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Biomedical subjects

A L Goodman

Publications and source records attributed to A L Goodman.

At least 19 recordsLinked to original sources
PubMed1999

Disparate actions of mifepristone (RU 486) on glands and stroma in the primate endometrium.

Besides being an antiprogestin, mifepristone (RU 486) was recently shown to antagonize oestrogen-dependent growth in the endometrium. To explore the molecular mechanisms for this phenomenon, we investigated whether or not the morphological effects of mifepristone are mediated by the progesterone receptor (PR) and whether mifepristone has disparate effects on the glandular epithelium and stroma. Six groups of hypogonadal, oestrogen-primed cynomolgus monkeys were treated for 2 weeks with: vehicle only (group I); mifepristone (group II); mifepristone plus progesterone at 0.2 mg/kg (group III), 1.0 mg/kg (group IV) or 5.0 mg/kg (group V); and progesterone only (5.0 mg/kg) (group VI). Histomorphological evaluation showed strikingly compacted stroma in the mifepristone-exposed endometria (group II), which was partially reversible by additional progesterone treatment (groups III-V). Glandular proliferation (pseudostratification, glandular mitoses) in mifepristone-treated monkeys was not significantly different from that in vehicle (oestradiol)-treated monkeys, but was inhibited by progesterone-only treatment. Cells containing vacuoles were scarce in the mifepristone-exposed endometrium, but detected frequently in progesterone-exposed endometria, indicating the strong antisecretory effect of mifepristone on glands. We conclude that oestrogen-dependent oedema in the stroma is antagonized by mifepristone. The reversal of this effect by progesterone suggests a PR-mediated mechanism. In glands, mifepristone is antiprogestogenic, but not antioestrogenic. Thus, stromal cells may be the target of antiprogestin-induced inhibition of oedema and endometrial growth.

Animals↗
PubMed1997

Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesterone-receptor ligands in vivo.

We investigated hormonal regulation of endometrial angiogenesis in menstruating primates. This study was designed to demonstrate: (i) that cell-specific vascular endothelial growth factor (VEGF) production and expression in monkey endometrium are regulated by steroid receptor ligands; and (ii) mifepristone (RU 486) alters VEGF production even in the absence of a progestin agonist. Endometrial VEGF production was compared by computer-assisted immunohistochemical analysis during induced hypoestrogenism and after oestradiol, progestin, or antiprogestin (mifepristone) treatment. VEGF gene expression was estimated by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in endometrial samples from castrate cynomolgus monkeys, from intact monkeys in the luteal phase, and from monkeys treated for 20 days with levonorgestrel (LNG) or mifepristone. VEGF staining intensities in glandular epithelium and VEGF mRNA expression were highest in hypoestrogenic monkeys. Progestin treatment induced intense VEGF staining in the stroma. Gene expression of VEGF-189, but not other isoforms, was higher in progesterone- and progestin (LNG)-exposed endometria compared to mifepristone-exposed endometria or endometria from anovulatory cycles (P < 0.04). Mifepristone abolished VEGF staining in glandular epithelium almost completely. We conclude that VEGF protein and VEGF mRNA expression levels in primate endometrium depend on the steroidal milieu. Anti-angiogenic effects of mifepristone via suppression of VEGF production might represent a mechanism for its quelling effects on endometrium.

Animals↗
PubMed1993

Ovarian angiogenesis in rabbits: endotheliotrophic chemoattractant activity from isolated follicles and dispersed granulosa cells.

To test the hypothesis that angiogenesis is an important variable in ovarian folliculogenesis, we measured endothelial cell migration (chemotaxis) in media conditioned by rabbit ovarian cells. Endothelial cell migration, a reliable predictor of angiogenesis in vivo, was stimulated by media conditioned by isolated intact follicles (0.4-2.2 mm in diameter) from either unstimulated or hCG-stimulated (pseudopregnant) rabbits. In separate experiments, endothelial cell migration was also stimulated by granulosa cell-conditioned media. Follicular chemoattractant activity was associated with a molecular weight greater than 30,000 but was not correlated with follicular size or steroid concentrations in the media, although there was no evidence to suggest that the biological activity detected in media conditioned by either intact follicles or dispersed granulosa cells was the same. Demonstration of nonsteroidal chemoattractant activity in media conditioned by intact follicles or by dispersed granulosa cells provides evidence that follicles secrete a vascular chemotactic factor, and is consistent with a role for angiogenesis in follicle growth.

Animals↗
PubMed1992

Evidence for the production of a nonsteroidal endotheliotropic factor by human granulosa cells in culture.

OBJECTIVE: To determine the cellular source of the angiogenic activity displayed by follicular fluid (FF). DESIGN: Human granulosa cells were harvested from 27 follicular aspirates obtained 34 to 36 hours after eight patients, previously treated with human menopausal gonadotropin (hMG), follicle-stimulating hormone plus hMG, or clomiphene citrate and hMG received human chorionic gonadotropin (10,000 IU intramuscularly). Granulosa cells from individual follicles were plated at 50,000 cells/cm2 in Medium 199 (Sigma, St. Louis, MO) supplemented with either 5% calf serum or 0.1% bovine serum albumin; media collected 24 hours later was assayed in vitro measuring endothelial cell migration. Fractions depleted of steroids by reversed phase C1 chromatography were assayed as well. RESULTS: Granulosa cell-conditioned media from 18 of 27 follicles significantly stimulated endothelial cell migration (P less than 0.05). Chemoattractant activity did not appear to be related to steroid accumulation in the media and was not diminished in steroid depleted fractions. CONCLUSIONS: These findings suggest that human granulosa cells are a source of (nonsteroidal) endotheliotropic-angiogenic activity in FF.

3T3 Cells↗
PubMed1990

Use of the levator scapulae muscle flap in head and neck reconstruction.

There are numerous techniques available for reconstruction of defects following composite resection of oral cavity and oropharyngeal tumors. No single technique is applicable in all situations. The levator scapulae muscle flap is well known for its application in carotid protection. Little attention is paid to its usefulness in other aspects of head and neck reconstruction. We have been using the levator scapulae muscle flap for a variety of reconstructive problems. The flap is useful for buttressing intraoral suture lines, closing intraoral defects, and providing soft tissue to fill in dead spaces and bulk out lateral and anterior oral defects. The levator flap was found to be easy to elevate, safe, and reliable with a minimum of wound complications. A review of 18 patients, representative case studies, and a discussion of surgical technique and relevant anatomy and blood supply is presented.

Aged↗
PubMed1990

Preliminary characterization of angiogenic activity in media conditioned by cells from luteinized rat ovaries.

Angiogenic activity was detected in media conditioned by ovarian cells from superovulated, pseudopregnant (PMSG/human CG treated) immature Holtzman rats. Media conditioned by cells from luteinized rat ovaries stimulated the directed migration of rabbit endothelial cells or mouse Balb/c3T3 cells, but was not mitogenic to either cell type. That endotheliotropic activity was not associated with a steroid was indicated by the finding that chemoattractant activity was detected in fractions after reversed-phase C18 chromatography, which removes more than 95% of steroids present in the media, and that chemoattractant activity was precipitated by ammonium sulfate and by ethanol. Full chemoattractant activity was recovered after boiling (95 C for 30 min), lyophilization, dialysis, Sephadex G-25 desalting columns, and pH changes from 3-10. After Sephadex G-200 chromatography, chemoattractant activity emerged at elution volumes corresponding to 20,000-30,000 mol wt. Chemoattractant activity was not retained by Concanavalin A-Sepharose or gelatin-Sepharose, and was only partially retained by heparin-agarose. Chemoattractant activity was also partially retained on both cation and anion exchange columns. Our collective findings indicate the presence of a nonsteroidal, heat-stable, pronase-sensitive factor, nominal mol wt of 20,000-30,000, in media conditioned by cells from luteinized rat ovaries; this factor is chemoattractive but not mitogenic to endothelial cells. Ovarian-derived chemoattractant activity appears to be distinct from fibroblast growth factor because it lacked detectable mitogenic activity, and because fibroblast growth factor was not active in our cell migration bioassay. Because stimulation of endothelial cell migration is a key event during angiogenesis, demonstration of an ovarian endotheliotropic chemoattractant is consistent with our hypothesis that angiogenesis factors play a role in the paracrine regulation of ovarian function.

Angiogenesis Inducing Agents↗
PubMed1987

Thyroid angiogenesis: endotheliotropic chemoattractant activity from rat thyroid cells in culture.

Thyroid enlargement in response to chronic hypersecretion of TSH reflects the coordinated growth of both parenchyma and stroma. Because Wollman et al. observed in propylthiouracil-fed rats that enlargement and remodeling of thyroid capillaries were strictly localized around follicles, they hypothesized that growth of perifollicular blood vessels is stimulated by angiogenic factors secreted by neighboring follicular epithelial cells. In support of this hypothesis, we report that media conditioned by rat thyroid cells were very active in an in vitro angiogenesis bioassay that measures stimulation of endothelial cell migration through chemotaxis membranes in microwell Boyden chamber assemblies. Primary cultures of thyroid cells from collagenase-dispersed glands from male or female Holtzman rats fed 0.01% propylthiouracil in the drinking water released activity that produced up to 5-fold increases in endothelial cell migration rates relative to those in identical unconditioned medium. Thyroid-derived activity was primarily chemotactic (i.e. only weakly chemokinetic) to both rabbit aortic and microvascular endothelial cells. That endotheliotropic activity is derived from thyroid parenchyma is indicated by the finding that media conditioned by FRTL cells, a clonally derived thyroid follicular epithelial cell line, produced parallel chemoattractant responses. Thyroid-conditioned media were also chemoattractant to mouse BALB/c-3T3 cells, which have endothelial cell characteristics. In contrast, thyroid-conditioned media did not increase the high spontaneous migration rate of Walker rat sarcoma (WR256) cells. T4, T3, thyroglobulin, bovine fibroblast growth factor (alpha and beta), and media conditioned by rabbit endothelial cells were inactive. Chemoattractant activity in serum containing conditioned media was retained by both 10,000 and 30,000 mol wt cut-off (MWCO) ultrafilters. Activity in serum-free thyroid-conditioned media was largely retained by 10,000 MWCO filters, but only partially retained by 30,000 MWCO filters; activity in the 30,000 filtrate was recoverable in a 10,000 MWCO retentate. These findings support the hypothesis that capillary growth during thyroid enlargement occurs, at least in part, as a result of a parenchymal-stromal (epithelial-mesenchymal) paracrine interaction mediated by specific endotheliotropic (angiogenic) factors released by follicular epithelial cells and distinct from T3, T4, and thyroglobulin.

Animals↗
PubMed1987

Heterogeneity of rabbit aortic endothelial cells in primary culture.

Factor VIII-related antigen (F8-RAg) and angiotensin-converting enzyme (ACE) are accepted diagnostic markers of endothelial cells in culture. However, when we isolated cells from rabbit thoracic aorta (after collagenase treatment and gentle scraping of the intima) and examined them with immunoperoxidase techniques, we observed two cell types which stained specifically for either F8-RAg or ACE, but not both. Each cell type was morphologically distinguishable in primary culture. F8-RAg-positive cells were recognizable in distinct patches as more elongated, tightly apposed, and firmly adherent cells; they exhibited only faint or no staining for ACE and no accumulation of a fluorescent, acetylated low-density lipoprotein probe (DiI-Ac-LDL), another endothelial cell marker. In contrast, ACE-positive cells were more rounded, less closely apposed, and grew as strict monolayers that exhibited a characteristic cobblestone appearance at confluence; ACE-positive cells were F8-RAg negative, but demonstrated intense labeling with DiI-Ac-LDL. Subcultures of ACE-positive cells were also stained by anti-rabbit thrombomodulin.

Animals↗
PubMed1987

Sequence of reconstitution of seven basement-membrane components following split-thickness wound induction in primate skin.

Recent studies have shown an orderly sequence of expression of structural antigens within the skin basement-membrane zone of the human fetus. Interestingly, these findings differ from those reported following split-thickness would induction in Yorkshire pigs. To readdress this apparent disparity, as well as to further extend such studies to include other basement-membrane antigens more recently identified, we produced split-thickness wounds in a primate species and serially examined the wounds by immunofluorescence technique for the expression of seven antigens normally found in intact primate skin basement membrane. By the fourth day following wounding, laminin, type-IV collagen, and fibronectin were all detectable along the dermoepidermal junction. In contrast, bullous pemphigoid antigen, epidermolysis bullosa acquisita antigen, cicatricial pemphigoid antigen, and KF-1 antigen were undetectable until days 6, 8, 10, and 11, respectively. These latter findings are in complete agreement with those previously reported in the developing human fetus. On the basis of the results of this study, we would suggest that primate rather than pig skin may be a more appropriate animal model for wound-healing studies. These data are consistent with previous reports suggesting that the basement-membrane antigens recognized by bullous pemphigoid and cicatricial pemphigold autoantibodies are indeed distinct. Finally, these data bring into question the functional role of bullous pemphigoid antigen during the early phase of wound healing in humans.

Animals↗
PubMed1986

Inhibin-like activity in ovarian venous serum after unilateral ovariectomy in prepubertal gilts.

To examine a role for inhibin in compensatory ovarian hypertrophy after unilateral ovariectomy (ULO) of prepubertal gilts, changes in inhibin activity in ovarian venous blood were estimated by bioassay. Three groups of 130-day-old gilts were unilaterally ovariectomized after collecting blood from an ipsilateral ovarian vein (Day O); blood samples were obtained from the remaining ovary on Day 2, 4, or 8. Coetaneous gilts underwent sham ovariectomy on Day 0, and venous blood was collected from both ovaries on Day 2, 4, or 8. An assay for inhibin activity, which measured inhibition of secretion of follicle-stimulating hormone (rFSH) by rat pituitary cells in culture, was validated for serum samples. Presumptive inhibin activity was always greater in ovarian venous serum than in peripheral serum samples. In the ULO groups, inhibin activity (in terms of a house reference preparation) in ovarian venous serum was 55 +/- 13 micrograms/ml (means +/- SE, n = 13) on Day 0, 251 +/- 79 (n = 5) on Day 2, 275 +/- 111 (n = 4) on Day 4, and 68 +/- 14 micrograms/ml (n = 4) on Day 8. The five-fold increases on Days 2 and 4 were significant (p less than 0.05). In contrast, no significant differences in inhibin activity were detected between ovarian venous serum (within gilts) or between Days 2, 4, and 8: 82 +/- 29, 73 +/- 30, and 99 +/- 48 micrograms/ml (n=4/day) in control groups. These results demonstrate that, in prepubertal gilts, the remaining ovary's response to ULO includes a major increase in release of inhibin-like activity.

Age Factors↗
PubMed1985

Evidence for a non-steroidal angiotropic factor from the primate corpus luteum: stimulation of endothelial cell migration in vitro.

After luteal cells from 7 midluteal phase cynomolgus monkeys were cultured for 72 h, luteal conditioned media were found to contain angiotropic activity that stimulated endothelial cell migration in vitro, using a 48-microwell chemotaxis assembly. The number of endothelial cells that migrated through 8 micron-pore polycarbonate membranes in 2 h was three-fold greater (P less than 0.01) with luteal cell-conditioned vs identical unconditioned media. Pre-treatment of luteal cultures with hCG, FSH, or testosterone did not enhance production of the endothelial cell migration stimulating activity (P greater than 0.25). Luteal angiotropic activity was both chemotactic and chemokinetic. Angiotropic activity was retained in steroid-depleted fractions after reversed-phase chromatography. These results demonstrate that monkey luteal cells secrete a non-steroidal factor(s) which directly stimulate(s) migration of endothelial cells in vitro. A luteal angiotropic factor may be an important intraovarian regulator of the formation and lifespan of the primate corpus luteum during the ovarian cycle.

Angiogenesis Inducing Agents↗
PubMed1984

In vitro evidence of a role for inhibin in female rabbits.

To examine a regulatory role for inhibin in female rabbits, an in vitro bioassay for inhibin activity was modified to use cultured rabbit pituitary cells and charcoal-extracted porcine follicular fluid (pFFx) as a reference preparation. pFFx inhibited follicle-stimulating hormone (FSH) release in a dose-dependent manner in cultures from both intact (I) and castrate (C) does at doses that also inhibited FSH release by cultured rat pituitary cells. Basal FSH release by I cells was inhibited greater than 10% by 0.02% (vol/vol) and greater than 90% by greater than or equal to 0.2% pFFx, whereas in C cells maximal inhibition of FSH release plateaued at only approximately 75%. FSH secretion was restored after removal of pFFx in day 2 media. Luteinizing hormone (LH) release by C cells was not inhibited at any dose of pFFx, but in I cells LH was progressively inhibited to approximately 60% of control levels during day 2 (but not day 1). Charcoal-extracted media (0.25-1%) in which 5 X 10(5) rabbit granulosa cells had been earlier cultured for 72 h produced a parallel inhibition of FSH release. The present findings demonstrate that 1) rabbit pituitary cells are responsive to inhibin, i.e., pFFx preferentially inhibited FSH secretion in a direct, graded, and reversible manner and 2) rabbit follicular granulosa cells secrete an inhibin-like substance.

Animals↗
PubMed1982

Granulosa cell pyknosis in the dominant follicle of monkeys.

One of the primary morphologic criteria used as the first sign of degeneration of an antral follicle is the presence of a pyknotic nucleus in granulosa cells lining the lumen. This study was undertaken to determine whether granulosa cells with a pyknotic nucleus are also present in the putative dominant follicle. Dominance was verified by elevations of estradiol either following luteectomy or during the later stages of the follicular phase of the menstrual cycle. Some pyknosis is normal even in the viable dominant follicle at cycle day 8 or 12. Therefore, when evaluating the morphologic status of a follicle, one should examine several areas to assure proper evaluation.

Animals↗
PubMed1982

Neurophysiological and psychopharmacological approaches to sensory deprivation phenomena.

1. Research concerned with neurophysiological aspects of sensory deprivation phenomena is surveyed. 2. A theory is developed regarding the neurophysiological processes involved in sensory deprivation phenomena. It is postulated that the high amplitude bursts of slow waves observed in the visual cortex and lateral geniculate nucleus in deafferentation studies represent a PGO-like substrate of dream initiation. Concurrent neurochemical alterations are hypothesized to consist of a decrease in central serotonergic activity and an increase in norepinephrine level. 3. Hallucinogenic drugs, which produce subjective effects similar to those reported in sensory deprivation, are noted to induce neurochemical changes similar to those hypothesized for sensory deprivation. 4. New directions for research in this field are suggested.

Animals↗