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Biomedical subjects

H N Ho

Publications and source records attributed to H N Ho.

At least 19 recordsLinked to original sources

Hormone replacement therapy reverses the decrease in natural killer cytotoxicity but does not reverse the decreases in the T-cell subpopulation or interferon-gamma production in postmenopausal women.

OBJECTIVE: To investigate the immunologic deviations of postmenopausal women before and after hormone replacement therapy (HRT). DESIGN: Prospective study. SETTING: University teaching hospital. PATIENT(S): Seventeen postmenopausal women (study group) and 17 women of reproductive age (control group). INTERVENTION(S): Continuous usage of E(2) valerate 2 mg/d and medroxyprogesterone acetate 5 mg/d in postmenopausal women in the study group. MAIN OUTCOME MEASURE(S): Immunophenotyping with flow cytometry, cytokine production with and without mitogen stimulation of the peripheral mononuclear cells, and a natural killer (NK) cell cytotoxicity test against K562 target cells by the (51)Cr-release assay were performed in the control group and in the study group before, 1 month after, and 6 months after HRT. RESULT(S): NK cytotoxicity, interferon-gamma production, and the T-cell subpopulation were significantly decreased, and the subpopulations of CD3(+)CD25(+) and CD3(+)HLA-DR(+) were increased in the study group before HRT when compared with those in the control group. After HRT was given for 6 months, however, the NK cytotoxicity increased significantly in the postmenopausal women to a value similar to that of the control group. CONCLUSION(S): Women after menopause are prone to impaired immune responses. Nevertheless, some of the impairment can be restored after HRT.

Adult↗

Cryopreservation of mature human oocytes by vitrification with ethylene glycol in straws.

OBJECTIVE: To examine the effect of vitrification with ethylene glycol (EG) for mature human oocytes in straws. DESIGN: Prospective, randomized, in vitro experiments. SETTING: Reproductive unit of a university hospital. PATIENT(S): Immature oocytes from 110 patients undergoing intracytoplasmic sperm injection (ICSI). INTERVENTION(S): The immature oocytes were incubated to reach metaphase II (MII). The MII oocytes were treated with EG-based cryoprotectants and vitrified in straws. They were diluted in sucrose solutions, inseminated by ICSI, and cultured in vitro. MAIN OUTCOME MEASURE(S): Survival, fertilization, and embryo cleavage. RESULT(S): The survival rates were greater for oocytes pretreated with 1.5 M of EG (65% for 0 minute, 93% for 5 minutes, and 96% for 10 minutes). The oocytes vitrified in 60 and 90 seconds had a greater rate of fertilization than those vitrified in 120 seconds. There were no differences in survival and fertilization for vitrified oocytes diluted by three or four steps. The cleavage rates to the six- to eight-cell stage were comparable with controls. However, no blastocyst formation was observed in vitrified oocytes. CONCLUSION(S): Vitrification of human oocytes with EG in straws achieves a high rate of survival, fertilization, and early cleavage of embryos. Further studies should be conducted for the improvement of blastocyst formation.

Cell Survival↗

Increase in the expression of killer cell inhibitory receptors on peritoneal natural killer cells in women with endometriosis.

OBJECTIVE: Malfunction of peritoneal natural killer cells (NK) may result in endometriosis. The present study was designed to determine whether the decrease in NK cytotoxicity occurs at early and advanced stages of endometriosis and is due to the increase in the NK inhibition receptors. DESIGN: A case control study. SETTING: A tertiary-care infertility center . PATIENT(S): A total of 44 women (controls, n = 11; women with early-stage endometriosis, n = 11; and women with advanced-stage endometriosis, n = 22) were included in this study. INTERVENTION(S): Laparoscopic examination. MAIN OUTCOME MEASURE(S): NK cytotoxicity was determined by assay of (51)Cr release against K562 cells, and the expression of killer cell inhibitory receptors (KIR, including NKB1, GL183, and EB6) in NK cells was examined by flow cytometry. RESULT(S): Women with endometriosis showed a decrease in peritoneal NK cytotoxicities against K562 at early and advanced stages of endometriosis. The expression of KIR (NKB1 and EB6) was significantly elevated in the peritoneal NK cells of women with advanced-stage endometriosis compared with controls. KIR (NKB1) was also significantly increased in peritoneal NK cells of women with advanced-stage endometriosis, compared with those of women with early-stage endometriosis. CONCLUSION(S): The results of this study suggest that the decrease in peritoneal NK cytotoxicities against K562 is observed and that this disease may be partially due to the increased expression of KIR on these NK cells.

Ascitic Fluid↗

Relationships of serum pro-inflammatory cytokines and vascular endothelial growth factor with liver dysfunction in severe ovarian hyperstimulation syndrome.

The aims of this study were to determine if differences in serum pro-inflammatory cytokines, vascular endothelial growth factor (VEGF) and clinical pregnancy rate, could be observed in women with severe ovarian hyperstimulation syndrome (OHSS) in those who did and did not have liver dysfunction. Twenty-nine in-vitro fertilization patients with severe OHSS were included. The patients were divided into the normal liver function tests (LFT) group (n = 14) and the abnormal LFT group (n = 15) according to the LFT on day of admission. Periodic measurements of serum interleukin (IL)-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), VEGF, oestradiol, progesterone concentrations, and LFT were performed during hospitalization. Concentrations of IL-6 in the active phase of OHSS were significantly higher in the abnormal LFT group than in the normal LFT group (19.7 +/- 15.7 versus 8.1 +/- 7.0 pg/ml, respectively). The severity of liver dysfunction was not correlated with concentrations of oestradiol, progesterone, haematocrit, white blood cell counts, or any studied cytokine. The clinical pregnancy rate was significantly lower in the abnormal LFT group (46.7%) than in the normal LFT group (85.7%). These results suggest that IL-6 cytokine system may play a role in the pathogenesis of liver dysfunction in severe OHSS. Abnormal LFT were associated with lower clinical pregnancy rates.

Adult↗

Open pulled straws for vitrification of mature mouse oocytes preserve patterns of meiotic spindles and chromosomes better than conventional straws.

Vitrification of oocytes has been applied recently for humans, but remains elusive. The microtubules of oocytes are vulnerable to cryoprotectants and thermal changes. Using mouse oocytes, the effects of vitrification in open pulled straws (OPS) were investigated on survival, the meiotic spindle, and chromosomes and compared with conventional straws. Mature oocytes were allocated to four groups for exposure to cryoprotectants, vitrification in conventional straws, or vitrification in OPS. They were diluted in stepwise sucrose solutions. Oocytes without treatments were used as controls. The surviving oocytes were stained for meiotic spindles and chromosomes. After dilution, all of the oocytes exposed to cryoprotectants survived. Vitrification sometimes resulted in lysis so that survival using OPS (62%) was significantly (P < 0.05) smaller than that using conventional straws (81%). Oocytes exposed to cryoprotectants or vitrified exhibited serious disturbances of microtubules immediately post-dilution. After 1 h incubation, the microtubules could repolymerize so that the OPS group had significantly (P < 0.05) more normal spindles (78%) than did the conventional straw group (21%). The former also tended to have more compact chromosomes (87%) than did the latter (78%). OPS for vitrification of oocytes achieve more rapid cooling, warming, and dilution and so reduce spindle injury. However, the lower survival rate in OPS needs improvement.

Animals↗

Value of serum and follicular fluid cytokine profile in the prediction of moderate to severe ovarian hyperstimulation syndrome.

The aim of this study was to examine the role of serum and follicular fluid pro-inflammatory cytokines and vascular endothelial growth factor (VEGF) in the prediction of ovarian hyperstimulation syndrome (OHSS). A total of 156 consecutive women undergoing in-vitro fertilization were recruited. The study group comprised 12 women who subsequently developed moderate (n = 7) or severe (n = 5) OHSS. The two control groups were comprised of a randomized selection of 12 high-risk and 12 low-risk women in whom OHSS did not develop. Serum was collected on days of human chorionic gonadotrophin, oocyte retrieval, and embryo transfer. Serum and follicular fluid concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), and VEGF were measured. Follicular fluid IL-6 concentrations at the time of oocyte retrieval and serum IL-8 concentrations at the time of embryo transfer were significantly higher in the OHSS compared to the two control groups (P = 0.026 and P = 0.017 respectively). Serum concentrations of TNF-alpha and VEGF showed no statistically significant difference between the OHSS group and the controls at any studied time point. This study suggests that follicular fluid IL-6 concentrations at the time of oocyte retrieval and serum IL-8 concentrations on the day of embryo transfer may serve as early predictors for this syndrome.

Adult↗

Luteinizing hormone up-regulates the expression of interleukin-1 beta mRNA in human granulosa-luteal cells.

PROBLEM: Previously, we observed that follicular fluid obtained from patients with premature luteinization contained elevated interleukin-1 beta (IL-1 beta) levels. In this study. we aimed to examine the effects of luteinizing hormone (LH) on IL-1 beta expression and IL-1 beta on steroidogenesis in human granulosa-luteal cells. METHOD OF STUDY: Human granulosa-luteal cells were obtained during oocyte retrieval. The cells were treated with either LH or IL-1 beta and subsequently were examined for the level of IL-1 beta transcript. The conditioned media were examined for IL-1 beta protein and steroid hormone levels. RESULTS: LH (250-500 mIU/mL) up-regulated the expression of IL-1 beta mRNA (up to a 4-fold increase over control; P<0.05) in the granulosa-luteal cells. IL-1 beta (5-50 ng/mL) increased the basal, but not LH-dependent, progesterone production from these cells in a dose-dependent manner after 96 and 144 hr of culture (P<0.05). However, an inhibitory effect of IL-1 beta on LH-dependent estradiol production was observed (up to 20% decrease, P<0.05). CONCLUSIONS: LH is capable of stimulating IL-1 beta transcript expression in human granulosa-luteal cells and may regulate ovarian steroidogenesis, at least partly through the activation of IL-1 beta.

Cells, Cultured↗

Reversed CD4/CD8 ratios of tumor-infiltrating lymphocytes are correlated with the progression of human cervical carcinoma.

BACKGROUND: To investigate the clinical significance of tumor-infiltrating lymphocytes (TILs) within the tumor milieu of human cervical carcinoma, the authors quantitatively measured and compared the subpopulations of lymphocytes infiltrating the neoplastic cervix. METHODS: A total of 30 patients with Stage Ia-IIa cervical carcinoma were enrolled. TILs were isolated from tissue specimens by means of a mechanical dispersal technique, and the immunocyte subsets were quantified with dual-color flow cytometry. Bulky tumor was defined as tumor size >4 cm in greatest dimension according to the 1995 staging of the International Federation of Gynecology and Obstetrics. RESULTS: The CD4/CD8 ratios of TILs were reversed in both cervical squamous cell carcinoma (n = 20) and cervical adenocarcinoma (n = 10). The proportion of CD4(+) T cells was significantly lower in tumors from patients with lymph node metastasis (n = 8) than in those from patients without lymph node metastasis (n = 22) (24.5 vs. 32.7, P = 0.001), as was the reversed CD4/CD8 ratio (0.50 vs. 0.81, P = 0.001). The proportion of CD4(+) T cells was much lower in bulky tumors (n = 5) than in nonbulky tumors (n = 25) (21.4 vs. 32.5, P < 0.001), reflecting in a more strongly reversed CD4/CD8 ratio (0.41 vs. 0.81, P = 0.001). CONCLUSIONS: Decreased proportions of tumor-infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma. The regional immune escape is of prognostic importance with regard to cancer progression.

Adenocarcinoma↗

Transmission of de novo mutations of the deleted in azoospermia genes from a severely oligozoospermic male to a son via intracytoplasmic sperm injection.

OBJECTIVE: To investigate the transmission of microdeletions in the deleted in azoospermia (DAZ) genes to a male offspring via intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: Reproductive unit of a university teaching hospital. PATIENT(S): A 29-year-old, severely oligozoospermic male with microdeletions of the DAZ genes in Yq interval 6 and his son, who was conceived via ICSI. INTERVENTION(S): DNA screening for the microdeletions in Yq interval 6 with 24 sequence tagged sites with the use of polymerase chain reaction amplification for the patient, the patient's father, and the patient's son. Paternity identification was performed using nine hypervariable short tandem repeats. MAIN OUTCOME MEASURE(S): Deletion mapping of Yq interval 6 from sequence tagged sites and electropherogram of short tandem repeats for DNA fingerprinting. RESULT(S): The son had the same microdeletions of the DAZ genes as the patient, and the patient's father had normal DAZ genes. The paternity of the patient, the patient's father, and the patient's son was verified. CONCLUSION(S): De novo DAZ microdeletions in an infertile male can be transmitted to a male offspring via ICSI. DNA screening tests for DAZ genes before ICSI may help in the genetic counseling of patients with idiopathic azoospermia or severe oligozoospermia.

Adult↗

Prognostic importance of serial cytokine changes in ascites and pleural effusion in women with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To determine the prognostic value of various cytokine levels in ascites and pleural effusion during the evolution of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: A longitudinal study. SETTING: University teaching hospital. PATIENT(S): Twenty patients with severe OHSS who required either paracentesis or thoracentesis or both from whom ascites (n = 56) or pleural effusion (n = 12) samples were obtained. Control peritoneal fluid was obtained from 20 patients undergoing ovarian stimulation for IVF. INTERVENTION(S): Abdominal paracentesis for tense ascites and thoracentesis for massive pleural effusion. Control peritoneal fluid was obtained before oocyte retrieval. MAIN OUTCOME MEASURE(S): Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), E2, and progesterone concentrations in ascites and pleural effusion. RESULT(S): Levels of VEGF and IL-6 in ascites dropped significantly during the course of OHSS and were not correlated with E2 concentrations. Levels of VEGF were significantly correlated with levels of IL-1 beta, IL-8, and TNF-alpha, as well as progesterone concentrations, hematocrit, and white blood cell counts. None of the cytokine levels measured in pleural effusion were correlated with the course of OHSS. CONCLUSION(S): These results suggest that local cytokines might be involved in the evolution of severe OHSS and possibly serve as prognostic markers for this syndrome.

Adult↗

Expression of leukemia inhibitory factor and its receptor in preimplantation embryos.

OBJECTIVE: To examine the expression of leukemia inhibitory factor (LIF) and its receptor (LIF-R) transcripts in human and murine preimplantation embryos. DESIGN: Prospective study. SETTING: University medical center. PATIENT(S): Human oocytes were obtained from patients undergoing IVF treatment. Two-cell murine embryos were obtained from ICR strain mice. INTERVENTION(S): Second-day intracytoplasmic sperm injection procedures were performed on oocytes that failed to be fertilized by IVF. Embryos were cultured to various stages and collected for study. MAIN OUTCOME MEASURE(S): The transcript levels of LIF and LIF-R in these embryos were examined and semiquantitated using single-cell reverse transcription-polymerase chain reaction methodology. RESULT(S): Leukemia inhibitory factor and LIF-R transcripts were detectable in most human preimplantation embryos (30 of 34 and 31 of 34 embryos showed LIF and LIF-R messenger RNA, respectively). There was a trend toward decreased expression of both transcripts in embryos at the four-cell stage and in embryos in which growth had been arrested for 24-48 hours. The expression of LIF and LIF-R genes in murine embryos was inconsistent. CONCLUSION(S): Preimplantation human embryos express LIF and LIF-R messenger RNA. It is suggested that LIF may be able to affect embryo development through its action at stages before implantation in an autocrine or paracrine manner.

Animals↗

The expression of killer cell inhibitory receptors on natural killer cells and activation status of CD4+ and CD8+ T cells in the decidua of normal and abnormal early pregnancies.

The establishment of the human placenta in early pregnancy is characterized by the presence of large numbers of natural killer cells within the maternal decidua. These NK cells have an unusual phenotype, CD3- CD16- CD56(bright), distinguishing them from peripheral blood NK cells. They may control trophoblast migration and placentation. Using a panel of monoclonal antibodies to several members of the KIR family and flow cytometry, we found that KIRs are expressed on decidual NK cells. There is variation in both the percentage of cells expressing a particular receptor and the density of receptor expression between decidual NK cells from different individuals. In anembryonic pregnancy, the proportions of decidual NK cells with a particular KIRs (GL183 and EB6) decreased significantly when compared with normal pregnancy (p = 0.01 and 0.01, respectively), raising the possibility that these NK receptors may be involved in recognition of the allogeneic fetus by the mother at the implantation site. In the decidua, more CD4+ and CD8+ T cells expressed CD69 and HLA-DR than in blood, indicating that T cells are regionally activated during early pregnancy. When compared with normal pregnancy, decidual HLA-DR+CD4+CD3+, CD69+CD8+CD3+ and HLA-DR+CD8+CD3+ T lymphocytes are significantly increased in anembryonic pregnancy. The over-activation of decidual T cells during anembryonic pregnancy may thus contribute to the increased NK cytotoxicity activity.

Antigens, CD↗

Association of endometrial blood flow as determined by a modified colour Doppler technique with subsequent outcome of in-vitro fertilization.

An endometrial thickness of 10 mm or more has been reported to be favourable for embryo implantation. Nevertheless, many women participating in in-vitro fertilization (IVF) programmes have adequate endometrial thickness but do not achieve satisfactory implantation. With the aid of power Doppler sonography, we examined the association between intra-endometrial vascularity and reproductive outcome. For this study, we enrolled only women with endometrial thickness >/=ISOdia>/=10 mm and excluded those with apparent endometrial pathologies. Of 95 women undergoing IVF cycles, there resulted 37 intrauterine pregnancies. The women were of similar age, body mass index, peak oestradiol concentration and endometrial thickness, and a similar number of embryos were transferred. Those women with an intra-endometrial power Doppler area (EPDA) <5 mm2 achieved a significantly lower pregnancy rate (23. 5 versus 47.5%, P = 0.021) and implantation rate (8.1 versus 20.2%, P = 0.003) than those with an EPDA >/=ISOdia>/=5 mm2. We conclude that, in addition to endometrial thickness, EPDA may serve as a factor indicative of endometrial receptivity. Women with adequate endometrial thickness but a small EPDA tended to have an unfavourable reproductive outcome.

Adult↗

Increase in the production of interleukin-6, interleukin-10, and interleukin-12 by lipopolysaccharide-stimulated peritoneal macrophages from women with endometriosis.

PROBLEM: To verify whether the peritoneal macrophage (PM) is activated in endometriosis. METHOD OF STUDY: We examined the synthesis of nitric oxide (NO), total antioxidant, interleukin (IL)-6, IL-10, and IL-12 by cultured PMs, which were either unstimulated or stimulated with lipopolysaccharide (LPS), from women with endometriosis (early, n = 12; advanced, n = 11) or without endometriosis (n = 13). RESULTS: After stimulation with 2 ng/mL LPS for 24 hr, PMs from women with early-stage endometriosis secreted more NO, IL-6, and IL-10 than the controls. Higher IL-12 levels were noted in women with advanced endometriosis when compared with the controls. After 2 ng/mL-LPS stimulation for 24 hr, we also detected higher total antioxidant levels in the advanced-endometriosis group than those in the early-endometriosis group. CONCLUSION: The increased production of IL-6, IL-10, and IL-12 by stimulated PMs confirmed previous observations that the PM is the principle source of these cytokines in peritoneal fluid.

Endometriosis↗

T lymphocytes and cytokine production in ascitic fluid of ovarian malignancies.

The activation status of T lymphocytes and the presence of various cytokines in ascitic fluid were examined to test peritoneal immunity in women with ovarian malignancies. Peripheral blood and peritoneal fluid were collected from 12 patients with primary ovarian cancer with ascites and 27 normal control subjects during laparoscopic examination. Lymphocyte subpopulations and the expression of activation markers on T lymphocytes were analyzed by dual-color flow cytometry. The concentrations of various cytokines and soluble interleukin (IL)-2 receptor-alpha were measured. CD8 T lymphocytes were the main component of peritoneal lymphocytes. CD69 and HLA-DR, but not CD25, were highly expressed on peritoneal T lymphocytes compared to those in peripheral blood. In ascitic fluid of ovarian malignancies, CD4 T lymphocyte concentrations were further decreased, resulting in a decreased CD4/CD8 ratio. Decreased expression of CD69 and CD25 was also noted on T lymphocytes from ascites compared with T lymphocytes in normal peritoneal fluid. IL-1b, tumor necrosis factor-alpha, IL-6, and soluble IL-2 receptor-alpha concentrations were increased significantly in the ascitic fluid of women with ovarian cancer. The decrease in activation markers on T lymphocytes is suggestive of an immunosuppressive state, despite the presence of abundant stimulatory cytokines. The immunosuppression may be multifactorial, attributed, in part, to the increased concentrations of soluble IL-2 receptor-alpha and other inhibitors.

Ascitic Fluid↗

Tumor immunology--when a cancer cell meets the immune cells.

Tumor immunology consists of two essential concepts: immune surveillance, which specifies the host immune reactions against tumor cells, and tumor immune escape, which refers to the tumor-cell evasion process against the host immune system. Effective antitumor immunity by the host immune surveillance is supposed to be dependent on the identification of tumor antigens. In the process of malignant transformation, genetic mutations with aberrant expression of cancer-related genes and protein products are potentially immunogenic, which may serve as rejection antigens. Several scenarios are proposed to be responsible for tumor immune-escape mechanisms. The elucidation of the immune deficit against cancer progression has been a difficult task and no solitary mechanism explains the complicated cancer-host immune interactions. Cancer cells may overcome immune surveillance through a common but effective pathway, either by changing the polarity of effector cells, thus down-regulating the proliferation of tumor-specific cytotoxic T cells, or altering the effector compositions of immune cells within the tumor milieu, or both. Understanding the interaction between cancer cells and host immune cells within the tumor milieu is of importance for further clinical applications of immunotherapy in cancer treatment.

Antigens, Neoplasm↗

Postpartum myocardial infarction rescued with an intraaortic balloon pump and extracorporeal membrane oxygenator.

A 37-year-old woman had postpartum myocardial infarction complicated with cardiogenic shock. The infarction was attributed to diffuse coronary artery spasm caused by methylergonovine, which had been used to treat the postpartum haemorrhage due to placenta increta. The haemodynamics could not be maintained with catecholamine infusion and intraaortic balloon counterpulsation. At last, an extracorporeal membrane oxygenator was used to save her life, and the patient was successfully weaned from the machine 100 h later; she made an uneventful recovery thereafter.

Adult↗

Pregnancy achieved by intracytoplasmic sperm injection using cryopreserved vasal-epididymal sperm from a man with spinal cord injury.

Anejaculation and poor semen quality are two major causes of infertility in men with spinal cord injury (SCI). The poor motility of retrieved sperm usually has low fertilization potential and is thought to be unfavorable for cryopreservation. This report describes a pregnancy after intracytoplasmic sperm injection (ICSI) with cryopreserved vasal-epididymal sperm from a man with SCI and anejaculation. An attempt was made to obtain sperm through electroejaculation, but no motile sperm were found in two trials. Therefore, the subject underwent vasal aspiration. The retrieved sperm had a concentration of 26 x 10(6)/mL and a motility of 3%. ICSI was considered to be the best choice for the couple, but the wife did not become pregnant in the first cycle of treatment. A successful pregnancy was achieved by ICSI in the second cycle using frozen-thawed sperm, supernumerary in the previous cycle, with a density of 5 x 10(6)/mL and 1% motility. A set of healthy twins, one boy and one girl, were delivered via cesarean section at 36 weeks of gestation. Complementary to other assisted reproductive techniques, ICSI may provide men with SCI a greater opportunity to father children. The supernumerary sperm, regardless of quality, should be cryopreserved to avoid the necessity and risk of repeated assisted ejaculations and aspirations of the genital tract.

Adult↗