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Biomedical subjects

Y Zilberman

Publications and source records attributed to Y Zilberman.

At least 37 records · Page 2Linked to original sources

High oligomycin concentrations augment 6-keto-PGF1 alpha production in ventricular cardiomyocytes.

Incubation of cultured ventricular cardiomyocytes with high oligomycin concentrations (100 micrograms/ml), either alone or combined with 2-deoxyglucose (20 mM), led to the rapid depletion of cellular ATP. Inositol (poly)phosphate production decreased, and 6-keto PGF1 alpha production was increased. In cells depleted of ATP, either by low oligomycin concentrations or by sodium azide, 6-keto PGF1 alpha was not appreciably increased. There was a 25% rise in the release of fatty acids from the sn-2 position in glycerophospholipids. We suggest that oligomycin at high concentrations causes the release of free arachidonic acid from phospholipids either by non-PIP2-specific PLC and DG lipase or by phospholipase D, phosphatidic acid phosphatase and DG lipase. The effect is unrelated to decreased cellular ATP content.

6-Ketoprostaglandin F1 alpha↗

Mitogenic activation of phosphoinositide turnover and DNA synthesis in murine CD4+8+ thymocytes.

Eighty percent of the lymphoid cells in the murine thymus are premature CD4+8+ (double positive) thymocytes. The vast majority of the double-positive cells do not maturate and die in the thymus. Although these cells are subjected to thymic selection processes, their activation competence has been an enigma. We have separated out CD4+8+ cells and studied their early and late responses to several mitogens. Concanavalin A, anti-CD3 (145-2C11) or anti-Thy1 (G7) monoclonal antibodies enhanced phosphoinositide turnover in double-positive thymocytes. However, DNA synthesis in the mitogen-stimulated cells was only accomplished if IL-2 or IL-4 was added. Alternatively, DNA synthesis could be induced by the calcium ionophore A23187 and phorbol myristate acetate (PMA). The latter mode of activation did not require the addition of exogenous lymphokines. CD4+8+ thymocytes did not secrete IL-2 or IL-4 following activation by either mitogens or A23187 and PMA. These findings demonstrate that CD4+8+ thymocytes resemble mature T cells in their ability to respond with DNA synthesis when activated by T-cell mitogens and IL-4 as well as IL-2. The results also delineate the difference between receptor mediated mitogenesis and pharmacological stimulation.

Animals↗

Resorbed lateral incisors adjacent to impacted canines have normal crown size.

The importance of detecting maxillary canine impaction is that it may compromise dental health, particularly since a small but significant proportion of impacted canines is associated with the resorption of the roots of neighboring teeth. It has been shown that the existence of small and peg-shaped lateral incisors is highly correlated with maxillary canine palatal impaction. To date, however, it has not been established whether the root resorption that occurs has a similar correlation or a predilection for one or other types of lateral incisor crown structure. Accordingly, a group of patients with buccally or palatally impacted canines, in which root resorption of the lateral incisor could be diagnosed roentgenographically, was examined and compared with a group of cases with palatally impacted canines, none of which showed root resorption, which served as controls. The mesiodistal crown dimension of the lateral incisor in the experimental group was found to be normal in all patients except three (13%), which was significantly different from the distribution of lateral incisor size in the control group (p < 0.001). In the majority of the cases, aggressive root resorption of the lateral incisor root had occurred. We would speculate that in these cases, the normal-sized and early developing lateral incisor root obstructs the deviated eruption path of the canine and consequently stands a considerably greater chance of being damaged by resorption.

Adolescent↗

Trauma as a possible etiologic factor in maxillary canine impaction.

A chain of events in the development of the dentition following trauma is described. Shortening of the root of the lateral incisor or displacement of the tooth bud, both as a sequel to trauma, may affect the path of eruption of the adjacent canine after dental injury. Special attention should be paid to the further development and eruption of the directly and indirectly affected teeth.

Child↗

Multiple effects of staurosporine, a kinase inhibitor, on thymocyte functions. Comparison with the effect of tyrosine kinase inhibitors.

The effects of staurosporine, a protein kinase inhibitor, on the signal transduction and proliferation of thymocytes were studied. Signal transduction in response to Concanavalin A (Con A) as well as Concanavalin A (Con A)-induced augmentation of [3H]inositol incorporation into phospholipids were inhibited by staurosporine (> or = 10(-8) M). Staurosporine inhibited thymocyte proliferation in response to Con A in the presence or absence of the phorbol ester, phorbol myristate acetate (TPA) (10 nM). This inhibition was observed regardless of whether staurosporine was added together with Con A or 3 hr later. High concentrations of staurosporine (> 10(-8) M) inhibited thymocyte proliferation induced by the calcium ionophore A23187 and the phorbol ester TPA, whereas lower concentrations of the inhibitor (< or = 10(-8) M) enhanced thymidine incorporation in response to these activators. This dual effect of staurosporine was also observed in the presence of the staurosporine-related kinase inhibitor, K252a. In contrast, the tyrosine kinase inhibitor, tyrphostin AG490, inhibited the response to A23187 and TPA at all concentrations of the inhibitor and no augmentation was seen. Interleukin 2 (IL-2)-driven mitogenesis in IL-2-dependent cells was also inhibited by staurosporine. We suggest that the inhibition of thymocyte proliferation by staurosporine results from inhibition of both protein kinase C and tyrosine kinase: the augmentation of the response to A23187 and TPA results from inhibition of protein kinase C. Inhibition of signal transduction as well as inhibition of IL-2-driven mitogenesis result from inhibition of tyrosine kinase.

Alkaloids↗

Stimulatory and inhibitory effects of 1,25-dihydroxyvitamin D3 on thymocyte mitogenesis induced by phorbol ester and calcium ionophore.

UNLABELLED: Mouse medullary thymocytes have specific receptors for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The mitogenic stimulation of these cells by phytohemagglutinin in the presence or absence of the phorbol ester TPA is inhibited by 1,25(OH)2D3. The calcium ionophore A23187 did not reverse the inhibition by 1,25(OH)2D3 of phytohemagglutinin. Stimulation of thymocytes with either TPA or A23187 alone did not result in proliferation. Co-stimulation of the thymocytes with TPA and A23187 induces cell proliferation. 1,25(OH)2D3 markedly enhanced the TPA and A23187-induced cell proliferation even when added 4 h after the initiation of the culture. In contrast, DNA synthesis by thymocytes incubated for 4 h in the presence of TPA and A23187 and then cultured in medium containing 1,25(OH)2D3 but in the absence of both TPA and A23187, was inhibited by 1,25(OH)2D3. The extent of inhibition was comparable to the inhibition of lectin-induced stimulation by the hormone. Using monoclonal antibodies to neutralize IL-2 and block IL-2 receptors we showed that 1,25(OH)2D3 enhanced the IL-2-independent component of the A23187- and TPA-induced mitogenesis. IN CONCLUSION: (1) The nature and presence of the mitogenic signal determines whether 1,25(OH)2D3 enhances or inhibits thymocyte stimulation. (2) Both stimulatory and inhibitory actions of 1,25(OH)2D3 seem to take place at points distal to the initial increase in intracellular calcium or activation of protein kinase C.

Calcimycin↗

Quintuplets with clefts: follow-up at ten years of age.

A set of quintuplets, three of which were born with various degrees of oral clefting, were followed up to the age of 10 years. Study models, as well as panoramic and intraoral roentgenograms were collected at ages 5 and 10 years. Cephalometric roentgenograms were added at the age of 10 years. Analysis of the growth charts for height and weight indicated normal somatic development, save for a persistent, albeit diminishing, lag for the two most severely affected siblings. The latter also demonstrated a more vertical craniofacial growth pattern. The dental arch dimensions were within normal range, except for the maxillary and mandibular widths in the two more affected siblings, who also exhibited a delay of one or two stages of dental development in an intersibling comparison. These findings indicate that in the more severely affected siblings, there was only partial growth catch-up at the age of 10 years.

Cephalometry↗

Functional and esthetic rehabilitation of an adolescent cleft lip and palate patient.

Many patients with clefts that also affect the alveolar ridge present with congenital absence of the permanent maxillary lateral incisors. This paper describes the treatment of an adolescent cleft lip and palate patient whose missing and unesthetic maxillary incisors were replaced by a combination of fixed and removable partial dentures.

Adolescent↗

Dissociation between inositol polyphosphate production and mitogenesis in mouse thymocytes.

Cortical and medullary thymocytes can be separated from each other by virtue of the fact that only cortical thymocytes bear peanut agglutinin (PNA) receptors. The mitogenic responses of subpopulations of thymocytes were studied. We have confirmed the results of Conlon et al. [(1982) J. Immun. 128, 797-801], that lectin-induced stimulation of unseparated cells, and PNA- but not PNA+ thymocytes, results in DNA synthesis. In contrast, both subpopulations, as well as unseparated cells, synthesize DNA in response to the calcium ionophore A23187 in the presence of the phorbol ester TPA, suggesting an impairment of signal transduction in PNA+ cells. However, comparable amounts of inositol phosphates were accumulated in PNA- and PNA+ thymocytes in response to Concanavalin A (Con A). We suggest that mitogenic lectins generate a third signal in addition to elevation of intracellular free calcium concentration and activation of protein kinase C. This signal is generated in PNA- but not in PNA+ thymocytes and is obligatory for lectin-induced stimulation.

Animals↗

Familial trends in palatal canines, anomalous lateral incisors, and related phenomena.

Our previous studies have established a strong link between small, peg-shaped and missing lateral incisors, and palatally-displaced maxillary canine teeth. Since these anomalies of lateral incisor development are known to be under strong genetic control, the hypothesis was that first degree relatives of patients with palatal canines would themselves show a raised prevalence of the anomalies. The present study also investigated a possible link between palatal canines and lateness in development of the dentition, and a relative absence of crowding, both of which are phenomena that have been mentioned both by us and elsewhere as similarly linked phenomena. Results showed that anomaly of the lateral incisors was found to be four times that of the general population and that positive links with late development of the dentition and a relative absence of crowding were also seen.

Adolescent↗

Effect of trauma to the primary incisors on the alignment of their permanent successors in Israelis.

117 children who had experienced trauma to their primary incisors were re-examined in their transitional or permanent dentition stage. The control group consisted of 174 children with a corresponding dental developmental age. All the children were examined clinically and the intra- and interarch relations of the anterior segments were recorded. The prevalence of patients with at least one malposed incisor was higher in the trauma group. Trauma to the primary dentition was found to be a contributing factor affecting the alignment of the permanent successors. Early loss of the primary incisors did not cause loss of space in most of the cases; however, it was associated with malposition of their permanent successors. Lack of eruption guidance or the direct effect of the injury on the position of the developing bud could be considered as contributing etiologic factors. There was a very low prevalence of more serious malocclusion features, like impaction, in the trauma group.

Child↗

Calcium regulates inositol 1,3,4,5-tetrakisphosphate production in lysed thymocytes and in intact cells stimulated with concanavalin A.

Lysed mouse thymocytes release [3H]inositol 1,4,5 trisphosphate from [3H]inositol-labelled phosphatidyl inositol 4,5-bisphosphate in response to GTP gamma S, and rapidly phosphorylate [3H]inositol 1,4,5-trisphosphate to [3H]inositol 1,3,4,5-tetrakisphosphate. The rate of phosphorylation is increased approximately 7-fold when the free [Ca2+] in the lysate is increased from 0.1 to 1 microM, the range in which the cytosolic free [Ca2+] increases in intact thymocytes in response to the mitogen concanavalin A. Stimulation of the intact cells with concanavalin A also results in a rapid and sustained increase in the amount of inositol 1,3,4,5-tetrakisphosphate, and a much smaller transient increase in 1,4,5-trisphosphate. Lowering [Ca2+] in the medium from 0.4 mM to 0.1 microM before addition of concanavalin A reduces accumulation of inositol 1,3,4,5-tetrakisphosphate by at least 3-fold whereas the increase in inositol 1,4,5-trisphosphate is sustained rather than transient. The data imply that in normal medium the activity of the inositol 1,4,5-trisphosphate kinase increases substantially in response to the rise in cytosolic free [Ca2+] generated by concanavalin A, accounting for both the transient accumulation of inositol 1,4,5-trisphosphate and the sustained high levels of inositol 1,3,4,5-tetrakisphosphate. Inositol 1,3,4,5-tetrakisphosphate is a strong candidate for the second messenger for Ca2+ entry across the plasma membrane. This would imply that the inositol polyphosphates regulate both Ca2+ entry and intracellular Ca2+ release, with feedback control of the inositol polyphosphate levels by Ca2+.

Animals↗

Eruption of rootless teeth in congenital renal disease.

Eruption of rootless mandibular premolars and other dental defects in a girl suffering from congenital kidney disease are described. The successful management of these excessively mobile teeth allowed them to develop roots of sufficient length. Hypotheses of tooth emergence are viewed in the light of these rootless eruptions.

Bicuspid↗

Quintuplets with clefts: follow-up at 5 years.

Follow-up observations are presented of a set of quintuplets at 5 years of age. Three of the children were born with different degrees of oral clefting. Height and weight comparisons between siblings with clefts and those without reveal that the most severely affected children lagged in their height measurements at the age of 5 years. This may indicate need for special awareness when caring for such children. A relative constriction of the anterior segment of the maxillary dental arch in two of the affected siblings may reflect a possible effect from previous surgical intervention.

Body Height↗