼: The natural history of idiopathic toe-walking has not been studied in many children; we identified only 1 prospective study. Of children without equinus contractures who were toe-walking before the age of 5.5 years, 59% had spontaneous resolution of toe-walking by 5.5 years of age, and 79%, by the age of 10 years. ¼: Adverse consequences of toe-walking into adulthood have not been reported, but may exist, and further research is needed to define and clarify. ¼: If parents desire treatment to resolve their child's toe-walking, surgical lengthening of the Achilles tendon is the treatment with the highest chance of success and lowest relapse rate, and thus far, no complications have been reported in any surgical series.


Assuntos
Tendão do Calcâneo , Dedos do Pé , Tendão do Calcâneo/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Marcha , Humanos , Estudos Prospectivos , Dedos do Pé/cirurgia
3.
Polymers (Basel) ; 11(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835723

RESUMO

Silver nanoparticles (AgNPs) have been widely studied for the control of biofouling on polymeric membranes due to their antimicrobial properties. However, nanoparticle leaching has posed a significant impediment against their widespread use. In this study, a one-step method of chemically embedding AgNPs on cellulose acetate (CA) membranes via their affinity to thiol group chemistry was investigated. The operational efficiency of the membranes was then determined via filtration and biofouling experiments. During filtration study, the average flux values of pure CA membranes was determined to be 11 ± 2 L/(m2·hr) (LMH), while membranes embedded with AgNPs showed significant increases in flux to 18 ± 2 LMH and 25 ± 9 LMH, with increasing amounts of AgNPs added, which is likely due to the NPs acting as pore formers. Leaching studies, performed both in dead-end and crossflow filtration, showed approximately 0.16 mg/L leaching of AgNPs after the first day of filtration, but afterwards the remaining chemically-attached AgNPs did not leach. Over 97% of AgNPs remained on the membranes after seven days of crossflow leaching filtration studies. Serratia marcescens were then used as target microorganisms in biofouling studies. It was observed that membranes embedded with AgNPs effectively suppressed the growth of Serratia marcescens, and specifically, membranes with AgNPs displayed a decrease in microbial growth by 59% and 99% as the amount of AgNP increased.

4.
Hip Int ; 17(3): 131-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-19197857

RESUMO

We studied the role of acetabulum geometry and head neck ratio in the development of osteoarthritis of the hip in young men. Contrary to previous studies we evaluated the significance of the anterior, posterior and total coverage of the femoral head, the influence of the femoral neck and the consequence of acetabular retroversion on standardized x-rays. Men aged 26-55 years who earlier had a total hip arthroplasty were included in the case group. This group was compared to a control-group of men treated as trauma patients. The study indicates that acetabular dysplasia and retroversion and a relative decreased head neck ratio are associated with osteoarthritis of the hip in young men.

5.
Arch Dis Child Fetal Neonatal Ed ; 88(5): F371-4, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12937039

RESUMO

OBJECTIVES: To define the incidence of congenital cytomegalovirus (CMV) infection in a defined population in Israel as diagnosed by urine polymerase chain reaction (PCR), and to assess the utility of this method for screening for congenital CMV infection. DESIGN: A convenient sample of urine specimens from asymptomatic newborns were subjected to CMV PCR. Positive results were validated by urine tube culture and by determination of serum CMV IgM antibodies. Maternal CMV IgG was determined in a representative sample of mothers. Newborns with positive urine specimens underwent full clinical evaluation. Epidemiological characteristics of the mothers were extracted from the medical records. SETTINGS: Two medical centres in Israel with different population characteristics. PATIENTS: A total of 2000 newborns (1000 in each medical centre). MAIN OUTCOME MEASURE: Presence of CMV DNA in the urine. RESULTS: Despite significant epidemiological differences between the populations in the two hospitals, the CMV seroprevalence was similar, 80.5% and 85%. Fourteen of the 2000 newborns screened (0.7%) were PCR positive. Urine culture was positive in nine of 10 specimens; IgM was positive in only two of 13 newborns with positive PCR. Eleven newborns underwent full or partial evaluation, and only one (9%) was symptomatic. CONCLUSIONS: The incidence of congenital CMV infection in the study population was 0.7%; over 90% were asymptomatic. Urinary CMV PCR is a reliable, rapid, and convenient method, and thus may serve as a screening tool for the detection of congenital CMV infection.


Assuntos
Infecções por Citomegalovirus/congênito , Reação em Cadeia da Polimerase/normas , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , DNA Viral/urina , Feminino , Sangue Fetal/virologia , Humanos , Imunoglobulina G/análise , Incidência , Recém-Nascido , Israel/epidemiologia , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Reação em Cadeia da Polimerase/métodos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Saúde da População Rural , Sensibilidade e Especificidade , Saúde da População Urbana
6.
Am J Med Genet ; 99(4): 325-7, 2001 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11252001

RESUMO

The incidence of the specific component deficiencies in various ethnic groups is not known, although there appears to be an ethnic predilection for C6 and C8alpha-gamma deficiencies in blacks, whereas C7 and C8beta deficiencies are predominantly noted in Caucasians. Infectious diseases, particularly recurrent meningococcal infections, are observed more commonly with late component deficiencies. In the current study, we have simplified the PCR technique by using site-directed mutagenesis and designer primers in a cohort of Israeli Moroccan Jewish blood donors to ascertain allele frequency in this ethnic group, which, based on earlier studies, was considered to be at risk for C7 deficiency. The total mutant allele frequency in this ethnic cohort was 1.1% of a total of 365 healthy Israeli Moroccan Jews, including one homozygote. The identification of mutant alleles was efficient and inexpensive, and hence a large cohort was studied. The finding of complement deficiency identifies individuals at risk for Neisserial infections, which are known to be potentially life-threatening. Conversely, when a patient of Moroccan ancestry is diagnosed with a Neisserial infection, it is important to determine the complement status.


Assuntos
Doadores de Sangue , Complemento C7/deficiência , Judeus/genética , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/etnologia , Transtornos da Coagulação Sanguínea/genética , Complemento C7/genética , Análise Mutacional de DNA , Frequência do Gene , Infecções Meningocócicas/etiologia , Marrocos/epidemiologia , Infecções por Neisseriaceae/etiologia , Reação em Cadeia da Polimerase , Prevalência
7.
Am J Kidney Dis ; 36(6): 1253-61, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11096050

RESUMO

Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage renal failure (ESRF) in children. Our previous studies have shown that Arab children in Israel have a worse prognosis compared with Jewish patients despite similar clinical presentation and management. Progression of proteinuric glomerular diseases has been associated with alterations in lipid metabolism, and similarities have been drawn between the mechanisms underlying atherosclerosis and glomerulosclerosis. Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated enzyme involved in preventing the oxidation of low-density lipoprotein (LDL), and an association has been shown between two genetic polymorphisms in PON1 and the risk of coronary artery disease. The aim of this study was to determine the frequency of these genetic polymorphisms in PON1 in Arab and Jewish children with FSGS and to determine any association with severity of outcome. Forty-seven children (21 Arab and 26 Jewish) with biopsy-proven FSGS and 274 healthy controls of matching ethnic origin were studied. The glutamine (A)-192-arginine (B) and the methionine (M)-55-leucine (L) polymorphisms were analyzed. The frequency of the A allele was similar in patients and controls (0.68 versus 0.71), as was that of the L allele (0.63 versus 0.6). When subgroups were analyzed, the prevalence of the LL genotype in Arab patients was significantly greater than in Jewish patients (57.1% versus 26.9%, P: < 0.05) and Arab controls (57.1% versus 28.9%, P: < 0.03). A trend in association was found between homozygosity for the L allele and progression of renal disease in Arab children. Homozygosity for the L allele is a risk factor for developing FSGS in Arab children and may be associated with a worse prognosis.


Assuntos
Árabes/genética , Esterases/genética , Glomerulosclerose Segmentar e Focal/genética , Judeus/genética , População Branca/genética , Adolescente , Adulto , Fatores Etários , Arildialquilfosfatase , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Glomerulosclerose Segmentar e Focal/enzimologia , Glomerulosclerose Segmentar e Focal/epidemiologia , Humanos , Lactente , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prevalência , Fatores de Risco
8.
J Am Soc Nephrol ; 10(11): 2352-8, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10541294

RESUMO

Primary hyperoxaluria type 1 is an autosomal recessive inherited metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of phenotypes ranging from renal failure in infancy to mere renal stones in late adulthood. Mutations in the AGXT gene, encoding the liver-specific enzyme alanine:glyoxylate aminotransferase, are responsible for the disease. Seven mutations were detected in eight families in Israel. Four of these mutations are novel and three occur in children living in single-clan villages. The mutations are scattered along various exons (1, 4, 5, 7, 9, 10), and on different alleles comprising at least five different haplotypes. All but one of the mutations are in a homozygous pattern, reflecting the high rate of consanguinity in our patient population. Two affected brothers are homozygous for two different mutations expressed on the same allele. The patients comprise a distinct ethnic group (Israeli Arabs) residing in a confined geographic area. These results, which are supported by previous data, suggest for the first time that the phenomenon of multiple mutations in a relatively closed isolate is common and almost exclusive to the Israeli-Arab population. Potential mechanisms including selective advantage to heterozygotes, digenic inheritance, and the recent emergence of multiple mutations are discussed.


Assuntos
Hiperoxalúria Primária/genética , Mutação Puntual , Árabes , Pré-Escolar , Haplótipos , Humanos , Hiperoxalúria Primária/etnologia , Lactente , Israel , Polimorfismo Genético
9.
Ment Retard ; 37(6): 435-48, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10635664

RESUMO

The generality of a peer-mediated exercise program designed to enhance aerobic fitness of 17 children with moderate and severe cognitive disabilities was evaluated. Two systematic replications of the program were conducted. Participants' ages, disability levels, and school settings varied. Target participants were paired with peers without disabilities. These students encouraged their peers to maintain requisite levels of exercise intensity and monitored their heart rates. A between-group multiple-baseline design was used to evaluate program effects. Results replicated earlier findings. Aerobic fitness of participants, measured by exercise heart-rates, improved when the exercise program was introduced. Results for individual participants reflected more variability than combined group data. Implications for overcoming motivational barriers and obtaining valued outcomes correlated with the program are discussed.


Assuntos
Exercício Físico , Deficiência Intelectual/psicologia , Grupo Associado , Aptidão Física , Adolescente , Criança , Feminino , Humanos , Masculino
10.
Kidney Int ; 54(6): 1843-9, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9853248

RESUMO

BACKGROUND: The clinical course of primary focal segmental glomerulosclerosis (FSGS) in children is variable, with some patients having a much more rapidly progressing course than others. The purpose of our study was to compare the frequency of three polymorphisms of the renin-angiotensin system (RAS) in children with FSGS with that in healthy controls of matching ethnic groups, and to determine whether the clinical outcome of FSGS was associated with different RAS genotypes. METHODS: Three RAS genotypes were examined in 47 Jewish and Arab children with biopsy-proven primary FSGS and in a large control group: the ACE insertion/deletion polymorphism in intron 16, the M235T mutation in the angiotensinogen gene, and the A1166C in the angiotensin II type 1 receptor gene (AT1R). RESULTS: Arab patients showed a greater tendency towards progressive renal disease than their Jewish counterparts (12 of 21 vs. 9 of 26, P = 0.05) and were less likely to achieve remission (3 of 21 vs. 11 of 26, P < 0.04), despite similar clinical presentation, medical management and follow-up. The RAS allele prevalence was similar among patients and controls of matching ethnic backgrounds, and no difference in allele frequency was found between Arabs and Jews. Homozygotes for the ACE insertion genotype (II) were significantly less likely to have progressive renal disease than patients with the other genotypes (ID and DD; 0 of 6 vs. 21 of 41; P < 0.022). The other RAS polymorphisms were not associated with variations in the clinical course of childhood FSGS. CONCLUSIONS: Homozygosity for the ACE insertion allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis. The D allele may exert a detrimental dominant effect on outcome. Neither the ACE gene polymorphism nor the other RAS polymorphisms studied are associated with disease prevalence. The AT1R and angiotensinogen gene polymorphisms are not associated with progression of renal disease in FSGS. Ethnic differences in the clinical course of the disease are not linked to these polymorphisms.


Assuntos
Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/fisiopatologia , Polimorfismo Genético/genética , Sistema Renina-Angiotensina/genética , Adolescente , Alelos , Angiotensinogênio/genética , Criança , Pré-Escolar , Elementos de DNA Transponíveis , Progressão da Doença , Feminino , Deleção de Genes , Glomerulosclerose Segmentar e Focal/epidemiologia , Humanos , Masculino , Peptidil Dipeptidase A/genética , Prevalência , Prognóstico
12.
Oncogene ; 17(2): 165-71, 1998 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-9674700

RESUMO

The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of c-Myc target genes in human oncogenesis induced by c-myc or N-myc. In MCF-7 breast cancer cells, the induction of c-myc expression by estrogen was followed by the induction of all the Myc targets that we examined, indicating that those genes can serve as c-Myc targets in human oncogenesis. Moreover, in breast tumors exhibiting c-myc overexpression, several Myc targets were also overexpressed. A clear correlation between the expression of c-myc and its targets was also detected in Burkitt's lymphomas, which involve a specific translocation of c-myc gene, but not in other lymphoma cells. Yet, in cells derived from a neuronal origin the pattern of expression of Myc targets was more complex. In a neuroepithelioma cell line that overexpresses c-myc, only some targets were expressed. In addition in neuroblastomas, in which N-myc is amplified and overexpressed, only ODC was overexpressed in all cell lines, while all other target genes were expressed in only some of the cell lines. The more complex expression pattern found for the Myc targets in neuroblastomas suggests that genes that were identified originally as targets for c-Myc regulation may be regulated by N-Myc, but other cell specific factors are also needed for transcription of the target genes.


Assuntos
Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Ornitina Descarboxilase/biossíntese , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transaminases , Fosfatases cdc25 , Neoplasias da Mama/genética , Linfoma de Burkitt/genética , Estradiol/farmacologia , Feminino , Humanos , Neuroblastoma/genética , Tumores Neuroectodérmicos Primitivos Periféricos/genética , Precursores de Proteínas/biossíntese , Proteínas Tirosina Fosfatases/biossíntese , Proteínas/genética , Timosina/análogos & derivados , Timosina/biossíntese
13.
Gynecol Oncol ; 67(2): 123-6, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9367693

RESUMO

To better understand the role of germline BRCA mutations in ovarian cancer in Ashkenazi Jews, we tested 29 consecutive patients admitted to our service for the three mutations common in this ethnic group. These mutations are 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2. Six patients had both breast and ovarian cancer, and 23 had ovarian cancer only. In the first group, all women had germline mutations, 2 with each mutation. Of 23 ovarian cancer patients, 11 were carriers (48%): 6 of 185delAG, 2 of 5382insC, and 3 of 6174delT. Regarding family history, of 13 women with no family history, 3 (23%) were carriers. Of 10 women with any family history of breast or ovarian cancer, 8 (80%) were carriers. We discuss possible explanations for this surprisingly high carrier rate, including a high proportion of familial disease coupled with lack of adequate family history, lower penetrance than previously expected, or increasing penetrance in recent generations due to nongenetic factors. Our data suggest that genetic testing is merited in all Ashkenazi women with ovarian cancer, regardless of family history.


Assuntos
Proteína BRCA1/genética , Mutação em Linhagem Germinativa , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética , Adulto , Idoso , Proteína BRCA2 , Feminino , Humanos , Judeus , Pessoa de Meia-Idade , Neoplasias Ovarianas/etnologia
14.
Am J Hum Genet ; 60(5): 1059-67, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9150153

RESUMO

Germ-line BRCA1 and BRCA2 mutations account for most of familial breast-ovarian cancer. In Ashkenazi Jews, there is a high population frequency (approximately 2%) of three founder mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. This study examined the frequency of these mutations in a series of Ashkenazi women with ovarian cancer unselected for family history, compared with the frequency of these mutations in families ascertained on the basis of family history of at least two affected women. Penetrance was compared, both according to the method of family ascertainment (i.e., on the basis of an unselected ovarian cancer proband vs. on the basis of family history) and for the BRCA1 founder mutations compared with the BRCA2 6174delT mutation. There was a high frequency (10/22; [45%]) of germ-line mutations in Ashkenazi women with ovarian cancer, even in those with minimal or no family history (7/18 [39%]). In high-risk Ashkenazi families, a founder mutation was found in 59% (25/42). Families with any case of ovarian cancer were significantly more likely to segregate a founder mutation than were families with site-specific breast cancer. Penetrance was higher in families ascertained on the basis of family history than in families ascertained on the basis of an unselected proband, but this difference was not significant. Penetrance of BRCA1 185delAG and BRCA1 5382insC was significantly higher than penetrance of BRCA2 6174delT (hazard ratio 2.1 [95% CI 1.2-3.8]; two-tailed P = .01). Thus, the high rate of germ-line BRCA1/BRCA2 mutations in Ashkenazi women and families with ovarian cancer is coupled with penetrance that is lower than previously estimated. This has been shown specifically for the BRCA2 6174delT mutation, but, because of ascertainment bias, it also may be true for BRCA1 mutations.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1/genética , Judeus/genética , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA2 , Neoplasias da Mama/epidemiologia , Europa (Continente)/etnologia , Feminino , Efeito Fundador , Frequência do Gene , Heterozigoto , Humanos , Irã (Geográfico)/etnologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/epidemiologia , Prevalência
15.
J Med Chem ; 39(16): 3174-8, 1996 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-8759639

RESUMO

The application of the concept of backbone cyclization to linear substance P (SP) analogs is presented. We describe the synthesis, characterization, and biological activity of a series of backbone-to-amino-terminus cyclic analogs of the C-terminal hexapeptide of SP. These analogs were designed on the basis of NMR data and molecular modeling of the selective NK-1 analog WS-septide (Ac[Arg6,Pro9]SP6-11). A series of peptides with the general formula: cyclo[-CH2)m-NH-CO-(CH2)n-CO-Arg-Phe-Phe-N-]-CH2-CO-Leu-Met-NH2 (n = 2, 3, 6 and m = 2, 3, 4) was synthesized by solid phase methodology using Fmoc chemistry for the main chain and Boc chemistry for the building units [Na-(omega-aminoalkyl)Gly] side chains. Cyclization was performed on the resin after removal of the Boc protecting group from the omega-aminoalkyl chain. Cyclic and precyclic analogs were compared. They were purified by HPLC and characterized by mass spectroscopy and NMR. Biological activity and selectivity to the NK-1 neurokinin receptor were found to depend on cyclization and the ring size: The most active and selective analog had a ring of 20 atoms. This analog was found to have enhanced metabolic stability in various tissue preparation compared to WS-septide.


Assuntos
Fragmentos de Peptídeos/farmacologia , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Receptores da Neurocinina-1/agonistas , Substância P/farmacologia , Sequência de Aminoácidos , Animais , Cobaias , Dados de Sequência Molecular , Músculo Liso/efeitos dos fármacos , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/metabolismo , Ligação Proteica , Conformação Proteica , Ácido Pirrolidonocarboxílico/análogos & derivados , Ratos , Receptores da Neurocinina-1/metabolismo , Relação Estrutura-Atividade , Substância P/síntese química , Substância P/química
16.
J Pept Sci ; 2(4): 261-9, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9231334

RESUMO

Novel backbone-to-side chain and backbone-to-backbone cyclic analogues of substance P (SP) were prepared by solid-phase synthesis and screened for biological activity. An analogue containing a thioetherlactam ring between positions 9 and 11 showed an EC50 value of 20 nM toward the neurokinin 1 (NK-1) and was inactive toward the NK-2 and NK-3 receptors. On the other hand, in a multiple backbone cyclic peptide library of similar analogues, in which the sulphur was excluded from the ring, very low activity was detected. The activity was re-evaluated and was found to be even lower (EC50 = 0.11 mM) than the previously published data. These results indicate that the thioether moiety has a crucial role in receptor activation. The results also show tolerance of the NK-1 receptor, but not NK-2 or NK-3, to cyclization of the C-terminal portion of the SP6-11 hexapeptide.


Assuntos
Substância P/síntese química , Substância P/metabolismo , Enxofre/fisiologia , Animais , Bioensaio , Ciclização , Cobaias , Íleo/efeitos dos fármacos , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/metabolismo , Receptores da Neurocinina-1/efeitos dos fármacos , Receptores da Neurocinina-2/efeitos dos fármacos , Receptores da Neurocinina-3/efeitos dos fármacos , Substância P/análogos & derivados , Enxofre/química
17.
Lancet ; 344(8935): 1473-4, 1994 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-7968122

RESUMO

The high frequency of mutations in the cystic fibrosis gene in patients with congenital bilateral absence of vas deferens (CBAVD) has raised the question whether all of them have a genital form of cystic fibrosis. We investigated 47 CBAVD patients by ultrasonography, 10 (21%) had renal malformations and 37 (79%) did not. In the former group, no cystic fibrosis mutations were found and sweat chloride concentrations were normal. In the latter group, 18 patients (49%) carried at least one cystic fibrosis mutation and sweat chloride was high in 17 of 26 tested (65%). Our findings suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis.


Assuntos
Fibrose Cística/genética , Rim/anormalidades , Ducto Deferente/anormalidades , Humanos , Infertilidade Masculina/etiologia , Rim/diagnóstico por imagem , Masculino , Mutação , Ultrassonografia , Ducto Deferente/diagnóstico por imagem
18.
Res Dev Disabil ; 14(5): 359-86, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8234957

RESUMO

Physical fitness of persons who are developmentally disabled has received relatively little attention in the special education literature when compared to intellectual functioning (e.g., learning, memory, and language) and to acquisition of functional skills (e.g., self-care, community, and vocational). Despite an increased interest in recreational programming stimulated by the concept of functional curricula, teachers may still be reluctant to include physical fitness activities in their students' schedules. Perhaps physical fitness programming for those with developmental disabilities would have wider appeal and application if it were embedded in the broader context of psychological and behavioral change (i.e., engagement in exercise produces generalized changes beyond direct improvement in physical well-being). This article is a review and critique of literature that focuses on the effects of participation in aerobic exercise on three classes of psychological/behavioral variables for persons with mental retardation and associated disabilities. The methodology that characterizes this literature is analyzed, and recommendations for future research are proposed.


Assuntos
Exercício Físico/psicologia , Deficiência Intelectual/reabilitação , Aptidão Física/psicologia , Pessoas com Deficiência/psicologia , Humanos , Deficiência Intelectual/psicologia , Qualidade de Vida
19.
Biopolymers ; 33(6): 915-26, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7686410

RESUMO

A highly potent and selective agonist to the tachykinin NK-3 receptor, [pGlu6,N-MePhe8,Aib9] substance P (6-11) (I), was synthesized via the solid phase method. The ED50 of I was 4 nM in the guinea pig ileum in the absence of atropine (NK-1+NK-3 receptors) and this agonist was 5000-fold less potent in the presence of atropine (NK-1 receptor). The analogue was virtually inactive in the rat vas deferens (NK-2 receptor). A detailed analysis of the solution conformation of this analogue in DMSO-d6 and in a DMSO-d6/H2O cryomixture was carried out by a combination of 1H-nmr 2D techniques (DQF-COSY, TOCSY, NOESY and ROESY) and model building based on empirical energy calculations. Peptide I exists as a mixture of isomers containing cis and trans Phe-N-MePhe peptide bonds. The main isomer, containing a cis Phe-N-MePhe peptide bond, shows a preferred folded conformation characterized by a type VI beta-turn with Phe and N-MePhe in the i + 1 and i + 2 positions. The turn is followed by a helical segment extending to the C-terminal. This conformation is compared to previously reported conformations of other selective tachykinin agonists and may be a promising lead for the design of novel NK-3 agonists with additional conformational constraints.


Assuntos
Fragmentos de Peptídeos/química , Receptores de Neurotransmissores/fisiologia , Substância P/análogos & derivados , Sequência de Aminoácidos , Animais , Cobaias , Técnicas In Vitro , Masculino , Dados de Sequência Molecular , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/farmacologia , Conformação Proteica , Ácido Pirrolidonocarboxílico/análogos & derivados , Ratos , Receptores de Taquicininas , Substância P/síntese química , Substância P/química , Substância P/farmacologia
20.
Biopolymers ; 31(6): 745-50, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-1718473

RESUMO

This article describes a new concept of medium- and long-range cyclization of peptides through "backbone cyclization." In this approach, conformational constraints are conferred on a peptide by linking omega-substituted alkylidene chains replacing N(alpha) or C(alpha) hydrogens in a peptidic backbone. Backbone cyclization, which is divided into N-backbone and C-backbone cyclizations, allow for new modes of cyclization in addition to the classical ones that are limited to cyclization through the side chains and/or the amino or carboxyl terminal groups. The article also describes the application of the N-backbone cyclization to the active region of substance P. Conformational constraints of this peptide by the classical cyclization modes led to inactive analogues whereas N-backbone cyclization provided an active, selective, and metabolically stable analogue.


Assuntos
Peptídeos/química , Conformação Proteica , Sequência de Aminoácidos , Ciclização , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Ácido Pirrolidonocarboxílico/análogos & derivados , Substância P/análogos & derivados , Substância P/química
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