Activation of 5-HT2 receptors facilitates depolarization of neocortical neurons by N-methyl-D-aspartate

We prospectively studied 63 children with transient hyperglycemia to determine their risk of acquiring insulin-dependent diabetes mellitus (IDDM) and to evaluate the predictive value of immunologic markers of prediabetes and of the intravenous glucose tolerance test. Children with transient hyperglycemia were identified by a prospective systematic review of the laboratory reports of a large children's hospital and an office-based pediatric practice and by referral from pediatricians. Transient hyperglycemia occurred in 0.46% of children seen in the children's hospital and in 0.013% of children attending a pediatric office practice. Insulin-dependent diabetes mellitus developed within 18 months of identification in 32% of children in whom transient hyperglycemia was discovered in the absence of a serious illness, compared with 2.3% of children identified during a serious illness (relative risk, 13.9; 95% confidence interval, 1.56 to 123.5). Islet cell antibodies and competitive insulin autoantibodies each had a 100% positive predictive value for IDDM; the negative predictive value of islet cell antibodies and competitive insulin autoantibodies was 96% and 98%, respectively. The stimulated insulin release during an intravenous glucose tolerance test, adjusted for age, had the highest overall accuracy of prediction. All children less than 6 years of age with stimulated insulin release levels < 85 pmol/L (12 microU/ml) subsequently had IDDM, as did an 11-year-old child whose stimulated insulin release level was below the 1st percentile of 170 pmol/L (24 microU/ml). To date, no child whose stimulated insulin release level was above the 5th percentile has had IDDM. We conclude that when transient hyperglycemia occurs during a serious intercurrent illness, the risk of progression to IDDM is low. In contrast, one third of children in whom transient hyperglycemia is identified without a serious illness can be expected to have IDDM within 1 year. A combination of islet cell antibodies, competitive insulin autoantibodies, and stimulated insulin release levels during an intravenous glucose tolerance test can accurately distinguish children with prediabetes from those with presumed benign transient increases in plasma glucose concentrations.     

A growth control approach to Class II, Division 1 cases during puberty involving the simultaneous application of maxillary growth restriction and mandibular forward induction

A simple method that used headgear and a functional appliance simultaneously was used for the correction of Class II, Division 1 cases with severe denture base discrepancy. The treatment restricted the forward growth of the maxilla and advanced the mandible. The functional appliance, referred to as the mandibular growth advancer (MGA), advances the mandible progressively with a splint, with the objective of remodeling the condyle and the glenoid fossa in the temporomandibular joint. Functional adaptation was achieved as the muscles that are attached to the mandible adjusted to new positions. In the two cases that illustrate this method, the ANB angle decreased and the Ar-B distance increased over a short period to four and six times the mean Japanese growth rate, respectively. After the correction of the denture-base discrepancy, a multibracket fixed appliance was used for dental alignment, and good skeletal, occlusal relationships and profiles were obtained. Treatment of severe denture-base discrepancy in this manner may reduce the skeletal abnormality, decrease the number of extraction cases, and shorten the subsequent multibracket treatment time. And it may reduce the iatrogenic side effects caused by prolonged mechanotherapy with a fixed appliance.     

Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation

Antigen receptor genes are assembled by site-specific DNA rearrangement. The recombination activator genes RAG-1 and RAG-2 are essential for this process, termed V(D)J rearrangement. The activity and stability of the RAG-2 protein have now been shown to be regulated by phosphorylation. In fibroblasts RAG-2 was phosphorylated predominantly at two serine residues, one of which affected RAG-2 activity in vivo. The threonine at residue 490 was phosphorylated by p34cdc2 kinase in vitro; phosphorylation at this site in vivo was associated with rapid degradation of RAG-2. Instability was transferred to chimeric proteins by a 90-residue portion of RAG-2. Mutation of the p34cdc2 phosphorylation site of the tumor suppressor protein p53 conferred a similar phenotype, suggesting that this association between phosphorylation and degradation is a general mechanism.     

Morphological and functional polymorphism within clonal thyroid nodules

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin. Only 3 out of the 24 clonal nodules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression were remarkably heterogeneous throughout the tumors. There were no histomorphological characteristics distinguishing these clonal tumors from polyclonal nodules. Even if a clonal thyroid tumor may be originally homogeneous in respect to the parameters studied here, mechanisms must exist that create wide heterogeneity of growth and of morphogenetic potential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular goiters than hitherto assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rely on morphological and functional criteria alone but requires molecular or cytogenetic analysis of clonality.     

Hematopoietic and lymphopoietic responses in human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor transgenic mice injected with human GM-CSF

Using a clonal assay of bone marrow (BM) cells from transgenic mice (Tg-mice) expressing the human granulocyte-macrophage colony-stimulating factor receptor (hGM-CSFR), we found in earlier studies that hGM-CSF alone supported the development not only of granulocyte-macrophage colonies, but also of erythrocytes, megakaryocytes, mast cells, blast cells, and mixed hematopoietic colonies. In this report, we evaluated the in vivo effects of hGM-CSF on hematopoietic and lymphopoietic responses in the hGM-CSFR Tg-mice. Administration of this factor to Tg-mice resulted in dose-dependent increases in numbers of reticulocytes and white blood cells (WBCs) in the peripheral blood. Morphological analysis of WBCs showed that the numbers of all types of the cell, including neutrophils, eosinophils, monocytes, and lymphocytes increased; the most remarkable being in lymphocytes that contained a number of large granular lymphocytes (LGLs) in addition to mature T and B cells. However, total cellularity of the BM of the Tg-mice decreased in a dose-dependent manner when hGM-CSF was injected. In sharp contrast to the BM, spleens of the Tg-mice were grossly enlarged. Although all types of blood cells and hematopoietic progenitors increased in the spleen, erythroid cells and their progenitors showed the most significant increase. Increased numbers of megakaryocytes and LGLs were also observed in spleen and liver of the treated Tg-mice. Flow cytometric analysis showed that LGLs expanded in Tg-mice expressed Mac-1+ CD3- NK1.1+. The thymus of Tg-mice treated with hGM-CSF exhibited a dose-dependent shrinkage and a remarkable decrease in CD4+ CD8+ cells. Thus, hGM-CSF stimulated not only myelopoiesis but also erythropoiesis and megakaryopoiesis of hGM-CSFR Tg-mice in vivo, in accordance with our reported in vitro findings. In addition, hGM-CSF affected the development of lymphoid cells, including natural killer cells of these Tg-mice.     

Drug therapy of hemiballism. Review of the literature and personal observations

Hemiballism is a rare hyperkinetic disorder which is characterized by irregular vigorous rotatory movements of the limbs of one side of the body. The disabling and exhausting movements with their high risk of severe injuries require an acute drug treatment. However, there are no common guidelines for the treatment of this disorder. Therefore we reviewed the available literature to establish a concept for a rational symptomatic drug treatment. Furthermore, own observations in 6 patients with hemiballism of different origins are reported.     

Solar/UV-induced photocatalytic degradation of three commercial textile dyes.

The photocatalytic degradation of three commercial textile dyes with different structure has been investigated using TiO(2) (Degussa P25) photocatalyst in aqueous solution under solar irradiation. Experiments were conducted to optimise various parameters viz. amount of catalyst, concentration of dye, pH and solar light intensity. Degradation of all the dyes were examined by using chemical oxygen demand (COD) method. The degradation efficiency of the three dyes is as follows: Reactive Yellow 17(RY17) > Reactive Red 2(RR2) > Reactive Blue 4 (RB4), respectively. The experimental results indicate that TiO(2) (Degussa P25) is the best catalyst in comparison with other commercial photocatalysts such as, TiO(2) (Merck), ZnO, ZrO(2), WO(3) and CdS. Though the UV irradiation can efficiently degrade the dyes, naturally abundant solar irradiation is also very effective in the mineralisation of dyes. The comparison between thin-film coating and aqueous slurry method reveals that slurry method is more efficient than coating but the problems of leaching and the requirement of separation can be avoided by using coating technique. These observations indicate that all the three dyes could be degraded completely at different time intervals. Hence, it may be a viable technique for the safe disposal of textile wastewater into the water streams.