Nathan G. Kase

Long-term culture and passage of human fetal liver cells that synthesize albumin.

SummaryLong-term cultures of hepatocytes were established from livers of human fetuses obtained by abortion at 18 to 23 wk of gestation. Cells obtained by collagenase dissociation of liver were maintained in defined serum-free medium on a substratum of positively charged plastic. Under these conditions, the cells divide and form a confluent monolayer. After multiple passages over a period of 3 mo., the cells retained an epithelioid morphology and continued to synthesize and secrete albumin.

Endometrial Cancer in Elderly Women: A Histologic and Steroid Receptor Study

Background: Information on steroid receptor content in endometrial tissue of aging women is limited and somewhat controversial. The high incidence of endometrial cancer (EC) and the implication of hormone replacement therapy (HRT) in this group prompted the investigation of steroid receptors and endometrial cancer histology in the elderly. Objective: Review of histologic characteristics correlated with estrogen and progesterone receptors (ER and PR) status in EC in women over 75 years of age in order to determine the prevalence of a more aggressive endometrial neoplasm arising in late postmenopausal atrophic endometrium of elderly patients. Methods: Histologic slides and deeper sections stained immunohistologically for ER/PR from 54 cases of EC in women aged 75–95 years were reviewed. The histologic characteristics and degree of differentiation were correlated with the steroid receptor status, evaluated on a scale of 0–3. Benign endometrial tissue from women of the same group was used as controls. Results: The 57.4% endometrioid adenocarcinomas were mostly moderately and poorly differentiated. The nonendometrioid carcinomas were anaplastic, papillary, clear cell, squamous cell, mixed müllerian and nongestational choriocarcinoma. The staining intensity for ER/PR decreased with the degree of dedifferentiation being weak or absent in nonendometrioid tumors. Conclusion: Elderly patients have less differentiated EC displaying histologically nonendometrioid patterns (‘alienation’) with no differential loss of receptors in cancer. ER/PR are partly preserved in endometrioid tumors and controls. We conclude that differential loss of receptor capacity is not a factor in pathogenesis of this age-related cancer.

Altchek's diagnosis and management of ovarian disorders /

Altcheks diagnosis and management of ovarian disorders / , Altcheks diagnosis and management of ovarian disorders / , کتابخانه دیجیتال جندی شاپور اهواز

CHAPTER 2A – The Normal Human Ovary Part I: Reproductive and Endocrine Functions

This chapter focuses on the description of ovary, its secretions, and reproductive and endocrine functions. The major functions of the human ovary are the nurture, development, and release of a mature oocyte ready for fertilization thus leading to the achievement of successful propagation of the species. Relevant to these processes, the ovary secretes steroid hormones, which stimulate growth and development of secondary sexual characteristics and are critically involved in an endocrine interchange, which directs orderly, repetitive cyclic ovulations, and finally supports successful uterine implantation and the early phase of pregnancy. It is noted from observations in prolonged physiologic (menopause) and nonphysiologic (gonadal failure) hypofunctional states that the ovarian steroid secretions have important influences on variety of nonreproductive organ systems, which in turn influence the quality of life and life expectancy of women. The advances in ovarian endocrinology, molecular biology, molecular genetics, and transgene and knockout technologies provide new and exciting insight into the life history of a human ovarian follicle, ovulation, and corpus luteum formation and function.

Aging, the menopausal transition, and hormone replenishment therapy: retrieval of confidence and compliance

The negative health consequences of age and the postmenopausal hypoestrogenic state and their clinical management are described in this paper. While some dysfunctional elements are irreversibly entrained, others can be modified by an updated menopausal hormone therapy (MHT) strategy reflecting revision and reassessment of the initial Womens Health Initiative (WHI) reports. However, until that positive outcome is realized, menopausal women and their healthcare providers must re‐establish willingness to utilize these effective strategies. This reluctance is fueled by persistent mistaken application of WHI results that reflect the bundled risk and benefits of MHT in asymptomatic women aged 50–79 (average age 63), as opposed to women in their 40s and 50s who initiate therapy because of vasomotor symptoms. The absolute risk of adverse outcomes is much lower and the benefits dramatically higher in these younger women. In addition, newer FDA‐approved formulations, lower dosage regimens, and transdermal delivery methodologies offer wider choice of approaches and promise even greater safety. The positive and negative lessons of the WHI have been learned and can be applied effectively.

Intrauterine Reprogramming of the Polycystic Ovary Syndrome: Evidence from a Pilot Study of Cord Blood Global Methylation Analysis

Polycystic ovary syndrome (PCOS) affects 5–15% of women. PCOS is a heterogeneous disorder displaying endocrine, metabolic, and reproductive dysfunction and cardiovascular risk manifestations. Evidence of heritability exists, but only a portion of the genetic transmission has been identified by genome-wide association studies and linkage studies, suggesting epigenetic phenomena may play a role. Evidence implicates intrauterine influences in the genesis of PCOS. This was a pilot study that aimed at identifying an epigenetic PCOS reprogramming signature by profiling the methylation of the DNA extracted from umbilical cord blood (UCB) from 12 subjects undergoing in vitro fertilization. Six subjects were anovulatory PCOS women diagnosed by Rotterdam criteria and six ovulatory non-PCOS women matched for age and body mass index. UCB was collected at delivery of the placenta; the DNA was extracted and submitted to methylation analysis. A differential methylation picture of prevalent hypomethylation affecting 918 genes was detected. Of these, 595 genes (64.8%) carried single or multiple hypomethylated CpG dinucleotides and 323 genes (35.2%) single or multiple hypermethylated CpG dinucleotides. The Ingenuity Pathway Analysis (IPA) online platform enlisted 908 of the 918 input genes and clustered 794 of them into 21 gene networks. Key features of the primary networks scored by IPA included carbohydrate and lipid metabolism, neurotransmitter signaling, cardiovascular system development and function, glycosaminoglycan signaling regulation and control of amino acid biosynthesis. Central to the network activities were genes controlling hormonal regulation (ESR1), mitochondrial activity (APP, PARK2), and glucose metabolism (INS). Regulatory pathways such as G-protein coupled receptor signaling, inositol metabolism, and inflammatory response were also highlighted. These data suggested the existence of a putative “PCOS epigenomic superpathway” with three main components: glucotoxic, lipotoxic, and inflammatory. If our results are confirmed, they hint at an epigenetic at risk PCOS “signature” may thus exist that may be identifiable at birth. Additional studies are needed to confirm the results of this pilot study.

Altchek's Diagnosis and Management of Ovarian Disorders: List of contributors

Altcheks diagnosis and management of ovarian disorders / , Altcheks diagnosis and management of ovarian disorders / , کتابخانه دیجیتال جندی شاپور اهواز

Altchek's Diagnosis and Management of Ovarian Disorders: Frontmatter

Altcheks diagnosis and management of ovarian disorders / , Altcheks diagnosis and management of ovarian disorders / , کتابخانه دیجیتال جندی شاپور اهواز

CHAPTER 2B – The Normal Human Ovary Part II: How Steroid Hormones Work

This chapter focuses on mechanism of action of the principal steroid secretory products of the ovary — namely, estradiol and progesterone. The chapter discusses the involvement of these hormones in the reproductive system and in nonreproductive physiologic systems. Estrogen (E) and progesterone (P) play significant role in both the endocrine and intracrine regulation of all aspects of female reproduction. Together they act at the level of hypothalamus, anterior pituitary, ovary, and uterus to coordinate neuroendocrine pulsatile secretion of gonadotropin releasing hormone, cyclic release of gonadotropins FSH and LH, ovulation, and endometrial development in preparation for implantation and maintenance of fertilized embryos. Both hormones are also essential for pubescent and pregnancy mammary gland development and are involved in the biology of the cardiovascular, immune, central nervous, and skeletal systems. Studies exhibit that both E and P are related to almost all aspects of human physiology leading to a valid basis for optimism that these hormones can successfully address mechanisms of human dysfunction and provide opportunities for development of new therapies as each of these hormones can become targets for manipulation by novel therapeutic interventions.

CHAPTER 24 – Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders. It is recognized as a heterogeneous syndrome involving chronic anovulation accompanied by hyperandrogenism, with clinical manifestations including hirsutism, acne, androgen dependent alopecia, and frequently, obesity. PCOS is the leading cause of anovulatory infertility. After initial onset in the peripubertal years, PCOS affected women develop signs and symptoms of elevated androgen levels, menstrual irregularity and amenorrhea, virilization, and bilaterally enlarged multicystic ovaries Metabolic derangements in PCOS are not limited to the sex steroids but are also affected on insulin resistance and compensatory hyperinsulinemia. Ovulatory women with hyperandrogenism, hirsutism, and polycystic ovaries accompanied by normal menstrual cycles display normal insulin sensitivity signifying that insulin resistance can be the primary process leading to anovulation. With recent advancement, treatment options result in higher pregnancy rates, and improved methods to counter the long-term deletrious effects on the health of women with PCOS. It is important to gain further insights by following a detailed approach so that new drugs can be studied and developed and existing drugs can be purified and produced at lower costs. The ultimate goal is to minimize harm and achieve optimal long-term outcome in patients with PCOS.