Benzo[a]pyrene diol epoxide I modification of DNA in human skin xenografts

Human skin xenografts were established on the subscapular area of skin of nude (nu/nu NIH-Swiss background) mice. When treated with benzo[a]pyrene diol epoxide I (BPDE I), specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the 32P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dpGp adducts were the major adducts. Xenografts pretreated with either allantoin or anthralin showed an increase in the major 7R- and 7S-BPDE I adducts compared to only BPDE I treatment. Likewise, we observed an increase in the quantity of different minor adducts. The ratios between the minor and major adducts in the pretreated grafts remained consistent with the ratio in the grafts treated with BPDE I only. We conclude that these modulators induce cells in the xenograft to enter S phase of the cell cycle. Moreover, we observed that these compounds altered the quantity of the minor carcinogen-DNA adducts without altering the overall ratios between the major 7R- and 7S-BPDE I-dpGp adducts and the minor carcinogen-DNA adducts.     

Ultrasonography in the detection of cervical incompetency

In 80 pregnancies with clinical and ultrasonic signs of cervical incompetency, the length of the cervix and the thickness of the anterior wall of a lower uterine segment have been evaluated ultrasonically. We have also measured the width of the endocervical canal and studied the prolapse of fetal membranes (with fetal parts) into the endocervical canal. We evaluated these same parameters in 80 healthy pregnancies. The length of the cervix, the thickness of the anterior wall of a lower uterine segment, and the width of the endocervical canal were followed longitudinally in the patients from the 10th to the 36th gestation week. No statistically significant differences between age groups were found. In four age groups at risk for cervical incompetency, cervical lengths and wall thickness were significantly different (p less than 0.001) from those in comparable controls. Forty-five percent of the patients in the at-risk group, with cervical cerclage, delivered at 37.3 (range: 32 to 41) weeks and 6.25% of pregnancies ended in abortion when the amniotic membrane herniated into the cervical canal, with or without some part of the fetus.     

MRI of transplanted pancreatic islets.

A promising treatment method for type 1 diabetes mellitus is transplantation of pancreatic islets containing beta-cells. The aim of this study was to develop an MR technique to monitor the distribution and fate of transplanted pancreatic islets in an animal model. Twenty-five hundred purified and magnetically labeled islets were transplanted through the portal vein into the liver of experimental rats. The animals were scanned using a MR 4.7-T scanner. The labeled pancreatic islets were clearly visualized in the liver in both diabetic and healthy rats as hypointense areas on T2*-weighted MR images during the entire measurement period. Transmission electron microscopy confirmed the presence of iron-oxide nanoparticles inside the cells of the pancreatic islets. A significant decrease in blood glucose levels in diabetic rats was observed; normal glycemia was reached 1 week after transplantation. This study, therefore, represents a promising step toward possible clinical application in human medicine.     

Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells.

Recent studies have shown inflammatory markers in affected neural tissues of amyotrophic lateral sclerosis (ALS) patients. We examined immunocytochemically spinal cord tissues of six patients with ALS, two with corticospinal tract degeneration secondary to cerebral infarcts and three control subjects without neuropathologic abnormalities. ALS spinal cords had dense macrophage infiltration (one log greater than control spinal cords) involving the white and gray matter, with heaviest infiltration of lateral and ventral columns and, in one patient, prefrontal gyrus and the occipital lobes of the brain. Macrophages in ALS spinal cord showed strong expression of cyclooxygenase-2 (COX-2) (one log greater than control tissues) and inducible nitric oxide synthase. In the gray matter, macrophages surrounded and appeared to phagocytize neurons (NeuN-positive) that appeared to be dying. Vessels showed damage to the tight junction protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive T lymphocytes. ALS spinal cords, but not control cords, were sparsely infiltrated with mast cells. In control cases with corticospinal tract degeneration following hemispheric cerebral infarction, macrophage infiltration of the white matter was COX-2-negative and restricted to lateral and anterior corticospinal tracts. Our data suggest that inflammation in ALS spinal cord and cortex is based on innate immune responses by macrophages and mast cells and adaptive immune responses by T cells.     

Multiple myeloma: epidemiological features in a well-defined population in Burgundy, France

Epidemiological features of multiple myeloma were studied over a seven-year period (1980-86) in the department of C?te d'Or (population 478,000). The crude annual incidence rates were 3.7/100,000 for males and 4.0/100,000 for females. The corresponding age-standardized rates were 2.5 and 2.1. The sex ratio was 1.2. Cumulative rates were 0.3% for both sexes. Age and specific incidence were low before 50 and increased with advancing age up to 85 years in males and females. There was no significant variation in incidence over the seven-year period. The risk of multiple myeloma was slightly higher in urban than in rural areas (the variations were not significant). The period between the beginning of the symptoms and the diagnosis was often short, less than one month in 56% of the cases. When compared to other population based registries the incidence rates are similar to those reported all over the world (except for registries with a high proportion of blacks in the population). Cases have been staged according to Durie and Salmon classification: 32% of the cases were classified as Stage I. This result suggests that globally cases diagnosed in a well-defined population are less severe than those reported in hospital statistics. Survival showed significant differences: there were better rates for patients under 75 and for patients at stage I and II compared with stage III patients. Percentage and morphology of plasma cells also influenced prognosis.     

Development of neoplastic phenotype following transfection of HNF cells with sarcoma DNA

DNA isolated from chondrosarcoma cells effectively transformedNIH-3T3 cells and human foreskin fibroblasts. The transfectedNIH-3T3 cells, directly implanted three or four passages later,formed progressively growing tumors ( 2.0 cm in diameter) subcutaneouslyin nude mice. No metastasis was evident upon pathological examinationof the tumor bearing mice. Transfected human foreskin fibroblaststhat exhibited anchorage independent growth formed only smalltumors in nude mice (<0.6 cm in diameter). The transfectedhuman cells which exhibited anchorage independent growth reactedwith the monoclonal antibody 345.134S, specific for an epitopeexpressed by human sarcoma cells. The transfected NIH-3T3 cellsdid not exhibit reactivity with the same monoclonal antibody.Southern blot analysis of the DNA prepared from the transfectedNIH-3T3 cells, that developed as a progressively growing tumorin a nude mouse, revealed the presence of human repetitive DNAsequences.     

Eccrine gland involvement in Krabbe's disease

Summary Lysosomal storage inclusions were observed in skin eccrine gland secretory and myoepithelial cells in three cases of Krabbe's disease. In addition to storage there were numerous degenerative changes, occasionally resulting in cell necrosis. These findings suggest a generalized nature of the storage process in this lysosomal enzymopathy and point to high galactocerebroside turnover in eccrine gland epithelium. This knowledge may be of value in the biopsy diagnosis of Krabbe's disease.