Immunoglobulin E and eosinophil-dependent protective immunity to larval Onchocerca volvulus in mice immunized with irradiated larvae

Mice immunized with irradiated Onchocerca volvulus third-stage larvae developed protective immunity. Eosinophil levels were elevated in the parasite microenvironment at the time of larval killing, and measurements of total serum antibody levels revealed an increase in the immunoglobulin E (IgE) level in immunized mice. The goal of the present study was to identify the role of granulocytes and antibodies in the protective immune response to the larval stages of O. volvulus in mice immunized with irradiated larvae. Immunity did not develop in mice if granulocytes, including both neutrophils and eosinophils, were eliminated, nor did it develop if only eosinophils were eliminated. Moreover, larvae were killed in na?ve interleukin-5 transgenic mice, and the killing coincided with an increase in the number of eosinophils and the eosinophil peroxidase (EPO) level in the animals. To determine if EPO was required for protective immunity, mice that were genetically deficient in EPO were immunized, and there were no differences in the rates of parasite recovery in EPO-deficient mice and wild-type mice. Two mouse strains were used to study B-cell function; micro MT mice lacked all mature B cells, and Xid mice had deficiencies in the B-1 cell population. Immunity did not develop in the micro MT mice but did develop in the Xid mice. Finally, protective immunity was abolished in mice treated to eliminate IgE from the blood. We therefore concluded that IgE and eosinophils are required for adaptive protective immunity to larval O. volvulus in mice.     

Follicular epithelial cell hypertrophy induced by chronic oral administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) affects the thyroid morphologically and/or functionally in adult animals. Recently, the National Toxicology Program conducted a 2-year gavage study of TCDD in female Harlan Sprague-Dawley rats. The only treatment-related alterations found in thyroid follicles were decreased luminal size and increased height of the follicular epithelial cells, without prominent protrusion into the lumen. The present study elucidated the nature of these follicular lesions. Thyroid glands of 10 rats each from the control, high (100 ng/kg/day)-dose, and stop-study (100 ng/kg/day, 30 weeks; vehicle to study termination) groups in the 2-year study were evaluated microscopically. Twenty randomly selected follicles were measured morphometrically in each animal. TCDD treatment significantly decreased the mean ratio of luminal/epithelial areas and increased the mean sectional epithelial height of the high-dose group compared to controls. Thyroid sections were immunostained with antibody against minichromosome maintenance (MCM) proteins, a novel cell-cycle biomarker. The MCM labeling index of the high-dose group was significantly higher than that of the control; however, the TUNEL labeling index was also higher in the high-dose group than the control. All data from the stop group were comparable to those from controls. These results indicate that the follicular cell response was hypertrophic and reversible. This information should contribute to diagnosis of nonneoplastic thyroid follicular lesions in rats.     

Diet salinity and vasopressin as reproduction modulators in the desert-dwelling golden spiny mouse (Acomys russatus)

The time for reproduction in mammals largely depends on the availability of water and food in their habitat. Therefore, in regions where rains are limited to definite seasons of the year, mammals presumably will restrict their breeding correspondingly. But while mammals living in predictable ecosystems would benefit by timing their season to an ultimate predictable cue, such as photoperiod, in unpredictable ecosystems (e.g., deserts) they will need to use a more proximate signal. We suggest a mechanism by which water shortage (low water content in plants) could act as a proximate cue for ending the reproductive season. The golden spiny mouse (Acomys russatus), a diurnal rodent living in extreme deserts, may face an increased dietary salt content as the summer progresses and the vegetation becomes dry. Under laboratory conditions, increased diet salinity lead to reproductive hiatus in females, notable in imperforated vagina, and a significant decrease in the ovaries, uteri, and body masses. In females treated with vasopressin (VP), a hormone expressed during water stress, the uteri and body masses have decreased significantly, and the ovaries exhibited an increased number of atretic follicles. VP has also led to a significant decrease in relative medullary thickness (RMT) of the kidney. It is thus suggested that VP could act as a modulator linking the reproductive system with water economy in desert rodents, possibly through its act on the energetic pathways.     

Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program

The NTP has a long history of using Fischer rats and has compiled a large database of incidences of lesions seen in control animals. Such a database is lacking for Harlan Sprague-Dawley (SD) rats. The intention of this paper is to report spontaneous lesions observed in female vehicle control Harlan SD rats, and to compare the incidence in 2 strains of rats (Fischer and Harlan SD) used in NTP studies. Female Harlan SD rats served as the test animals for a special series of 2-year studies. Male rats were not used in these studies. Complete histopathology was performed on all animals, and the pathology results underwent comprehensive NTP pathology peer review. The most commonly observed neoplasms in these female control Harlan SD rats were mammary gland fibroadenoma (71%), tumors of the pars distalis of the pituitary (41%) and thyroid gland C-cell tumors (30%). Female Fischer rats had incidences of 44% for mammary gland fibroadenomas, 34% for tumors of the pars distalis, and 16% for thyroid gland C-cell tumors. Fischer rats had a 15% incidence of clitoral gland tumors, while the Harlan SD rats had an incidence of < 1%. In contrast to Fischer F344 rats, the Harlan SD rats had a high incidence of squamous metaplasia of the uterus (44.2%). Squamous metaplasia is not a lesion commonly observed in NTP control Fischer rats. The Harlan SD rats had a very low incidence of mononuclear cell leukemia (0.5%), compared with an incidence of 24% in female Fischer rats.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

The immunological and virological response in human immunodeficiency virus type-1 (HIV-1) infected Indian individuals on HAART therapy: a one-year follow up study

Currently, antiretroviral therapy has become more affordable even in developing countries and it is being used in India. Fifteen HIV-1 infected individuals, who were on highly active antiretroviral therapy (HAART), were followed up for an average period of one year. The plasma viral load and CD4+ T cell estimation done at mean intervals of 5 months and 11 months after initiation of therapy showed a good response to therapy in 14 (93%) individuals.     

Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n = 49) and peripheral blood (n = 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P = 0.02). This difference was more pronounced in early (stage 1) endometriosis (P = 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P = 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.      

Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations

Fundic gland polyps (FGPs) are the most common gastric polyps in patients with familial adenomatous polyposis (FAP). FGPs have traditionally been regarded as nonneoplastic, possibly hamartomatous lesions, but the pathogenesis of FGPs in both FAP and sporadic patients remains unclear. FGPs in FAP can show foveolar dysplasia, and rarely invasive gastric adenocarcinoma has been reported in patients with FAP and fundic gland polyposis. Using direct gene sequencing and allelic loss assays at 5q, we analyzed somatic adenomatous polyposis coli (APC) gene alterations in 41 FAP-associated FGPs (20 with foveolar dysplasia, six indefinite for dysplasia, and 15 nondysplastic) and 13 sporadic FGPs. The foveolar epithelium and dilated fundic glands of the polyps were separately microdissected and analyzed in 25 of 41 FAP-associated FGPs and 13 of 13 sporadic FGPs. Somatic APC gene alterations were identified frequently (21 of 41 cases, 51%) in FAP-associated FGPs. Both the foveolar epithelium and the dilated fundic gland epithelium comprising the FGPs were shown to carry the same somatic APC gene alteration in 24 (96%) of 25 cases. Furthermore, there was no difference in the frequency of somatic APC gene alterations between FGPs with foveolar dysplasia (10 of 20, 50%), indefinite for dysplasia (four of six, 67%), and nondysplastic (seven of 15, 47%) in FAP patients (P: = 0.697). In contrast, FGPs from non-FAP patients showed infrequent (one of 13, 8%) APC gene alterations (P: = 0.008). These results show that FGPs in FAP patients are pathogenetically distinct from sporadic FGPs. Somatic, second-hit APC gene alterations, which precede morphological dysplasia in many FAP-associated FGPs, indicate that FGPs arising in the setting of FAP are neoplastic lesions.