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PubMed1995

Historical cohort study of spontaneous abortion among fabrication workers in the Semiconductor Health Study: agent-level analysis.

Risk of spontaneous abortion (SAB) was examined in relation to chemical and physical agents in a retrospective study of employees of 14 seminconductor manufacturers: After screening over 6,000 employees, 506 current and 385 former workers were eligible. If a woman had multiple eligible pregnancies, one was selected at random. Telephone interviews provided data on demographics and occupational and other exposures during the first trimester. Two groups of chemicals accounted for the 45% excess risk of SAB among fabrication-room (fab) workers: photoresist and developed solvents (PDS), including glycol ethers, and fluoride compounds used in etching. Women exposed to high levels of both these agents were at greater risk (RR = 3.21, 95% confidence interval [CI] = 1.29-5.96). In fab workers without these exposures, SAB rates were not elevated (adjusted relative risk [RR] = 0.98, 95% CI = 0.55-1.69). An association was seen with workplace stress, which was not limited to women exposed to PDS or fluoride, nor did stress explain the associations between these chemicals and SAB.

Abortion, Spontaneous↗
PubMed1994

Comparison of schizotypal relatives of schizophrenic versus affective probands.

In order to investigate possible heterogeneity in schizotypal personality disorder (SPD), two groups of schizotypals, one related to schizophrenic probands (FSPD) (n = 34) and one related to affective disorder probands (NFSPD) (n = 14), ascertained in the same family study, were compared. The FSPD group had more inadequate rapport; the groups did not differ in the frequency of any other symptoms of SPD. NFSPDs had higher rates of comorbid histrionic PD and a trend for higher rates of impulsive/dramatic cluster PDs. FSPDs had a trend for higher rates of anxiety disorders. There was a higher risk of bipolar disorder in the relatives of NFSPDs and higher risk for anxiety disorders in the relatives of FSPDs. The relatives of NFSPDs had higher rates for histrionic, narcissistic, and atypical PDs and for having at least one PD.

Adult↗
PubMed1989

Secondary structure of a core protein from pig skin proteodermatan sulfate: CD and Fourier transform IR spectroscopic studies in solution.

The secondary structure of a 38 kDa core protein from pig skin proteodermatan sulfate (PDS), was investigated in solution using CD and Fourier transform (FT) ir spectroscopy. Both techniques generally have provided complementary data on the secondary structures of proteins. CD spectral analysis has shown that the core protein contains 60% beta-turn and alpha-helical structures, the rest being "unordered" structure. FT ir data do not permit calculation of quantitative contributions of substructures, at the present time, to the overall secondary structure of the core protein. CD spectrum of the intact PDS is similar to the core protein CD spectrum.

Animals↗
PubMed2004

Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease.

BACKGROUND: Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease. OBJECTIVE: To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia. METHODS: We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation. RESULTS: This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD. CONCLUSION: Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.

Aged↗
PubMed2006

Posttraumatic stress disorder and general health problems following myocardial infarction (Post-MI PTSD) among older patients: the role of personality.

OBJECTIVES: This study aimed to: (1) investigate the degree to which older MI patients experienced post-MI PTSD and general health problems, and to (2) identify the association between five personality traits, post-MI PTSD and general health problems among these older people. METHODS: The sample comprised 96 older MI patients and were recruited from two general practices. They were interviewed using the Posttraumatic Stress Diagnostic Scale (PDS), the General Health Questionnaire-28 (GHQ-28) and the NEO-Five Factor Inventory (NEO-FFI). The control group comprised 92 older people who experienced no MI. They were assessed using the GHQ-28. RESULTS: The older MI patients experienced hyperarousal the most, followed by avoidance and re-experiencing symptoms. PDS revealed that 30% had full PTSD. The older patients were conscientious and agreeable individuals. They were also somewhat extraverted and open to experience. They also showed traits of neuroticism. Controlling for bypass surgery, heart failure, previous mental health difficulties, angina and angioplasty, regression analyses showed that neuroticism predicted re-experiencing and avoidance symptoms and general health total. Neuroticism and less agreeableness predicted hyperarousal symptoms. CONCLUSIONS: MI older patients could manifest PTSD symptoms and general health problems following their MI. Personality traits, particularly neuroticism and antagonism, played a role in the manifestation of these symptoms.

Aged↗
PubMed2001

Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease.

OBJECTIVES: To investigate whether Galantamine significantly improves the core symptoms of Alzheimer's disease (AD). BACKGROUND: Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (AChE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD. METHOD: A multicentre, randomized, parallel, double-blind, placebo-controlled trial was carried out to evaluate the efficacy and tolerability of galantamine 18, 24 and 36 mg/day administered for 3 months in 285 patients with mild-to-moderate probable AD. The primary outcome measure was the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog); secondary outcome measures were the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration Scale (PDS). RESULTS: Patients treated with galantamine 24 mg/day had a significantly better outcome than placebo on ADAS-cog; the treatment difference was 3 points on the intention-to-treat (ITT) analysis ( p = 0.01) and 4.2 points on per protocol analysis ( p = 0.001). Per protocol analysis showed that galantamine had a significantly better outcome than placebo on PDS ( 24-mg/day dose, p < 0.05) and CGIC (36-mg/day dose, p < 0.05). Galantamine was well tolerated at the lower doses of 18 and 24 mg/day where it produced mild, transient effects typical of cholinomimetic agents. CONCLUSION: This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer's disease.

Aged↗
PubMed2004

Immortalization without neoplastic transformation of human mesenchymal stem cells by transduction with HPV16 E6/E7 genes.

hMSCs derived from bone marrow are useful as a species-specific cell culture system for studying cell lineage differentiation and tissue remodeling. However, hMSCs usually have a short in vitro life span due to replicative senescence. We therefore used a high dose of retroviral vector LXSN-16E6E7 to transduce hMSCs of an aging donor and obtained an actively proliferating cell line, designated KP-hMSCs, which expressed HPV16 E6/E7 mRNA. Whereas parental hMSCs ceased to grow after 30 PDs, KP-hMSCs could be propagated beyond 100 PDs. With culture procedures to avoid selection pressure and crowded cell growth, KP-hMSCs showed no signs of neoplastic transformation as examined by soft-agar anchorage-independent growth and NOD-SCID mouse tumorigenicity assays. KP-hMSCs gave similar cytofluorimetric profiles of 31 CD markers to those of the parental primary hMSCs, except with some morphologic changes and expansion of an originally very minor CD34(dim)CD38(+)CD50+ cell population. Upon exposure to specific stimulating conditions in vitro, KP-hMSCs could respond and differentiate along the mesenchymal (bone, fat and cartilage) and nonmesenchymal (neuron) cell lineages. Our results indicated that hMSCs could be immortalized by transduction with HPV16 E6/E7, maintained without neoplastic transformation by careful culture procedures and thus useful for stem cell research and clinical application.

ADP-ribosyl Cyclase↗
PubMed2004

Evaluation of circulating thyroid-specific transcripts as markers of thyroid cancer relapse.

Circulating thyroid-specific transcripts have been suggested as potential molecular markers of residual or recurrent thyroid cancer. We assessed the accuracy of real-time RT-PCR-based detection of a panel of thyroid-specific markers, including TG, TPO, TSHR, NIS and PDS, in comparison with serum TG measurements in a series of 55 patients operated for differentiated thyroid cancer (DTC). Serum TG levels were higher in patients with residual thyroid tissue or metastatic cancer than in disease-free patients during thyroid hormone suppressive therapy (THST) and after stimulation with rhTSH (P < 0.05). Recombinant hTSH increased serum TG values in patients with tumor relapse (P < 0.05), but not in disease-free patients. This assay showed high specificity and good sensitivity in detecting tumor relapse (accuracy under THST = 81.4%; after rhTSH stimulation = 90.9%). TPO and TSHR mRNA, either under THST or after rhTSH, showed a significant correlation with disease status for molecular assays. Qualitative analysis of baseline and stimulated TG, NIS and PDS mRNA showed high sensitivity but low specificity in the prediction of thyroid cancer recurrence or metastases (accuracy under THST = 51%, 43% and 54%, respectively), whereas TPO and TSHR mRNA assays had higher specificity but low sensitivity, with accuracy under THST of 67% and 61%, respectively, that improved when these tests were combined. Our findings indicate that serum TG assay after TSH stimulation is the most accurate test for monitoring DTC. Combined measurements of TPO and TSHR mRNA levels during THST may represent a specific test for early detection of DTC relapse.

Adult↗
PubMed1991

Development of a new percutaneous access device for implantation in soft tissues.

The objective of this study was to evaluate a new type of percutaneous device (PD) designed to be implanted in soft tissues. The new PD consisted out of: (1) a flange-shaped subcutaneous component, made from sintered titanium fiber-web, and (2) a percutaneous component, made from dense sintered hydroxyapatite. The PDs were inserted in the back of 15 rabbits. The surgical procedure was performed in two steps. In the first session the subcutaneous component was placed. In the second session, after 3-4 months the percutaneous component was fixed in the subcutaneous component. The implants were left in situ for 1 and 4 months after the second implantation session. Clinical and histological investigations were performed. It is found, that there was only a limited epidermal down-growth in the percutaneous area. No inflammatory reaction was observed in the dermal connective tissue. Histological analysis also demonstrated that titanium fiber mesh evokes minor adverse effects of the surrounding tissues. In conclusion, these experiments have shown that stabilization of the PD in the hypodermal area by using a sintered titanium fiber-web structure favors the longevity of PDs implanted in soft tissues.

Animals↗
PubMed2005

Mechanical properties and in vitro degradation of bioresorbable fibers and expandable fiber-based stents.

Bioresorbable polymeric support devices (stents) are being developed in order to improve the biocompatibility and drug reservoir capacity of metal stents, as well as to offer a temporary alternative to permanent metallic stents. These temporary devices may be utilized for coronary, urethral, tracheal, and other applications. The present study focuses on the mechanical properties of bioresorbable fibers as well as stents developed from these fibers. Fibers made of poly(L-lactide) (PLLA), polydioxanone (PDS), and poly(glycolide-co-epsilon-caprolactone) (PGACL) were studied in vitro. These fibers combine a relatively high initial strength and modulus together with sufficient ductility and flexibility, and were therefore chosen for use in stents. The effect of degradation on the tensile mechanical properties and morphology of these fibers was examined. The expandable stents developed from these fibers demonstrated excellent initial radial compression strength. The PLLA stents exhibited excellent in vitro degradation resistance and can therefore support body conduits such as blood vessels for prolonged periods of time. PDS and PGACL stents can afford good support for 5 and 2 weeks, respectively, and can therefore be utilized for short-term applications. The degradation resistance of the stents correlates with the profile of mechanical property deterioration of the corresponding bioresorbable fibers.

Absorbable Implants↗
PubMed2004

Senescence occurs with hTERT repression and limited telomere shortening in human oral keratinocytes cultured with feeder cells.

We investigated the phenotypic and molecular alterations in normal human oral keratinocytes (NHOK) during in vitro replication in two different culture conditions. The cells were cultured either in chemically defined Keratinocyte Growth Medium (KGM) without feeder layers or in serum-containing flavin-adenine dinucleotide (FAD) medium with feeder layers. Primary NHOK underwent 22 +/- 3 population doublings (PDs) in KGM and 42 +/- 4 PDs in FAD medium, reflecting 52% increase in replication capacity with feeder layers. In both culture conditions, exponentially replicating NHOK demonstrated telomerase activity and expression of human telomerase reverse transcriptase (hTERT) gene. Telomerase activity and hTERT expression were rapidly diminished in senescing NHOK, which exhibited small decrease of telomere length for the remaining limited cellular replications until the complete arrest of cell division. However, telomere length in senescent NHOK was 6.7 +/- 0.5 kilobase pairs (kbps), significantly longer than that (5.12 kbps) of senescent human fibroblasts. The onset of senescence was accompanied with marked induction of p16(INK4A), and this occurred in both culture systems using either KGM or FAD medium. These results indicate that replicative senescence of NHOK is associated with loss of telomerase activity followed by limited telomere shortening.

Blotting, Southern↗
PubMed1980

Age-dependent decrease of growth responsiveness in density inhibited 3T3 cell populations and their interactions with SV 40-3T3 cells.

An aging process has been detected in stationary 3T3 cell cultures, especially in the presence of plasma-derived serum (PDS) from adult bulls. It leads to irreversible conversion of an increasing percentage of initially responsive cells of a stationary population into cells unresponsive to growth stimulation by newborn calf serum (NBCS) or reseeding at low cell density in the presence of NBCS. These unresponsive cells are viable in the sense that, following trypsinization, they reattach and spread on a new culture plate and can be maintained for many days. The conversion process is accelerated by increasing PDS concentration. It is antagonized by NBCS. It is accompanied by enhancement of growth-inhibiting interactions exerted by stationary 3T3 cell populations on SV 40-3T3 cells.

Animals↗
PubMed1979

Stimulation of human vascular endothelial cell growth by a platelet-derived growth factor and thrombin.

Repair of a vascular wound is mediated by migration and subsequent replication of the endothelial cells that form the inner lining of blood vessels. We have measured the growth response of human umbilical vein endothelial cells (HuE) to two polypeptides that are transiently produced in high concentrations at the site of a wound; the platelet-derived growth factor (PDGF) and the protease thrombin. When 10(4) HuE cells are seeded as a dense island (2-mm diameter) in the center of a 16-mm tissue culture well in medium containing 20% human serum derived from platelet-poor plasma (PDS), no increase in cell number or colony size is observed. With the addition of 0.5 ng/ml partially purified PDGF, colony size increases and the number of cells after 8 days is 4.8 X 10(4). When human thrombin (1 microgram/ml) is added along with the PDGF, the cell number rises to 9.2 X 10(4). Thrombin alone stimulates no increase in cell number. Although partially purified PDGF stimulates endothelial cells maintained in PDS as well as those maintained in whole blood serum (WBS), pure PDGF is active only when assayed in medium that contains WBS and is supplemented with thrombin. These results suggest the existence of a second class of platelet-derived factors that enable HuE cells to respond to the mitogenic activity of the purified platelet mitogen and thrombin.

Blood Platelets↗
PubMed1995

In vivo validation of magnetic resonance blood volume flow measurements with limited spatial resolution in small vessels.

The accuracy of magnetic resonance phase contrast volume flow measurements in small blood vessels is expected to be smaller than in large vessels, because of partial volume effects at the vessel boundary. Accuracy was validated in the dog femoral artery, diameter 3.5 +/- 0.7 mm, using an ultrasonic transit-time flowmeter (TT). The number of pixels per vessel diameter (ND) ranged from 1.6 to 4.8. The vessel cross-section was determined using a threshold in the magnitude image. Between the two methods the correlation coefficient was 0.95 (range 10-200 ml/min). The proportional difference (PD), (QTT-QMR)/1/2(QTT+QMR), was 0.8%, showing no systematic difference between the methods. The PDs standard deviation was 27%, and 19% for flow rates above 30 ml/min. Only a significant decrease of the PDs variance was found at the highest ND values, suggesting other sources of error than partial volume effects. It is concluded that with an ND value of about 3, accurate blood volume flow rates can be determined.

Animals↗
PubMed2004

HXT5 expression is under control of STRE and HAP elements in the HXT5 promoter.

Hexose transporter (Hxt) proteins transport glucose across the plasma membrane in the yeast Saccharomyces cerevisiae. Recently, we have shown that expression of HXT5 is regulated by the growth rate of the cells. Because gene expression is regulated by binding of specific transcription factors to regulatory elements in the promoters of genes, the presence of putative regulatory elements in the promoter of HXT5 was determined by computer-assisted analysis. This revealed the presence of two putative stress-responsive elements (STREs), one putative post-diauxic shift (PDS) element and two putative Hap2/3/4/5p (HAP) complex binding elements. The involvement of these elements was studied by using mutations in a HXT5 promoter-LacZ fusion construct. Growth during various conditions that result in low growth rates of yeast cells revealed that the STRE most proximal to the translation initiation site seemed to be involved in particular in regulation of HXT5 expression during growth at decreased growth rates. In addition, the HAP elements seemed to be required during growth on non-fermentable carbon sources. The PDS element and, to a lesser extent, the other STRE showed particular involvement in regulation of HXT5 expression during growth on ethanol. Finally, it was shown that the PKA pathway, which is known to be involved in expression of STRE-regulated genes, was also involved in regulation of HXT5 expression. A possible mechanism by which expression of HXT5 could be regulated by the transcriptional regulatory elements in the promoter is discussed.

Artificial Gene Fusion↗
PubMed1995

A procedure for the determination of monothiols in the presence of dithiothreitol--an improved assay for the reduction of disulfides.

4,4'-Dipyridyl disulfide (4-PDS) and sodium arsenite have been used to develop a rapid and sensitive assay for monothiols in the presence of dithiothreitol (DTT). The procedure is similar to that of Zahler and Cleland (J. Biol. Chem. 243, 716-719, 1968) but involves the use of a lower pH and 4-PDS, which is more effective than 5,5'-dithiobis-(2-nitrobenzoic acid) at low pH. Background reactions that interfere with the determination of slow reacting thiol groups are much reduced in the new assay procedure. The reduction of oxidized glutathione by DTT at three different pH values and a partial and the complete reduction of bovine serum albumin by DTT have been characterized in order to demonstrate the use of this procedure. In the first two cases monothiol groups were readily detected without interference from DTT. Lower than expected numbers of thiol groups in the case of three reduced and denatured model proteins appeared to reflect their partial complexation by arsenite. Equilibrium and kinetic constants for the formation and dissociation of the DTT-arsenite complex from pH 5 to 8 are presented.

Animals↗
PubMed1995

Antibodies to ICAM-1 protect kidneys in severe ischemic reperfusion injury.

ICAM-1 has been implicated in the pathophysiology of ischemic-reperfusion injury in a number of organs, but its role in mediating severe ischemic-reperfusion injury in the kidney has not been extensively studied. Uninephrectomized Sprague Dawley rats were pretreated with either control monoclonal antibody (mAb) or mAb to ICAM-1 and subjected to 60 min of renal artery occlusion. The serum creatinine, complete blood count and kidney histo-pathological damage scores (PDS) (Scale:0-4) were assessed prior to and 24 hours after ischemia. Mean serum creatinine (mg/dl) 24 hours after ischemia was significantly decreased in the anti-ICAM-1 group (1.38 +/- 0.23, p < 0.001) compared to control (2.87 +/- 0.34). PDS was also reduced in anti-ICAM-1 (2.55 +/- 0.20, p < 0.05) group compared to control (3.35 +/- 0.30). These data demonstrate that blocking ICAM-1 significantly mitigates severe ischemic acute renal failure, findings which may lead to improved therapy for this condition.

Animals↗
PubMed2002

Induction of tubulogenesis in telomerase-immortalized human microvascular endothelial cells by glioblastoma cells.

To facilitate the study of human endothelial cells we have used a replication defective retrovirus encoding the catalytic subunit of telomerase (hTERT) to derive populations of telomerase-immortalized human microvascular endothelial (TIME) cells. Whereas parental HMVECs became senescent on average within 35-45 population doublings (PDs), TIME cells have continued to proliferate for at least 200 PDs. TIME cells express readily detectable telomerase activity but display only a modest increase in telomere length. Karyotypic analysis reveals the cells to have a normal complement of human chromosomes with no evidence of gross genetic abnormalities. Furthermore, TIME cells retain many of the characteristics of the primary endothelial cells from which they were derived. For example, they express a panel of characteristic endothelial cell surface marker proteins such as CD31/PECAM-1 and alpha(v)beta3-integrin. In addition, TIME cells express receptors for low-density lipoprotein (LDL) receptor as they are competent for receptor-mediated endocytosis of fluorescent acetylated LDL. Importantly, when plated on matrigel, TIME cells undergo tubule formation. Moreover, when cocultured in the presence of human glioma cells, but not primary human astrocytes, TIME cells are induced to form stable tubules. Detachment of TIME cells from extracellular matrix leads to a form of programmed cell death known as anoikis. Conditional activation of the protein kinase Akt (Akt:ER*) significantly inhibited the onset of TIME cell anoikis under these conditions. We believe that the ability of hTERT to immortalize primary human endothelial cells, and the fact that such cells retain the endothelial characteristics of the cells from which they were derived, will greatly facilitate the analysis of human endothelial cell biology in vitro.

Apoptosis↗