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PubMed1971

Regulation of the immune response: suppressive and enhancing effects of passively administered antibody.

The ability of passively administered antibody to suppress the immune response against homologous antigenic determinants while concomitantly enhancing the response against other unrelated determinants of the same antigen molecule has been established in two distinct antigen-antibody systems: (a) guinea pig gamma(2)-immunoglobulin + passive anti-F(ab')(2) antibody, where suppression of anti-F(ab')(2) antibody synthesis is accompanied by enhancement of the anti-Fc response; and (b) human secretory IgA + passive anti-serum IgA antibody, where suppression of antibody production against the alpha and L chains accompanies augmentation of the response to the secretory component. The mechanisms of the suppressive and enhancing effects are probably unrelated for the following reasons: (a) Enhancement of the response to certain determinants may be obtained without discernible suppression of the response to the homologous determinants; and (b) the F(ab')(2) fragments of passive antibody can mediate immune suppression but were not observed to enhance the response against the unrelated determinants of the same antigen molecule. Also, the timing for achieving maximum suppression or enhancement of antibody formation is not the same; enhancement was obtained only at a later time. Both the enhancement and suppressive effects were obtained with the purified gammaG fraction of antisera. This finding rules out an exclusive role of gammaM antibody in the enhancement phenomenon.

Animals↗

PubMed2002

Immune-specific immunoglobulin G-mediated enhancement of human immunodeficiency virus-induced IFN-alpha production.

Interferon-alpha (IFN-alpha) is synthesized as an integral part of innate immunity to viral infection. We previously provided preliminary evidence that antibody-containing serum from HIV-infected individuals enhanced HIV-induced production of IFN-alpha. Subsequently, preparations of pooled human immunoglobulin G (IgG) have also been shown to enhance poliovirus (PV)-induced IFN-alpha production. The current work establishes IgG as the serum mediator that enhances induction of IFN-alpha by HIV. Our studies also establish the ability of sera from individual subjects to enhance PV-induced IFN-alpha production. HIV-induced IFN-alpha production was enhanced maximally by >4000-fold and by an average of 25-fold. Sera from 74 people enhanced PV- induced IFN-alpha from undetectable levels to an average of 615 units (range 7-4679 units). The ability of individual sera to enhance IFN-alpha production by HIV and PV persisted undiminished in patients with AIDS. IgG-mediated enhancement of IFN-alpha production was similar to that induced by IgG and PV and was blocked by IgG Fc fragments. Demonstration of the selective enhancement of HIV-induced IFN-alpha production by IgG from HIV-seropositive individuals provides further evidence for the existence of antigen-specific upregulation of a critical component of innate antiviral immunity by the adaptive Th2 immune response.

Adult↗

PubMed1982

Transcriptional 'enhancers' from SV40 and polyoma virus show a cell type preference.

Transcriptional "enhancers" have been identified in both the monkey virus SV40 and in the mouse polyoma virus. Here we report that these enhancers show a cell type preference. This was done, (i) by assaying for T antigen expression and viral DNA replication of polyoma DNA which contains its own enhancer or the enhancer of SV40 virus, and (ii) by linking either of the two enhancer elements to the rabbit beta 1-globin gene and measuring transient globin expression in mouse and primate cells. The results were consistent in all the assays: In mouse cells the polyoma enhancer is slightly more effective than the SV40 enhancer. However, in primate cells the SV40 enhancer induces a four to six fold higher level of gene expression than does the polyoma enhancer.

Animals↗

PubMed1997

An investigation of the relationship between ultrasound echo enhancement and Doppler frequency shift using a pulsatile arterial flow phantom.

RATIONALE AND OBJECTIVES: Based on the echo-enhancing effect of microbubbles, various agents have been developed to improve the diagnostic confidence in patients with inadequate Doppler signals. In the clinical trials of the echo enhancer Levovist, there were a few isolated cases in which the maximum flow velocities of the enhanced Doppler spectra appeared to higher than the velocities in the nonenhanced baseline spectra. This raised the concern that echo enhancement could give a false indication of maximum flow velocity. This study investigated whether a systematic association between echo enhancement and velocity shift exists. METHODS: A pulsatile flow phantom that simulated the elasticity of blood vessels and the acoustic attenuation of extravascular tissue was used to compare enhanced with unenhanced Doppler spectra under accurately reproducible flow conditions. The experiments were carried out with varied sound attenuation and evaluated with dedicated spectral analysis software that included a special averaging tool. RESULTS: Levovist enhanced the Doppler signal by 16 to 31 dB, and the enhanced and unenhanced power spectra presented identical distribution of spectral power density under all flow conditions. CONCLUSIONS: The measurements gave no evidence that echo enhancement with Levovist falsifies the Doppler measurement of flow velocity.

Blood Flow Velocity↗

PubMedDate not supplied

Differential diagnosis of early homogeneously enhancing hepatocellular carcinoma and hemangioma by two-phase CT.

PURPOSE: Our goal was to differentiate between early homogeneously enhancing hepatocellular carcinoma (HCC) and hemangioma by two-phase CT. METHOD: Two phase images of 51 HCCs and 28 hemangiomas showing homogeneous high attenuation in the first series (arterial dominant phase) were reviewed. Enhancement patterns of the lesions in the second series (parenchymal phase) were classified as homogeneous high, peripheral high, iso-, and low attenuation. The attenuation values of all and the enhancement values of some (21 HCCs and 18 hemangiomas) in the first series were calculated. RESULTS: Although low and peripheral high attenuation patterns were seen during the second series only in HCCs (n = 35), which could be used to correctly diagnose HCC, other nonspecific patterns were demonstrated in both HCCs (n = 16) and hemangiomas (n = 28). The attenuation values of 49 of the 51 HCCs and 5 of the 28 hemangiomas were below 130 HU on the first series. The enhancement values of all 21 HCCs and 3 of 18 hemangiomas were below 70 HU. Combining the enhancement patterns with a borderline attenuation value of 130 HU or borderline enhancement value of 70 HU yielded overall accuracies of 94 and 92%, respectively. CONCLUSION: The combined criteria (enhancement pattern plus attenuation or enhancement value) were useful for differentiating between early homogeneously enhancing HCCs and hemangiomas.

Adult↗

PubMedDate not supplied

Does contrast enhancement on CT suggest tumor response for chemotherapy in small cell carcinoma of the lung?

PURPOSE: The purpose of this article is to assess the correlation between contrast enhancement on CT and the tumor reduction ratio in small cell carcinoma of the lung after first-line chemotherapy. MATERIALS AND METHODS: Twenty-eight patients with small cell carcinoma of lung underwent preenhancement and postenhancement CT scans before and after first-line chemotherapy, followed by second-line chemotherapy in 7 patients who had relapsed. The authors retrospectively analyzed the correlation between the tumor reduction ratio and the CT numbers of contrast enhancement in each case by multiple regression analysis using SPSS. RESULTS: The mean tumor-reduction ratio was 58.2 +/- 43.2% after first-line chemotherapy, and the mean CT enhancement was 33.2 +/- 11.0 Hounsfield units (HU). The correlation coefficient between the tumor reduction ratio and the CT numbers of contrast enhancement was 0.57 (r = 0.32), and p value was < 0.002. After chemotherapy, more than 90% tumor reduction was seen in 11 patients. They revealed an average 41.9 +/- 7.6 HU tumor enhancement. Less than 50% tumor reduction was seen in 10 patients. They revealed an average 26.2 +/- 7.9 HU tumor enhancement. If these criteria of 30 HU contrast enhancement and 80% tumor reduction ratio were applied as a guide for chemotherapy response, the sensitivity, specificity, positive predictive value, and negative predictive value would be calculated as 85.7%, 84.6%, 85.7%, and 84.6%, respectively. CONCLUSION: In small cell carcinoma of the lung, it is statistically proven that the more enhanced tumor on CT, the better response to chemotherapy. Tumor enhancement of 30 HU is a suggestive guide for chemotherapy response in patients with small cell carcinoma.

Aged↗

PubMedDate not supplied

Role of fluid-attenuated inversion recovery in the diagnosis of meningitis: comparison with contrast-enhanced magnetic resonance imaging.

OBJECTIVE: Fluid-attenuated inversion recovery (FLAIR) has shown promise in the detection of subarachnoid space disease. The exact role of FLAIR in the diagnosis of meningitis has not been established. The purpose of this study was to evaluate FLAIR in the detection of meningitis in comparison with contrast-enhanced T1-weighted images (T1WI) in a blinded-reader study. We describe hyperintense sulci (HS) on FLAIR sequence in meningitis in relation to cerebrospinal fluid (CSF) protein and effective echo time (TE). METHODS: Two observers blinded to clinical information reviewed magnetic resonance (MR) images of patients with the diagnosis of meningitis and those of age-matched controls. The diagnosis was confirmed from chart review and CSF results. FLAIR images were obtained with 2 different TE values of 120 milliseconds and 150 milliseconds. FLAIR changes were correlated with CSF protein concentration and contrast-enhanced T1WI. RESULTS: Twenty-eight MR images of meningitis patients were reviewed. There were 23 abnormal MR images including 16 abnormal FLAIR scans with hyperintense sulci and 23 with leptomeningeal enhancement on contrast-enhanced T1WI. HS on FLAIR correlated with leptomeningeal enhancement on contrast-enhanced T1WI. Four viral and 1 bacterial meningitis had normal MR images (FLAIR and postcontrast TIWI). Two different TE values were used: 120 milliseconds (n = 15) and 150 milliseconds (n = 13). All patients with effective TE of 150 milliseconds. and CSF protein of more than 132 mg/dL had hyperintense sulci whereas patients with effective TE of 120 milliseconds and CSF protein of 257 mg/dL or more had HS. CONCLUSIONS: The sensitivity of contrast-enhanced T1WI was higher than FLAIR. HS on FLAIR correlated with contrast enhancement on T1WI. However, the sensitivity of FLAIR depends on CSF protein concentration threshold for (CSF hyperintensity) for a given effective TE. FLAIR cannot replace contrast-enhanced T1WI in diagnosing meningitis.

Adolescent↗

PubMed2004

Aortoiliac gadolinium-enhanced CT angiography: improved results with a 16-detector row scanner compared with a four-detector row scanner.

PURPOSE: To assess the level of vascular enhancement of gadolinium-enhanced aortoiliac computed tomographic (CT) angiography with a 16-detector row CT scanner and to compare it with the results of previous similar studies that used four-detector row CT units. MATERIALS AND METHODS: Eleven gadolinium-enhanced CT angiograms were obtained in 10 consecutive patients with contraindication to iodinated contrast medium with use of a 16-detector row CT scanner. In the region of interest, attenuation measurements (in HU) were obtained from the proximal abdominal aorta to the common femoral arteries during unenhanced, gadolinium-enhanced, and delayed acquisitions. The results were compared to those in the 15 consecutive patients who most recently had similar examinations performed on a four-detector row CT unit. Phantom studies with diluted gadolinium were conducted to compare attenuation between CT units. RESULTS: On four-detector row CT, throughout the scan length, mean enhancement values were 53.8 HU +/- 5.3 and 15.0 HU +/- 2.6 for gadolinium-enhanced and delayed series, respectively. For the 16-detector row CT unit, they were 76.1 HU +/- 3.4 and 21.3 HU +/- 1.3, respectively. As a result of a shorter scan time and a more optimal start time, the 16-detector row CT unit provided significantly greater and more consistent enhancement throughout the scan length compared with the four-detector row CT unit (P =.0106). Similar structures had significantly greater enhancement when 120 kV was applied instead of 140 kV (P =.0495) CONCLUSION: The 16-detector row CT scanner improved gadolinium-enhanced CT angiography results compared with the four-detector row CT unit.

Aged↗

PubMed2005

Population dynamics and potential of fisheries stock enhancement: practical theory for assessment and policy analysis.

The population dynamics of fisheries stock enhancement, and its potential for generating benefits over and above those obtainable from optimal exploitation of wild stocks alone are poorly understood and highly controversial. I review pertinent knowledge of fish population biology, and extend the dynamic pool theory of fishing to stock enhancement by unpacking recruitment, incorporating regulation in the recruited stock, and accounting for biological differences between wild and hatchery fish. I then analyse the dynamics of stock enhancement and its potential role in fisheries management, using the candidate stock of North Sea sole as an example and considering economic as well as biological criteria. Enhancement through release of recruits or advanced juveniles is predicted to increase total yield and stock abundance, but reduce abundance of the naturally recruited stock component through compensatory responses or overfishing. Economic feasibility of enhancement is subject to strong constraints, including trade-offs between the costs of fishing and hatchery releases. Costs of hatchery fish strongly influence optimal policy, which may range from no enhancement at high cost to high levels of stocking and fishing effort at low cost. Release of genetically maladapted fish reduces the effectiveness of enhancement, and is most detrimental overall if fitness of hatchery fish is only moderately compromised. As a temporary measure for the rebuilding of depleted stocks, enhancement cannot substitute for effort limitation, and is advantageous as an auxiliary measure only if the population has been reduced to a very low proportion of its unexploited biomass. Quantitative analysis of population dynamics is central to the responsible use of stock enhancement in fisheries management, and the necessary tools are available.

Animals↗

PubMed2026

Combined effects of Ret coding and enhancer loss-of-function alleles cause progressive loss of inhibitory motor neurons in the enteric nervous system.

Hirschsprung disease (HSCR) is a congenital enteric neuropathy caused by disrupted development of enteric neural crest-derived cells (ENCDCs). Although pathogenic coding variants in RET account for many cases, the largest genetic contribution to HSCR risk arises from a common noncoding variant (rs2435357) within a SOX10-bound RET enhancer (MCS+9.7) that reduces RET gene expression in vivo and triggers expression changes in other ENS genes in the human fetal gut. However, the ENS cell types affected by this enhancer and the mechanisms by which these transcriptional changes lead to HSCR remain unknown. Here, we investigated the role of this enhancer by generating mice carrying a deletion of the orthologous Ret mcs+9.7 enhancer (Δmcs+9.7). Single-cell RNA sequencing of E14.5 embryonic gut demonstrated that enhancer deletion reduced Ret expression by 8% without altering ENS cell composition. However, reduced Ret expression was restricted to differentiating neurons and inhibitory motor neuron lineages, revealing cell type-specific enhancer activity. To determine the functional consequences of further reducing Ret dosage, we generated compound heterozygous mice carrying both the enhancer deletion and a Ret coding null allele (+/Δmcs+9.7;+/CFP). These mice exhibited additive reductions in Ret expression, altered Sox10 expression, dysregulation of cell-cycle and neuronal differentiation programs, and selective depletion of developing inhibitory motor neuron lineages. These findings establish a cell type-specific role for the mcs+9.7 enhancer in modulating Ret dosage and reveal how subtle enhancer perturbations alter neural subtype specification without overt hypoganglionosis, suggesting that HSCR arises from a cascade of cellular defects triggered by >50% loss of Ret function.

Journal Article↗

PubMed1991

Evidence that angiotensin II enhances noradrenaline release from sympathetic nerves in mouse atria by activating protein kinase C.

1. Mouse atria were incubated with [3H]-noradrenaline and the outflow of radioactivity induced by electrical field stimulation (5 Hz, 60 s) was used as an index of noradrenaline release. Angiotensin II (1 x 10(-8) M) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity. 2. Phorbol 12-myristate 13-acetate (0.001-1.0 x 10(-6) M) and phorbol 12, 13-dibutyrate (0.001-1.0 x 10(-6) M), protein kinase C activating phorbol esters, significantly enhanced the S-I outflow of radioactivity. Phorbol dibutyrate produced a greater maximal enhancement of S-I outflow of radioactivity than phorbol myristate acetate. The enhancement of S-I outflow of radioactivity produced by the combination of phorbol dibutyrate (1.0 x 10(-7) M) and phorbol myristate acetate (1.0 x 10(-7) M) was no greater than that produced by phorbol dibutyrate (1.0 x 10(-7) M) alone. The enhancement of S-I outflow of radioactivity produced by phorbol myristate acetate (1.0 x 10(-7) M) was constant whether the tissue was exposed for 15, 45 or 75 min. 3. When angiotensin II (1.0 x 10(-8) M) was present with the maximally effective concentration of phorbol dibutyrate (1.0 x 10(-7) M) it did not increase S-I outflow of radioactivity. 8-bromo-cyclic AMP (9.0 x 10(-5) M) by itself increased the S-I outflow of radioactivity and in the presence of the maximally effective concentration of phorbol dibutyrate the enhancement of S-I outflow of radioactivity produced by 8-bromo-cyclic AMP was maintained. 4. A protein kinase inhibitor, K-252a (1.0 x 10(-6) M), did not affect S-I outflow of radioactivity. K-252a significantly reduced the enhancement of S-I outflow of radioactivity produced by both phorbol myristate acetate (0.03 or 0.1 x 10(-6) M) and phorbol dibutyrate (0.01 or 1.0 x 10(-6) M). 5. K-252a (1.0 x 10(-6) M) blocked the enhancement of S-I outflow of radioactivity produced by angiotensin II (1.0 x 10(-8) M) and tetraethylammonium (1.0 x 10(-4) M). 6. These results suggest that angiotensin II receptors may enhance noradrenaline release through the pool of protein kinase C that is activated by phorbol dibutyrate.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1996

Angiotensin II receptors involved in the enhancement of noradrenergic transmission in the caudal artery of the spontaneously hypertensive rat.

1. The effects of the AT1 receptor antagonist losartan and the AT2 receptor antagonist PD 123319, on actions of angiotensin II in isolated caudal arteries of spontaneously hypertensive (SH) and age-matched normotensive (Wistar-Kyoto) rats were compared. 2. Angiotensin II (0.1-3 microM) produced concentration-dependent increases in perfusion pressure in artery preparations from both SH and Wistar-Kyoto (WKY) rats, the maximal increase in the SH rat being significantly greater than the increase in WKY rats. The increase in perfusion pressure in preparations from both strains of rats was prevented by losartan (0.1 microM) and unaffected by PD 123319 (0.1 microM), indicating that the vasoconstrictor action of angiotensin II is subserved by AT1 receptors. 3. Angiotensin II (0.1-3 microM) produced concentration-dependent enhancement of both stimulation-induced (S-I) efflux of [3H]-noradrenaline and stimulation-evoked vasoconstrictor responses in isolated preparations of caudal artery from both SH and WKY rats, in which the noradrenergic transmitter stores had been labelled with [3H]-noradrenaline. The maximum enhancement of S-I efflux produced by angiotensin II (1 microM) was significantly greater in artery preparations from WKY rats than in preparations from SH rats, whereas the maximum enhancement of stimulation-evoked vasoconstrictor responses was greater in preparations from SH rats than in those from WKY rats. 4. In artery preparations from both WKY and SH rats, the AT1 angiotensin II receptor antagonist, losartan (0.01 and 0.1 microM), reduced or abolished the enhancement of both S-I efflux and vasoconstrictor responses by 1 microM angiotensin II. 5. The combination of 0.01 microM losartan and 0.1 microM angiotensin II enhanced both the S-I efflux and stimulation-evoked vasoconstrictor response in caudal artery preparations from WKY rats, whereas 0.1 microM angiotensin alone was ineffective. The AT2 receptor antagonist PD 123319 (0.01 and 0.1 microM) prevented the enhancement of both S-I efflux and stimulation-evoked vasoconstrictor responses by the combination of angiotensin II and losartan. 6. In contrast to findings in WKY preparations and those previously obtained for arteries from another normotensive strain (Sprague-Dawley), in artery preparations from SH rats there was no synergistic interaction between losartan and angiotensin II. Rather, combinations of 0.1 microM angiotensin II and PD 123319 (both 0.01 and 0.1 microM) enhanced S-I [3H]-noradrenaline efflux, whereas 0.1 microM angiotensin II alone was without effect. Moreover, losartan (0.1 microM) prevented the enhancement of S-I efflux by the combination of angiotensin II and PD 123319. 7. The present findings indicate that in the caudal artery of WKY and SH rats, and as previously found in Sprague-Dawley preparations, angiotensin II receptors similar to the AT1B subtype subserve enhancement of transmitter noradrenaline release. 8. As previously suggested for Sprague-Dawley caudal artery preparations, the synergistic prejunctional interaction of losartan and 0.1 microM angiotensin II in caudal artery preparations from WKY rats may be due to either the unmasking by losartan of a latent population of angiotensin II receptors subserving facilitation of transmitter noradrenaline release, or blockade by losartan of an inhibitory action of angiotensin II on transmitter release. 9. The synergistic interaction of PD 123319 and 0.1 microM angiotensin II in caudal arteries of SH rats may also be explained by either of the mechanisms proposed for the normotensive strains, but the involvement of different receptor subtypes would need to be postulated for each of the proposed mechanisms.

Angiotensin II↗

PubMed1997

Effects of different absorption enhancers on the permeation of ebiratide, an ACTH analogue, across intestinal membranes.

The permeation of ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), a novel ACTH analogue, across the intestinal mucosae has been examined by use of isolated intestinal membranes from rats in a modified Ussing chamber. Regional differences were observed in the permeation of ebiratide across intestinal membranes; the order of membrane permeability was jejunum > ileum > duodenum > colon. Overall, the permeation of ebiratide was relatively poor. The effects of various absorption enhancers were examined to increase the intestinal permeability to ebiratide. Sodium glycocholate and sodium caprate had no significant enhancing effect on the permeability of the jejunal membrane, but significantly enhanced the permeation of ebiratide through the colonic membrane. On the other hand, N-dodecyl-beta-D-maltopyramoside (LM) significantly enhanced the permeation of ebiratide through both jejunal and colonic membranes. In general, the absorption-enhancing effects of these agents were more predominant in the colon than in the jejunum. Membrane damage by the absorption enhancers was evaluated by measuring the amount of protein released from the intestinal membrane. It was found that all the absorption enhancers slightly increased the amount of protein released, but that the amounts of protein released in the presence of these enhancers were much less than in the presence of ethylenediaminetetraacetic acid (EDTA), used as a positive control. These findings suggest that the absorption enhancers, especially LM might be useful adjuvants for improving the intestinal absorption of peptide and protein drugs, including ebiratide.

Adrenocorticotropic Hormone↗

PubMed2003

Selective enhancement filters for nodules, vessels, and airway walls in two- and three-dimensional CT scans.

Computer-aided diagnostic (CAD) schemes have been developed to assist radiologists in the early detection of lung cancer in radiographs and computed tomography (CT) images. In order to improve sensitivity for nodule detection, many researchers have employed a filter as a preprocessing step for enhancement of nodules. However, these filters enhance not only nodules, but also other anatomic structures such as ribs, blood vessels, and airway walls. Therefore, nodules are often detected together with a large number of false positives caused by these normal anatomic structures. In this study, we developed three selective enhancement filters for dot, line, and plane which can simultaneously enhance objects of a specific shape (for example, dot-like nodules) and suppress objects of other shapes (for example, line-like vessels). Therefore, as preprocessing steps, these filters would be useful for improving the sensitivity of nodule detection and for reducing the number of false positives. We applied our enhancement filters to synthesized images to demonstrate that they can selectively enhance a specific shape and suppress other shapes. We also applied our enhancement filters to real two-dimensional (2D) and three-dimensional (3D) CT images to show their effectiveness in the enhancement of specific objects in real medical images. We believe that the three enhancement filters developed in this study would be useful in the computerized detection of cancer in 2D and 3D medical images.

Databases as Topic↗

PubMed1993

Adaptation of suppression as an explanation of enhancement effects.

Delaying the onset of a signal relative to the onset of a simultaneous notched masker often improves the ability of subjects to "hear out" the signal at both threshold and suprathreshold levels. Viemeister and Bacon [J. Acoust. Soc. Am. 71, 1502-1507 (1982)] suggested that such signal-enhancement effects might be attributable to adaptation of the suppression directed from the masker to the signal, thereby releasing the signal from suppression. In support of their hypothesis, Viemeister and Bacon reported that a masker, preceded by an enhancer having no component at the signal frequency, produced more forward masking than did the masker by itself. Here the masker enhancement described by Viemeister and Bacon, signal enhancement, and two-tone suppression were measured in the same six subjects. Parametric manipulations of the masker-enhancement stimulus produced results similar to those previously reported for parallel investigations of signal enhancement, indicating that the two types of enhancement are closely related effects. Although the present data reveal an inverse relationship between the amounts of suppression and enhancement, suggesting that the two processes may be interrelated, no support was obtained for the hypothesis that adaptation of suppression can account for enhancement.

Adaptation, Physiological↗

PubMed1989

In vivo activation of peripheral blood polymorphonuclear neutrophils by gamma interferon results in enhanced fungal killing.

The effect of in vivo administration of murine recombinant gamma interferon (IFN) on the fungicidal activity of murine peripheral blood polymorphonuclear neutrophils (PB-PMNs) was studied. Mice were injected intramuscularly with 250, 2,500, 25,000 or 250,000 U of IFN 5 h before collection of peripheral blood. Purified PB-PMNs were cocultured in vitro with Blastomyces dermatitidis yeast cells for 2 h. PB-PMNs from untreated mice killed 44.5 +/- 12.5% of the fungal inoculum, whereas PB-PMNs from mice treated with 25,000 or 250,000 U of IFN showed significantly enhanced in vitro killing (68.0 +/- 9.4% [P less than 0.005] and 72.3 +/- 1.1% [P less than 0.001], respectively). Treatment with 250 or 2,500 U of IFN or 25,000 U of heated (100 degrees C, 15 min) IFN had no effect. The IFN-induced activation of PB-PMNs was transitory. Significant enhancement of PB-PMN killing activity occurred 1, 2, or 5 h after in vivo IFN administration, but no enhancement was observed 16 or 24 h after IFN treatment. Enhanced fungicidal activity by PB-PMNs from mice treated for 5 h with 25,000 U of IFN correlated with an increased release of superoxide anion (O2-) in vitro after stimulation of PB-PMNs with phorbol ester; normal PB-PMNs and IFN-activated PB-PMNs, respectively, produced 2.2 +/- 2.5 and 23.5 +/- 4.8 nmol of O2- per 10(6) PB-PMNs per 30 min (P less than 0.005). The exogenous addition of compounds that antagonize or inhibit the formation of oxygen radicals (superoxide dismutase, catalase, dimethyl sulfoxide, or sodium azide) significantly inhibited fungal killing by both normal and IFN-activated PB-PMNs. In addition to the enhanced microbicidal activity and superoxide generation demonstrated in vitro with constant cell numbers, there was a transient leukocytosis (particularly neutrophilia) in peripheral blood at doses of IFN and at times after IFN administration where enhanced activity was also demonstrated. In summary, our results indicate that PB-PMNs can be activated in vivo for enhanced killing of a fungal target. The enhanced killing capacity of IFN-activated PB-PMNs is due at least in part to the enhancement of oxidative killing mechanisms.

Animals↗

PubMed1972

In vitro interactions between virus and enhancer.

Cell-free supernatant fluids of permissive host cells contained an enhancer for the m+ variant of echovirus 6. The enhancer activity remained in supernatant fractions after centrifugation at 110,000 x g for 4 hr. Under in vitro conditions, a complex between enhancer and virus formed rapidly. The complex was not dissociated by dilution and was sedimented by centrifugation. The effect of enhancer on the distribution of virus in CsCl density gradients was determined. In the absence of enhancer, virus was recovered in one peak at 1.33 g/ml. Incubation of enhancer with virus before centrifugation resulted in the formation of two peaks of infectivity at 1.33 g/ml and 1.24 g/ml. The heavier virus peak represented 43% of the recovered infectivity and could be enhanced. The light virus peak contained 26% of the infectivity and could not be enhanced. The density of enhancer was 1.20 g/ml and approximated the density of the light virus population.

Amnion↗

PubMed1986

Interspersed Homologous DNA of Autographa californica Nuclear Polyhedrosis Virus Enhances Delayed-Early Gene Expression.

The five regions of homologous DNA which are interspersed in the genome of the baculovirus Autographa californica nuclear polyhedrosis virus increased the expression of a delayed-early gene of this virus. Although this activity was first observed as a 10-fold trans effect, the homologous region 5 (hr5) enhanced the expression of linked genes 1,000-fold. The hr5 enhancer also exhibited the other characteristics associated with viral enhancer elements, including orientation independence and the abilities to function at a distance from the linked promoter, to regulate heterologous promoters, and to increase the number of RNA polymerase molecules transcribing the linked genes. The expression of the immediate-early regulatory gene was not enhanced by cis-linked hr5, although the enhancer function may require the immediate-early regulatory gene product. The hr5 enhancer was relatively insensitive to competition by an excess of enhancer molecules. The nucleotide sequence of hr5 revealed two different conserved repeats separated by nonhomologous DNA. Deletion analysis of the hr5 enhancer indicated that a 30-base-pair inverted repeat was essential for enhancer function.

Journal Article↗