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Biomedical subjects

L Sachs

Publications and source records attributed to L Sachs.

At least 55 records · Page 3Linked to original sources
PubMed1995

Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome.

The copper-zinc superoxide dismutase (CuZnSOD) gene resides on chromosome 21 and is overexpressed in Down syndrome (DS) patients. Transgenic CuZnSOD mice with elevated levels of CuZnSOD were used to determine whether, as in DS, overexpression of CuZnSOD was also associated with thymus and bone marrow abnormalities. Three independently derived transgenic CuZnSOD strains had abnormal thymi showing diminution of the cortex and loss of corticomedullary demarcation, resembling thymic defects in children with DS. Transgenic CuZnSOD mice were also more sensitive than control mice to in vivo injection of lipopolysaccharide (LPS), reflected by an earlier onset and enhanced apoptotic cell death in the thymus. This higher susceptibility to LPS-induced apoptosis was associated with an increased production of hydrogen peroxide and a higher degree of lipid peroxidation. When cultured under suboptimal concentrations of interleukin 3 or in the presence of tumour necrosis factor, bone marrow cells from transgenic CuZnSOD mice produced 2- to 3-fold less granulocyte and macrophage colonies than control. The results indicate that transgenic CuZnSOD mice have certain thymus and bone marrow abnormalities which are similar to those found in DS patients, and that the defects are presumably due to an increased oxidative damage resulting in enhanced cell death by apoptosis.

Animals↗
PubMed1995

A mutant p53 antagonizes the deregulated c-myc-mediated enhancement of apoptosis and decrease in leukemogenicity.

Myeloid leukemic M1 cells that do not express p53 and transfected M1 clones that constitutively express the [Val135]p53 mutant or deregulated c-myc or coexpressing both genes grew autonomously in culture with a similar growth rate and cloning efficiency. Expression of deregulated c-myc in M1 leukemic cells enhanced susceptibility to induction of apoptotic cell death and resulted in a reduced leukemogenicity when injected into isologous mice. Expression of the [Val135]p53 mutant did not change cell susceptibility to induction of apoptosis or leukemogenicity, but expression of this mutant p53 suppressed the effects of deregulated c-myc on these properties. The results indicate that the [Val135]p53 mutant can show a gain of function for susceptibility to apoptosis and leukemogenicity in leukemic cells with deregulated c-myc and, thus, enhance tumor development.

Animals↗
PubMed1995

Is there a pathology of prevention? The implications of visualizing the invisible in screening programs.

The preventive orientation that has been gaining ground in Sweden is indicative of ways in which our society is organized to sustain values like "a healthy life," "a healthy body," and "a healthy society." Search for health dangers and risks shows how medical technology has been integrated with our thinking about health. Preventive language, like all language of medicine, besides describing a pre-existing biological reality, creates in the process its own objects of analysis. This also has an impact and influences how lay people experience their bodies. The study presented focuses on one form of prevention in an attempt to describe how the ambition to secure a healthy society, through the detection of early disease, may have the opposite effect. Medical health-care ambitions in screening for cholesterolaemia will be related to implications for a group of men in whom cholesterol was found to be elevated. The men feel healthy yet are in some sense diseased. This raises the issue of visualizing the invisible in health care and the implications of such a process for the patients concerned.

Adult↗
PubMed1995

Cervical competence as a continuum: a study of ultrasonographic cervical length and obstetric performance.

OBJECTIVE: Our purpose was to investigate the hypothesis that cervical competence is a continuum that is related to cervical length and is reflected by pregnancy history. STUDY DESIGN: A cross-sectional study was performed of cervical length measured by transvaginal ultrasonography in women with prior preterm delivery at < or = 26 weeks, 27 to 32 weeks, and 33 to 35 weeks compared with women with cervical incompetence and normal controls delivered at term. RESULTS: Transvaginal cervical length was measured during pregnancy in 32 subjects with cervical incompetence, 98 with previous preterm birth < or = 26 weeks, 98 with previous preterm birth at 27 to 32 weeks, 127 with previous preterm birth at 33 to 35 weeks, and 106 normal controls. The relationship between obstetric history and cervical length was evaluated by analysis of variance. The gestational age at the first preterm delivery was significantly correlated with cervical length in the current pregnancy at each gestational interval between 20 and 30 weeks in a continuous manner. CONCLUSION: Cervical competence is a continuous rather than categoric variable and is indicated indirectly by measurement of the length of the cervix.

Adult↗
PubMed1995

Recruitment and retention strategies used by occupational therapy directors in acute care, rehabilitation, and long-term-care settings.

OBJECTIVES: Occupational therapy directors need to recruit and retain therapists to ensure both the delivery of high-quality services and the viability of their departments. At present, research on the recruitment and retention of occupational therapists is limited; recruitment and retention strategies can be cited, but their utility and effectiveness have not been determined. METHOD: A survey was designed to identify the recruitment and retention strategies used in various practice settings and the perceived level of effectiveness of those strategies that were used. The surveys were mailed to 500 occupational therapy directors. Once the sample size was adjusted to exclude ineligible subjects, the eligible sample size was 471. Of these, 320 (68%) were usable. RESULTS: Ten of the 23 recruitment strategies listed on the survey were used by more than 70% of the respondents. The top three recruitment strategies were staff member referrals, professional development opportunities, and newspaper advertisements. Seventeen of the 23 retention strategies listed on the survey were used by more than 70% of the respondents. The top three retention strategies were interpersonal staff member relationships, employee appraisals, and continuing education. CONCLUSION: Findings suggest that occupational therapy departments' recruitment and retention plans could be improved by expanding the number of strategies used and by incorporating techniques that appeal to a broader range of therapists.

Ambulatory Care↗
PubMed1995

Functioning and well-being of patients before and after elective surgical procedures.

BACKGROUND: Recent changes in health care delivery and financing have prompted interest in medical outcomes research. This study was performed to assess the effect of general surgical procedures on the health status of patients over time. STUDY DESIGN: The functional health status of patients undergoing elective surgical procedures was measured preoperatively, in the immediate postoperative period, and three and six months after surgery. Complete data were collected for 82 patients presenting to the general surgery service at the Ohio State University Medical Center for symptoms related to gallbladder disease (21), hemorrhoids (10), inguinal and incisional hernias (37), and clinically severe obesity (14). The Short Form-36 health status questionnaire was administered before the surgical procedure, at the first postoperative visit, and by telephone three months and six months following surgery. Hospital records were reviewed following the procedures, and preoperative anesthesiologist's risk status, American Society of Anesthesiologists scores, and complications were noted. Patient satisfaction was assessed using a questionnaire developed by Ohio State University. RESULTS: For all four elective procedures, a significant improvement in health status was demonstrated when preoperative function was compared to measurements three and six months postoperatively. Improvement was significant in all eight categories assessed, encompassing physical, social, mental, emotional, and general health, and pain relief. Dramatic improvement was reported by patients undergoing Roux-en-Y gastric bypass for clinically severe obesity. CONCLUSIONS: The Short Form-36 health status questionnaire proved to be a useful tool in assessing patient outcomes following elective surgical procedures. The general health status assessment will be especially useful for documenting the effectiveness of routine and innovative therapies.

Activities of Daily Living↗
PubMed1995

Regulation of bcl-2, bcl-XL and bax in the control of apoptosis by hematopoietic cytokines and dexamethasone.

Treatment of M1 myeloid leukemic cells with interleukin 6 (IL-6) or dexamethasone (DEX), both of which induce differentiation in these cells, down-regulated expression of the apoptosis-suppressing gene bcl-2 and the apoptosis-promoting gene bax but up-regulated expression of the apoptosis-suppressing gene bcl-XL. There was a higher expression of bcl-XL in cells treated with DEX or DEX plus IL-6 compared to cells treated with IL-6 alone. The alternatively spliced bcl-X gene, bcl-Xs, which interferes with the action of bcl-2, was not expressed. Treatment with IL-6 increased the susceptibility of these cells to induction of apoptosis by Adriamycin or cycloheximide, but treatment with DEX or with IL-6 and DEX did not. Withdrawal of DEX after up-regulation of bcl-XL resulted in a decrease in bcl-XL expression and a concomitant increase in cell susceptibility to induction of apoptosis. Another myeloid leukemia that shows barely detectable expression of bcl-2 also showed up-regulated expression of bcl-XL but no change in bax after induction of differentiation with granulocyte-macrophage colony-stimulating factor, and this reduced cell susceptibility to induction of apoptosis by Adriamycin or cycloheximide. The results indicate that the related apoptosis-regulating genes bcl-2, bcl-XL, and bax are differently regulated and that up-regulation of bcl-XL expression may compensate for down-regulation of bcl-2 in the balance between genes that control apoptosis.

Animals↗
PubMed1995

Interferon-gamma inhibits apoptosis induced by wild-type p53, cytotoxic anti-cancer agents and viability factor deprivation in myeloid cells.

Different hematopoietic cytokines including colony-stimulating factors and interleukins can inhibit apoptotic cell death induced in myeloid cells by the tumor-suppressor gene wild-type 53 and a variety of cytotoxic anti-cancer agents. In this study we identity interferon-gamma as an anti-apoptotic cytokine for myeloid cells in which apoptosis was induced by wild-type p53, cytotoxic anti-cancer agents or viability factor deprivation. The inhibition of wild-type p53-mediated apoptosis in myeloid leukemic cells by interferon-gamma was not associated with downregulated expression of wild-type p53 or the p53-induced cyclin-dependent kinase inhibitor gene WAF-1, or with upregulated expression of the apoptosis-inhibiting gene bcl-2. Interferon-gamma also inhibited induction of apoptosis by a p53-independent pathway. Interferon-gamma inhibited apoptotic cell death caused by withdrawal of viability factors in normal myeloid precursor cells, the interleukin 3-dependent 32D cell line and differentiating myeloid leukemic cells. Interferon-alpha/beta did not inhibit apoptotic cell death in any of these systems. The results indicate that although interferon-gamma can inhibit cell multiplication and differentiation in myeloid cells, it shares with other hematopoietic cytokines the ability to protect normal and leukemic myeloid cells from induction of apoptosis.

Animals↗
PubMed1995

Non-viral gene transfer: applications in developmental biology and gene therapy.

The main limitation of non-viral gene transfer methods is their relatively low efficiency in vivo. However, a number of approaches can be taken to improve their performances, whether the aim is studying gene function during development or employing these techniques for gene therapy. Three non-viral delivery systems that we have been particularly involved in in developing are described: the cationic lipid, dioctadecylamidoglycylspermine (DOGS), the cationic polymer polyethylenimine (PEI) and free DNA. The application of each of these methods to different in vivo situations is presented: the use of DOGS for transfecting embryos and the developing mammalian nervous system; the recent application of PEI to the nervous system; and how naked DNA can be employed for transfecting different muscles and brain. The relative efficiencies are compared on the basis of luciferase reporter gene expression assessed in each tissue with the most appropriate vector system. Finally, the perspectives for constructing composite vectors combining safety and efficiency are considered briefly.

Animals↗
PubMed1994

The network of hematopoietic cytokines.

Cell viability, multiplication, and differentiation to the various hematopoietic cell lineages are induced by a multigene cytokine family, and hematopoiesis is controlled by a network of interactions between these cytokines. This network includes positive regulators such as colony-stimulating factors and interleukins, and negative regulators such as transforming growth factor-beta and tumor necrosis factor. The functioning of the network requires an appropriate balance between positive and negative regulators, and the selective regulation of programmed cell death (apoptosis) by interaction of cytokines with their receptors. The cytokine network, which has arisen during evolution, allows considerable flexibility, depending on which part of the network is activated, and the ready amplification of response to a particular stimulus. This amplification occurs by autoregulation and transregulation of genes for the hematopoietic cytokines. There is also a transregulation by these cytokines of cytokine receptors. In addition to the flexibility of this network, both for response to present day infections and to infections that may develop in the future, a network may also be necessary to stabilize the whole system. The existence of a network and the cytokine-receptor regulation of apoptosis has to be taken into account in the clinical use of cytokines for therapy. Cytokines that regulate hematopoiesis induce the expression of genes for transcription factors. Cytokine signaling through transcription factors can thus ensure the autoregulation and transregulation of cytokine and receptor genes that occur in the network. Interactions between the cytokine network and transcription factors can also ensure production of specific cell types and stability of the differentiated state.

Biological Evolution↗
PubMed1994

Control of sensitivity to induction of apoptosis in myeloid leukemic cells by differentiation and bcl-2 dependent and independent pathways.

Induction of differentiation in M1 myeloid leukemic cells by the hematopoietic cytokines interleukin 6 and granulocyte-colony stimulating factor, or by the glucocorticoid dexamethasone, was associated with down-regulation of the apoptosis inhibiting gene bcl-2. The cytokine treated leukemic cells showed an increased sensitivity to induction of apoptotic cell death by the cancer chemotherapy compounds Adriamycin and cytosine arabinoside and by heat shock and cycloheximide. Dibutyryl cyclic AMP neither induced differentiation nor down-regulated bcl-2 expression, but it sensitized the cells to induction of apoptosis by some of these agents. Although dexamethasone induced differentiation and down-regulated bcl-2 expression, it did not sensitize the cells to induction of apoptosis and inhibited the apoptosis sensitizing effect of the cytokines and dibutyryl cyclic AMP. Dexamethasone did not inhibit induction of apoptosis by wild-type p53 or viability factor withdrawal. The apoptosis sensitizing effect of the cytokines and dibutyryl cyclic AMP was reversible upon their withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoptosis↗
PubMed1993

Hematopoietic cells from mice deficient in wild-type p53 are more resistant to induction of apoptosis by some agents.

Wild-type p53 is a tumor-suppressor gene that can induce cell death by apoptosis when expressed in myeloid leukemic and some other types of tumor cells. However, the question remained as to what extent wild-type p53 is a mediator of apoptosis in normal cells. We have used mice deficient in wild-type p53 to determine whether induction of apoptosis in hematopoietic cells from these p53 deficient mice is defective. We show here that bone marrow myeloid progenitor cells from p53-deficient mice are more resistant to induction of apoptosis when there was only a low concentration of the viability factors granulocyte-macrophage colony-stimulating factor; interleukins-1 alpha, -3, and -6; or stem cell factor; or when apoptosis was induced in these cells by irradiation or heat shock. The loss of one allele of wild-type p53 was sufficient for increased resistance. The higher resistance to apoptosis in p53-deficient mice was also found in irradiated thymocytes, but not in thymocytes treated with dexamethasone or in mature peritoneal granulocytes. The degree of resistance in irradiated myeloid progenitors and thymocytes showed a dosage effect of the number of wild-type p53 genes. The results show that wild-type p53 is involved in the induction of apoptosis by some agents in normal hematopoietic cells. Loss of wild-type p53 can, therefore, contribute to tumor development by decreasing cell death at low concentrations of viability factors and after exposure to a DNA-damaging agent. The results also show that there are wild-type p53-dependent and -independent pathways of normal cell apoptosis.

Animals↗
PubMed1993

Thyroid hormone-dependent transcriptional regulation of exogenous genes transferred into Xenopus tadpole muscle in vivo.

Metamorphosis in amphibians is marked by dramatic thyroid hormone-induced changes that include tail regression. To examine thyroid hormone effects on gene transcription during the early stages of tail resorption, we injected exogenous genes directly into the caudal skeletal muscle of Xenopus tadpoles and followed their expression in vivo. Gene expression was both strong and reproducible, and it correlated with the amount of DNA injected. Moreover, expression continued as long as the animals were blocked in prometamorphosis by antithyroid drugs (for up to 4 months). Thyroid hormone-dependent effects on transcription were examined by using a palindromic thyroid hormone response element linked to a chloramphenicol acetyltransferase reporter gene. Reporter gene expressions were normalized for transfection efficiency by using a constitutively expressed luciferase construct. Physiological concentrations of 3,5,3' triiodo-L-thyronine (1 nM), applied for 120 hr, produced a 5-fold increase in transcription (P < 0.05) from the thyroid hormone response element but did not modify transcription from constitutive viral promoters. This study thus demonstrates that by directly expressing genes in Xenopus tadpole muscle in vivo, one can exploit the powerful experimental advantages of gene transfer systems in an intact, physiologically normal animal.

Animals↗
PubMed1993

Control of programmed cell death in normal and leukemic cells: new implications for therapy.

Programmed cell death (apoptosis) is a normal process by which cells are eliminated during normal embryonic development and in adult life. Disruption of this normal process resulting in illegitimate cell survival can cause developmental abnormalities and facilitate cancer development. Normal cells require certain viability factors and undergo programmed cell death when these factors are withdrawn. The viability factors are required throughout the differentiation process from immature to mature cells. Although many viability factors are also growth factors, viability and growth are separately regulated. Viability factors can have clinical value in decreasing the loss of normal cells including the loss that occurs after irradiation, exposure to other cytotoxic agents or virus infection including AIDS. There is no evidence that occurs after irradiation, exposure to other cytotoxic agents or virus infection including AIDS. There is no evidence that cancer cells are immortal. Programmed cell death can be induced in leukemic cells by removal of viability factors, by cytotoxic therapeutic agents, or by the tumor-suppressor gene wild-type p53. All these forms of induction of programmed cell death in leukemic cells can be suppressed by the same viability factors that suppress programmed cell death in normal cells. A tumor-promoting phorbol ester can also suppress this death program. The induction of programmed cell death can be enhanced by deregulated expression of the gene c-myc and suppressed by the gene bcl-2. Mutant p53 and bcl-2 suppress the enhancing effect on cell death of deregulated c-myc, and thus allow induction of cell proliferation and inhibition of differentiation which are other functions of deregulated c-myc. The suppression of cell death by mutant p53 and bcl-2 increases the probability of developing cancer. The suppression of programmed cell death in cancer cells by viability factors suggests that decreasing the level of these factors may increase the effectiveness of cytotoxic cancer therapy. Treatments that downregulate the expression or activity of mutant p53 and bcl-2 in cancer cells should also be useful for therapy.

Apoptosis↗
PubMed1993

Nutritional concerns of women with breast cancer.

Health professionals should assess the nutrition information needs of women with breast cancer in order to provide appropriate services. Questionnaires were mailed to 143 Reach to Recovery volunteers who had had surgery for breast cancer, and 72% responded. The subjects were mostly concerned about and wanted information on diets for cancer prevention, low-fat diets, weight reduction, and vitamin supplements. Findings also showed the potential for excessive vitamin/mineral use among one-third of respondents and a tendency toward weight gain regardless of whether or not chemotherapy was received. The results provide direction for development of nutrition educational materials and programs for women with breast cancer.

Adult↗