Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.     

Acetylcholine receptors in human thymic myoid cells in situ: an immunohistological study

Myoid cells were studied by double immunofluorescence in sections of thymus from 47 patients with myasthenia gravis and 15 control subjects, using polyclonal sheep anti-troponin T and monoclonal antibodies to troponin I, striated muscle myosin, and acetylcholine receptor (AChR). The myoid cells were rare and located mainly in the medulla, and most were clearly positive for AChR; labeling was similar with four individual monoclonal antibodies specific for extrajunctional AChR and five that also recognize endplate AChR. They were mostly keratin-positive and consistently HLA-DR-negative. In the myasthenia gravis samples, the myoid cells were similar but largely confined to medullary epithelial areas; AChR labeling was slightly weaker, but otherwise they did not differ noticeably from those of control subjects. A preliminary finding was of even rarer AChR-positive/HLA-DR-positive antigen-presenting (possibly) cells seen in 9 of 9 myasthenia gravis samples and in none of 9 control samples. Although myoid-cell AChR appears antigenically similar to extrajunctional muscle AChR, and must therefore express the epitopes that myasthenics' antibodies recognize, these cells do not appear to be foci of immunological stimulation in myasthenia gravis.     

A persisting secular trend for body measurements in Dutch children. The Oosterwolde 11 study

To investigate whether the secular trend for growth in Dutch children still exists, the Oosterwolde I study of 1980 was repeated in 1989. A persisting secular trend was visible for height while the z scores of body proportions show no change during the past 10 years, which suggests that there is no change in the timing of puberty.     

A retrospective study to determine the risk of red cell alloimmunization and transfusion during pregnancy

A retrospective review of post-delivery antibody records was performed at a teaching hospital and a community hospital to determine the frequency of new red cell alloantibody production and transfusion during pregnancy. If alloantibody was undetected at delivery, it was assumed that alloimmunization had not occurred. When antibody was detected, a chart review was performed to determine if the antibody was present at the beginning of the pregnancy or was newly produced during the pregnancy. A total of 17,568 pregnancies were reviewed. Antibody was detected at delivery in 948 (5.4%) cases, of which 89.5 percent (848/948) involved passive anti-D or clinically insignificant antibodies. The remaining 100 pregnancies involved clinically significant IgG antibodies. In 58 pregnancies, the antibody was detected in the first trimester, and in 42, new antibody production occurred during the pregnancy. Thus, the prevalence of new antibody production during pregnancy was 0.24 percent (95% confidence interval [CI], 0.17-0.32). Transfusion records indicated that the prevalence of transfusions during pregnancy was 0.09 percent (95% CI, 0.04-0.14). None of the women with new alloantibody formation during their pregnancies required transfusion; hence, new alloantibody production and the need for transfusion appear to be independent events. The probability of these events occurring together was 2.1 × 10(-6), or 1 in 500,000 deliveries.     

Initiation of differentiation into skeletal muscle fiber types

A monoclonal antibody directed against a slow isoform of a 100-K myofibrillar protein has been used to study the differentiation of muscle fibers in the fast and slow muscles of the rat. Immunohistochemical studies have shown that initiation of differentiation into fast and slow muscle fibers occurs very early during development. The distribution pattern of cell types in different muscles is unique and is also determined very early during fetal muscle development. It is concluded that motor innervation is probably not essential to initiate differentiation into distinct muscle fiber types.