Background: Glycohemoglobin (GHB), reported as hemoglobin (Hb) A1c, is a marker of long-term glycemic control in patients with diabetes and is directly related to risk for diabetic complications. HbE and HbD are the second and fourth most common Hb variants worldwide. We investigated the accuracy of HbA1c measurement in the presence of HbE and/or HbD traits. Methods: We evaluated 23 HbA1c methods; 9 were immunoassay methods, 10 were ion-exchange HPLC methods, and 4 were capillary electrophoresis, affinity chromatography, or enzymatic methods. An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of HbE or HbD traits caused a statistically significant difference from HbAA results relative to the boronate affinity HPLC comparative method. Deming regression analysis was performed to determine whether the presence of these traits produced a clinically significant effect on HbA1c results with the use of ±10% relative bias at 6% and 9% HbA1c as evaluation limits. Results: Statistically significant differences were found in more than half of the methods tested. Only 22% and 13% showed clinically significant interference for HbE and HbD traits, respectively. Conclusions: Some current HbA1c methods show clinically significant interferences with samples containing HbE or HbD traits. To avoid reporting of inaccurate results, ion-exchange chromatograms must be carefully examined to identify possible interference from these Hb variants. For some methods, manufacturers’ instructions do not provide adequate information for making correct decisions about reporting results.

There is a growing body of evidence indicating that prostate-specific antigen (PSA) may be present in many steroid hormone-stimulated epithelial tissues other than that of the prostate. In particular, breast tumor cell lines treated with steroid hormone receptor agonists, breast tumors, and normal human breast have recently been found by our group to contain PSA. To investigate whether PSA may also be present in other human tumors, we employed a highly sensitive immunofluorometric assay technique to quantify PSA immunoreactivity in tumor extracts. Using a PSA-positivity cutoff value of 0.005 ng per mg of protein, 23 of 43 diverse tumors tested positive for PSA protein. Confirmatory analyses for PSA by a commercially available method (IMx) on six samples demonstrated a high degree of concordance between the two methods. To establish the molecular weight of the immunoreactive species, the most highly positive tumor extracts of each tumor type were fractionated by high performance liquid chromatography. Whereas the majority of tumors had immunoreactivity eluting at both 100 KDa and 33 KDa, corresponding to PSA bound to alpha 1-antichymotrypsin and free PSA, respectively, the colon and parotid tumors displayed immunoreactivity only at the 33 KDa fraction. We conclude that in addition to breast tumors and normal breast, colon, ovarian, liver, kidney, adrenal, and parotid tumors can also produce PSA. The physiological role of PSA in these tumors is currently under investigation.

Glycated hemoglobin is widely used in the management of diabetes mellitus. At least 300,000 Americans with diabetes mellitus have the hemoglobin (Hb) C or S trait. The accuracy of HbA1c methods can be adversely affected by the presence of these traits. We evaluated the effects of HbC and HbS traits on the results of 14 commercial HbA1c methods that use boronate affinity, enzymatic, immunoassay, and ion exchange methods. Whole blood samples from people homozygous for HbA or heterozygous for HbC or HbS were analyzed for HbA1c. Results for each sample type were compared with those from the CLC 330 comparative method (Primus Diagnostics, Kansas City, MO). After correcting for calibration bias by comparing results from the homozygous HbA group, method bias attributable to the presence of HbC or HbS trait was evaluated with a clinically significant difference being more than 10% (ie, 0.6% at 6% HbA1c). One immunoassay method exhibited clinically significant differences owing to the presence of HbC and HbS traits.

Human adipose tissue derives its cholesterol primarily from circulating lipoproteins. To study fat cell-lipoprotein interactions, low density lipoprotein (LDL) uptake and metabolism were examined using isolated human adipocytes. The 125I-labelled LDL (d = 1.025-1.045) was bound and incorporated by human fat cells in a dose-dependent manner with an apparent Km of 6.9 + 0.9 microgram LDL protein/mL and a Vmax of 15-80 microgram LDL protein/mg lipid per 2 h. In time-course studies, LDL uptake was characterized by rapid initial binding followed by a linear accumulation for at least 4 h. The 125I-labelled LDL degradation products (trichloroacetic acid soluble iodopeptides) accumulated in the incubation medium in a progressive manner with time. Azide and F- inhibited LDL internalization and degradation, suggesting that these processes are energy dependent. Binding and cellular internalization of 125I-labelled LDL lacked lipoprotein class specificity in that excess (25-fold) unlabelled very low density lipoprotein (VLDL) (d less than 1.006) and high density lipoprotein (HDL) (d = 1.075-1.21) inhibited binding and internalization of 125I-labelled LDL. On an equivalent protein basis HDL was the most potent. The 125I-labelled LDL binding to an adipocyte plasma membrane preparation was a saturable process and almost completely abolished by a three- to four-fold greater concentration of HDL. The binding, internalization, and degradation of LDL by human adipocytes resembled that reported by other mesenchymal cells and could account for a significant proportion of in vivo LDL catabolism. It is further suggested that adipose tissue is an important site of LDL and HDL interactions.

The effect of oral caffeine on resting ventilation (VE), ventilatory responsiveness to progressive hyperoxic hypercapnia (HCVR), isocapnic hypoxia (HVR), and moderate exercise (EVR) below the anaerobic threshold (AT) was examined in seven healthy adults. Ventilatory responses were measured under three conditions: control (C) and after ingestion of either 650 mg caffeine (CF) or placebo (P) in a double-blind randomized manner. None of the physiological variables of interest differed significantly for C and P conditions (P greater than 0.05). Caffeine levels during HCVR, HVR, and EVR were 69.5 +/- 11.8, 67.8 +/- 10.8, and 67.8 +/- 10.9 (SD) mumol/l, respectively (P greater than 0.05). Metabolic rate at rest and during exercise was significantly elevated during CF compared with P. An increase in VE from 7.4 +/- 2.5 (P) to 10.5 +/- 2.1 l/min (CF) (P less than 0.05) was associated with a decrease in end-tidal PCO2 from 39.1 +/- 2.7 (P) to 35.1 +/- 1.3 Torr (CF) (P less than 0.05). Caffeine increased the HCVR, HVR, and EVR slopes (mean increase: 28 +/- 8, 135 +/- 28, 14 +/- 5%, respectively) compared with P; P less than 0.05 for each response. Increases in resting ventilation, HCVR, and HVR slopes were associated with increases in tidal volume (VT), whereas the increase in EVR slope was accompanied by increases in both VT and respiratory frequency. Our results indicate that caffeine increases VE and chemosensitivity to CO2 inhalation, hypoxia, and CO2 production during exercise below the AT.