Viral co-infection, autoimmunity, and CSF HIV antibody profiles in HIV central nervous system escape.

Antiretroviral therapy (ART) suppresses plasma and cerebrospinal fluid (CSF) HIV replication. Neurosymptomatic (NS) CSF escape is a rare exception in which CNS HIV replication occurs in the setting of neurologic impairment. The origins of NS escape are not fully understood. We performed a case-control study of asymptomatic (AS) escape and NS escape subjects with HIV-negative subjects as controls in which we investigated differential immunoreactivity to self-antigens in the CSF of NS escape by employing neuroanatomic CSF immunostaining and massively multiplexed self-antigen serology (PhIP-Seq). Additionally, we utilized pan-viral serology (VirScan) to deeply profile the CSF anti-viral antibody response and metagenomic next-generation sequencing (mNGS) for pathogen detection. We detected Epstein-Barr virus (EBV) DNA more frequently in the CSF of NS escape subjects than in AS escape subjects. Based on immunostaining and PhIP-Seq, there was evidence for increased immunoreactivity against self-antigens in NS escape CSF. Finally, VirScan revealed several immunodominant epitopes that map to the HIV envelope and gag proteins in the CSF of AS and NS escape subjects. Whether these additional inflammatory markers are byproducts of an HIV-driven process or whether they independently contribute to the neuropathogenesis of NS escape will require further study.

Umbilical vessels of spontaneously hypertensive rats.

Umbilical vessels of spontaneously hypertensive rats, control strain Wistar-Kyoto rats and rats treated with alpha-methyldopa were compared using the scanning electron microscope and light microscope. Observations with the scanning electron microscope revealed that the venous endothelial cells were relatively flat, giving the luminal surface of the vein a smooth appearance. The nuclear region of the fusiform arterial endothelial cells was responsible for the bumpy appearance of the luminal surface of the artery. Microvilli were a consistent feature of the endothelium in both umbilical vessels. There was no consistent pattern of distribution or density of microvilli within either vessel, but microvilli were more abundant on the luminal surface of the artery than in the vein. The luminal surface of some endothelial cells of the artery had long straight processes which crossed several cells before terminating. Light microscopic observations revealed that the endothelial cells and cells of the tunica intima and media contained an abundance of glycogen. The same layers stained sparsely for acid glycosaminoglycans. Maternal hypertension and treatment of spontaneously hypertensive rats with the antihypertensive drug, alpha-methyldopa, did not result in significant morphological alterations of either the endothelium or tunica media of the umbilical blood vessels.

The effect of ligation or separation between the intrauterine device horn and adjacent ovary on implantation in the hamster.

The purpose of this study was to determine whether the luteolytic action of an intrauterine device (IUD) is suppressed following interruption of the continuity between the IUD uterine horn and the adjacent ovary. After several estrous cycles, a silk IUD was placed in the cervical end of one uterine horn of adult hamsters. The animals were then mated, and on day 6 of gestation the ovary and oviduct contralateral to the IUD were removed and a ligature was placed between the IUD horn and the adjacent ovary. The hamsters were killed on day 9 or day 13 of gestation. Fetal development in the contralateral horn was suppressed on day 13 but not on day 9. In the second study the animals were treated as in the first study except that the communication between the IUD horn and the adjacent ovary was severed completely. The hamsters were killed on day 9 or day 13. On both days 9 and 13 normal fetal development was observed in the control horn; no implantation sites were present in the IUD side. In the control (non-IUD) animals of each study, normal fetuses were present in both uterine horns. The study demonstrates that luteolysis does not occur if there is complete disruption of the communication between the IUD horn and ovary. The study also demonstrates that, since implantation did not occur in the IUD horn with a normally functioning ipsilateral ovary, the luteolytic action of the device is not the prime factor in suppressing implantation in the hamster.

Influence of the IUD on ovarian activitiy in the hamster and rat.

PIP: The efects of an unilaterally placed IUD on the maintenance of pregnancy in the contralateral horn was studied in rats and hamsters. Implantation and the number of corpora lutea were clearly affected by the IUD, but there was no effect on the number of eggs shed. There were no fetuses found in either horn in hamsters receiving a unilateral silk IUD. However, in rats, fetuses were found in the contralateral horn, though not in the IUD-bearing horn. Thus, the IUD has a different effect on ovarian function in rats and hamsters. The results suggest that the IUD causes regression of the corpus luteum in hamsters, and alters the uterine environment in rats.^ieng