Biomedical subjects
Publications and source records attributed to J de Graaf.
A 58-year-old woman developed Gradenigo's syndrome. The clinical signs and symptoms of the otitis were rather atypical and there was a considerable delay before the correct diagnosis was made. The pathophysiology, therapy and differential diagnosis of this syndrome, which has become rare since the introduction of antibiotics, are discussed.
An apolipoprotein B gene MspI RFLP was identified by the use of a probe to a portion of the 3' end of the gene. By Southern blotting analysis after digestion with MspI, this probe detected either a 9 kb or a 2.6 kb fragment. Family studies showed that these corresponded to alleles that segregated in a simple Mendelian fashion. The minor allele (9.0 kb) had a frequency of approximately 12% in an unrelated Caucasian population. Restriction mapping showed that the minor allele was due to the loss of an MspI site in exon 26. Sequencing of both alleles in the region containing the polymorphic MspI site revealed a single-base pair alteration which abolished the MspI site at codon 3611 of the mature apoB protein. In the major allele, this codon is CGG, which specifies Arg; whereas in the minor allele, it was CAG, which codes for Gln.
We report our results in profiling peripheral blood lymphocyte subpopulations with monoclonal antibodies in 17 multiple sclerosis (MS) patients, 22 patients with other neurological diseases (OND), and 11 healthy controls, using a blind experiment. Untreated patients with a chronic progressive MS have higher T-helper cell (OKT4+) counts and a higher ratio OKT4+/OKT8+ than other MS patients, OND or healthy controls. Two weeks after the onset of a relapse of MS there is a decreased T-helper and an increased T-suppressor cell percentage. Treatment with ACTH results in a significant increase of helper cells after 4 weeks of therapy. Patients with the lowest helper cell counts and the lowest helper/suppressor ratio show the best clinical improvement by ACTH. High OKT4+ cell percentages make a chronic progressive course of MS more probable.
Oxidative modification of low density lipoprotein (LDL) has been implicated as a factor in the generation of macrophage-derived foam cells, the hallmark of atherosclerotic plaques. Because LDL consists of discrete subfractions with different physicochemical characteristics, the question arises as to whether these LDL subfractions differ in their susceptibility to oxidative modification. To answer this question, three LDL subfractions, LDL1, LDL2, and LDL3, were isolated from the plasmas of 11 healthy volunteers by density gradient ultracentrifugation. The LDL subfractions were oxidatively modified by incubation with copper ions. Differences in the subfractions' susceptibilities to lipid peroxidation were studied by measuring the formation of the 234-nm-absorbing oxidation products every 3 minutes on an ultraviolet spectrophotometer. A significant inverse linear relation was found between LDL subfractions and lag time (regression coefficient = -8.50, p less than 0.001), indicating that both the dense LDL3 and the light LDL2 were less well protected against oxidative modification than the very light LDL1. The LDL subfractions showed a positive linear relation with the rate of oxidation (regression coefficient = 0.46, p less than 0.001) and the amount of conjugated dienes formed in the LDL subfractions after 4 hours of oxidation (regression coefficient = 9.24, p less than 0.001). Thus, both LDL3 and LDL2 were more extensively modified in time than LDL1, which may be explained by the significantly higher concentration of polyunsaturated fatty acids in LDL3 (micromoles per gram LDL cholesterol) compared with LDL1 (Tukey's test, p less than 0.05). These results indicate that the more dense LDL subfractions, that is, LDL2 and LDL3, are more susceptible to oxidative modification and therefore may contribute more to foam cell formation than the less dense LDL subfraction LDL1.