Gladis Shuttlesworth

Enhancement of A Spermatogonial Proliferation and Differentiation in Irradiated Rats by Gonadotropin-Releasing Hormone Antagonist Administration

The initial changes in the numbers, proliferation, and differentiation of A spermatogonia in irradiated rats after the administration of a GnRH antagonist, which is known to induce differentiation in this system, were investigated. LBNF1 rats were given 6 Gy ofγ -irradiation; some were treated with the GnRH antagonist Cetrorelix beginning 15 weeks after irradiation. Although the spermatogonia in the irradiated rats without hormone treatment continue to proliferate (labeling and mitotic indexes of 24% and 18%, respectively), they underwent apoptosis (apoptotic indexes of 21% by the terminal transferase-mediated end labeling assay and 9% by nuclear morphology), resulting in a constant number of A spermatogonia. Whole mount analysis of clones of A spermatogonia revealed that larger clones were more likely to undergo apoptosis than mitosis. Hormone administration decreased the intratesticular testosterone concentration to 6% of the level in irradiated rats within 1 week. Concomitantly, there was a decrease in...

Dibromochloropropane inhibits spermatogonial development in rats.

Exposure to the nematocide dibromochloropropane (DBCP) has caused prolonged oligo- and azoospermia in men. There are questions regarding the cellular targets resulting in this effect. In this study we characterized an animal model, in which four daily injections of DBCP produced prolonged oligospermia in LBNF(1) rats without any indication of recovery. Between 6 and 20 weeks after DBCP treatment, 70% of seminiferous tubules showed an epithelium with Sertoli cells but no differentiating germ cells. About 20% of tubules contained differentiating germ cells and 10% showed occlusion or major morphologic alterations to Sertoli cells. Since gonadotropin levels and intratesticular testosterone (ITT) concentrations were elevated in the DBCP-treated rats, the failure of spermatogonial development could not have been a result of lack of these hormones. The tubules without differentiating germ cells contained actively proliferating and dividing type A spermatogonia, which underwent apoptosis instead of differentiation. Thus, the target for the damaging effect appears not to be the killing of stem spermatogonia, but the loss of their ability to undergo differentiation. The presence of type A spermatogonia in the atrophic tubules indicates the potential for intervention to restore spermatogenesis.

Natural Language Processing As an Alternative to Manual Reporting of Colonoscopy Quality Metrics

BACKGROUND AND AIMS The adenoma detection rate (ADR) is a quality metric tied to interval colon cancer occurrence. However, manual extraction of data to calculate and track the ADR in clinical practice is labor-intensive. To overcome this difficulty, we developed a natural language processing (NLP) method to identify adenomas and sessile serrated adenomas (SSAs) in patients undergoing their first screening colonoscopy. We compared the NLP-generated results with that of manual data extraction to test the accuracy of NLP and report on colonoscopy quality metrics using NLP. METHODS Identification of screening colonoscopies using NLP was compared with that using the manual method for 12,748 patients who underwent colonoscopies from July 2010 to February 2013. Also, identification of adenomas and SSAs using NLP was compared with that using the manual method with 2259 matched patient records. Colonoscopy ADRs using these methods were generated for each physician. RESULTS NLP correctly identified 91.3% of the screening examinations, whereas the manual method identified 87.8% of them. Both the manual method and NLP correctly identified examinations of patients with adenomas and SSAs in the matched records almost perfectly. Both NLP and the manual method produced comparable values for ADRs for each endoscopist and for the group as a whole. CONCLUSIONS NLP can correctly identify screening colonoscopies, accurately identify adenomas and SSAs in a pathology database, and provide real-time quality metrics for colonoscopy.

Restoration of Spermatogenesis After Exposure to Toxicants: Genetic Implications

Many men have been sterilized by exposure to radiation and chemotherapy agents as treatment for cancer; radiation and almost all of the chemotherapeutics are also mutagens. In the United States alone, 17,000 men 15 to 45 years old are diagnosed each year with Hodgkin’s disease, lymphoma, bone and soft tissue sarcomas, testicular cancer, or leukemia (Landis et al., 1999). Of these, over 2,400 are long-term survivors that were treated with doses of alkylating agents, platinum drugs, or radiation sufficient to induce prolonged azoospermia. In addition, 6,000 boys under 15 are diagnosed each year with cancer, including leukemia, nervous system tumors, lymphomas, and other solid tumors. About 80% of them receive chemotherapy or gonadal irradiation, and about 550 of the long-term survivors are azoospermic when they reach adulthood.

Regulation of the Differentiation of the Undifferentiated Spermatogonia

In the seminiferous epithelium of adult nonprimate mammals, so-called A-single (As) spermatogonia are the stem cells of spermatogenesis (1–3). Upon division of the As spermatogonia, the daughter cells either migrate away from each other and become two new stem cells, or the cells stay together becoming A-paired (Apr) spermatogonia connected by an intercellular bridge. About half of the stem-cell population normally divides to form Apr spermatogonia, whereas the other half goes through self-renewing divisions, thereby maintaining stem-cell numbers (Fig. 5.1).