-
Journal of Biomedicine & Biotechnology 2011Amyloidosis is a group of disorders caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ... (Review)
Review
Amyloidosis is a group of disorders caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ function. Correct identification of the causal amyloid protein is absolutely crucial for clinical management in order to avoid misdiagnosis and inappropriate, potentially harmful treatment, to assess prognosis and to offer genetic counselling if relevant. Current diagnostic methods, including antibody-based amyloid typing, have limited ability to detect the full range of amyloid forming proteins. Recent investigations into proteomic identification of amyloid protein have shown promise. This paper will review the current state of the art in proteomic analysis of amyloidosis, discuss the suitability of techniques based on the properties of amyloidosis, and further suggest potential areas of development. Establishment of mass spectrometry aided amyloid typing procedures in the pathology laboratory will allow accurate amyloidosis diagnosis in a timely manner and greatly facilitate clinical management of the disease.
Topics: Amyloidogenic Proteins; Amyloidosis; Computational Biology; Humans; Mass Spectrometry; Peptide Mapping; Proteomics
PubMed: 22131817
DOI: 10.1155/2011/754109 -
The Journal of Experimental Medicine Sep 1922TWO MAIN FACTS WERE BROUGHT TO LIGHT BY THE PRECEDING EXPERIMENTS: first, the presence of growth-activating substances in the leucocytes; second, the setting free of...
TWO MAIN FACTS WERE BROUGHT TO LIGHT BY THE PRECEDING EXPERIMENTS: first, the presence of growth-activating substances in the leucocytes; second, the setting free of these substances in tissues and fluids where leucocytes accumulate. The existence of growth-promoting substances within the body of the leucocytes was to be expected. Leucocytes are embryonic cells and it is well known that embryonic tissues contain substances which stimulate cell proliferation. But the experiments gave a direct experimental proof of this fact. Then, during the whole life and even in extreme old age, there is a supply of growth-promoting substances within the organism which is potentially capable of restoring the activity of the resting cells. Embryonic tissue juice, as is known, can rejuvenate cells which have ceased to multiply in vitro and show evidences of degeneration. If the growth-activating substances of leucocytes can be transferred in vivo to tissue cells, they may play a similar rôle. Therefore, it was important to find out whether the growth-activating substances were set free either by the secretions of the living leucocytes or by diffusion from the body of the cells after they were injured or dead, and whether this phenomenon occurred actually in vivo. Indeed, the idea that leucocytes secrete substances necessary to normal physiological processes is by no means new. Long ago, Ranvier described the lymph cells as mobile unicellular glands, and Renaut thought that their function was to bring to fixed cells the necessary food material. This rôle of the leucocytes was considered by him as absolutely essential. According to his theory, differentiated cells could not live in the absence of the lymph cells, which supply them with the substances required for their activity. The presence of such substances in the leucocytes was shown by our experiments and the growth-activating power acquired by inflamed connective tissue demonstrated that the leucocytes could actually bring these substances to the fixed cells. Under certain conditions, this property of the white cells of the blood may cause the resumption of the activity of tissues which are in a resting state. In the adult organism, the tissues have ceased to grow and the blood plasma has acquired marked inhibiting properties. But growth-promoting substances are still stored in leucocytes, glands, and muscle tissue. The leucocytes could supply fibroblasts or epithelial cells with the necessary food material if they were present where cell proliferation is needed. The existence of mechanisms causing leucocytes to invade tissues in need of repair is certain. The initiation of healing seems to depend on the coming of the leucocytes to the wounded tissue. When they are missing, as happens when the wound is protected from all external irritation, cicatrization is greatly delayed. On the contrary, when staphylococci, turpentine, and other irritants are applied at the surface of the wound, granulations appear after less than 48 hours. These irritants, although different in nature, have the common characteristic of determining an inflammation of the tissues and the migration of leucocytes from the vessels to the surface of the wound. Possibly the white cells bring the substances which adult tissues require in order to cicatrize or regenerate. They would have the function of storing away the growth-promoting substances characteristic of embryonic tissues, and bringing them to the regions of the organism where they are needed.
PubMed: 19868680
DOI: 10.1084/jem.36.4.385 -
Bulletin Du Cancer Sep 2020Sickle cell disease is associated with severe complications and early mortality in adults. In children, hematopoietic stem cell transplant from HLA-identical sibling can... (Review)
Review
Sickle cell disease is associated with severe complications and early mortality in adults. In children, hematopoietic stem cell transplant from HLA-identical sibling can stop the progression of the disease and leads to more than 95% long-term free survival without sickle cell disease. The aim of this workshop was to define indications and modalities of allogeneic hematopoietic stem cell transplant in children and adults with sickle cell disease. Patient and sibling HLA typing should be proposed, early in the course of the disease, when intensification therapies are required. Indications of transplant from HLA-identical sibling in children and adults are, cerebral vasculopathy, occurrence of vaso-occlusive events despite hydroxycarbamide, renal and hepatic diseases related to SCD, chronic anemia<7g/dL despite hydroxycarbamide, need to maintain transfusion programs longer than six months, and major transfusion difficulties related to red blood cell alloimmunization. In children with an HLA-identical sibling donor, we recommend a myeloablative conditioning regimen associating high dose busulfan, cyclophosphamide and ATG, considering the excellent results of this approach In patients over 15 years of age, we recommend the NIH approach consisting of a reduced intensity conditioning regimen by alemtuzumab, and 3Gy total body irradiation, followed by peripheral hematopoietic stem cells and post-transplant immunosuppression by sirolimus In the absence of HLA-identical sibling donor, there is no definitive data for preferring transplant from unrelated versus haplo-identical donors but we recommend to evaluate these approaches in prospective trials.
Topics: Adult; Anemia, Sickle Cell; Child; Hematopoietic Stem Cell Transplantation; Humans; Transplantation, Homologous
PubMed: 32921398
DOI: 10.1016/j.bulcan.2020.06.003 -
Data in Brief Sep 2016Male Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days and obtained data...
Dataset of liver proteins of eu- and hypothyroid rats affected in abundance by any of three factors: in vivo exposure to hexabromocyclododecane (HBCD), thyroid status, gender differences.
Male Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days and obtained data compared with a previous study in females, "Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1]. Specifically, proteomic investigation of liver protein patterns obtained by 2D-DIGE was performed and differences between animals groups recorded, based on the factors exposure, thyroid status and gender. All proteins with significantly changed abundance in any of these comparisons were identified by mass spectrometry. General, hormone and proteomic data of both the present and the previous studies are discussed in Miller et al. (2016) [1] and in "Gender specific differences in the liver proteome of rats exposed to hexabromocyclododecane (HBCD)" Miller et al. (2016) [2].
PubMed: 27579339
DOI: 10.1016/j.dib.2016.07.063 -
PloS One 2016Seasonal weight loss (SWL) is the most important limitation to animal production in the Tropical and Mediterranean regions, conditioning producer's incomes and the...
Seasonal weight loss (SWL) is the most important limitation to animal production in the Tropical and Mediterranean regions, conditioning producer's incomes and the nutritional status of rural communities. It is of importance to produce strategies to oppose adverse effects of SWL. Breeds that have evolved in harsh climates have acquired tolerance to SWL through selection. Most of the factors determining such ability are related to changes in biochemical pathways as affected by SWL. In this study, a gel based proteomics strategy (BN: Blue-Native Page and 2DE: Two-dimensional gel electrophoresis) was used to characterize the mitochondrial proteome of the secretory tissue of the goat mammary gland. In addition, we have conducted an investigation of the effects of weight loss in two goat breeds with different levels of adaptation to nutritional stress: Majorera (tolerant) and Palmera (susceptible). The study used Majorera and Palmera dairy goats, divided in 4 sets, 2 for each breed: underfed group fed on wheat straw (restricted diet, so their body weight would be 15-20% reduced by the end of experiment), and a control group fed with an energy-balanced diet. At the end of the experimental period (22 days), mammary gland biopsies were obtained for all experimental groups. The proteomic analysis of the mitochondria enabled the resolution of a total of 277 proteins, and 148 (53%) were identified by MALDI-TOF/TOF mass spectrometry. Some of the proteins were identified as subunits of the glutamate dehydrogenase complex and the respiratory complexes I, II, IV, V from mitochondria, as well as numerous other proteins with functions in: metabolism, development, localization, cellular organization and biogenesis, biological regulation, response to stimulus, among others, that were mapped in both BN and 2DE gels. The comparative proteomics analysis enabled the identification of several proteins: NADH-ubiquinone oxidoreductase 75 kDa subunit and lamin B1 mitochondrial (up-regulated in the Palmera breed), Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (up-regulated in the Majorera breed) and cytochrome b-c1 complex subunit 1, mitochondrial and Chain D, Bovine F1-C8 Sub-Complex Of Atp Synthase (down-regulated in the Majorera breed) as a consequence of weight loss.
Topics: Amino Acid Sequence; Animals; Cattle; Chromatography, High Pressure Liquid; Electron Transport Chain Complex Proteins; Electrophoresis, Gel, Two-Dimensional; Goats; Mammary Glands, Animal; Mitochondria; Mitochondrial Proteins; Molecular Sequence Data; Proteome; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry; Weight Loss
PubMed: 27031334
DOI: 10.1371/journal.pone.0151599 -
Archives of Cardiovascular Diseases Oct 2014The increasing number of obese patients eligible for cardiac surgery requires risks and benefits to be balanced in this population.
BACKGROUND
The increasing number of obese patients eligible for cardiac surgery requires risks and benefits to be balanced in this population.
AIMS
To study the results of cardiac surgery in severely obese patients (body mass index [BMI]≥35 kg/m2).
METHODS
In this retrospective study of 3564 patients undergoing elective cardiac surgery between 2004 and 2012, the population was divided into two groups: BMI 20-34.9 kg/m2 (n=3282) and BMI≥35 kg/m2 (n=282). Patients with BMI<20 kg/m2 were excluded due to the well-known increased mortality risk. The primary endpoint was 90-day mortality. A multivariable analysis was performed to identify prognostic factors.
RESULTS
Among our patients, 58.2% and 27.7% underwent isolated coronary or valvular surgery, respectively; 9.7% had combined valvular and coronary surgery and 4.4% had other procedures. Severely obese patients were younger: 62.5±9.3 years vs 67.8±10.7 years (P=0.0001). Overall 90-day mortality was 4.0%. Severe obesity did not influence postoperative mortality. In the multivariable analysis, the interaction between preoperative renal failure and severe obesity was an important mortality prognostic factor (hazard ratio: 11.17; P=0.03). Mediastinitis rates were similar between groups in non-diabetic patients; in diabetic patients, severe obesity was associated with higher mediastinitis rates (P=0.002). Superficial wound infections were higher in severely obese patients (P=0.003).
CONCLUSION
Elective cardiac surgery in severely obese patients was not associated with increased perioperative morbimortality, but had a higher superficial wound infection risk. Nevertheless, severe obesity itself should not be a contraindication to elective surgery.
Topics: Aged; Body Mass Index; Cardiac Surgical Procedures; Elective Surgical Procedures; Female; France; Heart Diseases; Humans; Incidence; Male; Middle Aged; Obesity, Morbid; Postoperative Complications; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 25240606
DOI: 10.1016/j.acvd.2014.06.004 -
Data in Brief Jun 2016Female Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days. Changes in...
Female Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days. Changes in protein patterns obtained by 2D-DIGE were evaluated, and different animal groups compared taking into account their exposure and thyroid status. Proteins significantly altered in abundance in any of these comparisons were identified by mass spectrometry. These data, together with hormone data of the animals, are discussed in "Hexa-bromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1].
PubMed: 26977443
DOI: 10.1016/j.dib.2016.02.047