The College of American Pathologists, 1946-1996. Quality Assurance Service

Since its creation in 1970, the College of American Pathologists Quality Assurance Service Committee has provided important and highly respected interlaboratory programs for daily quality control. In 1988, this committee extended its domain by announcing Q-Probes, a unique benchmarking program for laboratory quality assurance. Because of the success and rapid growth of this program during the next 2 years, the Quality Assurance Service Committee expanded into two committees, namely, QAS-QC and QAS-QA, with expertise concentrated, respectively, in quality control and quality assurance. These committees have compiled a history of significant scientific and educational contributions to members, the international laboratory community, other physicians, and patients. New directions for both committees are now underway so that their contributions can continue in the rapidly changing field of pathology and laboratory medicine.     

Inhaled and oral bronchodilator therapy in exercise induced asthma

Measurements of peak expiratory flow rate during serial exercise tests were used to assess the efficacy of the beta adrenergic stimulants oral terbutaline (5 mg) and fenoterol aerosol (400 micrograms), in preventing post-exercise bronchoconstriction in 18 asthmatic subjects. While both compounds significantly elevated resting levels of peak expiratory flow rate for at least four hours, there were qualitative and quantitative differences in the effects of the two drugs on exercise induced bronchoconstriction. Oral terbulation did not significantly alter the pattern of response to exercise. However, the peak expiratory flow rates before during and after exercise were significantly higher compared with placebo at two, four and six hours after the drug. The importance of examination of actual values for peak expiratory flow rates as well as percentage changes when testing oral bronchodilators is emphasised. Aerosol fenoterol completely blocked post-exercise bronchoconstriction immediately after inhalation and for up to four hours in most subjects. Bronchodilatation occurred in all subjects during exercise in the presence of both the active and placebo drugs. It is postulated that the superiority of the aerosol in blocking exercise induced bronchoconstriction may be function of its activity at the surface of the bronchial mucosa.     

Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent's disease

Dent's disease, which is a renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is associated with inactivating mutations of the X-linked chloride channel, CLC-5. However, the manner in which a functional loss of CLC-5 leads to such diverse renal abnormalities remains to be defined. In order to elucidate this, we performed studies to determine the segmental expression of CLC-5 in the human kidney and to define its intracellular distribution. We raised and characterized antisera against human CLC-5, and identified by immunoblotting an 83 kDa band corresponding to CLC-5 in human kidney cortex and medulla. Immunohistochemistry revealed CLC-5 expression in the epithelial cells lining the proximal tubules and the thick ascending limbs of Henle's loop, and in intercalated cells of the collecting ducts. Studies of subcellular human kidney fractions established that CLC-5 distribution was associated best with that of Rab4, which is a marker of recycling early endosomes. In addition, confocal microscopy studies using the proximal tubular cell model of opossum kidney cells, which endogenously expressed CLC-5, revealed that CLC-5 co-localized with the albumin-containing endocytic vesicles that form part of the receptor-mediated endocytic pathway. Thus, CLC-5 is expressed at multiple sites in the human nephron and is likely to have a role in the receptor-mediated endocytic pathway. Furthermore, the functional loss of CLC-5 in the proximal tubules and the thick ascending limbs provides an explanation for the occurrences of low molecular weight proteinuria and hypercalciuria, respectively. These results help to elucidate further the patho-physiological basis of the renal tubular defects of Dent's disease.     

Chronic inhibition of NOS does not prevent plasticity of rat somatosensory (S1) cortex following deafferentation

Nitric oxide (NO) has been proposed as an intercellular messenger mediating postsynaptic to presynaptic information transfer in the induction of long-term potentiation. A number of studies support the possible involvement of NO in synaptic plasticity. NO may have a role in synaptogenesis and synaptic plasticity in developing rat brain and may play a fundamental part in the process of regeneration, plasticity, and retargeting of axons following injury. We examined the possible role of NO on plasticity in the rat first somatosensory cortex with [14C]2-deoxyglucose (2-DG) autoradiography in rats treated daily with l-nitroarginine (l-NA) following neonatal unilateral vibrissae deafferentation. After 6 weeks of l-NA treatment, the local cerebral glucose utilization (LCGU) and the spatial extent of the metabolic activation following stimulation of the spared whisker was measured. NOS catalytic activity exhibited significant inhibition throughout the treatment period. Vibrissae deafferentation produced a small but not statistically significant increase of LCGU in the vibrissa activated C3 barrel, and l-NA treatment did not alter the activation of LCGU in the deafferented cortex following whisker stimulation. Additionally, l-NA treatment did not alter the area of metabolic activation on either the non-deafferented side or the deafferented side. Deafferentation produced a 298% increase in the metabolic representation of the spared C3 barrel following stimulation in the saline treated animals, a 257% increase in the chronically l-NA treated animals, and a 256% increase in the short-term treated animals, all with respect to the response in the non-deafferented cortex. Metabolic plasticity in the barrel cortex was not attenuated by l-NA treatment. These results show that nitric oxide does not play a major role on developmental cortical plasticity induced by vibrissae deafferentation in the rat.