A chemistry department in transition. How we became a reference laboratory

By analyzing the arrival times of specimens and reorganizing laboratory instruments to accommodate a higher volume of tests, the author's chemistry department was able to profit from the additional reference testing it was able to handle.     

Use of pluronic micelles to overcome multidrug-resistance

Pluronic P-85 (poly(55)(oxypropylene)dipoly(s)(oxyethylene)) was used to form daunorubicin containing micelles. This new carrier was tested in vitro on sensitive and resistant ovarian cancer cell lines. Drug incorporation was measured by cytofluorometry and the cytotoxicity was measured by the tetrazolium formazan XTT assay. ID50 of 0.16 and 25 mu g/ml were obtained for conjugated and free daunorubicin respectively. The results obtained suggest that this approach may be used in combination with a chemotherapeutic agent to overcome multidrug resistance.     

The Morquio syndrome: neuropathology and biochemistry.

The activity of N-acetyl galactosamine-6-sulfate sulfatase was studied for the first time in the liver and brain of a patient with a clinically typical case of Morquio syndrome with keratosulfaturia. As has been demonstrated in the fibroblasts of patients with this syndrome, this enzymatic activity was markedly decreased in both organs. Neuropathological examination revealed moderately swollen neurons containing PAS-positive, coarse globular inclusions in the cerebral cortex, Ammon's horn, basal ganglia, and thalamic nuclei. Ultrastructurally, the inclusions consisted of stacked, straight or loose, wavy membranes of various lengths, often associated with pale or moderately electron dense homogeneous "lipid droplets." These ultrastructural features of the inclusions were closely similar to the granulomembranous bodies of Hurler syndrome and the inclusions described in type B of the Sanfilippo syndrome. Unlike those mucopolysaccharidoses, however, no abnormalities were found in the gangliosides in the brain of the patient with Morquio syndrome.     

A comparison of participants and nonparticipants in a worksite cholesterol screening

PURPOSE. The purpose of this study is to determine if worksite cholesterol screening reaches only those who are already aware of their cholesterol and interested in lifestyle modification. DESIGN. A voluntary worksite cholesterol screening was conducted followed by a survey of a random sample of nonparticipants. SETTING. A large university worksite was the setting for this study. SUBJECTS. Out of 9,137 university employees, 1,583 attended the voluntary screening, and a random sample of nonparticipants was obtained (n = 154), of which 87% (n = 138) responded. MEASURES. Subjects completed a questionnaire on health behaviors, perceived risk, self-efficacy for diet change, and attention to media messages. A capillary blood cholesterol level was also taken. RESULTS. Nonparticipants were more likely to be male (64% versus 39%) and smokers (17% versus 9%), more likely to exercise, to have had a prior cholesterol measurement (64% versus 49%), and to "know" their cholesterol value (56% versus 26%). The two groups were otherwise similar. Over half (51%) of the participants were receiving their first cholesterol measurement. These subjects were younger, less educated, had less perceived risk, were less attentive to media messages, and more likely to be from a minority group than those individuals who had prior measurements. DISCUSSION. These findings suggest that worksite cholesterol screening does not only reach those already aware of their cholesterols, but also can reach some persons not previously screened or concerned.     

Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans?

Clinical acute lung rejection (AR) occurs in lung allografts usually within 50 days after transplantation. While perivascular infiltrates characterize AR, with moderate-to-severe acute rejection small airway injury occurs. We investigated the significance of small airway injury in AR and its relationship to the development of bronchiolitis obliterans (OB) in 11 recipients of combined heart-lung or double-lung allografts. In general, the intensity and persistence of early acute rejection episodes associated with injury to bronchioles correlated with the development of histologic bronchiolitis obliterans. Early AR may "prime" lymphocytes for subsequent respiratory epithelial injury and airway fibrosis late in the postoperative period.     

Suramin potently inhibits the enzymatic activity of PSM

BACKGROUND: The polysulfonated napthlyurea suramin has shown significant antitumor activity in patients with hormone-refractory metastatic prostate cancer. The mechanism by which suramin exerts this effect is unknown. In 1993, prostate-specific membrane antigen (PSM) was identified as a prostate biomarker that is elevated in hormone-refractory and metastatic prostate cancer. PSM is a glutamate exocarboxypeptidase capable of cleaving the terminal alpha-linked glutamate from the dipeptide N-acetyl-aspartyl-glutamate (NAAG) and the gamma-linked glutamates from folate polyglutamate. METHODS: Using a NAAG hydrolytic radioenzymatic assay, we tested whether suramin had any effect on the enzymatic activity of PSM. RESULTS: We demonstrate that suramin potently inhibits the enzymatic activity of PSM with a K(i) = 15 nM and 68 nM for the membrane-associated and soluble forms of PSM, respectively. In addition, we show that suramin inhibition of PSM enzyme activity displays the kinetics of a classic competitive inhibitor. CONCLUSIONS: This is one of the most potent activities described for suramin to date and may represent a portion of its pharmacologic and/or toxicological mechanism of action.     

One- and two-year predictors of excess weight gain among elementary schoolchildren in multiethnic, low-income, inner-city neighborhoods

Longitudinal studies are needed to increase understanding of the causes of childhood obesity. To identify 1- and 2-year predictors of excess weight gain among preadolescents, the authors conducted a prospective cohort study of fourth- and fifth-grade students in 16 elementary schools located in multiethnic, low-income neighborhoods in Montreal, Quebec, Canada, that were participating in the evaluation of a school-based heart health promotion program. Subjects included 2,318 children aged 9-12 years with baseline and 1-year follow-up data and 633 children aged 9-11 years with baseline and 2-year follow-up data. One-year predictors of highest decile of change in body mass index (BMI) identified in logistic regression analyses included baseline BMI of 90th percentile or more (odds ratio (OR) = 2.66, 95% confidence interval: 1.80, 3.94) in boys and baseline BMI of 90th percentile or more (OR = 2.34, 95% confidence interval: 1.46, 3.76), no sports outside school (OR = 1.90, 95% confidence interval: 1.18, 3.06), and playing video games everyday (OR = 2.48, 95% confidence interval: 1.04, 5.92) in girls. Two-year predictors included baseline BMI of 90th percentile or more (OR = 3.26, 95% confidence interval: 1.52, 7.01), no sports outside school (OR = 2.14, 95% confidence interval: 0.96, 4.77), and least active (OR = 2.18, 95% confidence interval: 1.01, 4.71) in boys; only baseline BMI of 90th percentile or more (OR = 2.22, 95% confidence interval: 1.02, 4.81) was significant in girls. Results suggest the need for interventions to promote increased physical activity in children.