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Biomedical subjects

A Neri

Publications and source records attributed to A Neri.

At least 73 records · Page 4Linked to original sources
PubMed1997

Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts.

The NFKB-2 (Lyt-10) gene codes for an NF-kappaB-related transcription factor containing rel-polyG-ankyrin domains. Rearrangements of the NFKB-2 locus leading to the production of 3' truncated NFKB-2 proteins are recurrently found in lymphoid neoplasms, particularly cutaneous lymphomas. Such mutant NFKB-2 proteins have lost the ability to repress transcription that is typical of NFKB-2 subunit p52, and function as constitutive transcriptional activators. To verify whether the expression of abnormal NFKB-2 proteins can lead to malignant transformations in mammalian cells, we transfected human lymphoblastoid cell lines and murine fibroblasts (Balb/3T3) with expression vectors carrying the cDNAs coding for normal NFKB-2p52, Lyt-10C alpha or LB40 proteins, which are representative of the abnormal types found in lymphoma cases. The expression of both normal and mutant NFKB-2 proteins has a lethal effect on lymphoblastoid cells and a cytotoxic effect was also observed in murine fibroblasts. The fibroblast cell lines expressing Lyt-10C alpha or LB40, but not those expressing normal NFKB-2p52, were capable of forming colonies in soft agar. The analysis of individual clones revealed that cloning efficiency correlated with the expression levels of the abnormal proteins. Injection of the Lyt-10C alpha-transfected Balb cells in SCID mice led to tumor formation in all of the animals, whereas no tumors were observed in the mice injected with control or NFKB-2p52-transfected cells, thus indicating that abnormal NFKB-2 protein expression is tumorigenic in vivo. Our results show that mutant NFKB-2 proteins can lead to the transformed phenotype, and support the hypothesis that alterations in NFKB-2 genes may play a role in lymphomagenesis.

3T3 Cells↗
PubMed1997

Molecular and immunohistochemical analysis of the bcl-1/cyclin D1 gene in laryngeal squamous cell carcinomas: correlation of protein expression with lymph node metastases and advanced clinical stage.

BACKGROUND: The molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs) is still only partially understood, although genetic alterations affecting various protooncogenes or tumor suppressor genes have often been detected. METHODS: To improve their understanding of the role of cyclin D1 in the pathogenesis of LSCCs, the authors investigated the expression of cyclin D1 protein and the amplification status of the bcl-1/cyclin D1 locus in a panel of 58 pathologic samples. RESULTS: Expression of cyclin D1 protein was detected in 23 of the 58 patients (approximately 39%), 14 of whom had lymph node metastases (approximately 61%); of the remaining 35 patients without any detectable cyclin D1 expression, 7 had lymph node metastases (20%). Expression of cyclin D1 was detectable in 5% of the specimens of normal mucosa, 13% of those with mild-to-moderate dysplasia, and 25% of those with severe dysplasia. Amplification of the bcl-1/cyclin D1 locus was detected in 12 of the 49 LSCCs investigated (approximately 24%), 7 of which had lymph node metastases (approximately 58%); of the remaining 37 LSCCs with an apparently normal copy number of the cyclin D1 locus, 12 had lymph node metastases (approximately 32%). The authors found almost complete concordance between locus amplification and protein expression. Statistical analysis showed a correlation between cyclin D1 expression and both the presence of lymph node metastases (P < 0.01) and advanced clinical stage (P < 0.02). CONCLUSIONS: The authors' observations suggest that the deregulation of cyclin D1 expression may be involved in the pathogenesis of more aggressive LSCCs.

Adult↗
PubMed1997

Identification of a tumor-associated mutant form of the NF-kappaB RelA gene with reduced DNA-binding and transactivating activities.

Alterations of NF-kappaB family members have been found to be associated with various forms of lymphoid malignancies. In order to determine whether alterations of the RelA gene are involved in lymphomagenesis, we analysed a large and representative panel (200 cases) of such tumors. Southern blot analysis did not reveal any rearrangements or locus amplification, suggesting that structural alterations of the RelA gene may represent rare events in lymphoid neoplasia. By means of PCR-SSCP analysis, we were able to identify a single point mutation leading to amino acid substitution (codon 494, Glu-Asp) in the transactivating (TA) domain in one case of multiple myeloma. The mutated allele was expressed in the pathological bone marrow sample but not in the peripheral blood cells of the patient. We demonstrate that the RelA protein carrying this specific mutation (called RelA494D) has less transactivating ability than the normal RelA protein. Interestingly, the mutated protein has a lower affinity for kappaB binding sites both as a homodimer or in association with the NFKB1/p50 subunit. Transfection experiments using a Gal4-RelA494D fusion protein indicated that the mutation does not alter the intrinsic transactivating ability of the TA domain of RelA. Furthermore, in vitro translated RelA494D is able to dimerize efficiently with other NF-kappaB members, such as p50, cREL and Ikappa Balpha. Our data therefore suggest that this mutation may alter the specific structural conformation needed for the DNA interaction of RelA, and provide insights into the amino acid sequences involved in mediating the biological activities of RelA.

Animals↗
PubMed1997

Cyclin D1 protein expression is related to clinical progression in laryngeal squamous cell carcinomas.

The expression of cyclin D1 gene was investigated in 74 laryngeal squamous cell carcinomas (LSCCs) in order to determine its clinical and prognostic value. Overexpression of cyclin D1 was detected immunohistochemically using DCS6 monoclonal antibody on formalin-fixed, paraffin-embedded tissue sections. Cyclin D1 expression was detected in 22 of the 74 cases investigated (30 per cent), thirteen of which presented nodal metastases (59 per cent); of the patients without any detectable cyclin D1 protein expression, six presented nodal metastases (12 per cent). Cyclin D1 protein expression was found in five per cent of the specimens of normal mucosa, eight per cent of those with low-grade dysplasia and 20 per cent of those with high-grade dysplasia. A statistically significant association was found between cyclin D1 expression and the supraglottic site (p < 0.05), tumour extension (p < 0.001), the presence of lymph node metastases (p < 0.001), and advanced clinical stage (p < 0.001). Cyclin D1 expression analysis is an important tool in the selection of LSCC patients with an aggressive clinical course.

Aged↗
PubMed1997

Poor prognosis in non-villous splenic marginal zone cell lymphoma is associated with p53 mutations.

We have recently reported a series of 15 non-villous splenic marginal zone lymphoma patients, six of whom showed p53 mutations (40%). This molecular alteration did not correlate with any particular clinico-pathologic feature at diagnosis. After a median follow-up of 56 months, four cases evolved into aggressive fatal non-Hodgkin's lymphoma (NHL) and two had refractory progressive disease; interestingly, p53 mutations were demonstrated in five of these patients at diagnosis. As the patients with wild-type p53 presented responsive or indolent disease, this genetic alteration may be an early marker of aggressive transformation or refractoriness. p53 evaluation at diagnosis could be advisable in this particular subset of NHL.

Adolescent↗
PubMed1997

Isolated persistent fetal bradycardia in complete A-V block: a conservative approach is appropriate. A case report and a review of the literature.

Persistent fetal bradycardia is rarely encountered during pregnancy. When it is associated with a complete atrio-ventricular (A-V) block, it may prove dangerous to the fetus or newborn. The prenatal diagnosis is vital because it necessitates close follow-up during pregnancy to detect fetal compromise and proper preparation for delivery. We describe a woman who was found to be suffering from systemic lupus erythematosus during pregnancy. The fetus was diagnosed as having persistent fetal bradycardia due to complete A-V block at 28 weeks of gestation and was delivered at term with conservative management. The problems entailed in managing pregnancy and delivery of such fetuses are discussed.

Adult↗
PubMed1997

Incisional hernias after laparoscopy.

Laparoscopy, using a two-puncture technique, has been used for a variety of gynecologic indications for more than two decades. The procedure is considered safe and effective, although rare complications, such as incisional hernias, have been reported. In this review, the issue of postlaparoscopic incisional hernias is discussed in terms of incidence, predisposing factors, time of appearance, and preventive measures. With the evolvement of operative laparoscopy, larger trocars and cannulas have been introduced, increasing the incidence of postlaparoscopic incisional hernias. Awareness of the possibility of this complication will lead to the use of proper surgical techniques, as suggested, while knowledge of the postoperative signs and symptoms will lead to early diagnosis and prevention of sequelae.

Female↗
PubMed1997

High Prevalence of Vibrio cholerae Non-O1 Carrying Heat-Stable-Enterotoxin-Encoding Genes among Vibrio Isolates from a Temperate-Climate River Basin of Central Italy.

Vibrio spp. of clinical interest from the Arno River basin (Tuscany, Italy) were investigated in this study. Vibrios were isolated from 70% of water samples. Vibrio cholerae non-O1 was the most prevalent species (82% of isolates), followed by Vibrio mimicus (10%) and Vibrio metschnikovii (8%). Recovery of vibrios was correlated with temperature, pH, and various indicators of municipal pollution. None of the 150 Vibrio isolates carried ctx-related genomic sequences, whereas 18 (14.6%) of the 123 V. cholerae non-O1 isolates and 1 (6.7%) of the 15 V. mimicus isolates carried sto alleles. These findings indicate that considerable circulation of sto-positive vibrios may occur in temperate-climate freshwater environments.

Journal Article↗
PubMed1997

Clinical evaluation of a new model of a transcutaneous electrical nerve stimulation device for the management of primary dysmenorrhea.

Transcutaneous electrical nerve stimulation (TENS) has been proven effective in pain relief of primary dysmenorrhea (PD). We evaluated the efficacy of a new TENS device (Freelady, Life Care, Tiberias, Israel), designed to correct disadvantages of older models used in previous studies, in 102 nulliparous women with PD, who were treated with various types of pain relief medications. Marked pain relief was reported by 58 patients (56.9%) and moderate relief by 31 (30.4%). These subjective findings were supported by the fact that the same number of patients (58 and 31) either stopped analgesic use altogether during the trial or reduced the quantity of analgesics, respectively. The device examined proved to be efficient and safe in controlling the pain and disability caused by PD.

Adolescent↗
PubMed1997

MDM-2 oncoprotein overexpression in laryngeal squamous cell carcinoma: association with wild-type p53 accumulation.

The MDM-2 gene encodes for a nuclear phosphoprotein that binds p53 and inhibits its ability to activate transcription by concealing the p53 activation domain. It has been suggested that MDM-2 overexpression might represent an alternative mechanism by which p53-mediated pathways are inactivated in human tumors. MDM-2 overexpression can be detected by immunohistochemical analysis as a result of gene amplification and/or increased mRNA expression. We studied MDM-2 gene amplification and protein overexpression in 46 and 50 cases, respectively, of laryngeal squamous cell carcinomas previously analyzed for p53 gene alterations. Not one of the cases showed MDM-2 gene amplification, whereas MDM-2 nuclear immunoreactivity was found in 17 tumors (34%). In 10 of these, coexpression of p53 protein was detectable in the absence of gene mutations in exons 5 through 9 (P = .03). Likewise, MDM-2 was also overexpressed in 18 (46%) of 39 morphologically normal mucosa samples, 15 (50%) of 30 preneoplastic lesions, and 9 (40%) of 22 cases of severe dysplasia. Finally, we found no significant correlations between MDM-2 expression (neither per se nor in association with wild-type or mutated p53), and the evaluated clinicopathologic parameters of histologic grade, lymph node status, or clinical stage. Our results suggest that MDM-2 gene amplification might not occur in laryngeal carcinomas and that MDM-2 protein overexpression might represent an alternative mechanism by which p53 is inactivated in the early stages of laryngeal cancer tumorigenesis.

Adult↗
PubMed1997

Posttransplantation cutaneous B-cell lymphoma with monoclonal Epstein-Barr virus infection, responding to acyclovir and reduction in immunosuppression.

Posttransplantation lymphoproliferative disorders (PTLDs) represent an important complication of solid organ transplantation. The main causative factor of PTLDs seems to be the intensity and type of immunosuppressive therapy and the frequent occurrence of Epstein-Barr virus infection. PTLDs that are disseminated at diagnosis or present late after transplantation generally share an unfavorable prognosis and are unlikely to regress in response to reduction in immunosuppressive therapy. We describe a case of cutaneous B-cell lymphoma occurring 4 years after heart transplantation in which molecular analysis revealed a monoclonal pattern of Epstein-Barr virus infection and immunoglobulin gene rearrangement. In spite of its monoclonal nature and late occurrence, the lymphomatous lesions regressed completely after antiviral treatment and a reduction in immunosuppressive therapy.

Acyclovir↗
PubMed1997

Transcutaneous electrical nerve stimulation (TENS) as a pain-relief device in obstetrics and gynecology.

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological and non-invasive pain-relief method that has been proven effective for a variety of conditions. Electrical therapy has been recognized for a long time but its practical clinical application in the form of TENS has been evaluated only during the last 30 years as a result of several theories on pain. The most known of these with regard to TENS development is the "gate theory", although several others have also played a role. In obstetrics and gynecology, TENS has been found to be effective in alleviating labor pain and in the treatment of primary dysmenorrhea. It has also been used successfully following obstetric and gynecologic surgery. In order to be effective in clinical use for obstetric and gynecologic indications, a TENS device must have certain properties, which are detailed in this review. Although new TENS devices that meet all the necessary requirements have been developed and tested, their use is still far from widespread. Patients and medical staff should be encouraged to try the TENS device for obstetric and gynecologic indications, since it is non-invasive, efficient, and easy to use.

Dysmenorrhea↗
PubMed1996

Restoration of the transcription activation function to mutant p53 in human cancer cells.

The p53 tumor suppressor gene product is a sequence-specific transcription activator frequently mutated in a variety of human malignancies. Typically, tumor-derived p53 missense mutants are defective in DNA binding and this is likely to result in a failure to active p53-regulated genes. Hence, restoring function to mutant p53 represents an attractive target to develop a novel cancer chemotherapeutic agent. We now show that a small chemically modified peptide derived from p53 restores sequence-specific DNA binding to a subset of p53 mutants. Moreover, when microinjected into human colon carcinoma cells this peptide restores the transcription activation function to endogenous mutant p53 protein. This is the first example showing that a small peptide molecule can reverse the effect of several inactivating missense mutations and restore protein function.

Amino Acid Sequence↗
PubMed1996

The missing forgotten intrauterine contraceptive device.

Failure to locate the strings of an intrauterine contraceptive device may mean that the device is within the uterine cavity, was expelled or, worst of all, has perforated the uterine wall. We describe a 36-year-old woman complaining of infertility in whom two missing devices were found within the pelvis after having perforated the uterus. This report demonstrates the need to investigate every case of a missing intrauterine contraceptive device. An algorithm for the proper management of such cases is suggested.

Adult↗
PubMed1996

Women's attitudes towards menopause and hormone replacement therapy.

OBJECTIVES: To determine how women aged 50 years or more feel about menopause, and their knowledge, use of and attitude toward hormone replacement therapy (HRT). METHODS: All study participants resided in a single urban community in central Israel and were selected at random from the computerized government registry. Responses were collected by either telephone interview (n = 171) or mailed questionnaire (n = 41) and were analyzed for the group as a whole and by different demographic and attitudinal factors. RESULTS: Most (80%) of the women had a positive or neutral attitude to menopause. More than 80% had heard of HRT, 55% of whom from a physician. Of these, 12% were currently using HRT and 9.5% had done so in the past. Varied reasons were offered for starting or stopping treatment. CONCLUSIONS: Although the great majority of the participants had heard of HRT, and most of these had spoken about it with a doctor, only a small percentage were currently under therapy or had been in the past. We believe gynecologists should devote more effort to public education, in that those women who had discussed HRT with their physician were more likely to use it.

Aged↗
PubMed1996

Abdominal pregnancy following in vitro fertilization in a patient with previous bilateral salpingectomy.

BACKGROUND: We present the first case of abdominal pregnancy after in vitro fertilization and embryo transfer in a patient without oviducts. CASE: A 38-year-old woman, who previously had had two salpingectomies because of two tubal pregnancies, was admitted to our department with intermittent vaginal bleeding and abdominal pain, 21 days after embryo transfer. Exploratory laparotomy revealed a moderate amount of blood in the peritoneal cavity and a mass consisting of blood clots and tissue fragments attached to the posterior aspect of the right broad ligament. Pathologic examination confirmed the diagnosis of abdominal pregnancy. CONCLUSION: Abdominal pregnancy may be the outcome of embryo transfer and should hence be considered a potential complication of the procedure.

Adult↗
PubMed1996

Community screening to reveal iron deficiency in healthy menstruating women in Israelian suburbs.

OBJECTIVE: To determine the incidence of iron deficiency among healthy women of child-bearing age, study the predictive value of blood hemoglobin level for this condition and assess the efficacy of a community screening program. METHOD: All healthy women aged 18-45 years registered with one community outpatient clinic were requested to complete a questionnaire on present and past medical history; one-third also completed a second questionnaire on symptoms related to anemia. All underwent a blood test for hemoglobin, serum-saturated transferrin and ferritin levels. RESULTS: Of the 163 women who complied (83% of the targeted population), 25.8% were diagnosed as having iron deficiency; of these 40.5% had a hemoglobin level of 12 g% or higher. The most sensitive indicator proved to be serum ferritin level. Iron deficiency was more prevalent in women with a personal history of anemia. Only 34.1% of the study group completed follow-up. CONCLUSION: There is a high incidence of iron deficiency among women of childbearing age. However, because of the surprisingly low compliance with follow-up visits, preventive periodic screening of healthy menstruating women using routine blood tests is not recommended at this time, except for those with specific complaints or who are at high risk.

Adolescent↗