Mucosal immunity, HIV transmission, and AIDS.
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AIDS Vaccines↗
Biomedical subjects
C J Miller
Publications and source records attributed to C J Miller.
Simian immunodeficiency virus infection of the gastrointestinal tract of rhesus macaques. Functional, pathological, and morphological changes.
Gastrointestinal dysfunction and wasting are frequent complications of human immunodeficiency virus (HIV) infection. Nutrient malabsorption, decreased digestive enzymes and HIV transcripts have been documented in jejunal mucosa of HIV-infected patients; however, the pathogenesis of this enteropathy is not understood. Rhesus macaques infected with simian immunodeficiency virus (SIV) also exhibit diarrhea and weight loss; therefore, we investigated the use of this animal model to study HIV-associated intestinal abnormalities. A retrospective study of intestinal tissues from 15 SIV-infected macaques was performed to determine the cellular targets of the virus and examine the effect of SIV infection on jejunal mucosal morphology and function. Pathological and morphological changes included inflammatory infiltrates, villus blunting, and crypt hyperplasia. SIV-infected cells were detected by in situ hybridization in stomach, duodenum, jejunum, ileum, cecum, and colon. Using combined immunohistochemistry and in situ hybridization, the cellular targets were identified as T lymphocytes and macrophages. The jejunum of SIV-infected animals had depressed digestive enzyme activities and abnormal morphometry, suggestive of a maturational defect in proliferating epithelial cells. Our results suggest that SIV infection of mononuclear inflammatory cells in intestinal mucosa may alter development and function of absorptive epithelial cells and lead to jejunal dysfunction.
Animals↗
Genital secretory immune response to chronic simian immunodeficiency virus (SIV) infection: a comparison between intravenously and genitally inoculated rhesus macaques.
The humoral and genital secretory immune response to chronic SIV infection was compared between female Rhesus macaques inoculated by i.v. or intravaginal routes. Total IgG levels in serum were 10-fold higher in SIV-infected animals when compared with uninfected controls. Vaginal washes from normal macaques contained predominantly IgA and IgG, while those from SIV-infected animals contained high levels of IgG. The SIV-infected animals had high titres of SIV-specific IgG in serum, with lower but detectable IgA and IgM responses. The genital secretory immune response to SIV was similar in intravenously and intravaginally inoculated animals. The anti-SIV response in the vaginal washes consisted mainly of IgG. Within the lamina propria of the reproductive tract of animals chronically infected with SIV there were essentially no IgA or IgG plasma cells and only a small number of IgM plasma cells, while two normal animals had large numbers of IgA plasma cells. These results suggest that the mucosal immune system of the female reproductive tract is impaired in chronic SIV infection.
Administration, Intravaginal↗
Complex cranial base trauma resulting from recreational fireworks injury: case reports and review of the literature.
Two patients who sustained complex skull base trauma secondary to recreational fireworks injuries are reported. Initial assessment and management included axial and coronal computerized tomography, control of hemorrhage, debridement of wound and brain, isolation of brain from external environment, and reconstruction of the cranial base floor. Secondary orbital and facial reconstruction used available bone fragments and iliac bone graft in one patient and vascularized free tissue transfer in the other. In both patients, reconstruction of both the intracranial and extracranial compartments was successful with acceptable cosmetic result. Modification of multiple conventional approaches, along with a multispecialty surgical team, was used to deal effectively with these unique cases.
Adult↗
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Abstracting and Indexing↗
The effect of contraceptives containing nonoxynol-9 on the genital transmission of simian immunodeficiency virus in rhesus macaques.
The ability of two nonoxynol-9 spermicide preparations to prevent the genital transmission of SIV in rhesus macaques was compared. Administration of one mL of contraceptive foam before the intravaginal inoculation of cell-free SIV prevented the genital transmission of SIV to three of six animals, and using one mL of contraceptive gel prevented the genital transmission of SIV to two of six animals. Thus, both contraceptive foams and gels containing nonoxynol-9 provided protection against the genital transmission of SIV.
Animals↗
Langerhans cells, macrophages and lymphocyte subsets in the cervix and vagina of rhesus macaques.
BACKGROUND: The lower reproductive tract is an important site of contact with pathogenic microorganisms and local immune responses to a variety of antigens have been reported. The purpose of this investigation was to define the morphology of the mucosa-associated lymphoid tissue in the genital tract of rhesus monkeys. EXPERIMENTAL DESIGN: Monoclonal antibodies were used in an immunoperoxidase staining technique to identify immunophenotypic markers on mononuclear cells in the vaginal and cervical mucosa of 14 cycling, multiparous rhesus macaques. RESULTS: CD1a+ Langerhans cells were present in the stratified squamous epithelium of the vagina (14 animals) and ectocervix (11 animals). Surprisingly, CD1a+ dendritic cells were also found within the columnar epithelium of the endocervix (5 animals). Moderate numbers of CD68+ macrophages were located in the submucosa of the vagina, ectocervix, and endocervix of all the monkeys. In all of the animals, moderate numbers of CD8+ lymphocytes were present in the submucosa and squamous epithelia of the vagina and ectocervix. Variable numbers of CD20+ B cells and CD4+ lymphocytes were located in the submucosa of all the areas examined. Lymphoid nodules were present in the submucosa of vagina (14 animals) and ectocervix (4 animals), and these nodules contained macrophages, CD4+ T cells and B cells, with fewer numbers of CD8+ T cells and Langerhans cells. CONCLUSIONS: These observations provide a morphologic basis for mucosa-associated lymphoid tissue in the female genital tract. Langerhans cells in the vaginal mucosa and endocervix may be well suited to sample antigen in the lumen of the reproductive tract, travel to the draining lymph node, present the antigen to T lymphocytes and initiate an immune response. This pathway of antigen presenting cell migration from the mucosa to the genital lymph node may represent the inductive arm of the mucosal immune system in the lower female reproductive tract.
Animals↗
Localization of SIV in the genital tract of chronically infected female rhesus macaques.
Despite the fact that human immunodeficiency virus (HIV) is transmitted primarily by sexual contact, the biology of the sexual transmission of HIV is poorly understood. Simian immunodeficiency virus (SIV) can be transmitted to female rhesus macaques by placing cell-free virus into the vaginal canal, and SIV can be isolated from the vaginal secretions of infected rhesus macaques. The authors examined the genital tracts from 16 chronically infected female rhesus macaques and localized SIV-infected cells using in situ hybridization and immunohistochemistry. SIV-infected cells were found in the genital tract of 13 of the 16 animals examined, and in most cases the SIV-infected cells were located in the submucosa of the cervix and vagina. However, SIV-infected cells were also found in the vaginal epithelium. SIV-infected cells were more common in sites of inflammation than in normal areas. These findings suggest that SIV gains access to genital tract secretions from the cervix and vaginal epithelium.
Animals↗
Developmental toxicity of L-selenomethionine in Macaca fascicularis.
Forty pregnant long-tailed macaques were dosed via nasogastric intubation with 0, 25, 150, or 300 micrograms/kg of L-selenomethionine (Se) daily during organogenesis [Gestational Day (GD) 20-50]. Clinical examination of the dams, maternal body weights, sonographic evaluations, clinical chemistry screens, and measures of serum progesterone and urinary estrone conjugates were used as indicators of maternal and fetal status in all animals. The pregnancies of two to three dams from each dose group were followed until term (approximately GD 165); the remainder (N = 7/dose group) were scheduled for hysterotomy on GD 100 +/- 2. A standard teratologic evaluation was performed including visceral and skeletal examinations. Fetal liver, kidney, skin, and smooth, cardiac, and skeletal muscles were examined by light microscopy; heart muscle was also evaluated by transmission electron microscopy. Neonates delivered at term remained with the dams and were removed periodically for morphometric, neurologic, behavioral, and ophthalmologic assessments on Days 1, 8, 15, 22, and 30 of age. Dose-dependent maternal toxicity as evidenced by anorexia, vomiting, and a significant reduction in body weight increased with increasing duration of Se exposure. One growth-retarded fetus was recovered on GD 131 from a compromised dam exposed to 25 micrograms/kg-day; one early embryonic death (GD 35) and two fetal deaths [GD 68 (followed by maternal death) and GD 123] occurred among animals dosed with 300 micrograms/kg-day. Pregnancy loss among treated animals was not significantly different from concurrent or historical controls. No statistically significant treatment-related effects were observed at necropsy on GD 100 +/- 2. One infant exposed to 150 micrograms/kg-day prenatally exhibited a unilateral cortical cataract, which may have been a spontaneous occurrence. The limited developmental effects observed and reported teratogenesis in nonmammalian species suggest that comparative pharmacokinetic studies are required before the full public health significance of elevated Se is understood.
Animals↗
Transoral crossbow injury to the cervical spine: an unusual case of penetrating cervical spine injury.
The complexity of missile injuries to the cervical spine has increased as the technology that causes these injuries has become more sophisticated. Management requires adaptation of conventional neurosurgical approaches to the cervical spine in an effort to limit neurological deficit and establish stability. We report an unusual case of a 19-year-old man who suffered transoral penetration of the cervical spine by an arrow released by a crossbow at close range.
Adult↗
Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals.
Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.
Adjuvants, Immunologic↗
Effect of virus dose and nonoxynol-9 on the genital transmission of SIV in rhesus macaques.
One inoculation of cell-free SIVmac (50 TCID50) caused persistent viremia in nine of 13 female rhesus macaques inoculated intravaginally. Persistent viremia was produced in two of four male rhesus macaques by twice placing cell-free SIVMAC (50 TCID50) onto the skin and urethral os of the penis. Placing a spermicide containing nonoxynol-9 into the vaginal canal prior to repeated intravaginal inoculations of SIV prevented transmission of the virus in three of six female rhesus macaques.
Administration, Intravaginal↗
Morphologic development of the adrenal cortex in squirrel monkeys (Saimiri sciureus).
This study describes the morphology of the squirrel monkey (Saimiri sciureus) adrenal gland in the perinatal period. Adrenals of fetal monkeys had a broad central zone of large eosinophilic cells (fetal zone) surrounded by a subcapsular band of small dark cells (definitive zone). Adrenals of stillborn and neonatal monkeys had a reduced fetal zone and an expanded definitive zone that was differentiated into distinct zona fasciculata and zona glomerulosa. By day 18 postpartum, no remnant of the fetal zone remained.
Adrenal Cortex↗
Cervical cytology in a community laboratory.
A retrospective analysis of the results of 27,801 cervical smears from one year in a community laboratory was undertaken. This represented 23,820 individual patients. Abnormalities were seen in 9.3% of patients. Three point seven percent of patients had benign abnormalities, 5.5% had cervical intraepithelial neoplasia and 0.1% had major abnormalities. The incidence of cervical epithelial abnormality was highest in the 15-34 age group but major abnormalities were seen most often in the 55+ age group. Human papillomavirus was more commonly seen in the youngest age group. The presence of inflammation was reported in 65% of the smears. Thirty percent of smears had no endocervical cells and 0.6% were grossly inadequate. Fifteen percent of patients had repeat smears and 3% of total smears were judged unnecessary. Forty two point six percent of patients less than 55 years of age in the laboratory population base had a smear but only 7.9% of those over 55.
Adolescent↗
Genital mucosal transmission of simian immunodeficiency virus: animal model for heterosexual transmission of human immunodeficiency virus.
An animal model for the heterosexual transmission of human immunodeficiency virus (HIV) was developed by the application of simian immunodeficiency virus (SIV) onto the genital mucosas of both mature and immature, male and female rhesus macaques. Virus preparations were infused into the vaginal vaults or the urethras (males) of the animals through a soft plastic pediatric nasogastric feeding tube. The macaques that were infected by this route (six males and nine females) developed SIV-specific antibodies, and SIV was isolated from peripheral mononuclear cells of all seropositive animals. One male and one female infected by this route developed severe acquired immunodeficiency syndrome-like disease with retroviral giant-cell pneumonia. As few as two inoculations of cell-free SIV containing 50 50% tissue culture infective doses induced persistent viremia. Cell-free virus preparations were capable of producing infection by the genital route. Much higher doses of virus were required to transmit SIV by this route than are required for transmission by intravenous inoculation. Thus, it appears that the mucous membranes of the genital tract act as a barrier to SIV infection. Spermatozoa and seminal plasma were not required for the genital transmission of SIV. Rarely, SIV was recovered from mononuclear cells in semen and vaginal secretions. The SIV-rhesus macaque model is suitable for assessing the role of cofactors in heterosexual transmission of HIV and will be useful for testing the effectiveness of spermicides, pharmacologic agents, and vaccines in preventing the heterosexual transmission of HIV.
Acquired Immunodeficiency Syndrome↗
The smile line as a guide to anterior esthetics.
A sound, effective, and forthright method has been presented to maximize the esthetic quotient of the dental composition. This rationale will also assist in helping the dentist to achieve the establishment of a physiologically sound vertical dimension.
Adolescent↗
The impact of physico-chemical stress on the toxigenicity of Vibrio cholerae.
The expression of toxigenicity by Vibrio cholerae, before and after exposure to various conditions of salinity, pH and cation composition and concentration, has been measured. Exposure to these conditions did not select for hyper- or hypo-toxigenic strains. This suggests that toxigenic V. cholerae O1 are unlikely to lose their toxigenicity when exposed to environmental stress and that V. cholerae toxin production is not a response to the stresses included in this study. These results are consistent with an aquatic reservoir for toxigenic V. cholerae O1.
Cholera Toxin↗
Effects of pulsatile injection of GnRH into 6- to 14-wk-old Holstein bulls.
With the goal of hastening puberty, we evaluated the effects of dose of gonadotropin releasing hormone (GnRH) during pulsatile injection on luteinizing hormone (LH) secretion in bulls 6, 10 or 14 wk old, and of pulsatile administration of GnRH every 2 h to bulls from 6 to 12 wk of age on reproductive development. Based on response to the last three of 12 bihourly injections of 20, 200 or 2,000 ng GnRH/kg, only the two higher doses of GnRH induced secretion of LH at 6 wk. At all ages, 200 ng GnRH/kg induced maximal discharges of LH. Based on comparisons between seven treated bulls and their identical twins, bihourly injections of GnRH starting on d 42 elicited discharge of LH for less than or equal to 4 d in progeny of one sire and greater than 28 d but less than 42 d in progeny of another sire. After 14 d of treatment, both elicited and spontaneous discharges of LH were smaller in all treated bulls. Within 2 d after cessation of GnRH injections on d 84, LH discharges were similar in frequency and amplitude in treated and control twins. Testicular and body growth were similar in treated and control bulls, but puberty was delayed (P less than .05) in bulls in which exogenous GnRH suppressed endogenous discharges of LH.
Aging↗