Validity of screening for individuals at risk for type I diabetes by combined analysis of antibodies to recombinant proteins

OBJECTIVE: To determine whether screening for the presence of multiple antibody markers for IDDM is effective at identifying individuals with high risk for disease development. RESEARCH DESIGN AND METHODS: Antibodies to GAD and the tyrosine phosphatase-like protein 1A-2 were determined in sequential serum samples from 44 first-degree relatives of IDDM patients, identified as possessing islet cell antibody (ICA) and/or insulin autoantibody (IAA), who were followed prospectively for IDDM development, ICA, IAA, and antibodies to GAD and 1A-2 were also determined in 93 cases of new-onset nonfamilial IDDM. RESULTS: The presence of two or more antibodies in addition to ICA or IAA conferred high risk (61%) for development of IDDM within 5 years of entry into the study and identified 89% of those who have developed IDDM on current follow-up. None of the relatives positive for ICA or IAA alone, in the absence of other antibody markers, have developed IDDM. Antibodies to islet antigens could both appear and disappear in follow-up samples obtained after entry into the study. The majority (60%) of young (< 16 years), sporadic cases of IDDM had multiple antibodies to islet antigens, but this proportion was lower in older patients (37%). CONCLUSIONS: A screening strategy based on the analysis of antibodies to multiple islet antigens can predict IDDM at high sensitivity and specificity in families, and such a strategy may also be applicable to identify young individuals in the general population with high disease risk. Since appearance of antibodies to different antigens occurs sequentially rather than simultaneously, accurate assessment of diabetes risk based on the presence of multiple antibodies will require follow-up over a number of years after the first evidence of islet autoimmunity.     

EQUATIONS AND TABLES FOR SHRINKAGE,EXPANSION AND DESIGN CALCULATIONS1

Attention is drawn to an error in the equation for calculating linear shrinkage (per cent of dry length) from volume shrinkage (per cent of dry volume) which was given in the Report of the Committee on Standards, American Ceramic Society , Year Book, 1921–22. In order to avoid errors due to the use of incorrect equations, in future work, the more useful equations for making the ordinary shrinkage, expansion, and design calculations are derived and tabulated. To facilitate numerical computation, four figure tables are given by means of which the labor involved in the more usual ceramic calculations involving shrinkage and expansion can be greatly reduced. The use of the equations and tables is explained and illustrated by means of examples.     

THE EFFECT OF MECHANICAL PRESSURE ON THE IMBIBITIONAL AND DRYING PROPERTIES OF SOME CERAMIC CLAYS,I*

A number of ceramic clays in the plastic condition were held between water-permeable pistons under mechanical pressure of from 200 to 20,000 pounds per square inch in contact with water at atmospheric pressure until equilibrium was reached; the water in the pistons was removed by compressed air, the pressure released. and the moisture content, density, drying shrinkage, and other properties of the clays determined. In every case, the moisture content and drying shrinkage decreased with increasing pressure and with some clays at high pressures expansion occurred on drying. Rather complete data are given for a number of clays and their theoretical and practical significance is discussed.     

T helper cell regulation of normal and neoplastic B cell growth

Following challenge with a thymus-dependent antigen T helper cells regulate B cell growth and differentiation in several ways. Initially, the T cells physically associate with antigen presenting B cells. While in conjugate, the two cells communicate with each other through the actions of cell surface receptors whose ligands are integral membrane proteins expressed on the surface of the apposed cell. The ensuing biochemical pathways regulate the expression of genes required for B cell cycle progression. As a consequence of this interaction, the T cells are induced to synthesize and secrete soluble mediators that also affect B cell proliferation, as well as determining the ultimate fate of the activated B cell. We also suggest a role for normal, Th cells during the development, and continued expansion of certain types of B cell lymphomas.     

Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2

Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer and other human diseases. Fumagillin and ovalicin compose a class of structurally related natural products that potently inhibit angiogenesis by blocking endothelial cell proliferation. A synthetic analog of fumagillin, TNP-470, is currently undergoing clinical trials for treatment of a variety of cancers. A common target for fumagillin and ovalicin recently was identified as the type 2 methionine aminopeptidase (MetAP2). These natural products bind MetAP2 covalently, inhibiting its enzymatic activity. The specificity of this binding is underscored by the lack of inhibition of the closely related type 1 enzyme, MetAP1. The molecular basis of the high affinity and specificity of these inhibitors for MetAP2 has remained undiscovered. To determine the structural elements of these inhibitors and MetAP2 that are involved in this interaction, we synthesized fumagillin analogs in which each of the potentially reactive epoxide groups was removed either individually or in combination. We found that the ring epoxide in fumagillin is involved in the covalent modification of MetAP2, whereas the side chain epoxide group is dispensable. By using a fumagillin analog tagged with fluorescein, His-231 in MetAP2 was identified as the residue that is covalently modified by fumagillin. Site-directed mutagenesis of His-231 demonstrated its importance for the catalytic activity of MetAP2 and confirmed that the same residue is covalently modified by fumagillin. These results, in agreement with a recent structural study, suggest that fumagillin and ovalicin inhibit MetAP2 by irreversible blockage of the active site.     

Distribution of bacteria with the arylsulfate sulfotransferase activity

We herein report a simple method using intestinal clamps to prevent intraoperative contamination during an immediate mucocutaneous suture of the intestinal stoma. Using this technique, a protruded intestinal stoma can be constructed reliably without soiling. The technique can be used both for constructing an end as well as a loop intestinal stoma.     

Paramedian sternal bone plate reinforcement and wiring for difficult sternotomy wounds

The most common tumoral lesion of the bony orbital region is osteoma. It is an infrequent and benign tumor, and generally attacks the craniofacial skeleton, but intraorbital involvement is extremely rare. After necessary radiologic examinations (radiographs and computed tomography scanning), surgery should be planned according to the tumor's localization. In the case presented here, osteoma originated mainly from the medial orbital wall. Therefore, for better surgical exposure, extra- and intracranial approaches were planned and carried out. The mass was removed successfully. At the 3-year follow-up, no recurrence was shown.