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Biomedical subjects

N Kendall

Publications and source records attributed to N Kendall.

17 recordsLinked to original sources

Domestic ruminants as models for the elucidation of the mechanisms controlling ovarian follicle development in humans.

It is necessary to understand the basic physiology underlying the complex process of folliculogenesis to address common causes of infertility and to devise innovative strategies to increase the efficiency of assisted reproduction technologies. Availability of suitable ovarian tissue is a major constraint to research in this area in humans, and monovulatory domestic ruminants represent a physiologically relevant model to elucidate basic mechanisms before more focused clinical investigations. This paper reviews the development of several whole animal and cell culture models in ruminants that have allowed basic investigations into the endocrine and local mechanisms regulating preantral and antral follicle development in monovulatory species. Studies on preantral follicle development using the ovarian autograft model have shown, contrary to accepted dogma, that FSH may mediate the rate at which preantral follicles grow and have provided evidence to support the existence of local regulatory feedback mechanisms that influence the rate of primordial follicle initiation and preantral follicle development. Studies on the endocrine control of antral follicle development using the GnRH-antagonist model have shown that a pulsatile mode of LH delivery is not a requirement for normal patterns of follicle development and ovarian hormone secretion. Studies on the local control of somatic cell differentiation using physiological cell culture models have highlighted the essential relationship between somatic cell communication and expression of differentiative markers. We conclude that the domestic ruminant represents a valuable model system for the elucidation of the endocrine and local mechanisms controlling both early and terminal stages of follicle development in monovulatory species. The results of these investigations have direct strategic relevance within clinical medicine.

Animals↗

Casodex (a nonsteroidal antiandrogen) reduces cancellous, endosteal, and periosteal bone formation in estrogen-replete female rats.

Testosterone has been implicated in the preservation of the skeleton in women and female rats. In this study we investigated the role of androgens in estrogen-replete female rats by giving Casodex (pure nonsteroidal anti-androgen) daily and analyzing the effects on the skeleton using static and dynamic histomorphometric parameters after 3 weeks. There was a significant reduction in the bone formation rate in both the cancellous bone of the tibial metaphysis and in the periosteal and corticoendosteal diaphyseal bone (90%, 30%, and 100% reduction, respectively), compared with control animals, which was unaccompanied by a change in the indices of bone resorption. Casodex had no effect on cancellous bone volume and cortical bone area but this can be accounted for by the short duration of the experiment. The serum levels of dehydroepiandrosterone-sulfate and androstenedione were significantly reduced in the Casodex-treated rats compared with the control animals and there was no difference in the plasma levels of estrone, estradiol, or testosterone between the two groups. This study demonstrates that androgens play a physiological role in regulating osteoblast activity in female rats.

Androgen Antagonists↗

Conformationally biased analogs of human C5a mediate changes in vascular permeability.

A panel of conformationally constrained, decapeptide agonists corresponding to the C-terminal "effector" region of human C5a (C5a65-74 or ISHKDMQLGR) was evaluated for the ability to increase vascular permeability. One constrained analog, acyl-YSFKPMPLaR, expressed between 2 and 10% of full C5a activity in increasing vascular permeability, as measured by the extravasation of Evans blue dye in guinea pig skin. This analog was at least 10-fold more potent than its unconstrained sister analog C5a65-74465, F67++ (YSFKDMQLGR), which was used as an internal standard in these assays. Neither acyl-YSFKPMPLaR nor YSFKDMQLGR changed the transvascular equillibrium of an electrolyte, 86Rb, at the peptide injection site. However, both peptides effected a significant increase in the extravasation of two macromolecules, 125I-labeled bovine serum albumin and 131I-labeled monoclonal antibody BL-3. The extravasation of Evans blue dye mediated by 0.03 to 0.1 nmol of acyl-YSFKPMPLaR was nearly abolished by 1 to 10 nmol of the antihistamine diphenhydramine. For YSFKDMQLGR, however, the sensitivity toward diphenhydramine was observed only at low concentrations of the peptide (1 nmol). When incubated in human and mouse sera, acyl-YSFKPMPLaR was shown to be stable toward the actions of serum carboxypeptidases. However, the unconstrained analog YSFKDMQLGR was rapidly converted to the des-Arg form under the same conditions. Taken together, these results support a growing body of evidence that unique topochemical features expressed in conformationally constrained agonist analogs of C5a contribute favorably to their ability to modulate vascular permeability and to their stability in serum.

Amino Acid Sequence↗

The role of 1,25-dihydroxycholecalciferol and prostaglandin E2 in the regulation of human osteoclastic bone resorption in vitro.

Prostaglandins increase human osteoclast generation in vivo whereas they have been shown to exert the opposite effect in vitro: the latter results are based on enumeration of osteoclast-like cells, whose nature is controversial. We have generated human osteoclasts in vitro as assessed by bone resorption, a function unique to the osteoclast, and analysed the role of prostaglandin E2 (PGE2) in osteoclast activity. Human bone marrow cells were cultured to form a mature stroma and then sedimented onto bone slices with or without a recharge of non-adherent bone marrow cells. Bone resorption was increased by 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and PGE2 and inhibited by indomethacin: this inhibition was reversed by addition of PGE2. Our work supports the observation that PGE2 increases bone resorption in vivo and demonstrates the value of assessing osteoclast generation and activity in vitro using bone resorption.

Bone Marrow Cells↗

Experience with teenage pregnancy.

A retrospective study of 4224 deliveries to women age 19 or younger was conducted. The purpose of the study was to evaluate the characteristics of teenage pregnancy in an urban, predominantly nonwhite, socioeconomically depressed population. A total of 10,011 infants were delivered during the study period, with 42% (4224) of the infants born to teenagers. It is concluded that teenage pregnancy among the urban, nonwhite poor is characterized by poor outcome, primarily as a reflection of the high-risk obstetric population from which it derives, and only secondarily due to any risk inherent to maternal age. In addition, a striking characteristic of pregnancy in this age group is its tendency to repeat itself. Teenage pregnancy is a sociologic problem with medical consequences, and medical programs as they presently exist are incapable of bringing about the ultimate solution--prevention.

Adolescent↗