PubMed Health⌕ Search

Biomedical subjects

Andrew G Hendrickx

Publications and source records attributed to Andrew G Hendrickx.

6 recordsLinked to original sources

Reduced TCOF1 mRNA level in a rhesus macaque with Treacher Collins-like syndrome: further evidence for haploinsufficiency of treacle as the cause of disease.

Mutations in the human gene TCOF1 cause a mandibulofacial dysostosis known as Treacher Collins syndrome (TCS). An infant rhesus macaque (Macaca mulatta) that displayed the TCS phenotype was identified at the California National Primate Research Center. The TCOF1 coding region was cloned from a normal rhesus macaque and sequenced. The rhesus macaque homolog of TCOF1 is 91.6% identical in cDNA sequence and 93.8% identical in translated protein sequence compared to human TCOF1. Sequencing of TCOF1 in the TCS-affected rhesus macaque showed no mutations within the coding region or splice sites; however, real-time quantitative PCR showed an 87% reduction of spleen TCOF1 mRNA level in the TCS affected macaque when compared with normal macaque spleen.

Amino Acid Sequence↗

Serum leptin in nonpregnant and pregnant women and in old and new world nonhuman primates.

Leptin is a hormone that is produced during mammalian pregnancy in the placental trophoblast and other tissues, including! fetal and maternal adipocytes. Synthesis of the polypeptide and the presence of its specific receptors throughout the human maternal fetoplacental unit suggest direct effects on conceptus growth and development. However, both the physiologic roles of leptin and the mechanisms regulating leptin synthesis in human pregnancy differ from those in laboratory and domestic species, necessitating the development of non-human primate research models. Therefore, we compared serum leptin concentrations in nonpregnant and pregnant women with those in both old world nonhuman primates (i.e., baboon, rhesus monkey, cynomolgus monkey) and new world nonhuman primates (i.e., squirrel monkey, titi monkey). As expected, maternal leptin levels were elevated in human and baboon pregnancies (P < 0.05 and P < 0.001, respectively). Levels in both species of old world monkeys were also greatly enhanced (P < 0.001). Although maternal serum concentrations were slightly elevated compared to nonpregnant levels in both species of new world monkeys, overall concentrations were dramatically lower than for either old world primates or humans. Results provide comparisons of serum leptin concentrations in pregnant and nonpregnant humans and baboons with those in both old and new world monkeys and further characterize these nonhuman primates as models for the investigation of leptin dynamics in pregnancy.

Animals↗

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on chorionic gonadotrophin activity in pregnant macaques.

As many as 62% of all human conceptions are lost prior to 12 weeks of pregnancy and it is unknown how many of these losses result from environmental hazards. Previous studies have shown that single doses of 1, 2, and 4 microg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administrated orally to cynomolgus macaques during the peri-implantation period leads to early fetal loss (EFL) within 10-20 days. TCDD induced EFL is associated with a reduction in the biological activity of monkey chorionic gonadotrophin (mCG) but no change in the immunoreactive mCG profile. These studies are consistent with either a direct effect of TCDD on differentiation of the trophoblast and an indirect effect on mCG synthesis, or a direct effect on mCG synthesis and secretion independent of trophoblast development. The present study was designed to test the hypothesis that the action of TCDD is directly on mCG synthesis rather than on the differentiation of the trophoblast. Female macaques (Macaca fascicularis) were treated with a single dose of TCDD (4 microg/kg b.wt.) on Gestational Day 20, a stage of pregnancy following initial trophoblast differentiation and invasion. Circulating mCG concentrations were monitored for the next 6 days. Compared to the controls, the peak level of serum bioactive mCG was lower in the treated group (P<0.05), with a decrease observed on the day following exposure. The bioactive/immunoreactive mCG ratio was also lower in the treated group compared to the controls (P<0.05). There was no difference in serum immunoreactive mCG levels between the groups. Histological evaluation of the embryo-placental unit showed increased apoptosis and vascular congestion after treatment but was otherwise grossly normal. Because exposure of the conceptus to TCDD following differentiation of the trophoblast decreased the bioactivity of circulating mCG, we conclude that the action of TCDD in the placenta is directly on mCG synthesis.

Animals↗

Functional and morphological development of lymphoid tissues and immune regulatory and effector function in rhesus monkeys: cytokine-secreting cells, immunoglobulin-secreting cells, and CD5(+) B-1 cells appear early in fetal development.

Little is known regarding the timing of immune ontogeny and effector function in fetal humans and nonhuman primates. We studied the organization of lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus monkey fetuses during the second and third trimesters (65 to 145 days of gestation; term = 165 days). Immunoglobulin-secreting and cytokine-secreting cells were detected at day 80. The thymus, spleen, lymph nodes, and intestinal mucosa were examined for cells expressing CD3, CD5, CD20, CD68, p55, and HLA-DR. In the spleens of 65-day-old fetuses (early second trimester), the overwhelming majority of total lymphocytes were CD5(+) CD20(+) B-1 cells. The remaining lymphocytes were CD3(+) T cells. By day 80, splenic B and T cells were equal in number. Intraepithelial CD3(+) CD5(-) T cells and lamina propria CD20(+) CD5(+) B cells were present in the intestines of 65-day-old fetuses. By day 80, numerous CD20(+) CD5(+) B cells were present in the jejunums and colons and early lymphocyte aggregate formation was evident. The spleens of 80- to 145-day-old fetuses contained immunoglobulin M (IgM)-secreting cells, while IgA-, IgG-, interleukin-6-, and gamma interferon-secreting cells were numerous in the spleens and colons. Thus, by the second trimester, the lymphoid tissues of the rhesus monkey fetus have a complete repertoire of properly organized antigen-presenting cells, T cells, and B cells.

Animals↗

Persistent truncus arteriosus in a rhesus monkey (Macaca mulatta).

A 47-day-old female rhesus macaque (Macaca mulatta) was examined because of a severe holosystolic heart murmur (grade 5/6) and signs of congestive heart failure. Results of physical examination, thoracic radiography, and cardiac ultrasonography confirmed an advanced stage of congestive heart failure. Due to the animal's age and clinical signs of disease, a congenital heart defect was suspected. Necropsy revealed a rare congenital heart defect known as persistent (common) truncus arteriosus.

Animals↗

Development of the upper lip.

OBJECTIVES: To affirm and reanalyze George L. Streeter's "merging theory" of upper-lip development in primates by observing progressive embryologic stages in facial development using scanning electron microscopy (SEM) and to further understand upper-lip development. DESIGN: The study was conducted at the California Regional Primate Research Center, Davis. Twenty primate embryos (Macaca fascicularis) and 2 fetuses were examined with SEM. The development of the frontonasal prominence, maxillary prominence, medial nasal prominence, and lateral nasal prominence were sequentially observed. The contribution of these prominences to the formation of the upper lip and nose were carefully analyzed. RESULTS: The maxillary prominence and medial nasal prominence form the upper lip, whereas the lateral nasal, medial nasal, and maxillary prominences form the nose. There is fusion of the maxillary prominence with the medial nasal prominence. This fusion has not been previously described. This has resulted in a modification of the current theory of upper-lip development into one we refer to as the "dynamic fusion theory." CONCLUSIONS: The dynamic fusion theory explains the merging process of the mesenchymal and ecotodermal layers of the facial prominences that contribute to the upper-lip formation. The dynamic fusion theory of facial prominence movement details the interaction between epithelial layers: both epithelial layers must fuse properly to avoid cleft-lip deformities.

Animals↗