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Biomedical subjects

D A Freeman

Publications and source records attributed to D A Freeman.

At least 55 records · Page 3Linked to original sources
PubMed1994

Immunohistochemical localization of pregnancy-related placental protein 4 in nontumorous tissues and in gynecological tumors.

The aim of the study was to demonstrate the localization of placental protein 4 (PP4) in different nontumorous and tumorous tissues originating from the female genital tract. PP4 immunoreactivity was demonstrated using the peroxidase-antiperoxidase immunohistochemical technique. Tissue samples were obtained from the cervix and body of the uterus, ovary, vulva and from gestational trophoblastic tumors. PP4-positive cells were present in nontumorous tissues with various pathologic findings, and in many but not all benign gynecological tumors. Similar numbers of PP4-positive cells were located in malignant and benign gynecological tumors; however, PP4 staining intensity was greater in the malignant lesions. PP4-positive cells were found in hydatidiform moles and in choriocarcinoma. PP4 was distributed mainly in the cytoplasm, but it was also bound to the cell membrane. We conclude from these studies that PP4 is located in a variety of benign and malignant cells of the female genital tract and that these cells may be the source of plasma PP4 found in patients with these conditions.

Female↗
PubMed1994

Role of gonadal steroids and inhibitory photoperiod in regulating body weight and food intake in deer mice (Peromyscus maniculatus).

We investigated the role of declining daylength and gonadal steroids on body weight and food intake in male deer mice (Peromyscus maniculatus). This species was chosen for study because individual males display different reproductive responses to inhibitory daylength. About one-third of all mice exposed to short days undergo testicular regression and exhibit reduced circulating levels of luteinizing hormone and testosterone (reproductive responsive males). In contrast, testicular function and circulating levels of both these hormones remain unaffected in an equal number of mice (reproductive nonresponsive males). Previous studies have shown that each phenotype exhibits a distinct set of metabolic responses to short days, including adjustments in body weight. These characteristics make deer mice a useful animal model in which to study the interactive effects of gonadal steroids and photoperiod on neural substrates regulating body weight. A gonadectomy/steroid replacement experimental model was used to test the role of testosterone in regulating body weight and food intake in short day-housed male deer mice. Among gonad-intact males, short daylength caused a decline in body weight in both reproductive responsive and nonresponsive individuals. However, reproductive responsive mice lost significantly more body weight than did nonresponsive mice. Furthermore, while the weight loss was accompanied by a significant reduction in food intake in responsive mice, the relatively minor weight loss in nonresponsive mice was not accompanied by a change in food intake. Because changes in body weight and food intake (data not shown) occurred nearly simultaneously during the 8-week exposure to short daylength, results suggest that modifications in body weight are not responsible for the decline in food consumed, and vice versa. Gonadectomized reproductive responsive mice lost the same amount of weight as intact responsive mice but ate significantly more food. Among nonresponsive males, gonadectomy led to significantly greater weight loss, relative to intact mice, but caused an increase in food intake per gram body weight. Steroid replacement prevented weight loss and increased food intake in both gonadal phenotypes. Despite the observations that food intake was steroid dependent and the magnitude of the effect differed between reproductive phenotypes, changes in food consumption do not fully explain the inhibitory effects of short days on body weight in either phenotype. Taken together with previous studies, these results suggest that reproductive quiescence confers significant metabolic benefits to individual deer mice by reducing the amount of daily energy requirements via a reduction in body weight.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Plasma membrane cholesterol is utilized as steroidogenic substrate in Y-1 mouse adrenal tumor cells and normal sheep adrenal cells.

Previous studies from this laboratory indicate that plasma membrane cholesterol acts as an important source of steroidogenic substrate for MA-10 Leydig tumor cells. The present studies were designed to generalize these findings to other steroidogenic cells and to another species. Studies were performed using the Y-1 murine adrenal tumor cell line and primary cultures of sheep adrenocortical cells. Treating Y-1 cells with the acyl coenzyme A:cholesterol acyltransferase inhibitor, 58-035, caused cellular cholesteryl ester depletion and rendered more apparent the effect of dibutyryl-cAMP to cause cellular free cholesterol depletion. Radioactive 20 alpha-dihydroprogesterone was synthesized by Y-1 cells that had been plasma membrane-labeled with [3H]-cholesterol. Primary sheep adrenal cultures that had been cholesteryl ester-depleted also demonstrated cellular free cholesterol depletion after stimulation with dibutyryl cAMP. Plasma membrane label was converted to steroid hormones in these cells as well. Taken together, these data indicate that the use of plasma cholesterol is not restricted to the MA-10 cells. The present data indicate that both neoplastic mouse adrenal tumor cells and normal sheep adrenal cells utilize plasma membrane cholesterol.

Adrenal Gland Neoplasms↗
PubMed1993

Oviductal and uterine influence on the development of Day-2 equine embryos in vivo and in vitro.

The objective of this experiment was to contrast the influence of the oviductal and uterine environments on development of Day-2 embryos. Embryos were transferred to oviducts or uteri of synchronous recipient mares, or were incubated in oviductal co-culture, in uterine co-culture or in defined culture medium. Significantly more (P < 0.02) embryos transferred to the oviduct versus the uterus survived until Day 11 after ovulation (5 7 vs 0 7 , respectively). Significantly more (P < 0.001) embryos developed to expanded and hatched blastocysts in uterine co-culture than in culture medium (6 7 vs 0 7 , respectively). The rate of embryo development to expanded blastocysts was not significantly different (P > 0.1) in oviductal co-culture versus uterine co-culture (3 7 vs 6 7 , respectively), or in oviductal co-culture versus culture in medium (3 7 vs 0 7 , respectively). Three of 7 and 6 of 7 embryos developed to hatched blastocysts greater than 2000 mum in diameter during oviductal and uterine co-culture, respectively, while 0 of 7 embryos cultured in medium expanded to greater than 500 mum in diameter. Proportions of embryos that developed for at least 9 days.

Journal Article↗
PubMed1993

Ovarian follicles, ovulations and progesterone concentrations in aged versus young mares.

The objectives of this study were: 1) to document age-related ovulation failure in mares and 2) to contrast the number of ovarian follicles, occurrence of ovulations, and postovulatory concentrations of progesterone in aged versus young mares. In Experiment 1, 4 of 10 aged (25- to 33-years-old) mares were anovulatory between July 1 and September 1, 1989. In Experiment 2, two of 25 aged (20- to 30-years-old) and none of 21 young (3- to 12-years-old) mares were anovulatory between February 1 and June 30, 1990. The average (+/- SEM) day of the first ovulation was later (P<0.05) for aged versus young mares (May 9 +/- 7.1 vs April 25 +/- 7.4 days, respectively). There tended (P<0.10) to be fewer 11- to 20-mm ovarian follicles in aged versus young mares (2.8 +/- 0.2 vs 5.3 +/- 0.1, respectively), but there was no difference (P>0.10) in the total number of ovarian follicles in aged versus young mares (21.0 +/- 0.3 vs 26.1 +/- 0.2, respectively) during the pooled periovulatory period of the first and second (single) ovulations. The number of ovulatory cycles during the study period was less (P=0.01) for aged versus young mares (2.2 +/- 0.3 vs 3.2 +/- 0.3). Plasma progesterone concentrations on Days 10 and 15 of the first ovulatory cycle were higher (P<0.05) in aged versus young mares.

Journal Article↗
PubMed1993

The relationship of semen quality to pregnancy rate and litter size following artificial insemination in the bitch.

Artificial insemination of 31 bitches with fresh, undiluted, semen resulted in 22 31 conceptions (71%) and the birth of 124 puppies. Inseminations using at least 220 x 10(6) spermatozoa of normal morphology resulted in a mean pregnancy rate of 81.5% (22 27 ). The pregnancy rates were significantly influenced by the total number of progressively motile or morphologically normal sperm cells per ejaculate (P < 0.05). The pregnancy rate was not influenced by the percentage of progressively motile or morphologically normal sperm cells per ejaculate (P > 0.1). Litter size was not influenced by sperm motility or morphology (P > 0.1).

Journal Article↗
PubMed1993

Finasteride blocks progesterone synthesis in MA-10 Leydig tumor cells.

The 5 alpha-reductase inhibitor, finasteride, inhibits progesterone synthesis in the MA-10 Leydig tumor cells. Inhibition is dose-dependent with half maximal inhibition occurring at 10 ng/ml, a concentration significantly less than serum concentrations detected in finasteride-treated patients. Experiments to localize the site of inhibition by this compound revealed that the 3 beta-hydroxysteroid dehydrogenase delta 5-->delta 4 isomerase enzyme was not blocked by finasteride, but that cholesterol side-chain cleavage was inhibited. Thus, both dibutyryl-cAMP-stimulated and 22-hydroxycholesterol-stimulated steroidogenesis were inhibited by finasteride. This effect of finasteride to block cholesterol side-chain cleavage may be species-specific. Inhibition is readily detected in the mouse-derived MA-10 cells; however, human granulosa cell steroidogenesis is finasteride-insensitive while rat Leydig cell steroidogenesis is only minimally effected by finasteride.

Bucladesine↗
PubMed1992

Testicular feminization syndrome in a mare.

Testicular feminization syndrome was diagnosed in a mare with aggressive, stallion like behavior and a history of infertility. She was found to have a high baseline testosterone concentration suggesting that testicular tissue was present, and ovarian-like structures examined by use of transrectal ultrasonography had the appearance typical of testicular tissue. Although her external female genitalia appeared normal, her vagina ended in a blind sac, and no cervix or uterus were identified. Surgery was performed, and structures removed from the abdominal cavity were determined to be hypoplastic testicles. Removal of the testicular tissue resulted in complete resolution of her aggressive behavior. Chromosomal evaluation revealed that the mare had 64X,Y (normal male) karyotype. Testicular feminization syndrome is a condition characterized by insensitivity of reproductive tissues to androgens during development because of an abnormality in androgen receptors. This androgen insensitivity results in development of normal external female genitalia, with high testosterone concentrations being released from developing testicles. Testicular feminization syndrome has not been commonly diagnosed in horses, but should be considered as a differential diagnosis for overly aggressive mares with a history of infertility.

Aggression↗
PubMed1992

Prostaglandin E2 secretion by day-6 to day-9 equine embryos.

Prostaglandin E2 (PGE2) secreted by Day-6, Day-7, Day-8 and Day-9 equine embryos (ovulation = Day 0) during in vitro incubation was measured by radioimmunoassay. Embryonic PGE2 secretion (ng/embryo/24 hr) was detectable on Day 6 (0.27 +/- 0.39), tended to increase (P less than 0.1) on Day 7 (0.57 +/- 0.88), and increased significantly (P less than 0.05) on Day 8 (2.23 +/- 0.86) and Day 9 (4.13 +/- 0.71). Embryo diameter at the start of the incubation period was linearly correlated (P less than 0.01) to embryonic PGE2 secretion.

Animals↗
PubMed1992

Prostaglandin E2-specific binding to the equine oviduct.

Prostaglandin E2 (PGE2) bound specifically (P less than 0.001) to ampullary and isthmic tissue on Day 2 and Day 5 after ovulation. No significant differences (P greater than 0.8) were detected between Day 2 and Day 5 in the specific binding of ampullary or isthmic tissue. Significantly more (P less than 0.05) PGE2 bound specifically to ampullary versus isthmic tissue on both days. Detection of PGE2-specific binding in the oviductal isthmus on Day 2 and Day 5 indicates that the oviduct is responsive to PGE2 when it is capable of transporting equine embryos.

Animals↗
PubMed1992

Adrenal insufficiency and stage D carcinoma of the prostate.

A patient with stage D prostatic cancer but in reasonably good general health was discovered to have adrenal failure and tumor destruction of the adrenal glands. Because prostatic cancer is common and compatible with prolonged survival, we surveyed other patients with stage D prostatic cancer. On initial screening with the cosyntropin test, we found that 5 of 14 patients failed to respond with an increase in serum cortisol of 10 micrograms/dL, suggesting an adrenal failure incidence of 36%. Retesting, however, indicated that probably all of these were false-positive results.

Adenocarcinoma↗
PubMed1992

A cholesteryl ester hydrolase inhibitor blocks cholesterol translocation into the mitochondria of MA-10 Leydig tumor cells.

The present studies describe an unexpected action of a cholesteryl ester hydrolase inhibitor on MA-10 Leydig tumor cells. These studies were initially intended to use the inhibitor, diethylumbelliferyl phosphate, to block cholesteryl ester hydrolysis and, thus, determine the contributions of this form of cholesterol to steroidogenesis and reveal any direct hormone effects on cholesterol esterification. Although this compound acted as an effective inhibitor of the cholesteryl ester hydrolase in intact MA-10 cells, it inhibited steroidogenesis at lower concentrations and to a greater extent than could be explained by simple inhibition of the ester hydrolase enzyme. This compound proved not to be generally toxic, but blocked some process occurring between cAMP formation and cholesterol side-chain cleavage. The diethylumbelliferyl phosphate block of steroidogenesis was readily bypassed by 22-hydroxycholesterol. These data indicated that the compound inhibited cholesterol transport. The lesion in cholesterol transport was not general, but very specific; cholesterol translocation to the mitochondrial site of cholesterol side-chain cleavage was blocked by this organophosphate compound.

Biological Transport↗
PubMed1992

Embryo-initiated oviductal transport in mares.

The hypothesis that equine embryos initiate oviductal transport in mares was tested by placing day 6 uterine embryos in the oviducts of day 2 (n = 10) or day 5 (n = 10) recipient mares and attempting to collect the embryos from the uterus 48 h later. To determine whether the surgical transfer procedure initiated oviductal transport, medium alone was placed in the oviducts of day 2 (n = 10) inseminated mares (sham transfer), and uterine embryo collections were attempted 48 h later. Embryos were transported through the oviduct of day 2 recipients by day 4 (instead of day 5 to 6) in six of ten mares, which was not significantly less (P greater than 0.1) than in day 5 recipients (9 of 10). Oviductal transport was not primarily initiated by the surgical transfer procedure, since oviductal transport occurred in only one sham transfer. There was no significant difference (P greater than 0.1) in the diameter of embryos placed in the oviducts of day 2 and day 5 recipient mares (180 +/- 13.8 versus 187 +/- 11.3 microns, respectively). However, embryos collected from the uterus were significantly smaller (P less than 0.05) in day 2 than in day 5 recipients (375 +/- 85.4 versus 659 +/- 43.6 microns, respectively). One uterine embryo had shed its zona pellucida before being placed in, and transported through, the oviduct of the recipient mare.

Animals↗