Intrathymic inoculation of donor bone marrow at the time of transplantation plus a short course of tacrolimus induce long-term acceptance to rat lung allografts.
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Animals↗
Biomedical subjects
S Li
Publications and source records attributed to S Li.
Unilateral Blastomyces dermatitidis endophthalmitis and orbital cellulitis. A case report and literature review.
PURPOSE: The authors report the clinical, cytologic, and histopathologic findings of a unique presentation of concomitant unilateral endophthalmitis and orbital cellulitis secondary to Blastomyces dermatitidis. DESIGN: Case report. METHODS: A 29-year-old healthy woman with a history of pulmonary tuberculosis presented with a painful right eye and rapidly decreasing vision. Fundus examination showed a diffuse elevated choroidal lesion at the posterior pole. With an otherwise unremarkable systemic work-up, the patient was treated with systemic antibiotics and corticosteroids for a presumed diagnosis of choroidal tuberculous granuloma. After an initial response to the treatment, the patient's condition deteriorated rapidly with visual acuity decreasing from 20/25 to no light perception in 3 months. Ipsilateral proptosis developed with magnetic resonance imaging showing a poorly defined orbital mass. Surgical enucleation and an orbital biopsy were performed. RESULTS: Histopathologic examination of the orbital specimen and an intact enucleated globe showed a diffuse necrotizing granulomatous process with the presence of numerous yeasts consistent with B. dermatitidis. This subsequently was confirmed by positive culture of B. dermatitidis from the orbital specimen. CONCLUSIONS: This is a unique case of concurrent unilateral endophthalmitis and orbital cellulitis secondary to B. dermatitidis. Intraocular dissemination of blastomycosis should be suspected in the differential diagnosis of endophthalmitis in patients with previous or active pulmonary lesions of equivocal nature. Early diagnosis and prompt treatment with antifungal medications are essential.
Adult↗
CD4 dimerization and oligomerization: implications for T-cell function and structure-based drug design.
Recent studies of CD4 structure and function have revealed possible mechanisms for CD4 self-association, with implications for its role in T-cell activation. Here, the authors discuss the formulation of a hypothetical three-dimensional model of CD4 oligomerization and how it impacts on the understanding of T-cell function and rational drug design targeting specific CD4 surface functional sites.
CD4 Antigens↗
Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation.
The analgesic effect and adverse events of the weak opioid codeine is assumed to be mediated by its metabolite morphine. The cytochrome P-450 enzyme CYP2D6 catalysing the formation of morphine exhibits a genetic polymorphism. Two distinct phenotypes, the extensive (EMs) and poor metabolisers (PMs), are present in the population. The prevalence of PMs in the Caucasian population is 7% to 10%. Since PMs do not express functional CYP2D6, they have a severely impaired capacity to metabolise drugs which are substrates of this enzyme. Provided the analgesic effect and the adverse events of codeine are mediated by its metabolite morphine, large phenotype-related differences are to be expected and PMs, as they form only trace amounts of morphine, can serve as a model to test the hypothesis whether the analgesia and adverse events of codeine are mediated by the parent drug or its metabolite morphine. Therefore we have studied in a randomised placebo-controlled double-blind trial the analgesic effect of 170 mg codeine (p.o.) compared to 20 mg morphine (p.o.) and placebo in 9 EMs and 9 PMs using the cold pressor test. The duration and intensity of the side effects were assessed using visual analogue scales (VAS). Codeine and morphine concentrations were measured in serum and urine. Compared to placebo, 20 mg morphine caused a significant increase in pain tolerance in both phenotypes, EMs and PMs (16.2+/-27.4 vs. -0.66+/-27.4 s x h, n=18). However, following administration of codeine, analgesia was only observed in EMs but not in PMs (EMs: 54.9+/-42.2 vs. 1.7+/-4.2 s x h, P < 0.01; PMs: 9.6+/-10.9 vs. 3.3+/-23.7 s x h, not significant). Adverse events were significantly more pronounced after morphine and codeine compared to placebo in both EMs and PMs. In contrast to the phenotype-related differences in the analgesic effect of codeine, however, no difference in adverse events between the phenotypes could be observed. In the pharmacokinetic studies, significant differences between the two phenotypes in the formation of morphine after codeine administration could be observed. Whereas morphine plasma concentrations were similar in PMs (Cmax: 44+/-13 nmol/l: AUC: 199+/-45 nmol x h/l) and EMs (Cmax: 48+/-17 nmol/l); AUC: 210+/-65 nmol x h/l) after morphine administration, following 170 mg codeine, morphine plasma concentrations comparable to those after morphine application were only observed in EMs (Cmax: 38+/-16 nmol/l; AUC: 173+/-90 nmol x h/l). In PMs only traces of morphine could be detected in plasma (Cmax: 2+/-1 nmol/l; AUC: 10+/-7 nmol x h/l). The percentage of the codeine dose converted to morphine and its metabolites was 3.9% in EMs and 0.17% in PMs. The interindividual variability in analgesia of codeine which is related to genetically determined differences in the formation of morphine clearly indicate that this metabolite is responsible for the analgesic effect of codeine. In contrast to the analgesic effect, frequency and intensity of the adverse events did not present significant differences between the two phenotypes. These findings have implications for the clinical use of codeine. Since side effects occurred in both EM and PM subjects, the use of codeine as an analgesic will expose 7% to 10% of patients who are PMs to the side effects of the drug without providing any beneficial analgesic effects.
Adult↗
The octadecaneuropeptide-induced response of corticotropin-releasing hormone messenger RNA levels is mediated by GABA(A) receptors and modulated by endogenous steroids.
The involvement of endogenous benzodiazepine octadecaneuropeptide in the regulation of corticotropin-releasing hormone messenger RNA expression has been studied using in situ hybridization technique. Intracerebroventricular injection of octadecaneuropeptide (4 microg/kg) induced a 26% decrease in the corticotropin-releasing hormone messenger RNA expression in the hypothalamic paraventricular nucleus. Concomitant injection of octadecaneuropeptide and i.p. injection of the GABA(A) receptor agonist muscimol (4 mg/kg) potentiated the corticotropin-releasing hormone messenger RNA decrease ( - 34%). The depressing effect of octadecaneuropeptide on corticotropin-releasing hormone gene expression was totally reversed by pretreatment of the animals with the GABA(A) receptor antagonist picrotoxin (5 mg/kg; i.p.) or by pretreatment with the benzodiazepine receptor antagonist flumazenil (4 mg/kg; i.p.). To determine the reciprocal involvement of adrenal and sexual steroids in this regulation, animals are adrenalectomized and/or castrated. Adrenalectomy reversed the effect induced by octadecaneuropeptide, which increased corticotropin-releasing hormone messenger RNA expression (+21%), while castration did not modify the negative influence of octadecaneuropeptide. When rats were adrenalectomized and castrated, the adrenalectomy influence was predominant, since octadecaneuropeptide increased significantly the hybridization signal (+18%). The involvement of neurosteroids, especially reduced metabolites of progesterone was also investigated. The concomitant injection of octadecaneuropeptide and subcutaneous injection of the 5alpha-reductase inhibitor MK-906 (14 mg/kg) to adrenalectomized and castrated rats, reduced significantly by 60% the increase of corticotropin-releasing hormone messenger RNA expression induced by octadecaneuropeptide. These results indicate that in vivo the endogenous benzodiazepine octadecaneuropeptide, via an activation of the benzodiazepine sites of the GABA(A) receptor, negatively modulates corticotropin-releasing hormone neuronal activity and that this modulation can be negatively or positively influenced by central and peripheral steroids.
Adrenalectomy↗
A numerical study of radiofrequency deposition in a spherical phantom using surface coils.
The electromagnetic fields induced by a surface coil in a spherical phantom, having a wide range of electrical properties, is studied using numerical methods of calculation. The specific absorption rate (SAR), radiofrequency magnetic field (B1), magnetic field energy within the phantom (EB), and the volume-averaged SAR ( ) are calculated at 10, 63, and 200 MHz. They are analyzed with respect to dielectric constant, wavelength, and skin depth effects, which become increasingly important in high field magnetic resonance imaging (MRI) where safety and field homogeneity issues need further study. Particular attention is given to solutions representing neural tissue at each frequency. In general, the data at high field strengths have local maxima, with a quasi-harmonic behavior, when the following two resonant conditions are satisfied: 1) skin depth becomes comparable to, or larger than, the sample diameter Ds; and 2) Ds is near an integral multiple of the wavelength. These are also the solutions with maximum EB values and the least homogeneous B1. Samples undergoing resonance at 200 MHz are shown to have important off-axis B1 maxima (affecting field homogeneity) and large values. Some non-resonating 200-MHz phantoms, including simulations consistent with neural tissue, contain larger SAR maxima than the resonating samples, posing safety concerns in high field imaging of biologic tissue.
Computer Simulation↗
Osteolysis associated with cemented total knee arthroplasty.
Osteolysis has not been mentioned as a complication or cause of failure of cemented total knee arthroplasties in long-term follow-up studies. We are aware of a single case report of osteolysis after cemented total knee arthroplasty. We report the case of an 87-year-old woman with massive osteolysis beneath a cemented tibial component.
Aged↗
Use of commercial antibodies for detection of the primary antioxidant enzymes.
Fourteen commercial antibodies against human antioxidant enzymes were tested on whole cell lysates by Western analysis for specificity and species crossreactivity. All antibodies, except one, recognized pure protein antigen. All four catalase antibodies were of high quality, and they could also recognize the catalases from rat, mouse, dog, and hamster cells. Two CuZnSOD antibodies were very specific for CuZnSOD protein. They could also crossreact with CuZnSOD from rat, mouse, and hamster cells, but not from dog cells. All five MnSOD antibodies detected only very high levels of MnSOD. We believe that they could not properly be used in immunohistochemistry. Three GPX antibodies could not detect the specific GPX band from cell lysates. We believe that it is difficult to use these GPX antibodies in both Western blotting and immunohistochemistry.
Antibodies↗
Effect of blood and microbubble oxygen and nitrogen content on perfluorocarbon-filled dextrose albumin microbubble size and efficacy: in vitro and in vivo studies.
We hypothesized, on the basis of in vitro observations, that a higher oxygen partial pressure within perfluorocarbon-containing microbubbles (PCMB) would enhance inward nitrogen diffusion after venous injection, leading to improved myocardial contrast. The in vitro studies measured PCMB size and concentration after injection into arterial blood that was obtained during inhalation of either room air or 100% oxygen. We then compared the myocardial contrast produced from PCMB sonicated in the presence of either a nitrogen-free environment (100% oxygen) or room air in three closed chest dogs. PCMB exposed to oxygenated blood in vitro were significantly smaller after insonation than PCMB exposed to arterial blood obtained during room air inhalation, confirming the important role of dissolved nitrogen in stabilizing PCMB size. In vivo studies demonstrated that intravenous PCMB sonicated with 100% oxygen produced significantly greater anterior and posterior myocardial contrast than PCMB sonicated in the presence of room air.
Animals↗
The test-retest reliability of the frequency of multiple drug use in young drug users entering treatment.
Assessment of multiple drug use relies primarily on self-report. Several studies support the reliability of client self-reports of drug use but these studies have not involved assessment of the actual frequency of drug use. This test-retest reliability study assessed the frequency of drug use in a clinical sample of 103 multiple drug users, aged 16-25 years. At initial assessment, all participants completed the Drug Use History Form (DUHF) that inquired about the number of drug-using days and the daily frequency of use for 13 drug classes during four time intervals. The DUHF was readministered 2-4 weeks later. Reliability was assessed using Intra-class correlations (ICC's). The results indicated that clients do, in general, reliably report both the number of days of use and daily frequencies. The two frequency measures were not highly correlated. Reliability estimates declined over time but most markedly after 90 days, suggesting that assessments of drug use can be reliably extended beyond 30 days. Frequency estimates based solely on the number of days of use of a substance may be unreliable estimates of actual drug consumption, indicating limitations to this commonly used outcome measure.
Adolescent↗
Tirilazad inhibits surgically induced edema and interleukin-1 production. An experimental study in rats.
The aim of this study was to evaluate the anti-inflammatory effect of tirilazad mesylate on edema and interleukin-1 (IL-1) levels in serum following standardized surgical procedures. Four groups, each containing eight rats, were randomized for treatment as follows: A) no medication, B) low-dose tirilazad, C) high-dose tirilazad, and D) corticosteroids. The animals were examined by nuclear magnetic resonance imaging (NMRI) 24 and 72 hours after surgery and the NMRI data were used in the determination of soft tissue edema. In addition, serum was obtained for analysis of IL-1 levels. Four other groups of animals were subjected to the same treatment regimen as groups A-D), respectively, and 24 hours after surgery the animals were killed, whereafter serum was obtained for analysis of IL-1 levels. The present study demonstrated that low-dose tirilazad significantly reduces soft tissue edema compared with all other treatment regimens 24 hours postoperatively. At 72 hours postoperatively significant reduction of soft tissue edema was achieved at low-dose tirilazad when compared to high-dose tirilazad and steroids. In addition, a significant suppression of the expression of IL-1 was observed at 24 and 72 hours when comparing low-dose tirilazad and the control group.
Adrenal Cortex Hormones↗
Synthesis of new steroidal isoxazoles: inhibitors of estrogen synthase.
A novel class of steroidal A/B ring isoxazoles have been prepared by two independent reaction schemes using 3 beta,17 beta-diacetoxyandrost-5-ene (1) and 3 beta,17 beta-diacetoxyandrost-4-en-6-one (4) as synthetic precursors. The key common intermediate in these syntheses, 3 beta,17 beta-diacetoxyandrost-4-eno[6,5,4-c,d] isoxazole (3), was prepared by synthetic methods described in both schemes. Further chemical modification of 3 yielded 3 beta,17 beta-dihydroxyandrost-4-eno[6,5,4-c,d] isoxazole (6), androst-3,17-dione-4-eno[6,5,4-c,d] isoxazole (7), and 17 beta-hydroxyandrost-3-one-4-eno[6,5,4-c,d] isoxazole (9). Human placental estrogen synthase (aromatase) bioassays were conducted to obtain the following IC50 values resulting from a 50% reduction of enzymatic activity: 6, 120.5 microM; 7, 1.889 microM. 9, 18.57 microM.
Aromatase Inhibitors↗
Nonsense surveillance in lymphocytes?
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Codon, Nonsense↗
Preparation and characterization of a cocrystalline suspension of [LysB28,ProB29]-human insulin analogue.
Soluble preparations of [LysB28,ProB29]-human insulin analogue (LysPro) exhibit more rapid absorption than human insulin upon subcutaneous injection. Biphasic mixtures of LysPro and intermediate-acting insulin suspensions could provide advantages over current preparations for the treatment of diabetes. To prepare biphasic mixtures of LysPro, a suspension formulation of the analogue is required. We have devised a method for crystallizing LysPro with the basic peptide protamine yielding neutral protamine LysPro (NPL) suspension. The crystallization conditions are strongly dependent on the precipitation procedure and temperature. Using various techniques, the crystalline and suspension characteristics of NPL are found to be similar to human insulin (neutral protamine Hagedorn, NPH) (8:1 molar ratio insulin:protamine, rod-shaped crystals, particle size of 4.0-6.0 microns, and Point of Zero Charge at 6.0-7.0). Using a dog model with NPL or NPH injected subcutaneously and glucose levels clamped at basal, NPL was found to have kinetic and dynamic responses analogous to human insulin NPH [Cmax (maximal insulin or LysPro concentration, ng/mL) of 2.61 +/- 0.22, NPL; 2.58 +/- 0.36, NPH, attained at Tmax (min) of 93 +/- 22, NPL; 145 +/- 33 NPH, and Rmax (maximal rate of glucose infusion, mg/kg min) of 10.8 +/- 1.2, NPL; 13.2 +/- 1.9, NPH, attained at TRmax (min) of 277 +/- 58, NPL; 265 +/- 38, NPH]. There are no statistically significant differences between the insulin curves or the glucose responses. These results provide insight into the mechanism of action of NPH suspensions and the relationship to duration of action. Furthermore, the formulation of a suspension of LysPro having an intermediate time-action makes possible the preparation of stable biphasic mixtures containing LysPro and NPL.
Analysis of Variance↗
Folate-mediated targeting of antisense oligodeoxynucleotides to ovarian cancer cells.
PURPOSE: Receptors for vitamin folic acid are frequently overexpressed on epithelial cancer cells, especially ovarian cancer cells. In this study, we examined whether this expression might be exploited to specifically deliver antisense oligodeoxynucleotides (ODN) to tumor cells. METHODS: A conjugate was prepared by directly coupling folic acid to the 3' terminus of an anti-c-fos ODN and its cellular uptake and tumor inhibitory effect were evaluated using FD2008 cells that overexpress folate receptors. RESULTS: When a phosphorothioate (PS)/phosphodiester (PO) chimeric ODN was conjugated with folic acid, its uptake by FD2008 cells was increased by about 8-fold (P < 0.01). In contrast, conjugation of folate to the ODN did not increase its uptake by CHO cells that lack the expression of FBP (P > 0.05). Furthermore, the increase in the uptake of conjugated ODN by FD2008 cells could be blocked by adding an excess amount of folic acid. The PS/PO antisense ODN had some inhibitory effect on the growth of FD2008 cells. However, its activity was significantly increased following conjugation with folic acid (P < 0.01). ODN of scrambled sequences with and without conjugation with folic acid failed to inhibit the growth of FD2008 cells. Finally, the antisense effect of the conjugated ODN on FD2008 cells was inhibited by an excess amount of free folic acid, suggesting that the sequence-dependent effect of folate-antisense ODN conjugate was mediated by folate binding protein. CONCLUSIONS: Direct derivatization of ODN with folate significantly improves their targeting efficiency to tumor cells in vitro. The folate-conjugated ODN, due to their small size and possibly efficient extravasation at tumor site, has the potential for treating solid tumors that overexpress folate receptors.
Animals↗
Genetic variation and phylogenetic relationships among six populations of corn borers in China.
The genetic variation among and within six populations of the corn borer was determined by using random amplified polymorphic DNA (RAPD) markers. Extensive genetic variability was detected. Of the 802 RAPD markers obtained, 781 (97.4%) were polymorphic among populations. Genetic similarities and distances between each pair of individuals were calculated. UPGMA cluster analysis showed that the YN population (Ostrinia nubilalis Hübner) and the other five populations (Ostrinia furnacalis Guenée) made up branches of the corn borer lineage, instead of deviating; there was no significant genetic differentiation between YN and the other five corn borer populations.
Animals↗
Characterization of cationic lipid-protamine-DNA (LPD) complexes for intravenous gene delivery.
A previous study has shown an efficient, systemic transgene expression in mice via intravenous administration of a LPD formulation composed of DOTAP liposomes, protamine sulfate and plasmid DNA. In this study, factors affecting the in vivo performance of this formulation were further evaluated. A protocol in which liposomes were mixed with protamine before the addition of plasmid DNA was shown to produce small condensed particles with a diameter of about 135 nm. These particles were stable over time and gave a high level of gene expression in all tissues examined including lung, heart, spleen, liver and kidney with the highest level of expression in the lung. Inclusion of dioleoylphosphatidylethanolamine (DOPE) as a helper lipid significantly decreased the in vivo activity of LPD. In contrast, inclusion of cholesterol as a helper lipid increased the in vivo transfection efficiency of LPD and more importantly, decrease the amount of cationic lipid required for the maximal level of gene expression. Studies on the interaction between mouse serum and LPD showed that LPD became negatively charged after exposure to serum, and LPDs containing different helper lipids varied in the amount of associated serum proteins. LPD containing DOPE was more enriched in a protein corresponding to albumin in molecular weight. These results suggest that the mechanism of LPD-mediated intravenous gene delivery might be different from that of in vitro lipofection and that serum protein association might be a major factor limiting the in vivo transfection by LPD.
Animals↗
Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and CALM-AF10 fusion cDNAs produced by the t(10;11)(p13-14;q14-q21) suggests a potential role for truncated AF10 polypeptides.
The t(10;11)(p13;q14-21) is a non-random translocation that occurs primarily in T cell acute lymphoblastic leukemias (T-ALL), but has also been observed in leukemias and lymphomas of diverse lineages. In U937, a cell line established from a diffuse histiocytic lymphoma, a t(10;11)(p13;q14-21) fuses AF10 to CALM. AF10 is also fused to MLL by a translocation that appears quite similar at the cytogenetic level, the t(10;11)(p12;q23). Fluorescence in situ hybridization studies have demonstrated that AF10 and CALM are also involved in other hematological malignancies containing t(10;11)(p13;q21), but no data are available concerning the molecular details of AF10-CALM fusion in primary leukemias. Using RT-PCR, we amplified multiple different isoforms of AF10-CALM and CALM-AF10 fusion cDNAs from a primary T cell ALL containing a t(10;11)(p13-14;q14-21). These cDNAs arose via alternative splicing of exons from both AF10 and CALM, which we demonstrated can also occur in the native genes. We identified at least two novel AF10 exons that can be included in wild-type and fusion cDNAs. The majority of the AF10 and AF10-CALM cDNA isoforms that we identified are predicted to encode for truncated AF10 polypeptides, raising the possibility that these might have important cellular functions in normal and malignant cells, perhaps by acting as dominant negative inhibitors of full-length AF10 or related proteins.
Adaptor Proteins, Vesicular Transport↗