PubMed HealthSearch

Biomedical subjects

L Jaffe

Publications and source records attributed to L Jaffe.

15 recordsLinked to original sources

Developmental failure of chimeric embryos expressing high levels of H-2Dd transplantation antigens.

The absence of expression of class I products of the major histocompatibility complex at early stages of development is thought to play a key role in maternal tolerance of the fetal allograft. To test this, we developed a strategy that would allow us to describe the consequences of overexpression of the H-2Dd transplantation antigen in the developing embryo. A construct containing the H-2Dd gene under control of the human beta-actin promoter was transfected into pluripotent embryonic stem (ES) cells. Particularly in this case, since overexpression of major histocompatibility complex class I gene products may profoundly affect embryonic development, an important advantage of the ES cell system is the ability to analyze gene expression and study effects on cell growth and differentiation in vitro. ES cells do not constitutively express beta 2-microglobulin. Consistent with this, H-2Dd H chains expressed by ES cell transformants were not associated with beta 2-microglobulin or transported to the cell surface. Significant levels of beta 2-microglobulin and H-2Dd membrane glycoproteins were expressed following differentiation in vitro. H-2Dd-transfected ES cells gave rise to a wide range of differentiated cell types, and there was no evidence to suggest that expression of the introduced H-2Dd gene affects the differentiation abilities of ES cells in vitro. When introduced into blastocysts, H-2Dd-transfected ES cells extensively contribute to embryonic and extraembryonic tissues, but this results in the failure of chimeric conceptuses at midgestation. Considering that transgenic chimeras cannot be rescued by transfer into syngeneic foster females, it seems likely that nonimmunological mechanisms are responsible for these prenatal lethalities.

Animals

Predictors of repeat pregnancy outcome among black and Puerto Rican adolescent mothers.

This prospective study investigated predictors of repeat pregnancies by 12 months after the delivery of a first child and their outcomes in inner-city adolescent mothers. The sample included four groups: those who had therapeutic abortions, miscarriages, full-term deliveries, and no repeat pregnancy. The therapeutic abortion group had more pregnancies before their first delivery (41%) than did full term (20%) and no repeat (15%), p less than .01. More delayed grade placement was found in therapeutic abortion -1.6 years (1.3) and full term -1.8 years (.9) than in no repeat pregnancy -.6 years (1.1), p less .001. Reading achievement scores were higher in no repeat 86.3 (17.1) than in full term 75.0 (16.5), p less than .05. School attendance was higher in no repeat (65%) than in therapeutic abortion (35%) and full-term (24%) p less than .01 groups. Depressive symptoms at baseline were higher among therapeutic aborters 18.9 (9.9) than among full term 10.2 (8.2) and no repeat pregnancy groups 12.2 (6.2). Logistic regression analyses identified delayed grade placement as the most important predictor of pregnancy outcome.

Achievement

MHC class I surface expression in embryo-derived cell lines inducible with peptide or interferon.

It has long been recognized that the absence of expression of products of the major histocompatibility complex (MHC) during early development might allow the fetus to escape recognition by maternal lymphocytes. In addition to the MHC class I heavy chain and beta 2-microglobulin, antigenic peptide is an essential structural component of the class I molecule. Indeed, there is evidence that MHC-linked genes encoding peptide transporter molecules and possibly components of a proteolytic complex are necessary for MHC class I assembly and stability at the cell surface. Here we demonstrate that embryonic cells in general show a defect in MHC class I assembly. Surface expression was rescued in the presence of an appropriate antigenic peptide, or by treatment with interferon. Consistent with this, HAM1 messenger RNA was not constitutively expressed, but was inducible by interferon, and during differentiation in vitro. Thus, tolerance of the fetal allograft may in part be controlled at the level of peptide-dependent MHC class I assembly.

Animals

Distinct patterns of expression of MHC class I and beta 2-microglobulin transcripts at early stages of mouse development.

The class I surface Ag recognized during tissue graft rejection are composed of a 40- to 45-kDa H chain and a 12-kDa L chain, beta 2-microglobulin (beta 2m). Regulation of MHC gene expression during early development is thought to play an essential role in maternal tolerance of the fetal allograft. Here we used in situ hybridization techniques to characterize the temporal and spatial pattern of expression of MHC class I mRNA in the developing mouse embryo. MHC class I transcripts were initially detected at day 9.5 postcoitus in the primary and secondary trophoblast giant cell populations. At this stage, none of the remaining fetal components of the developing placenta expresses MHC class I mRNA. By contrast, the outer zone of trophoblast giant cells is the only trophectoderm-derived tissue in the developing placenta that does not express detectable levels of beta 2m mRNA. These findings indicate that the onset of MHC class I and beta 2m gene expression in early postimplantation stage embryos is not coordinately regulated. In addition, we made use of pluripotent embryonic stem (ES) cells to study developmental regulation of MHC class I and beta 2m gene expression in vitro. ES cells can be induced to form endoderm-like cells by the technique of suspension culture. In contrast to retinoic acid-treated F9 cells, the endoderm derived from ES cells expressed high levels of beta 2m mRNA, but no detectable MHC class I transcripts. These findings are consistent with results of our in situ hybridization experiments showing high levels of expression of beta 2m mRNA, and extremely weak expression of MHC class I transcripts in derivatives of the visceral endoderm in vivo.

Animals

Analysis of beta 2-microglobulin gene expression in the developing mouse embryo and placenta.

The major transplantation (MHC) Ag in the mouse are cell-surface glycoproteins composed of a 40- to 45-kDa H chain and a 12-kDa L chain, beta 2-microglobulin (beta 2 m). Regulation of MHC gene expression during early development is thought to play a critical role in maternal tolerance of the fetal allograft. We have used in situ hybridization techniques to characterize the temporal and spatial pattern of expression of the beta 2 m gene in the developing mouse embryo. beta 2 m mRNA is first detected in the extra-embryonic derivatives of the early primitive streak stage embryo where it is specifically restricted to the tissues of the ectoplacental cone and chorion. Expression of the beta 2 m gene continues in these tissues during formation of the definitive placenta. beta 2 m transcripts were also detected in the tissues of the visceral yolk sac starting at 10.5 days. Comparable levels of expression were observed in both the visceral yolk sac endoderm and the extra-embryonic mesoderm. These results clearly indicate that the onset of beta 2 m gene expression is not restricted to early hemopoietic cells. In the embryo-proper, significant levels of beta 2 m mRNA were not detected until day 9.5. At this stage, we observed a strong signal over the liver rudiment. The remaining somatic tissues expressed low levels of transcripts. Similar results were obtained at later stages of development, i.e., the fetal liver was consistently the most strongly positive organ. Overall these in situ hybridization studies define the pattern of beta 2 m gene transcription and thus potential sites of surface expression of class I proteins in specific cell lineages in the early postimplantation stage embryo.

Animals

Fertilization and ooplasmic movements in the ascidian egg.

Using light microscopy techniques, we have studied the movements that follow fertilization in the denuded egg of the ascidian Phallusia mammillata. In particular, our observations show that, as a result of a series of movements described below, the mitochondria-rich subcortical myoplasm is split in two parts during the second phase of ooplasmic segregation. This offers a potential explanation for the origin of larval muscle cells from both posterior and anterior blastomeres. The first visible event at fertilization is a bulging at the animal pole of the egg, which is immediately followed by a wave of contraction, travelling towards the vegetal pole with a surface velocity of 1.4 microns s-1. This wave accompanies the first phase of ooplasmic segregation of the mitochondria-rich subcortical myoplasm. After this contraction wave has reached the vegetal pole after about 2 min, a transient cytoplasmic lobe remains there until 6 min after fertilization. Several new features of the morphogenetic movements were then observed: between the extrusion of the first and second polar body (at 5 and 24-29 min, respectively), a series of transient animal protrusions form at regular intervals. Each animal protrusion involves a flow of the centrally located cytoplasm in the animal direction. Shortly before the second polar body is extruded, a second transient vegetal lobe ('the vegetal button') forms, which, like the first, resembles a protostome polar lobe. Immediately after the second polar body is extruded, three events occur almost simultaneously: first, the sperm aster moves from the vegetal hemisphere to the equator. Second, the bulk of the vegetally located myoplasm moves with the sperm aster towards the future posterior pole, but interestingly about 20% remains behind at the anterior side of the embryo. This second phase of myoplasmic movement shows two distinct subphases: a first, oscillatory subphase with an average velocity of about 6 microns min-1, and a second steady subphase with a velocity of about 26 microns min-1. The myoplasm reaches its final position as the male pronucleus with its surrounding aster moves towards the centre of the egg. Third, the female pronucleus moves towards the centre of the egg to meet with the male pronucleus. Like the myoplasm, the migrations of both the sperm aster and the female pronucleus shows two subphases with distinctly different velocities. Finally, the pronuclear membranes dissolve, a small mitotic spindle is formed with very large asters, and at about 60-65 min after fertilization, the egg cleaves.

Animals

The selected response procedure: a variation on Appelbaum's altered atmosphere procedure for the Rorschach.

This article introduces the Selected Response Procedure, which is a supplementary technique for expanding the scope of the Rorschach test. The procedure is conducted as follows: After the standard administration of the Rorschach test, patients are asked to look through all of the cards a second time and select one more response from any card of their choice. A rationale for this procedure is developed through a comparison to another supplementary Rorschach technique, the Altered Atmosphere Procedure. The importance of understanding the selected response within a theoretical framework, as well as the clinical context of each selected response, is highlighted by a clinical example using object relations theory. Finally, a number of didactic questions are offered as potential ways to query the possible meaning of selected responses.

Attention

Martial arts: a perspective on their evolution, injuries, and training formats.

The martial arts are very popular today as both spectator and participant sports, and a large percentage of the participants are children. More injuries are sustained in tournament competition and many are preventable by using protective gear and by limiting contact. Medical screening and proper execution of technique are also important prophylactic modalities.

Arm Injuries

Limited posterolateral surgical approach to the knee for excision of osteoid osteoma.

An 18-year-old man suffered four years of undiagnosed knee pain until a CAT scan revealed an epiphyseal osteoid osteoma of the tibia located subchondrally, just medial to the proximal tibiofibular joint. A nidus in this location is not easily accessible, and its proximity to the joint surface raised concerns about damage to the tibial plateau. To facilitate excision of the tumor, cadaveric dissections were performed to develop a limited posterior approach to the proximal, lateral portion of the tibia. The CAT scan was used to calculate the precise dimensions of the tumor and its relation to the posterior tibial cortex and the proximal tibiofibular joint. With the use of the exposure developed in the laboratory and the calculations derived from the CAT scan, the tumor could be excised by removing a single block of bone 15 mm3. Intraoperative radiographs confirmed the presence of the nidus within the excised block of bone. This case report reaffirms the frequent difficulties and tardiness in diagnosing osteoid osteomas and the need to include these tumors in the differential diagnosis of knee pain and epiphyseal lesions. Before CAT scans were used, the working diagnoses were torn meniscus, juvenile rheumatoid arthritis, and bone hemangiomatosis.

Adolescent

Continuing education.

Explore the source record for details and available documents.

Education, Medical, Continuing

Tropic responses of Funaria spores to red light.

The tropic responses of Funaria hygrometrica spores to continuous illumination with red light (610 to 690 mmu) have been studied over the intensity range from 10(-5) through 10(+6) erg/cm(2) second, using both plane polarized light and partial illumination with unpolarized light. From the relative frequency of outgrowth origin in different directions, the following is inferred. (1). The germination direction of chloronemal filaments is directly influenced by red light over this whole intensity range, while that of rhizoids tends to be opposite the chloronema. (2) Three photoreceptor systems direct chloronemal primordia: (a) A low intensity system acting from 10(-5) to 10(-0.5) erg/cm(2) second. It favors their growth from a cell's brightest part(s). Its photoreceptors are disoriented, excited by the electric vector, and probably are dispersed phytochrome molecules. (b) A medium intensity system which acts largely alone only at 10(0.5) erg/cm(2) second but is influential from 10(0) to 10(5) erg/cm(2) second. It likewise favors growth from a cell's brightest part(s); its receptor molecules are also excited electrically, but they are tangentially oriented. (c) A high intensity system which acts alone from 10(5) to 10(6) erg/cm(2) second and is influential down to 10(1) erg/cm(2) second. It favors growth of the chloronemas from a cell's darkest part. Its receptors probably are magnetically excited and tangentially oriented. The polarotropic responses of the chloronemas resemble those directing their origins. One new feature is that under intense (10(6) erg/cm(2) second) plane polarized and vertically directed light, many soon grow to form tight helices.

Biophysical Phenomena

Computed tomography (CT) arthrography of shoulder instabilities in athletes.

Sixty professional and recreational athletes underwent CT arthrography of the shoulder for evaluation of suspected shoulder joint derangement. These athletes, 46 males and 14 females ranging in age from 15 to 60 years (mean, 32 years), all had persistent pain that interfered with their sports activity and was resistant to conservative treatment. Seventeen patients had shoulder instability based on clinical manifestations and CT arthrographic findings. An additional five patients, also based on clinical manifestations and CT arthrographic findings, were considered to have an unobtrusive degree of anterior joint laxity. Patients with anterior instability (20 cases) all had an anteroinferior tear or detachment of the glenoid labrum, as well as some violation of the insertion of the joint capsule onto the scapula. Those with posterior instability (two cases) had a combination of labral and capsular tears. Two other major patterns of labral tears, both unaffiliated with shoulder instability, were identified. These included total or partial detachment of superior segments of the labrum, and anterior labral tears at the midglenoid level. Moreover, various degrees of labral attenuation (or, less often, enlargement), osteophyte formation, and alterations in articular cartilage were observed. Surgical correlation was obtained in 25 patients, with 95% accuracy of CT arthrographic findings. CT arthrography is a minimally invasive and highly accurate technique for investigation of glenohumeral derangement. Specifically, the extent of pathologic changes associated with instability can be determined and differentiated from other intraarticular causes of incapacity, such as labral tears caused by throwing, or degenerative changes.

Adolescent