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PubMed1988

Rheumatoid adherent synovial cells produce B cell differentiation factor activity neutralizable by antibody to B cell stimulatory factor-2/interleukin 6.

B cell differentiation factor (BCDF) activity assayed on SKW6-CL4 cells was found in adherent synovial cell (ASC) conditioned medium. ASC of patients with RA (n = 8) produced significantly larger amounts of BCDF than those of patients with osteoarthritis (n = 5) (219.0 +/- 212.1 vs 25.5 +/- 12.4 units/microgram.DNA, p less than 0.01). ASC clones, established by the limiting dilution technique, also produced this factor. Experiments with several neutralizing antibodies revealed that this BCDF is inhibited by anti-B cell stimulatory factor-2/interleukin 6 antibody (anti-BSF-2/IL-6 ab) up to 90%, but not by antiinterleukin 1, antiinterleukin 2 or antiinterferon-r antibodies. Our data suggest that ASC could participate in the B cell differentiation process in joint space by producing a molecule which has a similar active site to BSF-2/IL-6.

Aged↗

PubMed1983

Neutral amino acid transport in isolated rat pancreatic islets.

The neutral amino acid transport systems of freshly isolated rat pancreatic islets have been studied by first examining the transport of L-alanine and the nonmetabolizable analogue 2-(methylamino)isobutyric acid (MeAIB). By comparing the uptake of MeAIB and L-alanine for their pH dependency profile, choline and Li+ substitution for Na+, tolerance to N-methylation, and competition with other amino acids, the existence in pancreatic islets of both A and ASC amino acid transport systems was established. The systems responsible for the inward transport of five natural amino acids was studied using competition analysis and Na+ dependency of uptake. These studies defined three neutral amino acid transport systems: A and ASC (Na+-dependent) and L (Na+-independent). L-Proline entered rat islet cells mainly by system A; L-leucine by the Na+-independent system L. The uptake of L-alanine, L-serine, and L-glutamine was shared by systems ASC and L, the participation of system A being negligible for these three amino acids. An especially broad substrate specificity for systems L and ASC is therefore suggested for the rat pancreatic islet cells. The regulation of amino acid transport was also investigated in two conditions differing as to glucose concentration and/or availability, i.e. islets from fasted rats and islets maintained in tissue culture at high or low glucose concentrations. Neither alanine nor MeAIB transport was altered by fasting of the islet-donor rats. On the other hand, pancreatic islets maintained for 2 days in tissue culture at high (16.7 mM) glucose transported MeAIB at twice the rate of islets maintained at low (2.8 mM) glucose. Amino acid starvation of pancreatic islets during 11 h of tissue culture resulted in a 2-fold increase in MeAIB transport.

Alanine↗

PubMed1982

The transport of alanine, serine, and cysteine in cultured human fibroblasts.

The transport of L-alanine, L-serine, and L-cysteine has been studied in skin-derived diploid human fibroblasts in culture. Competition analysis, mathematical discrimination by nonlinear regression, and conditions varying the relative contribution of the various mediations have been used to characterize the systems engaged in the inward transport of these amino acids. All the adopted criteria yielded results showing that L-alanine, L-serine, and L-cysteine enter the cell by two Na+-dependent systems, System A and System ASC, and by a Na+-independent route, whose major component has been identified as System L. The apparent affinity of L-alanine, L-serine, and L-cysteine for the putative carrier was higher for System ASC than for System A. The transport Vmax for System A increased in response to cell starvation; after 12 h, its values were similar or higher than those exhibited by System ASC. At amino acid concentrations approaching those present in human plasma, System ASC appeared to be the primary mediation for the inward transport of L-alanine, L-serine, and L-cysteine in human fibroblasts. The contribution of System A was negligible in nonstarved cells and became appreciable under conditions of cell starvation. The Na+-independent System L made no substantial contribution to the uptake of L-alanine and L-serine and accounted for approximately one-fourth of the total uptake of L-cysteine.

Alanine↗

PubMed1994

Extracellular matrix regulates cell morphology, proliferation, and tissue formation.

The roles of extracellular matrix (ECM) components such as collagen, elastin, proteoglycan, and adhesive glycoprotein in the regulation of cell morphology, proliferation, and tissue formation were investigated. On a basement membrane gel, the perisinusoidal stellate cells (lipocytes, fat-storing cells, Ito cells) formed a mesh-like structure, proliferated slowly, and synthesized only a small amount of collagen. On polystyrene or type I collagen-coated culture dishes, the stellate cells spread well and extended cellular processes. The stellate cells proliferated better and synthesized more collagen on type I collagen-coated dishes than on polystyrene dishes. Co-cultures of hepatic parenchymal cells and fibroblasts formed a three-dimensional hepatic cord-like architecture in the medium supplemented with a long-acting vitamin C derivative, L-ascorbic acid 2-phosphate (Asc 2-P). Skin fibroblasts formed a three-dimensional dermis-like structure in the medium supplemented with Asc 2-P. Asc 2-P stimulated collagen synthesis of these cells. The stimulative effects of Asc 2-P on tissue formation were suppressed when collagen synthesis in these cells was inhibited. These data indicate that ECM can regulate cell morphology, proliferation and tissue formation. Regulation of cellular functions in other tissues such as mammary gland, thymus and prostate by ECM was also reviewed, and the molecular mechanisms of the regulation are discussed.

Adipocytes↗

PubMed1994

[Chemotherapy with autologous stem cell support for breast cancer].

The importance of dose intensity in breast cancer chemotherapy has been stressed in recent years with clear correlations demonstrated between dose intensity and clinical outcome of the patients in both therapeutic and adjuvant settings. In addition to various and intense supportive care, autologous stem cell support (ASCS) has been used over the past 15 years in order to overcome myelotoxicity of cancer chemotherapy. ASCS was initially practiced in the form of bone marrow transplantation, and more recently peripheral stem cell transplantation has been combined in addition to administration of G-CSF. Our pilot study in patients with recurrent/advanced breast cancer showed a higher response rate and a higher survival rate as compared to conventional chemotherapy, and there have been some long-term disease-free survivors with probable cures among complete responders with ASCS-supported chemotherapy. In adjuvant settings for patients with a high risk for recurrence who had been given a high-dose, the ASCS-supported regimen showed a higher disease-free survival rate as compared to those who were treated with conventional adjuvant therapy. Whether these apparently better results in our pilot studies hold true generally remains to be seen with well-scheduled randomized clinical trials.

Antineoplastic Agents↗

PubMed1994

Hepatitis B virus carrier with low titer of antibody to hepatitis B core antigen.

Of 798 hepatitis B virus (HBV) carriers, 22 had low titers (lower than 80% inhibition in 200- or 400-fold diluted serum) of antibody to hepatitis B core antigen (anti-HBc). Among these 22 patients, there were 12 (1.50%) with viremia who were positive for hepatitis B e antigen and had a high titer of HBV-associated DNA polymerase activity. Among these 12 patients, four showed no significant change in the anti-HBc titer, while four others showed significant increases in the anti-HBc titer during the follow-up periods. The former all remained asymptomatic carriers (ASCs), while the latter all developed chronic hepatitis (CH). The liver histology of four patients (ASC: 2, CH: 2) showed mild inflammation, and the localization of hepatitis B core antigen (HBcAg) in the liver specimens showed a nuclear pattern in the two ASCs, but a nuclear plus cytoplasmic pattern in the two CH cases. In HBV carriers, the increase in anti-HBc titer seems to be closely correlated to the change in HBcAg localization from the nucleus to the cytoplasm in the liver. Therefore, rising titers of anti-HBc were assumed to be associated with increased expression of HBcAg on the hepatocyte, and hence increased immune-mediated hepatic damage and the onset of hepatitis in ASC with low titer of anti-HBc.

Adolescent↗

PubMed1993

An airway hyperresponsiveness model in rat allergic asthma.

We attempted to obtain a new airway hyperresponsiveness model using DNP-Ascaris extract (DNP-Asc)-induced rat allergic asthma. Male Wistar rats were actively sensitized with DNP-Asc, and challenged in a non-anesthetized state by inhalation of the antigen for 10 min in a chamber. One, 6 and 24 hr after DNP-Asc challenge, the responsiveness of the airway smooth muscles to inhaled acetylcholine (ACh) was determined using a modified Konzett-Rössler method under anesthesia. Twenty four hr after the challenge, a significant and marked airway hyperresponsiveness was seen. The increase in airway responsiveness was significantly inhibited by pretreatments with a leukotriene antagonist, ONO-1078, and a thromboxane synthetase inhibitor, ozagrel, and tended to be inhibited by a PAF antagonist, CV-3988. The hyperresponsiveness induced by DNP-Asc challenge was accompanied by airway inflammation determined by dye exudation. From the above results, it is indicated that a model of airway hyperresponsiveness was established in rats with allergic asthma, and that the chemical mediators involved in the response might be leukotrienes, thromboxane A2 and PAF.

Acetylcholine↗

PubMed1995

Comparative cytoprotection of cultured corneal endothelial cells by water-soluble antioxidants against free-radical damage.

We reported previously that purpurogallin (PPG) markedly protects the cultured rabbit corneal endothelial cells (RCEC) against oxyradical damage generated with hypoxanthine (HX) and xanthine oxidase (XO)(1). In this study, we further compared the cytoprotective activities of PPG versus Trolox (TX, alpha-tocopherol, a water-soluble analogue of vitamin E) and ascorbate (Asc) in confluent cultured RCEC with phase contrast microscopy and confirmed by transmission electron microscopy. PPG prolonged survival of the oxyradical damaged cells longer than those without PPG present (18.6 +/- 1.4 min at 1.0 mM and 11.2 +/- 1.0 at 0.25 mM respectively vs. 7.3 +/- 0.8 min in control). At levels equimolar to PPG, TX, and Asc were less effective in delaying cell necrosis caused by HX and XO (p < 0.01). When exposed to superoxide radicals generated by menadione, RCEC necrosed at 29.8 +/- 1.5 min compared to PPG 47.2 +/- 1.0 min at 1.0 mM and 38.9 +/- 1.0 min at 0.25 mM. This was significantly different from TX and Asc at corresponding concentrations (p < 0.01). PPG scavenges not only HX-XO-generated oxyradicals, but also nonenzymatically produced superoxide radicals, more actively than two well known antioxidants--TX and Asc.

Animals↗

PubMed1996

Morphine-induced alterations in antibody levels: receptor and immune mechanisms.

We have previously shown that an acute administration of morphine (10 mg/kg, i.v.) decreases IgG, but not IgM, antibody levels to antigen administered before morphine. Further, decreases in IgG were blocked by previous administration of naltrexone, indicating that receptor binding is critical to the decreased antibody levels. These studies investigated potential receptor and immune mechanisms for these effects. To investigate potential receptor mechanisms, the stereoselectivity and location of receptor binding was determined. The results of these experiments suggest morphine must bind stereoselectively to central sites to decrease antibody levels after antigen administration. To investigate potential immune mechanisms for these changes, antibody secreting cells (ASC) for keyhole limpet hemocyanin-specific IgG and IgM were enumerated. Morphine decreased ASC for IgG but increased ASC for IgM. Two pathways for the genetic switch from IgM to IgG production were investigated. One pathway requires interferon-gamma to stimulate IgM-secreting cells to switch to IgG2a-secreting cells. Another pathway requires interleukin-4 to stimulate IgM-secreting cells to switch to IgG1- secreting cells. IgG1 and IgG2a levels were measured to determine if these pathways were differentially affected and only IgG2a levels were decreased. Further, these decreases were accompanied by decreased IFN-gamma levels but not by altered numbers of splenocytes. These data indicate that morphine may alter the ability of ASC to switch from IgM to IgG2a production, possibly by reducing the availability of IFN-gamma.

Animals↗

PubMed1997

[The toxicological, hygienic and clinical aspects of the action of low levels of organic solvents].

The article presents experimental data showing that Average Shift Concentration (ASC) and Maximal Single Concentration (MSC) for some solvents (tetrachloromethane, tetrachloroethane, dimethylformamide, benzene) are expedient to be justified. Clinical and hygienic materials proved significant health parameters (nervous system, peripheral blood) and urine levels of main metabolites to depend on chlorbenzene and toluene concentrations influencing the workers. Having analyzed the results, the authors recommended following hygienic norms in the air of workplace: for chlorbenzene ASC--50 mg/cu m, MSC--100 mg/cu m; biologic MAC for urine 4-chlorcatechol--0.05 g/l; for toluene ASC--50 mg/cu m, MSC--150 mg/cu m; biologic MAC for urine hippuric acid--1.5 g/l. The article shows some features of ASC and MSC practical application.

Air Pollutants, Occupational↗

PubMed1997

Gene regulation studies of aromatase expression in breast cancer and adipose stromal cells.

The expression of aromatase in human breast tumors was studied using the reverse transcription-polymerase chain reaction (RT-PCR) method on 70 breast tissue specimens. An RT-PCR analysis using two oligonucleotide primers derived from exon II of the human aromatase gene revealed that aromatase mRNA was detected in all but three tissue specimens. Furthermore, primer-directed RT-PCR was performed to determine the exon I usage in aromatase mRNA in these breast tumor specimens. The analysis revealed that exons I.3 and PII are the two major exons I present in aromatase mRNA isolated from breast tumors, suggesting that promoters I.3 and II are the major promoters driving aromatase expression in breast cancer and surrounding adipose stromal cells (ASCs). Recently, the regulatory properties of a 696-base pair region that contains promoter II, and is situated immediately upstream of exon II of the human aromatase gene, were investigated. Detailed DNase 1 footprinting analysis, DNA mobility shift assays, and chloramphenicol acetyltransferase (CAT) functional studies of this genomic region were performed and led to the identification of a segment (B1) that could act as a promoter (probably promoter I.3) in adipose stromal and breast cancer cells. The study further revealed that the B1 region could be divided into two domains which were designated RE1 and RE2. RE1 was found to have the promoter activity, and RE2 was found to regulate the promoter activity of RE1, but in different manners in MCF-7 cells (as an example of breast cancer cells) and in ASCs. RE2 was found to function as a positive regulatory element in MCF-7 cells and as a negative regulatory element in ASCs, respectively. It was also found that in several breast cancer cell lines, including MCF-7, the promoter activities of both promoter II and promoter I.3 were found to be suppressed by a negative regulatory element, a silencer, present in the 162 bp fragment which is located upstream from promoter II and downstream from promoter I.3. The precise position of the silencer element (termed S1) was localized by deletion mutation and DNase 1 footprinting analysis, and the silencing activity of S1 on promoter I.3 (in B1 fragment) was confirmed by CAT plasmid transfection experiments. UV crosslinking experiments are being performed to examine the regulatory proteins interacting with the silencer element. These studies serve as the basis for the further characterization of the regulatory mechanism of aromatase expression in human breast cancer and ASCs.

Adipose Tissue↗

PubMed1997

Coumarin-3-carboxylic acid as a detector for hydroxyl radicals generated chemically and by gamma radiation.

Coumarin-3-carboxylic acid (3-CCA) was used as a detector for hydroxyl radicals (.OH) in aqueous solution. The .OH was generated by gamma irradiation or chemically by the Cu2+-mediated oxidation of ascorbic acid (ASC). The excitation and emission spectra of 3-CCA, hydroxylated either chemically or by gamma irradiation, were nearly identical to those of an authentic 7-hydroxycoumarin-3-carboxylic acid (7-OHCCA). The pH-titration curves for the fluorescence at 450 nm (excitation at 395 nm) of 3-CCA, hydroxylated either chemically or by gamma radiation, were also identical to those of authentic 7-OHCCA (pK = 7.4). Time-resolved measurements of the fluorescence decays of radiation- or chemically hydroxylated 3-CCA, as well as those of 7-OHCCA, indicate a monoexponential fit. The fluorescence lifetime for the product of 3-CCA hydroxylation was identical to that of 7-OHCCA (approximately 4 ns). These data, together with analysis of end products by high-performance liquid chromatography, show that the major fluorescent product formed by radiation-induced or chemical hydroxylation of 3-CCA is 7-OHCCA. Fluorescence detection of 3-CCA hydroxylation allows real-time measurement of the kinetics of .OH generation. The kinetics of 3-CCA hydroxylation by gamma radiation is linear, although the kinetics of 3-CCA hydroxylation by the Cu2+-ASC reaction shows a sigmoid shape. The initial (slow) step of 3-CCA hydroxylation is sensitive to Cu2+, but the steeper (fast) step is sensitive to ASC. Analysis of the kinetics of 3-CCA hydroxylation shows a diffusion-controlled reaction with a rate constant 5.0 +/- 1.0 x 10(9) M(-1) s(-1). The scavenging of .OH by 3-CCA was approximately 14% for chemical generation with Cu2+-ASC and approximately 50% for gamma-radiation-produced .OH. The yield of 7-OHCCA under the same radiation conditions was approximately 4.4% and increased linearly with radiation dose. The 3-CCA method of detection of .OH is quantitative, sensitive, specific and therefore accurate. It has an excellent potential for use in biological systems.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

[Morpho-functional study of the kidney in patients with kidney disease and liver disease with magnetic resonance].

INTRODUCTION: We studied renal function and perfusion after the i.v. injection of Gd-DTPA-BMA, a nonionic paramagnetic contrast agent, to assess renal morphology and function in normal subjects, in renal insufficiency patients and in patients with hepatic failure and normal renal function. The latter were chosen because some patients with advanced hepatic failure may suffer from the hepatorenal syndrome, characterized by severe vasoconstriction in the renal cortical vessels. We investigated if dynamic MRI can detect early renal perfusion abnormalities in the patients who will eventually develop this syndrome. MATERIAL AND METHODS: Thirty MR examinations were carried out on 30 subjects after the i.v. injection of Gd-DTPA-BMA. Our series consisted of: 10 normal subjects; 10 renal insufficiency patients; 10 patients with hepatic failure and normal renal function. MR examinations were performed on a Philips ACS II scanner operating at 1.5 T. Two sequences were carried out in all cases: T1-weighted SE and T1-weighted TGE sequences after the bolus injection of .1 mmol/kg contrast agent. Renal longitudinal diameter and parenchymal thickness were measured in all cases and signal intensity time curves were always made. The signal intensity of the cortex, corticomedullary junction, medulla and pyelocaliceal system of each kidney was measured using a region of interest (ROI). The signal intensity curves were made considering quantitative parameters, including the area below the curve (ASC), the peak (P) and the time to peak (T-P). RESULTS: Longitudinal diameter and parenchymal thickness values were significantly lower in renal insufficiency patients than in normal subjects. Four phases were demonstrated after i.v. contrast agent injection in normal subjects, namely A) the cortical phase, B) the corticomedullary junction phase, C) the medullary phase, D) the pyelocaliceal phase. No signal intensity decrease in the medullary and pyelocaliceal curves was observed in renal insufficiency patients. Signal intensity curves values were lower in hepatic failure patients than in those with normal renal function. Hepatic failure patients could be divided into two groups: 5 patients had low P and ASC values and 4 had normal P and ASC values. The patients with lower P and ASC values developed the hepatorenal syndrome within a few months of the MR examination. DISCUSSION: Signal intensity decreased in the pyelocaliceal system phase in normal subjects because of the high paramagnetic contrast agent concentration. The lack of signal intensity decrease in renal insufficiency patients was caused by the reduced capability of concentrating Gd-DTPA-BMA. Lower signal intensity values in hepatic failure patients may be considered an early sign of the hepatorenal syndrome.

Adult↗

PubMed2002

Characterization of L-glutamine transport by a human neuroblastoma cell line.

This study characterized the Na+-dependent transport of L-glutamine by a human neuroblastoma cell line, SK-N-SH. The Na+-dependent component represented >95% of the total glutamine uptake. Kinetic studies showed a single saturable high-affinity carrier with a Michaelis constant (K(m)) of 163 +/- 23 microM and a maximum transport velocity (Vmax) of 13,713 +/- 803 pmol x mg protein(-1) x min(-1). Glutamine uptake was markedly inhibited in the presence of L-alanine, L-asparagine, and L-serine. Li+ did not substitute for Na+. These data show that L-glutamine is predominantly taken up through system ASC. Glutamine deprivation resulted in the decrease of glutamine transport by a mechanism that decreased Vmax without affecting K(m). The expression of the system ASC subtype ASCT2 decreased in the glutamine-deprived group, whereas glutamine deprivation did not induce changes in system ASC subtype ASCT1 mRNA expression. Adaptive increases in Na+-dependent glutamate, Na+-dependent 2-(methylamino)isobutyric acid, and Na+-independent leucine transport were observed under glutamine-deprived conditions, which were completely blocked by actinomycin D and cycloheximide. These mechanisms may allow cells to survive and even grow under nutrient-deprived conditions.

Amino Acid Transport System ASC↗

PubMed2003

Psychosocial factors and risk of hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

CONTEXT: Although psychosocial factors are correlated, previous studies on risk factors for hypertension have typically examined psychosocial factors individually and have yielded inconsistent findings. OBJECTIVE: To examine the role of psychosocial factors of time urgency/impatience (TUI), achievement striving/competitiveness (ASC), hostility, depression, and anxiety on long-term risk of hypertension. DESIGN, SETTING, AND STUDY POPULATION: A population-based, prospective, observational study using participant data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. A total of 3308 black and white adults aged 18 to 30 years (when recruited in 1985 and 1986) from 4 US metropolitan areas and followed up through 2000 to 2001. MAIN OUTCOME MEASURES: Fifteen-year cumulative incidence of hypertension (systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or taking antihypertensive medication). RESULTS: The incidence of hypertension at year 15 was 15% from baseline and 13.6% from year 5. After adjusting for the same set of hypertension risk factors and each of the psychosocial factors of TUI, ASC, hostility, depression, and anxiety in 5 separate logistic regression models, higher TUI and hostility were significantly associated with risk of developing hypertension at 15-year follow-up for the total sample. Compared with the lowest score group, the adjusted odds ratio (OR) for TUI was 1.51 (95% confidence interval [CI], 1.12-2.03) for a score of 1; 1.47 (95% CI, 1.08-2.02) for a score of 2; and 1.84 (95% CI, 1.29-2.62) for a score of 3 to 4 (P for trend =.001). Compared with the lowest quartile group, the adjusted OR for hostility was 1.06 (95% CI, 0.76-1.47) for quartile 2; 1.38 (95% CI, 1.00-1.91) for quartile 3; and 1.84 (95% CI, 1.33-2.54) for quartile 4 (P for trend <.001). No consistent patterns were found for ASC, depression, or anxiety. Race- and sex-specific analyses and multivariable models with simultaneous adjustment for all 5 psychosocial factors and other hypertension risk factors had generally similar results. CONCLUSION: Among young adults, TUI and hostility were associated with a dose-response increase in the long-term risk of hypertension.

Adult↗

PubMed1996

Frequency dependence of long-term potentiation and depression in the dentate gyrus of the freely moving rat.

Long-term potentiation (LTP) or long-term depression (LTD) can be produced in the dentate gyrus (DG) of the hippocampus with high-or low-frequency stimulation trains, respectively. Although LTP can be elicited in a variety of preparations, we know of no reports of LTD unaccompanied by seizure activity in the awake rat. In this experiment, test pulses at alternating high (95% of maximum response) and moderate (50-75% of maximum) intensities were presented at 0.05 Hz to the perforant path of freely moving rats in order to assess changes in DG population spike amplitude. Trains were delivered at 10-min intervals, and intratrain frequency was adjusted either upward from 3 Hz or downward from 400 Hz until all subjects had received three consecutive tetani at each of 3, 6, 12.5, 25, 50, 100, 200, and 400 Hz. Potentiation was observed at high frequencies regardless of whether ascending (ASC) or descending (DES) test order was used. Depression occurred at low frequencies, but only in ASC rats. The LTD observed in this preparation was not very robust and was clearly seen only when moderate-intensity test pulses were used. The threshold frequency (at which depression gives way to potentiation) was approximately 6-9 Hz for DES rats but was 100-120 Hz for ASC animals. Prior stimulation therefore affected the response to subsequent trains. These results are generally consistent with the hypothesis of a variable threshold for LTP induction. Our findings can also be explained by postulating a wide "labile range" at moderate frequencies within which no plastic changes occur.

Animals↗

PubMed2001

Kinetics of dissociative electron transfer to ascaridole and dihydroascaridole-model bicyclic endoperoxides of biological relevance.

The homogeneous and heterogeneous electron transfer (ET) reduction of ascaridole (ASC) and dihydroascaridole (DASC), two bicyclic endoperoxides, chosen as convenient models of the bridged bicyclic endoperoxides found in biologically relevant systems, were studied in aprotic media by using electrochemical methods. ET is shown to follow a concerted dissociative mechanism that leads to the distonic radical anion, which is itself reduced in a second step by an overall two-electron process. The kinetics of homogeneous ET to these endoperoxides from an extensive series of radical anion electron donors were measured as a function of the driving force of electron transfer (deltaG(o)ET). The kinetics of heterogeneous ET were also studied by convolution analysis. Together, the heterogeneous and homogeneous ET kinetic data provide the best example of the parabolic nature of the activation-driving force relationship for a concerted dissociative ET described by Savéant; the data is particularly illustrative due to the low bond-dissociation enthalpy (BDE) of the O-O bond and hence small intrinsic barriers. Analysis of the data allowed the dissociative reduction potentials (E(o)diss) to be determined as -1.2 and -1.1 Vagainst SCE for ASC and DASC, respectively. Unusually low pre-exponential factors measured in temperature-dependent kinetic studies suggest that ET to these O-O bonded systems is nonadiabatic. Analysis of ET kinetics for ASC and DASC by the Savéant model with a modification for nonadiabaticity allowed the intrinsic free energy for ET to be determined. The use of this approach and estimates for the BDE provide approximations of the reorganization energies. We suggest the methodology described herein can be used to evaluate the extent of ET to other endoperoxides of biological relevance and to provide thermochemical data not otherwise available.

Bridged Bicyclo Compounds, Heterocyclic↗

PubMed2003

ThinPrep versus conventional Papanicolaou smear in the cytologic follow-up of women with equivocal cervical smears.

BACKGROUND: The purpose of the current study was to compare the efficacy of liquid-based cytology and conventional smears in the cytologic follow-up of cases with "atypical squamous cells, cannot exclude a high-grade lesion" (ASC-H) or "atypical glandular cells" (AGC). METHODS: Cytologic follow-up was performed on 214 cases with ASC-H/AGC diagnosis an conventional smears using either ThinPrep (n = 100) or conventional Papanicoloau (Pap) tests (n = 114). Results were then compared with further histologic and/or cytologic follow-up. RESULTS: Repetition on conventional smears enabled a definite diagnosis (within normal limits [WNL], squamous intraepithelial lesion [SIL] or carcinoma) in 58 cases (50.9%). ASC/AGC was confirmed in 50 cases (43.9%), and 6 of the smears (5.3%) were inadequate. WNL, SIL, or carcinoma was diagnosed in 82 (82.0%) cases by following the patients with ThinPrep cytology, whereas ASC or AGC was confirmed in 18 cases (18.0%). No inadequate specimens were found. A diagnosis of SIL or greater (SIL +) was confirmed histologically in 11 of 11 (100.0%) conventional smears and in 31 of 34 (91.2%) ThinPrep specimens. Of the 87 WNL specimens, 9 (8 conventional smears and 1 ThinPrep specimen) developed a histologically confirmed SIL during further follow-up. Specimen adequacy was significantly better in the ThinPrep specimens compared with conventional smears. CONCLUSIONS: Because of better specimen adequacy, ThinPrep cervical cytology appears to significantly reduce the occurrence of ASC/AGC compared with conventional Pap smears.

Adult↗