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Biomedical subjects

R Jaffe

Publications and source records attributed to R Jaffe.

At least 19 recordsLinked to original sources

Expression of Epstein-Barr virus-encoded small RNA (by the EBER-1 gene) in liver specimens from transplant recipients with post-transplantation lymphoproliferative disease.

BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disease (PTLD) develops in 1 to 10 percent of transplant recipients, in whom it can be treated by a reduction in the level of immunosuppression. We postulated that the tissue expression of the small RNA transcribed by the EBER-1 gene during latent EBV infection would identify patients at risk for PTLD. METHODS: We studied EBER-1 gene expression in liver specimens obtained from 24 patients 2 days to 22 months before the development of PTLD, using in situ hybridization with an oligonucleotide probe. Control specimens were obtained from 20 recipients of allografts with signs of injury due to organ retrieval, acute graft rejection, or viral hepatitis in whom PTLD had not developed 9 to 71 months after the biopsy. RESULTS: Of the 24 patients with PTLD, 17 (71 percent) had specimens in which 1 to 40 percent of mononuclear cells were positive for the EBER-1 gene. In addition, 10 of these 17 patients (59 percent) had specimens with histopathological changes suggestive of EBV hepatitis. In every case, EBER-1-positive cells were found within the lymphoproliferative lesions identified at autopsy. Only 2 of the 20 controls (10 percent) had specimens with EBER-1-positive cells (P < 0.001), and such cells were rare. CONCLUSIONS: EBER-1 gene expression in liver tissue precedes the occurrence of clinical and histologic PTLD. The possibility of identifying patients at risk by the method we describe here and preventing the occurrence of PTLD by a timely reduction of immunosuppression needs to be addressed by future prospective studies.

Adolescent

Quantitative EEG in elderly depressives.

Thirty-one elderly depressive patients were evaluated with topographic, quantitative EEG using relative measures, absolute measures, and computations of interhemispheric asymmetry and interhemispheric coherence in four frequency bands: delta, theta, alpha and beta. Patients were found to have lower than normal delta, higher than normal theta, higher than normal alpha and lower than normal beta values. EEG values were greater over the left than the right hemisphere in theta, alpha and beta bands. Lower than normal anterior interhemispheric coherence was found in all four frequency bands.

Aged

Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: anti-SSEA-1 and MOPC 104E in mouse teratocarcinomas and normal tissues.

Methotrexate (MTX) was coupled to the tumor-targeting monoclonal IgM, anti-SSEA-1 and the non-targeting myeloma IgM, MOPC 104E. At 24-h intervals following injection, drug deposition in MH-15 teratocarcinomas and in several normal tissues was followed by immunoperoxidase microscopy using the M16 monoclonal antibody to MTX. MTX-anti-SSEA-1 was deposited on the surface and in the interior of living tumor cells 24 h after injection; at 48 h and after, only low-level binding to necrotic tissue was found. There was no significant gradation in staining from the outside to the interior of the tumors. In tumors, the control MOPC 104E immunoconjugate was detectable only in necrotic tissue. Binding to SSEA-1-expressing normal tissues was undetectable, except for pericryptal fibroblasts in the small intestine. No significant pathology was found in normal tissues that are SSEA-1 positive. High levels of the immunoconjugate were detected in the liver, where MTX was found predominantly in Kupffer cells and possibly in hepatocytes; again, no significant morphological changes were associated with this retention. Thus tumor-associated antigens can be suitable targets for antibody-drug conjugates even when present in normal tissues and in large quantities, provided that the antigens in normal tissues are inaccessible. Moreover, deposition in viable tumor tissue can be assessed using monoclonal antibodies to methotrexate.

Animals

Therapeutic maturation of endometrium in in vitro fertilization and embryo transfer.

OBJECTIVE: To provide an up-to-date review of studies that have examined the relative role of endometrial development in in vitro fertilization (IVF) and embryo transfer (ET) treatment in relation to the treatment outcome. DATA IDENTIFICATION: The most important published studies and personal communications related to this topic have been identified through a computerized bibliographical search (MEDLINE). STUDY SELECTION: Studies that have evaluated the endometrial maturation in IVF and ET treatment with respect to different treatment protocols of ovarian stimulation. Clinical trials exploring the efficacy of various combinations of hormonal supplementation that aim to improve the endometrial environment and treatment outcome. Publications and personal communications reporting a variety of treatment protocols and drugs utilized for the creation of artificial endometrial cycles in IVF treatment employing donated eggs. RESULTS: Ovarian stimulation frequently adversely affects the process of endometrial maturation. Various kinds of hormonal supplementation, used in clomiphene citrate- and/or human menopausal gonadotropin (hMG)-stimulated cycles have not improved treatment outcome. Human chorionic gonadotropin or natural progesterone (P) supplementation administered after controlled ovarian stimulation with gonadotropin-releasing hormone and hMG effectively corrected the luteal phase defect and resulted in an improved conception rate. The endometrium of agonadal women is highly conducive to hormonal manipulation. All estrogen preparations used effectively promoted endometrial growth and proliferation. Natural P is superior to synthetic progestins for induction of receptive secretory endometrium. CONCLUSION: The development of adequately receptive endometrium is a major factor determining the outcome of IVF and ET treatment.

Embryo Transfer

Uterine remodelling following conservative myomectomy. Ultrasonographic evaluation.

Uterine leiomyomata develop during the reproductive years and may interfere with fertility through mechanisms as yet not fully understood. A developing intramural or large submucosal leiomyoma causes hypertrophy of the myometrium. Conservative myomectomy, as opposed to hysterectomy, is the preferred surgical procedure for patients who wish to preserve their fertility. Ten patients were ultrasonographically evaluated at monthly intervals following myomectomy and the changes in uterine (myometrial) volume were assessed. There was a gradual decrease in uterine volume in all patients during the six months following removal of intramural and submucosal leiomyomata. The most remarkable decrease in size occurred during the initial two to three months for the majority of the patients. The impact of this process on fertility should be further evaluated. One of the intriguing questions is whether the period of uterine shrinkage represents the time of the healing process during which conception should be prevented.

Adolescent

Color Doppler imaging in the assessment of uteroplacental blood flow in abnormal first trimester intrauterine pregnancies. An attempt to define etiologic mechanisms.

The addition of color Doppler imaging (CDI) to the vaginal probe now enables sonographers to study more accurately the maternal-fetal circulation at the early stages of the gestation. Doppler studies of normal intrauterine first trimester gestations have been published, and our investigation was an attempt to study uteroplacental blood flow in abnormal intrauterine first trimester gestations. Although the calculated indices did not differ significantly from those found in normal gestations, we did find a higher rate of color detection in gestations defined as anembryonic as compared to those defined as missed abortions. Circulation abnormalities probably play a significant role in early pregnancy failures, and we believe CDI will help define the different etiologic mechanisms causing these early complications.

Abortion, Missed

Antenatal classification of hydrops fetalis.

Among 12,572 pregnant women referred for ultrasound examination from 1985-1990, 76 fetuses had ultrasonographic findings of hydrops fetalis, ten immune and 66 nonimmune. Fetuses with cystic hygroma (20), heart defects or arrhythmias (13), or other congenital anomalies (15) accounted for the majority of the nonimmune cases. Antenatal chromosomal studies were available in 42 fetuses with nonimmune hydrops, of which 14 (34%) were abnormal with seven monosomes and six trisomies. Seventeen cases of hydrops (22%) were classified as idiopathic because they had no recognizable etiology. It is concluded that: 1) The ultrasonographic incidence of fetal hydrops in referral centers can be as high as one in 165 pregnancies; 2) most cases of fetal hydrops are of the nonimmune type, which can occur in a low-risk population and can be detected with early second-trimester ultrasound screening; and 3) the complexity of this condition and the high rate of chromosomal abnormalities require referral to a high-risk center for evaluation and pregnancy management.

Chromosome Aberrations

Transvaginal color Doppler imaging in the assessment of uteroplacental blood flow in the normal first-trimester pregnancy.

Characteristic changes of low resistance and high diastolic blood flow velocity were identified by Doppler studies starting in the early phase of the second trimester. These changes were attributed by some authors to trophoblastic invasion of the uterine vasculature converting the uterus into a low-resistance organ. Because of technical limitations previous studies were confined to the uterine artery and its main branches. With the development of color Doppler and transvaginal ultrasonography we can now identify blood flow in various small vessels in the placental bed. This study was performed to assess the ability of color Doppler ultrasonography to evaluate subtrophoblastic blood flow by color identification in the early phase of normal pregnancy from 5 to 9 weeks' gestation. Results show that the characteristic increase in diastolic blood flow is evident as early as 5 weeks' gestation.

Female

The branchio-oculo-facial syndrome.

We review 13 reported cases and add the evaluations of 2 new patients with the branchio-oculo-facial (BOF) syndrome, a recently delineated autosomal dominant disorder with highly variable expression. This condition has a distinctive phenotype with characteristic craniofacial abnormalities consisting of aplastic or hemangiomatous cervical skin lesions with or without branchial sinuses; malformed, rotated auricles; and ocular abnormalities, which include microphthalmia or anophthalmia, coloboma, and cataract. The term pseudocleft has been used to describe the upper lip and philtrum abnormality found in mild cases, but the expression may extend to that of a complete cleft lip and palate. This unique disorder may go undetected in patients followed in cleft palate or craniofacial clinics and may not be recognized in patients with mild expressions. Genetic counseling for affected individuals is imperative because of the 50 percent recurrence risk. We emphasize the multidisciplinary care required to correct their craniofacial anomalies.

Branchial Region

The systemic distribution of Epstein-Barr virus genomes in fatal post-transplantation lymphoproliferative disorders. An in situ hybridization study.

The systemic distribution of Epstein-Barr virus (EBV) genomes was studied in paraffin-embedded tissues from 12 fatal cases of Post-transplantation lymphoproliferative disease (PTLD), using an in situ hybridization technique employing an alpha-35S-dCTP-radiolabeled BamHI-W fragment of EBV DNA. The presence of EBV was documented in various PTLD-involved organs. The hybridization signal for the virus localized predominantly in the abnormal lymphoid cells, but signals also were detected in hepatocytes and/or adrenal cortical cells in five cases. The distribution of autoradiographic label within the lymphoid cells was focal and its intensity varied from field to field suggesting a nonuniformity of the viral genomic load in the infected tissues. Recruitment of EBV genome-bearing cells was not observed into inflammatory mononuclear infiltrates found in organs without histopathologic evidence of PTLD.

Adrenal Glands

Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells.

Oral immunization with an attenuated Salmonella typhimurium recombinant containing the full-length Plasmodium berghei circumsporozoite (CS) gene induces protective immunity against P. berghei sporozoite challenge in the absence of antibody. We found that this immunity was mediated through the induction of specific CD8+ T cells since in vivo elimination of CD8+ cells abrogated protection. In vitro studies revealed that this Salmonella-P. berghei CS recombinant induced class I-restricted CD8+ cytotoxic T cells that are directed against the P. berghei CS peptide epitope spanning amino acids 242-253. This is the same peptide that previously was identified as the target of cytotoxic T lymphocytes (CTL) induced by sporozoite immunization. Salmonella-P. falciparum CS recombinants were constructed that contained either the full-length CS gene or a repeatless gene consisting of CS flanking sequences. Both of these vaccines were able to induce CD8+ CTL directed against P. falciparum CS peptide 371-390, which is identical to the target of CTL induced by sporozoites and vaccinia CS recombinants. These results directly demonstrate the ability of an intracellular bacteria such as Salmonella to induce class I-restricted CD8+ CTL and illustrate the importance of CD8+ CTL in immunity to malaria.

Animals

Primary paraovarian cystadenocarcinoma: clinical and management aspects and literature review.

Two cases of primary paraovarian-origin serous cystadenocarcinoma, one invasive and one of low malignant potential, are presented. Both were diagnosed in postmenopausal women and were initially treated surgically. As of this writing, both women have survived 48 months past their initial diagnosis and have no clinically detectable disease. Clinical aspects and management problems of this fairly recently identified and rare entity are discussed and the literature on primary paraovarian malignant epithelial tumors is reviewed.

Aged

Role of prolonged excessive estrogen stimulation in the pathogenesis of endometrial sarcomas: two cases and a review of the literature.

Two cases of endometrial sarcoma that developed many years after exposure to unopposed exogenous and endogenous estrogens, with no previous pelvic irradiation, are described. The literature is reviewed and the possible effect of prolonged unopposed estrogen stimulation is suggested as an etiologic factor in such extremely rare conditions. These cases add additional support to the assumption that prolonged and excessive endogenous or exogenous unopposed estrogen stimulation of the uterus may increase the risk of endometrial sarcoma.

Aged