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PubMed2003

Contrast-enhanced fluid-attenuated inversion recovery imaging for leptomeningeal disease in children.

BACKGROUND AND PURPOSE: To develop an MR imaging method that improves detection of leptomeningeal disease when compared with the current reference standard, contrast-enhanced T1-weighted imaging. METHODS: We investigated the cases of 10 children who were at high risk of intracranial leptomeningeal disease (Sturge-Weber syndrome and medulloblastoma). The cases of Sturge-Weber syndrome were investigated by using one MR imaging examination, and the cases of medulloblastoma were investigated by using four MR imaging examinations performed over 18 months. In all cases, contrast-enhanced fluid-attenuated inversion recovery (FLAIR) images were acquired in addition to the routine sequences. The parameters of the FLAIR sequence were chosen to maximize the T1 component of the signal intensity, to maximize detection of leptomeningeal enhancement. We made subjective and objective assessments of the presence and extent of leptomeningeal disease as shown on contrast-enhanced T1-weighted images and contrast-enhanced FLAIR images. RESULTS: In three of the four cases of Sturge-Weber syndrome, the T1 and FLAIR sequences showed comparable extent of leptomeningeal enhancement. For one child, FLAIR images showed unexpected bilateral disease and more extensive leptomeningeal enhancement on the clinically suspected side. In four of six cases of medulloblastoma, no leptomeningeal enhancement was shown on any examinations during the 18-month period. In two cases, FLAIR images showed more extensive leptomeningeal enhancement when compared with T1-weighted images. CONCLUSION: Contrast-enhanced FLAIR imaging seems to improve detection of leptomeningeal disease when compared with routine contrast-enhanced T1-weighted imaging. This seems to be partly because of suppression of signal intensity from normal vascular structures on the surface of the brain by FLAIR, which allows easier visualization of abnormal leptomeninges. We think that these findings can be extrapolated to the investigation of leptomeningeal disease of all causes and at all ages.

Cerebellar Neoplasms↗

PubMed2003

[Contrast enhanced fast fluid-attenuated inversion-recovery MR imaging for diagnosing cerebral venous angioma: report of two cases].

It has been reported that contrast-enhanced fluid-attenuated inversion-recovery (FLAIR) sequences were useful for detecting superficial abnormalities, such as meningeal disease, because they do not demonstrate contrast enhancement of cortical vessels with slow flow as do T1-weighted images. We reported the usefulness of contrast-enhanced FLAIR images to differentiate cerebral venous angioma from tumor in two patients. Case 1 was a 71-year-old man developed cortical hemorrhage. Post contrast-enhanced T1-weighted images showed an enhanced lesion around the hematoma, whereas contrast-enhanced FLAIR images showed no enhancement of the lesion, thus he was diagnosed as cortical hemorrhage from cerebral venous angioma. Case 2 was a 72-year-old woman, who was examined MR images because of the jugular foramen neurinoma. There was a T2-high-intensity lesion in the right frontal lobe, and post contrast-enhanced T1-weighted images showed an enhanced lesion in and around the T2-high-intensity lesion. Post-contrast FLAIR images showed no enhancement, and she was diagnosed as cerebral venous angioma. Contrast-enhanced fast FLAIR sequences was useful in differentiation between venous angiomas and tumors. Identification of these lesions was due to the flow-void phenomenon in vessels with slow-flowing blood such as venous angioma, which could not be differentiated from tumors on T1-weighted images.

Aged↗

PubMed2006

[Comparison by dynamic enhancement in spiral CT to differentiate peripheral squamous cell carcinoma from adenocarcinoma of the lung].

OBJECTIVE: To compare the manifestations of peripheral lung squamous cell carcinoma by CT dynamic enhancement with that of adenocarcinoma, and evaluate the difference of CT dynamic enhancement to distinguish peripheral lung squamous cell carcinomas from adenocarcinoma. METHODS: Thirty peripheral lung squamous cell carcinomas and 40 adenocarcinomas were examined with dynamic contrasted CT, enhancement at various phases recorded, based on which the time-intensity curves were produced. The enhancement patterns were compared and analyzed. RESULTS: There was no statistically significant difference in the enhancement degree and peak time between peripheral lung squamous cell carcinoma and adenocarcinoma (P > 0.05). The difference in enhancement pattern between these two different types of carcinoma was not statistically significant when the lesion was larger than 3 cm in diameter (P > 0.05), whereas it became statistically significant when the lesion is less than 3 cm (P < 0.05). Most of the squamous cell carcinoma showed heterogeneous enhancement or peripheral enhancement in the tumor zone, however, most of the adenocarcinomas had homogenous enhancement. CONCLUSION: The maximum enhancement and the peak time are not helpful in differentiating peripheral lung squamous cell carcinoma from adenocarcinoma. When the lesion is less than 3 cm in diameter, the enhancement pattern of peripheral squamous cell carcinomas is different from that of adenocarcinoma.

Adenocarcinoma↗

PubMedDate not supplied

MR imaging of the cranial meninges with emphasis on contrast enhancement and meningeal carcinomatosis.

MR imaging was used to investigate normal and abnormal meningeal enhancement, with an emphasis on meningeal carcinomatosis. Three groups of patients were studied on a 1.5-T system. In group 1, the normal meninges were examined in 20 patients and were found to show fine linear enhancement in short segments, especially in a parasagittal distribution. In group 2, all gadolinium-enhanced head scans were reviewed retrospectively. Abnormal meningeal enhancement was detected in 52 patients. In some of these, the enhancement was associated with pathologic conditions of the meninges, including leptomeningeal tumor and meningeal infections and other inflammatory conditions; in others the enhancement was adjacent to subdural hematomas, subacute infarcts, and skull lesions, such as metastases or postoperative defects. In group 3, 30 cases of meningeal carcinomatosis were studied prospectively. Enhancement was seen in approximately two-thirds of cases and usually was quite diffuse and applied to the inner table of the skull. Frank nodules were seen less often. Contrast-enhanced CT was equal to MR in the detection of nodules but was nearly always unable to show diffuse meningeal enhancement against the inner table of the skull. Contrast-enhanced MR was more sensitive than contrast-enhanced CT in the examination of normal and abnormal meninges. Abnormal findings, such as meningeal carcinomatosis, were demonstrated more often by MR than by CT.

Adolescent↗

PubMed1994

Differential interaction of the dual alpha tropomyosin/N5 enhancer with multiple DNA binding proteins: N5 is a putative novel z-ZIP DNA binding protein.

The alpha tropomyosin (TM)/N5 enhancer is an SV40-like mammalian enhancer comprised of a 99 bp repeat with modular cis-acting regulatory elements exhibiting apparent hierarchical organization. The enhancer differentially regulates the alpha TM and N5 transcription units which exhibit distinct tissue-specific expression patterns and interacts with multiple myotube-associated nuclear DNA binding proteins that varied in size and amount. To further characterize the interaction with multiple myotube nuclear factors, comparative southwestern blot analyses were done with a panel of strategic DNA probes representative of modular enhancer sequences in the alpha TM/N5 enhancer and respective alpha TM and N5 promoter regions. Results demonstrate that multiple DNA binding proteins, which vary in size and amount, can interact with a particular enhancer modular sequence (delimited to 18 bp- to 38 bp-long); and that likewise, a DNA binding protein can bind specifically to different DNA enhancer modular sequences with apparent different affinities. Results also demonstrate DNA binding proteins that differentially bind to both enhancer modular sequences and respective promoter regions supporting a putative parsimonious mechanism for the approximation of enhancer and promoter elements as an alternative to the multi-protein stereospecific enhancer complex. Cogent to this interesting "head to head"/shared enhancer gene arrangement, we investigated the primary structure of the "other" transcription unit, N5. Nucleotide sequence analysis of the N5 cDNA reveals that it is a putative DNA binding protein representing a new structural class of transcription factors exhibiting a novel combinatorial motif: single zinc finger (DNA-binding)-leucine zipper (dimerization)--making it a z-ZIP instead of a b-ZIP (basic region/leucine zipper) protein.

Amino Acid Sequence↗

PubMed1993

The role of viral enhancer "core" motif-related sequences in regulating T cell receptor-gamma and -delta gene expression.

T cells express clonally distributed alpha beta or gamma delta Ag receptor heterodimers. Transcriptional enhancers for the genes of all four subunits are active in both gamma delta and alpha beta T cells, but are less active or inactive in other cells. Conserved sequence motifs are present in all four enhancers, suggesting that common transcription factors regulate TCR gene expression. One of these motifs in the gamma 3 site of the TCR-gamma enhancer is similar to motifs found in several other lymphoid-specific and viral enhancers. This conserved "core" sequence is present in the enhancers of Moloney and SL3-3 murine leukemia viruses, important for transcription in T cells and in determining disease specificity. Here we characterize the gamma 3 site of the gamma enhancer and a corresponding homologous site, delta E3, of the TCR-delta enhancer. Our results suggest that the core site is critical for activity of the 200-bp gamma enhancer fragment and of the gamma 3 and delta E3 sites. Furthermore, we identify a nuclear factor in human T cell lines that specifically binds the core region in these and several other core-containing enhancers. This factor may be identical to or related to a purified bovine nuclear core binding factor that binds the core region of the Moloney murine leukemia virus enhancer, gamma 3 and delta E3 sites, suggesting that similar proteins regulate the TCR-gamma, delta and Moloney murine leukemia virus enhancers. Other sequences in the gamma 3 site upstream of the core sequence are also critical for activity in T cells, suggesting that at least two different factors are required for functional activity of the gamma 3 site.

Animals↗

PubMed1988

Structure-activity relationship of 1-alkyl- or 1-alkenylazacycloalkanone derivatives as percutaneous penetration enhancers.

Nine azacycloalkanone (5-, 6-, or 7-member ring) derivatives with an alkyl or alkenyl (terpene) chain (10, 15, or 20 carbons) were compared with 1-dodecylazacycloheptan-2-one (azone, 1) for their effects on the percutaneous penetration of 6-mercaptopurine (6-MP) through excised guinea pig skin. Pretreatment of skin with an enhancer markedly increased penetration and skin accumulation of 6-MP. Superior enhancing effects were observed for enhancers having a terpene chain of 10 carbons and an azacyclo ring with one carbonyl group. Enhancers with a C20 tail chain were less effective. Enhancer ring size had little effect on enhancing activity, whereas the increase in the number of carbonyl groups in the ring caused a decrease. Computer fitting of a penetration profile to Fick's diffusion equation gave two parameters corresponding to diffusion and partitioning of 6-MP. The diffusion parameter was little affected by pretreatment with an enhancer, whereas the partition parameter was markedly increased. This suggests that enhancement is determined by the ability to increase the drug partitioning into the skin and to enlarge the drug concentration gradient in the skin barrier. The primary skin irritation was examined with rabbit dorsal skin in vivo. The enhancers with an alkyl chain induced severer primary irritation (erythema and edema) than those with an alkenyl chain. From the balance between enhancing and irritating activities, it is concluded that 1-geranylazacycloheptan-2-one, 1-farnesylazacycloheptan-2-one and 1-farnesylazacyclopentan-2-one are favorable enhancers.

Animals↗

PubMed1995

Human skin permeability enhancement by lauric acid under equilibrium aqueous conditions.

An in vitro method was developed to investigate the enhancement of hydrocortisone transport across human stratum corneum (SC) by a model enhancer, lauric acid, in aqueous solutions under equilibrium conditions with respect to the enhancer. In contrast to classical (i.e., nonequilibrium) loading techniques, in which the enhancer is applied only to the donor side of SC either in pure form or in an organic solvent while enhancer-free aqueous buffers are placed in the receptor phase, this method allowed the investigation of pH effects, concentration effects, and reversibility of both enhancer uptake and enhancement of drug transport under thermodynamically well-defined conditions. The SC-buffer partition coefficients for lauric acid were linear with concentration and sigmoidal with pH, suggesting that both the neutral species and laurate anion partition into SC. Comparisons of partition coefficients in delipidized and untreated SC as a function of pH indicated that the uptake of lauric acid in neutral form is governed primarily by the lipid domain, whereas the protein domain accounts for anion uptake. The effects of lauric acid on skin permeability were > 80% reversible upon extraction of the enhancer from the membrane. However, the degree of enhancement of hydrocortisone permeability was nonlinearly dependent on the equilibrium concentration of lauric acid in either the aqueous buffer or the membrane, exhibiting thresholds in the appearance of enhancement with concentration. The enhancer concentration necessary to achieve isoenhancement of about 6-fold varied from approximately 1 x 10(-5) M at pH < pKa to approximately 1 x 10(-2) M at high pH (pH > 8) demonstrating the higher influence of the free acid species.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

PubMed2000

In situ and minimally invasive breast cancer: morphologic and kinetic features on contrast-enhanced MR imaging.

PURPOSE: This retrospective study was undertaken to investigate the morphologic and dynamic features of in situ and minimally invasive breast cancer on contrast-enhanced (c.-e.) MR imaging and to examine possible associations to pathology features. MATERIAL AND METHODS: A total of 71 patients underwent MR imaging. T1-weighted FLASH-3D images were obtained before and after intravenous administration of Gd-DTPA. Histopathologic analysis of 78 lesions revealed ductal carcinoma in situ (DCIS) n = 50 and DCIS with microinvasion n = 28. MR features were correlated with histopathologic findings. RESULTS: Enhancement in DCIS was focal (73%), diffuse (10%) or ductal (17%). No enhancement occurred in two cases (4%). In 65% enhancement speed was classified as delayed. There was a tendency toward a more ill-defined (83 vs. 43%) enhancement pattern in high grade DCIS and a more ductal (29 vs. 12%) and faster (50 vs. 29%) enhancement in comedo type DCIS. However, significant differences in the enhancement behaviour could neither be demonstrated between high grade and non high grade DCIS nor between comedo and non comedo type DCIS. No significant differences were noted between pure and microinvasive DCIS. CONCLUSION: In this retrospective analysis the majority (96%) of DCIS lesions show contrast enhancement. However, in only about 50% of DCIS the criteria of a so-called 'typical' enhancement behaviour was fulfilled, that means strong, early, focal ill-circumscribed or ductal. Enhancement that follows a duct is often associated with malignancy, however this feature was only present in 17% of the cases. c.-e. MR imaging allowed the detection of 25 additional foci of DCIS. Therefore malignant in situ lesions can be present with atypical enhancement, and should be taken into consideration in high-risk patients in particular.

Adult↗

PubMed2006

The enhancement of the subacute repeat dose toxicity test OECD TG 407 for the detection of endocrine active chemicals: comparison with toxicity tests of longer duration.

The OECD conventional 28-day repeat dose toxicity test (OECD TG 407) is widely employed in the initial hazard identification and characterization for commercial chemicals. The OECD has recently undertaken an international effort to "enhance" the conventional 28-day repeat dose toxicity test (OECD TG 407) in order to ensure that chemicals acting through (anti)estrogenic, (anti)androgenic, and (anti)thyroid mechanisms are identified. The enhancements include additional parameters based on the respective target organs from the male and female reproductive tracts, the thyroid, and circulating hormone levels. Ten chemicals with known endocrine modes of action and different potencies were administered using the "enhanced TG 407" test protocol to investigate the performance of this procedure. In the present evaluation, these "enhanced TG 407" protocol results, drawn from a report of the OECD validation studies, are compared to studies of the same or similar chemicals with longer and/or in utero exposures in order to evaluate the capability of the this "enhanced TG 407" in identifying the chemicals' mode of action. The major conclusions that can be drawn from these comparisons are: 1. The "enhanced TG 407" will reliably identify chemicals with a strong to moderate potential to act through endocrine modes of action on the gonads and the thyroid. In addition, this test method gives a first indication for the dose-related potency. 2. Substances with a low potency for an endocrine mode of action, i.e., having only marginal effects in the most comprehensive in vivo studies such as multi-generation studies, may not elicit clear endocrine-related effects in the "enhanced TG 407". In these cases, the primary or principal effects observed will be driven by other toxic actions of the test materials in the "enhanced TG 407". 3. It may be concluded from the present database that prolongation of exposure from 28 days up to 90 days is unlikely to improve the chance of detecting an endocrine-mediated effect 4. A number of higher tier studies with in utero and pubertal exposure show that prenatally exposed rats may be more sensitive to exposures to compounds with very low estrogenic or antiandrogenic potential in some cases than young adult rats as used in the "enhanced TG 407". 5. Overall, these comparisons support the use of the "enhanced TG407" for the detection of endocrine active chemicals. It is therefore recommended to fully accept the enhancements and include them in the test method for toxicological and regulatory use.

Animals↗

PubMed2001

Synovial sarcoma: dynamic contrast-enhanced MR imaging features.

OBJECTIVE: To determine whether previously described so-called malignant dynamic contrast-enhanced magnetic resonance (MR) imaging features--early start, peripheral enhancement and early plateau or washout phase--occur consistently in synovial sarcoma. DESIGN AND PATIENTS: Dynamic contrast-enhanced MR images of 10 patients with histologically proven synovial sarcoma were reviewed. The start, pattern and progression of tumor enhancement were assessed and correlated with histopathology. RESULTS: In all patients, the time interval between arterial and early tumor enhancement was less than 7 s (mean 4.40 s, SD 2.09 s). Six synovial sarcomas showed enhancement with a subsequent rapidly progressive linear increase in signal intensity followed by a plateau in one lesion and washout in five. Four lesions showed a late sustained increase in enhancement after the initial rapid increase in enhancement. The pattern of initial enhancement was peripheral in only two lesions, diffuse in four and heterogeneous in four lesions. CONCLUSIONS: Enhancement of tumor within 7 s after arterial enhancement is, of the three parameters described previously, the only sign that occurs consistently in synovial sarcoma.

Adolescent↗

PubMed2006

The dependence of force enhancement on activation in human adductor pollicis.

It has been well recognized that the steady-state isometric force after active muscle/fiber stretch is greater than the corresponding isometric force for electrically stimulated muscles and maximal voluntary contractions (MVC). However, recent evidence obtained for sub-MVC suggests that force enhancement properties are different from those observed for electrically induced and MVC. Specifically, it appears that force enhancement is activation-dependent and that there is a subject-specific threshold for force enhancement in sub-MVC. To address these suggestions, the relationship between force enhancement and voluntary activation during stretch was investigated in 11 healthy subjects. Human adductor pollicis muscles were studied and force enhancement was measured while muscle activation during the steady-state isometric phase was controlled at a level of 30% of MVC. In order to study the effects of activation on force enhancement, subjects performed stretch contractions at 0, 10, 30, 60, and 100% of maximal voluntary effort while the steady-state isometric force after stretch, obtained at 30% of activation in all cases, was compared to the corresponding values measured in the isometric reference contractions. There was no force enhancement if muscle stretching occurred passively but all subjects showed force enhancement when muscle stretching occurred at maximal voluntary effort. When increasing the level of activation during the stretch phase, force enhancement increased, and the number of subjects who showed force enhancement increased as well. We conclude from these results that force enhancement during voluntary contractions is activation-dependent with a threshold that is subject-specific.

Adaptation, Physiological↗

PubMed2005

Contrast-enhanced sonography of pancreatic carcinoma: correlations with pathological findings.

BACKGROUND: We examined contrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma in relation to the pathological findings in resected specimens to evaluate correlations between observations made by this modality and the pathological findings. METHODS: The pathological findings of surgical specimens obtained from 16 patients were examined in relation to the contrast-enhanced harmonic gray-scale sonography findings. Lesion vascularity was examined by contrast-enhanced harmonic gray-scale sonography from 20 to 50 s after the injection of Levovist (Schering, Berlin, Germany) (early phase), and lesion enhancement was also monitored at approximately 90 s after injection (delayed phase). RESULTS: Contrast-enhanced harmonic gray-scale sonography showed positive enhancement in 12 of the 16 lesions (peripheral tumor region alone, n = 9; entire tumor, n = 3), while the other 4 lesions showed no contrast enhancement in any region. Twelve enhanced regions (9 peripheral tumor region and 3 entire tumor regions) detected by contrast-enhanced harmonic gray-scale sonography showed: (1) mild fibrosis with inflammation, in 10 regions (83%); (2) the presence of both carcinoma cells and residual acinar cells in 8 (67%); and (3) presence of relatively large arteries in 2 (17%). In contrast, 13 non-enhanced regions (4 entire tumor regions and 9 central regions) showed: (1) severe fibrosis in 10 regions (77%); (2) necrosis in 7 (54%); and (3) mucin in 4 (31%). CONCLUSIONS: Contrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma are influenced by interstitial histological features associated with tumor growth.

Aged↗

PubMed1985

Evolution of alloantibodies and suppressor cells in allografted mice treated for passive enhancement.

The kinetics and quality of the alloimmune reaction were studied in CBA (H-2k) mice treated for passive enhancement of tumor allografts (Sa 1 indigenous of A/J (H-2a or H-2k/d) mice). Serum samples of treated animals were tested for their biological properties relevant to different antibody isotypes in vitro (hemagglutination, complement-dependent cytotoxicity, and anaphylaxis, i.e., mast cell degranulation involving all main Ig isotypes; IgM, IgG2, and IgG1, IgE, respectively) as well as in vivo (allograft enhancement). Spleen cells from these treated animals were examined for their capacity to interfere with the rejection of tumor allografts by adoptive transfers into syngeneic recipients. In vitro, 51Cr release cytolysis assays were performed in order to test their cytolytic and regulatory activities in comparison to rejecting control animals. It has been shown that: grafted mice, pretreated for passive enhancement, kept their grafts longer and synthetized anaphylactic antibodies (mainly IgG1) earlier and at higher titers than normal serum controls, which rejected the same Sa 1 allografts. Mice with enhanced tumors synthetized cytotoxic antibodies (mainly IgG2) later than rejecting controls. Serum samples from treated and control animals, harvested 10 days (early sera) and 30 days (late sera) after grafting, were injected with a "normal dose" (0.2 ml) and a "high" dose (0.4 ml) to new CBA recipients grafted with Sa 1. Early immune sera were only enhancing at high doses when derived from animals previously treated for enhancement (at the low dose both immune sera were enhancing). Late sera, presenting both complement-fixing, cytotoxic (predominantly IgG2), and IgG1 anaphylactic alloantibodies in the two groups, induced enhancement in all cases, but more strongly when derived from the group treated for Sa 1 enhancement. Adoptive transfer of spleen cells from animals treated for passive enhancement were able either to inhibit the accelerated rejection (Day 10) or to promote enhancement of Sa 1 allogeneic cells (Day 30) while similar cells taken (Day 10 and Day 30) from control graft-rejecting mice transferred accelerated rejection. Among the transferred T-cell sub-populations, the suppressive effect was mediated by Lyt 2 T cells. In vitro, these spleen cells showed a weaker cytolytic activity than those of allograft-rejecting mice. Moreover, they were able to regulate the cytolytic activity of cytotoxic effector cells from specifically immunized CBA mice.

Animals↗

PubMed1988

The biological activity of hydrogen peroxide. IV. Enhancement of its clastogenic actions by coadministration of L-histidine.

An enhancing effect of L-histidine (L-His) was detected on the induction by hydrogen peroxide (H2O2) of chromosomal aberrations of both the chromosome type and the chromatid type, in human embryonic fibroblasts. The maximum efficiency of induction was about 8-fold higher in the presence of L-His than in the presence of H2O2 alone, at a concentration of L-His of 50 microM. D-His and DL-His showed lower enhancing effects than L-His, with approximately 2-fold and 5-fold enhancement of induction of chromosomal aberrations, respectively. L-Histidinol and L-His-methyl ester, among various derivatives of L-His tested, also enhanced this process. However, the effects of these derivatives were smaller than those of L-His in a range of concentrations equivalent to that of the most effective dose of L-His (50 microM), while they produced greater enhancement than L-His at concentrations higher than 200 microM. Other derivatives of L-His, such as L-carnosine, urocanic acid, imidazolepyruvic acid, 1-methyl-L-His, imidazolelactic acid, imidazoleacetic acid and histamine and imidazole itself did not enhance the frequency of chromosomal aberrations induced by H2O2. These results indicate that at least both the imidazole ring and the amino group are essential components of the chemical structure of L-His required for the enhancing effect. Moreover, in order to cause such an enhancing effect, L-His had to be applied together with H2O2 to cells, because the enhancing effect of L-His was not observed with cells which were washed after pretreatment with L-His. The preliminary study suggested that this enhancing effect depends on the His-peroxide adduct derived from L-His and H2O2. None of the amino acids tested other than His produced any enhancing effect on the induction of chromosomal aberrations by H2O2.

Amino Acids↗

PubMed1986

Enhancement of UV survival, UV- and MMS-mutability, precise excision of Tn10 and complementation of umuC by plasmids of different incompatibility groups.

29 conjugative resistance and colicin plasmids from 19 different incompatibility (Inc) groups were examined for their ability to enhance post-ultraviolet (UV) survival and UV- and methyl methanesulfonate(MMS)-induced mutability in Salmonella typhimurium LT2 strains. 14 Muc+ plasmids enhanced each of the survival and mutation-related properties tested, while 14 Muc- plasmids showed no enhancing effects in any tests. One Muc+ plasmid, pRG1251 (IncH1), enhanced post-UV survival and each of the mutation-related properties tested, except MMS-induced mutagenesis. Two further noteworthy plasmids, R391 (IncJ) and R394 (IncT), produced apparent strain-dependent effects in S. typhimurium which differed from those reported to have been found in Escherichia coli. Plasmid R391 enhanced post-UV survival in S. typhimurium, in contrast to its UV-sensitizing effects in E. coli. In both hosts plasmid R391 enhanced UV- and MMS-induced mutagenesis. Plasmid R394 had no enhancing effects on UV survival or UV- and MMS-induced mutagenesis in S. typhimurium, in contrast to its reported enhancement of MMS-induced mutagenesis in E. coli. Conjugal transfer of R394 to E. coli strain AB1157 and assays of mutagenesis-related traits supported results observed in S. typhimurium. Muc+ plasmids were found to enhance the frequency of precise excision of the transposon Tn10 when inserted within hisG or trpA in S. typhimurium strains. Precise excision could be further enhanced in S. typhimurium by UV-irradiation. Analysis of Tn10 mutants with altered IS10 ends indicated that intact inverted repeats at the ends of Tn10 were required for efficient enhancement of precise excision.

Bacterial Proteins↗

PubMed2005

Effects of ionization and penetration enhancers on the transdermal delivery of 5-fluorouracil through excised human stratum corneum.

The purpose of this study was to determine the effects of ionization and penetration enhancers on the transdermal delivery of 5-fluorouracil (5-FU) through excised human stratum corneum. The in vitro transport of 5-FU was determined at three physiologically relevant pH values of 5.0, 7.4 and 8.0, and in the presence of suitable penetration enhancers, namely Azone (AZ), lauryl alcohol (LA), and isopropyl myristate (IPM). The results showed that passive permeation of 5-FU is dependent upon the pH of the donor solution, although did not fully conform to the pH-partition hypothesis. A further analysis of data suggested an inverse relationship (i.e., negative correlation) between steady-state flux and aqueous solubility of 5-FU at these pH values (correlation coefficient = -0.4205), although correlation was not statistically significant (p = 0.7237). In the absence of a penetration enhancer, the in vitro permeability of 5-FU was quite low (0.82+/-0.06 x 10(4) cm/h). This delivery rate was enhanced by approximately by 3, 4 and 24-fold, respectively, when IPM, LA, and AZ were incorporated into the donor solution. All these enhancements were statistically significant (p < 0.05) compared to control, and occurred regardless of the polarity (solubility parameters) of these enhancers. Out of three examined enhancers, AZ appears to be a suitable enhancer for enhancing transport of 5-FU, which merits in vivo investigation in a suitable animal model. Possible mechanisms of enhancement by these penetration enhancers are also discussed.

Administration, Cutaneous↗

PubMed2005

The role of passive structures in force enhancement of skeletal muscles following active stretch.

We recently found that force enhancement following active stretch in skeletal muscles is accompanied by an increase in passive force following deactivation (J. Exp. Biol. 205 (2002) 1275). However, it is not known if this increase in passive force contributes to the force enhancement observed in the active muscle, and if it is observed at all muscle lengths. The purposes of this study were to quantify the amount of passive force increase as a function of muscle lengths, and to determine if this passive force contributes to the force enhancement observed in the active muscle. Experiments were performed on cat soleus (n = 24) using techniques published previously (J. Biomech. 30(9) (1997) 865). Conceptually, tests involved comparisons of force enhancement and passive force increase for a variety of stretch tests in soleus. Furthermore, in one test, activation of the soleus was interrupted for 1s in the force-enhanced state, and soleus was then re-activated. We found that total force enhancement and passive force increase were positively correlated for all test conditions, that passive force increase following stretch of the active soleus only occurred at muscle lengths corresponding to the descending limb of the force-length relationship, that increases in passive force for a given stretch magnitude became greater at long muscle lengths, and that upon reactivation, there was a remnant passive force enhancement. We conclude from these results that the passive force enhancement following stretch of an active muscle contributes to the total force enhancement, that this passive contribution increases with increasing muscle length, and that there must be at least one other factor than passive force increase that contributes to the total force enhancement, as the passive force increase was always smaller than the total force enhancement. A by-product of this investigation was that we observed a shift in the passive force-length relationship that was dependent on muscle activation, stretch magnitude and muscle length. Therefore, the passive force-length relationship is not a constant property of skeletal muscle, but depends critically on the muscle's contractile history.

Animals↗