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1.
Phys Rev Lett ; 122(1): 011102, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31012650

RESUMO

Precision measurements of the inverse-square law via experiments on short-range gravity provide sensitive tests of Lorentz symmetry. A combined analysis of data from experiments at the Huazhong University of Science and Technology and Indiana University sets simultaneous limits on all 22 coefficients for Lorentz violation correcting the Newton force law as the inverse sixth power of distance. Results are consistent with no effect at the level of 10^{-12} m^{4}.

2.
BMC Health Serv Res ; 19(1): 38, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30646962

RESUMO

BACKGROUND: Patient satisfaction is an important outcome measure guiding quality improvement in the healthcare setting while the patient-centred care movement places increasing importance on patient engagement in clinical decision-making. However, the concept of patient satisfaction is not clearly defined, and beliefs of patients are not always evident in health surveys. Researchers rarely follow up on surveys to explore patient views and what they mean in greater depth. This study set out to examine perceptions of hospital care, through in-depth, qualitative data capture and as a result, to gather rich, patient-driven information on user experience and satisfaction in the Australian healthcare setting; and identify influencing factors. METHODS: Focus groups were undertaken in four St Vincent's Health Australia (SVHA) hospitals in 2017 where participants discussed responses to eight questions from the Press Ganey Patient Experience Survey. Thirty people who were inpatients at SVHA. RESULTS: Good communication and high-quality information at arrival and discharge were found to be important to patients. Communication breakdown was also evident, further exacerbated by a range of environmental factors such as sharing a room with others. Overall, patients' felt that while their spiritual needs were well-supported by the hospital staff at all SVHA hospitals, it was the clinical teams prioritised their emotional needs. Good communication and environments can improve patient experience and follow-up at home is vital. CONCLUSIONS: Patient-centred care needs careful planning with patients involved at entry and exit from hospital. Focused communication, environmental changes, attending to complaints, and clearer discharge strategies are recommended.


Assuntos
Hospitais Privados , Hospitais Públicos , Preferência do Paciente , Satisfação do Paciente , Austrália , Feminino , Grupos Focais , Pesquisas sobre Atenção à Saúde , Humanos , Masculino
3.
Phys Rev Lett ; 117(7): 071102, 2016 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-27563946

RESUMO

Short-range experiments testing the gravitational inverse-square law at the submillimeter scale offer uniquely sensitive probes of Lorentz invariance. A combined analysis of results from the short-range gravity experiments HUST-2015, HUST-2011, IU-2012, and IU-2002 permits the first independent measurements of the 14 nonrelativistic coefficients for Lorentz violation in the pure-gravity sector at the level of 10^{-9} m^{2}, improving by an order of magnitude the sensitivity to numerous types of Lorentz violation involving quadratic curvature derivatives and curvature couplings.

4.
J Exp Med ; 145(6): 1484-500, 1977 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-68093

RESUMO

Monolayer and suspension cell cultures prepared from Hodgkin's disease tumors in the spleen were examined microscopically and by cytogenetics, tested for lymphocyte and monocyte cell surface properties, and assayed for enzymes by histochemical and spectrophotometric techniques. Hodgkin's disease monolayer cultures were composed of rapidly proliferating round and polygonal cells that were capable of propagation in vitro for an indefinite period of time. Abnormal aneuploid chromosomes were found in short-term Hodgkin's disease monolayers that had been passaged 16-20 times, and in established cell lines carried in culture longer than 3 yr and passaged more than 200 times. Cells fromHodgkin's disease monolayers contained lysozyme (muramidase), fluoride-resistant alpha naphthol acetate esterase, acid and alkaline phosphatase, and chymotrypsin-like activity. The monolayers did not exhibit specific cell surface markers or phagocytosis. Suspension cultures derived from Hodgkin's disease monolayers were composed of cells with aneuploid karyotypes and similar enzymes. The Hodgkin's disease suspension culture cells had surface receptors for complement and IgGFc, lacked surface or cytoplasmic immunoglobulin, and did not form Erosettes, react with an antithymocyte serum, nor exhibit phagocytosis. Normal monolayer culture cells, derived from adult spleen and human fetal spleen and thymus, were composed of spindle cells with a diploid number of chromosomes that could be carried for only a finite period of time in vitro. Normal cultured cells contained similar esterases and phosphatases, but were devoid of lysozyme and chymotrypsin-like activity. The morphologic, cytogenetic, cell surface, and enzymatic findings indicate that our Hodgkin's disease monolayer and suspension cultures are composed of cells with many properties suggesting an origin from monocytes (macrophages) rather than lymphocytes or fibroblasts. The presence of aneuploid karyotypes is consistent with a neoplastic origin and derivation from a malignant cell of Hodgkin's disease.


Assuntos
Doença de Hodgkin/patologia , Neoplasias Esplênicas/patologia , Fosfatase Alcalina/metabolismo , Membrana Celular/imunologia , Células Cultivadas , Técnicas de Cultura , Doença de Hodgkin/enzimologia , Humanos , Fragmentos Fc das Imunoglobulinas , Técnicas Imunológicas , Linfócitos/enzimologia , Linfócitos/patologia , Linfócitos/ultraestrutura , Monócitos/enzimologia , Monócitos/patologia , Monócitos/ultraestrutura , Naftol AS D Esterase/metabolismo , Espectrofotometria , Neoplasias Esplênicas/enzimologia , Coloração e Rotulagem
5.
J Autism Dev Disord ; 49(12): 4919-4928, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473948

RESUMO

Knowledge about the quality of care delivered to children with autism spectrum disorders (ASD) in relation to that recommended by clinical practice guidelines (CPGs) is limited. ASD care quality indicators were developed from CPGs and validated by experts, then used to assess the quality of care delivered by general practitioners (GPs) and pediatricians in Australia. Data were retrospectively collected from the medical records of 228 children (≤ 15 years) with ASD for 2012-2013. Overall quality of care was high, but with considerable variation among indicators, and between GPs and pediatricians-e.g., GPs were less likely to complete the assessment care bundle (61%; 95% CI 21-92). Findings highlight potential areas for improvement in the need for standardized criteria for diagnosis.


Assuntos
Transtorno do Espectro Autista/terapia , Medicina Geral/normas , Qualidade da Assistência à Saúde , Austrália , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Criança , Pré-Escolar , Feminino , Medicina Geral/estatística & dados numéricos , Humanos , Masculino , Prontuários Médicos/estatística & dados numéricos
6.
J Clin Invest ; 65(2): 514-8, 1980 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6985918

RESUMO

Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous pyrogen from the two cell lines was similar and closely resembled that produced by normal human monocytes in antigenic properties as well as heat and pronase sensitivity. The Hodgkin's disease and histiocytic lymphoma cell lines do not require specific stimulation for the production of endogenous pyrogen suggesting that the mechanism of pyrogen release by neoplastic macrophage-related cells differs from that of normal phagocytic cells. The tumor-associated fever in some patients with malignant lymphoma may be caused by a release of endogenous pyrogen by proliferating neoplastic cells.


Assuntos
Doença de Hodgkin/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Pirogênios/biossíntese , Linhagem Celular , Febre/etiologia , Doença de Hodgkin/complicações , Humanos , Linfoma Difuso de Grandes Células B/complicações , Macrófagos/metabolismo
7.
J Natl Cancer Inst ; 58(2): 223-7, 1977 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-833873

RESUMO

An antigen in tissue cultures derived from Hodgkin's disease tumors was investigated by polyacrylamide gel electrophoresis, column chromatography, and isotopic antibody techniques. Fourteen long-term, serially passaged monolayer cultures prepared from tumor nodules of Hodgkin's disease in the spleen were studied; 11 monolayers derived from normal adult spleen and human fetal spleen and thymus were used as controls. Cell-free medium from Hodgkin's disease and normal cultures were centrifuged, and the pellet fractions were sedimented in a discontinuous sucrose gradient, solubilized with dodium dodecyl sulfate, and labeled with radioiodine. Gel filtration and electrophoresis revealed a component in samples prepared from medium of Hodgkin's disease cultures that was not observed in medium from normal cultures. An antiserum made in rabbits against this component reacted by radioiodine-labeled antibody assay with an antigen on the surface on cells from Hodgkin's disease cultures that was present in very small amounts, or in a cryptic state, on normal cultured cells. This antigen, intimately associated with propagation of cells obtained from the tumor in vitro, was not demonstrable in noncultured Hodgkin's disease tissue...


Assuntos
Antígenos de Neoplasias/análise , Doença de Hodgkin/imunologia , Membrana Celular/imunologia , Cromatografia em Gel , Técnicas de Cultura , Eletroforese em Gel de Poliacrilamida , Radioimunoensaio
8.
J Natl Cancer Inst ; 62(4): 787-97, 1979 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-372654

RESUMO

We examined the binding of soluble immune complexes in sera from patients with Hodgkin's disease to established tissue cultures derived from the tumor. Circulating immune complex levels were determined by the Raji cell assay, and the reaction of serum with cultured cells was examined with a radioimmune assay and by immunoferritin electron microscopy. Serum with elevated immune complexes was found to react with cells of Hodgkin's disease monolayers when tested with radioiodine-labeled antisera against human IgG heavy and light chains and the complement 3 (C3) component. When examined with the electron microscope, monolayers incubated with Hodgkin's disease serum containing immune complex and labeled with ferritin-conjugated antiserum to C3 contained surface-bound ferritin particles with a uniform but discontinuous pattern. Absorption of Hodgkin's disease serum with monolayer cells reduced immune complexes and decreased reactivity of the sample with cultured cells by radioimmune assay. Sera of patients with other disorders and aggregated gamma-globulin with complement, despite markedly elevated immune complex levels, did not react positively with monolayers derived from Hodgkin's disease tumors, and none of the sera reacted with normal cultured spleen. The approximate size of serum components reacting with Hodgkin's disease monolayers was estimated by sucrose density gradient centrifugation. Sedimentation fractions in the 19S region reacted with monolayer cells when tested with 125I-labeled antisera to both IgG and C3 and contained immunoglobulin-complement complexes by gel diffusion and immunoabsorption. A component sedimenting at 7-9S contained immunoglobulin not complexed with complement; this component reacted with monolayer cells when tested with anti-IgG antiserum but did not react when tested with antibody to C3. The reaction of Hodgkin's disease monolayers with serum containing immune complexes differed from that of two suspension culture lines composed of cells with surface complement and IgG Fc receptors. Inasmuch as cells of our long-term Hodgkin's disease monolayers do not contain these surface receptors, possibly the antibody component of the immune complex reacts with antigens on the surface of cultured cells.


Assuntos
Complexo Antígeno-Anticorpo , Doença de Hodgkin/imunologia , Complemento C3 , Técnicas de Cultura , Ferritinas/imunologia , Humanos , Imunoglobulina G , Técnicas de Imunoadsorção , Microscopia Eletrônica , Neoplasias Experimentais/imunologia , Radioimunoensaio/métodos
9.
Thromb Res ; 140 Suppl 1: S181, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27161702

RESUMO

INTRODUCTION: The close relationship between coagulation, thrombosis and cancer has long been established. Gynaecological cancers, in particular ovarian cancers, carry a high risk of thrombosis but coagulation activation is also thought to play a role in tumorigenesis and metastasis. In experimental animal models of metastasis, mice with a genetic procoagulant phenotype are prone to develop metastasis and anticoagulant therapy dramatically reduces pulmonary metastasis in these models. The aPC pathway is a key natural anticoagulant pathway, in addition to its role in venous thrombosis, dysregulation of this pathway is also thought to play a role in the pathogenesis of some cancers. No data exists in ovarian and endometrial cancers. AIM: The aim of this study is to determine the expression of key proteins of the activated protein C pathway in endometrial and ovarian malignant tumours compared to benign tumours and to assess their role in patient survival. MATERIALS AND METHODS: RNA was extracted from 78 (54 malignant and 24 benign) fresh frozen ovarian and endometrial tumours samples. Tumour biopsies were mRNA expression of endothelial protein C receptor (EPCR), protein S (PS), protein C (PC), thrombomodulin (TM), Factor V (FV) and VIII (FVIII) and PAR-1 and PAR-2 was measured using TaqMan Low Density Arrays. mRNA fold change relative to benign expression was determined using the 2 -delta delta Ct method with 18s as internal standard. All patients gave full and informed consent and the study had the approval of the hospital ethics committee. Total cell protein was extracted from ovarian tumour tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure protein plasma expression RESULTS: EPCR (P<0.001), protein S (P<0.0001) and Factor VIII (P<0.003) mRNA expression was significantly downregulated in malignant tumours compared with benign. Factor V and PAR-2 were significantly upregulated (P<0.001; P<0.004). Protein C was not consistently expressed. Reduced EPCR and TM protein expression was also observed in malignant tumours with increased plasma levels of Factor V. Reduced protein S and increased FV were associated with decreased survival. Plasma levels of Factor V were related to grade in the endometrial cancer group. PAR-2 mRNA expression was increased in ovarian tumours (P<0.001) however PAR-1 expression remained unchanged. CONCLUSIONS: Our results show reduced expression of key proteins associated with activation of protein C combined with increased expression in FV in gynaecological malignancies. These changes may contribute to local thrombin production and tumour progression and metastasis. Further work is required to determine the precise mechanisms involved.

10.
Biochim Biophys Acta ; 1458(2-3): 457-66, 2000 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-10838058

RESUMO

Most of what is known about the structure and function of subunit a, of the ATP synthase, has come from the construction and isolation of mutations, and their analysis in the context of the ATP synthase complex. Three classes of mutants will be considered in this review. (1) Cys substitutions have been used for structural analysis of subunit a, and its interactions with subunit c. (2) Functional residues have been identified by extensive mutagenesis. These studies have included the identification of second-site suppressors within subunit a. (3) Disruptive mutations include deletions at both termini, internal deletions, and single amino acid insertions. The results of these studies, in conjunction with information about subunits b and c, can be incorporated into a model for the mechanism of proton translocation in the Escherichia coli ATP synthase.


Assuntos
Escherichia coli/enzimologia , ATPases Translocadoras de Prótons/química , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Cisteína/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Modelos Moleculares , Dados de Sequência Molecular , Mutação , ATPases Translocadoras de Prótons/genética , Prótons
11.
Genetics ; 127(2): 417-28, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2004712

RESUMO

A method for simultaneously estimating the admixture proportions of a hybrid population and Wright's fixation index, FST, for that hybrid is presented. It is shown that the variance of admixture estimates can be partitioned into two components: (1) due to sample size, and (2) due to evolutionary variance (i.e., genetic drift). A chi-square test used to detect heterogeneity of admixture estimates from different alleles, or loci, can now be corrected for both sources of random errors. Hence, its value for the detection of natural selection from heterogeneous admixture estimates is improved. The estimation and testing procedures described above are independent of the dynamics of the admixture process. However, when the admixture dynamics can be specified, FST can be predicted from genetic principles. Two admixture models are considered here, gene flow and intermixture. These models are of value because they lead to very different predictions regarding the accumulation of genes from the parental populations and the accumulation of variance due to genetic drift. When there is not evidence for natural selection, and it is appropriate to apply these models to data, the variance effective size (Ne) of the hybrid population can be estimated. Applications are made to three human populations: two of these are Afro-American populations and one is a Yanomamö Indian village. Natural selection could not be detected using the chi-square test in any of these populations. However, estimates of effective population sizes do lead to a richer description of the genetic structure of these populations.


Assuntos
Genética Médica , Genética Populacional , Modelos Genéticos , Modelos Estatísticos , População Negra , Brasil , Frequência do Gene , Georgia , Humanos , Indígenas Sul-Americanos , Venezuela
12.
Genetics ; 112(3): 629-47, 1986 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3957006

RESUMO

The internal patterning of allelic correlations in the Gainj and Kalam swidden horticulturalists of highland Papua New Guinea is examined within the context of Sewall Wright's F-statistic model. A multiallelic extension of the model is given first, and multivariate variance-component estimators for the parameters are suggested. Then, it is shown that the expectation of the F-statistic set depends on the age structure of the population and that knowledge of the population and sample age structure is critical for meaningful analysis. The array of F-statistics estimated jointly over five polymorphic enzyme loci reveals the following features of Gainj and Kalam population structure: (1) significant departures from panmictic expectations and (2) characteristics of a continuously distributed breeding population, rather than those expected for populations subdivided into demes with discrete boundaries. Finally, the F-statistics estimated for the Gainj and Kalam are briefly compared to estimates obtained from other tribal populations. It is seen that the level of differentiation observed in the Gainj and Kalam is only about one-third that observed in South American swidden horticulturalists. Consequently, some conventional wisdom regarding the interrelationship of socioecological settings and genetic structures may require reevaluation.


Assuntos
Alelos , Modelos Genéticos , Análise de Variância , Biometria , Etnicidade , Genótipo , Humanos , Idioma , Papua Nova Guiné
13.
Genetics ; 117(2): 273-83, 1987 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3666443

RESUMO

The patterning of allele frequency variability among 18 local groups of Gainj and Kalam speakers of highland Papua New Guinea is investigated using new genetic distance methods. The genetic distances proposed here are obtained by decomposing Sewall Wright's coefficient FST into a set of coefficients corresponding to all pairs of population subdivisions. Two statistical methods are given to estimate these quantities. One method provides estimates weighted by sample sizes, while the other method does not use sample size weighting. Both methods correct for the within-individual and between-individual-within-groups sums of squares. Genetic distances among the Gainj and Kalam subdivisions are analyzed with respect to demographic, geographic, and linguistic variables. We find that a demographic feature, group size, has the greatest demonstrable association with the patterning of genetic distances. The pattern of geographic distances among groups displays a weak congruence with the pattern of genetic distances, and the association of genetic and linguistic diversity is very low. An effect of differences in group size on genetic distances is not surprising, from basic theoretical considerations, but genetic distances have not often been analyzed with respect to these variables in the past. The lack of correspondence between genetic distances and linguistic and geographic differences is an unusual feature that distinguishes the Gainj and Kalam from most other tribal populations.


Assuntos
Alelos , Etnicidade , Variação Genética , Biometria , Demografia , Idioma , Modelos Genéticos , Papua Nova Guiné
14.
Arch Gen Psychiatry ; 55(7): 593-602, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9672049

RESUMO

BACKGROUND: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Low turnover rate of this monoamine neurotransmitter is associated with impaired impulse control. We previously reported that, in Finns, TPH genotype was associated with suicidality, a pathophysiological mechanism that may involve impaired impulse control. METHODS: Association and sib-pair linkage analyses of a polymorphism in intron 7 of the TPH gene with suicidality, alcoholism, and the Karolinska Scales of Personality were conducted in 804 Finnish alcoholic offenders, controls, and their relatives, in a sample that included 369 sib pairs. RESULTS: The association of the TPH 17 779C (L) allele to suicidality in impulsive offenders reported previously was replicated in a new group of Finnish offenders (P=.001, n=122). The intron 7 variant in the TPH gene showed significant evidence for linkage to suicidality (P=.006 in unaffected sib pairs), severe suicide attempts (P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002). CONCLUSIONS: The status of the TPH A779C allele as a marker for suicidality was replicated and linkage with alcoholism and Karolinska Scales of Personality socialization score was also observed. A functional variant(s) in or close to the TPH gene may predispose individuals to suicidality and other behaviors thought to be influenced by serotonin.


Assuntos
Alcoolismo/genética , Marcadores Genéticos , Tentativa de Suicídio/estatística & dados numéricos , Triptofano Hidroxilase/genética , Adulto , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/genética , Família , Finlândia/epidemiologia , Ligação Genética , Variação Genética , Genótipo , Humanos , Íntrons , Masculino , Modelos Genéticos , Personalidade/classificação , Personalidade/genética , Polimorfismo Genético , Prisioneiros/estatística & dados numéricos , Análise de Regressão , Serotonina/genética , Tentativa de Suicídio/classificação
15.
Arch Gen Psychiatry ; 55(11): 989-94, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9819067

RESUMO

BACKGROUND: In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this serotonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism. METHODS: Linkage was first tested in 640 Finnish subjects, including 166 alcoholic criminal offenders, 261 relatives, and 213 healthy controls. This was followed by a study in a large multigenerational family derived from a Southwestern American Indian tribe (n=418) with a high rate of alcoholism. All subjects were psychiatrically interviewed, blind-rated for psychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects. RESULTS: In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to HTR1B G861C (P=.04) and weak evidence with D6S284 (P=.06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher HTR1B-861C allele frequency than the other 457 Finns we studied (P=.005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to HTR1B G861C (P=.01) was again observed, and there was also significant linkage to D6S284 (P=.01). CONCLUSION: These results suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15.


Assuntos
Alcoolismo/genética , Transtorno da Personalidade Antissocial/genética , Transtornos Disruptivos, de Controle do Impulso e da Conduta/genética , Ligação Genética , Receptores de Serotonina/genética , Adolescente , Adulto , Alcoolismo/epidemiologia , Animais , Transtorno da Personalidade Antissocial/epidemiologia , Sequência de Bases , Comorbidade , Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Feminino , Finlândia/epidemiologia , Finlândia/etnologia , Genótipo , Humanos , Indígenas Norte-Americanos/genética , Masculino , Camundongos , Dados de Sequência Molecular , Linhagem , Polimorfismo Genético , Receptor 5-HT1B de Serotonina , Sudoeste dos Estados Unidos/epidemiologia , Sequências de Repetição em Tandem/genética
16.
Arch Gen Psychiatry ; 55(10): 936-40, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9783565

RESUMO

BACKGROUND: The heritability of interindividual variation in anxiety and other aspects of personality establishes that variants of genes influence these traits. A functional polymorphism in the promoter of the human serotonin transporter gene (SLC6A4*C) was identified and found to be linked to an anxiety-related personality trait, Neuroticism. The polymorphism affects gene transcription and, ultimately, gene function. We have attempted to confirm the role of SLC6A4*C in anxiety-related personality traits by sibpair analysis and association studies. METHODS: Sibpair linkage analysis and association study were performed in 655 Finns. The index cases were 182 alcoholic criminal offenders, through which 258 relatives were ascertained to obtain 366 sibpairs. In addition, 215 unrelated population controls were collected. Each individual was psychiatrically interviewed, blind-rated for DSM-III-R diagnoses, and assessed with the Tridimensional Personality Questionnaire. RESULTS: The sibpair analysis revealed a positive linkage between SLC6A4*C and the 2 anxiety-related subdimensions of Harm Avoidance: HA1 (Anticipatory Worry) and HA2 (Fear of Uncertainty) (P = .003). However, there was no consistent association between SLC6A4*C and any Tridimensional Personality Questionnaire trait. CONCLUSIONS: In the present study we replicated the relationship of SLC6A4*C to anxiety by sibpair linkage analysis but found no evidence of association, raising the question of whether SLC6A4*C locus is itself affecting anxiety or is linked to another still unknown functional variant.


Assuntos
Ansiedade/genética , Proteínas de Transporte/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Personalidade/genética , Regiões Promotoras Genéticas/genética , Serotonina/genética , Alcoolismo/genética , Proteínas de Transporte/fisiologia , Crime , Ligação Genética , Humanos , Glicoproteínas de Membrana/fisiologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Regiões Promotoras Genéticas/fisiologia , Serotonina/fisiologia , Proteínas da Membrana Plasmática de Transporte de Serotonina , Transcrição Gênica/fisiologia
17.
Biol Psychiatry ; 46(6): 821-6, 1999 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10494451

RESUMO

BACKGROUND: Heritable variation in brain monoaminergic activity has been suggested to lead to interindividual differences in vulnerability to alcoholism, and many other behavioral disorders. We evaluated if a functional Cys23Ser polymorphism in the 5-HT2C receptor gene, the principal serotonin receptor in the brain, contributes to variation in serotonin, norepinephrine and dopamine activity, as indexed by their major metabolite concentrations in cerebrospinal fluid (CSF). Genotype-monoamine metabolite concentration associations were subsequently correlated to risk for alcoholism. METHODS: The study sample consisted of unrelated Finnish males, including 214 alcoholic, violent offenders and 222 population controls who were interviewed using the Structured Clinical Interview for DSM-III-R, blind rated for psychiatric diagnoses and typed for the HTR2C Cys23Ser polymorphism. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), the major metabolite of norepinephrine, and homovanillic acid (HVA), the major metabolite of dopamine were available from 195 individuals. RESULTS: The major finding in this study was that HTR2C CysSer23 significantly contributed to CSF MHPG concentrations (p = .012). Higher concentrations of CSF MHPG were observed both in alcoholic violent offenders and population controls with HTR2C Ser23 genotype. Despite the association of Cys23Ser to CSF MHPG, HTR2C genotype was not associated with alcoholism, nor with other psychiatric disorders present in this sample. CONCLUSIONS: We conclude that a functional HTR2C Cys23Ser polymorphism contributes to the interindividual genetic variation of CSF MHPG explaining 3% of the total variance. This finding suggests that 5-HT2C receptors are involved in the regulation of norepinephrine turnover in humans; however, HTR2C Cys23Ser does not appear to contribute to the risk of alcoholism, or its contribution to this complex and heterogenous disorder is too small to be detected by a sample of this size and structure.


Assuntos
Monoaminas Biogênicas/líquido cefalorraquidiano , Genes/genética , Transtornos Mentais/diagnóstico , Polimorfismo Genético/genética , Alcoolismo/genética , Encéfalo/metabolismo , Dopamina/metabolismo , Genótipo , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Masculino , Metoxi-Hidroxifenilglicol/líquido cefalorraquidiano , Norepinefrina/metabolismo , Escalas de Graduação Psiquiátrica , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo
18.
Am J Med ; 58(3): 300-6, 1975 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1090157

RESUMO

The surface of lymphocytes obtained from fresh biopsy specimens from 41 patients with malignant lymphoma and from 30 normal subjects or patients with non-neoplastic lymphadenopathy were investigated. Immunoglobulin on the cell surface was used to identify B cells, whereas T cells were recognized by their reactivity with an antithymocyte antiserum and their ability to form rosettes with sheep erythrocytes. Normal and inflammatory lymph nodes were composed predominantly of T lymphocytes, as were nodes from 14 patients with Hodgkin's disease. Two thymomas were T cell proliferations, whereas a node from a patient with ataxia-telangiectasia was devoid of T lymphocytes. The presence of immunoglobulin on the cell surface indicated that 19 of 21 lymphocytic lymphomas were B cell proliferations, whereas the cells from 3 histiocytic lymphomas (reticulum cell sarcomas) and 1 mixed histiocytic and lymphocytic lymphoma were devoid of surface immunoglobulin. In immunoglobulin-positive tumors, one predominant heavy chain and one predominant light chain could usually be identified, thus establishing the clonal character of the neoplastic proliferation. Ten of 11 diffuse poorly differentiated lymphocytic lymphomas were composed of cells with large amounts of surface immunoglobulin, whereas only 1 of 5 diffuse well differentiated lymphocytic tumors contained such abundant surface immunoglobulin. The surface immunoglobulin data indicate the existence of at least two subspecies of B cell neoplasms. A small lymphocyte with sparse surface immunoglobulin proliferates as diffuse well differentiated lymphocytic lymphoma and chronic lymphocytic leukemia, whereas a larger lymphocyte with abundant surface immunoglobulin proliferates as diffuse poorly differentiated lymphocytic lymphoma and lymphosarcoma cell leukemia.


Assuntos
Membrana Celular/imunologia , Doença de Hodgkin/imunologia , Linfócitos/imunologia , Animais , Soro Antilinfocitário , Linfócitos B/imunologia , Biópsia , Sobrevivência Celular , Cabras/imunologia , Doença de Hodgkin/patologia , Humanos , Reação de Imunoaderência , Soros Imunes , Linfonodos/imunologia , Linfonodos/patologia , Doenças Linfáticas/imunologia , Doenças Linfáticas/patologia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Ovinos/imunologia , Linfócitos T/imunologia , Timoma/imunologia , Timoma/patologia
19.
Am J Med ; 64(5): 851-8, 1978 May.
Artigo em Inglês | MEDLINE | ID: mdl-274070

RESUMO

A 54 year old woman presented with acute lymphocytic leukemia. Following an initial response to chemotherapy with vincristine and prednisone, progressive pancytopenia developed coincident with intense bone marrow infiltration by abnormal histiocytes. At autopsy two months later, no evidence of leukemia was found, but the bone marrow was replaced by abnormal histiocytes showing active erythrophagocytosis, consistent with histiocytic medullary reticulosis. Detailed morphologic, ultrastructural and histochemical studies performed throughout the course of the patient's illness served to confirm the transition from leukemia to histiocytosis. Four similar cases of acute lymphocytic leukemia terminating in histiocytic medullary reticulosis have been reported. This association may represent a distinct clinicopathologic syndrome.


Assuntos
Histiócitos , Leucemia Linfoide/complicações , Reticulócitos , Medula Óssea/patologia , Medula Óssea/ultraestrutura , Feminino , Humanos , Leucemia Linfoide/patologia , Microscopia Eletrônica , Pessoa de Meia-Idade
20.
Am J Med ; 64(2): 289-94, 1978 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-629278

RESUMO

Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 microgram/ml +/- 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (less than 15 microgram/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.


Assuntos
Complexo Antígeno-Anticorpo , Doença de Hodgkin/imunologia , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Radioimunoensaio
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