Immunity reduces reservoir host competence of Peromyscus leucopus for Ehrlichia phagocytophila

Infection with Ehrlichia phagocytophila in white-footed mice is transient and followed by a strong immune response. We investigated whether the presence of acquired immunity against E. phagocytophila precludes white-footed mice from further maintenance of this agent in nature. Mice were infected with E. phagocytophila via tick bite and challenged either 12 or 16 weeks later by Ixodes scapularis nymphs infected with the same agent. Xenodiagnostic larvae fed upon each mouse simultaneously with challenging nymphs and 1 week thereafter. Ticks were tested for the agent by PCR, and the prevalence of infection was compared to that in ticks that fed upon nonimmune control mice. Only 30% of immunized mice sustained cofeeding transmission of E. phagocytophila between simultaneously feeding infected and uninfected ticks, compared to 100% of control mice. An average of 6.3% of xenodiagnostic ticks acquired Ehrlichia from previously immunized mice when fed 1 week after the challenge, compared to 82.5% infection in the control group. Although an immune response to a single infection with E. phagocytophila in white-footed mice provided only partial protection against reinfection with the same agent, the majority of mice were rendered reservoir incompetent for at least 12 to 16 weeks. Immunity acquired by mice during I. scapularis nymphal activity in early summer may exclude a large proportion of the mouse population from maintaining E. phagocytophila during the period of larval activity later in the season.     

Modulation of the chemotactic properties of complement fragments C5a and C3 by the anti-inflammatory agent,SC-41930

Cleavage of the fifth component of complement yields C5a, a potent neutrophil (PMN) and eosinophil chemoattractant, and modulator of microvascular permeability. Similarly, but to a lesser degree, C3 increases vascular permeability and histamine release. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid), an orally-active antiinflammatory agent was tested in anin vivo model of dermal PMN chemotaxis induced by r-hu-C5a and hu-C3. Intradermal injection of C5a in the guinea pig resulted in a significant dose-dependent influx of PMNs at 4 hours as assessed by the dermal levels of myeloperoxidase (MPO). SC-41930 (20 mg/kg) given orally to guinea pigs with intradermal injections of 1 μg C5a significantly (p<0.001) reduced dermal MPO content. SC-41930 was less potent against C3, requiring 40 mg/kg to significantly reduce dermal MPO levels. Agents such as SC-41930, which nullify complement's proinflammatory properties, may well have therapeutic potential.     

Association of infection caused by Pseudomonas aeruginosa serotype O11 with intravenous abuse of pentazocine mixed with tripelennamine.

From July 1979 to June 1983, 25 of 40 intravenous drug addicts with systemic infections had Pseudomonas aeruginosa as the etiological agent; by 1982, P. aeruginosa had replaced Staphylococcus aureus as the most common pathogen. At least 21 of the 25 addicts with P. aeruginosa infection abused pentazocine mixed with tripelennamine (commonly known as T's and blues) compared with 6 of 15 addicts infected with other pathogens (P = 0.006). Of the 25 P. aeruginosa isolates, 23 were of serotype O11. Phenotypic patterns in isolates from addicts and in 22 serotype O11 control isolates from nonaddicts were determined by pyocin and electrophoretic enzyme typing, as well as by susceptibility to heavy metals and antibiotics. Of 25 isolates from addicts, 20 were identical or differed by only one marker, whereas the 22 nonaddict serotype O11 isolates were distributed among 17 distinct phenotypic patterns. We postulate that the emergence of P. aeruginosa as the major cause of deep infection in addicts is a consequence of contamination of their paraphernalia during preparation of pentazocine and tripelennamine for self-injection. The phenotypic similarity among isolates from addicts may reflect acquisition from related environmental sources and an unusual ability of certain serotype O11 strains to survive preparation of the drugs or to be invasive.     

Phenotype, cytotoxic, and helper functions of T cells from varicella zoster virus stimulated cultures of human lymphocytes

Blood mononuclear cells (MNC) were stimulated with VZV in the form of live cell-associated virus, glutaraldehyde-fixed VZV-infected fibroblasts or an extracted VZV antigen. After 7 days of culture with live virus, IL2 receptors (IL2R) were found on CD4 and CD8 cells while cultures stimulated with fixed or extracted antigen had IL2R only on CD4 cells. Clones derived by limiting dilution from these cultures were tested for specificity by cytotoxicity to autologous VZV-superinfected B lymphoblasts, and by proliferation in the presence of antigen and antigen presenting cells. The CD8+ clones were not VZV specific in tests of cytotoxicity or proliferation. 50% of the CD4+ clones with specificity for VZV also proliferated in cultures stimulated with individual VZV glycoproteins gp I, II or III. Included amongst these were clones cytotoxic for lymphoblast targets prepared with live VZV. Most of the VZV-specific T cell clones which failed to lyse targets prepared with live VZV lysed targets prepared with heat killed VZV. Target cells were susceptible to lysis after VZV antigens were no longer demonstrable on the cell surface by immunofluorescence and monoclonal antibodies to VZV glycoproteins failed to block cytotoxicity. 5 of 8 VZV-specific CD4+ clones provided antigen-specific help to B cells for IgG antibody production. The data are consistent with the view that CD4+ T cells respond to processed VZV antigen fragments, and that these fragments include epitopes present on gp I, gp II and gp III. Additionally, some the cloned progeny of VZV specific T cells were bifunctional (expressing cytotoxicity and help for B cells) in tissue culture.     

HLA antigens in East African black patients with Burkitt's lymphoma or nasopharyngeal carcinoma and in controls: A pilot study

A pilot study is reported of HLA-A, B, and C antigens in 141 East African Blacks comprising patients with Burkitt's lymphoma or nasopharyngeal carcinoma, either with active disease or in long-term remission, together with comparable controls. This study forms part of a wider program investigating host factors in these diseases. A protocol was selected for optimal testing of cells processed and cryopreserved between 1972 and 1976, largely under field conditions, which employed a two-color fluorochromasia typing procedure. Antigen distribution and computed haplotype frequencies in the total unrelated population are given. New findings include an approximately equal frequency of Aw23 and Aw24, a high (18%) incidence of Bw21, and the gametic associations of Aw36 with Bw44, and Aw30 with Bw45. Of the major group of B15-related antigens reported earlier, SV is the most common, and there are strong linkages of SV with Cw2 and Bw with Cw3. The possible presence of further variants at the A- and B-loci is reported. The proportion of B-locus antigen “blanks” in this study is 5.9%. Relationships have been sought between the HLA antigens and diseases studied: the antigen A29, possibly in linkage with Bw42, shows a correlation with disease susceptibility, and associations are suggested between Bw44 (in possible combination with Aw36) and resistance to both BL and NPC, and between Bw45 and long-term remission in NPC.     

Molecular Manipulations of Extracellular Superoxide Dismutase: Functional Importance for Learning

Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide (O ₂ ^- ), which is important for a variety of physiological pathways, including the primary means of inactivating nitric oxide (NO). The role of EC-SOD in neurobehavioral function has been until now unexplored. In the current studies, the phenotypic expression of genotypic alterations of EC-SOD production in mice were characterized for spatial learning and memory. Dramatic impairments in spatial learning in the win-shift 8-arm radial maze were seen in both EC-SOD knockout mice and EC-SOD overexpressing mice. The EC-SOD overexpressing mice were further characterized as having significant deficits in a repeated acquisition task in the radial-arm maze, which permitted the dissociation of long and short-term learning. Long-term learning was significantly impaired by EC-SOD overexpression, whereas short-term learning was not significantly affected by EC-SOD overexpression. NO systems have been shown to be importantly involved in learning and memory. This may be important in the current studies because EC-SOD has primary control over the inactivation of NO. We found that EC-SOD overexpressing mice were resistant to the cognitive effects of L-NAME (N^G-nitro-L-arginine methyl ester hydrochloride), an NO synthase inhibitor. Decreased NO catabolism in these mice may have served to counter the effects of NOS inhibition by L-NAME. The current finding that EC-SOD levels that were either higher or lower than controls impaired learning demonstrates that the proper control of brain extracellular (O ₂ ^- ) may be more vital than merely reduction of brain extracelluar (O ₂ ^- ) in maintaining adequate learning function.     

Scanning electron microscopy of teeth in dominant osteogenesis imperfecta: Support for genetic heterogeneity

Scanning electron microscopic studies were performed on 25 deciduous and permanent teeth from members of 7 kindreds with dominant nonlethal osteogenesis imperfects (OI). Two families had normal teeth on clinical and radiological examination; five familes had blue or brown opalescent teeth with specific radiologic findings. Enamel surfaces and prism organization were normal on all teeth. On fractured surfaces, the dentin tubules of normal teeth from patients with OI were evenly distributed and coursed regularly to the dentin-enamel junction. Opalescent teeth had few tubules and those present were short, narrow, and tortuous. Dentin calcification fronts of normal teeth were composed of many nodules with regularly spaced openings on their surfaces. Calcification fronts of opalescent teeth were composed of irregularly spaced, small nodules, which varied greatly in size and the nodules lacked tubule openings on their surfaces. The results of this study support the concept that at least two dominant forms of OI exist – one in which all individuals with IO have normal teeth, and the other in which all with OI have blue or brown opalescent teeth with characteristic changes on SEM.     

Smoking and female infertility: a systematic review and meta-analysis

The high prevalence of smoking among women in their reproductive years continues to be a matter of concern. The negative effects of smoking on general health are well known, but smoking may also affect fertility. The objective of the present study was to perform a systematic review of the literature to determine whether there is an association between smoking and risk of infertility in women of reproductive age, and to assess the size of this effect. In the 12 studies used for this meta- analysis, the overall value of the odds ratio (OR) for risk of infertility in women smokers versus non-smokers was 1.60 [95% confidence interval (CI) 1.34-1.91]. Studies of subfertile women undergoing in-vitro fertilization (IVF) treatment also show a reduction in fecundity among women smokers. A meta-analysis of nine studies found an OR of 0.66 (95% CI 0.49-0.88) for pregnancies per number of IVF- treated cycles in smokers versus non-smokers. Despite the potential limitations of meta-analyses of observational studies, the evidence presented in this review is compelling because of the consistency of effect across different study designs, sample size and types of outcome. However, continued reassurance is needed that the calculated overall effect is not in fact due to confounding variables.