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Isoelectric focusing studies of transferrin and haptoglobin subtypes in an Australian white population.

This investigation presents the results of Hp and Tf subtyping of sera from 307 Australian whites by means of isoelectric focusing. Five Hp alleles were detected, these being Hp1F = 0.168, Hp1S = 0.235, Hp2FF = 0.003, Hp2FS = 0.561 and Hp2SS = 0.033. In the Tf system six alleles were found, TfC1 = 0.761, TfC2 = 0.176, TfC3 = 0.054, TfC6 = 0.002, TfB = 0.006 and TfD = 0.002. The usefulness of IEF together with modifications was highlighted for differentiating Tf and Hp subtypes; in particular, the absence of Hp2FF and Hp2SS in some earlier studies could be related to the technique used. The implication of the simultaneous presence of B and D transferrin variants in Caucasian populations is discussed.

Alleles↗

A new cathodal Gc variant in Australia.

A new cathodal Gc variant and a known rare variant were found in a study of 307 Australian caucasian blood donors, each with a gene frequency of 0.28%. The frequencies of the other alleles were 0.161 (Gc1F), 0.557 (Gc1S) and 0.279 (Gc2), and were comparable with those of two earlier surveys.

Australia↗

Serum cholinesterase polymorphism in France: an epidemiological survey of the deficient alleles detected by an automated micro-method.

The polymorphism of the serum cholinesterase CHE 1 was determined using an automated micro-method. The procedure developed represents an improvement of the manual method and enabled us to study more than 2400 samples obtained in 15 different geographical areas in France. Four alleles were detected: CHE1* U, A, S and F. An exceptionally high frequency of an atypical variant (CHE1*A) was observed in the central part of France (Cevennes, Limousin and Dauphiné). The populations belonging to these areas are at particular risk in case of anaesthesia.

Adult↗

The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients: effects of supplementation with selenium or beta-carotene.

To investigate the effects of selenium or beta-carotene supplementation in human immunodeficiency virus (HIV)-infected patients, who are known to have deficiencies of selenium and vitamin A, we evaluated the blood enzymatic antioxidant system, including superoxide dismutase (SOD), selenodependent glutathione peroxidase (GPX), and catalase (Cat); glutathione (GSH) status; and plasma selenium concentration. The placebo group consisted of 18 HIV-infected patients with no supplementation, the selenium group was composed of 14 patients receiving oral selenium treatment, and the beta-carotene group comprised 13 patients receiving oral beta-carotene supplementation. All groups were studied for 1 y. At the beginning of the study, a significantly higher SOD activity (P < 0.001) was observed in all HIV-infected patients compared with uninfected control subjects, and GPX activity at baseline was higher in the placebo (P < 0.004) and selenium (P < 0.014) groups than in the control subjects. These higher enzyme activities could be related to an increased synthesis of these enzymes in erythrocyte precursors under oxidative stress. Moreover, we observed significantly lower GSH values in all HIV-infected patients than in control subjects at the beginning of the study (P < 0.001). After selenium or beta-carotene supplementation, no significant difference was observed for SOD activity compared with baseline. On the contrary, GPX activity increased significantly after selenium treatment (P < 0.04 between 3 and 6 mo), whereas a slight increase was found after beta-carotene treatment. Similarly, a significant increase in GSH values was observed at 12 mo compared with baseline both after selenium supplementation (P < 0.001) and beta-carotene supplementation (P < 0.01). Because GPX and GSH play an important role in the natural enzymatic defense system in detoxifying hydrogen peroxide in water, selenium supplementation could be of great interest in protecting cells against oxidative stress. The lower efficiency of beta-carotene could be attributed to the seriousness of the pathology at the time of recruitment into the beta-carotene group.

Acquired Immunodeficiency Syndrome↗

Autologous stem cell transplantation for primary refractory Hodgkin's disease: results and clinical variables affecting outcome.

BACKGROUND: Patients with primary refractory Hodgkin's disease (PR-HD) have a dismal prognosis when treated with conventional salvage chemotherapy. We analyzed time to treatment failure (TTF), overall survival (OS) and clinical variables influencing the outcome in patients undergoing autologous stem cell transplantation (ASCT) for PR-HD and reported to the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO). PATIENTS AND METHODS: Sixty-two patients, 41 males and 21 females with a median age of 27 years (range 13-55) were analyzed. Forty-two patients (68%) had advanced stage at diagnosis, 47 (76%) presented with B symptoms and 29 (47%) with a bulky mediastinal mass. Seventy-five percent of the patients had received more than one line of therapy before ASCT. Thirty-three patients received bone marrow as a source of hematopoietic progenitors, and 29 peripheral blood. Six patients were conditioned with high-dose chemotherapy plus total-body irradiation and 56 received chemotherapy-based protocols. RESULTS: One-year transplantation-related mortality was 14% [95% confidence interval (CI) 6% to 23%]. Response rate at 3 months after ASCT was 52% [complete remission in 21 patients (34%), partial remission in 11 patients (18%)]. Actuarial 5-year TTF and OS were 15% (95% CI 5% to 24%) and 26% (95% CI 13% to 39%), respectively. The presence of B symptoms at ASCT was the only adverse prognostic factor significantly influencing TTF [relative risk (RR) 1.75, 95% CI 0.92-3.35, P = 0.08]. The presence of B symptoms at diagnosis (RR 2.08, 95% CI 0.90-4.79, P = 0.08), MOPP-like regimens as first-line therapy (RR 3.84, 95% CI 1.69-9.09, P = 0.001), bulky disease at ASCT (RR 2.79, 95% CI 0.29-6.03, P = 0.009) and two or more lines of therapy before ASCT (RR 2.24, 95% CI 0.95-5.27, P = 0.06) adversely influenced OS. CONCLUSIONS: In our experience, although overall results of ASCT in PR-HD patients are poor, one-quarter of the patients remain alive at 5 years. Despite this, other therapeutic strategies should be investigated in this group of patients to improve the outcome.

Adolescent↗

Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse.

PURPOSE: To analyse outcome and prognostic factors for overall survival (OS) and time to treatment failure (TTF) in 357 patients with Hodgkin's lymphoma (HL) undergoing an autologous stem cell transplantation (ASCT) after a first relapse and reported to the The Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GEL/TAMO) Cooperative Group. METHODS: Two hundred and twenty males and 137 females with a median age of 29 years were autografted in second remission (n=181), first sensitive relapse (n=148) and first resistant relapse (n=28). RESULTS: Five-year actuarial TTF and OS were of 49% +/- 3% and 57% +/- 3%. Advanced stage at diagnosis, complementary radiotherapy before ASCT, a short first complete response (CR) and detectable disease at ASCT adversely influenced TTF. Year of transplant < or =1995, bulky disease at diagnosis, a short first CR, detectable disease at ASCT and > or =1 extranodal areas involved at ASCT were adverse factors for OS. CONCLUSIONS: ASCT constitutes a therapeutic option for HL patients after a first relapse. Promising results are observed in patients with low tumour burden at diagnosis, autografted after a long CR and without detectable disease at ASCT. Innovative approaches should be pursued for patients with risk factors at relapse.

Adolescent↗

A unique pattern of hepatocyte proliferation in F344 rats following long-term exposures to low levels of a chemical mixture of groundwater contaminants.

Most exposures of humans to environmental agents involve mixtures of chemicals, rather than individual chemicals. Some chemicals can cause hepatocellular proliferation and act as neoplastic promoters. Little is known concerning hepatocellular proliferation caused by chemical mixtures such as those found in groundwater at hazardous waste sites. Therefore, a 6 month study was performed to investigate hepatocellular proliferation and histopathological changes in F344 rats after long-term, low-level exposure to a mixture of groundwater contaminants. The seven chemicals used are among the most frequently detected contaminants associated with hazardous waste sites; arsenic, benzene, chloroform, chromium, lead, phenol and trichloroethylene. Male F344 rats were exposed to this mixture, or submixtures of the organic or inorganic chemicals, via drinking water for 6 months. The study design included a time-course experiment (i.e. 3 and 10 days and 1, 3 and 6 months) and a dose-response experiment. Hepatocellular proliferation studies were performed by subcutaneously implanting osmotic mini-pumps to continuously deliver 5-bromo-2'-deoxyuridine for 7 days, which labeled nuclei of proliferating cells. In all groups, there were no differences in weight gain, body weight, liver weight ratios or liver-associated plasma enzymes. Light microscopic evaluation revealed no lesions related to the treatments in any animals. However, significant increases in hepatocellular labeling were observed at the 3 and 10 day and 1 month exposure time points after treatment with the full mixture, as well as the organic or inorganic submixtures. Proliferating hepatocytes expressed a unique labeling pattern surrounding large hepatic veins (0.5-2.0 mm), but not central veins. This did not appear to be a regenerative response due to cytotoxic mechanisms, as assessed by the absence of increased plasma enzyme activity and the absence of hepatocellular lesions.

Animals↗

Patterns of chloroform-induced regenerative cell proliferation in BDF1 mice correlate with organ specificity and dose-response of tumor formation.

It has been reported that chloroform administered to BDF1 mice by inhalation for 2 years at concentrations of 5, 30 or 90 p.p.m. for 6 h/day, 5 days/week induced an increase in renal cell tumors in male but not female mice exposed to the doses of 30 and 90 p.p.m. A small increase in liver tumors was statistically significant in the female mice at 90 p.p.m. if the incidences of carcinomas and adenomas were combined. Because chloroform is not a DNA reactive mutagen, a 13-week time-course and dose-response study was conducted under conditions of the original bioassay to examine whether regenerative cell proliferation was an underlying mechanism of carcinogenesis. Mice were given bromodeoxyuridine via infusion during the last 3.5 days prior to necropsy to label cells in S-phase. Chloroform induced pathology and regenerative cell proliferation, measured as the labeling index (LI, percentage of cells in S-phase), were assessed microscopically and immunohistochemically. Male mice exposed to 30 and 90 p.p.m. exhibited a dose-dependent increase in regenerating tubules within the renal cortex and up to a 31-fold increase in LI. No renal lesions or increased LI were observed in females. Increased centrilobular to midzonal hepatocyte degeneration and vacuolation and a 7-fold increase over controls in the hepatocyte LI were observed in the female mice at 90 p.p.m. at 13 weeks. Males exhibited similar pathology, but the increase in LI was not sustained. The observed correlations between cytolethality and regenerative cell proliferation with tumor formation supports extensive evidence that chloroform induces cancer via a non-genotoxic-cytotoxic mode of action. A concentration of 5 p.p.m. is the no-observed-adverse-effect level for nephrotoxicity, cell proliferation and cancer. An appropriate safety factor applied to this value is a straightforward approach to cancer risk assessment that is consistent with the mode of action of chloroform.

Adenoma↗

Carcinoid heart disease: two cases of left heart involvement diagnosed by transthoracic and transoesophageal echocardiography.

We report two observations of significant left heart involvement in patients with the carcinoid syndrome assessed by transthoracic and transoesophageal echocardiography. Echocardiographic lesions of this kind have only been reported twice. In the present cases, there was mitral involvement with mitral regurgitation in one case and a mitro-aortic involvement with mitral and aortic regurgitation in the other. The mechanism of left heart lesions is unclear since in both cases no right-to-left cardiac shunt was present, as attested by colour Doppler and saline contrast transoesophageal echocardiography. The location of the primary tumour was unknown in one case and ileal in the other; no pulmonary metastasis was detected. The use of transoesophageal echocardiography might make it possible to detect left-sided cardiac lesions more frequently since they were found in anatomical series, in 30% of patients with carcinoid syndrome.

Aged↗

Ventricular arrhythmia revealing mitochondrial myopathy in a 69-year-old woman.

We report a case of mitochondrial myopathy (MM), assessed by histological and biochemical studies. This illness was diagnosed in a 69-year-old patient with myocardiopathy revealed by ventricular arrhythmias. The originality of this case lies in the patient's age, the mode of onset and the biochemical features (i.e. normal mitochondrial enzymatic complexes but very low respiration when using glutamate as a substrate).

Aged↗

Metabolic and hormonal changes induced by hypodermoclysis of glucose-saline solution in elderly patients.

BACKGROUND: Hypodermoclysis, i.e., infusion of solutions into the subcutaneous tissues, is an alternative method for hydration. The aim of our study was to describe the metabolic changes induced by hypodermoclysis of a glucose-saline solution in elderly patients. METHODS: Twelve experiments were conducted in a random cross-over study, intravenous infusion (IV) vs subcutaneous infusion (SC), in 6 hospitalized patients (81.5 +/- 9.8 years). The solution (1000 mL of 5% glucose solution containing 4 g NaCl) was infused over 6 hours in fasted patients who remained in bed. Blood was sampled at -10, 0, 30, 60, 90, 120, 180, 240, 300, and 360 minutes for measurement of plasma concentrations of glucose, insulin, free fatty acids, and beta-hydroxybutyrate. Plasma concentration of cortisol was analyzed only at T-10, T0, T180, and T360. RESULTS: The increases in glucose and insulin and the decrease in plasma concentrations of free fatty acids were lower with SC infusion than with IV infusion. The decrease in beta-hydroxybutyrate plasma concentration was lower at T300 with SC infusion than with IV infusion. The decrease in cortisol did not differ with the route. Plasma concentrations of all compounds were similar at T360. CONCLUSION: We conclude that hypodermoclysis of glucose-saline solution induced similar but smaller metabolic and hormonal changes than the IV infusion.

Aged↗

Increases in CD3+CD4-CD8- T lymphocytes in AIDS patients with disseminated Mycobacterium avium-intracellulare complex infection.

Human immunodeficiency virus type 1 (HIV-1)-infected persons frequently have increased numbers of T cells bearing the gamma delta T cell receptor for antigen (gamma delta TCR). HIV-1-seropositive patients with < 100 CD4+ cells/mm3 were selected and divided into 9 AIDS-defining illness groups. The percentages of CD4+, CD8+, or double-negative CD4-CD8- (DN) T cells (most of the latter expressing the gamma delta TCR) for 8 symptomatic groups were compared with those for a reference group of asymptomatic HIV-1-infected patients. DN T cells were increased only in patients with disseminated Mycobacterium avium-intracellulare complex (MAC) infection, toxoplasmosis, or Kaposi's sarcoma. Multivariate logistic regression analysis revealed that the percentage of DN T cells was a better predictor of MAC infection than was the percentage of CD4+T cells. The increased percentage of DN T cells might have important implications for the understanding of gamma delta T cell physiology and for the early diagnosis and management of MAC infections in AIDS patients.

AIDS-Related Opportunistic Infections↗