Immune reactions in human filariasis.

Sera from cases of elephantiasis due to Wuchereria bancrofti infection promoted an intense adhesion of peripheral blood leukocytes to W. bancrofti microfilariae in vitro. A similar adhesion was also seen using sera from some normal persons living for several years in areas where filariasis is endemic. No such adhesion was evident with sera from microfilaria carriers or from normal subjects from nonendemic areas. The adhesion was complement independent and was associated with the immunoglobulin G fraction of serum. 51Cr release studies suggested the occurrence of cell-mediated cytotoxicity to W. bancrofti microfilariae in the presence of elephantiasis serum. Microfilariae of Litomosoides carinii could be isolated free of blood cells, from the blood of infected rats. In the presence of serum, or its immunoglobulin G fraction, from patients with elephantiasis, L. carinii microfilariae adhered to human peripheral blood leukocytes or rat spleen cells.     

Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair

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Bacteria induce osteoclastogenesis via an osteoblast-independent pathway

Bacteria or their products may cause chronic inflammation and subsequent bone loss. This inflammation and bone loss may be associated with significant morbidity in chronic otitis media, periodontitis, endodontic lesions, and loosening of orthopedic implants caused by lipopolysaccharide (LPS)-contaminated implant particles. Currently, it is not clear how bacteria or endotoxin-induced bone resorption occurs and what cell types are involved. Here we report that Porphyromonas gingivalis, a periodontal pathogen, and Escherichia coli LPS induce osteoclastic cell formation from murine leukocytes in the absence of osteoblasts. In contrast, stimulation with parathyroid hormone had no effect. These multinucleated, tartrate-resistant acid phosphatase-positive cells were positive for receptor activator of NF-kappaB (RANK), the receptor for osteoprotegerin ligand (OPGL), also known as RANK ligand (RANKL). Blocking antibodies demonstrated that their formation was dependent upon expression of OPGL and, to a lesser extent, on tumor necrosis factor alpha. Mononuclear cells represented a significant source of OPGL production. In vivo, P. gingivalis injection stimulated OPGL expression in both mononuclear leukocytes and osteoblastic cells. Thus, these findings describe a pathway by which bacteria could enhance osteolysis independently of osteoblasts and suggest that the mix of cells that participate in inflammatory and physiologic bone resorption may be different. This may give insight into new targets of therapeutic intervention.     

Prophylaxis and treatment of experimental lung metastases in mice after treatment with liposome-encapsulated 6-O-stearoyl-N-acetylmuramyl-L-α-aminobutyryl-D-isoglutamine

A new lipophilic muramyl dipeptide analog, 6-O-stearoyl-N-acetylmuramyl-L--aminobutyryl-D-isoglutamine, when incorporated in liposomes, was effective in both the prevention and eradication of experimental pulmonary metastases in mice. Multilamellar vesicles composed of synthetic phospholipids (phosphatidylglycerol and phosphatidylcholine) containing saturated myristoyl or unsaturated dioleoyl acyl chains were found to potentiate the antimetastatic activity of this glycopeptide. Prophylactic and therapeutic efficacy was observed against the three murine tumors tested: FSa, an immunogenic fibrosarcoma; NFSa, a nonimmunogenic fibrosarcoma; and B16 melanoma. Neither the administration of empty liposomes or free glycopeptide, nor their coadministration, had a significant antimetastatic effect. This approach is promising for the therapy of cancer metastases in humans, particularly in the prevention of metastatic seeding and in the treatment of micrometastases.This is contribution No. 180 from the Institute of Bio-Organic Chemistry, Syntex Research.     

The middle cranial fossa approach: an anatomical study

Hearing preservation surgery has become an option for an increasing number of patients with vestibular schwannomas due to diagnosis at an earlier stage. The middle cranial fossa approach represents one such surgical approach for resection of vestibular schwannomas with hearing preservation. We have undertaken an anatomical study of the middle cranial fossa approach to the internal auditory meatus using 20 fresh temporal bones. By simulating the surgical approach it was possible to analyze critically two of the main recognized subapproaches to the internal acoustic meatus. The results confirmed that the angle subtended by the facial nerve and "blue-lined" semicircular canal was much less than 60 degrees but equally important was the degree of individual variability. Furthermore the roof of the geniculate fossa was not infrequently dehiscent. The distance measured from the inner table of the craniotomy to the superior semicircular canal was on average 22 mm, similar to previous reports and utilized by some in their approach in this challenging surgery. From this anatomical study it appears that safe dissection of this area is facilitated by observing the more acute angle between the facial nerve and superior semicircular canal and by taking advantage of the relationship between the inner table and important landmarks.     

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.     

Chemical modification of human neutrophil membrane proteins: effect on fMet-Leu-Phe binding and function

[3H]fMet-Leu-Phe binding to human neutrophil membrane proteins was shown to be inhibited by pretreatment of membranes with the histidine-preferring reagent diethylpyrocarbonate in a concentration- and time-dependent fashion. The inhibition was partially reversed by hydroxylamine and was affected by pH. The pH profile for inhibition and the partial reversibility of the inhibition by hydroxylamine are consistent with a modification of the histidine residue by diethylpyrocarbonate. The addition of unlabeled fMet-Leu-Phe to the membrane preparation prior to diethylpyrocarbonate treatment provided protection from the binding inhibition following washout of unlabeled fMet-Leu-Phe and unreacted reagent. Cells treated with diethylpyrocarbonate were inhibited in their ability to produce superoxide anions in response to fMet-Leu-Phe, but the concentration of the chemotactic factor required to obtain 50% of the response was alike for treated or untreated cells. These results suggest that a histidine residue at or near the receptor binding site for fMet-Leu-Phe is required for binding and cell activation. Neither N-acetylimidazole, an agent that preferentially reacts with tyrosine, nor acetic anhydride, which reacts with lysyl groups, affected [3H] fMet-Leu-Phe binding to plasma membrane proteins or superoxide production by intact cells. Scatchard analysis of the binding inhibition owing to diethylpyrocarbonate was consistent with a loss of receptor number rather than a change in affinity.     

Amyloid beta protein 1-40 and 1-42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease

We quantitated amyloid beta proteins 1-40 (Abeta40) and 1-42 (Abeta42), and alpha1- antichymotrypsin (ACT) in matched cerebrospinal fluid (CSF) and plasma of 50 patients with probable Alzheimer disease, and analyzed the relationships with age, sex, Mini-Mental State Examination (MMSE), and apolipoprotein E phenotype. There was no relation between CSF Abeta40 and Abeta42 levels with those of plasma. CSF and plasma Abeta40 and Abeta42 levels showed no association with age, sex, and MMSE score. There was a significant correlation between CSF ACT and plasma ACT levels. The data suggest that plasma ACT crosses the blood-brain barrier. However, a lack of correlation between CSF Abeta40 and Abeta42 levels with those of plasma suggests that Abeta in CSF and plasma originates from different sources.     

Protective immunity to experimental tuberculosis by mannophosphoinositides of mycobacteria

Mannophosphoinositides isolated from mycobacterial cells were found to induce both humoral and cell-mediated immune responses in mice when injected as mannoside-methylated bovine serum albumin (MBSA) complexes. Immunization of mice with mannoside-MBSA complexes elicited significant protection against challenge with LD₅₀ dose of M. tuberculosis H₃₇Rv as revealed by high survival rate, low values of root-specific lung weight, lung densities and colony forming units recovered from lung, liver and spleen, compared to the nonimmunized group. These observations were further substantiated by histopathological studies. The protective immunity elicited by mannoside-MBSA complexes against challenge with M. tuberculosis H₃₇Rv was mediated by the cooperation of T-B cells, as shown by the passive transfer of immune cells/sera into syngeneic sublethally irradiated recipient mice.