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Raccoon ascarid larvae as a cause of fatal central nervous system disease in subhuman primates.

To assess the danger of Baylisascaris procyonis (the common roundworm of raccoons) to subhuman primates, as well as the zoonotic potential of the parasite, 4 squirrel monkeys were inoculated by stomach tube with 5,000 or 10,500 infective B procyonis eggs. Fulminating severe CNS disease developed at 10-15 days after inoculation, and the monkeys died or were euthanatized at 12-19 days. At necropsy, numerous hemorrhagic migration tracks were visible in coronal brain slices. Histologically, numerous migration tracks and larvae were seen in the brain as well as the spinal cord. Larvae measured 60-65 micrometers in midbody diameter. Migration tracks averaged 508 micrometers X 354 micrometers in cross section and consisted of foci of malacia and microcavitation, with an influx of macrophages and leukocytes, and various degrees of hemorrhage. Also seen were extensive perivascular cuffing, gliosis, astrocytosis, and a mixed inflammatory cell infiltrate. Numerous larval granulomas were seen grossly and microscopically throughout the body; they were particularly abundant in the tissues of the head, neck, and thorax. It was concluded that B procyonis should be considered a threat to the health of subhuman primates and an important potential zoonosis in situations wherein infection of monkeys or human beings could take place.

Animals↗

Extensive TCR junctional diversity of V gamma 9/V delta 2 clones from human female reproductive tissues.

Panels of gamma delta T cell clones bearing the V gamma 9/V delta 2 form of TCR were derived from human first trimester decidualized endometrium and cervix. Seventy-three percent of these clones expressed the human mucosal lymphocyte Ag HML-1 compared with only 14% of PBL V gamma 9/V delta 2 clones, indicating that most clones were derived from the tissue itself rather than contaminating peripheral blood. All 13 clones isolated expressed V gamma 9JPC gamma 1- and V delta 2(D)J delta 1-encoded receptors; TCR gamma and delta junctional regions from most of these were sequenced and analyzed, together with the TCR-delta junctional region of a sequence obtained from bulk CD3+ decidual leukocytes. There was considerable junctional diversity of both gamma- and delta-chains with a similar extent of germline V and J gene trimming and N-region nucleotide addition to that found in PBL V gamma 9/V delta 2 cells. Eight of eleven TCR-delta junctional sequences contained a strongly hydrophobic amino acid in position 97, as has been found in > 90% o V gamma 9/V delta 2 clones. Thymic V gamma 9/V delta 2 cells show much less junctional diversity and less pronounced selection at residue 97 of the delta-chain. Thus, unlike the mouse, gamma delta T cells from human female reproductive tissues exhibit extensive TCR junctional as well as combinatorial diversity. This suggests that V gamma 9/V delta 2 cells in these human tissues have undergone selective but diverse peripheral expansion in response to antigenic stimuli in a similar manner to those in peripheral blood.

Amino Acid Sequence↗

Plasma concentration profile of epidural alfentanil. Bolus followed by continuous infusion technique in the parturient: effect of epidural alfentanil and fentanyl on fetal heart rate.

BACKGROUND AND OBJECTIVES: A combined bolus and continuous epidural infusion technique of opioid and bupivacaine mixture has been described, although no pharmacokinetic data for this technique exists. The study documents the plasma concentration profile of epidural alfentanil in parturients using this technique, and evaluates the fetal heart rate tracing for associated changes following opioid administration. METHODS: Twenty-four subjects were randomized to receive epidural alfentanil 500 micrograms in 10 mL 0.125% bupivacaine, group A, or fentanyl 50 micrograms in 10 mL 0.125% bupivacaine, group B, as a bolus dose, followed by continuous infusions of alfentanil 20 micrograms/mL in 0.125% bupivacaine (group A) or fentanyl 2 micrograms/mL in 0.125% bupivacaine (group B) for labor analgesia. Plasma drug levels for each group were examined using repeated measures analysis of covariance. RESULTS: Fetal heart rate tracings were recorded throughout the study and were retrospectively analyzed by a "blinded" perinatologist. Data from fetal heart rate tracings were examined by repeated measures analysis of variance. Mean infusion rates were 9.3 +/- 2.1 mL/hour and 9.6 +/- 1.7 mL/hour for groups A and B, respectively. Mean study duration was 3.7 hours in group A, and 3.0 hours in group B. Low plasma levels precluded analysis of fentanyl data. Group A subjects exhibited stability of drug levels over time. Fetal heart rate tracings in 21 patients demonstrated no changes associated with epidural opioid infusion in either group. CONCLUSIONS: With the dosage regimen used in this study, an initial epidural bolus with continuous infusion technique generates a steady state plasma concentration of alfentanil that is below levels associated with direct respiratory depression.

Adult↗

In vitro human lymphocyte proliferative responses to a glycoprotein of the yeast Saccharomyces cerevisiae.

Following reports of enhanced humoral immunity to Saccharomyces cerevisiae in patients with Crohn's disease, and identification of an immunodominant, high molecular weight glycoprotein (gp200), we have investigated the cellular immune response to this yeast in normal individuals. Following exposure to a crude saline extract (Sacc), peripheral blood mononuclear cells (PBMC) from these subjects demonstrated dose-dependent increases in tritiated thymidine incorporation, the time-course of which resembled that of the response to the known recall antigens PPD and TT. This was accompanied by increased cytotoxicity of the cultured cells for natural killer (NK)-sensitive and NK-resistant target cell lines. Furthermore, using a purified, high molecular weight, glycoprotein fraction of Sacc in culture, a dose-dependent lymphoproliferative response was again observed. Stimulation indices (SI) for thymidine incorporation by umbilical cord blood lymphocytes exposed to Sacc were low compared with those of normal adults. These results provide evidence for possible antigen-specific, cellular, immune sensitization of normal individuals to a ubiquitous dietary component.

Antigens, Fungal↗

Phenotypic and functional cellular differences between human CD3- decidual and peripheral blood leukocytes.

CD3- leukocyte clones derived from human decidualized endometrial tissue of first trimester pregnancy have been compared with CD3- PBL clones. Most CD3- decidual granulated leukocyte (DGL) clones were CD16- CD56+, whereas most CD3- PBL clones were CD16+ CD56+. CD3- DGL and PBL clones, whether CD16+ or not, showed MHC-nonrestricted NK cell activity. However, CD3- CD16- DGL clones had low cytotoxic activity against the NK-resistant cell line BSM, whereas CD3- CD16+ DGL and CD3- PBL clones were strongly cytotoxic. Cytolytic activity has also been investigated in respect of target cell HLA-G expression, because this nonpolymorphic class I MHC molecule is expressed selectively by invasive fetal cytotrophoblast. Class I HLA Ag loss cell mutants were killed efficiently by CD3- DGL clones. Expression of transfected HLA-B8 increased their sensitivity to lysis by most CD3- DGL clones, whereas expression of transfected HLA-G commonly led to decreased target cell killing. In addition, the effects of uncloned CD3- DGL on the one-way MLR have been examined. These cells were very poor responders and, unless cultured to induce expression of class II MHC molecules, were also very poor stimulators. When fresh CD3- DGLs were added as third-party cells, either autologous or allogeneic to responder cells, [3H]TdR incorporation was decreased in the MLR. Thus, CD3- DGL clones express MHC-nonrestricted cytolytic activity, notably against HLA-negative cells, but expression of HLA-G offers protection to target cells. In addition, CD3- DGL may function to suppress allogeneic responses.

Antigens, CD↗

T-cell receptor heterogeneity of gamma delta T-cell clones from human female reproductive tissues.

gamma delta T cells were isolated from human decidua parietalis, decidua basalis and cervix and cloned in the presence of interleukin-2 (IL-2). T-cell receptor (TcR) expression was then analysed and compared with that of a panel of gamma delta T-cell clones from peripheral blood. Only 17/40 (42.5%) clones from decidua parietalis were V gamma 9+/V delta 2+ as compared to 68/94 (72%) of peripheral blood clones (P < 0.005). Conversely, 50% of clones from decidua parietalis but only 15% of clones from peripheral blood were V delta 1+ (P < 0.001). At least seven distinct TcR types were identified among the panel of clones from decidua parietalis and at least six different types were expressed by the panel of 17 clones from cervix. This receptor heterogeneity was not a result of interdonor variation as in all instances where more than one clone was obtained from a single sample, individual clones having between two and five receptor types were identified. However, 23/24 (95.8%) of clones from decidua basalis were V gamma 9+/V delta 2+. Most clones from decidua parietalis and cervix, whether V gamma 9+/V delta 2+ or V delta 1+, were positive for the mucosal lymphocyte marker, HML-1, but expression was often heterogeneous within a single clone. In contrast, almost all gamma delta T-cell clones from peripheral blood were HML-1-. Thus, unlike the mouse, gamma delta T cells within these human female reproductive tissues have a diverse TcR repertoire which, in decidua parietalis, is distinct from that of peripheral blood.

Antigens, Neoplasm↗