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1.
Am J Epidemiol ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38751314

RESUMO

Most previous studies have found an elevated risk of endometrial cancer among women with polycystic ovary syndrome (PCOS). However, these have highly varying methods for ascertainment of PCOS diagnoses and have limitations such as few exposed women and short follow-up. In this cohort study, we investigated the association between PCOS and endometrial cancer among women born in Denmark between January 1, 1940, and December 31, 1993 (N=1,719,121). Data in this study, including PCOS and endometrial cancer diagnoses and covariates, were derived from nationwide registers. We used cox proportional hazard regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7862 endometrial cancer cases were identified during 23.7 years of follow-up (inter quartile range 37.7-61.9). We found an increased risk of endometrial cancer among women with PCOS compared with women without PCOS (HR: 3.02, 95% CI; 2.03-4.49). The risk was increased for premenopausal women (HR5.82, 95% CI: 3.64-9.30) whereas no marked association was seen for postmenopausal women. However, for postmenopausal women, results were limited by few cases and young age at end of follow-up. Mounting evidence of an increased risk for endometrial cancer among women with PCOS reinforces the need for prevention and early detection.

2.
Hum Reprod ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734928

RESUMO

STUDY QUESTION: Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation? SUMMARY ANSWER: Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies. WHAT IS KNOWN ALREADY: Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (PGT), and the length of time in in vitro culture. STUDY DESIGN, SIZE, DURATION: This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35-37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women's age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation. MAIN RESULTS AND THE ROLE OF CHANCE: The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13-23%, P < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18-28%, P < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13-40%, P < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2-26%, P = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27-45%, P < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4-19%, 0.005) lower in PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without PGT (Day 5 blastocysts). LIMITATIONS, REASONS FOR CAUTION: The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation. WIDER IMPLICATIONS OF THE FINDINGS: This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest. TRIAL REGISTRATION NUMBER: The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law.

3.
Blood ; 136(14): 1579-1589, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32777816

RESUMO

Red pulp macrophages (RPMs) of the spleen mediate turnover of billions of senescent erythrocytes per day. However, the molecular mechanisms involved in sequestration of senescent erythrocytes, their recognition, and their subsequent degradation by RPMs remain unclear. In this study, we provide evidence that the splenic environment is of substantial importance in facilitating erythrocyte turnover through induction of hemolysis. Upon isolating human spleen RPMs, we noted a substantial lack of macrophages that were in the process of phagocytosing intact erythrocytes. Detailed characterization of erythrocyte and macrophage subpopulations from human spleen tissue led to the identification of erythrocytes that are devoid of hemoglobin, so-called erythrocyte ghosts. By using in vivo imaging and transfusion experiments, we further confirmed that senescent erythrocytes that are retained in the spleen are subject to hemolysis. In addition, we showed that erythrocyte adhesion molecules, which are specifically activated on aged erythrocytes, cause senescent erythrocytes to interact with extracellular matrix proteins that are exposed within the splenic architecture. Such adhesion molecule-driven retention of senescent erythrocytes under low shear conditions was found to result in steady shrinkage of the cell and ultimately resulted in hemolysis. In contrast to intact senescent erythrocytes, the remnant erythrocyte ghost shells were prone to recognition and breakdown by RPMs. These data identify hemolysis as a key event in the turnover of senescent erythrocytes, which alters our current understanding of how erythrocyte degradation is regulated.


Assuntos
Eritrócitos/metabolismo , Hemólise , Baço/metabolismo , Baço/fisiopatologia , Animais , Biomarcadores , Envelhecimento Eritrocítico/efeitos dos fármacos , Deformação Eritrocítica , Membrana Eritrocítica , Transfusão de Eritrócitos , Eritrócitos/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica , Histocitoquímica , Humanos , Imunofenotipagem , Laminina/farmacologia , Macrófagos/metabolismo , Camundongos , Fagocitose
4.
Br J Anaesth ; 109(2): 191-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22710266

RESUMO

BACKGROUND: We aimed to investigate whether fluid therapy with a goal of near-maximal stroke volume (SV) guided by oesophageal Doppler (ED) monitoring result in a better outcome than that with a goal of maintaining bodyweight (BW) and zero fluid balance in patients undergoing colorectal surgery. METHODS: In a double-blinded clinical multicentre trial, 150 patients undergoing elective colorectal surgery were randomized to receive fluid therapy after either the goal of near-maximal SV guided by ED (Doppler, D group) or the goal of zero balance and normal BW (Zero balance, Z group). Stratification for laparoscopic and open surgery was performed. The postoperative fluid therapy was similar in the two groups. The primary endpoint was postoperative complications defined and divided into subgroups by protocol. Analysis was performed by intention-to-treat. The follow-up was 30 days. The trial had 85% power to show a difference between the groups. RESULTS: The number of patients undergoing laparoscopic or open surgery and the patient characteristics were similar between the groups. No significant differences between the groups were found for overall, major, minor, cardiopulmonary, or tissue-healing complications (P-values: 0.79; 0.62; 0.97; 0.48; and 0.48, respectively). One patient died in each group. No significant difference was found for the length of hospital stay [median (range) Z: 5.00 (1-61) vs D: 5.00 (2-41); P=0.206]. CONCLUSIONS: Goal-directed fluid therapy to near-maximal SV guided by ED adds no extra value to the fluid therapy using zero balance and normal BW in patients undergoing elective colorectal surgery.


Assuntos
Hidratação/métodos , Intestino Grosso/cirurgia , Cuidados Intraoperatórios/métodos , Volume Sistólico/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Ecocardiografia Transesofagiana/métodos , Feminino , Objetivos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Complicações Pós-Operatórias , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
5.
Int J Obes (Lond) ; 33(11): 1249-56, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19704410

RESUMO

OBJECTIVE: To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity. DESIGN: Cross-sectional study. SUBJECTS: A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR. RESULTS: Polycystic ovary syndrome (P<0.05) and obesity (P<0.05) were independently associated with increased expression of 11beta-HSD1 mRNA. The subgroups LP and OC had increased 11beta-HSD1 and 11beta-HSD2 mRNA expression compared with LC (P<0.05, P<0.05). There were no effects of PCOS or obesity on11beta-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11beta-HSD1, but neither 11beta-HSD2 nor H6PDH. CONCLUSION: Polycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11beta-HSD1.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Obesidade/enzimologia , Síndrome do Ovário Policístico/enzimologia , Gordura Subcutânea/enzimologia , Magreza/enzimologia , Absorciometria de Fóton , Adulto , Análise de Variância , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Resistência à Insulina/fisiologia
6.
J Clin Invest ; 67(3): 597-604, 1981 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7009645

RESUMO

The influence of insulin on unidirectional flux of glucose across the blood-brain barrier and on net uptake of glucose by the brain was investigated in seven fasting patients. The unidirectional extraction, E, of [14C]D-glucose was determined using 36Cl- as an intravascular reference, by the indicator dilution method. 0.4 U insulin/kg body wt was infused intravenously over 30 min while blood glucose was maintained constant by glucose infusion. Six determinations were made in each patient, two before, two during insulin infusion, and two after. In connection with each blood-brain barrier study, arterial and cerebral venous samples were taken for measurement of glucose, oxygen, insulin, K+, and phosphate. Cerebral blood flow (CBF) was measured in each patient. The main finding was an increased extraction of glucose from 14 to 21% and a highly significant increase in unidirectional flux (CBF X unidirectional extraction X arterial glucose concentration) from 0.46 to 0.66 mumol/g X min during insulin infusion (plasma insulin approximately 1,500 microU/ml). The net brain uptake of glucose (CBF X arterio-venous difference for glucose) as unaltered during the investigation period of 45 min, which is too short a time for insulin to penetrate the barrier. It follows that the backflux of glucose from the brain was increased during insulin application. The effect of insulin might be a speeding up of the glucose carrier in analogy to heart muscle.


Assuntos
Barreira Hematoencefálica , Encéfalo/metabolismo , Glucose/metabolismo , Insulina/farmacologia , Transporte Biológico/efeitos dos fármacos , Glicemia/metabolismo , Humanos , Consumo de Oxigênio/efeitos dos fármacos , Estimulação Química
7.
Cancer Res ; 45(3): 1159-62, 1985 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3838262

RESUMO

A human mesothelioma was heterotransplanted to nude mice, and the urinary excretions of hypoxanthine, xanthine, pseudouridine, orotic acid, 7-methylguanine, and 1-methylhypoxanthine have been followed before and after the tumor transplantation. The compounds were measured by means of isotachophoresis, which has been found a rapid and precise method. The tumor reached maximum size within 30 days, and at this time a significantly increased excretion of pseudouridine and hypoxanthine was observed. Tumor growth was stopped by chemotherapy (vincristine, cyclophosphamide, prednisolone, and Adriamycin), and corresponding to this, a decrease occurred in both pseudouridine and hypoxanthine excretion to normal values.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Hipoxantinas/urina , Mesotelioma/urina , Pseudouridina/urina , Uridina/análogos & derivados , Animais , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Hipoxantina , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Prednisolona/uso terapêutico , Vincristina/uso terapêutico
8.
Diabetes ; 32 Suppl 2: 83-7, 1983 May.
Artigo em Inglês | MEDLINE | ID: mdl-6400672

RESUMO

Our longitudinal study of urinary albumin excretion rate in long-term insulin-dependent diabetics without proteinuria (negative albustix) suggests that early detection of patients at high and low risk of developing persistent proteinuria, i.e., diabetic nephropathy, is possible by using a sensitive method for albumin determination. Our prospective studies in young insulin-dependent diabetics with diabetic nephropathy show that the rate of decline in glomerular filtration rate (GFR) varies considerably, with a mean of 0.75 ml/min/mo and a range from 0.1 to 1.50 ml/min/mo, and that an increase in arterial blood pressure to a hypertensive level is an early feature; 43% of the patients had diastolic blood pressure greater than 100 mm Hg. Early and aggressive antihypertensive treatment reduces both albuminuria and the rate of decline in GFR in young patients with diabetic nephropathy.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Hipertensão/tratamento farmacológico , Adulto , Albuminúria , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Rim/fisiopatologia , Estudos Longitudinais , Masculino , Proteinúria
9.
Genetics ; 125(3): 505-14, 1990 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2379823

RESUMO

The ges-1 gene of the nematode Caenorhabditis elegans codes for a nonspecific carboxylesterase that is expressed only in the intestinal lineage. This esterase has turned out to be a convenient biochemical marker for lineage-specific differentiation. In the present paper, we describe the production of several C. elegans strains that lack detectable activity of the ges-1 esterase. To isolate these ges-1 null strains, we first produced a strain of hermaphrodites in which the wild-type copy of the ges-1 gene was stably balanced over a previously isolated isoelectric focusing allele, ges-1(ca6); this parental strain was then mutagenized with EMS and isoelectric focusing gels were used to identify progeny populations that lacked either ges-1(+) or ges-1(ca6) esterase activity. This method is a straightforward and general approach to obtaining null mutations in any gene that has a biochemical or immunological assay. The ges-1 gene is not essential to worm survival, development or reproduction. Furthermore, lack of the ges-1 product has no obvious effect on the ability of worms (containing either normal or greatly reduced levels of acetylcholinesterases) to survive exposure to esterase inhibitors. The ges-1 gene product provides roughly half of the total esterase activity measured in crude extracts of L1 larvae or mixed worm populations. However, histochemical staining of individual ges-1(0) embryos shows that the ges-1 esterase is the first and essentially the only esterase to be produced during embryonic development, from the midproliferation phase up to at least the twofold stage of morphogenesis. These ges-1(0) strains now allow us to investigate the developmental control of the ges-1 gene by DNA-mediated transformation, in which the ges-1 gene acts as its own reporter.


Assuntos
Caenorhabditis/genética , Esterases/genética , Mutação , Animais , Northern Blotting , Caenorhabditis/enzimologia , Caenorhabditis/crescimento & desenvolvimento , Mapeamento Cromossômico , Cruzamentos Genéticos , Esterases/metabolismo , Feminino , Genes , Intestinos/enzimologia , Masculino
10.
Diabetes Care ; 3(6): 659-62, 1980.
Artigo em Inglês | MEDLINE | ID: mdl-7004812

RESUMO

The effect of guar gum on insulin requirements, mean blood glucose (MBG), and mean amplitude of glycemic excursions (MAGE) was investigated in seven insulin-dependent diabetic subjects without endogenous insulin secretion by means of an artificial pancreas (Biostator). Fifty-four hours after the withdrawal of long-acting insulin, the patients were controlled for two consecutive days by the artificial pancreas, under standardized identical conditions, except for the ingestion of guar gum before meals on the second day. The 24-h insulin requirements were significantly reduced by 12.4% on the day with guar gum (P < 0.05). No statistically significant effects were observed on MGG and MAGE.


Assuntos
Diabetes Mellitus/terapia , Galactanos/farmacologia , Insulina/administração & dosagem , Mananas/farmacologia , Polissacarídeos/farmacologia , Adolescente , Adulto , Órgãos Artificiais , Glicemia , Diabetes Mellitus/tratamento farmacológico , Humanos , Injeções Subcutâneas/métodos , Masculino , Pessoa de Meia-Idade , Pâncreas , Gomas Vegetais
11.
Diabetes Care ; 4(4): 459-63, 1981.
Artigo em Inglês | MEDLINE | ID: mdl-7049630

RESUMO

Urinary albumin excretion rate (radial immunodiffusion), glomerular filtration rate (GFR) (single-shot 51Cr-EDTA technique), and arterial blood pressure (BP) were measured in 12 juvenile-onset, insulin-dependent diabetic patients with persistent proteinuria (greater than 0.5 g/day) due to diabetic nephropathy. Mean age of the patients was 30 yr. All patients had a diastolic blood pressure greater than or equal to 95 mm Hg. Metoprolol, hydralazine, and furosemide or thiazide were used as antihypertensives. During the 12-mo treatment period, BP decreased from 151/104 to 133/85 mm Hg (P less than 0.001), the urinary albumin excretion rate diminished from 1447 to 613 micrograms/min (P less than 0.005), and GFR declined from 96 to 89 ml/in/1.73 m2 (P less than 0.01). A linear relationship between mean blood pressure and the logarithm of the albuminuria was found (r = 0.48, P less than 0.01). Arterial hypertension is an early feature of diabetic nephropathy in young insulin-dependent patients. Early and aggressive treatment of that condition decreases albuminuria, probably due to reduced intraglomerular filtration pressure. Whether sustained reduction in arterial blood pressure to near-normal levels during several years also reduces the rate of decline in GFR in diabetic nephropathy remains to be established.


Assuntos
Albuminúria , Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 1/urina , Nefropatias Diabéticas/urina , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade
12.
Int J Oral Maxillofac Surg ; 44(8): 1052-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25835759

RESUMO

Aim was to evaluate effect of unilateral distraction osteogenesis (DO) on mandibular morphology in rabbits with antigen-induced arthritis in the temporomandibular joint (TMJ). Forty 8-week-old rabbits were divided into four groups. In groups A,C, arthritis was induced in the right TMJ. Groups A,B underwent DO. Group D served as control group. Cephalometric analysis of mandibular angle, mandibular ramus height, mandibular collum height, and total posterior mandibular height was done on CT-scans preoperatively (T0), after distraction (T1), and at euthanasia (T2). Two-factor ANOVA evaluated the effect of DO and antigen-induced arthritis. No effect of DO or arthritis was observed on mandibular angle or mandibular collum height. For T0-T1, DO increased mandibular ramus height 12.3% (95% CI 5.2-19.4%) in group B (P=0.001) and total posterior mandibular height 6.2% (95% CI 0.3-12.1%) in group A (P=0.04) and 10.0% (95% CI 4.3-15.7%) in group B (P=0.001). For T1-T2, no significant changes occurred in arthritic rabbits (group A). In conclusion, DO increased total posterior mandibular height in rabbits with arthritis. Postoperatively, no significant effect of DO was observed in rabbits with arthritis. Mandibular DO could be a viable treatment modality in patients with TMJ-arthritis.


Assuntos
Osteoartrite/cirurgia , Osteogênese por Distração , Transtornos da Articulação Temporomandibular/cirurgia , Animais , Osteoartrite/diagnóstico por imagem , Coelhos , Interpretação de Imagem Radiográfica Assistida por Computador , Distribuição Aleatória , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Tomografia Computadorizada por Raios X
13.
Gene ; 189(2): 175-81, 1997 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-9168124

RESUMO

Uracil-DNA glycosylase (UDG) is the enzyme responsible for the first step in the base-excision repair pathway that specifically removes uracil from DNA. Here we report the isolation of the cDNA and genomic clones for the mouse uracil-DNA glycosylase gene (ung) homologous to the major placental uracil-DNA glycosylase gene (UNG) of humans. The complete characterization of the genomic organization of the mouse uracil-DNA glycosylase gene shows that the entire mRNA coding region for the 1.83-kb cDNA of the mouse ung gene is contained in an 8.2-kb SstI genomic fragment which includes six exons and five introns. The cDNA encodes a predicted uracil-DNA glycosylase (UDG) protein of 295 amino acids (33 kDa) that is highly similar to a group of UDGs that have been isolated from a wide variety of organisms. The mouse ung gene has been mapped to mouse chromosome 5 using fluorescence in situ hybridization (FISH).


Assuntos
Mapeamento Cromossômico , DNA Glicosilases , DNA Complementar/isolamento & purificação , Genes , N-Glicosil Hidrolases/genética , N-Glicosil Hidrolases/isolamento & purificação , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Éxons , Humanos , Hibridização in Situ Fluorescente , Íntrons , Camundongos , Dados de Sequência Molecular , N-Glicosil Hidrolases/química , Ligação Proteica/genética , Sequências Repetitivas de Ácido Nucleico , Análise de Sequência de DNA , Transcrição Gênica , Uracila-DNA Glicosidase
14.
J Immunol Methods ; 23(1-2): 127-35, 1978.
Artigo em Inglês | MEDLINE | ID: mdl-29929

RESUMO

A simple immunoprecipitation--dissociation technique for large scale purification of antibodies is described, which comprises selective denaturation of the antigen and recovery of the antibody fraction by exclusion chromatography at low pH. Its use is illustrated by the purification of antibodies to pregnancy zone protein. A purification factor of about 60 was achieved. An antigen consumption electroimmunoassay was also developed which permits quantitative determination of the antigen binding activity of antibodies with a given specificity. The methods have general application.


Assuntos
Anticorpos/isolamento & purificação , Proteínas Sanguíneas/imunologia , Eletroquímica , Feminino , Humanos , Concentração de Íons de Hidrogênio , Imunoensaio , Técnicas de Imunoadsorção , Gravidez , Terceiro Trimestre da Gravidez
15.
J Endocrinol ; 148(3): 517-22, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8778230

RESUMO

To ascertain whether repeated hypoxic stress would alter the response of the adrenal cortex to adrenocorticotropic hormone (ACTH), by premature activation of the hypothalamic-pituitary-adrenal axis, we studied fetal sheep subjected to daily reduction of arterial oxygen content by embolization of the fetal placental circulation with 15 microns microspheres for 8 days from about day 124 of gestation (term approximately 147 days) and sham-embolized controls. Starting before the final embolization (or sham-embolization) on day 8, and continuing for 24 h, the fetus was given an intravenous infusion of ACTH1-24 (0.5 microgram/h) or vehicle. Fetal and maternal blood samples were taken for determination of immunoreactive cortisol, and regional adrenal and fetal placental blood flows were measured by the microsphere technique at three time points: 1 h before infusion, 3 h after the start of the infusion (1 h after embolization), and after 24 h of infusion. Prior to infusion of ACTH or vehicle, fetal placental blood flow was lower in microsphere-embolized fetuses than in sham-embolized controls (199 +/ 15 vs 292 +/- 25 ml/min per 100 g tissue; mean +/- S.E.; P<0.01). However, plasma cortisol and adrenal cortical blood flow did not differ between embolized fetuses and controls. Adrenal vascular responses to the 24-h infusion of ACTH were similar in embolized and sham-embolized fetuses. Adrenal cortical blood flow increased 3-fold (P<0.05) due to decreased vascular resistance (P<0.01), with no change in adrenal medullary blood flow. Thus, while daily embolization of the fetal placental circulation caused a sustained decrease in cotyledonary blood flow, no evidence of altered responsiveness of the adrenal cortex to ACTH was found in these experiments.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Hormônio Adrenocorticotrópico/farmacologia , Hipóxia Fetal/fisiopatologia , Glândulas Suprarrenais/embriologia , Animais , Feminino , Sangue Fetal/química , Hidrocortisona/sangue , Microesferas , Placenta/irrigação sanguínea , Gravidez , Fluxo Sanguíneo Regional/efeitos dos fármacos , Ovinos
16.
Placenta ; 5(2): 175-82, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6483814

RESUMO

Intravenous injection of small amounts of monospecific rabbit IgG against pregnancy-associated murine protein I (PAMP-I) induced abortion in mice where there was a histocompatibility difference between mother and fetuses. No abortion could be induced in inbred mice by a similar treatment. The maternal serum level was found to be higher in inbred than in outbred mice. The abortive dose of antibodies did not influence the serum levels of PAMP-I. Histological examination of uterine, placental and liver tissue showed only morphological changes in the placental tissue of mice which aborted due to the treatment with anti-PAMP-I antibodies.


Assuntos
Proteínas da Gravidez/imunologia , Aborto Espontâneo/etiologia , Animais , Anticorpos/administração & dosagem , Feminino , Histocompatibilidade , Camundongos , Camundongos Endogâmicos , Placenta/patologia , Gravidez , Proteínas da Gravidez/antagonistas & inibidores , Proteínas da Gravidez/sangue
17.
Placenta ; 4(3): 291-4, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6194524

RESUMO

Three pregnancy-associated proteins, pregnancy-specific beta1-glycoprotein (SP-I), pregnancy-associated plasma protein A(PAPP-A), and placental lactogen (hPL) were examined by charge-shift immunoelectrophoresis. PAPP-A and hPL exhibited hydrophilic properties whereas SP-I was amphiphilic. These observations suggest that SP-I is a cell membrane protein.


Assuntos
Placenta/análise , Lactogênio Placentário/análise , Proteínas da Gravidez/análise , Proteína Plasmática A Associada à Gravidez/análise , Glicoproteínas beta 1 Específicas da Gravidez/análise , Detergentes , Feminino , Humanos , Imunoeletroforese Bidimensional/métodos , Placenta/imunologia , Gravidez
18.
APMIS ; 100(2): 154-8, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1554490

RESUMO

Major surgical procedures awake an endocrine metabolic stress response characterized by increased secretion of cortisol and lymphopenia. The purpose of this study was to clarify to which tissues the lymphocytes are redistributed after cortisol administration. Lymphocytes were isolated from 16 rabbits, labelled with indium-111-tropolone and reinjected into the rabbits. Eight of the rabbits received 25 mg of cortisol intravenously (group I), while eight received isotonic saline (group II). The redistribution of lymphocytes was imaged with a gamma camera and calculated by a connected computer before and two, four, and seven h after cortisol or saline administration. The radioactivity of cells from the spleen and bone marrow decreased to 84% and 56% of the initial values seven h after cortisol administration. The activity of the lymphatic tissues increased to 121% of initial values. It is concluded that during cortisol-induced lymphopenia the lymphocytes are redistributed from peripheral blood, spleen and bone marrow to lymphatic tissue.


Assuntos
Hidrocortisona/farmacologia , Linfócitos/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Hidrocortisona/administração & dosagem , Radioisótopos de Índio , Injeções Intravenosas , Linfócitos/fisiologia , Coelhos
19.
APMIS ; 100(7): 593-7, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1642846

RESUMO

Adrenergic activation is known to occur in sepsis and after major surgery or trauma. An elevated serum concentration of adrenaline is followed by lymphocytosis in peripheral blood even in splenectomized patients. The purpose of the present study was to clarify the redistribution of lymphocytes in the tissues during adrenaline infusion. Lymphocytes were isolated from 24 rabbits, labelled with indium-111-tropolone and reinjected into the rabbits. The next day the rabbits were anaesthetized. Eight rabbits received 3 micrograms of adrenaline i.v. followed by 0.2 micrograms/min, eight received 300 micrograms of adrenaline i.v. followed by 20 micrograms/min, while eight received a saline infusion and served as a control group. The activity of labelled cells was imaged with a gamma camera and computer before, during and after adrenaline infusion. The activity of the spleen decreased to 90% and 94% of initial values during low and high doses of adrenaline. The activity of the bone marrow decreased to 91% and 96%, respectively, while the activity of the heart/lung and the liver increased to 107% and 106% with the high dose of adrenaline. In peripheral blood the lymphocytes increased 10%. It is concluded that lymphocytes are redistributed from spleen and bone marrow to peripheral blood, lungs and liver during adrenaline infusion in this animal model.


Assuntos
Epinefrina/farmacologia , Linfócitos/efeitos dos fármacos , Linfocitose/induzido quimicamente , Animais , Medula Óssea/diagnóstico por imagem , Medula Óssea/efeitos dos fármacos , Feminino , Injeções Intravenosas , Linfócitos/diagnóstico por imagem , Linfocitose/diagnóstico por imagem , Masculino , Coelhos , Cintilografia , Baço/diagnóstico por imagem , Baço/efeitos dos fármacos
20.
J Reprod Immunol ; 3(6): 341-9, 1981 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6977028

RESUMO

Immunological cross-reaction between human pregnancy zone protein (PZP, SP-3, alpha 2-PAG) and pregnancy-associated murine protein-1 (PAMP-1) was demonstrated by countercurrent line immunoelectrophoresis using antibodies against the proteins raised in hens. The levels of PZP and PAMP-1 were measured during pregnancy and found to be very similar in the first half of pregnancy. Both proteins were found to be heterogeneous and separable according to surface properties. It is suggested that the murine PAMP-1 can be used to study the physiology of human PZP.


Assuntos
Proteínas da Gravidez/imunologia , Animais , Antígenos Heterófilos/imunologia , Fenômenos Químicos , Físico-Química , Galinhas , Contraimunoeletroforese , Reações Cruzadas , Feminino , Cabras , Humanos , Soros Imunes/farmacologia , Imunoeletroforese Bidimensional , Camundongos , Gravidez , Proteínas da Gravidez/sangue , Coelhos , Ácidos Siálicos
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