Biomedical subjects

N Lin

Publications and source records attributed to N Lin.

At least 55 records · Page 3Linked to original sources

PubMed1997

Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4.

Cyclin D1 plays an important role in the development of breast cancer and is required for normal breast cell proliferation and differentiation associated with pregnancy. We show that ectopic expression of cyclin D1 can stimulate the transcriptional activity of the estrogen receptor in the absence of estradiol and that this activity can be inhibited by 4-hydroxytamoxifen and ICI 182,780. Cyclin D1 can form a specific complex with the estrogen receptor. Stimulation of the estrogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4 activation. Cyclin D1 may manifest its oncogenic potential in breast cancer in part through binding to the estrogen receptor and activation of the transcriptional activity of the receptor.

Biomarkers, Tumor↗

PubMed1997

Vitamin D receptor polymorphisms, bone mineral density, and bone metabolism in postmenopausal Mexican-American women.

Common polymorphisms in the vitamin D receptor (VDR) gene have been shown to correlate with bone mineral density (BMD). However, attempts to replicate the original findings in other populations have yielded variable results. These disparities may reflect ethnic or environmental differences in the expression of the VDR effect upon BMD. We examined a relatively ethnically homogeneous group of 103 healthy postmenopausal Caucasian women of Mexican descent living in Northern California. We determined the VDR genotype and measured the BMD at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry, as well as several biochemical indices of mineral metabolism. The prevalence of the BB genotype, associated in previous studies with the lowest BMD, was 8% and highly linked to the tt genotype. Absolute and age-adjusted BMD at both hip and spine showed a trend toward lower BMD in the BB, AA, and tt genotypes, but this trend did not achieve statistical significance. There were no consistent intergroup differences in change in BMD over 2 years of follow-up, nor in mean serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, or total urinary pyridinolines. Intact parathyroid hormone concentrations were significantly higher in subjects with the AA genotype, with a trend toward higher values in those with the BB and tt genotypes as well. Our data suggest that there may be a decrease in BMD associated with the B, A, and t alleles, but the intergroup difference in BMD is 0.2-0.5 standard deviations (SD) at the lumbar spine and 0.3 SD at the femoral neck, decreases that are smaller than previously reported. Given the relatively low prevalence of the BB/tt genotype in Mexican-American Caucasians, a larger sample would be required to detect a significant association between VDR alleles and differences in BMD of the magnitude suggested by our data. We conclude that a genotype effect of this magnitude, if present, would be clinically relevant, but the impact on BMD is too small to detect with statistical significance in a study of this size.

Aged↗

PubMed1997

[The microspectra of chromosome].

The spectra of radicle chromosome of broad bean, marrow cell chromosome and marrow cell micro-nucleus of small white mouse were measured within the range of visible light by microspectrum technique. The differences among the spectra were found.

Animals↗

PubMed1997

Genetic and environmental contributions to smoking.

We estimate the magnitude of genetic and shared environmental contributions to risk of initiation and maintenance of smoking. Genetic models were fitted to data from 2,204 male-male monozygotic and 1,793 male-male dizygotic twin pairs from the Vietnam Era Twin Registry who responded to smoking questions on a 1987 mail and telephone survey. The best fitting model allowed for both genetic and shared environmental effects on smoking initiation, accounting for 50% and 30% of the variance in risk, but allowed for only genetic effects, (accounting for 70% of the variance in risk), on persistence in smoking among those who had become regular smokers. This finding of a major genetic influence on smoking persistence confirms similar results from studies in Scandinavia and Australia. The role of heritable traits such as nicotine sensitivity should be addressed in smoking prevention and cessation efforts.

Adult↗

PubMed1996

The influence of familial and non-familial factors on the association between major depression and substance abuse/dependence in 1874 monozygotic male twin pairs.

The co-occurrence of major depression (MD) with alcohol and illicit substance abuse/dependence (A/D) has been repeatedly observed. However, prior research has been unable to determine whether or not the co-occurrence is a result of familial vulnerability or non-familial influences. The present study examines the association of the lifetime diagnosis of MD with alcohol, cannabis, amphetamine, cocaine, and sedative A/D (DSM-III-R criteria) before and after controlling for familial factors in a non-clinical sample of 1874 middle aged, monozygotic male twin pairs. A lifetime diagnosis of MD was significantly associated with lifetime diagnosis of alcohol and illicit substance A/D prior to accounting for familial factors (odds ratios: 1.8-4.5). After employing a co-twin analytical technique to control for familial factors, a lifetime diagnosis of MD remained significantly associated only with lifetime diagnoses of cannabis, amphetamine and sedative A/D (odds ratios: 2.3-10.9). These results suggest that the association between MD and alcohol A/D is influenced by familial factors. In contrast, the association between MD and illicit substances of A/D is largely explained by non-familial factors.

Adult↗

PubMed1996

Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs.

Research and clinical experience indicate that drug use disorders tend to run in families. The objective of this study was to distinguish between the family environment and genetic factors as the source of this observed family resemblance. Data were collected by telephone interview from members of the Vietnam Era Twin Registry, comprising male twin pairs who served in the U.S. military between 1965 and 1975. There were 3,372 pairs in which both twins participated. Drug use disorder was defined as receiving a diagnosis of drug abuse or dependence according to DSM-III-R; 10.1% of the sample had abused or been dependent on at least one illicit drug. A significant difference between concordance rates for monozygotic (26.2%) vs. dizygotic (16.5%) twins indicated a genetic influence on drug use disorder. Biometrical modeling indicated that genetic factors (34% of the variance), the environment shared by twins (28% of the variance), and the nonshared environment (38% of the variance) had significant influences of similar magnitudes on the individual's risk of developing a drug use disorder. These results support the application of molecular genetic approaches to elucidate the genetic influence on drug use disorder, as well as the potential efficacy of environmental intervention to reduce risk.

Adult↗

PubMed1996

The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells.

In this study, we explored whether thrombopoietin (Tpo) has a direct in vitro effect on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC). We previously reported a cell separation method that uses the fluorescence-activated cell sorter selection of low Hoescht 33342/low Rhodamine 123 (low Ho/low Rh) fluorescence cell fractions that are highly enriched for LTR-HSC and can reconstitute lethally irradiated recipients with fewer than 20 cells. Low Ho/low Rh cells clone with high proliferative potential in vitro in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6 (90% to 100% HPP-CFC). Tpo alone did not induce proliferation of these low Ho/low Rh cells. However, in combination with SCF or IL-3, Tpo had several synergistic effects on cell proliferation. When Tpo was added to single growth factors (either SCF or IL-3 or the combination of both), the time required for the first cell division of low Ho/low Rh cells was significantly shortened and their cloning efficiency increased substantially. Moreover, the subsequent clonal expansion at the early time points of culture was significantly augmented by Tpo. Low Ho/low Rh cells, when assayed in agar directly after sorting, did not form megakaryocyte colonies in any growth condition tested. Several days of culture in the presence of multiple cytokines were required to obtain colony-forming units-megakaryocyte (CFU-Mk). In contrast, more differentiated, low Ho/high Rh cells, previously shown to contain short-term repopulating hematopoietic stem cells (STR-HSC), were able to form megakaryocyte colonies in agar when cultured in Tpo alone directly after sorting. These data establish that Tpo acts directly on primitive hematopoietic stem cells selected using the Ho/Rh method, but this effect is dependent on the presence of pluripotent cytokines. These cells subsequently differentiate into CFU-Mk, which are capable of responding to Tpo alone. Together with the results of previous reports of its effects on erythroid progenitors, these results suggest that the effects of Tpo on hematopoiesis are greater than initially anticipated.

Animals↗

PubMed1996

Müller and RPE cell response to photoreceptor cell degeneration in aging Fischer rats.

With increasing age, retinas of male Fischer rats gradually lose photoreceptor cells beginning at the ora serrata and extending to the central retina resulting in a pronounced peripheral retinopathy. In this study, we used immunocytochemical methods for glial fibrillary acidic protein (GFAP) and carbonic anhydrase II (CA II) to study the Müller cell response to age-related photoreceptor cell degeneration in the superior retina. Retinas of Fischer rats were also examined by electron microscopy to investigate retinal pigment epithelial (RPE) cell and Bruch's membrane structural changes with advancing age. Our study showed extensive photoreceptor cell loss in the region of the ora serrata beginning by 16 months, while few photoreceptor cells were found at 23 months. Neovascularization also occurred in the area of the peripheral retinopathy at the level of the RPE cells as determined by electron microscopy, as well as a thickening of Bruch's membrane with initial signs of small breaks. Dense areas of GFAP-immunostaining of Müller cell processes were found in the superior peripheral retina of 16-30 month-old rats where photoreceptor cells were degenerating. After 21 months, Müller cell processes extended into the subretinal space. However, in the central retina, where the photoreceptor cell population was more stable, GFAP-immunolabelled Můller cells were not detected. Immunoblots of retinal homogenates confirmed elevated GFAP levels at 18-30 months when compared to homogenates from retinas of 6-month-old Fischer rats. During photoreceptor cell degeneration, Müller cell processes were also prominently immunostained for CA II, which were seen to occupy the subretinal space at 18-30 months. Our results suggest that Müller cells respond to the age-related peripheral retinopathy in Fischer rats by increasing GFAP content and growth of their processes into the subretinal space to form a glial scar, but only in the area of severe photoreceptor cell loss. In addition, RPE and Bruch's membrane of aged retinas exhibit typical early age-related changes as also reported for aged human eyes.

Aging↗

PubMed1996

Repair of dGMP hydroxyl radical adducts by verbascoside via electron transfer: a pulse radiolysis study.

The repair activity of verbascoside (VER), isolated from Pedicularis spicata, towards the oxidizing hydroxyl radical adduct of dGMP and its reaction mechanism were studied using pulse radiolysis. Upon pulse radiolysis of nitrous oxide saturated aqueous solution of 2'-deoxyguanosine-5'-monophosphate (dGMP) and VER, it was found that the transient absorption spectrum of the hydroxyl adduct of dGMP decays with the formation of that of the phenoxyl radical of VER, several tens of microseconds after the electron pulse. From the formation kinetics of the phenoxyl radical of VER, the rate constant of the repair reaction was determined to be 1.12 x 10(9) dm(3) mol(-1) s(-1).

Antioxidants↗

PubMed1996

The association of antisocial personality symptoms with marijuana abuse/dependence. A monozygotic co-twin control study.

This study examines the association of symptoms of lifetime antisocial personality disorder (ASP) with marijuana abuse/dependence in Vietnam-era veteran male monozygotic twin pairs. In 1992, 1,874 monozygotic twin pairs responded to a structured psychiatric interview that obtained data on lifetime history of drug use and ASP. Among randomly selected individuals from each twin pair, 8 of 10 ASP symptoms were significantly more prevalent in persons with a lifetime history of marijuana abuse/dependence compared with those who had never abused any drug (p < .001). Among 99 marijuana discordant twin pairs, however, only two ASP symptoms, "failure to conform to social norms" (odds ratio, 2.8; 95% confidence interval, 1.5 to 5.5) and "reckless regard of own or other's personal safety" (odds ratio, 2.4; 95% confidence interval, 1.0 to 5.4) were significantly increased in marijuana abusing/dependent twins compared with their non-abusing/nondependent twin brother. After adjustment for conduct disorder, alcohol abuse/dependence, and exposure to combat in Vietnam, only "failure to conform to social norms of lawful behavior" (odds ratio, 2.42; 95% confidence interval, 1.12 to 5.21) remained significantly increased in twins with marijuana abuse/dependence.

Antisocial Personality Disorder↗

PubMed1996

Models of treatment seeking for alcoholism: the role of genes and environment.

We investigated the relative influence of genes and environment on the decision to seek treatment for alcoholism under three models of health care utilization. Lifetime alcohol dependence and two measures of treatment seeking for alcohol problems were determined from a 1992 telephone administration of the Diagnostic interview Schedule. Data were analyzed from 1,864 monozygotic and 1,492 dizygotic male twin respondents from the Vietnam Era Twin Registry. Genetic and environmental contributions to the decision to seek treatment for alcoholism were assessed under competing models for the relationship between genetic influences on alcoholism risk and genetic influences on treatment seeking among those who became alcoholics. Under the best-fitting model, genetic influence accounted for 41% of the variance in treatment seeking and 55% of the liability for alcoholism. Shared environment explained none of the variance in liability for alcoholism, but 40% of the variance in treatment seeking. The severity of alcoholism alone is an inadequate model of treatment seeking, because decisions to seek alcohol treatment are also influenced by substantial genetic and or shared environmental factors unrelated to the determinants of alcoholism.

Adult↗

PubMed1996

Stress in the life course: a life history approach.

This article examines the relationship between stress and distress in the life course, emphasizing the time elapsed between the event and measurement of psychological distress. Stressors are conceptualized as either distal or proximal based on how recently they occurred. Distal stressors are further classified as status changes or undesirable life changes. Using a life history calendar approach, we examine stressors occurring over a 15-year-period. We explore whether distal stressors affect current depressive symptomatology above and beyond the effect of more recent stressors and how these stressors vary in frequency and affect over 3 empirically defined age groups. While some events decrease in frequency over age, others occur consistently across age groups. Most important, distal stressors significantly impact current depressive symptomatology, independent of proximal stressors. Types of distal stressors affecting depression vary over age, indicating that the stage of life at which a stressor occurs is a significant determinant of the stressor's effect on depression.

Adult↗

PubMed1996

Increased synthesis of specific eicosanoids in rejected corneal grafts.

PURPOSE: Corneal injury stimulates the formation of both prostaglandins (PG) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), the major lipoxygenase metabolite. The purpose of this study was to investigate the metabolism of arachidonic acid (AA) in a model of corneal graft rejection. METHODS: Corneal tissue from Dutch belted rabbits was transplanted to vascularized corneas of New Zealand white rabbits. Rejected corneas were removed at the endstage of allograft failure. The allograft, the host corneal rim, the contralateral control cornea rim of equal size and normal Dutch belted cornea from the same site as the allograft were incubated with 0.25 microCi [3H]AA and the released eicosanoids were analyzed by high-performance liquid chromatography. RESULTS: The host corneal rims, adjacent to the failed allografts, produced up to five times as much 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) as contralateral control corneal rims. Additionally, prostaglandin E2 (PGE2) formation in the host rims increased 100% above controls, and 12(S)-HETE and PGE2 synthesis in the rejected corneal graft also increased. 12(R)-HETrE, an endogenous corneal angiogenic factor, was not detected in rejected corneas. CONCLUSIONS: The results point to the importance of selective AA pathways as the source key inflammatory components found in rejected allografts.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1996

Photoreceptor repair in response to RPE transplants in RCS rats: outer segment regeneration.

PURPOSE: We have previously shown that transplants of normal rat neonatal RPE cells rescued photoreceptor cells in retinas of Royal College of Surgeons (RCS) dystrophic rats for up to one year. In this study, we investigated the photoreceptor rescue effects in RCS rats within the first three weeks following transplantation in an attempt to determine if RPE transplants initiate repair mechanisms, specifically, outer segment (OS) regeneration. METHODS: Freshly isolated RPE cells from neonatal pigmented Long Evans rats were transplanted into the subretinal space of 22-23 day-old RCS rats using a transscleral approach. For controls, vehicle was similarly injected. RESULTS: When analyzed at 10 days post-transplantation, long inner segments were observed with short buds of outer segment growth in the area of the RPE-cell transplants. The outer segments were of insufficient length to be measured at 10 days, but by 14 and 21 days, OS were 2.02 +/- 0.32 microns and 18.80 +/- 2.78 microns, respectively. In vehicle-injected retinas from 10 to 21 days postsurgery, outer segments were not observed and the inner segments were three-fold shorter than in RPE-transplanted retinas. At 10 days post-transplantation, most RPE cells were seen in the subretinal space, but a few had attached to Bruch's membrane; however, by 21 days, many of the transplanted RPE cells had attached to Bruch's membrane, although a few were found free in the subretinal space. CONCLUSIONS: This study has shown that transplants of normal rat neonatal RPE cells have the capacity to support not only photoreceptor cell survival but also initiate early repair mechanisms as exhibited by outer segment regeneration in RCS retinas. These results also conclusively show the important role that the RPE plays in outer segment growth and maturation.

Animals↗

PubMed1996

Thrombopoietin expands erythroid, granulocyte-macrophage, and megakaryocytic progenitor cells in normal and myelosuppressed mice.

Thrombopoietin (Tpo), the ligand for the proto-oncogene receptor c-Mpl, increases megakaryocyte size, ploidy, and surface expression of platelet-specific glycoproteins, is inversely related to platelet mass, and is a potent in vivo stimulus of platelet production. However, several features of c-mpl biology, and that of its viral counterpart v-mpl, suggest that the action of Tpo may not be strictly limited to megakaryocytopoiesis. To investigate the possibility that Tpo might affect a multitude of cell lineages, we studied the effects of in vivo administration of the hormone on multiple types of marrow and splenic clonogenic hematopoietic progenitors. We report that Tpo acts to expand BFU-E, CFU-GM, and CFU-Mk and redistribute CFU-E in normal mice and to hasten the recovery of all of these progenitor cell types in myelosuppressed animals. These findings argue that the hematopoietic progenitor cell compartment responds to Tpo as a whole and that the in vivo effects of Tpo administration may be more wide-ranging than previously anticipated.

Animals↗

PubMed1996

Reaction of hydroxyl radical with phenylpropanoid glycosides from Pedicularis species: a pulse radiolysis study.

Using pulse radiolysis technique, the reaction between hydroxyl radical and 7 phenylpropanoid glycosides: echinacoside, verbascoside, leucosceptoside A, martynoside, pediculariosides A, M and N which were isolated from Pedicularis were examined. The rate constants of these reactions were determined by transient absorption spectra. All 7 phenylpropanoid glycosides react with hydroxyl radical at high rate constants within (0.97-1.91) x 10(10)L.mol-1.s-1, suggesting that they are effective hydroxyl radical scavengers. The results demonstrate that the numbers of phenolic hydroxyl groups of phenylpropanoid glycosides are directly related to their scavenging activities. The scavenging activities are likely related to o-dihydroxy group of phenylpropanoid glycosides as well.

Drugs, Chinese Herbal↗

PubMed1995

Thrombopoietin, the Mp1 ligand, is essential for full megakaryocyte development.

The development of megakaryocytes (MKs) from their marrow precursors is one of the least understood aspects of hematopoiesis. Current models suggest that early-acting MK colony-stimulating factors, such as interleukin (IL) 3 or c-kit ligand, are required for expansion of hematopoietic progenitors into cells capable of responding to late-acting MK potentiators, including IL-6 and IL-11. Recently, the Mp1 ligand, or thrombopoietin (Tpo), has been shown to display both MK colony-stimulating factor and potentiator activities, at potencies far greater than that of other cytokines. In light of these findings, we tested the hypothesis that Tpo is absolutely necessary for MK development. In this report we demonstrate that neutralizing the biological activity of Tpo eliminates MK formation in response to c-kit ligand, IL-6, and IL-11, alone and in combination, but that these reagents only partially reduce MK formation in the presence of combinations of cytokines including IL-3. However, despite the capacity of IL-3 to support the proliferation and initial stages of MK differentiation, elimination of Tpo prevents the full maturation of IL-3-induced MK. These data indicate that two populations of MK progenitors can be identified: one that is responsive to IL-3 but can fully develop only in the presence of Tpo and a second that is dependent on Tpo for both proliferation and differentiation. Thus, our results strongly suggest that Tpo is the primary regulator of MK development and platelet production.

Animals↗

PubMed1995

Stem cell factor modulates avidity of alpha 4 beta 1 and alpha 5 beta 1 integrins expressed on hematopoietic cell lines.

Interactions between hematopoietic cells and bone marrow (BM) stroma, composed of extracellular matrix and stromal cells, are crucial for hematopoiesis. Integrins facilitate these interactions by mediating adherence of hematopoiesis. Integrins facilitate these interactions by mediating adherence of hematopoietic cells to both the extracellular matrix and stromal cells. Marrow stromal cells secrete a variety of growth factors, including stem cell factor (SCF). Because treatment with SCF in vivo mobilizes primitive hematopoietic cells from the BM, we investigated the effect of the growth factor SCF of hematopoietic cell adhesion. These studies show that SCF modulates adhesive function in a dose- and time-dependent manner, but does not modulate expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 in the SCF-responsive cell line MO7E. Treatment of MO7E cells with SCF (200 ng/mL) produced a transient increase in adherence to cytokine-activated human umbilical vein endothelial cells (HUVECs) or to vascular cell adhesion molecule 1 (VCAM-1)-transfected Chinese hamster ovary (CHO) cells with peak adhesion at 30 minutes and return to baseline by 60 to 90 minutes. This increase in adhesion was paralleled by increased binding of the beta 1 activation-dependent monoclonal antibody (MoAb) 15/7, as determined by flow cytometry. However, prolonged incubation of MO7E with SCF induced a marked decrease in integrin-mediated adherence, with maximal inhibition by 24 hours. No change in expression of integrins, as determined by flow cytometry, was observed with short- or long-term incubation with SCF. SCF-treated cells were still able to respond to phorbol esters and to the activating beta 1 MoAb 8A2 with increased adherence, but not to the level seen in control cells. This suggests that a subpopulation of expressed alpha 4 beta 1 and alpha 5 beta 1 integrins is disengaged by prolonged incubation with SCF.

Animals↗