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Biomedical subjects

L S Stein

Publications and source records attributed to L S Stein.

At least 19 recordsLinked to original sources
PubMed1992

Effects of phorbol myristate acetate on rat and chick osteoclasts.

The role of protein kinase C in the regulation of osteoclast function is not known. We therefore compared the effect of phorbol myristate acetate (PMA), which activates protein kinase C, on the resorptive function, motility, and morphology of osteoclasts from rat and chick. PMA caused a significant reduction in resorption pit number in both species; rat osteoclasts were more sensitive, being significantly inhibited at doses of 10(-9)-10(-6) M compared with 10(-7)-10(-6) M for chick osteoclasts. The inactive analog PMA-alpha was without significant effect, and inhibition was not blocked by 10(-6) M indomethacin. In time course experiments, inhibition at 24 h was similar to or greater than inhibition at 6 h, indicating a persistent or progressive effect on bone resorption. Removal of PMA after 6 h prompted partial recovery of bone-resorptive ability in chick osteoclasts but not rat, at least over a 48 h incubation. In time-lapse video studies of rat osteoclasts, 10(-6) M PMA produced an immediate but transient cessation of motility and retraction of the cell margin into prominent filopodia. Motility resumed within 2.5 h after addition, but the osteoclasts remained partially contracted. Chick osteoclasts behaved similarly but showed no formation of filopodia at the cell periphery and a more rapid recovery of motility than rat osteoclasts; chick osteoclasts also underwent a transient vacuolation following PMA exposure, whereas rat osteoclasts did not. Despite differences in the sensitivity of rat and chick osteoclasts to PMA, these results suggest a fundamental role for protein kinase C in the inhibition of osteoclasts from both species.

Animals↗
PubMed1992

Cell-to-cell communication competence in simian virus 40-transfected rat ovarian cells is reduced following tumor selection.

A pSV3neo-transfected rat ovarian cell line (SV-GC) was developed from a primary granulosa culture (GC) to study gap junctional intercellular communication (GJIC) during Simian virus 40 (SV40) transformation. SV-GC expressed SV40 large T-antigen (T-ag), grew indefinitely in culture without luteinization, was anchorage independent, and formed tumors in nude mice. Ultrastructural analysis identified abundant gap junctional membrane and suggested that SV-GC was arrested at an early stage of differentiation. Functional GJIC, measured by a dye transfer technique (gap FRAP), was comparable to that observed in normal granulosa cells, suggesting that the expression of T-ag alone was insufficient to reduce GJIC. However, there was approximately a 50% loss in the rate of GJIC in the nude mouse SV-GC-tumor derived and G418 selected cell line (T-SV-GC). SV-GC----T-SV-GC also resulted in a transition from migration of cells as an epithelial sheet to the dissociation of individual fibroblastoid cells. Tumor cell detachment was also seen in migrating malignant human (A2780 and 547) and rat (DC3) ovarian cell lines. Co-culture combinations of normal (GC)----transformed (SV-GC)----tumor-derived (T-SV-GC) cells indicated that the rate of heterologous GJIC was characteristic of the least communicating partner. Taken together, these data suggested that SV-GC----T-SV-GC represented progression toward metastasis with concomitant reduction of GJIC and adhesiveness. These sequentially derived cell lines may be a useful in vitro model system for studies focusing on the mechanism involved in the detachment of cells during the progression of ovarian cancer.

Animals↗
PubMed1992

Reduced cell-cell communication between mitotic and nonmitotic coupled cells.

The effects of mitosis on gap junctional intercellular communication (GJIC) were quantified in a clonal cell line of spontaneously immortalized rat granulosa cells (SIGC) using a fluorescence recovery after photobleaching assay. Reduction of GJIC was associated with the process of mitosis and was first apparent at the onset of prophase. Resumption of GJIC between newly divided cells and surrounding cells occurred slowly, requiring several hours following cytokinesis before reestablishment of maximal rates. Mitotic rates of GJIC in SIGC were comparable to values obtained in interphase cells partially uncoupled by 0.5 mM octanol. Limited studies of other cell lines generalized the mitotic-associated reduction of GJIC observed in SIGC. The data suggest that mitosis is one process which alters GJIC. This could be of significance when there is a change in the rate of proliferation, such as in the acquisition of immortalization, an early stage of transformation.

1-Octanol↗
PubMed1991

Rat ovarian granulosa cell culture: a model system for the study of cell-cell communication during multistep transformation.

A spontaneously immortalized clonal granulosa cell line (SIGC) derived from primary rat ovarian granulosa cell cultures was developed as a model system to explore the process of transformation using an epithelial cell type. SIGC has an epithelial morphology and grows in culture without undergoing luteinization. The cell line is thought to represent an intermediate step in carcinogenesis because it seems to grow indefinitely in culture but does not form clones in soft agar or tumors in nude mice. Indirect immunofluorescence and Western blot analysis verified the constitutive expression of the recessive oncogene product p53 in the cell line, thereby suggesting a possible mechanism of immortalization. Ultrastructural studies indicated that SIGC cells are characterized by an undifferentiated phenotype with prominent intermediate filaments, desmosomes, and gap junctions. The identification of cytokeratin by indirect immunofluorescence and Western blot analysis suggests that SIGC functions as an epithelial cell type. Functional studies of cell-cell communication by a dye transfer technique (fluorescence recovery after photobleaching) showed reduced communication compared to normal primary granulosa cells in culture. SIGC cells were transfected with early region genes of SV40 virus in an attempt to generate fully transformed cell lines. The resulting cell line SV-SIGC expressed T-antigen, was anchorage independent, formed tumors in nude mice, and had reduced intercellular communication as compared to SIGC cells. Explants from the tumors in nude mice were used to generate another cell line (T-SV-SIGC), which exhibited further reduction in both the incidence and the rate of communication. These results clearly demonstrated a progressive loss of functional communication during multistep transformation of an ovarian cell type. These data demonstrate that this assay system based on an epithelioid cell type can be used to study the relationship between intercellular communication and the multistep process of carcinogenesis.

Animals↗
PubMed1990

The effects of parathyroid hormone (PTH) and PTH-related peptide on osteoclast resorption of bone slices in vitro: an analysis of pit size and the resorption focus.

The mechanism whereby PTH, a potent stimulator of bone resorption, may under certain circumstances exert anabolic effects on bone is not known, but it is possible that it involves reduction of the size of osteoclast resorption lacunae. We have therefore made a detailed in vitro study of the effects of PTH and PTH-related peptide (PTHrP) on resorption by neonatal rat osteoclasts paying particular attention to the plan area of resorption pits. In order to distinguish between increased resorption at a particular site and increased numbers of sites, we have used an eyepiece graticule to define a focus of resorption, namely an area occupying 1/116th of the bone slice, which may contain either one or several pits. In addition we have studied the relationship between the number of pits in a resorption focus and the total area of bone resorbed at the focus. We found that PTH and PTHrP, at doses between 2 x 10(-10) M and 2 x 10(-8) M, while exerting significant stimulatory effects on bone resorption, caused a reduction in the median plan area of pits. An increase in the number of resorption foci was the primary stimulatory effect of PTH and PTHrP, occurring within 6 h in the case of PTH. However, the plan area of bone resorbed at a focus showed no significant increase, despite an increase in the number of pits per focus, because as more pits were formed at a focus, the pits were smaller, thus partially dissipating the stimulatory effect of PTH on resorption. These results are consistent with the activation of new remodeling sites by PTH in vivo. Furthermore, the formation of smaller pits under the resorptive influence of PTH may, together with the maintenance of coupling between formation and resorption, play a role in the preservation of cancellous bone recorded in cases of primary hyperparathyroidism and the anabolic effect of exogenous PTH.

Animals↗
PubMed1976

A comparison of female and male neurotic depressives.

Female and male neurotic depressives in an outpatient psychiatric clinic were compared on measures of subjective distress, interpersonal concerns, and types of treatment given. There were essentially no differences between the two groups on the patient self-report measures. However, female patients were found to have significantly more therapy sessions that the male neurotic depressives. Also, the female patients were more likely than the male patients to receive psychotropic medication, especially the more potent antidepressant variety.

Adjustment Disorders↗
PubMed1976

The Democratic Values Scale and professional affiliation.

Therapists from four professional groups--nursing, psychiatry, psychology and social work--were compared on Lerner's Democratic Values Scale. Significant professional differences were found on this scale. The findings raise questions about the predictive power of this scale when a variety of mental health professionals are studied.

Attitude of Health Personnel↗