Insights into the development of polycystic ovary syndrome (PCOS) from studies of prenatally androgenized female rhesus monkeys.

The developmental pathophysiology of polycystic ovary syndrome (PCOS) is unknown. However, prenatally androgenized female rhesus monkeys exhibit ovarian and endocrinological features that mimic those found in women with PCOS. Thus, prenatal androgen excess may provide an etiology for hyperandrogenism and anovulation in adulthood.

The zonula, lens, and circumlental space in the normal iridectomized rhesus monkey eye.

Purpose: To document zonular orientation and suspension of the lens during accommodation, and age-related changes of the circumlental space (CLS) at rest and during accommodation, in living iridectomized rhesus monkey eyes.

Methods: The CLS was measured in 34 iridectomized eyes of 24 living rhesus monkeys, age 5.7 to 26 years, in the resting and accommodated state, and the orientation of the zonula and suspension of the lens during accommodation was assessed qualitatively.

Accommodative ciliary body and lens function in rhesus monkeys, I: normal lens, zonule and ciliary process configuration in the iridectomized eye.

Purpose: The underlying causes of presbyopia, and the functional relationship between the ciliary muscle and lens during aging are unclear. In the current study, these relationships were studied in rhesus monkeys, whose accommodative apparatus and age-related loss of accommodation are similar to those in humans.

Methods: Centripetal ciliary body and lens equator movements were measured during accommodation in 28 eyes of 21 rhesus monkeys (ages, 5.

Expression of aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) mRNA expression in human spermatozoa.

Background: The objective of this study was to determine if human spermatozoa express AHR (dioxin receptor) and ARNT and if mRNA levels for these transcription factors correlate with sperm concentration, motility or morphology.

Material/methods: This was a case-controlled cohort study in which AHR and ARNT mRNA levels in subjects with normal and abnormal semen analysis were compared. Semen analysis was performed by CASA.

Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses.

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, little is known about the influence of these MHC alleles on acute-phase cellular immune responses. Here we follow 51 animals infected with SIV(mac)239 and demonstrate a dramatic association between Mamu-A*01 and -B*17 expression and slowed disease progression.

Female sex hormones as regulatory factors in the vaginal immune compartment.

Sexually transmitted diseases (STD) are now considered to be among the most common human infections. The incidence of STD is on the rise, which is partly due to frequent transmission during the asymptomatic phase of infection. The compounded cost of STD just in the United States is estimated to exceed $10 billion annually.

Expression of the major histocompatibility complex class I molecule Mamu-A*01 is associated with control of simian immunodeficiency virus SIVmac239 replication.

Several HLA alleles are associated with attenuated human immunodeficiency virus disease progression. We explored the relationship between the expression of particular major histocompatibility complex (MHC) class I alleles and viremia in simian immunodeficiency virus SIV(mac)239-infected macaques. Of the common MHC class I alleles, animals that expressed Mamu-A*01 exhibited the best control of viral replication.

Increase in Lead Concentration in the Drinking Water of an Animal Care Facility.

We report here the unexpected detection, and subsequent correction, of a problem that resulted in an increase in lead concentration in the drinking water of an animal research facility. At the initiation of a study, analysis of a water sample obtained from the drinking spout of an animal cage revealed a lead concentration nearly twice the Environmental Protection Agency's maximum acceptable concentration. Because the municipal water supply routinely had been tested and found to be free of lead, it was assumed that this contamination was within the animal care facility.

Escape in one of two cytotoxic T-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class I molecule, Mamu-A*02: a paradigm for virus evolution and persistence?

It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited.

Effects of cytotoxic T lymphocytes (CTL) directed against a single simian immunodeficiency virus (SIV) Gag CTL epitope on the course of SIVmac239 infection.

Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency virus-challenged macaques. Therefore, we wanted to test the impact that vaccine-induced CTL responses against an immunodominant Gag epitope might have in the absence of other immune responses. By themselves, these strong CTL responses failed to control SIVmac239 replication.

A soluble isoform of the rhesus monkey nonclassical MHC class I molecule Mamu-AG is expressed in the placenta and the testis.

The nonclassical MHC class I locus HLA-G is expressed primarily in the placenta, although other sites of expression have been noted in normal and pathological situations. In addition, soluble HLA-G isoforms have been detected in the serum of pregnant and nonpregnant women as well as men. The rhesus monkey placenta expresses a novel nonclassical MHC class I molecule Mamu-AG, which has features remarkably similar to those of HLA-G.

Characterization of the peptide-binding specificity of Mamu-B*17 and identification of Mamu-B*17-restricted epitopes derived from simian immunodeficiency virus proteins.

The SIV-infected rhesus macaque is an excellent model to examine candidate AIDS virus vaccines. These vaccines should elicit strong CD8(+) responses. Previous definition of the peptide-binding motif and optimal peptides for Mamu-A*01 has created a demand for Mamu-A*01-positive animals.

Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239.

Producing a prophylactic vaccine for human immunodeficiency virus (HIV) has proven to be a challenge. Most biological isolates of HIV are difficult to neutralize, so that conventional subunit-based antibody-inducing vaccines are unlikely to be very effective. In the rhesus macaque model, some protection was afforded by DNA/recombinant viral vector vaccines.

Features associated with reproductive ageing in female rhesus monkeys.

Background: The specific aims were to determine the effects of maternal age on the meiotic and developmental competence of oocytes and incidence of chromosomal anomalies in oocytes from a population of fertile rhesus monkeys.

Methods: Monkeys were divided into two age groups (4-15 and 16-26 years of age) and underwent ovarian stimulation for collection of oocytes.

Results: In the older, compared with younger, monkeys, serum basal concentrations of FSH were elevated (P < 0.

Stromal decidualization of endometriosis in the rhesus macaque (Macaca mulatta): a case report.

During exploratory laparotomy, a 10-year-old female rhesus macaque was found to have a 6.0 x 9.5 x 2.

Molecular cloning of three nonhuman primate follicle stimulating hormone beta-subunit cDNAs.

The follicle stimulating hormone (FSH) beta-subunit cDNAs were cloned and sequenced for an old world primate, the rhesus monkey (Macaca mulatta), and two New World primates, the common marmoset (Callithrix jacchus) and pygmy marmoset (Cebuella pygmaea). The cDNA and predicted amino acid sequences of the rhesus monkey FSH beta-subunit were related most closely to the human FSH beta-subunit (> 96% identity). The common and pygmy marmosets have identical FSH beta-subunit cDNAs, whereas the marmoset FSH beta-subunit diverges from the rhesus and human molecules with less than 93% identity.

Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection.

Cytotoxic T-lymphocyte (CTL) responses peak coincident with the decline in acute HIV viremia. Despite two reports of CTL-resistant HIV variants emerging during acute infection, the contribution of acute CTL escape to HIV pathogenesis remains unclear. Difficulties inherent in studying acute HIV infection can be overcome by modeling virus-host interactions in SIV-infected rhesus macaques.

Analysis of the immune response and viral evolution during the acute phase of SIV infection.

Development of an effective vaccine against human immunodeficiency virus (HIV) will require knowledge of the immune responses that correlate with protection. During the acute phase of HIV infection the host immune responses appear to control viral replication. It is thought that virus-specific cellular immunity is intimately involved in this viral control.

Effects of food availability on serum insulin and lipid concentrations in free-ranging baboons.

The relationship between food availability and metabolic physiology was studied in groups of free-ranging baboons (Papio spp.) living in the Amboseli National Park and the Masai Mara National Reserve of Kenya. Three groups subsisted entirely on natural forage, while two other groups lived near tourist facilities and often consumed food wastes from these lodges.

Efficient method for expressing transgenes in nonhuman primate embryos using a stable episomal vector.

Transgenesis in the nonhuman primate can enhance the study of human biology by providing animal models for the study of primate-specific physiology, pathophysiology, and embryonic development. Progress with this technology has been hindered by the inherent inefficiency of transgenesis, transgene silencing, and practical restrictions on the production of sufficient pronuclear stage nonhuman primate zygotes. We have developed a novel technique using an Epstein Barr virus (EBV)-based episomal vector to produce rhesus monkey (Macaca mulatta) embryos expressing a transgene.

Tat-vaccinated macaques do not control simian immunodeficiency virus SIVmac239 replication.

The regulatory proteins of human immunodeficiency virus may represent important vaccine targets. Here we assessed the role of Tat-specific cytotoxic T lymphocytes (CTL) in controlling pathogenic simian immunodeficiency virus SIVmac239 replication after using a DNA-prime, vaccinia virus Ankara-boost vaccine regimen. Despite the induction of Tat-specific CTL, there was no significant reduction in either peak or viral set point compared to that of controls.

Impaired developmental competence of oocytes in adult prenatally androgenized female rhesus monkeys undergoing gonadotropin stimulation for in vitro fertilization.

To determine whether prenatal T propionate exposure beginning gestational d 40-44 (early-treated) or 100-115 (late-treated) affects oocyte competence, five early-treated and five late-treated prenatally androgenized and five normal monkeys underwent recombinant human FSH injections with oocyte-retrieval after hCG administration. Serum FSH, LH, estradiol (E(2)), progesterone (P(4)), androstenedione (A(4)), T, and dihydrotestosterone were measured basally, during gonadotropin stimulation and at oocyte-retrieval; fasting serum glucose and insulin also were determined basally and at oocyte-retrieval. Follicle fluid sex steroids were analyzed.

Cloning of rhesus monkey killer-cell Ig-like receptors (KIRs) from early pregnancy decidua.

To define the killer-cell Ig-like receptors (KIR) molecules expressed within the decidua in the rhesus monkey, an early pregnancy rhesus decidual library was screened with an oligonucleotide located within the KIR D2 domain. We obtained 26 full-length clones which represented 11 mRNAs. The cDNAs encode proteins containing 2 or 3 Ig domains, and short or long cytoplasmic domains.

Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess.

Objective: To determine whether there is an ovarian thecal cell component to hyperandrogenism exhibited in adult female rhesus monkeys exposed to androgen excess during prenatal life.

Design: Prospective nonrandomized study.

Setting: An academic research environment.