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Biomedical subjects

R Ber

Publications and source records attributed to R Ber.

At least 19 recordsLinked to original sources
PubMed2001

Twenty years of experience using trigger films as a teaching tool.

Trigger films or trigger videos that depict patient-physician encounters can be used to provoke reflection, stimulate discussion, help learners confront their feelings and give learners practice in responding to challenges. For more than 20 years at the B. Rappaport Faculty of Medicine, the authors have used trigger films to teach/demonstrate the doctor-patient relationship, medical ethics, diagnostic thinking, professional behavior, and the application of the principles of the Israeli Patient Bill of Rights, and have found them to be an excellent tool for provoking active participation in small-group discussions. The authors describe how they have effectively produced and used trigger films in an Introduction to Clinical Medicine course. They highly recommend the "homemade" production of trigger films.

Education, Medical↗
PubMed2000

Ethical issues in gestational surrogacy.

The introduction of contraceptive technologies has resulted in the separation of sex and procreation. The introduction of new reproductive technologies (mainly IVF and embryo transfer) has led not only to the separation of procreation and sex, but also to the redefinition of the terms mother and family. For the purpose of this essay, I will distinguish between: 1. the genetic mother--the donor of the egg; 2. the gestational mother--she who bears and gives birth to the baby; 3. the social mother--the woman who raises the child. This essay will deal only with the form of gestational surrogacy in which the genetic parents intend to be the social parents, and the surrogate mother has no genetic relationship to the child she bears and delivers. I will raise questions regarding medical ethical aspects of surrogacy and the obligation(s) of the physician(s) to the parties involved. I will argue that the gestational surrogate is "a womb to rent," that there is great similarity between gestational commercial surrogacy and organ transplant marketing. Furthermore, despite claims to freedom of choice and free marketing, I will claim that gestational surrogacy is a form of prostitution and slavery, exploitation of the poor and needy by those who are better off. The right to be a parent, although not constitutional, is intuitive and deeply rooted. However, the issue remains whether this right overrules all other rights, and at what price to the parties involved. I will finally raise the following provocative question to society: In the interim period between today's limited technology and tomorrow's extra-corporeal gestation technology (ectogenesis), should utilizing females in PVS (persistent vehetative state) for gestational surrogacy be socially acceptable/permissible--provided they have left permission in writing?

Depersonalization↗
PubMed2000

A multidisciplinary forum for ethics in medicine: our seven years experience.

The Rappaport Faculty of Medicine of the Technion established an Ethics in Medicine Forum in March 1993. The main objective of the forum was to increase awareness of the philosophical principles of ethics in medicine, as defined and developed in the western world during the last three decades. The multidisciplinary forum meets once a month during the academic year. Our 7 years experience is documented. Of the 45 meetings, 30 were clinically oriented and of these more than half were based on cases. Only 15 meetings were purely theoretical. Our principal assumption was that any and every topic could be discussed, including those covered by the law. We explored how well western philosophical principles and rules fit the Israeli picture. Many of the forum discussions related to the draft of the Patient's Bill of Rights, which came into effect on 12 May 1996. The role of the "legal" hospital ethics committees was compared to that of the "advisory" ethics committees whose members constituted a large share of our forum. The multicultural Israeli population and the practice of medicine therein raised many lively discussions. The principle of autonomy in the ultraorthodox and in the family setting was a highly controversial issue. The forum served as a workshop for examining traditional medical ethical principles, which we strongly feel needs to be amended in light of the 1996 Patient's Bill of Rights. From our 7 years experience with an Ethics in Medicine Forum we recommend that medical ethical deliberations focus on genuine medical cases.

Clinical Medicine↗
PubMed1998

Characterization and regulation of prolactin receptors in MA-10 Leydig cells.

The aim of this study is to further characterize the prolactin receptors (PRL-R) previously reported in the murine Leydig tumor MA-10 cell line, as well as to study their homologous and heterologous regulation. Two forms of PRL-R, a high and a low molecular weight form, were revealed by studies of covalent crosslinking of 125I-human GH to cultured MA-10 cells or cell membranes and immunoprecipitation of the solubilized PRL-R complexes with polyclonal anti PRL-R antibody, followed by SDS-PAGE and autoradiography. The long form had a molecular weight of 101 kDa and was predominant when the study was performed in the presence of protease inhibitors. The short form, with a molecular weight of 39 kDa, appeared, at least in part, to be a proteolytic product of the longer form. The same size forms of PRL-R were detected by crosslinking studies in the parental C57BL/6 mouse testicular Leydig cells, indicating the physiological relevance of the MA-10 cell model to the study of Leydig cell PRL-R. Homologous down-regulation of PRL-R was demonstrated in cultured MA-10 cells exposed for 24 h to increasing concentrations of PRL. In contrast, heterologous, 3 5-fold up-regulation of PRL-R was induced by various cAMP-elevating agents, including 8-bromo-cAMP (10(-4) -10(-3) M), dibutyryl cAMP (3 x 10(-3) M) and cholera toxin (1-10 ng/ml), although not by hCG (up to 100 ng/ml). This up-regulatory effect was apparently the result of a change in affinity, since cholera toxin caused a 2.4-fold increase in PRL-R affinity, with no change in the number of binding sites. In summary, these studies provide further evidence that MA-10 Leydig cells can serve as a physiologically relevant model for the study of PRL and PRL-R interactions, both at the functional level, as shown in our previous study, and at the structural and regulatory levels as shown in the current study.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

A new cryosurgical device for controlled freezing.

A new cryosurgical device was developed in this study to facilitate examination of factors affecting the outcome of cryotreatment. Special emphasis was placed on the control of the cooling rate at the freezing front. In the new computer-controlled cryosurgical device, the controlling variable is the cryoprobe temperature, which is calculated to ensure prespecified cooling rates at the freezing front. Details of the new cryodevice, results of a validation test, and the system characteristics are presented in Part I of this study. In this part of the study initial results of 13 in vivo experimental cryotreatments, including histological observations, are presented. The in vivo pilot investigations include the normal, healthy skin and the underlying skeletal muscle of the thighs in rabbits. Using low cooling rate-controlled freezing, the new cryosurgical device is demonstrated here as an effective surgical tool. An in vivo temperature measurement technique is employed based on miniature thermocouples and X-ray images. Thermal analysis of the heat transfer in the cryotreated tissue is presented, based on the temperature measurements and on numerical heat transfer simulations. Cryotreated tissue was extracted either immediately or 4 or 7 days following the procedure. The histological observations on the skeletal muscle of the 4- and 7-day postcryoinjury were not substantially different. The effective penetration depth of the cryolesion was in the range of 5-15 mm, possibly extending up to 25 mm, depending on the specific area treated and operating parameters. The cryotreatment resulted in complete destruction of cells in the skin followed by rapid replacement by epithelial cells. Histological responses to cryotreatment of skeletal muscle were similar to those resulting from a range of traumatic episodes, e.g., crush damage. It was also found that most of the blood vessels in the cryotreated region remained intact without histological evidence of extravasation of erythrocytes.

Animals↗
PubMed1996

Coordinate suppression of myeloma-specific genes and expression of fibroblast-specific genes in myeloma X fibroblast somatic cell hybrids.

In most instances, fusion of differentiated cell types with fibroblasts has resulted in the extinction of the differentiation-specific traits of the non-fibroblast parental cell. To explore the genetic basis of this phenomenon, we have studied a series of somatic cell hybrids between mouse myeloma and fibroblasts. All the hybrids were adherent having a fibroblast-like phenotype. Molecular analysis revealed that plasma cell specific genes like the productively rearranged Ig genes, the J chain gene and genes for the cell surface markers CD20 and PC1, were extinguished in the hybrids. In contrast, fibroblast specific genes like fibronectin, alpha 2(I) and III collagens, as well as the receptor for fibroblast growth factor (flg), were expressed. Extinction was not due to chromosomal loss or lack of the relevant genes. To learn about the mechanism(s) of this phenomenon we have looked for the presence of positive and negative transcription factors in our hybrids. Expression of the PU.1 transcription factor, a member of the Ets transcription factor family normally expressed in B cells and macrophages, was lost in the cell hybrids. Interestingly, we found that the B-cell-specific Oct-2 transcription factor was still expressed at somewhat variable levels in several of the hybrid cell lines. In contrast, expression of the recently identified octamer coactivator BOB.1/OBF.1 was extinguished in all cell hybrids. This supports a critical role of this transcriptional coactivator for B-cell-specific gene expression. In addition, the Id and HLH462 genes coding for proteins known to repress bHLH transcription factors by formation of heterodimers, were found to be expressed at increased levels in fibroblasts and in the hybrids, indicating that their increased levels might also contribute to the suppression of myeloma-specific genes. Our results show that in myeloma x fibroblast hybrids, the phenotype of the fibroblast is dominant. It is suggested that fibroblasts contain regulatory "master" genes that are responsible for activation of the fibroblast differentiation pathway and suppress differentiation programs of other cell types.

Animals↗
PubMed1996

Prolactin and MA-10 Leydig cell steroidogenesis: biphasic effects of prolactin and signal transduction.

The present investigation was designed to study the direct role of PRL on testicular Leydig cell steroidogenesis, using the MA-10 murine Leydig tumor cell line as a model system. We have previously reported on the presence of specific PRL binding sites in those cells, and we now demonstrate the functionality of those sites and the biological responses induced by the binding of PRL. When cultured MA-10 cells were exposed for 24 h to increasing concentrations of PRL, washed, and then subjected to a 3-h human CG (hCG) stimulation test, a clear dose-dependent biphasic effect of PRL on the steroidogenic response was observed, even though PRL had no effect on MA-10 cell proliferation: at low PRL concentrations (0.1-10 ng/ml), hCG-induced steroidogenesis was stimulated (maximal stimulation by 1 ng/ml PRL being 200-250% of control); at higher concentrations, hCG-induced steroidogenesis was inhibited (60% inhibition was achieved by 1000 ng/ml PRL). When steroidogenesis was induced with various concentrations of cholera toxin, instead of hCG, no effect of the prior exposure to increasing concentrations of PRL was observed, indicating that PRL acts either at the level of the LH/hCG receptor or at some stage proximal to adenylate cyclase. Indeed, further study revealed that 24 or 72 h exposure of MA-10 cells to PRL caused a dose-dependent reduction in hCG binding. Thus, the maximal inhibition of 62% after 72 h with 500 ng/ml PRL, may explain, at least in part, the inhibitory effects of high PRL concentrations on hCG-induced progesterone secretion. Evidence demonstrating possible involvement of a pertussis toxin-(PT-)sensitive G protein in the signal transduction mechanism of PRL receptors is also presented: 1. GTP caused a dose-dependent reduction in affinity (Ka) of PRL binding by its receptors (from Ka = 1.66 +/- 0.2 x 10(9) M(-1) for control MA-10 cell membranes to Ka 3.03 +/- 0.6 x 10(8) M(-1) for membranes incubated with 8 mM GTP). 2. Prior exposure of MA-10 cells to PRL (10 pg/ml) caused a significant reduction in the ability of a 44-kDa membrane protein to undergo PT-induced [32P]ADP-ribosylation. These results demonstrate that MA-10 Leydig cells possess highly specific and biologically functional PRL receptors mediating direct and dose-dependent biphasic effects of PRL on hCG-induced progesterone secretion. These cells thus offer a suitable model to study the mechanism(s) of PRL action and signal transduction of its receptor on a physiologically relevant differentiated function.

Animals↗
PubMed1994

Electrostatic attraction by surface charge does not contribute to the catalytic efficiency of acetylcholinesterase.

Acetylcholinesterases (AChEs) are characterized by a high net negative charge and by an uneven surface charge distribution, giving rise to a negative electrostatic potential extending over most of the molecular surface. To evaluate the contribution of these electrostatic properties to the catalytic efficiency, 20 single- and multiple-site mutants of human AChE were generated by replacing up to seven acidic residues, vicinal to the rim of the active-center gorge (Glu84, Glu285, Glu292, Asp349, Glu358, Glu389 and Asp390), by neutral amino acids. Progressive simulated replacement of these charged residues results in a gradual decrease of the negative electrostatic potential which is essentially eliminated by neutralizing six or seven charges. In marked contrast to the shrinking of the electrostatic potential, the corresponding mutations had no significant effect on the apparent bimolecular rate constants of hydrolysis for charged and non-charged substrates, or on the Ki value for a charged active center inhibitor. Moreover, the kcat values for all 20 mutants are essentially identical to that of the wild type enzyme, and the apparent bimolecular rate constants show a moderate dependence on the ionic strength, which is invariant for all the enzymes examined. These findings suggest that the surface electrostatic properties of AChE do not contribute to the catalytic rate, that this rate is probably not diffusion-controlled and that long-range electrostatic interactions play no role in stabilization of the transition states of the catalytic process.

Acetylcholinesterase↗
PubMed1994

Prolactin and testicular Leydig cell function: characterization of prolactin receptors in the murine MA-10 testicular Leydig cell line.

The direct role of prolactin (PRL) in testicular function is still unclear, mostly because of lack of a suitable in vitro model. To establish the suitability of the MA-10 murine tumor Leydig cell line for the study of PRL receptors (PRLR) and effects on steroidogenesis, we initially characterized PRLR on cultured MA-10 cells. The specific binding (Bs) of [125I]human growth hormone (hGH) depends on time, temperature, and Mg2+ ion and protein concentrations, with absolute specificity for the lactogenic hormones hGH and ovine PRL. Bs is saturable and is to a single class of high-affinity (Ka = 3.6 x 10(9) M-1) low-capacity (Bmax = 19.5 fmol/mg protein) binding sites. The molecular weight of PRLR, determined by cross-linking to [125I]hGH, SDS-PAGE and autoradiography, is 35 kDa for the free receptor, suggesting that the short-form PRLR protein, previously described in liver and mammary glands, is that primarily found in MA-10 cells. Thus, the demonstration of specific PRL binding sites on MA-10 Leydig cells, with characteristics similar to primary Leydig cell PRLR, suggests that this cell line can serve as a good model for both the study of PRLR mechanism of action and the role of PRL in Leydig cell function.

Animals↗
PubMed1993

Sequence analysis suggests a recent duplication of the growth hormone-encoding gene in Tilapia nilotica.

The sequence of two growth hormone(GH)-encoding genes from tilapia fish (Tilapia nilotica) is reported. Our data indicate that the presence of two GH in the tilapia genome is a consequence of a relatively recent duplication event. The two genes are highly homologous, having a similar intron (five)/exon (six) arrangement, and both encode an identical polypeptide. Sequence similarity extends up to bp -628 upstream to the transcription start point, after which the sequences of the two genes are not related to each other. The presence of two GH in the tilapia genome is supported both by the nucleotide sequence and by genomic DNA blot hybridization analysis. Tilapias, like salmonids, contain an extra intron compared with the mammalian GH structure. We suggest that within the superorder Teleostei, the insertion of intron 5 into GH took place after the evolutionary separation of Cyprinoidea, but before Isospondyli (salmonids) and Acanthopterygii (tilapias) were separated. Thus, the additional intron which is probably present in many teleost fish GH may provide an excellent natural marker for evolution and classification studies.

Amino Acid Sequence↗
PubMed1992

Structure and sequence of the growth hormone-encoding gene from Tilapia nilotica.

We report here the nucleotide (nt) sequence of the growth hormone (GH)-encoding gene (GH) of the tilapia fish (Tilapia nilotica). The T. nilotica GH gene, similar to that of the salmonidae fish, Atlantic salmon and rainbow trout, contains six exons and five introns. However, despite the presence of an additional intron (intron V), the size of the primary transcript of T. nilotica GH (1666 nt) is significantly shorter than that of all other currently characterized fish GH genes. Comparison of sequences upstream from the transcription start point of the tilapia, carp, rainbow trout and Atlantic salmon GH genes shows a region of high homology preceding the typical TATA box. This homology does not seem to extend to the regions further upstream of the compared fish GH genes and is not observed to be present in the corresponding region of the mammalian GH genes. A sequences search for putative DNA-binding domains for transcription factors shows the presence of short nt stretches similar to those considered to be involved in the tissue-specific expression of mammalian GH genes.

Amino Acid Sequence↗
PubMed1990

Extinction of Ig genes expression in myeloma x fibroblast somatic cell hybrids is accompanied by repression of the oct-2 gene encoding a B-cell specific transcription factor.

In most instances, fusion of differentiated cell types with fibroblasts has resulted in the extinction of differentiation-specific traits of the nonfibroblast parental cell. To explore the genetic basis of this phenomenon, we have used a series of somatic cell hybrids between myeloma cells and fibroblasts. Previous findings show that in these hybrids expression of the immunoglobulin (Ig) genes was extinguished at the transcriptional level. Our present results show that NF-kappa B transcription factor, known to be critical for kappa-chain enhancer activity, is present although in a lower amount, in the nucleus and in the cytosolic fraction of most of these hybrids (probably attached to the previously postulated I-kappa B inhibitor). In contrast, the expression of the NF-A2/OTF-2 transcription factor encoded by the oct-2 gene, which binds to the octameric motif located in the Ig promoters and heavy chain gene enhancer, is extinguished at the transcriptional level. Our data thus suggest that extinction of Ig genes expression occurs via an indirect mechanism in which a fibroblast factor suppresses transcription factor(s) which are critical for Ig transcription.

Animals↗
PubMed1990

Infection of tomato by the tomato yellow leaf curl virus: susceptibility to infection, symptom development, and accumulation of viral DNA.

Symptom development in tomato plants following whitefly-mediated inoculation with tomato yellow leaf curl virus (TYLCV) was related to the occurrence of viral DNA using a specific DNA probe. Although disease symptoms were first observed 15 days post-inoculation, viral DNA could be detected 7 days earlier. TYLCV-DNA concentrations reached an optimum 4 days before symptoms appeared. The highest concentrations of TYLCV-DNA were found in rapidly growing tissues (shoot apex, young leaves, roots) and in the stems; the lowest concentrations were found in the older leaves and cotyledons. Plants were also inoculated on specific sites. Young leaves and apices were the best targets for virus inoculation. In these tissues, the viral DNA replicated at the site of inoculation and was transported first to the roots, then to the shoot apex and to the neighboring leaves and the flowers. Inoculation through the oldest leaves was inefficient.

DNA Probes↗
PubMed1990

Administered dose and tumor dose of bleomycin labeled with cobalt-57 in mice and men.

Tumor concentrations of the chemotherapeutic drug, bleomycin, labeled with cobalt-57 (Co-bleo) were compared in mouse tumor models and in human lung tumors using quantitative single-photon emission computed tomography. Drug concentrations in histologically similar human tumors showed marked variability for the same injected dose (ID). Small cell carcinomas showed concentrations between 1.09 and 8.85 %ID/cc x 10(-3) while non-small cell lung tumors showed a concentration variation between 0.36 and 6.75 %ID/cc x 10(-3). In contrast to the situation in human tumors, uptake in mouse tumors showed only slight variability in animals with the same tumor model. EMT-6 tumors in mice showed at 6 hr significantly higher uptake of Co-bleo (p less than 0.001) and significantly higher tumor-to-lung ratio (p less than 0.001) when compared to murine fibrosarcomas. The EMT-6 tumors in contrast to the fibrosarcomas responded to bleomycin treatment in a dose dependent manner. The results indicate that while in mice the tumor dose closely follows the administered dose, in humans, the tumor dose and the tumor-to-lung ratio in the individual patient cannot be predicted from the administered dose.

Aged↗
PubMed1989

The concentration of bleomycin labeled with Co-57 in primary and metastatic tumors.

The concentration over time of bleomycin labeled with Co-57 was measured in 39 primary and metastatic tumor sites in 16 patients using a newly developed and validated single photon emission computed tomography (SPECT) method. There were nine primary tumors, 15 metastatic tumors, and five multifocal lymphomas. Co-bleomycin concentrations also were measured in primary and metastatic B-16 melanoma tumors in mice. In humans, metastases to lymph nodes (1.58 +/- 0.51 %ID/ml X minutes) showed significantly higher (P less than 0.01) tumor cumulative concentrations of Co-bleomycin than metastases to liver, bone, lung, and brain (0.76 +/- 0.20 %ID/ml X minutes). The cumulative concentrations of Co-bleomycin in human lymphomas (1.1 +/- 0.25 %ID/ml X minutes) also were significantly higher (P less than 0.01) than the concentrations in human metastases other than lymph nodes. The cumulative concentration in cerebral metastases (0.65 +/- 0.18 %ID/ml X minutes) was significantly lower (P less than 0.05) than in noncerebral metastases (1.22 +/- 0.53 %ID/ml X minutes). Primary tumors in humans showed higher concentrations of Co-bleomycin than metastases, except for lymph nodes. In contrast with humans, murine metastases showed higher concentrations of Co-bleomycin (6.20 +/- 2.65 %ID/g) than primary tumors (2.94 +/- 0.90 %ID/g) (P less than 0.001). The concentrations of Co-bleomycin in murine tumors that were affected by bleomycin were about three orders of magnitude higher than in human tumors. The results of this in vivo study document the differences in drug delivery of Co-57-labeled bleomycin to human primary and metastatic tumors and show differences in drug delivery between human and murine tumors.

Adolescent↗
PubMed1989

Multiple forms of SppI (secreted phosphoprotein, osteopontin) synthesized by normal and transformed rat bone cell populations: regulation by TGF-beta.

Metabolic labeling has revealed that rat bone cell populations in culture synthesize several forms of the secreted phosphoprotein, SppI. Most cell populations produced two major [32PO4]-labeled forms that behaved anomolously on SDS-PAGE migrating at 60 kDa and 56 kDa on 10% gels and 55 kDa and 44 kDa on 15% gels. Minor forms of intermediate sizes were also resolved. In normal bone cells the 60 kDa form was predominant and was the only form produced by the clonal bone cell line, RCA 11, whereas the 56 kDa a form predominated in the transformed bone cell line, ROS 17/2.8. In all populations [35S]-methionine-labeling revealed SppIs at approximately 60 kDa but no 56 kDa form. Each form of SppI was specifically cleaved by thrombin which generated fragments of approximately 28 kDa. Transforming growth factor beta 1 increased SppI mRNA levels 3 to 6-fold within 24 h in the normal bone cells, but no increase occurred in the ROS 17/2.8 cells. The elevated expression of SppI was reflected in a selective increase in the synthesis of the [32PO4]-and [35S]-methionine-labeled 60 kDa SppIs.

Animals↗