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Biomedical subjects

C D Chen

Publications and source records attributed to C D Chen.

At least 19 recordsLinked to original sources
PubMed1999

Binding of hnRNP H to an exonic splicing silencer is involved in the regulation of alternative splicing of the rat beta-tropomyosin gene.

In the rat beta-tropomyosin (beta-TM) gene, exons 6 and 7 are spliced alternatively in a mutually exclusive manner. Exon 6 is included in mRNA encoding nonmuscle TM-1, whereas exon 7 is used in mRNA encoding skeletal muscle beta-TM. Previously, we demonstrated that a six nucleotide mutation at the 5' end of exon 7, designated as ex-1, activated exon 7 splicing in nonmuscle cells. In this study, we show that the activating effect of this mutation is not the result of creating an exonic splicing enhancer (ESE) or disrupting a putative secondary structure. The sequence in exon 7 acts as a bona fide exonic splicing silencer (ESS), which is bound specifically by a trans-acting factor. Isolation and peptide sequencing reveal that this factor is hnRNP H, a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. Binding of hnRNP H correlates with the ESS activity. Furthermore, addition of antibodies that specifically recognizes hnRNP H to the splicing reactions or partial depletion of hnRNP H from nuclear extract activates exon 7 splicing in vitro and this effect can be reversed by addition of purified recombinant hnRNP H. These results indicate that hnRNP H participates in exclusion of exon 7 in nonmuscle cells. The involvement of hnRNP H in the activity of an ESS may represent a prototype for the regulation of tissue- and developmental-specific alternative splicing.

Alternative Splicing↗
PubMed1999

Donor site competition is involved in the regulation of alternative splicing of the rat beta-tropomyosin pre-mRNA.

The rat beta-tropomyosin (beta-TM) gene encodes both skeletal muscle beta-TM mRNA and nonmuscle TM-1 mRNA via alternative RNA splicing. This gene contains eleven exons: exons 1-5, 8, and 9 are common to both mRNAs; exons 6 and 11 are used in fibroblasts as well as in smooth muscle, whereas exons 7 and 10 are used in skeletal muscle. Previously we demonstrated that utilization of the 3' splice site of exon 7 is blocked in nonmuscle cells. In this study, we use both in vitro and in vivo methods to investigate the regulation of the 5' splice site of exon 7 in nonmuscle cells. The 5' splice site of exon 7 is used efficiently in the absence of flanking sequences, but its utilization is suppressed almost completely when the upstream exon 6 and intron 6 are present. The suppression of the 5' splice site of exon 7 does not result from the sequences at the 3' end of intron 6 that block the use of the 3' splice site of exon 7. However, mutating two conserved nucleotides GU at the 5' splice site of exon 6 results in the efficient use of the 5' splice site of exon 7. In addition, a mutation that changes the 5' splice site of exon 7 to the consensus U1 snRNA binding site strongly stimulates the splicing of exon 7 to the downstream common exon 8. Collectively, these studies demonstrate that 5' splice site competition is responsible, in part, for the suppression of exon 7 usage in nonmuscle cells.

Alternative Splicing↗
PubMed1999

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↗
PubMed1998

Mobility of cytochrome P450 in the endoplasmic reticulum membrane.

Cytochrome P450 2C2 is a resident endoplasmic reticulum (ER) membrane protein that is excluded from the recycling pathway and contains redundant retention functions in its N-terminal transmembrane signal/anchor sequence and its large, cytoplasmic domain. Unlike some ER resident proteins, cytochrome P450 2C2 does not contain any known retention/retrieval signals. One hypothesis to explain exclusion of resident ER proteins from the transport pathway is the formation of networks by interaction with other proteins that immobilize the proteins and are incompatible with packaging into the transport vesicles. To determine the mobility of cytochrome P450 in the ER membrane, chimeric proteins of either cytochrome P450 2C2, its catalytic domain, or the cytochrome P450 2C1 N-terminal signal/anchor sequence fused to green fluorescent protein (GFP) were expressed in transiently transfected COS1 cells. The laurate hydroxylase activities of cytochrome P450 2C2 or the catalytic domain with GFP fused to the C terminus were similar to the native enzyme. The mobilities of the proteins in the membrane were determined by recovery of fluorescence after photobleaching. Diffusion coefficients for all P450 chimeras were similar, ranging from 2.6 to 6.2 x 10(-10) cm2/s. A coefficient only slightly larger (7.1 x 10(-10) cm2/s) was determined for a GFP chimera that contained a C-terminal dilysine ER retention signal and entered the recycling pathway. These data indicate that exclusion of cytochrome P450 from the recycling pathway is not mediated by immobilization in large protein complexes.

Animals↗
PubMed1998

A conserved proline-rich sequence between the N-terminal signal-anchor and catalytic domains is required for assembly of functional cytochrome P450 2C2.

In cytochrome P450 2C2, the region which links the N-terminal signal anchor with the catalytic domain contains a highly conserved proline-rich region with the sequence, 30-PPGPTPFP-37. Mutation of proline-30 or proline-33 diminished activities of the mutants expressed in COS-1 cells (Chen, C., and Kemper, B. (1996) J. Biol. Chem. 271, 28697-28611). Substitution of alanine, proline, or arginine for glycine-32 abolished laurate hydroxylase activity of the proteins expressed in COS-1 cells, which suggests that this residue is also functionally important. To determine the basis for the decreased activity in COS-1 cells, the activities and spectral properties of mutant proteins expressed in insect cells and bacteria were determined. Substitution of alanine for either proline-30 or -33 resulted in reduced expression in insect cells of functional cytochrome P450 hemoprotein and an increase in the expression of inactive cytochrome P420. In contrast, substitution of alanine for proline-31, -35, or -37 resulted in hemoproteins with spectra similar to cytochrome P450 2C2 so that the amount of cytochrome P450 expressed in insect cells correlated with the activities of the mutants in COS-1 cells. The laurate hydroxylase activities per nanomole of cytochrome P450 in insect microsomes were similar for wild type and all mutants, indicating that, once folded, the catalytic activity of membrane-bound cytochrome P450 was not affected by the mutations. Expression in bacteria resulted in diminished expression of cytochrome P450 for all mutants, with the greatest decrease for the proline-30 and -33 mutants, and increased cytochrome P420. In contrast to the insect cell studies, the proline-30 and -33 mutants were inactive, while the other mutants had specific activities 30-70% of cytochrome P450 2C2. These data are consistent with a role for the proline-rich region in efficient assembly of cytochrome P450 2C2 in eukaryotic cells. Mutations of this region also may affect the conformational integrity of the proteins, which was revealed by assays of solubilized bacterially expressed proteins.

Animals↗
PubMed1998

The simplified two-pipette technique is more efficient than the conventional three-pipette method for blastomere biopsy in human embryos.

OBJECTIVE: To evaluate the efficiency and efficacy of a simplified two-pipette technique in comparison to the conventional three-pipette method; in the two-pipette method, a single, larger drilling/biopsy pipette is used to perform zona pellucida (ZP) drilling and blastomere aspiration for embryo biopsy. DESIGN: A preclinical, prospective, randomized, in vitro experiment. SETTING: The reproductive unit of a university teaching hospital. PATIENT(S): Ninety-five excess embryos at the two- to four-cell stage were obtained from 35 patients undergoing IVF. INTERVENTION(S): At the six- to eight-cell stage, 88 embryos were allocated randomly to three groups: group I for the conventional method (n = 29), group II for the simplified technique (n = 30), and group III for controls (n = 29). The embryos then were cultured in vitro. The retrieved blastomeres were fixed and examined with fluorescence in situ hybridization using X and Y probes simultaneously. MAIN OUTCOME MEASURE(S): Biopsy time, successful retrieval of a blastomere, fixation of the cell, signals developed from fluorescence in situ hybridization, and growth potential and hatching capacity of the biopsied embryos were evaluated. RESULT(S): The mean time (+/- SD) for biopsy of each embryo in group I (435 +/- 137 seconds) was significantly longer than that in group II (126 +/- 32 seconds). The success rates for obtaining an intact blastomere were not different between group I (93%) and group II (97%). The growth capacity to the blastocyst stage was similar among the three groups (34%, 37%, and 38%, respectively). However, the ZP-drilled and biopsied embryos of groups I and II had higher percentages of hatching (34% and 37%, respectively) and complete hatching (17% and 20%, respectively) than did those of group III (10% and 0, respectively). The blastomeres obtained by biopsy in groups I and II were equally fixed (90% vs. 90%, respectively) and shown in fluorescence in situ hybridization (79% vs. 80%, respectively). CONCLUSION(S): Compared with the conventional method, the simplified technique is more efficient and equally efficacious for blastomere biopsy in preimplantation genetic diagnosis.

Biopsy↗
PubMed1998

Effects of repeated abdominal paracentesis on uterine and intraovarian haemodynamics and pregnancy outcome in severe ovarian hyperstimulation syndrome.

The aims of this study were to investigate the effects of paracentesis on uterine and intraovarian haemodynamics by colour Doppler ultrasound and the influences of repeated paracentesis on pregnancy outcome in severe ovarian hyperstimulation syndrome (OHSS). Forty-one abdominal paracenteses were performed on seven pregnant women with tense ascites and eight thoracocenteses were performed on three pregnant women with pleural effusion. Pulsatility index (PI) and maximum peak systolic velocity (MPSV) of uterine and intraovarian arteries were measured before and after each intervention. The mean PI of uterine arteries was decreased significantly after paracentesis, but not after thoracocentesis. Furthermore, uterine PI was decreased in 13 out of 14 (92.9%) paracenteses with <2500 ml ascites removed, compared with eight out of 13 (61.5%) with >2500 ml ascites removed. After paracentesis, there were no significant changes in the intraovarian PI and MPSV in either group. The 24-hour urine output increased significantly in the paracentesis group, but not in the thoracocentesis group. There were no significant changes in haematocrit and electrolytes as a result of paracentesis. However, gradual falls in serum total proteins and albumin concentrations were observed in all patients after repeated paracentesis, necessitating post-paracentesis albumin infusion. There was no significant difference in miscarriage rates between the two groups. We conclude that repeated abdominal paracentesis increases uterine perfusion and has no adverse effects on pregnancy outcome in severe OHSS. Extraction of 2500 ml of ascitic fluid did not impair uterine perfusion.

Adult↗
PubMed1998

Cornual pregnancy after IVF-ET. A report of three cases.

BACKGROUND: Ectopic pregnancy is a well-known complication of in vitro fertilization/embryo transfer (IVF-ET). Although ectopic pregnancy after IVF-ET in patients with prior bilateral salpingectomy is uncommon, it can occur and may be a cornual implantation. Because of the possibility of early rupture with severe hemorrhage, special attention to cornual pregnancy after IVF-ET is warranted. CASES: Three cases of cornual pregnancy occurred after IVF-ET. Two of these patients had prior bilateral salpingectomy, whereas another had prior tuboplasty for tubal disease. CONCLUSION: Patients who had prior salpingectomy or tuboplasty with cornual patency undergoing IVF-ET are at risk for cornual pregnancy. Close monitoring of pregnancies in these patients is important to prevent a deleterious delay in treatment of a cornual pregnancy.

Adult↗
PubMed1997

Efficient assembly of functional cytochrome P450 2C2 requires a spacer sequence between the N-terminal signal anchor and catalytic domains.

Cytochromes P450 (P450) are anchored to the endoplasmic reticulum membrane by an N-terminal transmembrane sequence with the catalytic domain facing the cytoplasmic side. Within the peptide sequence linking these two domains in P450 2C2 is a glycine-rich region from residues 22 to 28. To examine the role of this region, deletion and substitution mutations were constructed, and the activities and spectral properties were determined for the mutant proteins expressed in COS-1 cells, insect cells, and bacteria. Deletion of residues 22 to 28 or substitution of 7 valines for this region inactivated the proteins in COS-1 cells, and no P450 species was detected for these mutations in bacteria or insect cells. Substitution of the three glycine residues with alanine or proline or the entire sequence from 22 to 28 with 7 alanines did not reduce lauric acid hydroxylase activity of the proteins expressed in COS-1 cells. Reducing the number of alanines substituted to 4, 3, and 2 progressively decreased activity in COS-1 cells to undetectable levels when 2 alanines were substituted. The loss of activity in COS-1 cells correlated with decreased expression of hemoprotein with a reduced difference spectrum of 450 nm (P450 species) and a corresponding increase in the inactive P420 species in insect cells and bacteria. The activities expressed per nanomole of P450 in insect microsomes were similar for P450 2C2 and the alanine substitution mutants, including the mutant with 2 alanines which was inactive in COS-1 cells. The rates of conversion of P450 to P420 resulting from incubation at 48 degrees C in vitro were not changed sufficiently to explain the increase in expressed P420 observed for the mutants with 3 or 7 alanines substituted. These data are consistent with a role for the residue 22-28 region as a linker that facilitates the folding of P450; however, once the protein is properly folded into the functional P450 species, this region has little influence on the stability and activity of the enzyme.

Animals↗
PubMed1997

Intravenous albumin does not prevent the development of severe ovarian hyperstimulation syndrome.

OBJECTIVE: To determine the efficacy of IV albumin in the prevention of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective study group with historical control. SETTING: University hospital-based IVF program. PATIENT(S): Between 1993 and 1995, 42 consecutive patients undergoing IVF-ET or tubal ET who had serum E2 levels > or = 3,600 pg/mL (conversion factor to SI unit, 3.671) on the day of hCG administration and/or > or = 20 oocytes retrieved were considered at high risk for severe OHSS and were selected as the control group. From December 1995 to October 1996, IV albumin was given to 30 consecutive patients who fulfilled these criteria. INTERVENTION(S): The treatment group received IV albumin after oocyte retrieval. MAIN OUTCOME MEASURE: Occurrence of severe OHSS. RESULT(S): None of the 16 patients in the treatment group in nonconception cycles developed severe OHSS, compared with 5 (21.7%) of 23 in the control group. In conception cycles, 4 (28.6%) of 14 patients in the treatment group developed severe OHSS, compared with 9 (47.4%) of 19 in the control group. All 4 patients with multiple pregnancies in the treatment group developed severe OHSS, compared with 3 (60%) of 5 in the control group. None of the 10 patients with singleton pregnancies in the treatment group developed severe OHSS, compared with 6 (42.9%) of 14 in the control group. CONCLUSION(S): Intravenous albumin prevents severe OHSS in high-risk patients who did not conceive or who carried singleton pregnancies, but not in the patients with high-order pregnancies.

Adult↗
PubMed1997

Peritoneal interleukin-10 increases with decrease in activated CD4+ T lymphocytes in women with endometriosis.

This study was performed to determine whether peritoneal T cells are suppressed in the CD4+ or CD8+ T cell subpopulation and whether they are Th1 or Th2 predominant in women with endometriosis. Immune cells in the peritoneal fluid (PF) were obtained from women undergoing laparoscopy for endometriosis or tubal ligation. Three-colour flow cytometry was utilized for immunophenotyping of peritoneal fluid mononuclear cells (PFMC). Concentrations of interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) produced by PFMC with and without mitogen stimulation and concentrations of IL-10 and IL-12 were measured in PF. The peritoneal T lymphocytes were predominantly of the Th1 type that produced much more IFN-gamma but less IL-4 or IL-5 in women with or without endometriosis. The decrease in peritoneal lymphocytes was significant in the HLA-DR+ CD4+ CD3+ subpopulation and the concentrations of peritoneal IL-10 and IL-12 were significantly elevated in women with early stage endometriosis. There was impaired IL-5 production by PFMC after phytohaemagglutinin stimulation in women with advanced stage endometriosis. We concluded that the activated peritoneal CD4+ Th1 cells from the women with endometriosis were decreased in number. The suppression of these T cells may be due to the elevation of IL-10 and IL-12 in the peritoneal fluid.

CD4-Positive T-Lymphocytes↗
PubMed1997

Paired human chorionic gonadotrophin determinations for the prediction of pregnancy outcome in assisted reproduction.

The aim of this study was to determine the prognostic value of single and paired measurements of serum concentrations of human chorionic gonadotrophin (HCG) for successful pregnancy following in-vitro fertilization (IVF) and tubal embryo transfer (TET). We analysed serum HCG concentrations 15 and 22 days after IVF or TET in 198 conception cycles. Cut-off values of serum HCG were determined by a receiver operating characteristic (ROC) curve. On the basis of single HCG samples on day 15 (HCG15) after transfer, using a cut-off value of HCG15 = 150 mIU/ml, the sensitivity was 71% and the specificity was 77%. The positive predictive value (HCG15 > or = 150 mIU/ml indicating a normal pregnancy) was 89%, while the negative predictive rate (HCG15 < 150 mIU/ml indicating an abnormal pregnancy) was 51%. Patients with HCG15 < 150 mIU/ml but HCG22/HCG15 ratio > or = 15, still had a 90% chance of normal pregnancy. However, in patients with HCG15 < 150 mIU/ml and an HCG22/HCG15 ratio < 15, there was an 84% chance of an abnormal pregnancy. We conclude that a single HCG15 determination combined with the ratio of HCG22 to HCG15 has a higher diagnostic accuracy for prediction of pregnancy outcome than either analysis alone.

Chorionic Gonadotropin↗
PubMed1997

Total antioxidant status and nitric oxide do not increase in peritoneal fluids from women with endometriosis.

To explore the role of nitric oxide (NO) and oxidative stress in the pathogenesis of adhesion formation and in endometriosis-associated infertility, we examined the peritoneal total antioxidant status (TAS) and the concentrations of products of NO metabolism in women with endometriosis (early stage, n = 12; advanced stage, n = 12) and in fertile women without endometriosis (n = 10). Peritoneal CA 125 and oestrogen and progesterone concentrations were also measured to examine their contributions to TAS and the production of NO. We failed to demonstrate any significant difference in TAS and in the products of NO metabolism in peritoneal fluids among women with early and advanced stages of endometriosis compared with fertile women without endometriosis during the early follicular phase. TAS and the concentration of the products of NO metabolism were not related to concentrations of CA 125, oestrogen or progesterone. The concentration of CA 125 in serum, but not in peritoneal fluid, was positively correlated with the severity of endometriosis. The volume of peritoneal fluid and the progesterone concentration were significantly increased in the group with advanced endometriosis. TAS and the concentration of the products of NO metabolism did not increase in peritoneal fluids from women with endometriosis during the early follicular phase. Their role in the pathophysiology of endometriosis needs to be explored further.

Antioxidants↗
PubMed1997

Acute management of complex cardiac injuries.

BACKGROUND: Injury to the heart has been studied extensively. However, a small group of patients with injuries to the coronary arteries or intracardiac structures may require a different operative approach. METHODS: Retrospective review of a cardiovascular injury database. RESULTS: Over a 20-year period, 711 cardiac injuries were treated. The mean age of the victims was 31.1 (90% men). Causes were primarily stab wounds (54%) and gunshot wounds (42%). Cardiac chambers injured included the right ventricle (40%), left ventricle (40%), right atrium (24%), and left atrium (3%). The overall mortality was 47%. Sixty complex injuries occurred. Of 21 left anterior descending coronary artery injuries (76.2% mortality), two patients presented with sufficient signs of life to warrant emergent coronary artery bypass (mortality 50%). There were seven circumflex/obtuse marginal coronary artery injuries, all treated with ligation (mortality 71.4%). Eight right/posterior descending coronary artery injuries (mortality 62.5%) were seen, and all but one were treated with ligation. The one patient not treated with ligation underwent coronary bypass and died. Delayed mitral valve replacement was performed for two valvular injuries (mitral). There were a total of 14 intracardiac fistulas (mortality 35.7%). All six of the surviving patients with ventricular septal defect required reoperation. CONCLUSION: The mortality for complex injuries (coronary, septal, valvular) was 53%. This group was a specific population that self-selected by surviving to operation. Acute operations for complex injuries (beyond cardiorrhaphy) were primarily heroic life-saving efforts. Reoperation for cardiac injuries was most common for septal or valvular injuries. Only 2% of all survivors required reoperation to correct a residual defect.

Acute Disease↗
PubMed1997

Serum estradiol level and oocyte number in predicting severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a relatively common and potentially life-threatening complication of ovarian stimulation, the pathogenesis of which remains unclear. To clarify the predictive values of serum estradiol levels and oocyte number in severe OHSS, and to investigate the impact of high serum estradiol levels on pregnancy outcome, we retrospectively analyzed clinical data from 431 cycles of ovarian stimulation for assisted reproduction performed from 1993 through 1995. Receiver operating characteristic plots were used to estimate the predictive power of the measured variables. The overall frequency of severe OHSS was 5.5%. Using a serum estradiol level of 3,600 pg/mL as the minimum cut-off value, the sensitivity was 58%, with a specificity of 92%, a positive predictive value of 29%, and a negative predictive value of 97%. The predictive power was similar when a cut-off point of 20 oocytes retrieved was used. The two criteria together gave a sensitivity of 33%, a specificity of 92%, a positive predictive value of 40%, and a negative predictive value of 98%. One of seven oocyte donors developed severe OHSS. The pregnancy rate was higher in patients with severe OHSS than in patients who did not develop this syndrome (73.9% vs 32.5%) but the pregnancy outcomes were not significantly different. We conclude that elevated estradiol concentrations and oocyte number appear to be helpful in predicting severe OHSS, but neither parameter by itself is predictive. This syndrome is rare in the absence of luteal hCG support, either exogenous or pregnancy-derived; when it occurs, there are usually extremely high preovulatory estradiol concentrations and numerous oocytes retrieved. High serum estradiol levels are unlikely to have adverse effects on pregnancy outcome in patients with severe OHSS.

Adult↗
PubMed1996

Different structural requirements at specific proline residue positions in the conserved proline-rich region of cytochrome P450 2C2.

Cytochrome P450 is anchored to the endoplasmic reticulum membrane by an N-terminal transmembrane sequence with the catalytic domain facing the cytoplasmic side. Within the peptide sequence linking these two domains is a highly conserved proline-rich region. In cytochrome P450 2C2, this region has the sequence 30PPGPTPFP37. To examine the structural requirements at these proline residues, each proline was replaced with alanine, glycine, valine, or an acidic amino acid, and the activities of the mutated proteins were determined in transfected COS-1 cells. Lauric acid 1omega-hydroxylase activities of Pro30 and Pro33 mutants were less than 10% of wild type for each substitution except for alanine, which was 25-30%. In striking contrast, substitutions at Pro31, including an acidic residue, did not substantially alter activity. At positions 35 and 37, acidic amino acid substitutions reduced activity to less than 10% of wild type while substitution of the other three amino acids had little effect. The tolerance of substitutions of charged residues at Pro31 suggests that the side chain at this position is exposed to a polar environment; conversely, the reduced activity with charged substitutions, but not with uncharged substitutions at positions 35 and 37, suggests that these residues are exposed to a hydrophobic environment, presumably within the folded protein. The loss of activity with substitutions at Pro30 and Pro33 implies that the motif PXXP is important for the formation of a functional cytochrome P450 and that this sequence might have a helical structure with a repeat of three, as in the left-handed poly-L-proline II helix. Insertion of alanine between positions 29 and 30 did not substantially affect activity, but insertions between either 33 and 34 or 37 and 38 resulted in activity less than 25% of wild type. These data indicate that the position of PXXP, relative to the sequence flanking it on the C-terminal side, may be important for its function.

Amino Acid Sequence↗
PubMed1996

Malignant ovarian germ cell tumors.

OBJECTIVES: Fifty patients with malignant ovarian germ cell tumors, which accounts for 10.8% of all ovarian malignancies, were treated from 1977 through 1994. Their cases are reviewed. METHODS: The histology includes endodermal sinus tumor (EST) in 15 patients, immature teratoma in 14, dysgerminoma in 13, and mixed germ cell tumor in eight. The mean age at presentation was 21.5 years and mean primary tumor diameter was 16 cm. All patients underwent surgery as the initial treatment, and 10 received more than one operation. Postoperative adjuvant chemotherapy was not given to cases with stage Ia immature teratoma and dysgerminoma. VAC (vincristine, actinomycin D, cyclophosphamide) and BVP (bleomycin, vinblastine, cisplatin) regimens were utilized in early 1980s for EST and advanced-stage tumors of immature teratoma and dysgerminoma. BEP (bleomycin, etoposide, cisplatin) and EP (etoposide, cisplatin) regimens were applied in advanced-stage disease and some stage I disease since 1990. VIP (VP-16, ifosfamide, cisplatin) regimen was employed as salvage regimen in cases where other combinations failed. RESULTS: alpha-Fetoprotein (AFP) was elevated in every tumor containing endodermal sinus element, and AFP served as a good indicator for prediction of tumor recurrence. The follow-up time ranged from 5 to 144 months with the mean of 54.5 months. CONCLUSIONS: The survival rate for EST was 54%, that for immature teratoma and dysgerminoma was 85% and 90%, respectively.

Adolescent↗