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Biomedical subjects

R Bronson

Publications and source records attributed to R Bronson.

85 records · Page 5Linked to original sources

The effect of prostaglandins F2alpha and E2 on pregnancy in mice during implantation.

The uterine content of prostaglandins (PGs) increases following insertion of an intrauterine device (IUD). Such IUD-bearing uteri also exhibit impaired decidualization. Although prostaglandins have been shown to be luteolytic in several species, it is not clear that inhibition of decidualization is mediated solely through alterations in ovarian steroidogenesis. In these experiments, ovariectomized, hormone-replaced pregnant mice, as well as intact mice, were treated systemically with either PGE2 or PGF2alpha so that the extraovarian actions of prostaglandins upon decidualization could be segregated from effects mediated by alterations in ovarian steroidogenesis. The results suggest that the effect of PGF2alpha upon decidualization was mediated via an alteration in ovarian steroidogenesis, but that PGE2 acted independently of the ovary. The hypothesis is presented that alterations in the ratio of E to F prostaglandins elicited within the endometrium by an IUD inhibit decidualization at the uterine level, and that this effect might be mediated by impairment of histamine release from endometrial mast cells.

Animals↗

Long term post-traumatic retrograde corticospinal degeneration in man.

The spinal cord and brain of a man who died 18 years after a crush injury of lumbar segments contained some unusual lesions. There was a reduced number of myelinated axons in the corticospinal tracts as high as the fifth cervical segment. Such retrograde degeneration has been described in human pyramidal tracts only a few times. The results of reported studies of experimental retrograde degeneration have been inconsistent. The course of the fasciculus gracilis, as delineated by gliosis, was atypical, and an unusual glial nodule, possibly neoplastic, was present in the dorsal columns at C8.

Accidents, Traffic↗

Gamete interactions in vitro.

A method was devised that allowed observation of individual sperm in vitro in the presence or absence of unfertilized eggs. Sperm traversing microcapillary tubes in the absence of eggs moved in linear tranjectories. Sperm in the environs of unfertilized eggs moved in erratic paths, owing to repeated adherence of the sperm head to the wall of the microcapillary tube. However, translational velocity was unaltered. Increased adhesiveness was not noted when sperm were exposed to unfertilized eggs following removal of the cumulus oophorus with hyaluronidase. Gamete interactions in vitro were also studied at varying sperm to egg ratios. When gametes were mixed at high sperm to egg ratios (approximately 10(6):1) the cumulus oophorus was rapidly dissolved, and sperm became adherent to the zona pellucida. At low ratios (approximately 10(2):1), the cumulus oophorus remained intact. Binding of sperm to individual cumulus cells was noted. A hypothesis is presented that cumulus oophorus plays a role in fertilization by selectively trapping mature sperm within the perimeter of the egg and, in so doing, extending the duration of time in which gametes remain within close proximity, thus increasing the likelihood of egg contact by capacitated sperm.

Adhesiveness↗

Effectiveness of prostaglandin f 2 alpha in restoration of HMG-HCG induced ovulation in indomethacin-treated rhesus monkeys.

Six mature female rhesus monkeys were treated with HMG-HCG in control cycles at doses adjusted to induce ovulation while avoiding superovulation. Occurrence of ovulation was determined by observation of fresh ovulation points at laparotomy 48 to 120 hours following HCG. In subsequent cycles animals were treated with indomethacin (treatment days 4 through 10) together with the established dose of HMG-HCG. In 8 cycles indomethacin 5 mg/kg was given i.m. once daily; in 9 cycles 10 mg/kg i.m. was administered in 2 divided doses. Following this, PGF2alpha (3 mg t.i.d. s.c.) was administered for 3 days together with indomethacin 10 mg/kg and HMG-HCG, beginning on the day prior to HCG. Determinations of progesterone were performed by RIA on treatment days 4, 7, 10, and 11. Eleven of the 13 control cycles were ovulatory. With indomethacin 5 mg/kg/day, 5 of 8 cycles were ovulatory but ovulation was delayed in 2 instances. Of 9 cycles using indomethacin 10 mg/kg/day only 1 was ovulatory. When PGF2alpha was administered in susequent cycles along with indomethacin (10 mg/kg) and HMG-HCG, ovulation occurred in 13 of 19 cycles. These data suggest that local ovarian PGF2alpha may be essential in the mechanics of follicle rupture in gonadotropin-treated rhesus monkeys.

Animals↗

Transfer of uterine implantation blastocysts to the oviduct in mice.

Although ectopic pregnancy is a common occurrence in humans, it occurs only rarely in other species. In the mouse, confinement of the blastocyst to the oviduct fails to result in implantation at that level. In prior studies, these confined blastocysts had not been exposed to the uterine environment. We transferred blastocysts from the uterus, at a time when implantation would normally occur, to ligated oviducts of pseudopregnant mice. Although enlargement of the blastocysts, loss of the zona pellucida, and adherence to the tubal epithelium were noted, implantation did not occur. The contributions to the embryo by the uterine environment were not sufficient to allow implantation within the oviduct.

Animals↗

Calorie restriction increases light-dependent photoreceptor cell loss in the neural retina of fischer 344 rats.

We investigated the effect of > or = 8 months of 40% caloric restriction (CR) on photoreceptor cell loss in 12, 18, and 24 month-old Fischer 344 rats (N = 154). Rats were reared at the NIA Biomarkers Program, National Center for Toxicological Research. Photoreceptor cell density, assessed histologically, declined with age in both the CR-fed and ad lib (AL)-fed cohorts (P < 0.000), but declines were more pronounced in the CR cohort (P < 0.0005). The deleterious effect of CR was most pronounced in the central as opposed to the peripheral retina (P = 0.008), suggesting a light-dependent mechanism. Photoreceptor cell density was inversely associated with rearing under bright light (300-750 lux) as compared with rearing under lower illuminance (< or = 200 lux) (P < 0.0005). However, the deleterious effect of bright light on photoreceptor cell density was more pronounced in the CR cohort (P = 0.04). Effects of CR on circadian activity are likely to increase the actual light exposure of the CR cohort and may explain the apparent inability of CR to delay retinal aging in albino rats.

Aging↗

Detection of spontaneous schwannomas by MRI in a transgenic murine model of neurofibromatosis type 2.

Spontaneous schwannomas were detected by magnetic resonance imaging (MRI) in a transgenic murine model of neurofibromatosis type 2 (NF2) expressing a dominant mutant form of merlin under the Schwann cell-specific P0 promoter. Approximately 85% of the investigated mice showed putative tumors by 24 months of age. Specifically, 21% of the mice showed tumors in the intercostal muscles, 14% in the limb muscles, 7% in the spinal cord and spinal ganglia, 7% in the external ear, 14% in the muscle of the abdominal region, and 7% in the intestine; 66% of the female mice had uterine tumors. Multiple tumors were detected by MRI in 21% of mice. The tumors were isointense with muscle by T1-weighted MRI, showed strong enhancement following administration of gadolinium-DTPA, and were markedly hyperintense by T2-weighted MRI, all hallmarks of the clinical manifestation. Hematoxylin and eosin staining and immunohistochemistry indicated that the tumors consisted of schwannomas and Schwann cell hyperplasias. The lesions stained positively for S-100 protein and a marker antigen for the mutated transgenic NF2 protein, confirming that the imaged tumors and areas of hyperplasia were of Schwann cell origin and expressed the mutated NF2 protein. Tumors were highly infectable with a recombinant herpes simplex virus type 1 vector, hrR3, which contains the reporter gene, lacZ. The ability to develop schwannoma growth with a noninvasive imaging technique will allow assessment of therapeutic interventions.

Animals↗

Is the oocyte a non-professional phagocyte?

Although fertilization has been described as a series of events during which the spermatozoon penetrates the oocyte, introducing its nuclear contents, there is strong evidence that either gamete can be the active partner at different stages of this process. Indeed, while sperm motility is essential for its penetration of the egg vestments, immotile spermatozoa are capable of entering the ooplasm once they adhere to the oolemma. Entry of the spermatozoon into the oocyte appears to require two distinct but perhaps related events, namely gamete cell membrane fusion, at the level of the equatorial segment of the sperm acrosome with the oolemma, and a quasi-phagocytic event involving the incorporation by the oocyte of the rostral portion of the acrosome-reacted spermatozoon head within an oolemmal-derived vesicle. This review explores the biology of phagocytosis by macrophages and non-professional phagocytes, and in particular the roles played by phagocytosis-promoting receptors (FcgR, complement receptors and integrins), in both signal transduction and their linkage with the cytoskeleton. It asks whether the oocyte might not utilize similar mechanisms during its incorporation of the spermatozoon.

Animals↗

Identification of human sperm surface glycoproteins recognized by autoantisera from immune infertile men, women, and vasectomized men.

To identify the surface antigens of human sperm recognized by antisera from immune infertility patients and vasectomized men, we labeled sperm surface proteins with 125I- and used patient antisera for immunoprecipitation. Sera were studied from 27 infertile males, 18 infertile females, and 4 vasectomized males, each possessing anti-sperm antibodies detected by immunobead binding. Sera from different infertile males, different infertile females, and vasectomized males were remarkably similar in their surface antigen recognition. The different sera specifically immunoprecipitated the same small group of 125I-labeled surface proteins, which included polypeptides in the region 90 kDa, 40-45 kDa, and 26 kDa. Treatment with N-glycanase showed that the proteins of 90 kDa, 40-45 kDa, and 26 kDa were glycoproteins with N-linked carbohydrate. The immunoprecipitated 125I-labeled proteins and the total extract of 125I-labeled surface proteins were compared on two-dimensional (2D) gels. The results show the 90 kDa polypeptide is a major sperm surface component, whereas 40-45 kDa and 26 kDa polypeptides are minor components. The 2D gel comparison also indicates that 90 kDa, 40-45 kDa, and 26 kDa are a small subset of the total ensemble of sperm surface proteins. Clinical data suggest antibodies to these few proteins interfere with sperm function.

Autoantibodies↗

Characterization of integrin beta6 and thrombospondin-1 double-null mice.

To identify overlapping and non-overlapping functions for TSP-1 and alphavbeta6, we crossed TSP-1-null and beta6-null mice and compared the phenotype of the double-null mice with those of wild-type and single-null mice. The double-null mice exhibited focal acute and organizing pneumonia that was more severe than the wild-type and single-null mice as well as a significantly higher incidence of inflammation in tissues other than the lung. The TSP-1-null and beta6-null mice exhibited a five to eight-fold increase in granulocyte recruitment to the lung three days after exposure to lipopolysaccharide. They also had abnormalities that were infrequently observed in the wild-type and single-null mice, including heart degeneration (8.35% in wild-type and 28.1% in double-null mice), hyperplasia of the glandular of the stomach (2.8% in wild-type and 21.1% in double-null mice) and endometrial hyperplasia (0% in wild-type and 38.5% in double-null females). Furthermore, the beta6-null and double-null mice displayed a significant elevation in benign and malignant cancers. Stomach papillomas, squamous cell carcinomas of the ear and stomach, and adenocarcinomas of the lungs, vagina/cervix and colon were observed with the highest frequency. These data demonstrate that TSP-1 and alphavbeta6 are involved in regulation of the immune system and epithelial homeostasis. They also indicate that alphavbeta6 functions as a tumor suppressor gene and that activation of TGFbeta by TSP-1 and alphavbeta6 contributes to normal tissue architecture and function.

Alopecia↗