Biomedical subjects

R W Redline

Publications and source records attributed to R W Redline.

16 recordsLinked to original sources

PubMed1992

Human HOX4E: a gene strongly expressed in the adult male and female urogenital tracts.

Homeobox-containing genes (Hox genes) are believed to play a fundamental role in development and positional identity. Four homologous Hox gene complexes are found in humans and mice. Genes at the 3' ends of these complexes tend to be expressed rostrally while those at the 5' end are expressed caudally. Whereas complete open reading frames have been reported for rostrally expressed 3' Hox genes, structural information is lacking for the more 5' genes. Genomic and cDNA clones containing the human HOX4E (also known as human Hox 4.5) gene were isolated. The gene contains two exons and spans about 5 kb of DNA. The N-terminal portion of the HOX4E activation domain contains several consensus sequence elements also found in other mammalian AbdB family genes. Further downstream, however, HOX4E contains a novel 37-amino-acid stretch containing 30% acidic residues. Northern blot analysis of HOX4E expression in adult tissues showed a major human transcript of 1.8 kb, the expression of which was largely limited to tissues of the male and female urogenital tracts. Expression was particularly strong in the uterus. This suggests that aside from its effects during embryogenesis, the HOX4E gene may play a continuing role in adult genitourinary tract function.

Adult↗

PubMed1992

Macrophage functions are regulated by murine decidual and tumor extracellular matrices.

Because of their paternal antigens, the fetus and placenta may be considered an allograft in the maternal host. Understanding the mechanisms which prevent maternal immunological rejection of the fetus remains a fundamental unsolved problem in immunology. We have previously reported that macrophages are inhibited by maternal decidual stromal cells residing at the maternal-fetal interface. In view of the central role of macrophages in cell-mediated immunity, this inhibition may contribute to preventing maternal antifetal responses. We now report that it was the solid phase signals embedded in the extracellular matrix (ECM) made by decidual cells which are responsible for inhibiting macrophage-mediated lysis of TNF-alpha-resistant P815 mastocytoma cells. The latter macrophage function is acquired after stimulation by interferon gamma and endotoxin. All these macrophage functions were also inhibited by ECM isolated from the Engelberth-Holm-Swarme (EHS) tumor. This tumor ECM has a similar biochemical composition to decidual ECM. This ECM inhibited the effector, as opposed to the stimulator, phase of macrophage-mediated tumor lysis. Laminin, type IV collagen, and heparan sulfate proteoglycans, the major known components of decidual and EHS ECMs, did not inhibit the above macrophage functions. Altogether these data indicate that macrophages were inhibited by solid phase signals embedded in decidual and EHS ECMs. Whether the solid phase signals in these two ECMs are biochemically identical remains to be determined. To our knowledge, such signals are a novel pathway of inhibiting macrophage functions which may be important in understanding the maternal-fetal immunologic relationship, and the pathogenesis of perinatal infections. Furthermore, the ability of EHS tumor ECM to inhibit macrophage functions may indicate that some tumors may defend themselves against host macrophage responses using solid phase signals. This may be important in understanding some host-tumor relationships.

Animals↗

PubMed1992

Homeobox genes and congenital malformations.

In this review we have built a case for abnormal Hox gene expression in human congenital malformations without presenting any direct evidence of their involvement. This approach is justified by the dramatic advances in developmental genetics which emphasize the considerable similarity in the primary processes and molecules used to guide early morphogenesis in all species. Hox genes occupy a central role in this scheme, being activated in a specific rostral-caudal order after initial specification of the basic embryonic axes and, thereafter, specifying positional identity by influencing downstream "realizator" genes that carry out the position-specific program. These theoretical arguments, together with the dramatic results obtained in an evolutionarily similar organism (the mouse) using the transgenic and gene deletion approaches, make it highly likely that abnormalities in Hox gene structure and expression will soon be implicated in specific human congenital malformation syndromes. In parallel with this phenotypic analysis, we can expect that the animal models discussed in this review will provide greater detail regarding the upstream regulators and downstream targets of Hox gene products. Together these approaches promise to finally elucidate some of the underlying mechanisms responsible for human congenital malformations.

Animals↗

PubMed1991

Detection of enteroviral infection in paraffin-embedded tissue by the RNA polymerase chain reaction technique.

A method using the RNA polymerase chain reaction technique to diagnose infection retrospectively using single-stranded RNA enteroviruses in paraffin-embedded tissue blocks is reported. This method takes advantage of extreme sequence conservation in the 5' untranslated region of the enteroviral genome and uses two rounds of amplification with nested oligonucleotide primers, thus allowing rapid diagnosis without the use of radioactive reagents. The technique should prove useful in cases in which viral infection is suspected after histopathologic evaluation, when fresh or frozen tissues often are unavailable. The sensitivity of the method is demonstrated by successful amplification of Enterovirus 11 RNA extracted from 4-year-old liver tissue obtained at autopsy examination that was initially fixed and embedded 45 hours after death.

Base Sequence↗

PubMed1991

Pathologic features of sharp curettings in complete hydatidiform mole. Predictors of persistent gestational trophoblastic disease.

The medical records and pathologic specimens were reviewed from 33 patients with complete molar pregnancy at Brigham and Women's Hospital between 1980 and 1989. Two pathologists (D.R.G. and R.W.R.) reviewed all slides from the original sharp curettage to identify pathologic features that may be associated with persistent gestational trophoblastic tumor (GTT). The pathologic features evaluated were implantation site, presence of myometrium, presence of villi, presence and degree of atypia in cytotrophoblast, syncytiotrophoblast and intermediate trophoblast, presence of fibrinoid, presence of implantation site inflammatory cells, volume of tissue and area of trophoblastic tissue. Only one pathologic feature, fibrinoid deposits, identified in sharp curettings was associated with the development of persistent GTT. While 12 (48%) of 25 patients who attained remission without chemotherapy had fibrinoid deposits, only 1 (12.5%) of 8 patients who developed persistent GTT had them (P less than .10).

Adult↗

PubMed1990

Macrophage functions are regulated by the substratum of murine decidual stromal cells.

Because of their paternal antigens, the fetus and placenta may be considered an allograft in the maternal host. Local properties of the maternal-fetal interface, the placenta and decidua basalis, are important in preventing maternal immunologic rejection of the fetoplacental allograft. However, the exact nature of these local properties remains a fundamental unsolved problem in immunology. We now report that three macrophage functions were inhibited by the substratum formed by monolayers of decidual stromal cells via a novel pathway. Solid-phase inhibitors blocked macrophage adhesion, spreading, and lysis of tumor necrosis factor-alpha-resistant P815 mastocytoma tumor cells. Inhibition was not solely attributable to an inability of macrophages to adhere to decidual substratum because there were differences in macrophage functions on this surface versus polyhema where no adherence occurred. Because macrophages play a central role in cell-mediated immunity, including allograft rejection, inhibiting their function in the decidua basalis may help prevent maternal antifetal responses.

Animals↗

PubMed1989

Pregnancy as a natural model of allograft tolerance. Interactions between adherent macrophages and trophoblast populations.

From an immunologic viewpoint, the fetus with its paternal antigens may be considered a successful allograft in the maternal host. Understanding the basis of this host-allograft relationship remains a fundamental unsolved problem in transplantation immunobiology. We have previously demonstrated that local immunoregulation in the murine placenta prevented macrophage activities necessary for an effective response against the intracellular bacterium Listeria monocytogenes. Given the central role of macrophages both as antigen-presenting and cytolytic effector cells, such local immuno-regulation may ordinarily help prevent rejection of the fetoplacental unit with its paternal alloantigens by the maternal immune system. We therefore examined two types of interaction between macrophages and the placental cells that populate the maternal-fetal interface. (1) Upon activation to kill listeria efficiently, macrophages also acquire cytolytic capacities against some tumor and embryonic cells. We tested the hypothesis that macrophage activation in the placenta was inhibited to prevent macrophages from lysing fetal trophoblasts. We found, however, that trophoblasts isolated by dispase dispersion, differential isopyknic centrifugation, and adherence were not lysed by three different populations of cytolytic macrophages: (a) those activated in vivo during listeriosis, (b) peptone-elicited macrophages activated in vitro by recombinant interferon gamma and other lymphokines, and (c) the macrophage cell line RAW 264.7 activated in vitro. (2) Previous studies had demonstrated that cells from the placental region and their conditioned media inhibited a variety of lymphocyte functions. However, we found that these did not inhibit activation of adherent macrophages as assessed by induction of cell-surface Ia and acquisition of tumoricidal activity. In addition, under conditions where placental cells inhibited the proliferative response of a cloned CD4+ anti-Listeria T cell line to fixed, antigen-pulsed macrophages, the secretion of macrophage-activating lymphokines was not affected. These studies are important because they indicate that previously described suppressor systems in the murine placental region do not account for the profound local deficits in macrophage function seen during listeriosis.

Animals↗

PubMed1989

Localization of fetal major histocompatibility complex antigens and maternal leukocytes in murine placenta. Implications for maternal-fetal immunological relationship.

An immunohistochemical study of the days 14-19 murine placenta and uterus using a panel of antibodies specific for maternal and paternal class I major histocompatibility complex (MHC) antigens, specific leukocyte subsets, and other lineage-specific markers was performed to elucidate the nature of the maternal tolerance of the fetal implant in the uterus. Fetally derived trophoblast lining maternal blood spaces lacked MHC antigens, but other interstitial trophoblasts expressed fetally derived polymorphic class I MHC determinants. The latter class I MHC-bearing trophoblasts were most prominent in the maternal decidua basalis where they were mixed with maternal cells. Our results identify two factors that may be relevant for understanding why these alloantigen-bearing fetal cells are not rejected by the mother: a paucity of la-bearing antigen presenting cells, macrophages, and mature T and B lymphocytes and the presence of large numbers of Thy-1+ asialo-GM-1+ CD4- CD8- bone marrow-derived (CLA/Ly5+) cells of maternal origin in the decidua basalis. These latter cells correspond to previously described granulated metrial gland cells that may be involved in local immunoregulation.

Alkaline Phosphatase↗

PubMed1989

Angiomyxoma of the umbilical cord with massive cystic degeneration of Wharton's jelly.

Tumors of the umbilical cord, and especially angiomyxomas, are extremely unusual placental lesions. Sonography three weeks after the finding of a slightly elevated amniotic fluid alpha-fetoprotein, detected a cystic lesion of the umbilical cord in a 35-year-old woman at 19.5 weeks gestation. Two prior sonograms had been normal (16.2 and 17.5 weeks gestational age). After delivery of a normal female infant at 38.5 weeks, a pathologic examination revealed an angiomyxoma of the umbilical cord with massive cystic degeneration of Wharton's jelly. The tumor was twice the size of cases cited previously and cystic degeneration was massive. Serial sonography afforded a unique opportunity to study the development of this lesion in utero.

Adult↗

PubMed1988

Specific defects in the anti-listerial immune response in discrete regions of the murine uterus and placenta account for susceptibility to infection.

Infection of the murine uteroplacental region by the intracellular pathogen Listeria monocytogenes results in uncontrolled local bacterial growth. In this paper we examined infected and noninfected uteroplacental tissues by immunocytochemistry to delineate the nature of the aberrant anti-listerial response. Overall the data support the hypothesis that local immunoregulation, which ordinarily prevents maternal anti-fetal, responses also prevents an effective anti-listerial response at the maternal-fetal interface. Different types of response were seen in different anatomic regions. Listeria first localized to the maternal decidua basalis, which contains a mixture of fetal class I MHC-bearing trophoblast and maternal cells. Here the listeria proliferated in an uncontrolled manner due to a striking inability of monocyte/macrophages and lymphocytes to reach foci of infection. A second type of abnormal response was seen in the fetal chorioallantoic plate, a nontrophoblastic region of the placenta. Although macrophages were present, they were not appropriately activated as evidenced by a lack of Ia Ag and the presence of extracellular listeria colonies. Purely maternal tissues adjacent to the placenta had a normal anti-listerial response. During listeriosis, class I MHC expression was augmented throughout the placenta on cells normally bearing these Ag: trophoblast in the decidua basalis and both fetal and maternal stromal cells. Class II MHC Ag were induced on maternal and fetal endothelial cells but never appeared on trophoblast.

Animals↗

PubMed1988

Defective anti-listerial responses in deciduoma of pseudopregnant mice.

Two different hormonal regimens to induce pseudopregnancy resulted in a pronounced increase in the susceptibility of the murine uterus to intraluminal injections of Listeria monocytogenes. Preimmunization, which profoundly augments systemic listeria resistance, had no effect on this increased uterine susceptibility. Anti-listerial responses in other organs were unaffected by pseudopregnancy. Animals manifesting increased susceptibility formed distinct uterine swellings in response to the combination of hormones and uterine listeria. These swellings correspond to previously described deciduoma and closely mimic the decidualized endometrium of pregnancy. The nature of the defective response to listeria was investigated by immunocytochemistry. Increased bacterial titers were correlated with an inability of macrophages and T lymphocytes to reach tissue listeria in discrete regions of deciduoma-bearing uteri. Control uteri showed a normal granulomatous pattern of inflammation. These findings closely parallel previous findings in the murine decidua basalis and suggest that properties of decidualized endometrial stromal cells regulate local immune responsiveness.

Animals↗

PubMed1987

Role of local immunosuppression in murine fetoplacental listeriosis.

Recent evidence suggests that local immunoregulation may prevent rejection of the placenta by the mother. This local immunoregulation may also compromise the response to placental infection. Listeria monocytogenes infection in 121 pregnant mice and 1,050 fetoplacental units was examined and the kinetics of bacterial growth in various maternal and fetal tissues were determined. A subset of pregnant mice developed overwhelming placental listeria infections. Pregnancy did not impair the maternal immune response in the liver and spleen. Pregnant mice without placental infection had numbers of listeria equivalent to nonpregnant controls and mice immunized during pregnancy had significantly less listeria than nonimmunized controls. The secondary response in immunized pregnant mice had no effect on the development of placental infection and the histologic features of placental infection were distinct from those in other organs. Our data suggest that an ineffective local immune response may contribute to the pathogenicity of listeria for the placenta.

Animals↗

PubMed1987

A sonographic sign which predicts which fetuses with hydrocephalus have an associated neural tube defect.

We report a sonographic sign which reliably distinguishes those hydrocephalic fetal heads associated with a neural tube defect from those which are not, particularly in the second trimester. This sign involves a "pointed" deformity of the frontal aspect of the skull in fetuses with hydrocephalus, indicating the presence of a neural tube defect. A retrospective review of 36 cases of hydrocephalus demonstrates that this sign is particularly helpful in the second trimester, where it was present in all the fetuses with hydrocephalus and neural tube defect. It was less reliable in the third trimester; however, this sign was not present in any of the fetuses with hydrocephalus who did not have a neural tube defect. Angulation or pointing of the fetal frontal bone when hydrocephalus is present, particularly in the second trimester, seems to be a reliable predictor of an associated neural tube defect and mandates a careful search for this defect.

Female↗

PubMed1986

Invasive partial mole.

A case of invasive partial hydatidiform mole requiring chemotherapy and hysterectomy in a 30-year-old white woman is presented. This is the first histologically and cytogenetically documented partial mole with persistent elevation of human chorionic gonadotropin (hCG) level and invasion of myometrium. There was no evidence of distant spread.

Adult↗

PubMed1985

Clinical and pathologic aspects of recurrent placental villitis.

In a retrospective survey, recurrent villitis was identified in ten of 59 patients in whom placental villitis had been diagnosed. The ten patients had a total of 41 pregnancies, with a reproductive loss of 60 per cent. In addition to enhanced fetal losses in all trimesters of gestation and postnatally, the incidences of fetal growth retardation and premature delivery were increased. There was no evidence of recent TORCH (toxoplasma, rubella, cytomegalovirus, herpes) infection, but all patients tested had rubella immunity. In six patients genital cultures were positive for gonorrhea and assorted microorganisms. Uterine abnormalities, including two septate uteri, one incompetent cervix, one submucosal leiomyoma, and one retroflexion, were common, and vaginal bleeding had occurred in five patients. Other factors included obesity (five patients) and clinical and laboratory evidence of autoimmunity (four of the five patients tested). In a control group of 20 patients with nonrecurrent villitis, the perinatal loss rate (37 per cent) was lower, and the incidences of positive cultures, uterine structural anomalies, obesity, and autoimmunity were also lower. Placental histologic findings included decidual plasma cell and intervillous fibrin and histiocytic infiltration, in addition to villous inflammation. These lesions, although consistent for a given patient, defined two clinically relevant groups of patients. The results of this study suggest that recurrent villitis is more frequent than previously reported, that it is associated with high perinatal mortality, and that immunologic and structural abnormalities in the host may play a role in its pathogenesis.

Adolescent↗

PubMed1985

Systemic Malassezia furfur infections in patients receiving intralipid therapy.

Systemic infection with Malassezia furfur was first reported in 1981 as a specific complication of Intralipid therapy in a neonate. Six additional patients, including three older than 16 years of age, were identified subsequently. All had received prolonged Intralipid infusion through central venous catheters. Pulmonary infection was documented in tissue in three cases, the clinical presentation was characterized by pulmonary infiltrates, fever, and, in the infants, thrombocytopenia. Two subgroups of patients appear to be at the greatest risk for Malassezia infection: neonates with cardiopulmonary disease and adults with severe gastrointestinal disease and immunosuppression. The documentation of pulmonary arterial lipid deposits in vessels that had been infiltrated by Malassezia organisms and the observation of organisms in small pulmonary thromboemboli suggest that these lipophilic and lipid-dependent organisms are introduced into the bloodstream from venous catheters and require high lipid concentrations to proliferate in tissue.

Adolescent↗