The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies
suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane
protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in
the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n=72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant
difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients and controls. These results suggest a possible intervention of presenilin-1 in the
pathogenesis of amyotrophic lateral sclerosis.
Received: 14 February 2000 / Received in revised form: 20 April 2000 / Accepted: 4 June 2000 相似文献
Haemoglobinopathies are the most common hereditary disorders in Greece. Although there is a successful national prevention program, established 35 years ago, there is lack of an official registry and collection of epidemiological data for haemoglobinopathies. This paper reports the results of the first National Registry for Haemoglobinopathies in Greece (NRHG), recently organized by the Greek Society of Haematology. NRHG records all patients affected by thalassaemia major (TM), thalassaemia intermedia (TI), "H" Haemoglobinopathy (HH) and sickle cell disease (SCD). Moreover, data about the annual rate of new affected births along with deaths, between 2000 and 2010, are reported. A total of 4,506 patients are registered all over the country while the number of affected newborns was significantly decreased during the last 3 years. Main causes for still having affected births are: (1) lack of medical care due to financial reasons or low educational level; (2) unawareness of time limitations for prenatal diagnosis (PD); due either to obstetricians' malpractice or to delayed demand of medical care of couples at risk; and (3) religious, social or bioethical reasons. Cardiac and liver disorders consist main causes for deaths while life expectancy of patients lengthened after 2005 (p < 0.01). The NRHG of patients affected by haemoglobinopathies in Greece provides useful data about the haemoglobinopathies in the Greek population and confirms the efficacy of the National Thalassaemia Prevention Program on impressively decreasing the incidence of TM and sickle cell syndromes. 相似文献
Scientific data regarding intravenous iron supplementation in peritoneal dialysis (PD) patients are scarce. In attempting to administer the minimum monthly IV iron dose that could improve erythropoiesis, we wanted to assess the safety and efficacy of monthly maintenance intravenous administration of 100 mg iron sucrose in PD patients.
Methods
In a 9-month prospective study, all clinically stable PD patients received intravenously 200 mg of iron sucrose as a loading dose, followed by monthly doses of 100 mg for five consecutive months. Levels of hemoglobin (Hb), ferritin, transferrin saturation (TSAT), reticulocyte hemoglobin content (CHr) and C-reactive protein (CRP) were measured before each administration and 3 months after the last iron infusion. Also, doses of concurrent erythropoietin administration were recorded.
Results
Eighteen patients were eligible for the study. Mean levels of Hb and ferritin increased significantly (from 10.0 to 10.9 mg/dL, p?=?0.01 and from 143 to 260 ng/mL, p?=?0.005), as well as the increase in TSAT levels approached borderline significance (from 26.2 to 33.1%, p?=?0.07). During the 6 months of iron administration, the erythropoietin dose was reduced in five patients and discontinued in one. During the 3 months following the last iron infusion, three of them again raised the erythropoietin dose to previous levels. None of the patients experienced any side effects related to IV iron administration.
Conclusions
A monthly maintenance intravenous dose of 100 mg iron sucrose may be a practical, effective, and safe in the short term, treatment of anemia in PD patients resulting in improved hemoglobin levels, iron indices, and erythropoietin response.
The incidence of Human-papillomavirus-positive (HPV+) tonsillar and base-of-tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) is increasing epidemically, but they have better prognosis than equivalent HPV-negative (HPV−) cancers, with roughly 80% vs. 50% 3-year disease-free survival, respectively. The majority of HPV+ TSCC and BOTSCC patients therefore most likely do not require the intensified chemoradiotherapy given today to head and neck cancer patients and would with de-escalated therapy avoid several severe side effects. Moreover, for those with poor prognosis, survival has not improved, so better-tailored alternatives are urgently needed. In line with refined personalized medicine, recent studies have focused on identifying predictive markers and driver cancer genes useful for better stratifying patient treatment as well as for targeted therapy. This review presents some of these endeavors and briefly describes some recent experimental progress and some clinical trials with targeted therapy. 相似文献
Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets. Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations. Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4+ T and B cells, as well as granulocytes. CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity. The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8+ regulatory T cells, the highest levels of CD56+CD16− NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response. A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence. 相似文献
Macrophages, the central mediators of innate immune responses, being in the first-line of defense, they have to readily respond to pathogenic or tissue damage signals to initiate the inflammatory cascade. Such rapid responses require energy to support orchestrated production of pro-inflammatory mediators and activation of phagocytosis. Being a cell type that is present in diverse environments and conditions, macrophages have to adapt to different nutritional resources. Thus, macrophages have developed plasticity and are capable of utilizing energy at both normoxic and hypoxic conditions and in the presence of varying concentrations of glucose or other nutrients. Such adaptation is reflected on changes in signaling pathways that modulate responses, accounting for the different activation phenotypes observed. Macrophage metabolism has been tightly associated with distinct activation phenotypes within the range of M1-like and M2-like types. In the context of diseases, systemic changes also affect macrophage metabolism, as in diabetes and insulin resistance, which results in altered metabolism and distinct activation phenotypes in the adipose tissue or in the periphery. In the context of solid tumors, tumor-associated macrophages adapt in the hypoxic environment, which results in metabolic changes that are reflected on an activation phenotype that supports tumor growth. Coordination of environmental and pathogenic signals determines macrophage metabolism, which in turn shapes the type and magnitude of the response. Therefore, modulating macrophage metabolism provides a potential therapeutic approach for inflammatory diseases and cancer. 相似文献