HLA polymorphism and T cell recognition of a conserved region of p190, a malaria vaccine candidate.

We have examined T cell recognition of a recombinant polypeptide (190L), corresponding to a 175-amino-acid-long conserved region of the major surface antigen (p190) of Plasmodium falciparum merozoites. We show that 190L contains a variety of T cell epitopes, and can be recognized in association with many different MHC class II molecules, including HLA-DR, DP, and DQ antigens. Most of the epitope-containing peptides are able to bind to more than one DR, and a single DR molecule can bind to different peptides. These findings, together with the fact that humans are generally heterozygous at the DR, DQ, and DP beta chain loci, suggest that MHC restriction should not be a major constraint in the development of malaria subunit vaccines.     

Immunodeficiency and infantile bone and joint infection

Fifteen patients with infantile bone and joint infections were studied immunologically and clinically, 3 at the time of illness and 12 later. Abnormality of immunoglobulins, or complement, or phagocytes was found in 9 patients; 6 were within normal limits for the tests undertaken. Immunodeficiency is probably responsible for the subdued clinical signs of infection and for delayed diagnosis in some patients. It was also related to the extent of femoral head damage in infective arthritis of the hip and to the incidence of wound infection in late elective surgery.     

Activated protein C resistance in anterior ischaemic optic neuropathy

PURPOSE: Protein C is a major component of the natural anticoagulant pathway. Resistance of coagulation factor V (FV) to activated protein C (APC), mostly due to FV Leiden mutation, is the most common cause of inherited thrombophilia. The aim of this retrospective study was to determine the prevalence of APC resistance and Leiden mutation in patients with non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: A total of 25 patients with NAION were examined between 1997 and 2002. The patients were screened for APC resistance and FV Leiden mutation as well as for acquired risk factors of vascular disease such as diabetes mellitus, hypercholesterolaemia, hypertonia and ischaemic heart disease. A control group of subjects without ocular vascular disease and with homogenous distribution of the same risk factors was used for comparison. RESULTS: Six of the 25 patients (24%) with NAION had APC resistance due to the heterozygous Leiden mutation of FV. The frequency of the same genetic mutation in the control group was only 5.9%. Odds ratio calculations showed that patients with the Leiden mutation were at a significantly higher risk of NAION than control patients (p < or = 0.021). CONCLUSION: The high frequency of Leiden mutation in NAION suggests a pathogenic role of the mutation in the disease.     

Case of desmoplastic infantile ganglioglioma secreting ceruloplasmin

Desmoplastic infantile ganglioglioma is a rare World Health Organization (WHO) grade I tumor commonly arising in early infancy and usually presenting with both solid and cystic components. We report a case of a large midline-enhancing desmoplastic infantile ganglioglioma in which newly formed cysts in communication with lateral ventricles contained highly proteinaceous fluid. Proteomic analysis of the fluid showed three proteins not normally found in cerebrospinal fluid. Immunohistochemical analysis of the tumor sample showed that the desmoplastic infantile ganglioglioma produced a high concentration of ceruloplasmin, which probably accounts for most of the 30- to 40-fold increase in protein compared with normal cerebrospinal fluid. To our knowledge, this is the first report of ceruloplasmin secretion by a brain tumor, and ongoing studies on the mechanism might yield novel approaches to reducing cyst production and protein content in an otherwise stable solid tumor.     

Increased vascular endothelial cell production of interleukin-6 in severe preeclampsia

OBJECTIVE: The purpose of this study was to determine whether plasma from women with severe preeclampsia stimulates the production of endothelial cell interleukin-6 production and whether vitamin E could inhibit this process. STUDY DESIGN: Human umbilical vein endothelial cells were cultured in the presence of 5% plasma from women with severe preeclampsia (n = 12) or healthy pregnant women at term (n = 12), with or without 50 micromol/L vitamin E. Levels of interleukin-6 in plasma and human umbilical vein endothelial cell-conditioned media were measured by enzyme-linked immunosorbent assay. RESULTS: Interleukin-6 levels were elevated 5-fold in preeclamptic plasma compared with normal pregnant plasma (P <.05). Human umbilical vein endothelial cell interleukin-6 production was increased 25% by preeclamptic plasma compared with normal pregnant plasma (P <.005), and increased interleukin-6 production by preeclamptic plasma was inhibited by vitamin E. CONCLUSION: Endothelial cell activation by preeclamptic plasma stimulates interleukin-6 production, which is inhibited by vitamin E. These findings provide a potential cellular mechanism for the beneficial effects of antioxidant therapy in preeclampsia.     

Ochronotic arthropathy

The authors report on 18 members of four generations of an alkaptonuric family. All three males in the third generation are clinically affected; two members of the family tree have undergone major joint surgery.     

Guided bone regeneration around titanium plasma-sprayed,acid-etched,and hydroxyapatite-coated implants in the canine model

BACKGROUND: Endosseous dental implants with rough surfaces have been designed to improve early healing, especially in areas of poor bone or insufficient bone quantity. The aim of this study was to histomorphometrically assess the bone-to-implant contact on 3 different rough-surfaced implants following guided bone regeneration. METHODS: Mandibular premolars and first molars were extracted in 12 dogs, and healing was allowed for 6 months. Six implant osteotomy sites were prepared, 3 per side, followed by the creation of 7.3 mm wide by 5 mm deep surgical defects in the coronal section of the osteotomy sites. Ten-mm long titanium screw-type implants with titanium plasma-sprayed (TPS), hydroxyapatite-coated (HA), or acid-etched (AE) surfaces were placed; the surrounding defects were filled with canine demineralized freeze-dried bone allograft; implants/grafts were covered with expanded polytetrafluoroethylene membranes; and the tissue was closed. Following a healing period of 4 months, the animals were sacrificed and mandibular blocks were harvested for histomorphometric analysis. RESULTS: The mean percentage of bone-to-implant contact in the defect and non-defect areas for the different implant surfaces was: AE 16.24% defect, and 28.78% non-defect; TPS 25.08% defect, and 16.96% non-defect; and HA 48.25% defect and 26.60% non-defect. Within the defect, the mean difference in the bone-to-implant contact was significant for HA compared to TPS (P < 0.0001) and HA versus AE (P < 0.0001); TPS versus AE was not significant (P = 0.063). In the non-defect areas, the mean difference in the bone-to-implant contact was significant for AE versus TPS (P = 0.010); all other comparisons were not significant. There were 18 membrane exposures in the 72 implant sites. Data were analyzed again to assess the impact of membrane complications. Using a 1-way analysis of variance, the bone-to-implant contact was compared between the sites with and without membrane complications. No significant differences were seen in the defect areas or in the non-defect areas between the sites with and without membrane complications. CONCLUSION: In this study, the bone-to-implant contact in regenerated bone was greatest when an HA-coated implant was used.     

Detection and localization by the monoclonal anti-interleukin 2 receptor antibody AMT-13 of IL 2 receptor-bearing cells in the developing thymus of the mouse embryo and in the thymus of cortisone-treated mice

During embryonic development of the mouse, before expressing classical T cell markers, the blast cells colonizing the thymus react with the monoclonal antibody AMT-13 shown previously to detect interleukin 2 receptors. The proportion of AMT-13+ cells decreases as gestation time increases. On the other hand, the proportion of Thy-1+, Lyt-1+ and Lyt-2+ cells increases during ontogenesis. On the 19th day of gestation when the thymus architecture is comparable to the adult thymus, the AMT-13+ cells become localized in the subcapsular area of the cortex. In the adult thymus after cortison treatment the regenerating cells express the AMT-13 antigen. The AMT-13 antigen presumably the interleukin 2 receptor is the first marker of the early embryonic thymocytes reported until now that may be related to cellular function.     

Natural history of fetal position during pregnancy and risk of nonvertex delivery

OBJECTIVE: To examine the natural history of fetal position throughout pregnancy and the likelihood for nonvertex delivery. METHODS: We examined fetal positions at 15-22 weeks, at 31-35 weeks, and at delivery using data from the Routine Antenatal Diagnostic Imaging with Ultrasound trial. Characteristics of women with nonvertex and vertex presentation at delivery were compared. Multivariable logistic regression analysis was performed to determine risk factors for nonvertex presentation at delivery, and odds ratios were calculated for those risk factors found to be statistically significantly associated with nonvertex presentation. RESULTS: Data for 7,045 women who underwent routine prenatal ultrasound examinations were analyzed. We found no association between nonvertex presentation at 15-22 and at 31-35 weeks of gestation. A nonvertex fetus at 35 weeks had a 45% chance of spontaneous version by delivery. Multivariable logistic regression analysis found that multiparous women had half of the risk of nonvertex presentation as nulliparous women. Smoking during pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.10-1.96), low volume of amniotic fluid at 31-35 weeks (OR 3.74, 95% CI 1.85-7.53), and fundal position of the placenta at late ultrasound examination (OR 1.85, 95% CI 1.23-2.78) were all associated with significant increases in the risk of nonvertex position at delivery. CONCLUSION: Spontaneous version of a nonvertex fetus at 35 weeks of gestation is still likely.