Biomedical subjects

L Ku

Publications and source records attributed to L Ku.

At least 19 recordsLinked to original sources

PubMed2001

The fragile X mental retardation protein inhibits translation via interacting with mRNA.

Fragile X syndrome is a frequent form of inherited mental retardation caused by functional loss of the fragile X mental retardation protein, FMRP. The function of FMRP is unknown, as is the mechanism by which its loss leads to cognitive deficits. Recent studies have determined that FMRP is a selective RNA-binding protein associated with polyribosomes, leading to the hypothesis that FMRP may be involved in translational regulation. Here we show that purified recombinant FMRP causes a dose-dependent translational inhibition of brain poly(A) RNA in rabbit reticulocyte lysate without accelerated mRNA degradation. In our translation reaction FMRP interacts with other messenger ribonucleoproteins and pre-exposure of FMRP to mRNA significantly increased the potency of FMRP as a translation inhibitor. Translation suppression by FMRP is reversed in a trans-acting manner by the 3'-untranslated portion of the Fmr1 message, which binds FMRP, suggesting that FMRP inhibits translation via interacting with mRNA. Consistently FMRP suppresses translation of the parathyroid hormone transcript, which binds FMRP, but not the beta-globin transcript, which does not bind FMRP. Moreover, removing the FMRP-binding site on a translation template abolishes the inhibitory effect of FMRP. Taken together, our results support the hypothesis that FMRP inhibits translation via interactions with the translation template.

Animals↗

PubMed2000

Use of reproductive health services among young men, 1995.

PURPOSE: To analyze the extent to which teenage males receive preventive reproductive health services and identify demographic and health factors associated with their receipt. METHODS: Bivariate and multivariate analyses of nationally representative data from the 1995 National Survey of Adolescent Males were conducted using logistic regression to determine which factors predicted whether teenagers had a physical examination and whether they discussed reproductive health topics with a medical professional, had a human immunodeficiency virus (HIV) test, or had a sexually transmitted disease (STD) test. RESULTS: Although 71% of males aged 15-19 years received a physical examination in the past year, only 39% of them received any of the three reproductive health services. Less than one-third of all young men discussed reproductive health with their doctor or nurse. Among sexually experienced males, one-sixth had an STD test and one-quarter an HIV test. In multivariate analysis, males who had a physical examination were more likely to have an STD or HIV test, but were no more likely to discuss reproductive health topics. Minority and low-income youth were more likely to receive these reproductive health services, as were young men with multiple sex partners and those with health problems. CONCLUSIONS: In general, the proportion of teenage men receiving reproductive health services is low, although levels are higher among minority youth and certain groups at risk. To reduce rates of teen pregnancy and STDs, physicians and nurses need to incorporate reproductive health care into routine health services for teenage males, as well as females.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Adolescent sexual behavior, drug use, and violence: increased reporting with computer survey technology.

Surveys of risk behaviors have been hobbled by their reliance on respondents to report accurately about engaging in behaviors that are highly sensitive and may be illegal. An audio computer-assisted self-interviewing (audio-CASI) technology for measuring those behaviors was tested with 1690 respondents in the 1995 National Survey of Adolescent Males. The respondents were randomly assigned to answer questions using either audio-CASI or a more traditional self-administered questionnaire. Estimates of the prevalence of male-male sex, injection drug use, and sexual contact with intravenous drug users were higher by factors of 3 or more when audio-CASI was used. Increased reporting was also found for several other risk behaviors.

Adolescent↗

PubMed1998

Adolescent males' combined use of condoms with partners' use of female contraceptive methods.

OBJECTIVE: Protection from both sexually transmitted diseases and pregnancy is best obtained by the combined use of male condoms and effective female contraceptive methods. This research examines dual contraceptive method use among teenage men. METHOD: Analyzed data from the 1995 National Survey of Adolescent Males, a nationally representative survey of 15 to 19-year-old males. Used bivariate analyses and logistic regression to examine the correlates of combined use of condoms and female methods. RESULTS: At last intercourse, 17% of sexually active males reported use of a condom and a female method of contraception. Condom use, alone and in combination with a female method, was positively associated with talking with the partner about contraception and condoms, believing that males have a responsibility for contraception, and being in an earlier stage of a relationship. Only high levels of worry about sexually transmitted diseases differentially influenced dual method use, increasing the likelihood of using a condom with a female method, but not using condoms alone. CONCLUSIONS: The results suggest that efforts to increase condom use in general should also influence young men's use of condoms when their partner is using a female method. Providing information to young males about the high prevalence and serious consequences of sexually transmitted diseases may increase dual method use among adolescents.

Adolescent↗

PubMed1998

Changes in sexual behavior and condom use among teenaged males: 1988 to 1995.

OBJECTIVES: This study examines shifts in sexual experience and condom use among US teenaged males. METHODS: Results from the 1988 and 1995 National Surveys of Adolescent Males were compared. RESULTS: The proportion of never-married 15- to 19-year-old males who had had sex with a female declined from 60% to 55% (P = .06). The share of those sexually active using a condom at last intercourse rose from 57% to 67% (P < .01). Overall, the proportion of males who had sex without condoms last year declined from 37% to 27% (P < .001). CONCLUSIONS: Although protective behaviors among teenagers have increased, significant proportions of teenagers--especially Black and Hispanic males--remain unprotected.

Adolescent↗

PubMed1998

Medicaid managed care and the marketplace.

In 1994 and 1995, Tennessee, Hawaii, Rhode Island, and Oklahoma began massive expansions of Medicaid managed care, growing from three health plans covering a few enrollees to 27 plans covering the great majority a year later. Some firms aggressively pursued expansion, while others had very limited business objectives. Although established insurers often dominated the Medicaid markets, newly developed firms, some provider-sponsored, were also important. Despite the relatively low Medicaid capitation rates in the 1996-97 period, Medicaid plans in three states had an average 1% net profit margin.

Capitation Fee↗

PubMed1997

Reactive oxygen species stimulate insulin-like growth factor I synthesis in vascular smooth muscle cells.

OBJECTIVES: The objective was to study potential regulation of insulin-like growth factor I (IGF I), its binding proteins, and the IGF I receptor by reactive oxygen species in vascular smooth muscle cells. METHODS: We used cultured rat aortic smooth muscle cells exposed to xanthine (100 microM) and xanthine oxidase (5 microU/ml) or H2O2 (200 microM) and measured IGF I mRNA levels by solution hybridization/RNase protection assays, IGF I protein levels by radioimmunoassay, and IGF binding proteins by Western ligand blotting. Additionally, we measured the effect of anti-IGF I antiserum on xanthine/xanthine oxidase- and H2O2-stimulated [3H]thymidine incorporation. RESULTS: Xanthine/xanthine oxidase and H2O2 stimulated increases in IGF I mRNA and protein levels and reduced IGF binding protein-4 levels in conditioned medium. The effect of xanthine/xanthine oxidase was inhibited by the scavengers superoxide dismutase and catalase. Xanthine/xanthine oxidase- and H2O2-stimulated DNA synthesis was completely inhibited by a neutralizing anti-IGF I antiserum. CONCLUSION: Reactive oxygen species increased vascular smooth muscle cell synthesis of IGF I and reduced levels of the inhibitory IGF binding protein-4. Furthermore, reactive oxygen species-induced DNA synthesis was inhibited by an anti-IGF I antiserum. These findings suggest that the autocrine IGF I system plays an important role in vascular smooth muscle cell growth responses to reactive oxygen species. Furthermore, the findings have important implications for understanding biological responses to changes in redox state.

Animals↗

PubMed1997

The promise of integrated representative surveys about sexually transmitted diseases and behavior.

BACKGROUND: It has been difficult to conduct representative surveys measuring both sexually transmitted disease prevalence and behavioral data. This article reviews the literature, describes a recent pretest of the feasibility of integrated surveys, and discusses the potential implications. METHODS: Several national surveys are reviewed, including the National Health and Nutrition Examination Surveys, National Health and Social Life Survey, and National Survey of Adolescent Males. The 1994 pretest of the National Survey of Adolescent Males collected urine specimens of male respondents, which were tested for Chlamydia trachomatis using ligase and polymerase chain reaction tests. RESULTS: There have not been any prior national surveys that collect clinical measures of STD infection and detailed behavioral data. In the pretest, 85% of the eligible interview respondents provided a urine specimen. Of those tested, 6% were positive for C. trachomatis. CONCLUSIONS: Combining behavioral surveys with collection of urine specimens for STD testing in representative samples is feasible. However, STD testing adds new operational and ethical challenges to the conduct of household surveys.

Adolescent↗

PubMed1996

Insulin-like growth factor 1 binding protein 3 synthesis by aortic endothelial cells is a function of cell density.

Proliferating bovine aortic endothelial cells in culture do not express the insulin-like growth factor 1 binding protein 3 gene, in contrast to the genes encoding binding proteins 2, 4, 5, and 6. The binding protein 3 gene is activated only at cell confluency with continual transcription thereafter, for at least an eight-day post-confluent period, both in the presence or absence of serum. Secretion of protein product into the medium parallels transcription. DNA synthesis is inversely related to the amount of total insulin-like growth factor 1 binding protein 3 in the culture medium. The addition of anti-binding protein 3 antibody to media significantly increases the rate of DNA synthesis by extensively post-confluent cells. These data suggest (1) aortic endothelial cells are an important source of circulating binding protein 3, (2) binding protein 3 has an inhibitory effect upon the growth of endothelial cells, (3) the triggering of binding protein 3 synthesis after confluency suggests a role in maintaining the growth-arrested monolayer state of the cells in vivo.

Animals↗

PubMed1996

G-protein coupled and tyrosine kinase receptors: evidence that activation of the insulin-like growth factor I receptor is required for thrombin-induced mitogenesis of rat aortic smooth muscle cells.

IGF I is an ubiquitous peptide that activates a membrane tyrosine kinase receptor and has autocrine/paracrine effects on vascular smooth muscle cells. Thrombin activates a G-protein coupled receptor and is also a mitogen for vascular smooth muscle cells. To assess the potential role of IGF I as a mediator of thrombin's effects, we characterized expression of IGF I and of its receptor on vascular smooth muscle cells exposed to thrombin. Thrombin dose-dependently decreased IGF I mRNA levels and caused a delayed decrease in IGF I secretion from vascular smooth muscle cells. This effect was mimicked by the hexapeptide SF-FLRN (that functions as a tethered ligand) and was inhibited by hirudin. In contrast, thrombin doubled IGF I receptor density on vascular smooth muscle cells, without altering binding affinity (Kd). An anti-IGF I antiserum markedly reduced thrombin-induced DNA synthesis, whereas nonimmune serum and an anti-fibroblast growth factor antibody were without effect. Cell counts confirmed these results. Downregulation of IGF I receptors by antisense phosphorothioate oligonucleotides likewise markedly inhibited thrombin-induced DNA synthesis. These data demonstrate that a functional IGF I-IGF I receptor pathway is essential for thrombin-induced mitogenic signaling and support the concept of cross talk between G-protein coupled and tyrosine kinase receptors.

Amino Acid Sequence↗

PubMed1995

Regulation of vascular smooth muscle cell insulin-like growth factor I receptors by phosphorothioate oligonucleotides. Effects on cell growth and evidence that sense targeting at the ATG site increases receptor expression.

We have recently shown that insulin-like growth factor I (IGF I) is a mediator of angiotensin II-induced mitogenesis in vascular smooth muscle cells (Delafontaine, P., and Lou H. (1993) J. Biol. Chem. 268, 16866-16870). To study the role of the IGF I receptor in vascular smooth muscle cell growth, phosphorothioate oligonucleotides were used to modulate IGF I receptors. An antisense oligonucleotide targeting the ATG site inhibited basal and serum-induced DNA synthesis in vascular smooth muscle cells. Mismatch oligonucleotide had no effect, while surprisingly sense oligonucleotide increased IGF I receptor number and basal and serum-induced DNA synthesis. A 51% reduction in IGF I receptor number following exposure to 5 microM antisense oligonucleotide markedly inhibited angiotensin II-induced mitogenesis. A 70% increase in IGF I receptor number following exposure to 5 microM sense oligonucleotide resulted in a 4-fold increase in basal [3H]thymidine incorporation, and angiotensin II (1-1000 nM) had no additive stimulatory effect. An antisense oligonucleotide targeting a sequence starting at +109 base pairs (relative to ATG) also reduced IGF I receptor number, however, the corresponding sense oligonucleotide was without effect. These findings demonstrate that alterations in vascular smooth muscle cell IGF I receptor density play a critical role in the proliferative response of vascular smooth muscle cells to serum and to angiotensin II. In addition, the surprising observation that an ATG-directed sense oligonucleotide up-regulates IGF I receptors identifies a novel effect of oligonucleotides on gene expression.

Angiotensin II↗

PubMed1995

Insuring the poor through Section 1115 Medicaid waivers.

With the demise of health care reform at the national level, much of the attention has shifted to state-level efforts. Recently, several states have begun looking to the Medicaid program as a way to solve their health care problems. A principal way in which states are implementing health care reform is through the Section 1115 research and demonstration Medicaid waiver program. The 1115 waiver authority provides states considerable flexibility to restructure their Medicaid programs to offer health care to new populations and thus has great potential for covering large segments of the uninsured population. While it shows great promise, however, there are many obstacles states must overcome both in implementing and in maintaining an 1115 program.

Eligibility Determination↗

PubMed1995

Medicaid disproportionate share and other special financing programs.

Medicaid disproportionate share hospital (DSH) and related programs, such as provider-specific taxes or intergovernmental transfers (IGTs), help support uncompensated care and effectively reduce State Medicaid expenditures by increasing Federal matching funds. We analyze the uses of these funds, based on a survey completed by 39 States and case studies of 6 States. We find that only a small share of these funds were available to cover the costs of uncompensated care. One method to ensure that funds are used for health care would be to reprogram funds into health insurance subsidies. An alternative to improve equity of funding across the Nation would be to create a substitute Federal grant program to directly support uncompensated care.

Data Collection↗

PubMed1995

Self-measurement of blood pressure: assessment of equipment. Canadian Coalition for High Blood Pressure Prevention and Control.

Equipment for the self-measurement of blood pressure is readily available to consumers. These devices use one or more surrogate (indirect) measures of pressure to estimate systolic and diastolic blood pressure. Manual auscultatory devices using stethoscope and sphygmomanometer have been adapted for home use, but a variety of automated devices based on auscultation, oscillometry, and other techniques are available and may be more suitable for individuals who have limited vision, hearing or dexterity. Despite the existence of voluntary evaluation protocols and mandatory manufacturing standards, blood pressure readings from some automatic devices may not be accurate. Some devices are packaged with insufficient information to ensure proper use, and most individuals need some form of guidance in their use and calibration testing. If self-measurement of blood pressure is to be of benefit, the health care professional must recommend only those devices that are accurate and suitable to the patient or client. The Canadian Coalition for High Blood Pressure Prevention and Control will endeavour to develop a regular means by which health care professionals can keep informed of available devices for blood pressure self-measurement.

Blood Pressure Determination↗

PubMed1995

Self-measurement of blood pressure: recommendations of the Canadian Coalition for High Blood Pressure Prevention and Control.

OBJECTIVE: To provide health care professionals with guidelines on the use of blood pressure self-measurement. METHODS: Recommendations were devised after consideration of expert reviews and guidelines, personal files, international standards documents, personal communication with investigators and the results of a MEDLINE search (1966-94) using the term 'blood pressure determination'. BENEFITS, HARMS, COSTS: Self-measurement of blood pressure can be used to detect white coat hypertension, monitor changes in blood pressure closely, more rapidly achieve desired blood pressure goals, increase adherence to antihypertensive therapy and improve patient self-reliance. However, self-measured blood pressure readings may be misleading because there is insufficient normative, prognostic and outcome data and because some patients may not take accurate measurements. The use of self-measurement of blood pressure has a relatively small direct cost and may result in an overall reduction in treatment costs. RECOMMENDATIONS: Self-measured blood pressure readings can be a valuable supplement to clinic (or office) blood pressure readings. However, self-measurement is appropriate neither for patients who are physically or mentally incapable of accurate assessment and interpretation of readings nor for those who do not want to participate. Patients who self-monitor blood pressure require careful training in blood pressure measurement and instruction on the recording and interpretation of blood pressure readings. Advice to patients using monitoring equipment must take into account the needs and abilities of the patient. Although only a few electronic devices for the self-measurement of blood pressure have met recommended performance standards, their use may be more appropriate for some patients and the training requirements fewer than if manual devices are used. VALIDATION: The guidelines of several expert groups were examined in the preparation of these recommendations. The recommendations were presented at the World Conference on Hypertension Control in 1995 and were reviewed by the parent societies of the Canadian Coalition for High Blood Pressure Prevention and Control.

Blood Pressure Determination↗

PubMed1995

Reproductive health care delivery. Patterns in a changing market.

Providers of reproductive health services, including clinics and office-based physicians, face new challenges as the American health system progresses toward managed care. Although services for low-income women are often subsidized, the average out-of-pocket payments for reproductive health services are the same for women with incomes below and above 200% of the poverty level. Although many women, especially those classified as low income, use clinics, most say that they would prefer to receive care in a private physician's office and in a place where they can get general health care as well. Multivariate analyses indicate the importance of type of insurance and source of primary health care in affecting a woman's selection of her reproductive health care provider. Specialized providers such as family planning clinics need to consider how they can blend with managed care plans.

Adult↗

PubMed1994

Epitope mapping of the alpha-chain of the insulin-like growth factor I receptor using antipeptide antibodies.

Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells (VSMC). The IGF I receptor (IGF IR) is a heterotetramer composed of two cross-linked extracellular alpha-chains and two membrane-spanning beta-chains that contain a tyrosine-kinase domain. It has a high degree of sequence similarity to the insulin receptor (IR), and the putative ligand-specific binding site has been localized to a cysteine-rich region (CRR) of the alpha-chain. To obtain insights into antigenic determinants of the IGF IR, we raised a panel of site-specific polyclonal antibodies against short peptide sequences N-terminal to and within the CRR. Several antibodies raised against linear epitopes within the CRR bound to solubilized and native rat and human IGF IR by ELISA, did not cross-react with IR, but unexpectedly failed to inhibit 125I-IGF I binding. A polyclonal antibody directed against a 48-amino acid synthetic peptide, corresponding to a region of the CRR postulated to be essential for ligand binding, failed to react with either solubilized, reduced or intact IGF IR. Three antibodies specific for the N-terminus of the alpha-chain reacted with solubilized and native IGF IR. One of these, RAB 6, directed against amino acids 38-44 of the IGF IR, inhibited 125I-IGF I binding to rat aortic smooth muscle cells (RASM) and to IGF IR/3T3 cells (overexpressing human IGF IR) by up to 45%. Immunohistochemical analysis revealed strong IGF IR staining in the medial smooth muscle cell layer of rat aorta. These findings are consistent with a model wherein conformational epitopes within the CRR and linear epitopes within the N-terminus of the alpha-chain contribute to the IGF I binding pocket. These antibodies should provide a valuable tool to study structure-function relationships and in vivo regulation of the IGF IR.

Amino Acid Sequence↗

PubMed1994

Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

Animals↗