Bone mineral density among Korean females aged 20-50 years: influence of age at menarche (The Korea National Health and Nutrition Examination Survey 2008-2011).

To evaluate a possible correlation between bone mineral density (BMD) and age at menarche, the present study used the BMD dataset of the Korea National Health and Nutrition Examination Survey IV-V (KNHANES IV-V). Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. INTRODUCTION: To investigate any correlation between bone mineral density (BMD) and age at menarche in Korean females using data from the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-V; 2008-2011). METHODS: In total, 37,753 individuals participated in health examination surveys between 2008 and 2011. A total of 5032 premenopausal females aged 20-50 years were eligible. Age, height, weight, and age at menarche were assessed. RESULTS: Results from the univariate linear regression and analysis of covariance (ANCOVA) indicated that age (per 1 year), height (per 1 cm), weight (per 1 kg), exercise (per 1 day/week), familial osteoporosis history (yes), parity (n = 0 to ≥4), and menarche age distribution were associated with BMD of the total femur, femur neck, and lumbar spine. After stratifying the bone area and adjusting for age, parity, alcohol intake, smoking, exercise, and familial osteoporosis history, no effect was seen for the total femur or femur neck. Age at menarche 16~17 and ≥18 years groups were associated with BMD of the lumbar spine only. CONCLUSIONS: Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. Females with late menarche may achieve lower peak bone mass at some skeletal sites, which may put them at greater risk for osteoporosis in later life.

Association of KIR genes and HLA-C alleles with HPV-related uterine cervical disease in Korean women.

This study investigated whether killer-cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA)-C alleles, receptors and ligands of natural killer cells are associated with the development of human papillomavirus (HPV)-related cervical disease in Korean women. Blood samples from 132 women with HPV-related cervical disease and 159 women without HPV infection were collected for genotyping of KIR genes and HLA-C alleles. Although no relationship was found between KIR genes and HPV-related cervical disease, a significant relationship was found between HLA-C alleles as ligands of KIR and HPV-related cervical disease. Women with HPV-related cervical disease were found to be significantly more likely to carry HLA-C*0303, particularly those with HPV 16 or 18 infection, and less likely to carry HLA-C*01 compared to women without HPV infection. HLA-C*0303 was found to confer susceptibility to HPV-related cervical disease, whereas HLA-C*01 was found to confer a protective effect against HPV-related cervical disease.

A case of a borderline mucinous tumor of the ovary with sarcoma-like mural nodules producing granulocyte colony-stimulating factor.

Borderline ovarian tumor with sarcoma-like mural nodule is rare. Malignant mural nodules usually occur in the wall of an atypical proliferative mucinous tumor or a mucinous carcinoma. The authors report one case of unfavorably progressive borderline tumor of the ovary with sarcoma-like mural nodule that produced granulocyte colony-stimulating factor (G-CSF).

"Can laparoscopy really complete full surgical staging?" A case of early recurrence and malignant transformation of borderline ovarian tumor.

Ovarian borderline tumor (BOT) with noninvasive implants traditionally is considered to be non-aggressive. Recurrences are delayed and transformations to high-grade carcinoma are rarely documented. We report on a patient with BOT with early recurrence and high-grade carcinoma transformation in a short interval after complete laparoscopic staging. A 27-year-old unmarried woman presented with a 26 cm in size ruptured left ovarian mass. Laparoscopic left salpingo-oophorectomy with right ovarian biopsies, multiple peritoneal biopsies, omental biopsy and washing cytology were performed. FIGO Stage I ovarian serous borderline tumor with microinvasion was confirmed. About ten months later, a 15 cm in size left BOT recurred and was resected by laparoscopic cystectomy including staging surgery. Seven months after the second surgery, we found a pelvic mass by sonogram and elevated CA125. A third diagnostic laparoscopy revealed invasive serous carcinoma with multiple peritoneal implants. In spite of radical surgery and adjuvant chemotherapy, the patient died of a progressive metastatic liver tumor. A case of early recurrence with malignant transformation of BOT is presented together with a brief review.

Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis.

Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

Persistence of human papillomavirus as a predictor for treatment failure after loop electrosurgical excision procedure.

We aimed to investigate whether postconization human papillomavirus (HPV) DNA testing can predict treatment failure and improve the accuracy of conventional follow-up in women with high-grade cervical intraepithelial neoplasia (CIN). Between March 2001 and October 2005, 120 patients with confirmed CIN 2 or 3 were treated with loop electrosurgical excision procedure (LEEP) and were enrolled. Six patients were lost to the follow-up. Postconization follow-up was performed at every 3-6 months during the first year and then annually. Specimens were tested for the presence of HPV, using the Hybrid Capture 2 (Digene Co, Gaithersburg, MD) and HPV DNA chip (Mygene Co, Seoul, Korea) test. Persistent HPV infection was defined as persistently (two times or more) positive HPV tests with the same HPV subtype(s) at initial diagnosis. Twenty-two (19.3%) patients showed treatment failure after conization. The only significant risk factor for redevelopment of CIN after conization was persistence of the same HPV subtype (P < 0.0001). And women with recurrent or residual CIN had higher HPV load during the 6-month follow-up postconization. In conclusion, the persistence of the same HPV subtype after LEEP conization was an important predictor of treatment failure. The follow-up protocol after conization of CIN should include both cervical cytology and HPV test, and HPV DNA chip test is needed to detect a persistent HPV infection.

Using a three-dimension head mounted displayer in audio-visual sexual stimulation aids in differential diagnosis of psychogenic from organic erectile dysfunction.

We designed this study to compare the efficacy of using a three-dimension head mounted displayer (3-D HMD) and a conventional monitor in audio-visual sexual stimulation (AVSS) in differential diagnosis of psychogenic from organic erectile dysfunction (ED). Three groups of subjects such as psychogenic ED, organic ED, and healthy control received the evaluation. The change of penile tumescence in AVSS was monitored with Nocturnal Electrobioimpedance Volumetric Assessment and sexual arousal after AVSS was assessed by a simple question as being good, fair, or poor. Both the group of healthy control and psychogenic ED demonstrated a significantly higher rate of normal response in penile tumescence (P<0.05) and a significantly higher level of sexual arousal (P<0.05) if stimulated with 3-D HMD than conventional monitor. In the group of organic ED, even using 3-D HMD in AVSS could not give rise to a better response in both assessments. Therefore, we conclude that using a 3-D HMD in AVSS helps more to differentiate psychogenic from organic ED than a conventional monitor in AVSS.

Growth Suppression of Ovarian Cancer Cells by Interferon-gama.

PURPOSE: Growth regulation of cancer cells very frequently involves tumor suppressor gene p53, Rb and cell cycle regulator, however the molecular biologic mechanisms of growth regulation in ovarian carcinoma cells are not fully defined. To assess the mechanism of growth suppression, we treated IFN-gama in ovarian carcinoma cells. MATERIALS AND METHODS: Growth suppression by treatment of IFN-gama was determined by cell proliferation assay in ovarian carcinoma cell lines. Apoptosis was determined by DNA fragmentation assay and electron microscopy. Molecular mechanism of the apoptosis in ovarian carcinoma cell by IFN-gama was further analyzed by the western blot. RESULTS: We found that IFN-gama had remarkable growth- suppressive effects in PA-1 and A2774 ovarian carcinoma cells in a time-dependent manner. Apoptosis was observed in PA-1 and A2774 cell following treatment of IFN- gama by DNA fragmentation assay and EM. The expression of IRF-1 protein from A2774 and PA-1 cell extracts was elevated by increasing the concentration of IFN-gama. IFN-gama caused an increased expression of the important apoptosis-related gene, ICE (interleukin-1beta-converting enzyme) protein in A2774 and PA-1. CONCLUSION: The coordinate induction of IRF-1 and ICE by IFN-gama in ovarian carcinoma cells suggests a functional relationship between these proteins in programmed cell death. The significance of this study is the molecular biologic background of IFN-gama considered as an alternative treatment trial of ovarian cancers.

Regulation of cell growth and HPV genes by exogenous estrogen in cervical cancer cells.

Human papillomavirus (HPV) infection is known as the major cause of the development of cervical cancer. The E6 and E7 proteins of oncogenic HPV can play critical roles in immortalization and malignant transformation of cervical epithelial cells. From the previous epidemiologic data, it has been determined that long-term use of oral contraceptives may be a risk factor for cervical cancer. Investigation of the estrogenic and antiestrogenic effects on the proliferation of cervical cancer cells and the gene expression of HPV would help to explain the role of estrogen in the HPV-associated pathogenesis of cervical cancer. In this study, cervical cancer cells (HeLa, CaSki, and C33A) were cultured in vitro in the presence of 17beta-estradiol or tamoxifen to observe their regulatory growth effect and HPV E6/E7 gene expression. The estrogenic effect on the promoter activity of HPV URR was further confirmed by transient transfection assay, which was conducted in C33A cells using the HPV-18 URR-CAT reporter plasmid. The supplemental effect of estrogen receptors on URR promoter activity was also evaluated. The proliferation of HeLa and CaSki cells was stimulated by estradiol at physiologic concentration levels (

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q.

Uterine leiomyoma is a benign smooth muscle tumor of the myometrium and is the most commonly encountered neoplasm in women of reproductive age. As for most benign tumors, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. The purpose of this study was to perform a genome-wide allelotype analysis to identify potential sites of tumor suppressor gene inactivation. Fifty-two cases of uterine leiomyoma were subjected to allelotype analysis by using matched pairs of tumor and blood DNA. Loss of heterozygosity (LOH) was assessed at 61 microsatellite markers distributed throughout the genome and representing all 41 chromosome arms. In general, LOH was very rare except on chromosome 7q, where LOH was observed in 34% of all informative tumors. Fine-deletion mapping with 25 microsatellite markers from the 7q22 region revealed a minimal deletion unit of approximately 4 cM, bounded by the markers D7S2453 proximally and D7S496 distally, that probably harbors a novel tumor suppressor gene involved in the etiology of this tumor.

Prevalence and risk factors of urinary stones in Koreans.

To estimate the prevalence of urinary stone disease in Koreans, and to determine the inter-relationships between urinary stone disease and various epidemiological factors, 1,521 controls and 1,177 cases with urinary stones were evaluated. Of special interest in this study were: 1) proportion of past urinary stone history among controls; 1.9% 2) the point prevalence rate of urinary stones among controls; 0.2% 3) the recurrence rate of urinary stones (the proportion of past history of urinary stone) among cases; 56.8% 4) high incidences (76.3%) in the thirties to the fifties among cases 5) the risk factors for urolithogenesis; obesity [higher than 25 of BMI (body mass index, weight/height2)], more than 10 year-experience as a production worker, past stone history, familial stone history, low physical activity (< 2,000 Kcal/day), and low intake of fruit. However, the well-known risk factors for urinary stones; over intake of meat or fish and milk or dairy products, perspiration, amount and kind of drinking water, and stress unexpectedly were not significantly different between the controls and the cases.

Role of nitric oxide in penile erection.

The present study was undertaken to investigate the role of nitric oxide (NO) in erectile physiology by correlating its action with the existence and activity of nitric oxide synthase (NOS), which produces NO. We applied Western blot analysis in both human and rat penile tissue. In the rat, reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and spectrophotometric assay were also performed, in addition to in vivo electroerection study with pharmacological manipulation. Western blot analysis identified a protein of 155 KDa identical to the neural form of NOS in the human and rat penis. The NOS blot densities in the two species were similar, and both were lower than that in the rat cerebellum. Histochemical staining localized NOS to neurons innervating the corpora cavernosa, including the pelvic plexus, the cavernosal nerves and their terminal fibers within the corporeal erectile tissue, and dorsal penile nerves. NOS activity was also found in the cerebellum, urethra, penis, and urinary bladder, in decreasing order of intensity. Intracavernous injections of NOS inhibitor (L-NOARG or L-NAME in concentrations from 10(-6) M to 10(-3) M suppressed electrostimulation-induced erection in a concentration-dependent manner. Subsequent intracavernous injection of L-Arginine (10(-2) M) partially restored the erection. The neural form of constitutive NOS in the corpora cavernosa synthesizes NO, which mediates penile erection. Determination of cavernosal NOS expression or activity may permit characterization of certain pathological conditions that cause impotence.

Effects of site-directed mutagenesis of basic residues (Arg 94, Lys 95, Lys 99) of lipopolysaccharide (LPS)-binding protein on binding and transfer of LPS and subsequent immune cell activation.

LPS-binding protein (LBP) is a 60-kDa acute phase glycoprotein capable of binding the LPS of Gram-negative bacteria and facilitating its diffusion. This process is thought to be of potential importance in inflammatory reactions and pathogenic states such as septic shock syndrome. Here, we report on the identification of a LPS binding domain within the LBP molecule and on the identification of single amino acids important for binding of LPS by LBP. Several synthetic LBP peptides inhibited LPS-LBP interaction, and amino acids Arg 94 and Lys 95 were centrally located in these inhibitory peptides. LBP mutants with amino acid exchanges within this region were expressed and tested in five different functional assays: binding to immobilized LPS; facilitation of binding of LPS aggregates to monocytes; transfer of LPS monomers from aggregates to soluble CD14; transfer of soluble CD14-bound LPS monomers to high density lipoprotein (HDL); and enhancement of LPS-induced cell activation. The double mutant Glu 94/Glu 95 was completely lacking LPS binding, transfer, and cell stimulatory activity, indicating that the integrity of amino acids 94 and 95 is required for LBP function. While mutations of amino acids Arg 94 or Lys 95 into alanine reduced the LPS binding activity of LBP dramatically, the ability to facilitate binding of LPS aggregates to membrane CD14 at the cell surface was retained. These findings emphasize the distinction between binding of LPS aggregates to cells, which is not associated with cell stimulation, and binding of LPS monomers to CD14, which leads to cell stimulation.

CUMC-6, a new diploid human cell line derived from a squamous carcinoma of the uterine cervix.

A new cell line, CUMC-6, has been derived from an invasive nonkeratinizing squamous cell carcinoma of the uterine cervix in a 31-year-old patient. It has been maintained in long-term culture for 61 months, and passaged over 300 times. Monolayer-cultured cells were polygonal in shape, showing a pavement-like arrangement and a tendency to pile up without contact inhibition. The epithelial nature of the cultured CUMC-6 cells was confirmed by transmission electron microscopy which demonstrated the presence of desmosomes and tonofilaments. The subcutaneous injection of cultured cells into nude mice gave rise to fast-growing tumors. The transplanted tumor showed similar histological features, but poor differentiation compared to the original tumor. Cultured CUMC-6 cells produced human chorionic gonadotropin beta-subunit (beta-HCG) and alpha-fetoprotein (AFP). Cytosol estrogen and progesterone receptors were not measured in this cell line. The results of isozyme analyses were distinct from the HeLa cell line. Repeated chromosome analysis from passage 6 to 300 revealed that most metaphases of this cell line contained diploid number of chromosomes. The structural abnormality consistently observed in this cell line was the elongation of short arm of chromosome 1. The G- or R-banded pattern of this chromosome suggested inv dup (1) (1pter-->1p34[symbol: see text] 1p21-->1p34[symbol: see text] 1p34-->1qter). Human leukocyte antigen (HLA) typing of CUMC-6 cells indicated the presence of DR12 and DQw3. Analysis of the DNA extracted from the CUMC-6 cells showed the presence of human papillomavirus (HPV) type 16 and 18 DNAs. The results of oncogene analyses using Southern blotting technique revealed amplification and rearrangement of oncogene c-myc and no amplification of oncogene L-myc. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, we have screened CUMC-6 cells for p53 mutation in exons 4 to 9. No mobility shift was observed in this cell line. These results suggest that chromosome 1 abnormality, oncogene alteration, and HPV infection work together in cervical tumorigenesis.

Effect of vasoactive intestinal peptide and acetylcholine on penile erection in the rat in vivo.

We investigated the effect of vasoactive intestinal peptide (VIP) and its combination with acetylcholine (ACh) on the erectile response in 52 adults rats. Intracavernous injection of VIP (10(-8) to 10(-5)M, ACh (10(-9) to 10(-5), or a combination of VIP (10(-7) to 10(-5) with ACh (10(-6 M) additively enhanced that erection but did not lead to a full erection. VIP-antagonist (10(-9) to 10(-5 M), as well as atropine alone (10 (-7) to 10(-5 M), partially suppressed full erection induced by cavernous nerve stimulation (1 Hz, 3-6 V) in a dose-dependent manner, and the combination of VIP-antagonist (10(-9) to 10(-5 M) with atropine (10(-6 M) showed an additive effect. The results indicate that although VIP as well as ACh in involved in penile erection, they are not likely to be principal neurotransmitters. Their clinical application in the treatment of impotence may be confined to use in conjunction with another vasoactive agent.

Aberrations of the p53 tumor suppressor gene in human epithelial ovarian carcinoma.

Aberrations of the p53 gene in 26 surgical specimens of human epithelial ovarian carcinomas were examined by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products. Seven (27%) of the tumors demonstrated a SSCP band shift in exons 4 to 9 of the gene, including 5 in the region encompassing exons 5 and 6, 1 in exon 7, and 1 in the region encompassing exons 8 and 9. Mutations were clustered in exon 5 in highly conserved regions of the p53 gene. All of the abnormal DNA fragments have been further characterized by direct DNA sequencing. These include five missense mutations (five transitions), a one-base-pair deletion introducing, by frameshift, a stop codon further downstream, and a two-base-pair insertion introducing a stop codon downstream by frameshift. Most mutations were base substitutions, and were clustered in exon 5 (71%), especially codons 175 and 179. The aberrations of the p53 gene were only found in tumors of FIGO stages III and IV. Histologic grading was also reviewed with respect to p53 aberrations. The aberrations were absent in well-differentiated carcinomas. The more undifferentiated the primary tumor, the more frequent p53 mutation (P < 0.05). Our results indicated that the aberrations of the p53 gene were common in epithelial ovarian cancers and p53 aberration may occur late during ovarian cancer evolution.

Acute disruption of polytetrafluoroethylene grafts adjacent to axillary anastomoses: a complication of axillofemoral grafting.

PURPOSE: Acute disruption at or adjacent to axillary anastomoses of axillofemoral grafts has been sporadically reported. We have recently reported the patency and limb salvage results of a large number of axillofemoral grafts. In this report we describe a series of axillary artery-graft disruptions that occurred in these patients. METHODS: Beginning in 1983, axillofemoral bypass was performed by the authors using standardized operative technique and a single prosthetic graft material (8 mm externally supported polytetrafluoroethylene). Axillary anastomoses were placed on the first portion of the artery and were performed with the arm abducted and with the graft redundant. The records and operative reports of all patients with disruption were reviewed for findings and subsequent hospital course. RESULTS: Two hundred two axillofemoral grafts were performed from 1983 to 1993. Ten patients (5%) had axillary disruption at intervals ranging from 1 to 46 days (mean 21 days) after operation. Ischemia was the indication for operation for seven of the patients and infected aortic prostheses for three. Infection did not occur in any of the axillary wounds and was not the cause of any of the disruptions. Four disruptions occurred with arm abduction/shoulder elevation movements; three awakened patients from sleep, and one occurred while the patient was sitting quietly. For the other two patients, preceding activity was unknown. Brachial plexus deficit was present in one patient. Four of the 10 disrupted grafts were also acutely occluded. Operative findings included sutures pulling out of the artery in four cases, tearing or sutures pulling out of the graft in four cases, and cause unknown in two cases. Treatment included arterial ligation in one patient, and restoration of circulation through revision of the axillofemoral grafts in the other nine patients. There were no operative deaths. One patient had a prolonged hospital course followed by nursing home placement and died 9 months later. The brachial plexus deficit did not resolve. There have been no repeat disruptions. CONCLUSIONS: We conclude that axillofemoral grafting includes the potential for disruption of the proximal anastomosis, which has occurred in 5% of our patients. Although multiple steps have been recommended to avoid this complication, occasional cases continue to occur despite observing all precautions.

Isolated bypass to the superior mesenteric artery for intestinal ischemia.

OBJECTIVE: A number of reports indicate revascularization for intestinal ischemia should include the superior mesenteric artery (SMA) and the celiac artery. However, no controlled or randomized studies have proven this approach superior to SMA bypass alone. We report our results using bypass to only the SMA for intestinal ischemia. DESIGN: Retrospective review with mean follow-up of 40 months (range, 2 to 110 months). SETTING: University medical center and Veterans Affairs hospital. PATIENTS/METHODS: The records of patients who underwent intestinal revascularization of the SMA alone from 1982 through 1993 were reviewed. Patients were assessed for indication for operation, operative technique, perioperative mortality, and long-term outcome. The SMA grafts were examined for patency within the last 6 months using duplex scanning or arteriography. Patient survival and graft patency rates were calculated using life-table methods. RESULTS: Twenty-nine bypasses to only the SMA were performed in 26 patients (16 female and 10 male; mean age, 59 years; age range, 13 to 81 years). Indication for operation was symptomatic chronic mesenteric ischemia in 23 cases and acute intestinal ischemia in five cases. One bypass was performed for asymptomatic SMA occlusion. There were three perioperative deaths (10% mortality rate), all in patients with acute intestinal ischemia and previous mesenteric arterial surgery. Life-table 4-year primary graft patency and patient survival rates were 89% and 82%, respectively. Symptomatic improvement was maintained in all patients available for follow-up. CONCLUSION: Revascularization of only the SMA for intestinal ischemia provides excellent graft patency with acceptable perioperative mortality and long-term patient survival. The SMA bypass alone for intestinal ischemia appears as successful as bypasses to multiple visceral vessels.