[Treatment of trigeminal neuralgia with intranervous injection of adriamycin: Analysis of 102 patients]
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Journal Article↗
Biomedical subjects
Y Ma
Publications and source records attributed to Y Ma.
Correction for partial volume effects in PET: principle and validation.
UNLABELLED: The accuracy of PET for measuring regional radiotracer concentrations in the human brain is limited by the finite resolution capability of the scanner and the resulting partial volume effects (PVEs). We designed a new algorithm to correct for PVEs by characterizing the geometric interaction between the PET system and the brain activity distribution. METHODS: The partial volume correction (PVC) algorithm uses high-resolution volumetric MR images correlated with the PET volume. We used a PET simulator to calculate recovery and cross-contamination factors of identified tissue components in the brain model. These geometry-dependent transfer coefficients form a matrix representing the fraction of true activity from each distinct brain region observed in any given set of regions of interest. This matrix can be inverted to correct for PVEs, independent of the tracer concentrations in each tissue component. A sphere phantom was used to validate the simulated point-spread function of the PET scanner. Accuracy and precision of the PVC method were assessed using a human basal ganglia phantom. A constant contrast experiment was performed to explore the recovery capability and statistic error propagation of PVC in various noise conditions. In addition, a dual-isotope experiment was used to evaluate the ability of the PVC algorithm to recover activity concentrations in small structures surrounded by background activity with a different radioactive half-life. This models the time-variable contrast between regions that is often seen in neuroreceptor studies. RESULTS: Data from the three-dimensional brain phantom demonstrated a full recovery capability of PVC with less than 10% root mean-square error in terms of absolute values, which decreased to less than 2% when results from four PET slices were averaged. Inaccuracy in the estimation of 18F tracer half-life in the presence of 11C background activity was in the range of 25%-50% before PVC and 0%-6% after PVC, for resolution varying from 6 to 14 mm FWHM. In terms of noise propagation, the degradation of the coefficient of variation after PVC was found to be easily predictable and typically on the order of 25%. CONCLUSION: The PVC algorithm allows the correction for PVEs simultaneously in all identified brain regions, independent of tracer levels.
Algorithms↗
bcl-2/bax expression and p53 gene status in human bladder cancer: relationship to early recurrence with intravesical chemotherapy after resection.
PURPOSE: Studies have shown that the effects of chemotherapy depend on some biochemical mechanisms to induce apoptosis. Many genes are involved in apoptosis modulation, including p53, bcl-2 and bax. We determined the roles of p53 status and the ratio of bcl-2/bax proteins for predicting the recurrence of bladder superficial transitional cell carcinoma that had been treated with intravesical chemotherapy after resection. MATERIALS AND METHODS: We performed Western blot analysis to express bcl-2 and bax proteins, and PCR-SSCP to determine the alteration in the p53 gene in 43 patients with transitional cell carcinoma of the bladder treated with intravesical chemotherapy after tumor resection. RESULTS: The expression of bcl-2 or bax did not correlate with histological grade, clinical stage or relapse. In cases of relapse within 1 year after resection bcl-2/bax was greater than and less than 1 in 50 and 11%, respectively (p <0.01). Recurrence within 1 year after the initial operation was also more common in patients with than without p53 gene mutation (64 versus 22%, p <0.05). Furthermore, bcl-2/bax greater than and less than 1 was associated with p53 gene mutation in 38 and 11% of cases, respectively (p <0.05). CONCLUSIONS: A bcl-2/bax ratio greater than 1 and p53 gene mutation were closely associated with early relapse in patients with superficial transitional cell carcinoma of the bladder during intravesical chemotherapy after resection. This finding suggests that the relative levels of bcl-2 and bax, and p53 gene status may contribute to drug sensitivity and progression, and help to predict recurrence. Moreover, bcl-2/bax correlated with p53 status, which implies that cross talk among bcl-2, bax and p53 has a role in influencing drug induced apoptosis and regulating resistance to chemotherapy.
Carcinoma, Transitional Cell↗
[Structure and function of serum mannan-binding protein involved in innate immunity].
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Acetylglucosamine↗
Gender differences in social desirability and social approval bias in dietary self-report.
Social desirability (the tendency to respond in such a way as to avoid criticism) and social approval (the tendency to seek praise) are two prominent response set biases evident in answers on structured questionnaires. These biases were tested by comparing nutrient intakes as estimated from a single 24-hour diet recall interview (24 HR) and a 7-day dietary recall (7DDR). Data were collected as part of the Worcester Area Trial for Counseling in Hyperlipidemia, a randomized, physician-delivered nutrition intervention trial for hypercholesterolemic patients conducted in Worcester, Massachusetts, from 1991 to 1995. Of the 1,278 total study subjects, 759 had complete data for analysis. Men overestimated their fat and energy intakes on the 7DDR as compared with the 24HR according to social approval: One unit increase in the social approval score was associated with an overestimate of 21.5 kcal/day in total energy intake and 1.2 g/day in total fat intake. Women, however, underestimated their dietary intakes on the 7DDR relative to the 24HR according to social desirability: One unit increase in the social desirability score was associated with an underestimate of 19.2 kcal/day in energy intake and 0.8 g/day in total fat. The results from the present study indicate that social desirability and social approval biases appear to vary by gender. Such biases may lead to misclassification of dietary exposure estimates resulting in a distortion in the perceived relation between health-related outcomes and exposure to specific foods or nutrients. Because these biases may vary according to the perceived demands of research subjects, it is important that they be assessed in a variety of potential research study populations.
Adult↗
Chymase cleavage of stem cell factor yields a bioactive, soluble product.
Stem cell factor (SCF) is produced by stromal cells as a membrane-bound molecule, which may be proteolytically cleaved at a site close to the membrane to produce a soluble bioactive form. The proteases producing this cleavage are unknown. In this study, we demonstrate that human mast cell chymase, a chymotrypsin-like protease, cleaves SCF at a novel site. Cleavage is at the peptide bond between Phe-158 and Met-159, which are encoded by exon 6 of the SCF gene. This cleavage results in a soluble bioactive product that is 7 amino acids shorter at the C terminus than previously identified soluble SCF. This research shows the identification of a physiologically relevant enzyme that specifically cleaves SCF. Because mast cells express the KIT protein, the receptor for SCF, and respond to SCF by proliferation and degranulation, this observation identifies a possible feedback loop in which chymase released from mast cell secretory granules may solubilize SCF bound to the membrane of surrounding stromal cells. The liberated soluble SCF may in turn stimulate mast cell proliferation and differentiated functions; this loop could contribute to abnormal accumulations of mast cells in the skin and hyperpigmentation at sites of chronic cutaneous inflammation.
Binding Sites↗
Intracoronary Doppler assessment of moderate coronary artery disease: comparison with 201Tl imaging and coronary angiography. FACTS Study Group.
BACKGROUND: Coronary angiography may not reliably predict whether a stenosis causes exercise-induced ischemia. Intracoronary Doppler ultrasound may enhance diagnostic accuracy by providing a physiological assessment of stenosis severity. The goal of this study was to compare intracoronary Doppler ultrasound with both 201Tl imaging and coronary angiography. METHODS AND RESULTS: Fifty-five patients with 67 stenotic coronary arteries underwent coronary angiography with intracoronary Doppler ultrasound and had exercise 201Tl testing within a 1-week period. Coronary flow reserve was measured, and analyses were performed by independent core laboratories. The mean stenosis was 59+/-12%; 51 of 67 stenoses were intermediate in severity (40% to 70%). A coronary flow reserve < 1.7 predicted the presence of a stress 201Tl defect in 56 of 67 stenoses (agreement=84%; kappa=0.67; 95% CI=0.48 to 0.86). In the patients who achieved 75% of their predicted maximum heart rate, the Doppler and 201Tl imaging data agreed in 46 of 52 stenoses (agreement=88%; kappa=0.77; 95%CI=0.57 to 0.97). Scatter was evident when angiography was compared with coronary flow reserve (r=.43), and the angiogram did not reliably predict the results of the 201Tl stress test (kappa=0.21; agreement=57% to 63%). CONCLUSIONS: Doppler-derived coronary flow reserve accurately predicts the presence of exercise-induced ischemia on stress 201Tl imaging, and coronary angiography does not reliably assess the physiological significance of an intermediate coronary stenosis.
Aged↗
Peptide separation by pH-zone-refining countercurrent chromatography.
Peptides without protecting groups have been successfully separated by pH-zone-refining countercurrent chromatography (CCC) using an ion-pair reagent, di-(2-ethylhexyl)phosphoric acid (DEHPA), as a modifier in the stationary phase. Preliminary studies indicated that two parameters, i.e., the DEHPA concentration in the stationary phase and hydrophobicity of the solvent system should be adjusted according to the hydrophobicity of the analytes. Hydrophobic and hydrophilic groups of dipeptides were each separated under optimized conditions. The method was successfully applied to gram-quantity separations of bacitracin complex and bovine insulin.
Animals↗
Positional isomers of monopegylated interferon alpha-2a: isolation, characterization, and biological activity.
The success of recombinant interferon alpha in the clinic in part is limited by two properties of the protein: short serum half-life and immunogenicity. To improve these properties, interferon alpha-2a was conjugated with polyethylene glycol (PEG-5000). A homogeneous preparation of monopegylated interferon alpha-2a was subjected to vigorous analytical and activity characterization. A newly developed ampholyte-free chromatofocussing-like cation-exchange HPLC method utilizing a sulfopropyl resin was used to separate the monopegylated protein into 11 species. Peptide mapping, sequencing, and mass spectrometric analyses indicated that these species are positional isomers where each isomer represents a single polymer molecule conjugated to one specific lysine residue. No species with a modification at the amino terminus was observed. All 11 isomers show antiviral and antiproliferative activities in the same range as the parent monopegylated interferon alpha-2a.
Animals↗
Asialoglycoprotein/asialoglycoprotein receptor (AGP-AGPr) interaction is an important mechanism for the uptake of FK506 by hepatocytes.
Hepatic tissue concentrations of FK506 have been correlated with early acute rejection following liver transplantation. Asialoglycoproteins (AGP) reputedly bind FK506 in blood. AGP are removed from the circulation by the liver via the AGP receptor (AGPr), which resides on hepatocytes. This study was undertaken to determine if the AGP-AGPr mechanism enhances the delivery of FK506 to hepatocytes. Human orosomucoid (OM) was used as a representative AGP. asialoOM (aOM) was prepared by desialation of OM. Fresh rat hepatocytes were isolated by collagenase digestion. Tritium labeled FK506 (FK) was used to identify and quantitate FK506. Quantitation of FK in serum and culture media was by direct counting. FK in animal tissues used a method developed in our laboratory for the purpose. AGPr on resting hepatocytes was demonstrated by flow cytometry using FITC-orosomucoid and FITC-BSA controls. AGPr were enhanced by 2 g glucose/L. Two serum FK-binding fractions, 44 kD and 15 kD, were identified by gel filtration. Exogenous OM avidly bound FK and displaced FK activity from the 15 kD fraction. Serum (1%) and the 44 kD fraction enhanced the uptake of FK by hepatocytes, while serum depleted of OM-aOM by affinity chromatography was only 72.5% as effective as control serum; aOM enhanced the uptake of FK by hepatocytes to a degree similar to that of control serum but OM did not significantly affect the uptake of FK. Cold FK506 blocked the uptake and was dose dependent; cold CsA had no effect. Affinity extraction of OM from serum to which FK had previously been added removed 28.4% of FK activity. Following i.v. infusion, the kidney had the highest and liver the lowest tissue concentration of FK at 1 hr and 3 hr. In contrast, after oral administration the liver had the highest concentrations of the other tissues tested. The AGP-AGPr mechanism plays a significant role in the delivery of FK506 to hepatocytes and is likely responsible for the differences in bioavailability observed after oral and i.v. administration. Factors governing the AGP-AGPr mechanism are germane to understanding both the efficacy and toxicity of FK506 and the development optimal therapeutic strategies.
Administration, Oral↗
Aging- and ovariectomy-related skeletal changes in spontaneously hypertensive rats.
BACKGROUND: The skeletal impact of estrogen deficiency on subjects with hypertension has not been studied previously. In this study, we examined the skeletal characteristics of female spontaneously hypertensive rats (SHR) and their normotensive genetic control Wistar-Kyoto rat (WKY). We aimed to reveal: 1) the skeletal characters of female SHR, and 2) the response of SHR to ovariectomy (ovx) when compared to WKY and other strains. METHODS: Undecalcified double-fluorescent labeled cancellous (proximal tibial metaphysis, PTM) and cortical (tibial shaft, TX) bones from 23-weeks-old, and from rats 2 and 8 weeks post-ovx were studied. RESULTS: The SHR showed lower body weight, higher heart rate, and higher blood pressure than the WKY. Female SHR possessed more percent cancellous bone, less net cortical bone, smaller tissue area, and thinner cortex than WKY. Furthermore, SHR exhibited an age-related cancellous (-18%) and cortical (-7%) bone loss associated with a decrease in the longitudinal growth rate and bone balance and a decrease in periosteal bone formation in cortical bone. In contrast, the WKY maintained most of these parameters unchanged at their 23-week-old levels. Ovariectomy induced earlier and greater cancellous bone loss in the SHR than in the WKY, with greater increases in bone turnover rate, eroded surface, activation frequency, and a decrease in the ratio of labeled to eroded perimeter in PTM at 2 weeks postsurgery. However, the two groups exhibited no differences in bone loss at 8 weeks after ovx in PTM and TX. CONCLUSIONS: Spontaneously hypertensive rats were highly sensitive to estrogen deficiency. This might have clinical relevance to those postmenopausal women who suffer from hypertension, in that they may be more susceptible to osteopenia. If so, preventive measures should be initiated sooner than otherwise.
Aging↗
The production of soluble interleukin 4 receptors is preferentially regulated by the murine Th2 cell subset.
In order to understand how the endogenous production of soluble IL-4 receptors (sIL-4r) is regulated, the authors tested prototypic clones of Th1 and Th2 murine CD4+ T cell subsets for their ability to regulate their expression of sIL-4r. Results showed that although both types of clones produced low levels of sIL-4r under resting conditions, only the Th2 clones upregulated sIL-4r expression following antigenic stimulation. Inhibition of endogenous IL-4 with a neutralizing anti-IL-4 mAb had only a minor (approximately 20%) inhibitory effect on sIL-4r production by the Th2 cells, and addition of rIL-4 to Th1 cells resulted only in a modest two-fold increase in sIL-4r levels, suggesting that IL-4 is not the only factor that regulates sIL-4r production and that the ability of Th2 clones to upregulate sIL-4r expression can be relatively independent of IL-4. Indeed, the production of sIL-4r by Th2 cells was found to be regulated by cell contact and/or IL-1 mediated signals. Transcripts for both sIL-4r and mIL-4r were detected by RT-PCR on both resting and activated Th1 and Th2 cells, with the relative levels of expression being moderately higher in the Th2 clones. Moreover, the expression of sIL-4r-specific transcripts appeared to increase to a greater extent than those of mIL-4r after activation of Th2 cells with APCs, both in the presence and absence of antigen. Taken together, these results predict that increased sIL-4r production in vivo might be preferentially associated with Th2-type responses and indicate that even though the production of IL-4 and sIL-4r is mediated by the same cells (i.e. Th2 cells), the synthesis of sIL-4r can be regulated independently from that of IL-4 through alternative signals such as cell contact and/or IL-1. These properties may allow for changing ratios of sIL-4r to IL-4 and sIL-4r to mIL-4r during different phases of an immune response and are consistent with a regulatory role for sIL-4r on IL-4 activity in vivo.
Animals↗
Determining surface areas of marine alga cells by acid-base titration method.
A new method for determining the surface area of living marine alga cells was described. The method uses acid-base titration to measure the surface acid/base amount on the surface of alga cells and uses the BET (Brunauer, Emmett, and Teller) equation to estimate the maximum surface acid/base amount, assuming that hydrous cell walls have carbohydrates or other structural compounds which can behave like surface Brönsted acid-base sites due to coordination of environmental H2O molecules. The method was applied to 18 diverse alga species (including 7 diatoms, 2 flagellates, 8 green algae and 1 red alga) maintained in seawater cultures. For the species examined, the surface areas of individual cells ranged from 2.8 x 10(-8) m2 for Nannochloropsis oculata to 690 x 10(-8) m2 for Dunaliella viridis, specific surface areas from 1,030 m2.g-1 for Dunaliella salina to 28,900 m2.g-1 for Pyramidomonas sp. Measurement accuracy was 15.2%. Preliminary studies show that the method may be more promising and accurate than light/electron microscopic measurements for coarse estimation of the surface area of living algae.
Cell Division↗
Establishment of a novel radioligand assay using eukaryotically expressed cytochrome P4502D6 for the measurement of liver kidney microsomal type 1 antibody in patients with autoimmune hepatitis and hepatitis C virus infection.
BACKGROUND/AIMS: Liver kidney microsomal type 1 antibody (LKM1) is the diagnostic marker of autoimmune hepatitis (AIH) type 2 and is also found in patients with hepatitis C virus (HCV) infection. Cytochrome P4502D6 (CYP2D6) is the documented target antigen of LKM1 in AIH, but not in HCV infection. To compare the reactivity in the two conditions, we established a radioligand assay using eukaryotically expressed CYP2D6 as target. METHODS: A 1.2-kb human CYP2D6 cDNA was isolated from a human liver cDNA library and subcloned into an in vitro transcription vector pSP64 Poly(A). Recombinant CYP2D6 was then produced by in vitro transcription/translation, metabolically labelled with 35S methionine and used in the immunoprecipitation assay. Antibodies that bound radiolabelled CYP2D6 were immunoprecipitated and their levels assessed as cpm. Sera from 50 LKM1-positive patients (26 with AIH; 24 with HCV infection), 128 LKM1-negative patients and 57 normal controls were tested. RESULTS: Reactivity to 35S labelled CYP2D6 was observed in all LKM1-positive sera from patients with AIH and HCV infection, but in none of the controls. The cpm in both conditions were significantly higher than in normal controls (p<0.0001), and were correlated with the immunofluorescence titres of LKM1 (r 0.87, p<0.001 and r=0.64, p<0.001 for AIH and HCV infection, respectively). Reactivity to 35S labelled CYP2D6 was inhibited by addition of an excess of eukaryotically expressed CYP2D6. CONCLUSIONS: CYP2D6 is a major target antigen of both AIH and HCV infection. The novel radioligand assay is highly sensitive and specific.
Adolescent↗
Alendronate prevents cyclosporin A-induced osteopenia in the rat.
Post-transplantation bone disease is an increasingly recognized clinical entity whose etiology is multifactorial. The immunosuppressant agent cyclosporine-A (CsA) has repeatedly been shown experimentally to induce a high-turnover osteopenic state. Alendronate (Alen.) is a new generation bisphosphonate having far greater antiresorptive potency than previous bisphosphonates. It inhibits osteoclast resorption in vitro and in vivo without adversely affecting bone mineralization. This study was designed to investigate whether alendronate could prevent CsA-induced osteopenia in the rat. Forty-eight 8-month-old male Sprague Dawley rats were randomized into four groups to receive the following for 28 days: (1) CsA vehicle (veh.) p.o. daily and alendronate vehicle subcutaneously (s.c.) twice/week, (2) CsA 15 mg/kg p.o. daily and Alen. veh. s.c. twice/week, (3) Alen. 70 micrograms/kg s.c. twice/ week and CsA veh. p.o. daily, and (4) CsA 15 mg/kg p.o. daily and Alen. 70 micrograms/kg s.c. twice/week. Rats were weighed and bled and serum was assayed serially for calcium, PTH, 1,25(OH)2vit.D, and osteocalcin. Tibiae were removed following sacrifice on day 28, after double demeclocycline and calcein labeling, for histomorphometric analysis. Treated groups were compared to the vehicle-treated control. We confirmed previous findings that CsA produces elevated 1,25(OH)2 vitamin D and serum osteocalcin levels. Alendronate treatment by itself decreased osteocalcin by day 28 and resulted in a marginal decrease in serum total calcium on day 14. The histomorphometry findings reconfirmed that the administration of CsA induces a state of high-turnover osteopenia. Alendronate prevented CsA's adverse effects, particularly in maintaining trabecular bone volume, presumably by decreasing bone remodeling. Alendronate would seem to hold therapeutic promise in post-transplantation bone disease.
Administration, Oral↗
Thermophysiology of Streptococcus mutans and related lactic-acid bacteria.
The temperature ranges for growth of Streptococcus mutans GS-5 and S. sobrinus 6715 were found to be very narrow, from about 30 to 47 degrees C, with optimal growth around 37 degrees C. Thus, the organisms showed little potential to grow in the environment outside of the animal host. In contrast wider ranges were found for Enterococcus hirae, S. rattus and S. sanguis. Detailed study of S. mutans GS-5 showed that energetic coupling, reflected in yields of biomass per mol of glucose utilized, were not greatly affected by changes in temperature within the growth range. However, since glycolysis occurred over a wider temperature range (about 10 to 52 degrees C) than growth, yield values dropped to zero at temperatures above or below the growth range. The temperature range for glycolysis could be related to temperature sensitivity of the phosphoenolypyruvate: sugar phosphotransferase system for sugar uptake. F-ATPases were active over a similar range of temperatures, but with a broad optimal range from about 30 to 50 degrees C. Proton permeability of S. mutans increased steadily with temperature in a manner similar to that of other mesophilic bacteria, such as Escherichia coli. Growth of the bacteria in media supplemented with various fatty acids had major effects on proton permeabilities but the effects were not well reflected by changes in growth or glycolysis of the bacteria. The overall conclusions were that S. mutans is a typical mesophile in relation to membrane and catabolic functions but its narrow temperature range for growth is related to temperature sensitivities of anabolic systems.
Adenosine Triphosphatases↗
Alcohol dehydrogenase: a target of humoral autoimmune response in liver disease.
BACKGROUND & AIMS: Liver-specific membrane lipoprotein (LSP) is a heterogeneous liver preparation that has been widely used to study autoreactivity in liver disease. The aim of this study was to identify autoantigens in LSP. METHODS: Guinea pig anti-LSP serum was used to screen a human liver complementary DNA (cDNA) library. Humoral immune responses to isolated potential autoantigens were investigated by immunoblotting in 91 pediatric patients with various liver diseases, 20 adult patients with alcoholic liver disease and 20 with autoimmune thyroid disease, 37 healthy children, and 20 healthy adults. RESULTS: A 1.6-kilobase cDNA insert isolated from the cDNA library was found to encode amino acids 61-374 of the human alcohol dehydrogenase (ADH)-gamma 1 subunit. Antibodies to this or other ADH subunits were found significantly more frequently in autoimmune liver diseases (19 of 39 patients; 49%), Wilson's disease (5 of 13 patients; 38%), and alcoholic liver disease (10 of 20 patients; 50%) than in normal controls (P < 0.0001, P < 0.005, and P < 0.05, respectively) and correlated with disease activity in autoimmune liver disease. CONCLUSIONS: ADH has been identified as a new antigenic component of the LSP using a xenogeneic antiserum to immunoprobe a human cDNA liver library and seems to be a target autoantigen in liver disease. This approach may be useful in identifying other potential autoantigens.
Adolescent↗
Complement-modulating properties of a kaempferol 7-O-rhamnosylsophoroside from the leaves of Morinda morindoides.
A kaempferol 7-O-rhamnosylsophoroside isolated from the leaves of Morinda morindoides showed dose-dependent complement-modulating properties towards both the classical (inhibiting effect) and alternative (activating effect) pathways of the complement system. Its structure was elucidated by chemical and spectroscopic methods as kaempferol 7-O-[alpha-L-rhamnopyranosyl-(1-->6)]-[beta-D-glucopyranosyl-(1-->2)]-be ta-D-glucopyranoside, a new natural product which was named morindaoside.
Carbohydrate Sequence↗