Prenatal diagnosis of fetal chromosomal anomalies: current opinion on amniocentesis versus chorionic villus sampling.
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Amniocentesis↗
Biomedical subjects
S Friedman
Publications and source records attributed to S Friedman.
Differential transforming abilities of non-secreted and secreted forms of human fibroblast growth factor-1.
Fibroblast growth factor (FGF)-1(1-154), the precursor for acidic FGF-1(21-154), is a potent angiogenic polypeptide, the structure of which lacks a signal peptide sequence for secretion. To investigate the biological significance of this structural feature, we have attempted forced secretion of FGF-1 through fusion of the entire FGF-1 coding frame with the signal peptide (sp) from the hst/KS3 gene, a secretory member of the heparin-binding growth factor family. We also studied the transforming ability of the signal-less forms of FGF-1 comprising FGF(1-154) and FGF-1(21-154). The presence of a soluble and biologically active form of FGF-1 was readily detected in the conditioned medium of NIH 3T3 cells transfected with sp-hst/KS3:FGF-1(1-154) as demonstrated by Western blot analysis and DNA synthesis assays, whereas sp-hst/KS3:FGF-1(21-154) was not detectable in conditioned medium even though the protein was detected in cellular extracts. The secreted form of sp-hst/KS3:FGF-1(1-154) stimulated the proliferation of human umbilical vein endothelial cells in vitro and was able to induce receptor-mediated tyrosine phosphorylation. Furthermore, the forced secretion of biologically active FGF-1 resulted in NIH 3T3 cell transformation as demonstrated by altered morphology in vitro, the formation of discrete colonies in soft agarose, growth under serum-free conditions, and ability to rapidly form highly vascular tumors in vivo. Interestingly, sp-hst/KS3:FGF-1(21-154) also mediated the transition to a transformed phenotype despite the inability to detect extracellular FGF-1 in the media conditioned by these NIH 3T3 cell transfectants. Although the transfection of FGF-1(21-154) yielded similar NIH 3T3 cell morphologic changes, these transfectants did not grow under serum-free conditions or yield colonies in soft agarose, and formed tumors in vivo with delayed kinetics. Furthermore, the FGF-1(1-154) NIH 3T3 cell transfectants did not exhibit morphologic changes, and this may be due to the inability of mRNA to express protein. These data suggest that although non-sp forms of FGF-1 may alter the monolayer phenotype of NIH 3T3 cells in vitro, the ability of FGF-1 to transform NIH 3T3 cells requires the function of a sp-directed secretory pathway and suggests that this pathway increases tumorigenicity in vivo.
3T3 Cells↗
Autogenous regulation of the EcoRII methylase gene at the transcriptional level: effect of 5-azacytidine.
mRNA of the EcoRII methylase (M.EcoRII), a type II modification enzyme, was induced when Escherichia coli carrying a cloned M.EcoRII gene was exposed to the bacteriocidal drug 5-azacytidine. Induction occurred only when transcription was initiated from its own promoter. When the 5' promoter sequences were deleted or replaced with the lac promoter sequences, no induction occurred. The induction was independent of the template DNA level, but the presence of an intact M.EcoRII protein was a requirement. The drug is incorporated into DNA which then inhibits M.EcoRII by binding tightly to the enzyme. A deletion within the M.EcoRII coding region caused a marked increase in the basal level of mRNA transcribed from the M.EcoRII promoter, but no induction occurred upon 5-azacytidine treatment. The level could be reduced to normal by M.EcoRII in trans. In vitro, the enzyme bound to the sequences upstream of the transcription start sites and inhibited the initiation of transcription. These experiments indicate that expression of the M.EcoRII gene was autogenously regulated at the transcriptional level. Similar regulation is also noted in another DNA (cytosine-5) methylase, M.MspI.
Azacitidine↗
Antenatal ultrasound diagnosis of congenital cystic adenomatoid malformation of the lung: spontaneous resolution in utero.
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Adult↗
Oral cancer prevention: the case for carotenoids and anti-oxidant nutrients.
The most convincing evidence for a preventive role for any modality is obviously demonstration of incidence reduction produced by that modality. However, cancer prevention trials with cancer incidence as an endpoint have logistic problems rendering them essentially impossible to conduct for most malignancies. Hence a workable strategy often involves analysis of other, indirect lines of evidence to reach conclusions. For oral cancer, dietary epidemiologic evidence points to a protective role for foods rich in carotenoids. Other anti-oxidants, such as vitamin C, are also implicated. Similarly, laboratory evidence points to a carcinogenesis inhibitory role for both retinoids and carotenoids. Clinical studies have targeted premalignant lesions, i.e., oral leukoplakia. For over two decades the efficacy of retinoids, natural and synthetic, has been known. Nevertheless, it has been difficult to translate this into a recommendation for prevention because of the toxicity of retinoids. The synthetic retinoid most often used in these trials is 13-cis-retinoic acid. This compound is toxic even at very low doses (0.1 mg/kg/day), particularly when given over several weeks to months. Hence, although effective, it cannot be advocated for prevention or oral cavity cancer. Studies with nontoxic antioxidants, such as beta-carotene, are much more recent. Early results are promising in that beta-carotene, alone or in combination with other nutrients, can reverse oral leukoplakia without toxicity in short-term trials. Studies currently under way will demonstrate whether durable remissions can be obtained using this strategy. It should be emphasized that such long-term trials are problematic to conduct with the toxic retinoids because the risks of prolonged exposure to them outweighs the chance of cancer development in the usual leukoplakia lesion.
Animals↗
The role of reduced nicotinamide adenine dinucleotide phosphate in glucose- and temperature-dependent doxorubicin cytotoxicity.
The mechanism of doxorubicin resistance induced by glucose deprivation was examined using an L929 cell system. Resistance developed even when the synthesis of glucose-regulated proteins was suppressed by supplementing glucose-deprived cultures with uridine. Resistance was also not correlated with pyruvate availability, with DNA strand breaks, or with intracellular drug or nucleotide levels. However, intracellular concentrations of reduced nicotinamide adenine dinucleotide phosphate (NADPH) decreased to undetectable levels in glucose-deprived cells with or without uridine supplementation. NADPH depletion induced by treating glucose-fed cells with low concentrations of methylene blue afforded the same degree of protection as glucose deprivation, and normal sensitivity could be restored to glucose-deprived cells by adding NADPH to the culture medium. These results suggest that decreased NADPH availability is responsible for the doxorubicin resistance induced by glucose deprivation. Although drug uptake and NADPH production increased with temperature, these effects could not fully account for the > 1000-fold decrease in clonogenic survival observed over the 25 degrees-37 degrees C temperature range. Similarly, manipulation of NADPH levels confirmed a role for drug bioreduction in the cytotoxic mechanism but did not suggest that NADPH availability was rate-limiting for this process at any temperature employed.
Animals↗
Prognosis of intracoronal bleaching with sodium perborate preparation in vitro: 1-year study.
Bleaching materials containing hydrogen peroxide have been used for treating discolored nonvital teeth but their use was occasionally associated with external root resorption. In a previous study it was found that the immediate results of bleaching teeth in vitro were equal for sodium perborate mixed with either water or hydrogen peroxide. The purpose of this study was to compare the bleaching prognosis of sodium perborate mixed with water or hydrogen peroxide over a 1-yr period. Extracted human teeth with intact crowns were discolored with human erythrocytes and bleached by sodium perborate mixed with either 30% hydrogen peroxide (group A), 3% hydrogen peroxide (group B), or water (group C). The bleaching materials were placed in the pulp chambers of the discolored teeth and sealed with IRM. They were replaced with fresh preparations after 3 and 7 days. After 14 days the coronal access cavities were sealed with composite resin and the teeth photographed with a color slide film under standardized conditions. The teeth were stored in artificial saliva for 1 yr and photographed after 3, 6, and 12 months. Two separate evaluators ranked the teeth by comparing them with the shades before and after bleaching. The bleaching success rates of the tested groups at each time interval were compared and analyzed statistically. It was found that after 1 yr all of the teeth in groups A and C maintained their shades. In 20% of the teeth in group B there was color regression. Statistically, these differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Borates↗
Gallbladder activity appearing 6 minutes after the intravenous injection of Tc99m MAG3 simulating a picture of obstructive uropathy of the right kidney.
Two cases of Tc-99m MAG3 renograms performed on the same day are presented. Both of them show considerable liver activity, which is a known drawback for MAG3 by distribution. In the first case, gallbladder activity appeared after 6 minutes, at the same time when tubular drainage and caliceal activity started to show in both kidneys. The gallbladder activity was superimposed over the upper calyces of the right kidney and simulated an obstructive pattern in the time-activity curves. This early gallbladder activity after intravenous injection of Tc-99m MAG3 has not been previously reported. The second case is presented for the purpose of confirming that nothing in the preparation of the kit contributed to this phenomenon.
Adult↗
Residue of gutta-percha and a glass ionomer cement sealer following root canal retreatment.
A previous report indicates that root canals obturated with a new glass ionomer cement endodontic sealer (Ketac-Endo, Espe, Germany) and laterally condensed gutta-percha can be retreated by ultrasonic instrumentation. To address the possibility of Ketac-Endo being used without condensation of gutta-percha, the purpose of this study was to evaluate the efficacy of ultrasonic retreatment in canals obturated with single-cone gutta-percha and Ketac-Endo. Thirty root canals were prepared in a standardized way to ISO size 40 and obturated with gutta-percha and Ketac-Endo. Either a size 40 gutta-percha cone was used with and without lateral condensation, or a size 25 single cone, without condensation. After 14 days, the canals were retreated using chloroform and ultrasonic instrumentation. The roots were split vertically, and the amount of residual debris on the canal walls was assessed by three examiners using a dissecting microscope. Debris was recorded in the apical, middle and coronal canal levels according to a preset evaluation scale. The mean scores for each group were compared by ANOVA and Mann-Whitney U-test, with a 5% level of significance. In the roots obturated with lateral condensation the amounts of residual debris in the coronal and middle canal levels was lower than in the other two groups, whereas in the apical level it was higher. Statistically, only the differences in the apical level were significant (P < 0.03). It was concluded that ultrasonic retreatment may be performed effectively in root canals obturated with single-cone gutta-percha and Ketac-Endo.
Analysis of Variance↗
Induction of EcoRII methyltransferase: evidence for autogenous control.
The cytosine analog 5-azacytidine kills Escherichia coli cells that carry plasmids expressing EcoRII DNA (cytosine 5)methyltransferase under control of its own promoter. We previously showed that this enzyme binds tightly to azacytidine-containing DNA in vitro and proposed that such binding is lethal in vivo. In support of this proposal, we now show that the enzyme sediments with the nucleoid of azacytidine-treated cells. Azacytidine treatment led to an increase in the amount of enzyme, and this increase required sequences in the ecoRIIM promoter region. Enzyme inducibility correlated with drug sensitivity: plasmids carrying the methyltransferase gene but lacking the wild-type promoter did not confer sensitivity. These results suggested that the ecoRIIM gene was under autogenous control. Transcriptional ecoRIIM'-lacZ fusions in E. coli were, therefore, constructed. They showed that expression from the ecoRIIM promoter was inhibited when EcoRII DNA (cytosine-5)methyltransferase was introduced into the cell in trans and inhibition was reversed by treating the cells with azacytidine. These results provide evidence that the expression of the ecoRIIM gene is under autogenous regulation and that cell death induced by azacytidine is due, in part, to the disruption of autoregulation.
Azacitidine↗
Anxiety disorders in a neuromuscular clinic.
Twenty patients with myasthenia gravis and 15 patients with polymyositis/dermatomyositis were assessed with a structured interview. Fifteen patients (43%) were diagnosed with an anxiety disorder. Significantly more myasthenic patients (40%) than polymyositis/dermatomyositis patients (7%) were diagnosed with panic disorder/agoraphobia. These findings suggest that the symptoms of myasthenia gravis may predispose vulnerable individuals to panic disorder/agoraphobia.
Adolescent↗
Cesarean section after maternal acetaminophen overdose.
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Acetaminophen↗
Reporting efficiency during a measles outbreak in New York City, 1991.
OBJECTIVES: During an epidemic of measles among preschool children in New York City, an investigation was conducted in 12 city hospitals to estimate reporting efficiency of measles to the New York City Department of Health. METHODS: Measles cases were identified by review of hospital emergency room and infection control logs and health department surveillance records. The Chandra Sekar Deming method was used (1) to estimate the total number of measles cases in persons less than 19 years old who presented to the 12 hospitals from January through March 1991 and (2) to estimate reporting efficiency. Information on mechanisms for reporting measles cases was collected from hospital infection control coordinators. RESULTS: The Chandra Sekar Deming method estimated that 1487 persons with measles presented to the 12 hospitals during the study period. The overall reporting efficiency was 45% (range = 19% to 83%). All 12 hospitals had passive surveillance for measles; 2 also had an active component. These 2 hospitals had the first and third highest measles reporting efficiencies. CONCLUSIONS: The reporting efficiency of measles cases by New York City hospitals to the health department was low, indicating that the magnitude of the outbreak was substantially greater than suggested by the number of reported cases.
Adolescent↗
Hypertonic saline compresses: therapy for complicated exit-site infections.
We review our experience with hypertonic saline compress therapy in 17 patients with complicated peritoneal dialysis catheter exit-site infections (ESIs). Compresses consisted of exit-site application of 4-5 gauze pads soaked with warm 3% saline for 5-10 minutes, three times daily, for 2-4 weeks, followed by once-daily use thereafter. The mechanism of action involves inhibition of bacterial growth by a hypertonic medium. Eleven patients with cultures positive for Staphylococcus aureus or Pseudomonas were treated with local exist-site measures (cleansers, antiseptics, antibiotic ointments). Therapy, which included multiple courses of systemic antibiotics, failed in 8 patients; in 3 patients, who were intolerant to antibiotics, ESI remained unresolved after local care only. Six patients with culture-negative ESIs received no systemic antibiotics and were unimproved following local therapy. Factors associated with therapy failure included malnutrition, diabetes, obesity, and dermal sensitization and injury associated with prolonged topical agent use. Following hypertonic saline compress therapy, we observed resolution of ESI in all patients without recurrence for follow-up intervals of 3-12 months (mean 6.5 months). Advantages of this therapy include excellent patient acceptance, ease of use, lack of adverse effects on exit site, adjacent skin, catheter or systemic reaction, and minimal expense. Future potential applications include routine daily use for infection prophylaxis and as therapy combined with antibiotics for established ESIs.
Administration, Topical↗
ARTEMIS: a collaborative framework for health care.
Patient centered healthcare delivery is an inherently collaborative process. This involves a wide range of individuals and organizations with diverse perspectives: primary care physicians, hospital administrators, labs, clinics, and insurance. The key to cost reduction and quality improvement in health care is effective management of this collaborative process. The use of multi-media collaboration technology can facilitate timely delivery of patient care and reduce cost at the same time. During the last five years, the Concurrent Engineering Research Center (CERC), under the sponsorship of DARPA (Defense Advanced Research Projects Agency, recently renamed ARPA) developed a number of generic key subsystems of a comprehensive collaboration environment. These subsystems are intended to overcome the barriers that inhibit the collaborative process. Three subsystems developed under this program include: MONET (Meeting On the Net)--to provide consultation over a computer network, ISS (Information Sharing Server)--to provide access to multi-media information, and PCB (Project Coordination Board)--to better coordinate focussed activities. These systems have been integrated into an open environment to enable collaborative processes. This environment is being used to create a wide-area (geographically distributed) research testbed under DARPA sponsorship, ARTEMIS (Advance Research Testbed for Medical Informatics) to explore the collaborative health care processes. We believe this technology will play a key role in the current national thrust to reengineer the present health-care delivery system.
Computer Communication Networks↗
Analysis of endogenous and exogenous nuclear translocation of fibroblast growth factor-1 in NIH 3T3 cells.
Nuclear localization of fibroblast growth factors (FGF) have been reported by many laboratories. We demonstrate here that FGF-1, the precursor for acidic FGF contains a putative nuclear translocation sequence (NTS) NYKKPKL, which is able to direct the expression of the bacterial beta galactosidase (beta gal) gene to the nucleus of transfected NIH 3T3 cells. However, this NTS is unable to target either FGF-1 itself or a FGF-1-beta gal fusion protein into the nucleus, suggesting that FGF-1 may contain an additional sequence which prevents endogenously expressed FGF-1 from being translocated into the nucleus. Indeed, when FGF-1 was fused to the NTS derived from the yeast histone 2B gene, the chimeric construct also failed to be transported into the nucleus either by itself or as a beta gal fusion protein. Interestingly, when 125I-FGF-1 was used to stimulate quiescent NIH 3T3 cells, a significant amount of internalized 125I-FGF-1 (approximately 10%) was found within the nucleus and the nuclear localization of FGF-1 through the exogenous pathway could be significantly reduced by suramin, an inhibitor of the interaction of FGF-1 with its receptor. These data suggest that while FGF-1 contains a NTS, nuclear translocation requires an exogenous and not an endogenous pathway.
3T3 Cells↗
Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells.
Fibroblast growth factor 1 (FGF-1) is a potent angiogenic and neurotrophic factor whose structure lacks a classical signal sequence for secretion. Although the initiation of these biological activities involves the interaction between FGF-1 and cell surface receptors, the mechanism responsible for the regulation of FGF-1 secretion is unknown. We report that murine NIH 3T3 cells transfected with a synthetic gene encoding FGF-1 secrete FGF-1 into their conditioned medium in response to heat shock. The form of FGF-1 released by NIH 3T3 cells in response to increased temperature (42 degrees C, 2 hr) in vitro is not biologically active and does not associate with either heparin or the extracellular NIH 3T3 monolayer matrix. However, it was possible to derive biologically active FGF-1 from the conditioned medium of heat-shocked NIH 3T3 cell transfectants by ammonium sulfate fractionation. The form of FGF-1 exposed by ammonium sulfate fractionation is similar in size to cytosolic FGF-1 and can bind and be eluted from immobilized heparin similarly to the recombinant human FGF-1 polypeptide. Further, the release of FGF-1 by NIH 3T3 cell transfectants in response to heat shock is reduced significantly by both actinomycin D and cycloheximide. These data indicate that increased temperature may upregulate the expression of a factor responsible for the secretion of FGF-1 as a biologically inactive complex that requires an activation step to exhibit the biological activity of the extracellular polypeptide mitogen.
3T3 Cells↗
Binding of the EcoRII methyltransferase to 5-fluorocytosine-containing DNA. Isolation of a bound peptide.
The properties of the interaction of 5-fluorocytosine-containing DNA with the EcoRII methyltransferase were studied. The DNA used was either a polymer synthesized in vitro, or a 20-mer containing one CCA/TGG sequence. The DNA could be methylated by the enzyme. In the process the enzyme formed a tight binding adduct with the DNA that could be identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Enzyme activity was inhibited by this interaction. The 20-mer could be used to titrate the active site of the enzyme. The DNA polymer formed a tight binding complex that could be identified following digestion of the DNA with pancreatic deoxyribonuclease or micrococcal nuclease. A peptide-DNA adduct could be isolated after digestion of the EcoRII-DNA adduct with staphylococcal protease V8 by high pressure liquid chromatography and polyacrylamide gel electrophoresis. Sequencing of the peptide indicated the DNA bound to a region of the protein that is conserved in all procaryotic DNA(cytosine-5)-methyltransferases. We have previously shown that this region contains a cysteine that can be photomethylated with adenosylmethionine. This region, in addition to forming part of, or being adjacent to, the AdoMet binding site, also forms part of the DNA binding site.
Amino Acid Sequence↗