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Biomedical subjects

L Sachs

Publications and source records attributed to L Sachs.

At least 91 records · Page 5Linked to original sources
PubMed1991

Drug use and the role of patients and prescribers.

In order to move towards rational drug use in any national or local setting the methods of inquiry have to be expanded. Both the public and private sector have to be addressed. In the latter the pharmacists might be studied using a tracer, fictitious client. One important factor influencing prescribing, drug information, has rarely been assessed scientifically. Experimental studies using group randomization are, however feasible even in developing countries. The individual human being must be in the focus of drug studies and health care and health in the foreground. The combination of qualitative and quantitative methods will assist us to achieve rational drug use that is culturally acceptable, economically feasible and pharmacologically sound.

Developing Countries↗
PubMed1991

The oncogenic potential of an activated Hox-2.4 homeobox gene in mouse fibroblasts.

The homeobox gene Hox-2.4 is transcriptionally activated in cells of the mouse myeloid leukemia WEHI-3B. The constitutive Hox-2.4 expression in WEHI-3B cells is due to insertion of a transposable element belonging to the family of intracisternal A particles. In this study, we demonstrated the oncogenic potential of this activated homeobox gene. NIH 3T3 fibroblast clones bearing the activated Hox-2.4 gene produced fibrosarcomas in nude mice.

Animals↗
PubMed1991

The network of hemopoietic regulatory proteins in myeloid cell differentiation.

There are clones of myeloid leukemic cells that can be induced to undergo terminal cell differentiation to macrophages by normal hemopoietic regulatory proteins. Induction of differentiation in two different clones of myeloid leukemic cells with interleukin 6 (IL-6) or granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in induction of mRNA for the hemopoietic regulatory proteins IL-6, GM-CSF, interleukin 1 alpha and interleukin 1 beta, tumor necrosis factor, and transforming growth factor beta 1. In one of these clones, induction of differentiation with GM-CSF was also associated with induction of mRNA for macrophage colony-stimulating factor (M-CSF) but not for the receptor for M-CSF (c-fms), whereas in the other clone, induction of differentiation with IL-6 was associated with induction of mRNA for both c-fms and M-CSF. The clones also differed in their responsiveness to these regulators. There was no induction of mRNA for granulocyte colony-stimulating factor or interleukin 3 during differentiation of either clone. The results indicate that the genes for a nearly normal network of positive and negative hemopoietic regulatory proteins are induced during differentiation of these myeloid leukemic cells and that there are leukemic clones with specific defects in this network.

Animals↗
PubMed1990

Selective regulation of the activity of different hematopoietic regulatory proteins by transforming growth factor beta 1 in normal and leukemic myeloid cells.

The viability of normal bone marrow myeloid precursor cells induced by interleukin-6 (IL-6) or IL-1 alpha and the ability of IL-6 and IL-1 alpha to induce the formation of colonies of granulocytes, macrophages, or megakaryocytes in densely seeded bone marrow cultures was suppressed by transforming growth factor-beta 1 (TGF-beta 1). Induction of normal bone marrow colony formation by IL-3 was much less sensitive to TGF-beta 1, and there was little or no effect of TGF-beta 1 on colony formation induced by macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF). In different clones of myeloid leukemic cells, TGF-beta 1 suppressed differentiation induced with IL-6, IL-1 alpha, or lipopolysaccharide (LPS), but did not suppress differentiation induced with IL-3 or GM-CSF. The effect of TGF-beta 1 on differentiation of the leukemic cells can be dissociated from its effect on cell growth. TGF-beta 1 suppressed the production of IL-6 in normal bone marrow cells cultured with IL-1 alpha and the production of IL-6 and GM-CSF in leukemic cells cultured with IL-1 alpha or LPS. The suppression of IL-6 production can explain the suppression by TGF-beta 1 of the effects of IL-1 alpha and LPS that are mediated by IL-6. TGF-beta 1 also suppressed differentiation in clones of myeloid leukemic cells induced with differentiation factor/leukemia inhibitory factor and tumor necrosis factor. In different leukemic clones TGF-beta 1 suppressed or enhanced induction of differentiation with dexamethasone. The results show that TGF-beta 1 can selectively control the activity of different molecular regulators of normal and leukemic hematopoiesis.

Animals↗
PubMed1990

The symbolic role of drugs in the socialization of illness behaviour among Swedish children.

Medicine is never a neutral agent in people's lives. Children may get introduced to the use of drugs either in relation to more or less dramatic situations when they feel ill or for the sake of staying healthy, as when they are given vitamins or other health-promoting preparations. Whether and how the drugs children use when ill, has something to do with the process of socialization of illness behaviour is the question on which this paper is focused. The aim of the study is to see whether Swedish children at the age of 6-7 years can give a description that makes it possible to visualize how such a socialization goes on. It transpired that drug use has an important role in the socialization of illness behaviour among these children. They clearly show in drawings as well as in their words, the 'gatekeeping' role of their parents. They also show that drugs are used in the healing process, given to them by their parents. How they have learned what message this is supposed to give is a result of their continuous socialization of illness behaviour. The relationship between the notion of the sweet drug that parents give and the notion of a cosy illness episode on the one hand and that of drugs as normalizing fenomena which heal an illness more quickly than if it were treated is discussed. How children are socialized into ways of behaving when feeling uneasy has obviously to do with the use of drugs as they may manipulate illness episodes to fit into a pattern of life, social relationships and family structure.

Child↗
PubMed1990

The control of growth and differentiation in normal and leukemic blood cells.

The establishment of a cell culture system for the clonal development of hematopoietic cells has made it possible to discover the proteins that control growth and differentiation of different hematopoietic cell lineages and the molecular basis of normal and abnormal cell development in blood-forming tissues. A model system with myeloid cells has shown that normal hematopoietic cells require different proteins to induce cell multiplication and cell differentiation, and that a cascade of interactions between proteins determines the correct balance between immature and mature cells in normal development. Gene cloning has shown that there is a family of different genes for these proteins. Normal protein regulators of hematopoiesis can control the abnormal growth of certain types of leukemic cells and suppress malignancy by inducing differentiation to mature nondividing cells. Genetic abnormalities that give rise to malignancy in these leukemic cells can be bypassed and their effects nullified by inducing differentiation, which stops cells from multiplying. These hematopoietic regulatory proteins are active in culture and in vivo and have been used clinically to correct defects in blood cell development. The results provide new approaches to therapy.

Animals↗
PubMed1990

The effect of postpartum lactation counseling on the duration of breast-feeding in low-income women.

We investigated the effectiveness of a program of intensive postpartum support for low-income, breast-feeding women and identified potential predictors of prolonged breast-feeding in this population. Ninety-seven low-income women were randomized to receive intensive postpartum education and support for breast-feeding or to receive only the routine assistance provided by the obstetrical nurses. Both groups were telephoned 6 weeks post partum to determine the method of infant feeding then, and those still breast-feeding were contacted monthly until complete weaning had occurred. No significant difference in breast-feeding duration between the two groups was noted. There was no association between duration of nursing and race, marital status, or the need to return to work or school. Earlier age at introduction of supplement, younger maternal age, and participation in prenatal classes predicted breast-feeding duration by logistic regression.

Breast Feeding↗
PubMed1990

Effect of septal kindling on glutamate binding and calcium/calmodulin-dependent phosphorylation in a postsynaptic density fraction isolated from rat cerebral cortex.

Postsynaptic density (PSD) fractions were isolated from the cerebral cortices of control and kindled rats and assayed for glutamate and gamma-aminobutyric acid-binding capacities and for the Ca2+/calmodulin-dependent protein kinase. Glutamate binding was found to be increased by approximately 50% in the PSDs isolated from kindled rats as compared to controls; this increase was almost completely from an increase in Bmax; Kd decreased only slightly. Studies with inhibitors indicate that the receptors involved were of the N-methyl-D-aspartate and quisqualate types. PSDs isolated from control and kindled rats did not differ in gamma-aminobutyric acid or flunitrazepam binding. The in vitro autophosphorylation of the Ca2+/calmodulin-dependent protein kinase was depressed by 45-76% in PSDs isolated from kindled rats as compared to controls, with little change in amount of the kinase. Therefore, we infer that (i) the kindled state is associated with an increase in glutamate activation of postsynaptic sites, allowing Ca2+ to enter dendritic spines, (ii) a change has occurred in activity of the protein kinase, which is the major cerebral cortex PSD protein, and (iii) perhaps major alterations in the PSD are a concomitant to the long-lasting nature of the kindled state.

Animals↗
PubMed1990

Pattern of interleukin 6 gene expression in vivo suggests a role for this cytokine in angiogenesis.

Interleukin 6 (IL-6) is a cytokine that acts on various cell types. Here we show that IL-6 mRNA is produced in vivo in two self-limiting physiologic angiogenic processes: (i) the formation of the vascular system accompanying development of ovarian follicles and (ii) the formation of a capillary network in the maternal decidua following embryonic implantation. In situ and RNA blot hybridization analyses detected transient expression of IL-6 mRNA in gonadotropin-primed hyperstimulated ovaries, with maximal mRNA levels coinciding with the period of formation of a capillary network around follicles. Expression of IL-6 mRNA was detected in the vasculature extending from the ovarian medulla to the forming capillary sheath in the thecal layer of individual growing follicles. No expression was detected in more-developed preovulatory follicles once angiogenesis had been completed. IL-6 mRNA was also detected in the uterus of pregnant mice 9.5 days postcoitum, and there was no appreciable IL-6 mRNA at later stages of embryonic development. Expression in the uterus was confined to cords of endothelial cells in the process of formation of an anastomosing network that traversed the maternal decidua towards the developing embryo. The expression of IL-6 mRNA in two independent physiological angiogenic processes and the transient nature of its expression in endothelial cells suggest a role for IL-6 in angiogenesis.

Animals↗
PubMed1990

Demographic variables in medical school admission.

Admission committees report that demographic variables, although accurate, reliable, and easily obtained from applicants to medical schools, are only moderately important in their decision making. This may be because the committees are concerned about the validity and legality of using such data as admissions criteria. This essay discusses the research on the validity of demographic variables and the recommendations for their legal use in selecting students for medical school. The relationships of age, gender, size of hometown, parental education, parental occupation, parental income, and marital status to medical school outcomes of preclinical performances, clinical performance, attrition, specialty choice, and practice location are summarized. [Race or ethnic group is discussed in a separate essay in this issue.] Although the authors focus on the predictive value of demographic variables, these variables play a more important role as the moderator variables for other predictors of medical school outcomes. The full value of using demographic variables derives from data obtained in local validity studies. To comply with the equal-protection and due-process requirements, admission officers must assure that the use of demographic information in the admission process is explicit in bulletins given to applicants and is uniformly applied in the evaluation of all applicants.

Adult↗
PubMed1990

The infant feeding decision in low and upper income women.

Few studies have described the woman who chooses breast-feeding by more than simple demographics. The purpose of our study was to characterize new mothers by their infant feeding decisions, by demographic and obstetrical data, and by sources of personal support they received during their pregnancies and in making their infant feeding decisions. To this end, 220 were interviewed, including 116 who chose to breastfeed. Breast-feeding women were more likely to be older, more educated, married, more affluent, experienced with breast-feeding, to have demonstrated good prenatal habits, and to have received support from other sources than those who chose bottle feeding. Participation in Lamaze classes, previous successful breast-feeding, and maternal education were significant predictors of feeding choice, and mode of delivery predicted duration of breastfeeding. Low income women who chose breastfeeding resembled low income bottle feeders in certain medical/social factors, but they showed support patterns similar to middle to upper income women.

Adolescent↗
PubMed1990

Management of diabetes mellitus and pregnancy: a survey of obstetricians and maternal-fetal specialists.

To ascertain current practice trends among obstetricians and maternal-fetal subspecialists regarding the care of pregnancies complicated by diabetes mellitus, a questionnaire was sent to all members of the Society of Perinatal Obstetricians (SPO) and a randomly selected group of American College of Obstetricians and Gynecologists (ACOG) Fellows. A total of 273 of 356 SPO members (77%) and 198 of 504 ACOG Fellows (39%) responded. When divided according to years post-residency (ACOGa, less than 15 years; ACOGb, 15 years or more), significant differences in practice patterns were observed for ACOG Fellows. The SPO responses were similar among these subgroups. Despite current ACOG recommendations, most clinicians practice universal screening for gestational diabetes. Significant discrepancies appear to exist between ACOGb versus ACOGa and SPO with regard to methods of glucose surveillance and the threshold for initiating insulin therapy in gestational diabetes. Intensive fetal surveillance, elective delivery, and high cesarean rates are common in pregnancies complicated by insulin-dependent diabetes mellitus, which is most often managed by a perinatologist or by an obstetrician in consultation with an internist. Few insulin-dependent patients seek preconceptional care.

Adult↗
PubMed1990

The proteins that control haemopoiesis and leukaemia.

The establishment of a cell culture system for the clonal development of haemopoietic cells has made it possible to identify the proteins that control growth and differentiation of different haemopoietic cell lineages and to discover the molecular basis of normal and abnormal cell development in blood-forming tissues. A model system with myeloid cells has shown that normal haemopoietic cells require different proteins to induce cell multiplication and cell differentiation, and that a cascade of interactions between proteins determines the correct balance between immature and mature cells in normal development. Gene cloning has shown that there is a family of different genes for these proteins. Normal protein regulators of haemopoiesis can control the abnormal growth of certain types of leukaemic cells and suppress malignancy by inducing differentiation to mature, non-dividing cells. Genetic abnormalities that give rise to malignancy in these leukaemic cells can be bypassed and their effects nullified by inducing differentiation, which stops cells from multiplying. These haemopoietic regulatory proteins are active in culture and in vivo and have been used clinically to correct defects in blood cell development. The results provide new approaches to therapy.

Animals↗
PubMed1990

Cancer genetics and cancer suppression.

Identification of normal growth and differentiation-inducing proteins and how they interact in normal development has made it possible to identify the molecular basis of normal development and the mechanisms that uncouple growth and differentiation so as to produce malignant cells. When normal cells have been changed into cancer cells, the malignant phenotype can again be suppressed. Results on the molecular control of growth and differentiation in normal myeloid hematopoietic cells, changes in the normal developmental program in myeloid leukemia, and the suppression of malignancy in myeloid leukemia and sarcomas have shown that (1) malignancy can be suppressed either with or without genetic changes in the malignant cells, (2) suppression of malignancy by inducing differentiation does not have to restore all the normal controls, and (3) genetic abnormalities which give rise to malignancy can be bypassed and their effects nullified by inducing differentiation which stops cells from multiplying.

Cell Differentiation↗
PubMed1990

Induction of genes for transcription factors by normal hematopoietic regulatory proteins in the differentiation of myeloid leukemic cells.

Induction of differentiation to macrophages in two different clones of myeloid leukemic cells by the hematopoietic regulatory proteins interleukin-6 (IL-6), or by granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), is shown to be associated with sustained accumulation of c-jun, jun-B, and c-fos mRNA that code for proteins that form complexes that are transcription factors (AP-1). In one but not in the other of these leukemic clones, differentiation is also associated with sustained accumulation of mRNA for the putative transcription factor zif/268. The results indicate that differentiation of myeloid cells by normal hematopoietic regulatory proteins is associated with induction of sustained elevated levels of mRNA for transcription factors that can regulate and maintain gene expression in the differentiation program, and that zif/268 gene expression is not essential for differentiation to macrophages.

Animals↗
PubMed1989

Induction of dependence on hematopoietic proteins for viability and receptor upregulation in differentiating myeloid leukemic cells.

There are different types of myeloid leukemic cells that can be induced to differentiate to mature granulocytes or macrophages by different hematopoietic regulatory proteins. One type of leukemic clone can be induced to differentiate by recombinant macrophage and granulocyte differentiation-inducing protein-type 2 (MGI-2), which we have shown is Interleukin-6 (IL-6), and another type of leukemic clone can be differentiated by recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3. There was no subpopulation of growth factor-responsive or differentiation-defective cells before induction of differentiation in either type of clone. In both clones, induction of differentiation-induced requirement for a hematopoietic protein for cell viability. Viability of the cells was maintained by IL-6, IL-3, or macrophage colony-stimulating factor (M-CSF) but not by GM-CSF in the cells differentiated by IL-6, and by GM-CSF or IL-3 but not by IL-6 or M-CSF in the cells differentiated by GM-CSF or IL-3. The viable cells with a differentiated phenotype continued to multiply. In undifferentiated leukemic cells with no or few surface receptors for some of these proteins, there was an upregulation of the number of receptors during differentiation for the proteins to which the cells responded. But there were also differentiating leukemic cells with an upregulation of GM-CSF receptors although GM-CSF could not maintain the viability of the differentiating cells. The results indicate that induction of hormone responsiveness and upregulation of the hormone receptors can both occur in differentiating leukemic cells, and that the regulation of these two events can be separated.

Animals↗