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Biomedical subjects

K G Gould

Publications and source records attributed to K G Gould.

At least 19 recordsLinked to original sources
PubMed1992

Preservation of bone mass in hypogonadal female monkeys with recombinant human growth hormone administration.

This study examined the effect of human recombinant GH supplementation on bone loss in female monkeys made hypogonadal with GnRH agonist (GnRH-Ag). Animals were randomly assigned to three treatment groups: vehicle, GnRH-Ag, and GnRH-Ag and GH. After an initial 5-month pretreatment period during which all animals were maintained on a normal monkey chow diet containing a high level of calcium (1%) animals were maintained on a normal monkey chow diet containing a high level of calcium (1%), animals were shifted to a lower calcium diet (0.1%) for 4 to 5 months before the beginning of treatment and were maintained on this diet throughout the remainder of the study. Monkeys were treated continuously for 10 months with 25 micrograms/day GnRH-Ag or vehicle. GH was administered by im injection three times per week at a dose of 100 micrograms/kg body wt/day. Animals treated with GnRH-Ag were amenorrheic throughout the treatment period, and serum estradiol and progesterone levels were below minimum levels of detection. Vehicle-treated animals continued to cycle throughout the study. Monkeys treated with GnRH-Ag alone showed a significant decline (12%) in bone mineral density (BMD) of the lumbar spine. BMD was reduced below pretreatment levels from 6 months of GnRH-Ag treatment through 3 months post treatment in this group. GH supplementation reduced the decline of BMD in GnRH-Ag-treated monkeys. BMD did not change significantly with time in the GH-supplemented group. BMD values in GH supplemented animals between 5 and 10 months of the treatment period exceeded levels in animals treated with GnRH-Ag alone, but BMD levels during this interval were lower than in the vehicle-treated group. In the vehicle-treated group, there was small, but significant, increase in BMD over the course of the study. Serum osteocalcin concentrations were elevated above pretreatment values after 6 and 9 months of GnRH-Ag treatment alone or with GH supplementation, but did not change in vehicle-treated animals. GH also increased serum insulin-like growth factor 1 levels. In response to the lower calcium diet, serum PTH levels increased approximately 200% in vehicle-treated monkeys and animals treated with GnRH-Ag alone. GH attenuated this increase in serum PTH. The data indicate that the level of calcium in the diet of adult monkeys can be reduced more than 10-fold without affecting lumbar BMD provided ovarian function is normal, but if animals are made hypogonadal with a GnRH-Ag, bone mass declines.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Hormone levels and anogenital swelling of female chimpanzees as a function of estrogen dosage in a combined oral contraceptive.

A combined oral contraceptive consisting of ethinyl estradiol (EE2) in three dosages (50, 100, and 400 micrograms) and norethindrone (0.5 mg) was given to female chimpanzees to determine the effect on endogenous sex hormone levels and anogenital swelling. Serum levels of EE2 increased with increasing dosages of EE2, estradiol decreased, and luteinizing hormone, progesterone and testosterone were maintained at approximately midfollicular phase levels. Urinary levels of EE2 glucuronide increased with the increasing dosages of EE2, whereas estrone and pregnanediol glucuronide were essentially undetectable. The cyclic increase in female anogenital swelling was abolished when the norethindrone was combined with 50 micrograms of EE2 and relatively constant and low levels of swelling were recorded. Relatively constant but successively higher levels of swelling were recorded when the norethindrone was combined with the higher dosages of EE2. These effects of oral contraceptives on female genital tissues are relevant to our laboratory studies of sexual behavior in chimpanzees given oral contraceptives and could also have implications for women taking oral contraceptives.

Anal Canal↗
PubMed1991

Characterization of two distinct major histocompatibility complex class I Kk-restricted T-cell epitopes within the influenza A/PR/8/34 virus hemagglutinin.

Cytotoxic T-lymphocyte (CTL) clones specific for the influenza A/PR/8/34 virus hemagglutinin (HA) were isolated by priming CBA mice with a recombinant vaccinia virus expressing the HA molecule. The epitopes recognized by two of these clones, which were CD8+, Kk restricted, and HA subtype specific, were defined by using a combination of recombinant vaccinia viruses expressing HA fragments and synthetic peptides. One epitope is in the HA1 subunit at residues 259 to 266 (numbering from the initiator methionine), amino acid sequence FEANGNLI, and the other epitope is in the HA2 subunit at residues 10 to 18 (numbering from the amino terminus of the HA2 subunit), sequence IEGGWTGMI. These two peptides are good candidates for naturally processed HA epitopes presented during influenza infection, as they are the same length (eight and nine residues) as other naturally processed viral peptides presented to CTL. A comparison of the sequences of these two new epitopes with those of the three previously published Kk-restricted T-cell epitopes showed some homology among all of the epitopes, suggesting a binding motif. In particular, an isoleucine residue at the carboxy-terminal end is present in all of the epitopes. On the basis of this homology, we predicted that the Kk-restricted epitope in influenza virus nucleoprotein, previously defined as residues 50 to 63, was contained within residues 50 to 57, sequence SDYEGRLI. This shorter peptide was found to sensitize target cells at a 200-fold lower concentration than did nucleoprotein residues 50 to 63 when tested with a CTL clone, confirming the alignment of Kk-restricted epitopes.

Amino Acid Sequence↗
PubMed1991

Effect of clomiphene citrate upon periovulatory endometrial development in the baboon.

Endometrial histology in baboons (Papio cynocephalus anubis) was evaluated after five days of clomiphene citrate (CC) treatment initiated on either cycle day six (n = 8) or ten (n = 4). Biopsies performed before and after a human chorionic gonadotropin (hCG) induced ovulation were compared to non-CC treated controls. Although CC had a definite antiestrogenic effect on perineal skin, no significant effect of endometrial proliferation was demonstrable.

Animals↗
PubMed1990

A potential primate model for bone loss resulting from medical oophorectomy or menopause.

This study examined the potential use of the GnRH agonist-treated female monkey as a model for bone loss after medical oophorectomy or the onset of menopause in women. Three female rhesus monkeys (13-16 yr of age) were treated continuously for 10 months with 25 micrograms/day GnRH agonist using osmotic minipumps. All three animals exhibited normal menstrual cycles before treatment. Within 5 weeks of the beginning of GnRH agonist treatment, serum progesterone and estradiol concentrations had fallen to low values and did not rise significantly during the remaining treatment period. The decline in ovarian steroidogenesis was correlated with a reduction in bone mineral density (BMD; bone mineral content/bone width) of the caudal vertebrae and humerus. The reduction of BMD of the caudal vertebrae occurred gradually. The downward trend was evident during the first 3 treatment months, but did not fall significantly below pretreatment levels until 9 months of GnRN agonist treatment. The overall decline in BMD for the caudal vertebrae was approximately 14% after 9 months of GnRH agonist treatment. The measured decline in BMD of the humorous was 11%. Serum osteocalcin levels rose more than 10-fold above pretreatment values between 4 and 7 months of GnRH agonist treatment before declining to levels that approached pretreatment concentrations between 8 and 10 months of treatment. Menstrual cycles were reinitiated within 4 weeks after the termination of treatment, as shown by luteal phase increases in serum progesterone concentrations. BMD of the humerus and caudal vertebrae remained subnormal 2 months posttreatment, but by 5 months had recovered to near-pretreatment values. These data suggest that ovarian hormone deprivation induced by GnRH agonist administration is associated with a decline in BMD in female monkeys, and that this animal model may be an excellent model for postmenopausal bone loss or bone reduction resulting from medical oophorectomy. The GnRH agonist-treated monkey also has the potential to be developed as a model for type I postmenopausal osteoporosis.

Amino Acid Sequence↗
PubMed1990

Techniques and significance of gamete collection and storage in the great apes.

Rectal probe electroejaculation (RPE) is the most frequently used method for semen recovery in the great apes. Artificial insemination has been successful in the chimpanzee and gorilla. Oocytes can be recovered using laparoscopic techniques similar to those used in human medicine. At this time there has been no successful in vitro fertilization with birth of an infant in the great apes. Semen can be successfully frozen in the apes, as documented by recovery of motility of sperm after thawing. Pregnancies have been initiated in the chimpanzee and gorilla using frozen thawed semen.

Animals↗
PubMed1989

Effects of age and sex on bone density in the rhesus monkey.

Normative data for bone density of cortical and trabecular bone in the rhesus monkeys is described in the present study. Changes of bone density (g/cm2) for the humerus, the third lumbar vertebra, and the eighth caudal vertebra of the rhesus monkey show differences due to age and sex of the subjects (males n = 57; females n = 49). In general, bone density increased with age and then reached a plateau at approximately 3 to 4 years in all bones measured. In the humerus, older females (greater than 30 years) had a significantly lower bone density than females of 4 to 24 years, while bone density in older males did not decrease. In the vertebrae, some evidence of advanced age-related decreases in bone density was found in both sexes. These results indicate that the rhesus monkey shows a natural pattern of change in bone mineralization which parallels that seen in humans. The physiological similarity between the rhesus monkey and human further suggests a potential role for this species in the future investigation of osteoporosis.

Aging↗
PubMed1989

Blockade of neonatal activation of the pituitary-testicular axis: effect on peripubertal luteinizing hormone and testosterone secretion and on testicular development in male monkeys.

The objective of this study was to examine the effect of blockade of neonatal activation of the pituitary-testicular axis, using a GnRH agonist, on sexual development in male rhesus monkeys. Monkeys were treated with either a GnRH agonist (10 micrograms/day; n = 8) or vehicle (n = 9) for 112 days using osmotic minipumps beginning at 10-13 days of age. In control monkeys serum LH and testosterone concentrations during the first 3 postnatal months were similar to those in adults; they then declined to very low levels. GnRH agonist administration caused an immediate and precipitous decline in serum LH and testosterone concentrations to very low levels, and both remained low throughout the rest of the agonist administration period. Neither group had any significant elevation in serum LH or testosterone concentrations during the next 2 yr. In the control monkeys serum LH and testosterone began to rise during the third year, with a rapid increase occurring during the fall coincident with the breeding season. This peripubertal rise of LH and testosterone secretion was associated with rapid enlargement of the testes and the appearance of sperm in ejaculates. The monkeys who had received GnRH agonist had subnormal serum LH and testosterone increases, and testicular enlargement was also attenuated compared to that in the control animals during the third year of life. Semen samples were recovered from only 50% of the GnRH agonist-treated monkeys during this period, and the sperm count per ejaculate was suppressed. The serum LH responses of the GnRH agonist-treated monkeys to an iv bolus dose of GnRH (5 micrograms/kg BW) during the third year were normal. These results suggest that the induction of reversible hypogonadotropin-hypogonadism in neonatal male monkeys alters subsequent testicular development and peripubertal endocrine changes. Thus, neonatal activation of the pituitary-testicular axis may be a critical developmental event in the process of sexual development in male primates.

Animals↗
PubMed1989

Evaluation of the possible direct effects of gonadotrophin-releasing hormone analogues on the monkey (Macaca mulatta) testis.

In Exp. 1, the effect of treatment with a GnRH agonist on basal concentrations of serum testosterone and peak values of serum testosterone after administration of hCG was determined. One group of adult male monkeys was treated with a low dose (5-10 micrograms/day) and a second group with a high dose (25 micrograms/day) of a GnRH agonist for 44 weeks. Basal and peak testosterone concentrations were both significantly reduced by GnRH agonist treatment in all groups compared to untreated control animals, but the % rise in serum testosterone above basal values in response to hCG administration was unchanged by agonist treatment. In Exp. 2, the GnRH agonist (100 or 400 ng) or a GnRH antagonist (4 micrograms) was infused into the testicular arteries of adult monkeys. The agonist did not alter testosterone concentrations in the testicular vein or testosterone and LH values in the femoral vein. In Exp. 3, testicular interstitial cells from monkeys were incubated with three concentrations (10(-9), 10(-7) and 10(-5)M) of the GnRH agonist or a GnRH antagonist with and without hCG. After 24 h, neither basal nor hCG-stimulated testosterone production was affected by the presence of the GnRH agonist or antagonist. The results from all 3 experiments clearly suggest that GnRH agonist treatment does not directly alter steroid production by the monkey testis.

Animals↗
PubMed1988

Primates.

Nonhuman primates demonstrate marked similarities to humans in almost all aspects of their anatomy, endocrinology, and physiology. These similarities underlie the value of these animals for appropriate studies in neurobiology, immunology, pathology, reproductive biology, teratology, neonatology, endocrinology, cardiology, and psychology. Investigations with nonhuman primates has made, and continues to make, significant contributions to biomedical and behavioral research. This review provides an overview of basic and applied studies for which primates are appropriate subjects and a summary of the advantages and problems of using nonhuman primates in research.

Aging↗
PubMed1988

Comparison of electrostimulation methods for semen recovery in the rhesus monkey (Macaca mulatta).

Electroejaculation of 17 rhesus monkeys was performed at intervals during a 15-month period using both penile and rectal probe stimulation. The semen quality was compared for the two stimulation methods. Both methods were effective in approximately 90% of attempts, and there was no difference in fertilizing capacity of the sperm. A seasonal difference in semen quality was detected, and samples recovered by penile stimulation showed higher sperm count.

Animals↗
PubMed1987

Mouse H-2k-restricted cytotoxic T cells recognize antigenic determinants in both the HA1 and HA2 subunits of the influenza A/PR/8/34 hemagglutinin.

We have constructed two chimeric influenza hemagglutinin (HA) genes in which the HA1 and HA2 subunits of the HA molecule have been interchanged between influenza A/PR/8/34 (H1 subtype) and A/NT/60/68 (H3 subtype). These genes were used to construct recombinant vaccinia viruses that expressed intact chimeric HA. These recombinant viruses were used to test whether murine CTL recognize antigenic determinants in either the HA1, HA2, or both subunits. We found that both subunits of the HA molecule contain determinants for CTL. This implies that CTL have, at least in part, separate antigenic determinants from B lymphocytes, which recognize mainly epitopes within the HA1 subunit.

Animals↗
PubMed1987

Changes in binding of a 27-kilodalton chimpanzee cauda epididymal protein glycoprotein component to chimpanzee sperm.

Motility patterns of caput epididymal chimpanzee sperm, caput epididymal chimpanzee sperm incubated in vitro with chimpanzee cauda epididymal fluid, and cauda epididymal chimpanzee sperm were assessed quantitatively. Sperm recovered from the caput epididymis showed no motility, whereas sperm recovered from cauda epididymis showed progressive forward motility. After incubation in cauda fluid, approximately 25% of caput epididymal sperm showed some motile activity. Electrophoretic analysis of 125I-labeled sperm plasma membrane preparations revealed that the surface of caput epididymal sperm, incubated in cauda fluid, was modified by the appearance of a major protein-glycoprotein surface component with an apparent molecular weight of 27 kilodaltons (kD). THis 27-kD component was not detected on caput epididymal sperm incubated in buffer or in caput fluid. However, it was present in cauda fluid and on cauda epididymal sperm. Binding to caput epididymal sperm was cell specific in that chimpanzee erythrocytes incubated in cauda fluid did not bind this 27-kD cauda fluid component. Motility patterns of ejaculated chimpanzee sperm and of ejaculated chimpanzee sperm incubated in the uterus of adult female chimpanzees also were assessed quantitatively. Ejaculated sperm showed progressive forward motility, whereas in utero incubated ejaculated sperm showed hyperactivated motility typical of capacitated sperm. Electrophoretic analysis of 125I-labeled sperm plasma membrane preparations revealed the loss of a 27-kD component from the surface of ejaculated sperm after in utero incubation. No significant change in the 125I-distribution pattern was detectable when ejaculated sperm were incubated in buffer. These results suggest that the lumenal fluid component, which becomes adsorbed to the surface of chimpanzee sperm during maturation in the epididymis and which is removed from the surface of mature chimpanzee sperm in the female reproductive tract, affects sperm motility.

Animals↗
PubMed1987

Induction of follicular growth in the squirrel monkey (Saimiri sciureus): enhanced recovery of mature ova for fertilization in vitro.

In order to improve the rate of recovery of mature ova over those previously reported, we evaluated a new hormonal regimen for induction of follicular growth in the squirrel monkey. This regimen, which consisted of 50 IU pregnant mare's serum (PMS) per day for 4 days followed by 50 IU PMS and 250 IU human chorionic gonadotropin (hCG) on the 5th day, gave an average yield of 2.3 mature ova per animal from 14 experiments involving 11 animals. Ova were recovered through laparotomy or laparoscopy 18 h after PMS and hCG. This number reached 3.3 per animal when ova matured in vitro were included. The fertilization rate was significantly higher for ova matured in vivo (44%) than for in vitro-matured ova (7%) (P less than 0.05), showing the importance of recovering mature ova for successful fertilization in vitro. In agreement with previous observations, a seasonal pattern was noted for the response of animals to induction of follicular development, with a reduction in response occurring during a summer period from July to September. Our observations also suggest the occurrence of immunologic problems associated with the use of PMS in the squirrel monkey.

Animals↗
PubMed1987

Serum levels of cholesterol and lipoproteins in rhesus monkeys: comparison of the effect of gonadotropin-releasing hormone agonist and the progestin, levonorgestrel.

Levonorgestrel, a progestational steroid, and the more widely used antigonadotropin, danazol have been used in the treatment of endometriosis. Both of these agents decrease serum levels of HDL cholesterol. Recently, GnRH agonists came into use for treatment of endometriosis. Our objective in this study was to compare the effects of levonorgestrel and a GnRH analog on serum cholesterol levels in rhesus monkeys being treated for surgically induced endometriosis. A high dose of levonorgestrel significantly reduced total serum cholesterol and HDL cholesterol during a 12-week treatment period. Levonorgestrel had no significant effects on the concentration of LDL/VLDL cholesterol or the percentage of total cholesterol in the HDL fraction. Conversely, the GnRH agonist had no significant effect on total serum cholesterol, HDL cholesterol, LDL/VLDL cholesterol, or the percentage of HDL cholesterol. Because the concentration of HDL cholesterol is closely correlated with atherosclerotic risk, this factor should be weighed in the overall risk/benefit analysis for the patient with endometriosis.

Animals↗