Joseph W. Hoffmann

Cloning and characterization of the human β-glucuronidase gene

Abstract We have isolated a cosmid clone that contains GUSB, the human gene encoding β-glucuronidase. The 21-kb gene contains 12 exons ranging from 85 to 376 bp in length. Exon 6 corresponds to the 153-bp deletion in the shorter of two types of cDNAs reported earlier, supporting the hypothesis that this cDNA arose by alternate splicing leading to exon skipping. The insert contains 4.2 kb of sequence upstream from the first exon and 6 kb 3′ of the last exon. The clone expresses human β-glucuronidase in stably transformed rat XCtk − cells. Comparison of the human gene organization with that recently reported for the murine β-glucuronidase gene revealed that the intron/exon boundaries are identical. In the splice junctions, the most highly conserved regions are those identified as consensus sequences, and these are at least as highly conserved as bases encoding the translated portion of the gene.

The evolution of immune memory and germinal centers

Antibody responses in homoiothermic and poikilothermic vertebrates are significantly different in their heterogeneity and affinity range, and in the speed of the secondary response following repeated antigenic stimulation. This article presents the hypothesis that the evolutionary development of unique lymphoid structures, the germinal centers, in combination with the development of a distinct B-cell lineage, is a determining feature of these differences.

Misidentification of propionic acid as ethylene glycol in a patient with methylmalonic acidemia

Reexamination of serum from a child thought to have died of ethylene glycol poisoning showed that the child had methylmalonic acidemia. The gas chromatographic peak identified as ethylene glycol by a clinical laboratory was actually due to propionic acid. Proof of a metabolic basis for the childs symptoms eventually exonerated his mother of the charge of murder.

Hypertrophic cardiomyopathy in a newborn infant

the feet was appreciated. Bilateral hydroceles were noted. Results of neurologic examination were normal. A chest x-ray film showed marked cardiomegaly and normal pulmonary vascularity. Sinus tachycardia was apparent from the electrocardiogram with a heart rate of 160/min, QRS axis 120°. The PR interval was shortened to 0.08 seconds; there was severe biventricular hypertrophy with ST-T wave changes. The echocardiogram revealed severe left and right ventricular hypertrophy with compressed ventricular cavities (Fig 1). The left ventricular end-diastolic dimension was 18 mm (normal, 20 mm), and the end-systolic dimension was 6 mm (normal 13 mm). The left ventricular end-diastolic wall thickness was 12 mm (normal, 3.5 mm). The left ventricular shortening fraction was increased to 50%. There was anterior motion of the mitral valve during systole, and Doppler study showed mild subaortic obstruction. There was no aortic valve stenosis or coarctation of the aorta. Results of a skeletal survey were normal. Initial laboratory evaluation revealed: creatine kinase, 17.10 microkatal (μkat)/L (normal, 0.50 to 3.67 μkat/L [1026 U/L; normal, 30 to 220 /U/L]); serum total carnitine, 11 nmol/mL (normal, 17 to 46 nmol/mL); free carnitine, 8 nmol/mL (normal, 10 to 29 nmol/mL); urine catecholamines, 8 μg/24 h (normal, <540 μg/24 h). Results of urine hexuronic acid analysis (26 mg/g) were normal. Leukocyte lysosomal enzyme panel (including α-glucosidase CASE PRESENTATION Dr Chen

Effectiveness of Glucose Monitoring Systems Modified for the Visually Impaired

OBJECTIVE To compare three glucose meters modified for use by individuals with diabetes and visual impairment regarding accuracy, precision, and clinical reliability. RESEARCH DESIGN AND METHODS Ten subjects with diabetes and visual impairment performed self-monitoring of blood glucose using each of the three commercially available blood glucose meters modified for visually impaired users (the AccuChek Freedom [Boehringer Mannheim, Indianapolis, IN], the Diascan SVM [Home Diagnostics, Eatontown, NJ], and the One Touch [Lifescan, Milpitas, CA]). The meters were independently evaluated by a laboratory technologist for precision and accuracy determinations. RESULTS Only two meters were acceptable with regard to laboratory precision (coefficient of variation <10%)—the Accuchek and the One Touch. The Accuchek and the One Touch did not differ significantly with regard to laboratory estimates of accuracy. A great discrepancy of the clinical reliability results was observed between these two meters. The Accuchek maintained a high degree of reliability (y = 0.99X + 0.44, r = 0.97, P = 0.001). The visually impaired subjects were unable to perform reliable testing using the One Touch system because of a lack of appropriate tactile landmarks and auditory signals. CONCLUSIONS In addition to laboratory assessments of glucose meters, monitoring systems designed for the visually impaired must include adequate tactile and audible feedback features to allow for the acquisition and placement of appropriate blood samples.