Persistent GAD 65 antibodies in longstanding IDDM are not associated with residual beta-cell function, neuropathy or HLA-DR status

Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with insulin-dependent diabetes mellitus (IDDM) of long duration. The source of the stimulus for this autoimmune reactivity is still unknown. Because the GAD 65 isoform is mainly expressed in pancreatic beta-cells and in the nervous system we investigated in the present study of the largest number of well characterized patients with longstanding IDDM (n = 105; median duration: 21 years; range: 10-46 years) the presence of autoantibodies to GAD 65 and their relationship to a residual C-peptide response or peripheral and autonomic neuropathy. Additionally we studied the HLA-DR status relative to GAD 65 antibodies in 86 out of the 105 individuals. One hundred healthy control subjects and 100 recent onset IDDM patients were also studied for GAD 65 antibodies. GAD 65 antibodies were detected in a radioligand-binding-assay with recombinant human GAD 65 and were present in 32% of the long-term diabetic patients, 82% of the recent onset IDDM patients and in 3% of the healthy control subjects. A preserved C-peptide response to i.v. glucagon (Hendriksen criteria) was observed in 23% of the long-term IDDM patients. Autonomic neuropathy and peripheral neuropathy was identified using criteria based on both symptoms and formal testing giving a frequency of 67% vs 79%. The HLA specific DR 4/X was observed in 47% and HLA-DR 3/X in 22% of the long-term IDDM patients. Patients who were heterozygous for DR3/DR4 were found in 23% of the cases. GAD 65 antibodies were significantly less frequent in the long-term IDDM patients compared to recent onset IDDM (p < 0.001), and diabetes duration showed a significant negative correlation with GAD 65 antibody index levels (r = 0.22, p < 0.01). Interestingly, GAD 65 antibodies were not significantly correlated either with residual beta-cell function or neuropathy and no particular HLA-DR status was associated with persistent GAD 65 antibodies. In conclusion neither residual beta-cell function nor diabetic neuropathy or a certain HLA-DR specificity are exclusively associated with persistent autoimmunity directed to GAD 65 in longstanding IDDM. The stimulus for the persistent humoral immune response and its significance for the disease process and its complications remain to be established.     

Potential difference and photovoltaic effect arising from distortion of the electron wave function in a GaAs quantum well with a thin AlGaAs barrier

This paper discusses changes in the spectrum and distortion of the electron wave function of a GaAs quantum well when a thin AlGaAs barrier is introduced into it. The potential difference generated across the quantum well by distortion of the electron wave function is calculated, along with its dependence on the position of the barrier in the quantum well. The photovoltaic response of the structure to optical intersubband excitations is also calculated, along with the role of wave function and electronic spectrum distortion as well as intersubband nonradiative transitions in generating this response. The suitability of a GaAs quantum well with a thin barrier for use as an infrared detector is considered. Fiz. Tekh. Poluprovodn. 32, 1246–1250 (October 1998)     

Successive interference cancellation for multiuser asynchronousDS/CDMA detectors in multipath fading links

There has been an increasing interest in the use of code-division multiple access (CDMA) in cellular mobile and wireless personal communications. The choice of such multiaccess technique is attractive because of its potential capacity increases and other technical factors such as privacy and multipath rejection capabilities. However, it is well known that the performance of CDMA can be significantly degraded due to cochannel interference (CI) and the near-far effects. We consider the performance of direct-sequence (DS)-based CDMA over fading channels that are modeled as slowly varying Rayleigh-fading discrete multipath channels. Specifically, we propose and analyze an adaptive multistage interference cancellation strategy for the demodulation of asynchronous DS spread-spectrum multiple-access signals. Numerical results show that the proposed multistage detector, which alleviates the detrimental effects of the near-far problem, can significantly improve the system performance     

Pharmacokinetics of dolasetron after oral and intravenous administration of dolasetron mesylate in healthy volunteers and patients with hepatic dysfunction

In previous studies, dolasetron was shown to have both renal and hepatic elimination mechanisms. This study was conducted to determine the impact of varying degrees of hepatic dysfunction on the pharmacokinetics and safety of dolasetron and its reduced metabolites. Seventeen adults were studied: six healthy volunteers (group I), seven patients with mild hepatic impairment (Child-Pugh class A; group II), and four patients with moderate to severe hepatic impairment (Child-Pugh class B or C1; group III). Single 150-mg doses of dolasetron mesylate were administered intravenously and orally, with a 7-day washout period separating treatments. After intravenous administration, no differences were observed between healthy volunteers and patients with hepatic impairment in maximum plasma concentration (Cmax), areas under the plasma concentration-time curve (AUC), or elimination half-life (t1/2) of intact dolasetron. No significant differences were found in Cmax, AUC, or apparent clearance (C(lapp)) of hydrodolasetron, the primary metabolite of dolasetron. The mean t1/2 increased from 6.87 hours in group I to 11.69 hours in group III. After oral administration, C(lapp) of hydrodolasetron decreased by 42%, and Cmax increased by 18% in patients with moderate to severe hepatic impairment. There were less changes in patients with mildly hepatic impairment. Total percentage of dose excreted as metabolites was similar for healthy volunteers and patients with hepatic impairment, although urinary metabolite profiles differed slightly. Dolasetron was well tolerated and there were no apparent differences in adverse effects between groups or treatments. Because hepatic impairment did not influence Cl(app) of hydrodolasetron after intravenous administration, and the range of plasma concentrations of hydrodolasetron after oral administration was not different from those observed in healthy volunteers, dosage adjustments are not recommended for patients with hepatic disease and normal renal function.     

The pickup and delivery problem: Faces and branch-and-cut algorithm

This paper formulates the pickup and delivery problem, also known as the dial-a-ride problem, as an integer program. Its polyhedral structure is explored and four classes of valid inequalities developed. The results of a branch-and-cut algorithm based on these constraints are presented.     

Analysis of distribution of Campylobacter jejuni and Campylobacter coli in broilers by using restriction fragment length polymorphism of flagellin gene

The incidence of Campylobacter jejuni and Campylobacter coli in broiler farms was 33.9% (19/56). C. jejuni-positive flocks accounted for 20.0% (17/85) and C. coli-positive ones was 4.7% (4/85). There were 14 patterns (fla type) of restriction fragment length polymorphism (RFLP) of flagellin A gene among these 22 strains of C. jejuni and C. coli including the standard strain C. jejuni ATCC 33560. Different fla types of Campylobacter were isolated from broilers in different growing cycles on the same farms. Four strains of C. jejuni were isolated from four breeder farms and four fla types of C. jejuni were detected from their progenies reared on growing farms. Three fla types of C. jejuni detected from the progenies were different from those of each breeder. Also, the other three fla types of C. jejuni were detected from different progenies of each growing farm during the next growing cycle. These findings indicate that the RFLP analysis may contribute to epidemiological studies of C. jejuni and C. coli contamination of broilers and suggest the risk of contamination with different types of Campylobacter in every growing cycle of broilers on the farm even on the same farm. They also supported that there was little likeliness of the vertical transmission of C. jejuni and C. coli from breeders to broilers.     

From particle-mass to multibody systems: graph-theoretic modeling

The distinction between geometry and dynamic interactions is fundamental for the consistent dynamic analysis of physical systems. A unified treatment of such systems is possible when we adopt a hierarchical mathematical model with a consistent set of embedded abstractions. This new view is adopted in the general formulation strategy for obtaining a simplified dynamics model of mechanical systems. We show that there exists a consistent general extension from the model of constrained particle-mass systems (PMS) to the model of multibody systems (MBS) based entirely on graph-theoretic concepts     

Microfabricated Lamb wave device based on PZT sol-gel thin film formechanical transport of solid particles and liquids

The fabrication using silicon micromachining and characterization of an acoustic Lamb wave actuator is presented. The intended use of the device is for mass transport and sensor applications. The device consists of dual interdigitated transducers patterned on a thin-film composite membrane of silicon nitride, platinum, and a sol-gel-derived piezoelectric ceramic (PZT) thin film. The acoustic properties of the device are presented along with preliminary applications to mechanical transport and liquid delivery systems. Improved acoustic signals and improved mass transport are achieved with PZT over present Lamb wave devices utilizing ZnO or AlN as the piezoelectric transducer