Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus, and polyendocrine autoimmunity

BACKGROUND: Glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in stiff-man syndrome (SMS) and insulin-dependent diabetes mellitus (IDDM). GAD autoantibodies (GAD-Abs) are reported in a few patients with cerebellar ataxia, but their relevance is unclear. We describe three patients with cerebellar ataxia and GAD-Abs. METHODS: GAD-Abs were assayed by radioimmunoassay (RIA) and immunohistochemistry and confirmed by immunoblot of recombinant human GAD65. The GAD-Ab levels of the three patients with cerebellar ataxia were compared with those of five with SMS, 49 with IDDM, 64 with cerebellar ataxia of probable degenerative origin without associated autoimmune features, 14 non-IDDM islet cell antibody-positive first-degree relatives of IDDM patients, and 91 normal subjects. RESULTS: The three patients with ataxia and GAD-Abs were women (mean age, 63 years) with an isolated progressive cerebellar disorder, family history of IDDM, late-onset IDDM, and several positive serum organ-specific autoantibodies. Two patients had autoimmune thyroiditis, and one had pernicious anemia. CSF analysis demonstrated oligoclonal IgG bands and intrathecal synthesis of GAD-Abs. By RIA, GAD-Ab titers from the three patients were similar to those of SMS and significantly higher, without overlap, than the titers of IDDM patients. GAD-Abs were absent in the 64 patients with cerebellar ataxia and no evidence of autoimmune disorders. CONCLUSIONS: These findings suggest a link of GAD autoimmunity not only with SMS but also with cerebellar dysfunction. GAD-Abs should be sought in patients with cerebellar ataxia who have late-onset IDDM and other organ-specific autoimmune manifestations.     

Humidification and perceived indoor air quality in the office environment

The DNA content of 85 ductal breast cancers of different histological grades was evaluated using static cytometry and correlated with immunocytochemical expression of p53 protein in tumour cells in cytological material. A statistically significant difference was observed between p53 protein expression and grade of malignancy (P < 0.001). The percentage of euploid tumours significantly decreased from grade I through grade II to grade III tumours (P < 0.001). Clonal DNA heterogeneity was observed in 26.6% of cases analysed and was correlated with p53 protein expression (P < 0.001). These changes probably reflect genomic alterations which may affect potential malignancy of breast cancer.     

Grating-assisted coupling of light between semiconductor and glasswaveguides

Floquet-Bloch theory is used to calculate the electromagnetic fields in a leaky-mode grating-assisted directional coupler (LM-GADC) fabricated with semiconductor and glass materials. One waveguide is made from semiconductor materials (refractive index ≈3.2) while the second is made from glass (refractive index ≈1.45). The coupling of light between the two waveguides is assisted by a grating fabricated at the interface of the glass and semiconductor materials. Unlike typical GADC structures where power is exchanged between two waveguides using bound modes, this semiconductor/glass combination couples power between two waveguides using a bound mode (confined to the semiconductor) and a leaky mode (associated with the glass). The characteristics of the LM-GADC are discussed. Such LM-GADC couplers are expected to have numerous applications in areas such as laser-fiber coupling, photonic integrated circuits, and on-chip optical clock distribution. Analyses indicate that simple LM-GADC's can couple over 40% of the optical power from one waveguide to another in distances less than 1.25 mm     

The role of glucose 6-phosphate in the control of glycogen synthase

Elevated blood glucose concentrations result in increased intracellular levels of glucose 6-phosphate in liver, skeletal muscle, and adipose tissue. In liver, blood glucose concentrations are the main factor in control of the synthesis of glycogen; insulin has only a potentiating effect. In skeletal muscle and adipocytes, glucose alone has little effect on the activity of glycogen synthase, the limiting enzyme in glycogen synthesis. However, insulin released as a result of elevated blood glucose stimulates the translocation of specific glucose transporters to the cell membrane, increases the uptake of glucose, and causes the covalent, dephosphorylation-mediated activation of glycogen synthase. We present evidence that elevated intracellular contents of glucose 6-phosphate provoke the activation of glycogen synthase in liver, muscle, and adipose tissue. In addition, glucose 6-phosphate may inhibit the phosphorylation of glycogen synthase by cyclic AMP-stimulated protein kinase. We show that the stimulated glucose uptake and phosphorylation appear to play a major role in the control by insulin of the enzymes involved in glycogen synthesis.     

Satellite systems for personal communications

A number of industry groups are planning to construct satellite systems that will provide a personal communications service (PCS) (typically voice, data, and fax) to users over small, hand-held, cellular-type telephones. Some of these systems (e.g., Iridium and Globalstar) will be constructed using satellites in low Earth orbit. Two (Ellipso and ICO) will employ medium Earth orbit (3-8-h period), and still others (ACeS and Agrani) will operate from geostationary altitude. The origin and evolution of mobile satellite communications is discussed first, including the Inmarsat system and several land-based mobile satellite systems in operation. The rival approaches to the PCS market are then described, and some of the technical challenges inherent in each are indicated. This paper concludes with speculation on the factors influencing the likelihood of business success for the various PCS systems     

GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis

We have found that, during the early stages of cortical neurogenesis, both GABA and glutamate depolarize cells in the ventricular zone of rat embryonic neocortex. In the ventricular zone, glutamate acts on AMPA/kainate receptors, while GABA acts on GABAA receptors. GABA induces an inward current at resting membrane potentials, presumably owing to a high intracellular Cl- concentration maintained by furosemide-sensitive Cl- transport. GABA and glutamate also produce increases in intracellular Ca2+ in ventricular zone cells, in part through activation of voltage-gated Ca2+ channels. Furthermore, GABA and glutamate decrease the number of embryonic cortical cells synthesizing DNA. Depolarization with K+ similarly decreases DNA synthesis, suggesting that the neurotransmitters act via membrane depolarization. Applied alone, GABAA and AMPA/kainate receptor antagonists increase DNA synthesis, indicating that endogenously released amino acids influence neocortical progenitors in the cell cycle. These results demonstrate a novel role for amino acid neurotransmitters in regulating neocortical neurogenesis.