Lipooligosaccharide of Campylobacter jejuni prevents myelin-specific enteral tolerance to autoimmune neuritis--a potential mechanism in Guillain-Barre syndrome?

Campylobacter jejuni-induced enteritis is the most common infection preceding Guillain-Barre syndrome (GBS), an immune-mediated polyradiculoneuritis. The acute autoimmune attack is thought to be based on C. jejuni antigens which may mimick antigens of the peripheral nervous system. Additional pathomechanisms, like disturbance of natural T cell immunoregulation by C. jejuni, have not been evaluated so far. In experimental autoimmune neuritis (EAN), a T lymphocyte-mediated animal model of human GBS, tolerance to myelin-derived autoantigens can be induced by oral feeding of the respective antigen. Here we investigated whether the lipooligosaccharide (LOS) fraction of C. jejuni may directly alter immunologic tolerance through gastrointestinal pathways. While EAN, actively induced by immunization with bovine peripheral nerve myelin could be ameliorated by precedent feeding of myelin, feeding of C. jejuni LOS along with the myelin antigen not only prevented the tolerizing effects of oral myelin but even accelerated the onset of overt EAN and augmented the myelin-specific B cell response. These findings provide evidence that LOS of C. jejuni, as produced in the gut during C. jejuni-induced enteritis, can disturb natural tolerance to definite proteins which may be or may mimic peripheral nerve antigens. In human patients this may be one of the potential mechanisms to explain why C. jejuni enteritis is a common trigger of GBS.     

Seasonal malaria transmission and variation of anopheline density in two distinct endemic areas in Brazilian Amazonia

Studies on seasonal anopheline fauna variation were performed in two distinct settlements in the State of Rond?nia, Brazil: one at the Madeira River banks (Portuchuelo) with stable native Amazonian population; the other at an inland lumber-extracting farm (Urupá) in dry land, in which adults are mostly migrants. During a 6-yr period (1994-2000), 8,638 adult anophelines were collected: 2,684 in Urupá and 5,954 in Portuchuelo. Anopheles darlingi represented >95% of total mosquitoes caught. Dissection of 4,424 A. darlingi females yielded a very low sporozoite infection index below 0.1%. Oocysts were found in both localities in approximately 0.1% of dissected mosquitoes. Determination of the hour biting rates disclosed seasonal variations in both localities. However, in Portuchuelo, mosquito density peaked at the acme of the rainy season, whereas at Urupá it peaked in the dry season. The increase in mosquito density and incidence of malaria cases were coincident. The high mosquito densities observed in the riverine settlement of Portochuelo sector B, which permits evaluation in > 10,000 mosquitoes' bites/person/year, could explain, in spite of the low mosquito's infection index, the previously described development of natural immunity in the local population that is not observed in the dry land agroindustrial settlement of Urupá.     

Phagocytosis and Chemiluminescence Response of Granulocytes to Monodisperse Latex Particles of Varying Sizes and Surface Coats

The response of human granulocytes to polystyrene latex beads of diameter 0.1–7 m was measured by luminol-dependent chemiluminescence. In all instances, the response to beads of 3–7 m was definitely higher than with smaller beads. In protein-free medium, the chemiluminescence response was slow compared to that of opsonized zymosan, and the highest response was only 9% of the response to opsonized zymosan. Scanning electron microscopy showed that granulocytes in suspension bound the particles, occasionally by extending rope-like protrusions. When the beads were coated with albumin, the chemiluminescence diminished to about 1/3 of that seen with uncoated beads; however, preincubating the beads in serum led to a large increase with beads of 1.1 m (to 25% of the maximal response to opsonized zymosan) and 3.19 m (to 42%), but with the smallest beads, no increase was noted. "Priming" of the cells with tumor necrosis factor- caused a further increase with serum-coated beads. When uncoated beads of 1.1 m were tested with "primed" cells, there was an increase of 6 times in the chemiluminescence compared to un-"primed" cells.     

Assessing lymphocyte functions in neonates for revealing abnormal prenatal development of the immune system

Because it is difficult to assess prenatally induced functional deficits of the human immune system, we developed an ex vivo method for differentiation and maturation of peripheral lymphocytes of newborn, preferentially using umbilical cord blood. Many lymphocyte subsets of newborn infants are "immature" with respect to defined surface receptors. An example of such an immaturity is the almost complete lack of "memory"-type helper T cells (also designated as helper-inducer cells), characterized by expressing the surface receptors: CD4(+)CD45R0(+)CD45RA(-)CD29(high). On the other hand, umbilical cord blood contains many "naive"-type helper T cells (often designated as suppressor-inducer cells), with the receptors: CD4(+)CD45R0(-)CD45RA(+)CD29(low). In this report, we demonstrate that the immature helper lymphocyte population of umbilical cord blood is capable of differentiating to mature cells following stimulation with pokeweed mitogen (PWM) and other stimulants ex vivo. The obtained receptor pattern is virtually indistinguishable from the one observed on the mature cells of adults. Such an extensive differentiation can only be achieved with cells of newborns. As intermediates during differentiation in culture, CD45R0(+)CD45RA(+) cells may be observed which are rather rare in vivo. Additionally, the appearance of several activation (CD25, CD69, HLA-DR) and adhesion (CD11a, CD11b, CD11c, CD18, CD49b, CD49d, CD54) receptors on CD4 cells were analyzed. With this model system evidence for the sequence of events during differentiation and maturation may be obtained. This ex vivo-model is capable of studying the capacity of lymphocytes for differentiation and activation processes barely accessible in vivo. It may also be expected to represent an interesting tool for measuring the capacity for maturation and differentiation in the blood of children of different ages under normal and pathological conditions ex vivo. In addition, substance-induced effects may be studied in vitro with this approach on immature cells from newborn, or infants during culturing. Teratogenesis Carcinog. Mutagen. 20:171-193, 2000.     

The cytotoxic HLA-DQ3 reactive human hybridoma antibody 4166 that May distinguish DQ7 + 8 from DQ9

The human cytotoxic hybridoma antibody 4166 (IgM_χ) was generated by fusing an in vitro EBV-transformed B-LCL from a multiparous woman with the mouse-human heteromyeloma fusion partner CB-F7. In microcytotoxicity and IIF tests with B-LCLs as target cells, the mAb 4166 was specific for DQ3 ( = DQ7 + 8 + 9). However, when used for DQ typing of class-II-positive PBMCs, 4166 could be rendered functionally specific for DQ7 + 8and did not react with DQ9⁺ PBMCs. Binding of mAb 4166 to DQ8-positive cells was efficiently blocked by several allotype-specific mAbs recognizing DQ8. Other HLA class-II-specific mAbs were unable to inhibit. With the use of mAb 4166, it is possible to discriminate DQ7 + 8 from DQ9 in serologic DQ typing.     

Immunomodulatory properties of cyclic hexapeptide oxytocin antagonists.

The thymic repertoire of neuroendocrine 'self' antigens has been previously described on the basis of the intrathymic expression of neurohypophysial (NHP)- and tachykinin-related peptide signals and receptors. According to that model, the cryptocrine signalling between thymic epithelial/nurse cells and thymocytes through NHP-related signals and receptors constitutes one accessory pathway in the process of T-cell differentiation and/or activation. A pharmacological manipulation of that novel type of cell-to-cell signalling was tested by the investigation of the immunomodulatory properties of novel cyclic hexapeptide oxytocin (OT) antagonists (MSD Research Laboratories). These compounds were found to significantly inhibit the productions of cytokines (mainly IL-1 beta and IL-6) elicited by anti-CD3 treatment of human whole blood cell cultures. Cytokine productions were more significantly reduced by OT antagonists in whole blood cell cultures derived from female volunteers than in those obtained from male donors, suggesting an influence of the gonadal steroid environment on the expression of NHP peptide receptors by immune cells. These observations support the concept of novel immunomodulating approaches through immune-specific neuropeptide antagonists, as well as the pharmacological value of such strategies in selective immunotherapy.     

Measurement of fatty acid oxidation in premature newborn infants with the 13C-triolein breath test

The 13C-triolein breath test is a method giving evidence of extent and rate of fatty acid oxidation in newborn infants on parenteral nutrition. The test has the special advantage of being non-invasive. Triolein labeled with the stable carbon isotope 13C and emulsified in soybean-oil is used as a tracer. 10 mg of 13C triolein per kg body weight are administered intravenously. The 13CO2 resulting from the fatty acid oxidation is analysed in expired breath by ratio-mass-spectrometry. The calculated 13C elimination is representative of the rate of fatty acid oxidation during the examination period. First studies on 15 premature infants have shown that an average of 27.0 +/- 1.8% of the dose administered is oxidized within 4 h. The present results suggest that the oxidation rate may be related to the maturity of the prematurely born infants.     

The value of radiographic film for the characterization of intensity-modulated beams

In this paper the performance of radiographic film (KODAK X-Omat V) for analysing intensity-modulated (IM) beams in a plane at reference depth (5 cm for 6 MV, 10 cm for 18 MV) was investigated. The field size dependence of the film response was studied for small and medium field sizes. The dose rate dependence of the response and possible effects of fractionating the dose were assessed. In the end, profiles were measured for two clinically delivered IM beams, and the results were compared with diamond detector data. We found that the response of the radiographic film increases with field size, but for field sizes up to 15 x 15 cm the deviations remain within 3% for measurements with the films in a plane at reference depth. We found that the response of the films decreases with decreasing dose rate, and that the extent of this effect differs from film batch to film batch. For clinical IM beams the effect can amount to about 9% at the location of shielded organs at risk. Also, fractionating the dose reduces the net optical density, but this effect is normally small when assessing IM beams. In low-dose regions low-energy photons have an important contribution, resulting in a higher response at these positions. This may counteract the dose rate dependence of the response. In the high-dose regions of the two IM beams that were studied, the relative dose measurements with film are within 1% of those obtained with a diamond detector, when the results of three films are averaged. In shielded organs at risk the deviations can mount to about 3%, depending on the film batch. In conclusion, radiographic film is a suitable detector for characterizing IM beams in a plane at reference depth.     

ISA--Information System Anesthesia. Decision support by a computer-based information system

"ISA"-Information System Anesthesia-will support the anesthesiologist by presenting information concerning the anesthesia approach. In addition to computing patient data (monitoring), there are three special fields where computers are used in anesthesia: (1) simulation systems for anesthesia training (preventing critical incidents); (2) critiquing systems to comment on the planned anesthesia decisions; and (3) reference systems for rapid information gathering. Simulation and critiquing systems are mainly useful for personal training. Reference systems present information concerning the anesthesia problems to aid in decision-making. ISA is a reference system designed to support the decision process for neurosurgical operations; a new method of presenting information by personal computer in the surgical working area. For each neurosurgical operation there is a graduation of condensed and detailed information with the option of also obtaining general anesthesia knowledge.     

A decision tree for the treatment of caries in posterior teeth

Because of a better understanding of the caries process, a decrease in the prevalence of caries, and the rapid development of dental materials, a renewed approach to the treatment of dental caries in the posterior region is possible. A decision tree for the treatment of caries in posterior teeth, taking into account some of the most recent tooth substance-saving treatment options, is presented. These possibilities gradually evolve from nondestructive to conventional cavity preparations. In addition, the "preventive Class II restoration" is introduced. The application of this conservative attitude toward invasive techniques offers great advantages for both the patient and the dentist. Unfortunately, this approach is time-consuming. Long-term clinical evaluation of the application of the proposed decision tree on a wide scale is needed to confirm its potential benefits or to modify and improve treatment options.