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1.
Eat Weight Disord ; 27(8): 3627-3635, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36495463

RESUMO

PURPOSE: Psychopathology and disordered eating behaviours are putative pre-operative risk factors for suboptimal outcomes post-bariatric surgery. Documented psychopathology prevalence rates vary in bariatric candidate samples. Further, less attention has been paid to vulnerable subgroups such as people with diabetes who might be at an elevated risk. For these reasons, this study aimed to investigate the rates of psychopathology and disordered eating in pre-surgical candidates with type 2 diabetes mellitus (T2DM). METHODS: Participants were 401 consecutive patients from a state-wide bariatric surgery service for people with T2DM. Psychopathology was measured using multi-modal assessment including diagnostic interview and battery of validated questionnaires. The mean age of the sample was 51 years with a mean BMI of 46 kg/m2. The majority of the sample was female (60.6%), born in Australia (87%) and 18.2% identified as Aboriginal and/or Torres Strait Islander. RESULTS: Rates of current psychopathology in this sample included: major depressive disorder (MDD; 16.75%), generalised anxiety disorder (GAD; 20.25%), insomnia (17.75%) and binge eating disorder (BED; 10.75%). There were no significant differences on measures between people who endorsed Aboriginal and/or Torres Strait Islander status compared to those who did not endorse. The mean total score on the BES was 21.82 ± 10.40 (range 0-39), with 8.2% of participants meeting criteria for severe binge eating. Presence of an eating disorder was not significantly associated with degree of glycemic compensation. Average emotional eating scores were significantly higher in this study, compared to reference samples. Significantly increased binge eating severity and emotional eating severity was revealed for people with T2DM and comorbid MDD, social anxiety and eating disorders. Binge eating severity was associated with GAD, food addiction, substance use disorders, and history of suicide attempt but not emotional eating severity. CONCLUSION: Amongst people with T2DM seeking bariatric surgery, MDD, GAD and emotional eating were common. Psychopathology in a sample of people with T2DM seeking bariatric surgery was significantly associated with severity of disordered eating. These findings suggest people with T2DM seeking bariatric surgery may be vulnerable to psychopathology and disordered eating with implications for early identification and intervention. LEVEL OF EVIDENCE: Evidence obtained from cohort or case-control analytic studies.


Assuntos
Cirurgia Bariátrica , Transtorno da Compulsão Alimentar , Bulimia , Transtorno Depressivo Maior , Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Humanos , Feminino , Pessoa de Meia-Idade , Transtorno Depressivo Maior/complicações , Diabetes Mellitus Tipo 2/complicações , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Obesidade Mórbida/psicologia , Transtorno da Compulsão Alimentar/complicações , Transtorno da Compulsão Alimentar/epidemiologia , Transtorno da Compulsão Alimentar/diagnóstico , Comportamento Alimentar/psicologia , Bulimia/psicologia , Cirurgia Bariátrica/psicologia
2.
Insect Mol Biol ; 19(4): 451-61, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20374304

RESUMO

It has been proposed that a honey bee (Apis mellifera) worker's preference for foraging for pollen or nectar is modulated by a gene network that was originally involved in regulating the reproductive cycles of an ancestral solitary species. We used carbon dioxide to induce narcosis in queens and workers. This treatment is known to initiate oogenesis in queens, reduce oogenesis in queenless workers and to change worker foraging preference. We then assessed changes in gene expression of genes suspected to be involved in either foraging behaviour or reproduction. We show that some genes change expression in the opposite direction between castes in response to treatment. Our results therefore support the hypothesis that reproductive and foraging traits are causally related in the honey bee.


Assuntos
Abelhas/efeitos dos fármacos , Abelhas/genética , Dióxido de Carbono/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Entorpecentes/farmacologia , Pólen/metabolismo , Animais , Feminino , Análise Multivariada , Ovário/efeitos dos fármacos , Ovário/metabolismo , Pólen/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Reprodução/genética , Predomínio Social
3.
Hernia ; 12(4): 351-8, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18235999

RESUMO

BACKGROUND: Biologic matrices offer a new approach to the management of abdominal wall defects when the use of other foreign material is not ideal. A member of our team (GEA) developed a biological decellularized matrix generated from harvested blood vessels of swine blood vessel matrix (BVMx). The aim of our study was to investigate whether this novel collagen-based biological matrix is safe and effective for the repair of abdominal wall hernia defects in a rat model. METHODS: Full thickness abdominal wall defects were created in rats and repaired with our BVMx. After implantation as an underlay for 30 and 90 days, animals were sacrificed and the implanted material evaluated for herniation, adhesions, breaking strength, inflammation, and revascularization. RESULTS: No evidence of herniation was noted at 30 (n = 7) or 90 (n = 7) days after repair. Adhesions, if present, were filmy and easily separated. The mean area of visceral adhesions to the BVMx was 18.9 +/- 11.0% at 30 days and 7.1 +/- 3.1% at 90 days post implantation (P = 0.33). The breaking strength of the BVMx-fascial interface was 4.5 +/- 0.8 N at 30 days and 4.5 +/- 2.4 N at 90 days post implantation (P = 0.98). Histologic analysis demonstrated that the BVMx elicited a mild transient inflammatory response and supported fibroblast migration, deposition of newly formed collagen, and neovascularization. CONCLUSIONS: These data confirm that this BVMx supports vascular ingrowth and provides adequate strength for the repair of abdominal wall defects. Future studies in a large animal model are required to assess its validity for human application.


Assuntos
Vasos Sanguíneos/transplante , Hérnia Abdominal/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Telas Cirúrgicas , Animais , Modelos Animais de Doenças , Seguimentos , Masculino , Ratos , Ratos Sprague-Dawley , Suínos , Engenharia Tecidual , Resultado do Tratamento
4.
Mol Ecol Resour ; 8(3): 669-70, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-21585866

RESUMO

Gender assignment for some aquatic mammals in the field is difficult. Molecular sexing from tissue biopsies is possible as males are heterogametic. Here we describe a multiplex PCR assay that amplifies the male specific SRY gene and differentiates ZFX and ZFY gametologues in two sirenian species, dugong (Dugong dugon) and West Indian manatee (Trichechus manatus). The assay was validated with animals of known gender and proved accurate and robust to experimental failure.

5.
Obstet Gynecol ; 98(5 Pt 1): 726-31, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11704160

RESUMO

OBJECTIVE: To explore the outcome and long-term follow-up of fertility sparing surgery for cervical adenocarcinoma in situ and early invasive adenocarcinoma. METHODS: Between 1985 and 1996, all women with adenocarcinoma in situ (AIS) and stage I adenocarcinoma were identified. Data were abstracted from clinical records and pathology reviewed. RESULTS: One hundred thirty three women with stage I adenocarcinoma of the cervix were treated. Twenty subjects met the criteria for International Federation of Gynecology and Obstetrics stage IA1 lesions. Fourteen subjects were treated with radical hysterectomy, whereas two were treated with simple hysterectomy. Because of the desire to preserve fertility, four women with adenocarcinoma were treated with cervical conization alone, and three women have gone on to deliver viable infants. Forty-two women with adenocarcinoma in situ were identified, of whom 20 were treated with fertility sparing surgery (conization). Five women treated with conization had positive margins recurring in two, and one developed an invasive adenocarcinoma 5 years after conization. None of the women with adenocarcinoma treated with cervical conization have developed recurrent disease after a median follow-up of 48 months. Cone margin status was predictive of residual disease at hysterectomy. CONCLUSION: Women with adenocarcinoma in situ and negative margins may be treated with conservative, fertility sparing surgery. Education is essential regarding the risks of residual/recurrent disease because subjects can develop lethal recurrent disease. The fertility sparing management of invasive stage IA1 adenocarcinoma of the uterine cervix may also be entertained among women who desire future fertility and have negative margins of resection.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma in Situ/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adulto , Colo do Útero/patologia , Conização , Feminino , Fertilidade , Seguimentos , Humanos , Histerectomia , Gravidez , Resultado da Gravidez , Fatores de Tempo
6.
Cancer Epidemiol Biomarkers Prev ; 10(10): 1029-35, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11588128

RESUMO

To evaluate the effect of daily beta-carotene (30 mg) versus placebo over a 2-year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions. Human papillomavirus (HPV) typing was done to determine whether lesion regression was related to HPV. Micronutrient levels were measured to determine whether levels were predictive of regression. Variables that influence the risk of HPV infection and CIN, such as cigarette smoking and sexual behavior, were evaluated. Women were randomized to beta-carotene or placebo, with cytology and colposcopy every 3 months. Cervical biopsies were performed before treatment and after 6 and 24 months to evaluate response. Persistence of or progression to CIN 3 resulted in removal from the study, whereas treatment continued for 2 years on all others. The presence and type of HPV was determined by PCR. Response was defined as an improvement in CIN by 2 grades. Mantel-Haenszel chi(2) test was used to analyze response to treatment. Fisher's exact test was used to determine the effect of HPV and CIN grade on response Wilcoxon's rank-sum tests were used to compare micronutrient levels between groups. Twenty-one of 124 enrolled women were not randomized because they either moved, became pregnant, voluntarily withdrew, or the pathological review of their initial cervical biopsies did not confirm CIN 2 or 3. Of the remaining 103 women, 33 experienced lesion regression, 45 had persistent or progressive disease, and 25 women did not complete the study and were considered nonresponders in the final analysis. The overall regression rate (32%) was similar between treatment arms and when stratified for CIN grade. Data on 99 women with HPV typing showed that 77% were HPV-positive and 23% HPV-negative at enrollment. HPV-positive lesions were subdivided into indeterminate-, low-, and high-risk categories; the response rate was highest for women with no HPV detected (61%), lower for indeterminate/low-risk (30%), and lowest for high-risk (18%; P =.001). CIN regression was negatively correlated with retinol levels. In conclusion, beta-carotene does not enhance the regression of high-grade CIN, especially in HPV-positive subjects.


Assuntos
Antioxidantes/administração & dosagem , Displasia do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , beta Caroteno/administração & dosagem , Administração Oral , Adolescente , Adulto , Biópsia por Agulha , Suplementos Nutricionais , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Modelos Logísticos , Assistência de Longa Duração , Pessoa de Meia-Idade , Probabilidade , Valores de Referência , Índice de Gravidade de Doença , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal , Displasia do Colo do Útero/diagnóstico
7.
Obstet Gynecol ; 97(4): 555-60, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11275027

RESUMO

OBJECTIVE: To determine if estrogen replacement therapy, in women with a history of endometrial cancer, increases the risk of recurrence or death from that disease. METHODS: Two hundred forty-nine women with surgical stage I, II, and III endometrial cancer were treated between 1984 and 1998; 130 received estrogen replacement after their primary cancer treatments and 49% received progesterone in addition to estrogen. Among this cohort, 75 matched treatment-control pairs were identified. The two groups were matched by using decade of age at diagnosis and stage of disease. Both groups were comparable in terms of parity, grade of tumor, depth of invasion, histology, surgical treatment, lymph node status, postoperative radiation, and concurrent diseases. The outcome events included the number of recurrences and deaths from disease. RESULTS: The hormone users were followed for a mean interval of 83 months (95% confidence interval [CI] 71.0, 91.4) and the nonhormone users were followed for a comparable mean interval of 69 months (CI 59.1, 78.7). There were two recurrences (1%) among the 75 estrogen users compared with 11 (14%) recurrences in the 75 nonhormone users. Hormone users had a statistically significant longer disease-free interval than nonestrogen users (P =.006). CONCLUSION: Estrogen replacement therapy with or without progestins does not appear to increase the rate of recurrence and death among endometrial cancer survivors.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias do Endométrio/mortalidade , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP) , Recidiva Local de Neoplasia/mortalidade , Adenocarcinoma/cirurgia , California/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos
8.
Behav Res Methods Instrum Comput ; 33(4): 540-3, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11816458

RESUMO

A new Windows-based word processor for preparing journal articles and student papers is described. In addition to standard features found in word processors, the present word processor provides specific help in preparing manuscripts. Clicking on "Reference Help (APA Form)" in the "File" menu provides a detailed help system for entering the references in a journal article. Clicking on "Examples and Explanations of APA Form" provides a help system with examples of the various sections of a review article, journal article that has one experiment, or journal article that has two or more experiments. The word processor can automatically place the manuscript page header and page number at the top of each page using the form required by APA and Psychonomic Society journals. The "APA Form" submenu of the "Help" menu provides detailed information about how the word processor is optimized for preparing articles and papers.


Assuntos
Manuscritos como Assunto , Psicologia/educação , Processamento de Texto , Redação , Humanos , Publicações Periódicas como Assunto , Software
9.
Anticancer Res ; 20(6B): 4205-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11205249

RESUMO

BACKGROUND: To evaluate the use of D-methionine(D-met) as a cytoprotectant in the context of clinically relevant doses of cisplatin. MATERIALS AND METHODS: Forty five Fischer rats were injected intraperitoneally with 10(6) NuTu-19 cells and treated as follows: group 1 was the control group and received no treatment, group 2 received cisplatin 4 mg/kg and group 3 received cisplatin 4 mg/kg plus D-met. There were two groups that received high dose cisplatin. Group 4 received cisplatin 8 mg/kg and group 5 received cisplatin 8 mg/kg plus D-met. Treatment was initiated four weeks after injection of the NuTu-19 cells, and consisted of four weekly intraperitoneal injections. Serum BUN and creatinine levels in the high dose groups evaluated nephrotoxicity and clinical outcome was measured by mean survival using Kaplan Meier analysis. RESULTS: There were no significant elevations in serum BUN or creatinine levels in any of the rats treated with high dose cisplatin. In the animals given cisplatin 8 mg/kg plus D-met, death from toxicity was prevented and all animals completed four treatments. In contrast, only two animals in group 4 (cisplatin 8 mg/kg alone) completed 4 treatments. There was a significant improvement in survival for the animals given D-met. (p = .0001) In all treated groups except for group 4, there was an improvement in survival compared to the control group. When comparing groups 2 and 3 (4 mg/kg +/- D-met), there was a subjective decrease in tumor response for group 3 but mean survival was not statistically different. (91 vs. 81 days; p = 0.07) A comparison of groups 2 and 5 revealed no survival benefit using high dose cisplatin with D-met. (91 vs. 79 days; p = 0.10). CONCLUSIONS: Our results indicate that D-methionine provides cytoprotection against cisplatin toxicity without significant compromise of antitumor activity. All though D-methionine allowed for significant dose intensification of cisplatin above standard doses, there was no survival advantage noted in this group of animals. The indications for its use in the treatment of ovarian cancer remain to be determined.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Modelos Animais de Doenças , Metionina/farmacologia , Animais , Antineoplásicos/efeitos adversos , Nitrogênio da Ureia Sanguínea , Cisplatino/efeitos adversos , Creatinina/sangue , Avaliação Pré-Clínica de Medicamentos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Ratos , Ratos Endogâmicos F344
10.
Neurosci Lett ; 273(3): 183-6, 1999 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-10515189

RESUMO

P2X4 receptors are expressed in specific brain areas. We now describe site-specific splice variations of the human P2X4 receptor subunit, occurring at residue [YVIG / WVFV(W)] near the end of the first predicted transmembrane domain. p2X4(b) is formed by the insertion of an additional 16 amino acids. p2X4(C) is formed by deleting a cassette of 130 amino acids, including six of the 10 conserved extracellular cysteine residues. Transfection of P2X4(a), but not p2x4(c), formed functional channels in Xenopus oocytes and human 1321N1 cells. After transfection of p2X4(b) small, inconsistent ATP-evoked responses were detected only in the human cells, but when co-expressed, p2x4(b) may alter the function of P2X4(a) in oocytes. The distribution of splice variant RNA within human brain suggests regionally-dependent expression. These data indicate that the functions of the human P2X4 receptor may be altered by alternative splicing.


Assuntos
Processamento Alternativo/genética , Neuropeptídeos/genética , Receptores Purinérgicos P2/genética , Trifosfato de Adenosina/farmacologia , Processamento Alternativo/efeitos dos fármacos , Sequência de Aminoácidos/genética , Animais , Células Cultivadas , DNA/genética , Humanos , Dados de Sequência Molecular , Neuropeptídeos/efeitos dos fármacos , Neuropeptídeos/metabolismo , Oócitos , Receptores Purinérgicos P2/efeitos dos fármacos , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2X4 , Transfecção/genética , Xenopus
11.
Compr Ther ; 25(3): 144-50, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10200903

RESUMO

Ovarian malignancies in reproductive age women often provide the physician and patient with a management dilemma. Many investigators have proposed conservative management in early-stage disease. This article provides evidence supporting fertility-sparing management in young women with early ovarian malignancies.


Assuntos
Fertilidade , Procedimentos Cirúrgicos em Ginecologia , Neoplasias Ovarianas/cirurgia , Adenocarcinoma/cirurgia , Carcinoma Embrionário/cirurgia , Quimioterapia Adjuvante , Disgerminoma/cirurgia , Tumor do Seio Endodérmico/cirurgia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Radioterapia Adjuvante , Ruptura Espontânea/cirurgia , Teratoma/cirurgia
12.
J Am Assoc Gynecol Laparosc ; 5(2): 141-8, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9564061

RESUMO

STUDY OBJECTIVES: To determine the feasibility of macroscopic visualization of small ovarian cancer metastases in vivo by fluorescence after intravenous administration of 5-aminolevulinic acid (ALA); to assess the time after drug injection when fluorescence of small metastases is maximum; and to correlate macroscopic in vivo fluorescence with both microscopic ex vivo fluorescence and histologic findings. DESIGN: Controlled animal study (Canadian Task Force classification I). SETTING: University-based facility. SUBJECTS: Twenty-four healthy, female Fischer rats. INTERVENTION: Diffuse peritoneal metastatic cancer was induced in Fischer 344 rats by intraperitoneal injection of 1 million syngeneic ovarian cancer cells (NuTu-19). Four weeks after induction ALA100 mg/kg was injected intravenously, and diagnostic laparotomy was performed 1, 3, 6, or 9 hours thereafter. MEASUREMENTS AND MAIN RESULTS: The peritoneal cavity was illuminated with the Wood's lamp (ultraviolet light). Fluorescence was determined by direct visualization and compared with a calibrated fluorescent disk. Tissues were collected, sectioned, and examined by fluorescence and conventional light microscopy. Within 1 to 3 hours after intravenous injection of ALA, in vivo fluorescence of tumor nodules (diameter 0.4-5.0 mm) was macroscopically visible. Tumor-free peritoneum did not show fluorescence and was significantly distinguishable from cancer nodules. Fluorescence from intestinal tissues was comparable with tumor nodules. Microscopic fluorescence analysis showed similar values for tumor nodules and peritoneum. Stained histologic specimens of peritoneal surface revealed a superficial layer of cancer cells responsible for fluorescence. The time course of the fluorescence curve in the intestine peaked twice, at 1 and 6 hours after ALA injection. Macroscopically fluorescing nodules were histology confirmed as malignant. CONCLUSIONS: Fluorescence detection of small cancer nodules after intravenous injection of ALA is feasible for nodules smaller than 0.5 mm on the peritoneum. One to 3 hours after drug injection is optimal for diagnosis of metastases.


Assuntos
Ácido Aminolevulínico , Fluorescência , Neoplasias Intestinais/patologia , Neoplasias Intestinais/secundário , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Ácido Aminolevulínico/administração & dosagem , Animais , Modelos Animais de Doenças , Feminino , Injeções Intravenosas , Laparoscopia , Microscopia , Transplante de Neoplasias , Ratos , Ratos Endogâmicos F344 , Sensibilidade e Especificidade
13.
Obes Res ; 5(5): 387-94, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9385611

RESUMO

The obese Zucker rat (OZR) exhibits a missense mutation in the cDNA for the leptin receptor, producing a single amino acid substitution in the extracellular domain of the receptor. A mutation in the leptin receptor gene of the db/db mouse prevents the synthesis of the long splice variant of the receptor. The possibility that the OZR, like the db/db mouse, is refractory to the actions of murine leptin was tested by infusing the protein intracerebroventricularly via a minipump for 7 days. Lean Zucker rats (LZR) infused with leptin acted as positive controls, and other groups of OZR and LZR were infused with vehicle. In LZR, leptin reduced bodyweight and food intake and increased brown adipose tissue (BAT) temperature. Plasma corticosterone increased (61%) in these rats, and plasma triglycerides fell (78%). Leptin treatment improved tolerance to an oral glucose load (16% reduction in the area under the blood glucose curve) while lowering plasma insulin. In OZR, the actions of leptin were blunted. Food intake was slightly, but not significantly, reduced. Although there was a reduction in the rate of increase in body mass, the effect of leptin was about half that seen in LZR. BAT temperature and glucose tolerance were unchanged. In contrast to the elevated plasma corticosterone seen in LZR, leptin reduced the level of this hormone (27%) in OZR. In OZR and LZR treated with leptin, the plasma leptin levels were increased 24-fold and 47-fold, respectively. The results suggest that leptin retains some efficacy in OZR, although these rats are less responsive than LZR.


Assuntos
Encéfalo/efeitos dos fármacos , Obesidade/fisiopatologia , Proteínas/farmacologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/fisiopatologia , Animais , Glicemia/metabolismo , Temperatura Corporal , Peso Corporal/efeitos dos fármacos , Corticosterona/sangue , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético , Bombas de Infusão Implantáveis , Insulina/sangue , Leptina , Masculino , Camundongos , Proteínas/administração & dosagem , Proteínas/metabolismo , Ratos , Ratos Zucker , Proteínas Recombinantes/farmacologia , Triglicerídeos/sangue
14.
Diabetes ; 46(3): 335-41, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9032086

RESUMO

Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.


Assuntos
Tecido Adiposo Marrom/metabolismo , Proteínas de Transporte/biossíntese , Ventrículos Cerebrais/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Hipotálamo/fisiologia , Proteínas de Membrana/biossíntese , Neurônios/fisiologia , Neuropeptídeo Y/metabolismo , Neuropeptídeo Y/farmacologia , Biossíntese de Proteínas , Proteínas/farmacologia , Tecido Adiposo Marrom/efeitos dos fármacos , Animais , Ventrículos Cerebrais/efeitos dos fármacos , Hiperfagia , Hipotálamo/efeitos dos fármacos , Infusões Parenterais , Canais Iônicos , Leptina , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Mitocondriais , Neurônios/efeitos dos fármacos , Neuropeptídeo Y/administração & dosagem , Obesidade , Sondas de Oligonucleotídeos , Proteínas/administração & dosagem , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Proteínas Recombinantes/farmacologia , Transcrição Gênica/efeitos dos fármacos , Proteína Desacopladora 1 , Aumento de Peso/efeitos dos fármacos
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 53A(2): 165-72, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9097901

RESUMO

Applicability of the nitromethane selective quenching rule for discriminating between alternant vs. nonalternant polycyclic aromatic hydrocarbons (PAHs) is examined for 18 representative PAH solutes dissolved in micellar cetyltrimethylammonium chloride (CTACl), micellar dodecyltrimethylammonium bromide (DTAB), micellar Brij-35 and micellar sodium octanoate (SO) solvent media. Experimental results show that nitromethane quenched fluorescence emission of only the 10 alternant PAHs in the two cationic (CTACl and DTAB) and nonionic Brij-35 surfactant solvent media as expected. Emission intensities of nonalternant PAHs, except for the few exceptions noted previously, were unaffected by nitromethane addition. Unexpected quenching behavior was observed, however, in the case of nonalternant PAHs dissolved in micellar sodium octanoate solvent media. Nitromethane quenched fluorescence emission of all nonalternant PAHs studied in the SO solvent media, which is contrary to the selective quenching rule.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos/química , Espectrometria de Fluorescência/métodos , Corantes Fluorescentes , Metano/análogos & derivados , Micelas , Estrutura Molecular , Nitroparafinas , Tensoativos
16.
S D J Med ; 49(7): 217-21, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8755457

RESUMO

A family, with a strong history of dominant breast and ovarian cancer, is described. Using highly polymorphic microsatellite markers within the BRCA1 breast cancer gene on chromosome 17q21; three affected sisters, their father and a paternal second cousin once removed, are shown to share the same "abnormal" haplotype. Because of this informative linkage, the carrier status of the unaffected siblings can be established by determining whether they inherited their father's "normal" or "abnormal" haplotype. Presymptomatic diagnosis is important in decisions regarding prophylactic surgery or follow-up care. However, the widespread general population presymptomatic DNA testing of breast cancer is currently not recommended because of inherent problems in the sensitivity and specificity of DNA testing.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1/genética , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , DNA de Neoplasias/análise , Feminino , Testes Genéticos , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Linhagem , Medição de Risco , Sensibilidade e Especificidade
17.
Yeast ; 12(4): 319-31, 1996 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-8701605

RESUMO

Exogenous fatty acids transcriptionally control the expression of a wide variety of eukaryotic genes, many of which encode proteins involved in lipid metabolism. To identify gene products involved in the lipid signalling pathway, a reporter plasmid containing the 5'-upstream region of a gene demonstrated to be repressed by unsaturated fatty acids (OLE1) was fused in frame to the Escherichia coli gene lacZ encoding beta-galactosidase. Saccharomyces cerevisiae mutants defective in transcriptional control by lipids were identified and this class of mutants has been named frm (fatty acid repression mutant). The mutants were organized into six complementation groups designated frm1-6. Mutants from two of the complementation groups, frm1 and frm3, were also defective in their ability to activate a reporter construct containing the 5'-upstream region of POX1. POX1 has been shown to be transcriptionally activated in the presence of unsaturated fatty acids. frm2 was rescued by a region of DNA localized to chromosome III. This region contained an open reading frame of 579 nucleotides predicted to encode a M(r) 21 116 polypeptide. The upstream region of FRM2 contained a number of potential response elements which have previously been identified as important in regulating gene expression in response to glucose and certain fatty acids. Consistent with this observation, lacZ activity driven by FRM2 or frm2 promoters was induced two- to three-fold dependent upon the carbon and fatty acid source utilized. The properties of FRM2 suggest that it functions in the fatty acid signalling pathway and that it is itself regulated by fatty acids.


Assuntos
Ácidos Graxos/farmacologia , Genes Fúngicos , Mutação , Saccharomyces cerevisiae/genética , Transcrição Gênica/efeitos dos fármacos , Sequência de Bases , Clonagem Molecular , Dados de Sequência Molecular
18.
J Comp Neurol ; 353(1): 25-37, 1995 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-7714247

RESUMO

The spinal cord of the larval sea lamprey contains identified giant axons that readily regenerate following spinal transection. In this study, we used serial light and electron microscopy to analyze the early ultrastructural consequences of axotomy in the proximal stumps of these axons near the lesion site. Axotomy results in two types of striking ultrastructural changes: 1) changes associated with the degeneration of axoplasm and subsequent retraction of the cut axon from the lesion and 2) changes associated with the early stages of axonal regeneration. Degenerative changes include the disruption of mitochondria to form large vacuoles, the collapse of neurofilaments into closely packed masses (condensed filamentous cores; CFCs), and the appearance of amorphous electron-dense bodies (dense granular masses; DGMs). Events associated with regeneration include the disappearance of vacuoles, DGMs, and CFCs and the appearance of small, sprout-like projections from the axon stump. Thus, we show that degenerative and regenerative events can be clearly separated from one another in identified axons, unlike the situation in the central nervous systems of amniote vertebrates such as mammals.


Assuntos
Axônios/ultraestrutura , Citoesqueleto/ultraestrutura , Medula Espinal/ultraestrutura , Animais , Axônios/fisiologia , Citoesqueleto/fisiologia , Denervação , Imuno-Histoquímica , Lampreias , Larva , Microscopia Eletrônica , Regeneração Nervosa , Medula Espinal/fisiologia
19.
FEBS Lett ; 345(2-3): 147-50, 1994 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-8200447

RESUMO

A synthetic version of the human D4 (hD4) dopamine receptor was prepared. The G/C content of the natural gene was reduced by 14% without altering the amino acid composition of the corresponding protein sequence. HEK293 cells were transfected with the synthetic hD4 gene and stable clones resistant to G418 selected. The hD4 receptor expressed from the synthetic gene had identical pharmacological characteristics to the native hD4 receptor [(1991) Nature 350, 610-619; (1992) Nature 358, 149-152]. Functional studies with cells expressing the synthetic hD4 gene indicated negative coupling of this receptor to adenylate cyclase.


Assuntos
Receptores de Dopamina D2 , Receptores Dopaminérgicos/biossíntese , Receptores Dopaminérgicos/metabolismo , Adenilil Ciclases/metabolismo , Animais , Sequência de Bases , Ligação Competitiva , Linhagem Celular , Chlorocebus aethiops , Colforsina/farmacologia , DNA/química , DNA/metabolismo , Ergolinas/farmacologia , Genes Sintéticos , Humanos , Rim , Cinética , Dados de Sequência Molecular , Plasmídeos , Quimpirol , Receptores Dopaminérgicos/genética , Receptores de Dopamina D4 , Mapeamento por Restrição , Espiperona/metabolismo , Espiperona/farmacologia , Transfecção
20.
Gene ; 132(1): 67-73, 1993 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-8104848

RESUMO

The molecular cloning of DNA from the telomere of one chromosome of Cladosporium fulvum, a fungal pathogen of tomato, is described. The telomeric DNA exhibits tandem repeats of the sequence TTAGGG running 5' to 3' toward the chromosome end. At least 16 tracts of TTAGGG repeats are present in the C. fulvum genome. All such tracts are telomeric, and all chromosome-sized DNAs separated by pulsed-field gel electrophoresis exhibit the repeats. It is probable that tracts of these repeats are present at all chromosome termini. The cloned telomeric DNA exhibits 19 copies of the TTAGGG hexanucleotide motif, and evidence is presented indicating that all tracts of TTAGGG repeats are quite short. Telomere-linked restriction-fragment length polymorphisms between races of C. fulvum have been detected, and groupings based on these polymorphisms are consistent with those determined previously. Sub-telomeric DNA, centromere proximal to the cloned telomeric DNA, contains sequences reiterated many times in the genome; some of these repeats are at non-terminal locations. Partial sequence analysis indicates an absence of homology with the sub-telomeric DNA of other organisms.


Assuntos
Cladosporium/genética , DNA Fúngico , Telômero , Sequência de Bases , Cromossomos Fúngicos , Clonagem Molecular , Dados de Sequência Molecular , Polimorfismo de Fragmento de Restrição , Sequências Repetitivas de Ácido Nucleico
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