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Biomedical subjects

M A Lieberman

Publications and source records attributed to M A Lieberman.

At least 19 recordsLinked to original sources
PubMed1992

Response of a human megakaryocytic cell line to thrombin: increase in intracellular free calcium and mitogen release.

The CHRF-288-11 cell line has been previously shown to exhibit properties consistent with a megakaryocytic origin. The response of these cells to thrombin has now been investigated. Thrombin treatment of CHRF-288-11 cells results in both an increase in intracellular free calcium levels and secretion of mitogenic activity and beta-thromboglobulin. Cell viability is not affected. The mitogenic activity released from the cells is due primarily to the presence of basic fibroblast growth factor. Immunohistochemical data indicate a packaging of basic fibroblast growth factor into granular structures. Trypsin and phorbol 12-myristate 13-acetate also initiate release of mitogenic activity from this cell line, whereas under non-stirred conditions collagen and ADP do not. Through measurements of intracellular calcium levels it was determined that thrombin pretreatment of cells ablates a further response to thrombin, but does not block an increase in intracellular calcium levels due to trypsin. This suggests that these two agonists may act through different mechanisms. The thrombin-induced release reaction is inhibited almost completely by the reagents hirudin and dipyridamole, and only partially by indomethacin. These data indicate that the CHRF-288-11 cell line should provide an excellent model system in which to study the packaging of factors into granules which undergo regulated release.

Calcium↗
PubMed1992

Control of Ha-ras-mediated mammalian cell transformation by Escherichia coli regulatory elements.

Inducible eukaryotic promoters, particularly those responsive to glucocorticoids or heavy metals, have been extensively used to study the consequences of induction of a target gene in mammalian cells. An alternative approach, intended to improve the selectivity of gene induction and to minimize perturbation of chromatin structure, is to utilize elements from prokaryotic regulatory systems that are unlikely to be shared by mammalian cells. We and others previously have shown that the lac repressor can function in mammalian cells and repress expression of a reporter gene controlled by a eukaryotic promoter containing a lac operator sequence. The reporter gene can be specifically activated by administration of the lactose analogue isopropyl beta-D-thiogalactoside. The target genes tested so far encode the biochemical and histochemical markers, chloramphenicol acetyltransferase and beta-galactosidase. As a model system to establish whether or not the lactose regulatory system can also be used to effectively modulate a cellular phenotype, NIH 3T3 cells were made transgenic for a constitutively expressed lacI gene, encoding lac repressor, and an activated human Ha-ras gene directed by a simian virus 40 promoter within which a lac operator sequence had been embedded. In the absence of inducer, cells were phenotypically untransformed. Consequent to isopropyl beta-D-thiogalactoside administration, four biological end points characteristic of a transformed phenotype were observed. Consistent with transformation, the cells assumed an altered morphology; they displayed a reduced density inhibition of growth; they acquired the capacity to grow in soft agar; and they were released from a G0 block following serum deprivation. The data demonstrate that regulation of gene expression in mammalian cells by the lactose regulatory system affords a sensitive means for modulating cellular phenotype.

3T3 Cells↗
PubMed1992

Brief group psychotherapy for the spousally bereaved: a controlled study.

A consecutive sample of mid- and late-life bereaved spouses were randomly assigned to treatment and no-treatment groups. Two hypotheses were tested: (1) that brief group psychotherapy during the early stages of loss would facilitate adjustment assessed by measures of mental health, positive psychological states, social role, and mourning; and (2) that positive effects would be maximized for subjects who were more distressed psychologically. Although group participants, compared with untreated controls, did over 1 year show modest improvement on role functioning and positive psychological states, overall the study failed to find substantial support for the two major hypotheses. Both experimental and control groups showed improvement over the year, particularly on measures of mental health and mourning. Differential benefit was not observed for the high-risk group.

Adaptation, Psychological↗
PubMed1991

Potentiation of the activity of mouse liver-derived HBGF-1-like growth factor by heparin and dithiothreitol: evidence for the involvement of a plasma factor.

The potentiation of mouse liver derived heparin binding growth factors 1 and 2 (HBGF-1, HBGF-2) activity has been investigated. It was found that both heparin and various sulfhydryl reagents (such as dithiothreitol, DTT) markedly potentiated HBGF-1 activity, but not HBGF-2 activity. Further studies with HBGF-1 indicated that the growth factor would interact with a plasma factor, in a temperature-dependent manner, to become inactive, and that sulfhydryl reagents would reverse this inactivation. Inactivation would not occur either in the presence of heparin or DTT, indicating that heparin and DTT can protect the growth factor from plasma inactivation. When assayed in the absence of plasma, both heparin and DTT were required to reactivate plasma inactivated HBGF-1-ML. A model is presented to explain these data. This model predicts that either DTT or heparin can block the plasma induced inactivation process, but that once inactivation has occurred only sulfhydryl reagents can restore activity. Furthermore, heparin is thought to activate growth factor activity in the absence of plasma by blocking non-productive growth factor binding to the extracellular matrix. The identification of a plasma inactivating factor for mouse liver derived HBGF-1 has important implications for understanding the regulation of extracellular growth factor activity.

Animals↗
PubMed1991

Bereavement and heightened existential awareness.

"Ask not for whom the bells toll; they toll for thee." John Donne's admonition, though written 350 years ago, endures with astonishing freshness; it speaks to something self-evident, to a truth that is well known to many who have experienced bereavement--that the death of a significant other has the potential to hurl the survivor into a confrontation with his/her own death. A confrontation with death--should we seek it? There is evidence in the clinical literature that in terminally ill patients such a confrontation may lead to pronounced positive psychological changes. Research (Yalom 1980) has documented that terminally ill patients may undergo a series of positive personal changes; they communicate more openly with family and close friends, they experience fewer fears, they rearrange their life priorities, they are less preoccupied with the trivialities of life, they live life more immediately rather than postpone experience and pleasure into the future. Does spousal bereavement in our culture confront individuals with their own personal death? Does it cause some widow/widowers to regard their existence in a different manner? If so, might it be possible that those bereaved individuals who examine their life deeply may have a different course of bereavement than those who do not look within? Might it even be possible that bereavement, for some individuals, results in psychological shifts analogous to the positive changes reported by terminally ill patients? These are the basic questions of our research inquiry. We designed a project which would allow us to determine, in a nonclinical sample of bereaved spouses, differences in the degree of existential awareness and the consequences of such awareness on the course of bereavement. We also attempted to determine which subjects were more likely to develop heightened existential awareness. The participants studied were part of an intervention project on bereavement in which we studied a sample of widows and widowers in the first few months of bereavement and then offered them an opportunity to participate in an eight-meeting support group. Reports of the clinical issues emerging in our short-term bereavement groups and of the efficacy of these groups were published elsewhere (Yalom and Vinogradov 1988; Lieberman and Yalom 1991).

Awareness↗
PubMed1991

Factors affecting decisions to institutionalize demented elderly.

This study followed 321 community-based patients with documented dementias, 22% of whom were institutionalized after 1 year. Multivariate analyses indicated that none of the patient characteristics, such as level of cognitive, psychiatric, or neurological impairment, predicted institutionalization. Social psychological characteristics, type and number of caregivers, and subjective caregiver distress did predict which patients were ultimately institutionalized. Implications for treatment planning are discussed.

Aged↗
PubMed1991

Liver contains heparin-binding growth factors as the major growth factor for cultured fibroblasts.

The presence of heparin-binding growth factors in liver was investigated by measuring the DNA synthesis stimulatory activity of liver extracts using quiescent fibroblasts as target cells. It was found that cytosolic fractions of mouse, rat and human liver, as well as isolated rat hepatocytes, contain a large amount of growth stimulatory activity. Most liver cytosolic activity is due to heparin-binding growth factors, because greater than 90% of the activity bound to a heparin affinity column in the presence of 0.8 mol/L NaCl, and was quantitatively eluted with 2 mol/L NaCl. Purification of these factors from both mouse and rat liver indicated the presence of both heparin-binding growth factor-1 and 2 in liver extracts. The level of the heparin-binding growth factors, as estimated from the biological activity, is approximately 1 microgram/gm mouse liver and 0.1 microgram/gm rat and human liver. Heparin-binding growth factor-1-like factors were 10 times as abundant as heparin-binding growth factor-2-like factors. These data indicate that the cytosolic fractions of mouse, rat and human liver contain heparin-binding growth factors as the primary growth factor for fibroblasts, and heparin binding growth factor-1-like molecules account for most of the cytosolic activity in both mouse and rat liver.

Animals↗
PubMed1991

Macrodontia of maxillary central incisors: case reports.

Two cases of maxillary anterior macrodontia, resulting from fusion and gemination, were treated orthodontically. Problems of esthetics and overjet were solved in the first patient by sectioning and extraction of a fused mesiodens, and in the second patient by treating toward an Angle Class III buccal occlusion.

Child↗
PubMed1990

In vitro establishment and characterization of a human megakaryoblastic cell line.

A human megakaryoblastic cell line, designated CHRF-288-11, has been established in vitro through the use of adherent stromal cells in long-term human bone marrow culture. Long-term bone marrow cultures were required for the initial adaptation of the megakaryoblastic cells to culture conditions; however, once adapted, the cells were weaned from the stromal layer until they proliferated in the complete absence of any feeder layers. The seed cells for the establishment of this line were derived from a solid tumor; the cloned cell line derived from this tumor exhibits markers characteristic of megakaryocytes and platelets. Specifically, the cells express platelet peroxidase, platelet factor 4, and platelet Ca+(+)-adenosine triphosphatase (ATPase), glycoprotein IIb-IIIa (CDw41), factor VIII antigen, and the MY7 (CD13) and MY9 (CD33) antigens. The cells do not express the erythroid markers glycophorin A and hemoglobin, the myeloid marker myeloperoxidase, nor markers specific for T and/or B cells. The established cell line produces both basic fibroblast growth factor and transforming growth factor-beta, properties demonstrated previously for the solid tumor. The clonal cell population exhibited a unique, singular karyotype, indicating cellular homogeneity. The cells display a doubling time of approximately 33 hours in either 25% horse or calf serum. Treatment of the cells with 1 X 10(-8) mol/L phorbol 12-myristate 13-acetate (PMA) leads to the induction of multi-nucleation and hyperploidy in the cells, with approximately 35% of the cells exhibiting two or more nuclei per cell, and greater than 80% of the cells enlarging in size. The establishment of this unique cell line under defined culture conditions will be beneficial for the future study of megakaryocytic properties expressed by this cell line.

Blotting, Northern↗
PubMed1990

Mitogen accumulation in von Recklinghausen neurofibromatosis.

Most, but not all, patients with von Recklinghausen neurofibromatosis develop tumors (neurofibromas) that contain large numbers of Schwann cells and fibroblasts. To begin to understand the molecular events that contribute to cell proliferation in these benign tumors, we have analyzed extracts of neurofibromas to determine whether they contain mitogens for Schwann cells or fibroblasts, or both. Schwann cell and fibroblast mitogens are present in neurofibroma extracts. All the neurofibromas analyzed contain a Schwann cell mitogen similar to a neuronal cell surface molecule known to stimulate Schwann cell proliferation during normal development; this mitogen also stimulates fibroblast proliferation. Basic fibroblast growth factor is present in 60% of tumors evaluated. Accumulation of mitogenic substances may contribute to the growth of neurofibromas.

Cell Division↗
PubMed1990

Understanding how groups work: a study of homogeneous peer group failures.

The study examines thirty-six homogeneous peer support groups that failed to positively benefit most of the participants. Outcomes were assessed pre and one-year post using measures of mental health, marital relationships, and motherhood role indices. Four central group process characteristics previously found to be common in successful peer support groups were used as a framework for developing a series of post hoc hypotheses. The groups were found to be low on cohesiveness defined behaviorally, saliency, cognitive structures for reframing common dilemmas, and limited in the range of therapeutic experiences.

Adult↗
PubMed1990

A group therapist perspective on self-help groups.

The author provides an overview of self-help groups in terms of their origins, growth, scope, and effectiveness, and then compares these groups with professionally conducted psychotherapy groups. A framework for evaluating group helping systems is proposed which includes five principal dimensions: the helping group as a social microcosm; technological complexity/simplicity; psychological distance/closeness between helper and helpee; specificity/generality of help methods; and differentiation versus nondifferentiation among participants. The author concludes his article by recommending four strategies for how group therapists can contribute to self-help groups.

Attitude of Health Personnel↗
PubMed1989

Group properties and outcomes: a study of group norms in self-help groups for widows and widowers.

Despite the nearly universally shared agreement among group therapists about the importance of group norms, empirical studies have rarely demonstrated a positive relationship between specific norms in psychotherapy groups and patient benefit. The study explored this relationship by examining the linkages between norms, a specific therapeutic process, and patient outcome. Examined were seventy-two spousal bereavement groups. Subjects' responses to a thirty-one item behavioral inventory were used to define norms; outcomes were based upon Time 1/Time 2 differences on a series of eleven measures indexing depression, anxiety, somatic symptoms, abuse of psychotropic medication, coping mastery, well-being, self-esteem, target problem rating, several measures of role stress and strain, and stigma. The findings suggest that normative characteristics were linked to a process, reciprocal social exchange, that influences positive outcomes. The results are preliminary, since they only serve to demonstrate such a relationship can exist.

Adaptation, Psychological↗
PubMed1989

Identification of an acidic fibroblast growth factor-like activity in a mesoblastic nephroma.

An acidic fibroblast growth factor-like activity was detected in a primary mesoblastic nephroma. Identification was based upon Northern blot analysis of renal tumor RNA and by a biochemical characterization of the growth factor activity. The activity extracted from the tumor stimulated DNA synthesis in both mouse fibroblasts and bovine endothelial cells. This activity was heat-sensitive and enhanced in the presence of heparin. The extract activity bound to immobilized immobilized heparin, eluting at 1.2 M NaCl, and cross-reacted with antiserum to recombinant acidic fibroblast growth factor. We also present evidence for acidic fibroblast growth factor-like molecules in normal immature human kidney, although the amount of the activity detected is less than that in the mesoblastic nephroma. These data suggest that acidic fibroblast growth factor-like activity is present in the developing normal human kidney, and that some renal tumors can continue to express a similar activity.

Blotting, Northern↗
PubMed1988

Growth factor production by a human megakaryocytic tumor cell line.

A recently described human megakaryocytic tumor cell line was analyzed for the presence of growth factor activity and was found to produce large quantities of transforming growth factor beta-like (TGF-beta) and basic fibroblast growth factor-like (bFGF) activities. Growth factor activities were identified using a radioreceptor assay for the TGF-beta-like activity, a heparin-binding assay for the b-FGF-like activity, and a demonstration of distinct biological activities for each type of factor. Tumor poly-A+ RNA revealed strong signals when probed with complementary DNA corresponding to bovine basic FGF and human TGF-beta and weak signals when probed with cDNA corresponding to epidermal growth factor (EGF) and TGF-alpha. The levels of EGF and TGF-alpha produced in the tumor line were too low to be detected by radioreceptor assays. Relative levels of messenger RNA encoding each of the growth factors reflected the relative levels of each of the respective factors tested. These data represent the first definitive identification of FGF-like activities in megakaryocytic-like cell lines. Interestingly, the line displayed little activity similar to platelet-derived growth factor (PDGF) when assayed either biochemically or by poly-A+ RNA analysis.

Animals↗
PubMed1988

The neuronal cell-surface molecule mitogenic for Schwann cells is a heparin-binding protein.

The cell surface of embryonic peripheral neurons provides a mitogenic stimulus for Schwann cells. We report (i) the solubilization of this mitogenic activity from rat dorsal root ganglion neurons grown in tissue culture and (ii) the solubilization and partial purification of mitogenic activity from neonatal rat brains. Extracted mitogenic activity is peripheral rather than intrinsic to the membrane, stable after extraction, and active as a mitogen in the absence of serum (the most stringent criterion defining the neuronal mitogen). We have previously provided evidence suggesting that a neuronal cell-surface heparan sulfate proteoglycan is required for expression of the neurons' mitogenic activity. We now show that mitogenic activity can be extracted from the membrane dissociated from proteoglycan as assayed by its ability to bind to immobilized heparin. After dissociation, low concentrations of heparin (1 micrograms/ml) inhibit the ability of the mitogen to stimulate Schwann cell division. Basic fibroblast growth factor (FGF) is weakly mitogenic for Schwann cells, but it is not present in mitogenic brain extracts (based on immunoblotting). Immunodepletion experiments with specific antibodies to FGF indicate that the mitogenic activity extracted from neurons is not a form of this heparin-binding mitogen. Acidic FGF is not mitogenic for Schwann cells and is not present in mitogenic brain extracts. We suggest that these and previous data indicate the neurite mitogen is a proteoglycan-growth factor complex that limits mitogenic activity to the axonal surface, protects mitogen against inactivation by other proteoglycans, and provides for effective presentation of mitogen to the Schwann cell.

Animals↗
PubMed1987

Differential effects of epidermal growth factor and transforming growth factor-beta on synthesis of Mr = 35,000 surfactant-associated protein in fetal lung.

Differentiation of pulmonary Type II epithelial cells in late gestation is associated with the synthesis of pulmonary surfactant required for adaptation to air breathing at birth. In the present work, induction of synthesis of a Type II epithelial cell protein, surfactant-associated glycoprotein of Mr = 35,000 (SAP-35) was studied in human fetal lung tissue obtained at 15-24 weeks of gestation. SAP-35 content increased during organ culture in the absence of exogenous hormones. Epidermal growth factor or triiodothyronine stimulated the induction of SAP-35 synthesis during culture. Stimulation by epidermal growth factor (EGF) was detected as early as 2 days and persisted for up to 5 days in culture. Response to EGF was dose-dependent (0.01-10 ng/ml) and was associated with enhanced incorporation of [35S]methionine into immunoprecipitable SAP-35. Increased SAP-35 synthesis was associated with increased SAP-35 RNA as assessed by Northern blot and hybridization assays with human SAP-35 cDNA. Effects of EGF were comparable to the induction of SAP-35 synthesis by 8-bromo-cAMP. In contrast to the stimulatory effect of EGF and triiodothyronine, SAP-35 content was inhibited by transforming growth factor-beta. Both the stimulatory and inhibitory effects of these agents on SAP-35 content were associated with concomitant changes in SAP-35 synthesis. These findings demonstrate multihormonal control of SAP-35 expression and strongly implicate both EGF and transforming growth factor-beta in the regulation of surfactant apoprotein synthesis.

DNA↗