Biological markers as indicators of exposure and pneumoconiotic risk: Prospective study

This research is designed to evaluate a number of biological markers to estimate harmful exposure on coal miners from different mining regions in France and to relate the outcome to differences in prevalence of coal worker pneumoconiosis (CWP) between these regions. Eight epidemiological groups of active and ex-miners (smokers and non-smokers) have been selected in the French collieries (North, Lorraine and Provence) according to their occupational and pneumoconiotic status. The following biomarkers have been evaluated: cellularity of sputum, elementary analysis of particles in TEM/EDAX, plasma neutral metalloendo peptidase elastase type (NMEP), leucocyte elastase (HLE), fibronectin (FN) and elastin peptides. Pulmonary alveolitis, expressed by sputum cellularity, is different between active workers groups but not related to the general background of pneumoconiosis prevalence in the French collieries. In the plasma parameters, fibronectin, HLE and NMEP significantly increased in all groups of coal mine workers as compared to the control group, except for fibronectin parameter in Lorraine collierie. The degree of increase of these parameters allow us to discriminate the different groups and suggest that plasma FN, HLE and NMEP may be considered as biological markers of chronic inhalation of coal mine dust particles. The decrease of elastin peptides level in the Lorraine group alone suggests a specific alteration of elastin metabolism. These parameters were not related to the development of pneumoconiosis and its degree of severity.     

Myofibroblasts and the progression of diabetic nephropathy

Background. The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study.Subjects and methods. We have studied by immunohistochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; &agr;-smooth-muscle actin (&agr;-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue for three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression renal cytoskeletal proteins. Results. In normal kidneys, cells expressing &agr;-SMA were confined to the vascular media and adventia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing &agr;-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial &agr;-SMA proved to be a predictor of progressive diabetic nephropathy (R² for 1/serum Cr slope=0.608, P=0.00001). This predictive parameters; tubular atrophy (R²=0.477, P=0.00004) and interstitial fibrosis (R²=0.28, P=0.001). Conclusion. We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.     

Diabetes in sex offenders

Thirteen diabetic male sex offenders were compared to 13 nondiabetic sex offenders matched on age, education and offense type. A standard battery of tests administered in the assessment of sex offenders was used to compare the two groups. The tests examine sexual history and preference, substance abuse, violence, personality, and neuropsychological impairment. Results showed that diabetics more often than controls complained of impotence and were nonresponders during phallometric testing. Diabetics, as adults, tended to have less sexual experience with adults and more with pubescent females. The two groups did not differ in number of sexual or nonsexual offenses. The diabetics reported more problems controlling their emotions and more often than controls presented in assessment with inappropriate and/or aggressive behavior and poor cooperation. MMPI results showed diabetics to have more overall clinical disturbance than controls including anxiety, health concerns, family problems, authority problems, criminality, confused thinking and ruminating. Diabetics and controls did not differ in reported frequency of violent behavior but the diabetics responded more extremely, given the circumstances. Diabetics tended to show more violence to their own children. The role of diabetes in the relapse cycle model of offending is discussed.     

Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n=13) or a mean dosage of 0.07 mg/kg per day (n=4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient,P<0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in preadolescents receiving FK-506 but no prednisone (P<0.02 andP<0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.     

Alcohol and Platelet Function

Epidemiological studies have shown that moderate consumption of alcoholic beverages is inversely related to the incidence of the complications of coronary artery disease. The protective effect of ethanol may be partially attributable to an inhibitory effect of ethanol on platelets. This article summarizes the experimental observations that ethanol inhibits platelet responses to specific physiological agonists. In alcoholics, various platelet defects have been observed, but these may be influenced by metabolic factors rather than the presence of ethanol alone. The acute effects of ethanol on platelet functions both in vivo and ex vivo will be reviewed. Evidence will be presented demonstrating that ethanol added acutely in vitro inhibits phospholipase A₂ in stimulated platelets. The interaction of ethanol with other signal transduction pathways will also be discussed.     

Molecular breakpoint analysis and relevance of variable mosaicism in a woman with short stature,primary amenorrhea,unilateral gonadoblastoma,and a 46,X,del(Y)(q11)/45,X karyotype

Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM‐mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease–associated gene to cause intestinal aganglionosis. © 2002 Wiley‐Liss, Inc.     

Diagnosing intramuscular myxoma by fine-needle aspiration: A multidisciplinary approach

The gross and microscopic appearances of aspirates from ten intramuscular myxomas are reported. The specimens were obtained from seven women and three men, ages 43 to 75, who had tumors involving the muscles of the thigh (7), upper arm (2), and forearm (1). Magnetic resonance (MR) imaging performed in six of the ten cases revealed well-defined, sharply demarcated tumors exhibiting low signal intensity relative to muscle on the T1-weighted images. The tumors were hyperintense to muscle on T2-weighted images. All aspirated tissues were clear, tenacious, and viscous. Smears contained few spindled and histiocytoid cells in an abundant mucoid background. Spindle cells demonstrated long cytoplasmic processes that in areas intertwined to form fibrillar tangles. Nuclei were oval to spindled with fine chromatin and inconspicuous nucleoli. Capillaries were sparse with simple (nonplexiform) branching. The differential diagnosis of myxoid lesions of the extremities includes benign entities such as myxoid schwannoma and neurofibroma, mesenchymal repair, and ganglion cyst, as well as malignant neoplasms such as myxoid liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, and extraskeletal chondrosarcoma. The findings of this study revealed that, although the cytologic features were suggestive of intramuscular myxoma, a definitive diagnosis was often difficult, owing to scant cellularity and lack of distinctive cytologic features. The MR imaging findings may be utilized as an adjunct to the cytologic features to more confidently suggest a diagnosis of intramuscular myxoma. Diagn Cytopathol 1994;11:255–261. © 1994 Wiley-Liss, Inc.     

Prostaglandin synthesis by squamous carcinoma cells of head and neck, and its inhibition by non-steroidal anti-inflammatory drugs

The purpose of this study was to determine the nature and amounts of prostaglandins (PGs) produced by squamous carcinoma cells (SCC) and the sensitivity of these cells to non-steroidal anti-inflammatory drugs. SCC of four lines of the tongue and one line of facial epidermis of humans were incubated in phosphate buffer solution with ¹⁴C-arachidonic acid (AA). Radioactive metabolites in aqueous methanol were chromatographed on Sep-Pack CIS cartridges, separated and quantitated by means of TLC, autoradiography, and liquid scintillation counting. The results showed that cyclooxygenase products, PGs, were the major products formed by all cell lines, and PGE₂ was predominant among the PGs detected. Two radioactive bands corresponding to PGF_2α and three unseparated standards of PGA₂, 15-keto-PGE₂, and 13,14-dihydro-15-keto-PGE₂were detected in lesser amounts. Very small amounts of the lipoxygenase products 12-and 15-HETE were found. The concentrations of indomethacin, ibuprofen and aspirin required to inhibit 50% of PGE₂ synthesis (IC₅₀) by SCC lines were .008- .080, .080–6.4 and 32–88 μM, respectively.