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Biomedical subjects

S Eliyahu

Publications and source records attributed to S Eliyahu.

At least 19 recordsLinked to original sources

Methotrexate as a possible cause of ovarian cysts formation: experience with women treated for ectopic pregnancies.

OBJECTIVE: To evaluate ovarian morphology after either salpingostomy or local injection of methotrexate (MTX) to cause regression of tubal pregnancies and to define potential correlation to other clinical parameters. DESIGN: Prospective longitudinal follow-up. SETTING: Department of Obstetrics and Gynecology, Haemek Medical Center, Afula, Israel. PATIENT(S): One hundred one women who were treated for tubal pregnancy: 58 by salpingostomy and 43 by local MTX injection. INTERVENTION(S): Serial blood sampling for beta-hCG and serial transvaginal sonographic evaluation. MAIN OUTCOME MEASURE(S): Appearance of cysts in the ovaries and their location with regard to the side in which the tubal pregnancy occurred. RESULT(S): In 6 of 42 (14.3%) patients who were treated with MTX, multiple (range, three to six) ovarian cysts occurred, as compared with 1 of 55 (1.8%) in those who underwent salpingostomy. The largest cyst was 9.4 cm in diameter. No relation of cyst occurrence to the side of the ectopic pregnancy was recorded. The women who developed cysts did not differ in either initial serum beta-hCG levels or in the rate of its subsequent regression. CONCLUSION(S): Multiple ovarian cysts may occur in 15% of patients who are treated with intra-amniotic MTX to cause regression of tubal ectopic pregnancy.

Adult↗

Early sonographic diagnosis of Jarcho-Levin syndrome: a prospective screening program in one family.

The purpose of this study was to evaluate the possibility of early diagnosis of Jarcho-Levin syndrome by ultrasound examination of the fetus. Over a period of 5 years, nine women from one Arab family, known to carry an autosomal recessive form of the disease, were prospectively and repeatedly examined using ultrasound. Out of eight pregnancies, four fetuses were diagnosed as being affected by the disease as early as 12 gestational weeks. Three elected to terminate the pregnancy before viability and one was born at term. There were no misdiagnoses. We conclude that early prenatal ultrasonographic diagnosis of Jarcho-Levin syndrome is feasible, although later sonographic confirmation is often warranted.

Abnormalities, Multiple↗

Essential thrombocythemia during pregnancy.

Essential thrombocythemia is a myeloproliferative disorder characterized by a persistent increase in the platelet count. The disease occurs more often in late middle age, but reports confirm the possibility of earlier occurrence. When the disease affects women during pregnancy, an adverse pregnancy outcome is possible: abortion, intrauterine fetal death, abruptio placentae, intrauterine growth retardation, and premature delivery. The possibility of thrombosis formation in this disease encouraged many physicians to use various treatments aimed at lowering the platelet count. Treatments used during pregnancy include acetylsalicylic acid, dipyridamole, heparin, and plateletpheresis. This article describes pregnancy outcomes and reviews the suggested treatments.

Adult↗

Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression.

Four of ten HLA-A2-restricted melanoma specific CTL that were derived from tumor-infiltrating lymphocytes (TIL) and administered to patients recognized the gp100 melanoma Ag and nine of ten recognized the MART-1 Ag. Adoptive transfer of the four gp100-reactive CTL, but not the other TIL, resulted in tumor regression when infused into autologous patients along with IL-2. Tumor regression was thus correlated with the recognition of gp100 by the administered T cells (p = 0.0048). To identify the epitopes recognized by these four gp100-reactive CTL, 169 peptides containing HLA-A2.1 binding motifs were synthesized and screened for their recognition by TIL using cytotoxicity and IFN-gamma release assays. Five gp100 epitopes (two for TIL620, three for TIL660, one for TIL1143, and two for TIL1200) were recognized by CTL derived from different patients. Five of eight HLA-A2 binding melanoma epitopes (five gp100, one MART-1/Melan-A, two tyrosinase) had intermediate binding affinity to HLA-A2.1. These gp100 epitopes may be responsible for mediating tumor rejection in vivo and thus may be useful for the development of immunotherapies for patients with melanoma.

Amino Acid Sequence↗

Comparison of 12- and 72-hour expectant management of premature rupture of membranes in term pregnancies.

OBJECTIVE: To compare 12-hour and 72-hour expectant management of premature rupture of membranes (PROM) in singleton term pregnancies. METHODS: In a prospective, nonrandomized study, 566 low-risk women with singleton term pregnancies presenting with PROM were assigned to either 12-hour or 72-hour expectant management. Patients who had not entered labor at the end of the assigned period were induced with oxytocin. The pregnancy outcome of both methods was compared with regard to infectious complications and method of delivery. RESULTS: There was no statistical difference in the rate of chorioamnionitis between the 12-hour and 72-hour expectant management groups (11.7 versus 12.7%; relative risk [RR] 0.9, 95% confidence interval [CI] 0.6-1.5; P = .83). Cesareans were performed to a similar degree in both groups (4.7 versus 6.7%; RR 0.7, 95% CI 0.3-1.4; P = .39). Fifty-five percent of the 12-hour group underwent oxytocin induction, compared with 17.5% of those in the 72-hour group (RR 5.8, 95% CI 3.9-8.5; P < .001). Women undergoing induction after 72-hour expectant management had an increased risk of cesarean delivery compared with those after a 12-hour wait (RR 5.9, 95% CI 2.3-15.1; P < .001). Overall, women in the 12-hour group had shorter admission-to-discharge times than the 72-hour group (5 versus 6 days, 95% CI of the difference 0.6-1.3; P < .01). CONCLUSION: Regimens of 12-hour and 72-hour expectant management of PROM are comparable regarding infectious complications and pregnancy outcome. However, the longer wait prolongs the interval to delivery and increases hospitalization costs.

Adolescent↗

Identification of MART-1-specific T-cell receptors: T cells utilizing distinct T-cell receptor variable and joining regions recognize the same tumor epitope.

Tumor-specific cytotoxic T lymphocytes (CTLs) can mediate tumor regression in patients with metastatic melanoma and play a central role in the immune response to cancer. The recent identification of shared melanoma antigens has raised the possibility of a limited melanoma-specific T-cell receptor (TCR) repertoire, but subsequent studies have been controversial and difficult to interpret without knowing which tumor-associated antigens (TAAs) are being recognized by specific TCRs. However, the recent cloning of several melanoma TAAs now allows for the identification of the specifically recognized TAA and its epitope. We evaluated the TCR of two clonal CD8+ CTL lines, A42 and 1E2, from two HLA-A2+ patients with metastatic melanoma. Both CTL lines were MART-1 specific, and both demonstrate reactivity to the same epitope when presented in an HLA-A2.1 context. The TCR genes of the two clones were sequenced. All of the productively rearranged A42 TCR beta chain genes were V beta 7/D beta 2.1/J beta 2.7/C beta 2; the TCR alpha chain genes were V alpha 21/J alpha 42/C alpha. The 1E2 TCR beta chain genes were V beta 3/D beta 1.1/J beta 1.1/C beta 1, and TCR alpha chains were V alpha 25/J alpha 54/C alpha. This study is the first report of TCR sequences specific for a melanoma epitope. These TCR clones may be useful for the development of more effective immunotherapies and in studies of the mechanism of T-cell recognition of tumor antigen. They also provide direct evidence that the immune system can provide more than one TCR capable of recognizing a TAA epitope.

Antigens, Neoplasm↗

Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection.

The cultured T-cell line TIL1200, established from the tumor-infiltrating lymphocytes (TILs) of a patient with advanced metastatic melanoma, recognized an antigen on most HLA-A2+ melanomas and on all HLA-A2+ cultured neonatal melanocytes in an HLA-A2 restricted manner but not on other types of tissues or cell lines tested. A cDNA encoding an antigen recognized by TIL1200 was isolated by screening an HLA-A2+ breast cancer cell line transfected with an expression cDNA library prepared from an HLA-A2+ melanoma cell line. The nucleotide and amino acid sequences of this cDNA were almost identical to the genes encoding glycoprotein gp100 or Pmel17 previously registered in the GenBank. Expression of this gene was restricted to melanoma and melanocyte cell lines and retina but was not expressed on other fresh or cultured normal tissues or other types of tumor tested. The cell line transfected with this cDNA also expressed antigen recognized by the melanoma-specific antibody HMB45 that bound to gp100. A synthetic 10-amino acid peptide derived from gp100 was recognized by TIL1200 in the context of HLA-A2.1. Since the administration of TIL1200 plus interleukin 2 resulted in regression of metastatic cancer in the autologous patient, gp100 is a possible tumor rejection antigen and may be useful for the development of immunotherapies for patients with melanoma.

Adult↗

Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes.

Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase-related protein-1 (gp75) were evaluated for recognition by HLA-A2-restricted melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recognized MART-1), but none of the TIL recognized tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART-1 were synthesized in an attempt to identify the epitopes recognized by TIL. Three peptides were recognized by TIL when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies.

Amino Acid Sequence↗

Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor.

By cDNA expression cloning we have isolated a gene encoding a shared human melanoma antigen recognized by HLA-A2 restricted autologous and allogenic tumor-infiltrating lymphocytes (TILs) from patients with metastatic melanoma. By using both transient and stable expression systems, transfection of this gene into non-antigen-expressing HLA-A2+ cell lines resulted in recognition by the antigen-specific TILs. The sequence of this cDNA revealed a previously undescribed putative transmembrane protein whose expression was restricted to melanoma and melanocyte cell lines and human retina but no other fresh or cultured normal tissues tested or other tumor histologies. Thus, we have identified a gene encoding a melanocyte lineage-specific protein (MART-1; melanoma antigen recognized by T cells 1) that is a widely shared melanoma antigen recognized by the T lymphocytes of patients with established malignancy. Identification of this gene opens possibilities for the development of immunotherapies for patients with melanoma.

Amino Acid Sequence↗

Sonographic presentation of Hirschsprung's disease. A case of an entirely aganglionic colon and ileum.

Prenatal sonographic presentation of Hirschsprung's disease has been considered non-specific and uncommon. This report presents a second-trimester fetus with an aganglionic colon and ileum diagnosed by the sonographic presentation of dilated fetal bowel loops, increased abdominal circumference, and mild polyhydramnios. The prenatal sonographic diagnosis of Hirschsprung's disease helped to expedite early neonatal treatment.

Adult↗

p53Val135 temperature sensitive mutant suppresses growth of human breast cancer cells.

One common step in the malignant progression of a wide variety of human cancers seems to be inactivation of the p53 gene, via point mutation or deletion or both; or overexpression of mutated protein with dominant transforming activity. This study shows a suppressive effect of wild type p53 on the growth of human breast cancer cells. Introduction of wild type p53 versus mutant into five human breast cancer cell lines containing mutant p53 resulted in a marked reduction in colony formation. Two of these were transfected with human wt p53 expression vectors and the other three were infected with retroviruses packaging human wt p53, both showing similar reduction in the number of surviving colonies, suggesting a role for wt p53 in suppression of breast cancer cell growth. Direct evidence for growth suppression was obtained by introduction of the temperature sensitive p53Val135 into Hs578T human breast cancer cells containing a mutant p53. This murine mutant allele p53Val135 functions as an oncogene at 37 degrees C as a tumor suppressor at 32 degrees C. The cell line generated was strongly growth inhibited at the restrictive temperature (31.5 degrees C), at which temperature the suppressor form is expressed. This inhibition of proliferation was reversible upon a temperature upshift. Analysis of the cell cycle distribution shows these growth suppressed cells to be inhibited in the G1 phase of the cell cycle. Thus wt p53 may have an important role in breast cancer tumorigenesis.

3T3 Cells↗

Routine thyroid function tests in infertile women: are they necessary?

To investigate the yield of routine thyroid function testing in infertile women, the records of 444 infertile women were categorized to standard infertility groups. Thyroid function was evaluated by measuring plasma free thyroxine and thyroid-stimulating hormone. All free thyroxine values were in the normal range (0.8 to 1.8 ng/ml), and only three thyroid-stimulating hormone values were higher than the normal range (0.15 to 4.5 mIU/L). The three women had ovulatory dysfunction. Thyroid function testing is more prudent in screening the subset of infertile women with ovulatory dysfunction and not as a routine measure in the infertile population.

Female↗

Laparoscopic management of adnexal cystic masses in postmenopausal women.

OBJECTIVE: To evaluate laparoscopic treatment of postmenopausal women with an adnexal cystic mass predicted to be benign. METHODS: Selection criteria were transvaginal sonographic appearance other than a complex cyst and a normal serum CA 125 level. During the period May 1988 to June 1993, 55 women fulfilled the criteria and underwent operative laparoscopy. During the same period, 75 postmenopausal women underwent exploratory laparotomy for an adnexal cystic mass that was complex in appearance or associated with elevated serum CA 125. RESULTS: Laparoscopic bilateral oophorectomy was performed in all 55 women. All had benign masses (positive predictive value 100%). Malignant tumors were found in 23 of the 75 women undergoing laparotomy (negative predictive value 30.7%). There was no significant difference in size of the tumors between women undergoing laparoscopy or laparotomy. CONCLUSION: Because of its safety and efficacy, laparoscopic management is the preferred procedure in postmenopausal women with a non-complex adnexal mass and a normal CA 125 level.

Adnexal Diseases↗

A successful pregnancy after bone marrow transplantation for severe aplastic anaemia with pre-transplant conditioning of total lymph-node irradiation and cyclophosphamide.

Pregnancy after bone marrow transplantation (BMT) for severe aplastic anaemia (SAA) is now an encouraging reality. We present a successful pregnancy, 4 years after BMT for SAA, in a woman being immunosuppressed before transplantation with cyclophosphamide and total lymph-node irradiation (TLI). No fetal complication was diagnosed.

Adolescent↗

Differential expression of MAGE-1, -2, and -3 messenger RNA in transformed and normal human cell lines.

The MAGE-1 gene codes for a tumor-specific antigen, MZ2-E, that elicited a cytotoxic T-lymphocyte response in the melanoma patient from whom it was derived. We have developed a simplified method, using polymerase chain reaction amplification of exon 3 followed by restriction enzyme pattern analysis, to distinguish expression of the MAGE-1 gene from MAGE-2 and MAGE-3, other members of this gene family. MAGE-1 mRNA was expressed in 53% of 17 melanoma lines, two of seven Epstein-Barr virus-transformed B-cell lines, and 2 of 5 breast cell lines including a line established form normal breast epithelium. MAGE-1 is not likely to be the common melanoma antigen recognized by the other HLA-A1- or HLA-A2-restricted cytotoxic T-lymphocytes examined in this study, but the fact that it is expressed in about 50% of melanoma cell lines makes it a reasonable target for the immunotherapy of patients bearing HLA-A1.

Antigens, Neoplasm↗