Adrenocortical Toxicity of 3-Methylsulfonyl-DDE in Mice: II. Mitochondrial Changes following Ecologically Relevant Doses

Transmission electron microscopy was used to characterize earlyultrastructural lesions in the adrenal zona fasciculata of femaleC57BL mice given a single ip injection of the adrenocorticolyticDDT-metabolite 3- methylsulfonyl-DDE (MCSO₂-DDE Following 3mg/kg, mitochondrial changes were observed 6 hr after dosing.At 12 and 24 hr the mitochondrial changes were conspicuous,with disorganization and disappearance of central cristae. Atdoses of 6, 12, and 25 mg/kg body wt initial (6 hr) mitochondrialvacuolization was observed, followed by disappearance of mitochondria(6–12 mg/kg) or cellular necrosis (25 mg/kg). The metabolicactivation and binding of MeSO₂-[¹⁴C]DDE in adrenal homogenateswere determined in vitro. The irreversible binding of MeSO₂-[¹⁴C]to the mitochondria-containing adrenal S-9 pellet fraction was50 times higher than that to the postmitochondrial S-12 supernatantfraction. The apparent K_m was 2.1 µM and the apparentV_max was 104 pmol/mg protein/30 mm for the binding of MeSO₂-[¹⁴C]to S-0.3 supernatants. The irreversible protein binding wasinhibited by metyrapone (K₁=1 µM) and 11-deoxycorticosterone(K₁=3 µM). In conclusion, the adrenal metabolic activationof MeSO₂-[¹⁴C]DDE is suggested to be mediated by a mitochondrialcytochrome P450 form, presumably P450 (11ß). A primarymitochondrial lesion develops and subsequently leads to degenerationand necrosis of the zona fasciculata.     

Sensory-Motor and Cognitive Functioning in Children Who Have Undergone Bone Marrow Transplantation

ABSTRACT. Sensory-motor and cognitive functioning was investigated in a group of 32 children treated with bone marrow transplantation (BMT), 1–6 years after treatment. Twenty-five of the patients had suffered from leukemia. The BMT procedure had involved a regimen of cytostatic drugs and, for leukemia patients, total body irradiation at a dose of 10 Gy, administered in one session. Cytostatic drugs and irradiation are known to be potentially neurotoxic, particularly when combined. The examination involved four neuropsychological tests of sensory-motor and cognitive functioning, as well as an age-appropriate intelligence test. For control the bone marrow donors (n=32), siblings of the patients, were also investigated. A pronounced delay in motor development was found in four children, who had been treated with BMT including total body irradiation before 3 years of age. Patients between 3 and 11 years of age at BMT were at a slight disadvantage, compared to donors, on tasks involving perceptual and fine motor speed. In older patients no deficits were observed.     

Adult xanthogranulomatosis associated with abnormal plasma apolipoprotein levels

A case of adult xanthogranulomatosis was investigated in depth for lipid abnormalities. The xanthogranulomatous lesion was shown to be composed primarily of cholesterol esters and triglycerides. Fasting plasma lipid levels and lipoprotein concentrations were within normal limits. Plasma lipoprotein electrophoresis and immunoelectrophoresis demonstrated normal high-density lipoprotein (HDL) and low-density lipoprotein mobilities. Polyacrylamide-gel isoelectric-focusing electrophoresis revealed increased levels of very-low-density apolipoprotein (apo) E, especially apo E-III. In the HDL fraction, apo-C-III and apo-E levels were both found to be slightly elevated. These findings might imply a causal relationship between the abnormal plasma apolipoprotein levels and the xanthogranulomatous disease.     

A study of HLA antigen association in localized and generalized granuloma annulare

HLA-A and -B antigen frequencies were studied in 78 patients, 35 with localized granuloma annulare and 43 with generalized granuloma annulare (GA). Twenty-eight patients in each group were also typed for HLA-DR antigens. A group of 200 healthy age-matched subjects served as controls. HLA-A31 and B35 were increased significantly in patients with generalized GA, but not in the localized form. HLA-DR antigen distribution showed no significant variation.     

Relationship of insulin clearance and secretion to insulin sensitivity in non-diabetic Mexican Americans

The antecedents of type II diabetes, while still controversial, are thought to involve decreased insulin sensitivity and compensatory hypersecretion of insulin. Mexican Americans have a three-fold excess risk of type II diabetes and non-diabetic Mexican Americans are characterized by hyperinsulinaemia and insulin resistance. Few data exist, however, on whether there are defects in insulin secretion and/or clearance in this population. We examined insulin sensitivity, secretion and clearance using combined insulin and C-peptide measurements analysed by the minimal model technique of Bergman and colleagues in 10 non-obese, normoglycaemic Mexican Americans and 11 age, sex and obesity-matched non-Hispanic whites. Mexican Americans had significantly decreased insulin sensitivity (SI 4.06 s. 7.56, P = 0.017), higher first phase insulin secretion (1.03 nM vs. 0.72 nM) and decreased insulin clearance (0.099 vs. 0.161) than non-Hispanic whites. Thus, normal Mexican Americans have higher rather than lower insulin secretion suggesting that lower insulin sensitivity may be an early defect in this ethnic group. In addition, they have reduced insulin clearance. Moreover, insulin sensitivity and insulin clearance were positively correlated. We thus speculate that decreased insulin clearance may represent a further autoregulatory mechanism in addition to increased insulin secretion to compensate for decreased insulin sensitivity.     

Cross-sectional study of patients fitted with fixed partial dentures with special reference to the caries situation

Abstract – The caries situation among 30 patients with fixed partial dentures was examined 3 yr after cementation of the constructions. The fit of the crowns on the abutment teeth, the size of the interproximal areas and the relation between the crown margin and the gingival margin were registered. Risk factors for caries development, such as salivary factors, microbiologic factors, oral hygiene and diet were evaluated for each patient. During the 3-yr period 54 caries lesions occurred in 25 patients. Eleven lesions were found on abutment teeth. Two were located on the root surfaces unconnected with the crown margin (>2mm from the gingival margin), three were recurrent lesions, where the crown margin was located above the gingival margin but closer than 2 mm and six were recurrent lesions where the crown margin was located under the gingival margin. No single caries risk factor seemed to be so closely correlated to the number of caries lesions developed that it could be used alone to select of patients at risk. When the sum of the assumed negative factors was used, more caries was found among the patients with three or more factors with negative values in the group as a whole. However, predicting the development of caries in an individual case with a high degree of probability seems to be complicated. Generally speaking there was no indication that caries disease development was caused by the presence of the fixed partial denture per se.     

On naevi and melanomas in dysplastic naevus syndrome patients

Cutaneous melanoma may occur as isolated, so-called 'sporadic’cases or in association with multiple atypical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20–39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12–66 years. Men had significantly more naevi of a size 2 mm or 5 mm on the back than women (P=0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and sire in familial DNS, analogous to earlier reports on sporadic melanoma.^1,2