Global transcriptome analysis identifies weight regain-induced activation of adaptive immune responses in white adipose tissue of mice.

OBJECTIVE: Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain. DESIGN: We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses. RESULTS: In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-associated molecular patterns. CONCLUSIONS: Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.

Laparoscopic tubal anastomosis: fertility outcome in 202 cases.

OBJECTIVE: To evaluate the fertility outcome after laparoscopic tubal anastomosis for reversal of sterilization. DESIGN: Retrospective clinical study. SETTING: A private practice affiliated with a university medical school. PATIENT(S): Two hundred two women who desired reversal of tubal sterilization. INTERVENTION(S): Laparoscopic tubal anastomosis. MAIN OUTCOME MEASURE(S): The cumulative pregnancy rate (PR) and factors that influenced the fertility outcome. RESULT(S): The cumulative PR in the 186 patients for whom follow-up data were available was 60.3%, 79.4%, and 83.3% at 6, 12, and 18 months after operation, respectively. Five patients (3.2%) had ectopic pregnancies; one of these patients subsequently conceived normally. There were no statistically significant differences in the PR according to the sterilization method used, the site of the tubal anastomosis, or the length of the fallopian tube after surgery. The intrauterine PR was 87.1% (149/171) with bilateral anastomosis and 60% (9/15) with unilateral anastomosis. The PR decreased with increasing patient age (mean [+/- SD], 35+/-3.6 years) but was still 70.6% (12/17) in patients aged 40-45 years. CONCLUSION(S): Our findings suggest that laparoscopic tubal anastomosis is a highly successful procedure. This less invasive approach could be considered the procedure of choice in patients who desire reversal of tubal sterilization.

Fertility outcome after laparoscopic microsurgical tubal anastomosis.

OBJECTIVE: To evaluate fertility outcome after laparoscopic microsurgical tubal anastomosis. DESIGN: A retrospective study. SETTING: Infertility Medical Center affiliated with University Medical School. PATIENT(S): Fifty-four patients, who had previously undergone tubal sterilization, seeking reversal. INTERVENTION(S): Laparoscopic microsurgical tubal anastomosis was performed. MAIN OUTCOME MEASURE(S): Pregnancy success was assessed. RESULT(S): The overall pregnancy rate (PR) was 77.5% (38/49) and 29 patients already have delivered healthy offspring. Pregnancy in seven patients is ongoing and one case ended in abortion. There was one case of ectopic pregnancy. The pregnancy success according to the method of previous tubal sterilization was 16 of 24 with the Fallope-ring method, 14 of 15 in cases of cauterization, and 8 of 10 in patients in whom the Pomeroy technique was used. The pregnancy success according to the site of anastomosis was 3 of 4 in cornual-isthmic, 4 of 5 in isthmic-isthmic, 26 of 35 in isthmic-ampulla, 3 of 3 in cornual-ampulla, and 2 of 2 in ampulla-ampulla. The pregnancy success according to the tubal length was 5 of 7 at a length < or = 4 cm, 3 of 5 at 5 cm, 15 of 17 at 6 cm, and 15 of 20 at lengths > or = 7 cm. CONCLUSION(S): Considering the high PR in our minimal follow-up period of 12 months, laparoscopic microsurgical tubal anastomosis could be an alternative procedure to microsurgical laparotomy in patients requesting reversal of tubal sterilization.

Estrogen and progesterone receptor assay in carcinoma of the cervix with monoclonal antibodies.

The normal cervix has been shown to contain estrogen and progesterone receptors (ER and PR), but there have been controversial reports on the presence of these receptors in cervical carcinoma. Thus to explore the relationships between the steroid receptor status and cervical carcinoma, tissues of 34 patients with invasive cervical carcinoma prior to treatment and 30 cases of control who underwent hysterectomy due to benign gynecologic diseases at Yonsei Medical Center were analyzed for ER and PR using immunocytochemical assay with monoclonal antibodies and the results were compared with those of conventional steroid binding assay. ER and PR were positive in 65 and 71% of all tumors, respectively, and 59% of the cases were positive for both receptors simultaneously. No significant difference in receptor levels was noted when stratified according to menopausal status or clinical stage. With regard to tumor size, lesions greater than 3 cm had significantly lower receptor positivity when compared with the control. For the histological cell types, a statistically significant higher mean ER level was noted in adenocarcinoma compared to squamous cells. Even though the potential therapeutic significance of these findings is not yet known, they are consistent with the concept that steroid receptors can be used as a guide to endocrine therapy with respect to other prognostic parameters. However, the small number of advanced-stage carcinomas and the absence of data regarding survival rate in this study preclude any definite conclusions.

Studies on the prenatal chromosomal analysis and the changes of maternal serum alpha-fetoprotein following chorionic villus sampling.

Transcervical chorionic villus sampling (CVS) was performed in 174 patients between 7 & 12 menstrual weeks of pregnancy opting for prenatal diagnosis. Advanced maternal age was the most common indication for CVS (39.7%). The sampling success rate was 95.4% (166/174), representing 88.9% at 7 to 8 weeks, 98.9% at 9 to 10 weeks & 92.7% at 11 to 12 weeks gestation. In 139 of 174 patients (80%), successful sampling was accomplished in one or two catheter passages only. Four spontaneous fetal losses (2.3%) occurred. The cytogenetic analysis routinely used was the direct overnight & long-term culture methods which revealed 4 abnormalities (2.4%). To date, 90 of the women have been delivered & all infants are doing well and the remaining 65 pregnancies are continuing uneventually. Maternal serum alphafetoprotein (MSAFP) concentration was determined in 72 patients immediately before & after CVS. A significant increase of 20% or more, comparable to pre CVS levels, was noted immediately after sampling in 56 of 72 patients (77.8%). The increase in MSAFP concentration correlated with the amount of villi sampled (r = 0.498, p less than 0.001) & with the number of sampling attempts (p less than 0.05). Estimated CVS related fetomaternal hemorrhage (FMH) ranged from 0.005 to 0.1552 ml and in 5 of 72 patients (6.90%) 0.06 ml or more of FMH was noted. Two of the 5 patients had FMH of 0.1 ml or more.