Bo Yu, MD

Abstract

T-cell activation involves multiple signaling pathways. In this report, we conducted in vitro and in vivo immune function analysis of tumor-draining lymph node (TDLN) cells after anti-CD3/anti-CD28 activation versus anti-CD3 activation alone in a murine tumor model. In cytokine release assays, the doubly activated TDLN cells secreted significantly greater amounts of IFN-gamma and GM-CSF in response to specific tumor antigen compared with anti-CD3 activated cells. In adoptive immunotherapy, the doubly activated TDLN cells were more effective in mediating regression of 3-day pulmonary metastases compared with anti-CD3 activated cells. Although there was predominant proliferation of CD8+ cells after either activation procedure, the mean-fold expansion of CD4+ cells was significantly greater after anti-CD3/anti-CD28 activation than anti-CD3 activation alone. Using magnetic bead-enriched T-cell subsets, we found that either CD4+ or CD8+ doubly activated TDLN cells could independently mediate tumor regression. Furthermore, the doubly activated CD4+ cells were more effective than CD8+ cells in adoptive immunotherapy on a per-cell basis. The antitumor activity mediated by CD4+ or CD8+ cells could be significantly enhanced with the exogenous administration of IL-2. CD28 co-stimulation of tumor-primed lymphoid cells promotes the generation of potent tumor reactive effector cells, particularly CD4+ T cells, with antitumor activity in adoptive immunotherapy.

View details for DOI 10.1097/00002371-200207000-00002

View details for PubMedID 12142553

Abstract

To report three cases of severe ovarian hyperstimulation syndrome (OHSS) among oncofertility patients receiving a long-acting GnRH agonist for ovarian suppression after controlled ovarian hyperstimulation (COH) with a GnRH antagonist protocol METHODS: Chart abstraction was completed for three patients at a single academic medical center. Patients included were undergoing fertility preservation prior to gonadotoxic chemotherapy. All patients underwent COH with GnRH antagonist protocol and embryo cryopreservation immediately followed by ovarian suppression with long-acting GnRH agonist. Main outcome measure was development of OHSS.Despite using GnRH agonist trigger and freezing all embryos, patients developed ascites, intermittent hyponatremia and hemoconcentration consistent with severe early-onset OHSS after receiving long-acting GnRH agonist immediately following oocyte retrieval for ovarian preservation.Risk of severe OHSS may be increased when a long-acting GnRH agonist is used for ovarian suppression immediately following oocyte retrieval. A delay in initiating long-acting GnRH agonist after oocyte retrieval in patients at high risk for developing OHSS should be considered.

View details for DOI 10.1007/s10815-020-02051-7

View details for PubMedID 33471229

Abstract

Purpose: To determine the relationship between pubertal development and postpubertal gonadal function in childhood cancer survivors. Methods: Childhood cancer survivors (10 years of age) who received follow-up care in a pediatric oncology group in an academic medical center during the period from January 1, 1985, to July 1, 2010 were included in this case series. Their pubertal development and gonadal function were evaluated. Results: The cohort consists of 39 males (age 10-21 years) and 35 females (age 10-29 years) with a variety of cancer diagnosis and treatments. The average age at diagnosis was 7.5 years. The average age at the time of the study was 16 and 16.7 years in males and females, respectively, representing a mean follow-up interval of 9 years. Despite the fact that 60% of survivors received cyclophosphamide equivalents and 16.2% received cranial radiation or brain tumor resection, the majority of survivors (68%) presented with both normal puberty and normal gonadal functions at the time of follow-up. In 27% of survivors, puberty development did not predict gonadal function in early adulthood: 20% of survivors had normal puberty, but abnormal gonadal function; 7% of survivors had abnormal puberty, but gonadal function remained normal as young adults. Conclusions: Most childhood cancer survivors had normal puberty and gonadal function despite a variety of cancer treatment modalities. However, normal puberty did not predict normal gonadal function later in life in many survivors. Therefore, close follow-up with gonadal function in adolescent and early adulthood years is essential.

View details for DOI 10.1089/jayao.2019.0138

View details for Web of Science ID 000524993500001

View details for PubMedID 32186962

View details for PubMedCentralID PMC7415869

Abstract

Transmission fidelity of CpG DNA methylation patterns is not foolproof, with error rates from less than 1 to well over 10% per CpG site, dependent on preservation of the methylated or unmethylated state and the type of sequence. This suggests a fairly high chance of errors. However, the consequences of such errors in terms of cell-to-cell variation have never been demonstrated by experimentally measuring intra-tissue heterogeneity in an adult organism.We employ single-cell DNA methylomics to analyze heterogeneity of genome-wide 5-methylcytosine (5mC) patterns within mouse liver. Our results indicate a surprisingly high level of heterogeneity, corresponding to an average epivariation frequency of approximately 3.3%, with regions containing H3K4me1 being the most variable and promoters and CpG islands the most stable. Our data also indicate that the level of 5mC heterogeneity is dependent on genomic features. We find that non-functional sites such as repeat elements and introns are mostly unstable and potentially functional sites such as gene promoters are mostly stable.By employing a protocol for whole-genome bisulfite sequencing of single cells, we show that the liver epigenome is highly unstable with an epivariation frequency in DNA methylation patterns of at least two orders of magnitude higher than somatic mutation frequencies.

View details for DOI 10.1186/s13059-016-1011-3

View details for PubMedID 27380908

View details for PubMedCentralID PMC4934005

Abstract

To compare the cost effectiveness of proceeding with oocyte retrieval vs. converting to intrauterine insemination (IUI) in patients with 4 mature follicles during assisted reproductive technology (ART) cycles.Probabilistic decision analysis. The cost effectiveness of completing ART cycles in poor responders was compared to that for converting the cycles to IUI.Not applicable.Not applicable.Cost-effectiveness analysis.Cost effectiveness, which was defined as the average direct medical costs per ongoing pregnancy.In patients with 1-3 mature follicles, completing ART was more cost effective if the cost of a single ART cycle was between $10,000 and $25,000. For patients with 4 mature follicles, if an ART cycle cost<$18,025, it was more cost effective to continue with oocyte retrieval than to convert to IUI.In patients with 4 mature follicles following ovarian stimulation in ART cycles, it was on average more cost effective to proceed with oocyte retrieval rather than convert to IUI. However, important factors, such as age, prior ART failures, other fertility factors, and medications used in each individual case need to be considered before this analysis model can be adapted by individual practices.

View details for DOI 10.1016/j.fertnstert.2014.05.015

View details for PubMedID 24951366

View details for PubMedCentralID PMC4119511

Abstract

To describe the prevalence of "genuine" empty follicle syndrome (EFS) and "false" EFS at assisted reproductive technology (ART).Retrospective cohort.Large private fertility center.A total of 12,359 patients who underwent ART between 2004 and 2009.None.The failure to recover an oocyte during oocyte retrieval at ART, with and without adetectable serum -hCG on the day of retrieval.Two cases of genuine EFS and nine cases of false EFS were identified in the cohort examined. The prevalence of genuine EFS was 0.016%, and the prevalence of false EFS was 0.072%. Only two out of 11 cases of EFS were considered genuine.Genuine EFS is a rare occurrence. Because this syndrome tends to recur with dismal pregnancy rates at ART, continued identification and further investigation of the syndrome are needed.

View details for DOI 10.1016/j.fertnstert.2011.09.047

View details for PubMedID 22130102

View details for PubMedCentralID PMC3576020

Abstract

To review the physiologic functions and clinical significance of peripheral GnRH receptors.Literature review. All peer-reviewed journal articles published before 2010 on peripheral GnRH receptors were searched for in the Pubmed database, and relevant findings were summarized.Peripheral GnRH/GnRH receptor systems may serve as regulators of hCG synthesis and implantation, and play crucial roles in antiproliferation and apoptosis. Currently, GnRH agonists have been used in cancer treatment and ovary protection during chemotherapy, taking advantage of the local direct effect mediated by peripheral GnRH receptors.The ubiquitous GnRH/GnRH receptor system in human tissues has been shown to have some important physiologic functions. Further research to clarify functions of these peripheral GnRH receptors may lead to discovery of new therapeutic options.

View details for DOI 10.1016/j.fertnstert.2010.08.045

View details for PubMedID 20888559

Abstract

The prevalence of moderately elevated TSH levels consistent with subclinical hypothyroidism (2.5-4.0 IU/mL) was 23% in a cohort of 1,231 women pursuing assisted reproductive technologies. Preconception elevated levels of TSH were associated with diminished ovarian reserve but were not associated with adverse assisted reproductive technology or pregnancy outcomes.

View details for DOI 10.1016/j.fertnstert.2011.02.056

View details for PubMedID 21457968

View details for PubMedCentralID PMC3124612

Abstract

Cervical ectopic pregnancy accounts for less than 1% of all ectopic gestations. The most effective, fertility sparing treatment of a cervical ectopic pregnancy is still unclear due to limited reported experience.The diagnosis and management of a 32-year-old with a cervical ectopic pregnancy after in vitro fertilization and embryo transfer is described. The patient had multiple risk factors, including Asherman's syndrome following an abdominal myomectomy and three uterine curettages, for a cervical ectopic pregnancy. Due to her desire for future childbearing, conservative management strategies were chosen. This patient was successfully treated with uterine artery embolization followed by immediate dilation and evacuation of the pregnancy.This report demonstrates that UAE followed by immediate evacuation of a cervical ectopic pregnancy effectively terminates a viable gestation with minimal blood loss while maintaining fertility capacity.

View details for DOI 10.1007/s00404-008-0775-4

View details for PubMedID 18791728

Abstract

To compare the efficacy of recombinant human FSH (rhFSH) with rhFSH with four additional O-linked carbohydrates (rhFSH-CTP), rhFSH with four additional N-linked carbohydrates (rhFSH-N4), and the current gold standard for rodent ovarian stimulation, pregnant mare serum gonadotropin (PMSG), on fertility parameters in mice.Animal study.Academic research center.Adult C57Bl/6J female mice.Ovarian stimulation with 5 IU of rhFSH, rhFSH-CTP, rhFSH-N4, or PMSG. Forty-six hours later, 5 IU of hCG was injected to promote ovulation and females were mated overnight.Eggs retrieved after ovulation, in vitro embryo development, delivery rate, and litter size.The hyperglycosylated FSH analogs, rhFSH-CTP and rhFSH-N4, enhanced ovulation and embryo maturation significantly better than rhFSH. RhFSH-N4 produced more eggs (28.5 +/- 1.9 per mouse) and embryos (17.8 +/- 1.6) compared with rhFSH-CTP (18.3 +/- 1.2 and 9.0 +/- 1.0, respectively). Treatment with rhFSH, rhFSH-N4, and PMSG produced statistically equivalent delivery rates and litter sizes. The delivery rate was surprisingly lower with rhFSH-CTP (14%) compared with PMSG (33%).Compared with rhFSH, treatment with hyperglycosylated rhFSH-CTP and rhFSH-N4 led to superior rates of ovulated eggs and subsequent in vitro embryo development. RhFSH-N4 was equivalent to PMSG, while all of the fertility parameters studied were lower with rhFSH-CTP than with PMSG therapy.

View details for DOI 10.1016/j.fertnstert.2007.11.013

View details for PubMedID 18249396

View details for PubMedCentralID PMC2748679

Abstract

Nearly 130,000 American women are human immunodeficiency virus (HIV) seropositive. The present study sought to establish a comprehensive programme to address their fertility needs in order to minimize infectious, medical and reproductive risks to prospective patients. Forty women, aged 27-42 years, were evaluated. HIV was diagnosed 7.2 +/- 0.7 years prior to their seeking care, and most women (n = 38) were on highly active antiretroviral therapy. Their prenatal CD4 counts were 712.2 +/- 56 cells/mm(3) (range 327-1881) and HIV-1 concentrations were undetectable in all cases prior to initiating treatment. HIV-seropositive women were statistically identical to their age-matched HIV-seronegative counterparts with respect to the IVF clinical outcome parameters measured. Throughout the pregnancies, maternal HIV-1 RNA concentrations remained undetectable and CD4 counts were stable. All infants, tested at birth and at 3 and 6 months of age, remained HIV negative. This is the first report of an institutional paradigm in the USA dedicated to evaluate and treat HIV-seropositive women. Using a multidisciplinary approach to care, HIV-seropositive women may be successfully managed in a programme of assisted reproduction.

View details for DOI 10.1016/s1472-6483(10)60082-x

View details for PubMedID 19712564

Abstract

To document the treatment of refractory chyle leaks using thoracoscopic thoracic duct ligation and provide systematic guidelines to manage chyle leaks.The medical records of 2 patients with chyle leaks are reviewed, followed by a review of the literature on chyle leaks and their thoracoscopic management.Initial treatment of chyle fistula is aimed at conservative medical management. Persistent high-output fistulas (>500 cm(3)) should be considered for neck reexploration as conservative management is likely to fail. Thoracoscopic thoracic duct ligation provides a safe and efficient means of treating chyle leaks refractory to repeated surgical and medical intervention. It should also be considered as a primary surgical intervention for patients with: (1) chyle output exceeding 500 cm(3)/day where prior intraoperative attempts at ligation have failed, (2) severe metabolic and nutritional complications, (3) coexisting chylothorax with respiratory compromise, and (4) low-output fistulas (<500 cm(3)/day) of long duration (>14 days).

View details for DOI 10.1159/000079335

View details for PubMedID 15316236