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N Stern

Publications and source records attributed to N Stern.

At least 19 recordsLinked to original sources
PubMed2002

6-Carboxymethyl genistein: a novel selective oestrogen receptor modulator (SERM) with unique, differential effects on the vasculature, bone and uterus.

The novel genistein (G) derivative, 6-carboxymethyl genistein (CG) was evaluated for its biological properties in comparison with G. Both compounds showed oestrogenic activity in vitro and in vivo. On the other hand G and CG differed in the following parameters: (i) only CG displayed mixed agonist-antagonist activity for oestrogen receptor (ER) alpha in transactivation assays and (ii) only CG was capable of attenuating oestrogen (E(2))-induced proliferation in vascular smooth muscle cells and of inhibiting oestrogen-induced creatine kinase (CK) specific activity in rat tissues. On the other hand only G enhanced the stimulatory effect on CK specific activity in the uterus. In comparison to the selective oestrogen receptor modulator (SERM) raloxifene (RAL), CG showed the same selectivity profile as RAL in blocking the CK response to E(2) in tissues derived from both immature and ovariectomized female rats. Molecular modelling of CG bound to the ligand binding domain (LBD) of ERbeta predicts that the 6-carboxymethyl group of CG almost fits the binding cavity. On the other hand, molecular modelling of CG bound to the LBD of ERalpha suggests that the carboxyl group of CG may perturb the end of Helix 11, eliciting a severe backbone change for Leu 525, and consequently induces a conformational change which could position Helix 12 in an antagonist conformation. This model supports the experimental findings that CG can act as a mixed agonist-antagonist when E(2) is bound to its receptors. Collectively, our findings suggest that CG can be considered a novel SERM with unique effects on the vasculature, bone and uterus.

Analysis of Variance↗
PubMed2001

Increased oxidative stress in ataxia telangiectasia evidenced by alterations in redox state of brains from Atm-deficient mice.

Ataxia-telangiectasia (A-T) is a genetic disorder caused by mutational inactivation of the ATM gene. A-T patients display a pleiotropic phenotype and suffer primarily from progressive ataxia caused by degeneration of cerebellar Purkinje and granule neurons. Disruption of the mouse Atm locus creates a murine model of A-T that exhibits most of the clinical features of the human disease. We previously hypothesized that some aspects of A-T, such as the preferential loss of certain neurons, could result from a continuous state of increased oxidative stress (G. Rotman and Y. Shiloh, Cancer Surv., 29: 285-304, 1997; G. Rotman and Y. Shiloh, BioEssays, 19: 911-917, 1997). The present work tests this hypothesis by analyzing markers of redox state in brains of Atm-deficient mice. We found alterations in the levels of thiol-containing compounds in Atm (-/-) brains, as well as significant changes in the activities of thioredoxin, catalase, and manganese superoxide dismutase in Atm (-/-) cerebella. These changes are indicative of increased levels of reactive oxygen species, which are seen primarily in the cerebellum of Atm-deficient mice. Our findings support the hypothesis that the absence of functional ATM results in oxidative stress, which may be an important cause of the degeneration of cerebellar neurons in A-T.

Animals↗
PubMed2001

Effects of phytoestrogens on DNA synthesis and creatine kinase activity in vascular cells.

BACKGROUND: The aim of this study was to assess the effect of phytoestrogens on the human vascular wall in vitro. METHODS: We compared the effects of E2 to those of genistein (G), daidzein (D), biochanin A (BA), equol (EQ), and quecertin (Qu) on 3[H] thymidine incorporation and creatine phosphokinase (CK) activity in human vascular smooth muscle cells (VSMC) and in a human endothelial cell line (E304). RESULTS: In VSMC, E2, the estrogen antagonist raloxifene (RAL), G, and D stimulated DNA synthesis at low concentrations and suppressed 3[H] thymidine incorporation at higher concentrations. In contrast, BA and EQ had a monophasic stimulatory effect on 3[H] thymidine incorporation (87% +/- 9% and 54% +/- 17%, respectively) whereas Qu had only an inhibitory effect (-36 +/- 16% at 30 nmol/L). In E304 cells, all phytoestrogens stimulated DNA synthesis in a dose-related manner. In both cell types E2, RAL as well as all phytoestrogens increased CK-specific activity. The administration of phytoestrogens to immature female rats resulted in increased CK in the aorta (Ao) (60% to 220%) and in the left ventricle of the heart (Lv) (45% to 160%). Similar increases in Ao and Lv CK were also induced by E2 and all five phytoestrogens in ovariectomized (OVX) female rats. RAL antagonized phytoestrogen-induced CK activity in human vascular cells and in the rat Ao and Lv tissue but did not block phytoestrogen effects on DNA synthesis in human VSMC. CONCLUSIONS: Although phytoestrogens have estrogen-mimetic effects on cell growth and CK in cultured human vascular cells and on CK in rat vascular tissues in vivo, the effects on human VSMC replication are highly dependent on the concentration and the particular phytoestrogen under investigation.

Animals↗
PubMed2001

Genetic heterogeneity of familial hyperkalaemic hypertension.

BACKGROUND: Familial hyperkalaemic hypertension (FHH) is a Mendelian form of low-renin hypertension characterized by hyperkalaemia and hyperchloraemic acidosis despite a normal glomerular filtration rate. To date, three different loci have been identified, on chromosomes 1, 17 and 12. OBJECTIVE: To test for genetic linkage between the three FHH loci and three new affected kindreds. DESIGN AND METHODS: Clinical, biological and genetic analyses were made of three kindreds, including 11 affected individuals among 25 members. Genotyping was performed using four series of microsatellite markers spanning the chromosomes 1, 17 and 12 loci, and the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene. RESULTS: Segregation of the trait in each kindred was compatible with an autosomal transmission, the affected individuals displaying reasonably consistent biochemical abnormalities and the expected variability in arterial hypertension. Multipoint linkage analysis excluded linkage with the four candidate loci in kindreds 1 and 2, but not with the chromosome 1 locus in kindred 3. CONCLUSION: These results demonstrate further genetic heterogeneity and that a fourth gene is responsible for FHH in at least two unrelated kindreds. They suggest a variety of molecular defects leading to FHH.

Adolescent↗
PubMed2001

A novel form of platelet-type 12-lipoxygenase mRNA in human vascular smooth muscle cells.

The lipoxygenase pathway has been implicated in the growth, migration, and contraction of vascular smooth muscle cells (VSMCs). However, the precise type of lipoxygenase present in the vascular wall has not been characterized. In this study, we used a specific reverse-transcriptase polymerase chain reaction method with 2 sets of specific primers on total RNA and polyA (+)RNA of normal human VSMCs prepared from umbilical artery. Two forms of platelet-type 12-lipoxygenase mRNA were present in human VSMCs: the already published form cloned from human erythroleukemia cells and a variant form of platelet-type 12-lipoxygenase, which includes 2 additional sequences consistent with the 2 introns (D and E). This novel form of 12-lipoxygenase poly A (+)RNA was downregulated by lipopolysaccharide (10 ug/ml) and upregulated by epidermal growth factor (100 ng/ml) but was not affected by angiotensin II (10(-7) mol/l). We developed a rabbit anti-human platelet-type 12-lipoxygenase polyclonal antibody directed against a 24-amino acid peptide encoded within exon 4. Western immunoblotting of protein extracted from VSMCs and umbilical artery and platelet extract with this antibody showed a coordinate 110-kDa protein and the already-described 70-kDa band detected in platelets and cord homogenate. Another 120-kDa protein was consistently detected in cord extracts but not in platelet or VSMC homogenates. The immunohistochemistry study performed with the same antibody showed extensive cytoplasmic staining of VSMCs. The specific role of these different forms of platelet-type 12-lipoxygenase is subject to further investigation.

Alternative Splicing↗
PubMed2000

Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cells.

There is an increasing demand for natural compounds that improve women's health by mimicking the critical benefits of estrogen to the bones and the cardiovascular system but avoiding its deleterious effects on the breast and uterus. The estrogenic properties of glabridin, the major isoflavan in licorice root, were tested in view of the resemblance of its structure and lipophilicity to those of estradiol. The results indicate that glabridin is a phytoestrogen, binding to the human estrogen receptor and stimulating creatine kinase activity in rat uterus, epiphyseal cartilage, diaphyseal bone, aorta, and left ventricle of the heart. The stimulatory effects of 2.5-25 microg/animal glabridin were similar to those of 5 microg/animal estradiol. Chemical modification of glabridin showed that the position of the hydroxyl groups has a significant role in binding to the human estrogen receptor and in proliferation-inducing activity. Glabridin was found to be three to four times more active than 2'-O-methylglabridin and 4'-O-methylglabridin, and both derivatives were more active than 2',4'-O-methylglabridin. The effect of increasing concentrations of glabridin on the growth of breast tumor cells was biphasic. Glabridin showed an estrogen receptor-dependent, growth-promoting effect at low concentrations (10 nM-10 microM) and estrogen receptor-independent antiproliferative activity at concentrations of > 15 microM. This is the first study to indicate that isoflavans have estrogen-like activities. Glabridin and its derivatives exhibited varying degrees of estrogen receptor agonism in different tests and demonstrated growth-inhibitory actions on breast cancer cells.

Animals↗
PubMed2000

The molecular mechanism of dopamine-induced apoptosis: identification and characterization of genes that mediate dopamine toxicity.

Parkinson's disease (PD) is a progressive neurological disorder caused by rather selective degeneration of the dopaminergic (DA) neurons in the substantia nigra. Though subject to intensive research, the etiology of this nigral neuronal loss is still enigmatic and treatment is basically symptomatic. The current major hypothesis suggests that nigral neuronal death in PD is due to excessive oxidative stress generated by auto- and enzymatic oxidation of the endogenous neurotransmitter dopamine (DA), the formation of neuromelanin and presence of high concentrations of iron. We have found that DA toxicity is mediated through its oxidative metabolites. Whereas thiol-containing antioxidants provided marked protection against DA toxicity, ascorbic acid accelerated DA-induced death. Using the differential display approach, we sought to isolate and characterize genes whose expression is altered in response to DA toxicity. We found an upregulation of the collapsin response mediator protein (CRM) and TCP-1delta in sympathetic neurons, which undergo dopamine-induced apoptosis. The isolation of these genes led us to examine the expression and activity of CRM and TCP-1delta related genes. Indeed, we found a significant induction of mRNAs of the secreted collapsin-1 and the mitochondrial stress protein HSP60. Antibodies directed against collapsin-1 provided marked and prolonged protection of several neuronal cell types from dopamine-induced apoptosis. In a parallel study, using antisense technology, we found that inhibition of TCP-1delta expression significantly reduced DA-induced neuronal death. These findings suggest a functional role for collapsin-1 and TCP-1delta as positive mediators of DA-induced neuronal apoptosis.

Animals↗
PubMed2000

Vitamin D analogs modulate the action of gonadal steroids in human vascular cells in vitro.

We have previously reported that estradiol (E2) and dihydrotestosterone (DHT) regulate cell growth in human umbilical arterial smooth muscle cells (SMC) and in an endothelial cell line (E304). In SMC both gonadal steroids stimulated DNA synthesis at low concentrations and suppressed 3[H] thymidine incorporation at high concentrations, whereas in E304 cells E2 and DHT dose dependently enhanced DNA synthesis. In both cell types gonadal steroids also induced the specific activity of creatine kinase BB (CK). Previous evidence suggets that the in vitro and in vivo CK responses to gonadal steroids in bone cells are upregulated by pretreatment with vitamin D analogs due to increased level of cellular estrogen receptors (ER). Here we analyzed the interaction of the vitamin D analogs hexafluorovitamin D (FL), JK-1624 F2-2 (JKF), and CB 1093 (CB) with gonadal steroids in regulating DNA synthesis and CK activity in human vascular cells in vitro. In E304 cells, daily treatment with FL, JKF, or CB (1 nmol/L for 3 days) increased DNA synthesis by 110 +/- 11%, 65 +/- 16%, and 88 +/- 23% respectively. In contrast, the same analogs inhibited 3[H] thymidine incorporation by 52 +/- 21%, 46 +/- 19%, and 50 +/- 10%, respectively, in SMC. In both cell types all three analogs increased CK by 25% to 75% and amplified the CK response to E2 and to DHT by twofold to threefold. In E304 cells the vitamin D analogs also increased DNA response to gonadal steroids from 50% to 60% to 200% to 280%. In SMC these analogs did not modify the DNA synthetic response to a low E2 concentration, but prevented the suppression of DNA synthesis exerted by high concentrations of E2 and DHT. Vitamin D inhibitors known to block cellular calcium mobilization, had no effect on the proliferative activity induced by vitamin D analogs. However, the inhibitor of the nuclear effects of vitamin D, ZK 159222, blocked the stimulatory effects of CB on DNA synthesis in E304 cells. Finally, both 1,25(OH)2 D3, and JKF decreased the expression of ERbeta proteins in SMC and increased the ERalpha isoform in E304 cells by 40% to 75%. The results indicate that vascular cells are targets for both vitamin D and gonadal steroid action and suggest a possible interaction between these hormones in the regulation of cell proliferation via modulation of vascular ER or interaction with proteins associated with ER.

Androgens↗
PubMed2000

Low-dose (1 microgram) adrenocorticotrophin (ACTH) stimulation as a screening test for impaired hypothalamo-pituitary-adrenal axis function: sensitivity, specificity and accuracy in comparison with the high-dose (250 microgram) test.

OBJECTIVE: We have shown previously that in contrast to the standard high-dose 250-microgram ACTH test, a low-dose 1-microgram ACTH stimulation test correctly identified all patients with pituitary disease who had impaired hypothalamo-pituitary-adrenal (HPA) function. In this study we further compared the performances of these two tests as screening procedures for possible HPA impairment. DESIGN: A comparison of the 1-microgram and the 250-microgram ACTH stimulation tests in healthy controls and in patients with pituitary disease whose HPA axis status was characterized formally by a gold standard test. SUBJECTS: A total of 89 subjects were investigated: 27 healthy normal controls, 43 patients with pituitary disease and normal HPA function, and 19 patients with various pituitary diseases and impaired HPA function. MEASURES: All 89 subjects underwent stimulation with 1 microgram ACTH; 80 also underwent the high-dose 250-microgram ACTH test. A receiver operating characteristic analysis (ROC) was performed to compare the tests. RESULTS: Using a stimulated cortisol > 500 nmol/l as the criterion for a normal response, the 1-microgram ACTH stimulation identified 18 of the 19 subjects with impaired HPA function (94.7% sensitivity with a likelihood ratio of 0.0588 for a negative test). In contrast, 15/16 passed the high-dose test (a 6.2% sensitivity with a likelihood ratio of 0.875 for a negative test). All normal controls, and 36/43 patients with preserved HPA function, passed the 1-microgram ACTH test (90% specificity). This degree of accuracy was unrivalled by the high dose test at all the cut-off levels considered. CONCLUSIONS: More sensitive and accurate, the low-dose 1-microgram ACTH test is as simple and safe as the standard 250-microgram test. We suggest it should replace it in screening for adrenal insufficiency.

Adrenal Insufficiency↗
PubMed2000

Risk factor clustering in hypertensive patients: impact of the reports of NCEP-II and second joint task force on coronary prevention on JNC-VI guidelines.

INTRODUCTION: Although the association of hypertension with established risk factors has been noted in several population studies, the recent redefinition of dyslipidaemia, hypertension and diabetes calls for reassessment of the prevalence and pattern of risk factor clusters in essential hypertension. OBJECTIVE: To analyse the risk factor profile of Israeli patients with essential hypertension seen by primary care physicians and in hypertension specialty clinics, based on current definitions of dyslipidaemia hypertension and diabetes and JNC-VI guidelines for the assessment of risk factors. DESIGN AND SETTING: We analysed the risk profile of 324 Israeli hypertensive subjects using the JNC-VI risk table and risk grouping. A total of 122 consecutive patients were recruited from primary care clinics and 212 consecutive patients were recruited from a hospital based hypertension clinic. RESULTS: Amongst hypertensive individuals with no known target organ damage, only 1.5% had no risk factors other than hypertension, whereas all hypertensives with coronary artery disease had additional risk factors. Of the six listed major JNC-VI risk factors (smoking, dyslipidaemia, diabetes, age, sex, family history of cardiovascular disease), hypertensive subjects without coronary artery disease (coronary artery disease-negative) had 3.02 +/- 0.10 risk factors, whereas hypertensive subjects with coronary artery disease (coronary artery disease positive) had 3.6 +/- 0.07 risk factors other than hypertension (P < 0.01). Dyslipidaemia defined by NCEP-II criteria was the most common associated risk factor identified in 93% of coronary artery disease-positive and 77% of the coronary artery disease-negative hypertensive subjects. The most common dyslipidaemic abnormality was an increased LDL cholesterol (79.2% of the cohort), followed by hypertriglyceridaemia (31.7%) and low HDL cholesterol (22.3%). Nevertheless, in nearly half of the coronary artery disease-negative patients, LDL cholesterol concentrations were within 30 mg dL-1 of the target levels. The most common dyslipidaemic variant was isolated hypercholesterolaemia (42%), whereas the syndrome X dyslipidaemic combination of hypertriglyceridaemia and low HDL was strikingly uncommon, observed in 2.8% of the coronary artery disease-positive and 0.8% of the coronary artery disease-negative patients. CONCLUSIONS: (i) JNC-VI group risk A patients (no risk factors) comprise a very small minority in this cohort (< 5%); (ii) dyslipidaemia is exceedingly common with mild hypercholesterolaemia being the most prevalent variant and hypertriglyceridaemia with low HDL the least common form.

Cardiovascular Diseases↗
PubMed2000

Effect of prefabricated metal post-head design on the retention of various core materials.

Retention of various post heads to core restorative materials is an important factor in the selection of prefabricated post systems and restorative materials for the restoration of endodontically treated teeth. This study examines the retention of a post-core prefabricated system in relation to core material and post-head design. A total of 60 samples were prepared using two different post systems (ParaPost Plus (PP) and ParaPost Unity (PU), with amalgam, composite or glass-ionomer as one of the core materials. The samples were tested using the Instron testing machine. The PP was superior to the PU prefabricated post with respect to the retention of various core materials. Retention values in descending order of magnitude were found to be: composite, amalgam and glass-ionomer (significantly lower). The rhomboid serrated design of PP was superior in retention to the rounded smooth UP system. Composite material proved to be superior in retention, closely followed by amalgam, with glass-ionomer significantly less retentive.

Analysis of Variance↗
PubMed2000

Trauma history as a predictor of psychologic symptoms in women with breast cancer.

PURPOSE: To identify predictors of psychiatric problems in women with early-stage breast cancer. PATIENTS AND METHODS: One hundred sixty women with early-stage breast cancer were recruited from three treatment centers. They filled out self-report questionnaires, including a medical history and demographic survey, the Trauma History Questionnaire, Life Event Questionnaire, Brief Symptom Inventory, Beck Depression Inventory, and Duke-UNC Functional Social Support Questionnaire, and were evaluated using the Structured Clinical Interview for DSM-III-R. RESULTS: Hierarchical regression analyses indicated that four of five variable sets made a significant incremental contribution to outcome prediction, with 35% to 37% of the variance explained. Outcomes were predicted by demographic variables, trauma history variables, precancer psychiatric diagnosis, recent life events, and perceived social support. Cancer treatment variables did not predict outcome. CONCLUSION: The findings highlight the important roles of trauma history and recent life events in adjustment to cancer and have implications for screening and treatment.

Adult↗
PubMed1999

Contaminant eluted from solid-phase plasmid affinity-purification protocol columns is not found using liquid-phase methods and can be prevented.

The preparation of high quality plasmid DNA is a necessary requirement for most molecular biology applications. We compared four different large plasmid preparation protocols, which were based on either a liquid-phase approach (Triton lysis) or purification of alkaline lysis bacterial extracts followed by supercoiled plasmid purification on affinity columns. Two host Escherichia coli strains, JM 109 and INValphaF', were used to grow the test plasmids for comparison of product plasmid DNA produced from the four different plasmid isolation methods. While the DNA grown in E. coli strain JM109, prepared by liquid-phase Triton lysis was appropriately restricted by 12 restriction enzymes, this was not the case for any of the JM109-grown DNA purified by any of the affinity column solid-phase approaches. In contrast to this, when the plasmid DNA was grown in E. coli strain INValphaF', most restriction enzymes cut DNA appropriately, irregardless of the plasmid preparation protocol used. It seems that an impurity commonly eluted with the DNA from all three of the solid-phase DNA columns had an equal effect on the above enzymes using the common host strain JM109, but not strain INValphaF'.

Chromatography, Affinity↗
PubMed1999

TRH is a tonic secretagogue in growth hormone secreting but not in nonfunctioning pituitary tumors.

In most patients with growth hormone (GH) secreting pituitary adenomas and clinically nonfunctioning pituitary tumors (NFPT) the intravenous injection of thyrotropin releasing hormone (TRH) augments the secretion of GH and subunits of gonadotropin hormones respectively. Similar hormone responses to TRH have been detected in rat pituitary cell lines and in primary human pituitary tumor cultures in vitro. Nevertheless the TRH effect on tumor hormonal secretion has not been well characterized. In the present study we examined TRH-induced hormone secretion in GH secreting tumors and in NFPT in vitro. Cultured cells secreted betaLH and betaFSH (NFPT) or GH (GH secreting adenomas) up to 14 days in culture. In NFPT TRH (10(-8) mol/l) elicited peak betaLH and betaFSH secretion at 60 to 90 min, with no further increase at 24 h. TRH-stimulated GH secretion peaked at 90-120 min, and decreased after 3 h, but a secondary rise occurred after 24 h of incubation. Chronic daily exposure to TRH followed by an acute TRH challenge resulted in a further increase of GH secretion after one hour. In contrast, acute TRH administration following chronic exposure did not elicit increased P-subunits secretion in NFPT. Coadministration of cycloheximide did not change TRH induced beta-subunits secretion in NFPT. However, when it was administered 24 h prior to TRH, it blocked both basal and TRH induced beta-subunits levels in NFPT. Cycloheximide had no effect on basal or stimulated GH secretion when administered concomitantly or 24 h before TRH. Incubation of cultured GH secreting tumors with cycloheximide during 5 days blocked both basal and TRH stimulated GH secretion, thus indicating dependency on protein synthesis during the chronic, secondary phase. Since the acute secretion was not affected by coadministration of cycloheximide, these early increases in hormone levels apparently reflect the release of stored hormone. In summary, GH secreting adenomas and NFPT differ significantly in their hormonal response to continuous exposure to TRH. The mechanisms underlying the sustained effect of TRH on GH secretion in vitro remain to be investigated. If endogenous TRH exerts a similar continuous effect it may contribute to the disregulated GH secretion in acromegaly.

Adenoma↗
PubMed1999

Platelet-derived endothelial cell growth factor inhibits DNA synthesis in vascular smooth muscle cells.

Platelet-derived endothelial cell growth factor (PD-ECGF) is linked to angiogenesis in human cancer. Direct studies have demonstrated that PD-ECGF is a potent mitogen for endothelial cells in vivo. Because endothelial repair and smooth muscle cell proliferation are two processes that affect arterial wall structure and tone, we analyzed the effects of PD-ECGF on DNA synthesis and creatine kinase BB-specific activity (CK) in human umbilical artery smooth muscle cells (SMC) and in a human umbilical endothelial cell line (E304). In SMC, PD-ECGF (0.001 to 10 U/mL) inhibited DNA synthesis dose dependently (-24% + 6% to -63% + 15%) assessed by 3[H]thymidine incorporation into DNA, whereas in E304 it stimulated DNA synthesis dose dependently (30% + 4% to 100% + 4%). In both SMC and E304, however, PD-ECGF elicited an increase in CK-specific activity by 54% to 130% and 79% to 163%, respectively. These effects were reversed by a specific anti-PD-ECGF antibody. In E304 cells PD-ECGF enhanced 17beta-estradiol (E2) or dihydrotestosterone (DHT)-induced DNA synthesis from 56% to 122% and from 127% to 359%, and CK activity from 70% to 180% and from 90% to 190%, respectively. In SMC PD-ECGF, an inhibitor of 3[H]thymidine incorporation by itself, markedly enhanced the stimulatory effect of low concentrations of E2 and DHT on 3[H]thymidine incorporation. It also increased E2 and DHT CK induction from 40% to 140% and from 52% to 120%, respectively. In both E304 and SMC, PD-ECGF inhibited the proliferative and the CK-inducing effects of platelet-derived growth factor (PDGF) and immunoglobulin F1 (IGF1). Thus, PD-ECGF, an established growth promoter for endothelial cells, is a potent inhibitor of DNA synthesis in human arterial SMC. However, in both E304 endothelial cells and SMC, PD-ECGF enhances the stimulatory effect of low concentrations of gonadal steroids on 3[H]thymidine incorporation. PD-ECGF antagonizes PDGF- and IGF1-induced DNA synthesis in both E304 and SMC cells. By inhibiting arterial SMC proliferation and accelerating endothelial cell replication, PD-ECGF may buffer the effect of PDGF and favorably modulate arterial wall response to injury.

Cell Division↗
PubMed1999

Thyroxine replacement therapy enhances clearance of chylomicron remnants in patients with hypothyroidism.

To further confirm the benefit of replacement therapy in terms of risk for coronary artery disease, we evaluated the effect of T4 on postprandial lipoproteins in patients with hypothyroidism. Nine normolipidemic patients (aged 62.75+/-7.6 yr) with TSH of 32.2+/-13.2 mU/L and free T4 of 0.66+/-0.17 ng/mL were treated with T4 (50-100 microg/day) for at least 4 months. The behavior of postprandial lipoproteins was assessed before and during treatment by determining retinyl palmitate levels in the total plasma, chylomicrons (Sf >1000) and chylomicron remnants (Sf <1000) fractions for 8 h after a mixed meal plus vitamin A. During T4 treatment, serum levels of TSH and FT4 were 4.4+/-4.9 mU/L and 1.2+/-0.34 ng/mL (P = 0.001 and P = 0.002), respectively. Fasting low density lipoprotein cholesterol decreased from 166+/-35 to 135+/-23 mg/dL (P = 0.035). Retinyl palmitate (RP) levels in the chylomicron remnant fraction was reduced significantly during therapy from 6948+/-2790 to 5174+/-2401 microg/L x h (area under the curve +/-SD; P = 0.014). Total plasma RP and chylomicron RP remained unchanged. We conclude that T4 enhances the clearance of chylomicron remnants in normolipidemic patients with hypothyroidism.

Cholesterol, HDL↗
PubMed1999

Effect of TRH on beta-gonadotropin subunits in patients with pituitary microincidentalomas.

OBJECTIVE: To explore the hypothesis that most of the pituitary abnormalities compatible with the diagnosis of microadenoma, and detected in about 10% of the normal adult population, represent asymptomatic gonadotropinomas. DESIGN: Patients diagnosed with pituitary microincidentalomas at the Institute of Endocrinology of the Tel Aviv Medical Center were evaluated. Circulating beta-subunits of gonadotropin hormones were measured before and 30, 45, 60 and 90 min after the intravenous injection of 400 microgram TRH. PATIENTS: Twenty-two patients with pituitary incidentaloma and 16 normal volunteers were tested. RESULTS: In 16 of the 22 patients, an abnormal beta-subunit response was detected after the TRH challenge. Three patients had an abnormal increase in both beta-FSH and beta-LH after TRH administration. Isolated pathological beta-FSH or beta-LH responses were demonstrated in five and eight patients respectively. Six patients had normal basal and stimulated gonadotropin subunit values, raising the possibility that their lesions were not pituitary microadenomas. There was a significant overall difference between the response to TRH of the patient and control groups. In the gonadotropin positive group, comprising 16 patients, serum beta-FSH increased from 6.4+/-1.6 ng/ml to 9.2+/-1.3 ng/ml (P=0.042) 1 h after TRH stimulation, whereas no changes were detected in the control group after TRH injection (basal: 4.1+/-0.8 ng/ml, peak: 5.1+/-0.8 ng/ml; P=0.15). Serum beta-LH increased from 10.5+/-3.2 ng/ml to 23.4+/-4.9 ng/ml (P=0.0037) at this time, in contrast to a lack of response in controls (basal: 6.4+/-1.5 ng/ml, peak: 8.2+/-2.3 ng/ml; P=0.24). CONCLUSION: In about 73% of patients with pituitary incidentalomas smaller than 10 mm, TRH elicits an increase in gonadotropin beta-subunits. This observation raises the possibility that non-functioning pituitary micro- and macroadenomas, which share a similar response to TRH, originate in a common ancestor cell type, probably a pituitary gonadotrope.

Adenoma↗