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Biomedical subjects

Kirk C Lo

Publications and source records attributed to Kirk C Lo.

8 recordsLinked to original sources

Evaluation and treatment of ejaculatory duct obstruction in infertile men.

OBJECTIVES: The purpose of this review is to survey the growing literature on ejaculatory duct obstruction and to provide a comprehensive overview of the current trends in the diagnosis and management of patients with this disorder. MATERIALS AND METHODS: Review of current literature on ejaculatory duct obstruction. RESULTS: Ejaculatory duct obstruction is a surgically treatable cause of male infertility. It is usually suspected in an infertile male who has low ejaculate semen volume but normal testicular size and normal secondary male sexual characteristics. CONCLUSION: Transrectal ultrasonography is the initial investigation method used to visualize and locate the presence of a cyst or calcifications that may contribute to the obstruction. Transurethral resection of the ejaculatory ducts represents the best treatment modality, resulting in marked improvement in the semen parameters and pregnancy rate in well selected cases.

Ejaculatory Ducts↗

Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID.

The establishment and maintenance of spermatogenesis in mammals requires specialized networks of gene expression programs in the testis. The gonad-specific TAF4b component of TFIID (formerly TAF(II)105) is a transcriptional regulator enriched in the mouse testis. Herein we show that TAF4b is required for maintenance of spermatogenesis in the mouse. While young Taf4b-null males are initially fertile, Taf4b-null males become infertile by 3 mo of age and eventually exhibit seminiferous tubules devoid of germ cells. At birth, testes of Taf4b-null males appear histologically normal; however, at post-natal day 3 gonocyte proliferation is impaired and expression of spermatogonial stem cell markers c-Ret, Plzf, and Stra8 is reduced. Together, these data indicate that TAF4b is required for the precise expression of gene products essential for germ cell proliferation and suggest that TAF4b may be required for the regulation of spermatogonial stem cell specification and proliferation that is obligatory for normal spermatogenic maintenance in the adult.

Aging↗

Stem cells: implications for urology.

Stem cells are characterized by their potential immortality and are capable of self-renewal and differentiation. Stem cells are proposed to provide the potential to cure degenerative diseases and to give important clues regarding human development and aging. However, stem cell research has evoked enthusiasm and passionate debate regarding the ethics of their use in medicine and reproduction. In this article, the current understanding of the biology of stem cells, their application in urology, and some of the controversies regarding their use are discussed. Although the clinical application of stem cell technologies to urologic practice is likely to be well in the future, advances in this field hold great promise for the correction of a number of illnesses. Nevertheless, scientists and ethicists will continue to struggle with their ethical responsibilities to the patient and society.

Biomedical Research↗

Treatment options for the infertile male with cancer.

The detrimental effects of cancer on male fertility are multifactorial and may be secondary to the disease process itself or to therapeutic interventions. Patients and their doctors need to be better informed about the options men with cancer have to preserve their fertility status. Sperm banking is a safe and effective means of storing sperm before chemotherapy, radiotherapy, or surgery. Advances in assisted reproductive techniques allow in vitro fertilization to occur with the injection of a single sperm into an egg (IVF-ICSI); consequently, the requirement for the amount of sperm needed from cryopreservation is minimal. Pregnancies have been achieved using IVF-ICSI with cryopreserved sperm from patients with a history of malignancy. Similarly, successful sperm retrieval using testicular sperm extraction combined with IVF-ICSI can be accomplished for men with nonobstructive azoospermia after chemotherapy. New techniques such as spermatogonial cell transplantation offer the potential to restore fertility in patients who have received radiation or chemotherapy.

Antineoplastic Agents↗

Isolation and enrichment of murine spermatogonial stem cells using rhodamine 123 mitochondrial dye.

Stem cells possess enormous therapeutic potential in tissue replacement. To study stem cells further, they must be isolated. Techniques are available for enrichment and study of hematopoietic stems cells, but thus far, techniques for purification of spermatogonial stem cells have not been described. Enrichment techniques for hematopoietic stem cells include the use of fluorescence-activated cell sorter analysis with Hoechst 33342 and rhodamine 123 (Rho) dyes. Use of Hoechst dye to isolate spermatogonial stem cells has been unsuccessful in our laboratory, and our results have conflicted with those from other laboratories. Taking advantage of the differential staining of the Rho dye, we report a novel method to enrich murine spermatogonial stem cells. Testicular cells are harvested from cryptorchid ROSA26 male mice. Populations of these cells are then stained with the Hoechst and Rho dyes, allowing them to be sorted by flow cytometry into a side population (SP) of Hoechst low-intensity cells and populations of low (Rho(low)) or high (Rho(hi)) fluorescent intensity. Sterile recipients, W/W(v) mice, with an intrinsic germ cell deficiency were transplanted with the Hoechst SP cells, Rho(low), Rho(hi), and nonsorted donor cells. No spermatogonial stem cell colonies were derived from the Hoechst SP cells. The number of spermatogonial stem cell colonies from transplanted Rho(low) cells showed a 17- and 20-fold enrichment over those of Rho(hi) and nonsorted cells, respectively.

Animals↗

De novo testosterone production in luteinizing hormone receptor knockout mice after transplantation of leydig stem cells.

Mesenchymal stem cells or Leydig cell progenitors are rare and difficult to isolate from adult testes. The property of differential efflux of Hoechst 33342 dye by the multi-drug-like transporter enriches murine hematopoietic stem cells from bone marrow. Our work on testicular cell transplantation suggests that the "Hoechst dim" side population (SP) also contains Leydig stem cells or progenitors that proliferate and differentiate into mature functional Leydig cells. We harvested testicular cells from cryptorchid ROSA26 mice, stained them with Hoechst dye, and isolated the cell population that excludes the dye using flow cytometry. Mice with targeted deletion of the LH receptor (LHR) gene were used as the recipients of the transplanted cells. These mice are hypogonadal and infertile. Both testicular SP and non-SP cells were transplanted into the interstitium of the LHR knockout recipients' testes. Serial serum testosterone assays revealed a significant increase in the circulating testosterone levels and restoration of spermatogenesis in the LHR-knockout recipients transplanted with the SP cells compared with that of those transplanted with non-SP. A SP cell concentration- and time-dependent increase in circulating testosterone was observed. This demonstrates the successful transplantation of functional putative Leydig stem cells into a hypogonadal recipient. The increase in testosterone concentration indicates the de novo synthesis of androgen by the transplanted SP cells. This method offers a novel technique to isolate Leydig stem cells and to study Leydig cell development.

Animals↗

Stem cell research: the facts, the myths and the promises.

PURPOSE: Stem cells, the potentially immortal cells capable of self-renewal, are the focus of research for the ultimate cure for degenerative diseases and the key to the mystery of human development and aging. No area of research since gene therapy has evoked so much enthusiasm and passionate debate as stem cell research. We present a glance of the current progress and controversies surrounding embryonic stem cells, and an overview of the evolving theory of potentially pluripotent adult stem cells. MATERIALS AND METHODS: We review and compare the literature on animal and human models that have provided the basis for significant research advances in recent years. The historical development and the most promising results to date are presented. RESULTS: The embryonic stem (ES) cell can differentiate into cells of all 3 germ cell layers. The therapeutic potential of the differentiated cells can modulate the symptoms of degenerative neurological disorders in animal models. However, the tumorigenic potential and ethical dilemma of human ES cell acquisition trouble many critics and have led to federal regulations on the development and use of human ES cells. Adult stem cells may provide an answer to circumvent these ethical issues and hold great promise for the future. CONCLUSIONS: While embracing the quest for advances in biomedicine, we cannot overlook the ethical responsibility to the patient and society. Regardless of the approach to harvest or culture stem cells human therapeutic application may still be years in the future.

Animals↗