Search PubMed⌕ Search

Biomedical subjects

K J Kim

Publications and source records attributed to K J Kim.

At least 145 records · Page 8Linked to original sources
PubMed1996

Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation.

Chronic immune responses and inflammatory reactions in rheumatoid arthritis (RA) often cause severe destruction of cartilage and bone, but its mechanism is still a matter of controversy. We reported that interleukin-6 (IL-6) alone does not induce osteoclast formation, but soluble interleukin-6 receptors (sIL-6R) triggered the formation in the presence of IL-6 in cocultures of murine osteoblastic cells and bone marrow cells. In this study, we examined the involvement of sIL-6R and IL-6 in joint destruction in patients with RA. Although the frequency of patients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) and osteoarthritis (OA) patients (43%), the number of osteoclast-like cells found in the synovium was greater in the former than in the latter. Multinucleated cells obtained from RA synovium expressed the osteoclast-specific phenotype such as tartrate-resistant acid phosphatase, carbonic anhydrase II, vacuolar proton-ATPase and vitronectin receptors at similar levels to those from a human giant cell tumor of bone. The concentration of both IL-6 and sIL-6R was significantly higher in the synovial fluids from patients with RA than with OA. The concentration of IL-6 and sIL-6R correlated well with the roentgenologic grades of joint destruction. Dose-response curves for human IL-6 and human sIL-6R in inducing osteoclast-like cell formation in cocultures indicated that the RA synovial fluids contained sufficient IL-6 and sIL-6R to induce osteoclastogenesis. When synovial fluids from RA and OA patients were added to the cocultures, some of the RA synovial fluids containing high levels of IL-6 and sIL-6R stimulated osteoclast-like cell formation, which was strikingly inhibited by adding anti-IL-6R antibody simultaneously. These results suggest that IL-6 in the RA synovial fluids is at least in part responsible for joint destruction in the presence of sIL-6R through osteoclastogenesis.

Acid Phosphatase↗
PubMed1996

Age-dependent expression of P-glycoprotein gp170 in Caco-2 cell monolayers.

PURPOSE: To determine whether the expression and activity of the P-glycoprotein (P-GP) drug efflux pump vary with the culture age of Caco-2 cell monolayers. METHODS: Caco-2 cell monolayers were grown for 3-27 days on tissue culture-treated Transwells. P-GP efflux function was determined by measuring transmonolayer fluxes of cyclosporin A (CsA) and verapamil, while P-GP expression level was evaluated by Western blot analysis using monoclonal antibody C219. RESULTS: The apparent permeability coefficient (Papp) of CsA (0.5 microM) in the basolateral-to-apical (B-->A) direction increased with culture age and was higher than the apical-to-basolateral (A-->B) direction at all times. Net secretory Papp significantly increased from day 17 onward compared to that observed during day 3 through 13. Verapamil (100 microM) significantly inhibited CsA transport in the B-->A direction from day 17 to 27, while elevating CsA transport in the A-->B direction from day 6 to 27. Interestingly, the Papp of verapamil (0.5 microM) in the B-->A direction was significantly higher than in the A-->B direction from day 6 to 27, rendering increases in net secretory Papp of verapamil with culture age. Western analysis revealed that P-GP expression level was in the order of 4 weeks approximately 1 week > 3 weeks > 2 weeks at equal loading of cell proteins. CONCLUSIONS: P-GP is continuously expressed throughout the culture period, but it may not be fully functional at an early age. Caco-2 cell monolayers of day 17 to 27 appear to be a good model to evaluate the functional role of P-GP in drug efflux.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Horseradish peroxidase transport across rat alveolar epithelial cell monolayers.

PURPOSE: To evaluate the transport characteristics of horseradish peroxidase (HRP, a nonspecific fluid-phase endocytosis marker) across an in vitro model of tight (> 2,000 ohm-cm2) rat alveolar epithelial cell monolayers grown on tissue culture-treated polycarbonate filters. METHODS: Unidirectional HRP fluxes were estimated from the appearance rate of HRP in the receiver fluid following instillation in the donor fluid as a function of donor [HRP] and temperature. Molecular species present in either bathing fluid were determined at the end of flux experiments using fluorescein isothiocyanate (FITC)-labeled HRP by gel permeation chromatography. Cell-associated HRP activity at the end of the transport experiment was determined, as were the rates of recycling and transcellular movement of HRP. An enzymatic assay was uses to quantify HRP activity in the bathing fluid and cells. RESULTS: Unidirectional HRP fluxes were symmetric and increased linearly with up to 50 microM donor [HRP]. The apparent permeability coefficient of HRP was reduced by 3.5 times upon lowering the temperature from 37 to 4 degrees C. About 50% of the FITC-labeled species present in either receiver fluid was intact HRP. Cell-associated HRP estimated from apical HRP incubation was about 4 times greater than that from basolateral incubation. Recycling into apical fluid of cell-associated HRP following apical incubation occurred rapidly with a half-time (T1/2) of approximately 5 min, reaching a plateau at approximately 67% of the initial cell-associated HRP, while transcellular movement of HRP (into basolateral fluid) took place with a T1/2 of approximately 20 min, attaining a steady-state at approximately 13% of the initial cell-associated HRP. Basolateral recycling of HRP was also rapid (T1/2 = approximately 5 min) reaching a steady-state at approximately 35% of the initial basolaterally-bound HRP. Transcellular movement of HRP following basolateral incubation was slower (T1/2 = approximately 70 min), leveling off at 50% of the initial cell-associated HRP. CONCLUSIONS: HRP appears to be transported relatively intact (approximately 50%) across rat alveolar epithelial barrier via nonspecific fluid-phase endocytosis. The transepithelial pinocytotic rate of alveolar epithelial cells is estimated to be about 25 nL/cm2/h.

Animals↗
PubMed1996

Cyclic AMP modulation of active ion transport in the pigmented rabbit conjunctiva.

This study was conducted to determine whether active ion transport in the pigmented rabbit conjunctiva was subjected to cyclic AMP modulation. 8-BrcAMP and compounds that may affect intracellular cAMP levels were tested for their effects on the conjunctival short-circuit current (Isc) following mucosal application. Conjunctival Isc was increased by 1 mM 8-BrcAMP, 0.001-20 microM forskolin, 0.01-2 mM theophylline, 2 microM 1-epinephrine, and 20 microM terbutaline in a Cl(-)-containing but not in a Cl(-)-free medium. The increase in Isc induced by 1 mM 8-BrcAMP was reversed by 1 mM N-phenylanthranilic acid, suggesting enhancement of Cl- secretion by cAMP. Similarly, the increase in Isc induced by 20 microM terbutaline was blunted by 1 microM timolol, suggesting a role for beta 2 adrenergic modulation of Cl- secretion. Collectively, these results are consistent with the notion of cAMP modulation of conjunctival active ion transport.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Liarozole inhibits human epidermal retinoic acid 4-hydroxylase activity and differentially augments human skin responses to retinoic acid and retinol in vivo.

Metabolic inactivation of all-trans retinoic acid to 4-hydroxy retinoic acid occurs via a cytochrome P-450 enzyme. We investigated the effects of liarozole on the retinoic acid 4-hydroxylase activity of human epidermis and its ability to modify in vivo human skin responses to retinoic acid and all-trans retinol. Retinoic acid 4-hydroxylase activity induced in vivo by 4 d treatment with retinoic acid (0.1%) was inhibited in vitro by liarozole in a concentration-dependent manner. Comparable micromolar concentrations of liarozole were extracted from stratum corneum-free epidermis treated with 3% liarozole. Retinoic acid levels in liarozole-treated skin increased to 19 +/- 5 ng/g wet wt (mean +/- SEM, p < 0.002, n = 17) at 18 h and to 6 +/- 2 ng/g wet wt (p = 0.38, n = 17) at 48 h as compared to vehicle (not detectable). At 48 h, retinoic acid 4-hydroxylase activity was induced 9-fold over vehicle (p < 0.03, n = 8). At 96 h, no significant erythema or increased epidermal thickness was found when either retinoic acid (0.001%), all-trans retinol (0.0250%), or liarozole (3%) was applied individually, but when 0.001% retinoic acid and 3% liarozole were applied together, both erythema and increased epidermal thickness occurred. In contrast, 0.025% all-trans retinol and 3% liarozole together caused increased epidermal thickness but no erythema. These data demonstrate that, at doses used here, liarozole, although an effective inhibitor of retinoic acid 4-hydroxylase, cannot function alone like a retinoid in vivo, probably because of retinoic acid 4-hydroxylase induction. In the presence of a low dose retinoic acid or all-trans retinol, however, liarozole can amplify human skin responses to each retinoid in a manner characteristic of the retinoid at a higher dose (erythema and hyperplasia with retinoic acid; no erythema but hyperplasia with all-trans retinol).

Androgen Antagonists↗
PubMed1996

Enhancement of airway epithelial Na+,K(+)-ATPase activity by NO2 and protective role of nordihydroguaiaretic acid.

We examined the effects of nitrogen dioxide (NO2) on guinea pig tracheobronchial (GPTE) ouabain-sensitive 86Rb uptake, as an index of Na+,K(+)-ATPase activity, and specific [3H]ouabain binding. A 1-h exposure of GPTE monolayers to 5 ppm NO2 increased ouabain-sensitive 86Rb uptake (nmol.mg protein-1.30 min-1) to 512 +/- 39 compared with an air-control value of 278 +/- 20. Similarly, 1 ppm NO2 increased 86Rb uptake to 336 +/- 19 from an air control of 219 +/- 31. The specific [3H]ouabain-binding capacity (Bmax) for monolayers exposed to 5 ppm NO2 was increased to 23.2 +/- 1.2 pmol/mg protein in comparison with an air-control value of 18.4 +/- 0.4; however, there was no change at 1 ppm NO2. Binding constants (Kd) for 1 or 5 ppm NO2 were increased to 0.64 +/- 0.02 and 0.79 +/- 0.08 microM, respectively, in comparison with an air-control value of 0.53 +/- 0.02 microM. Changes of Bmax and Kd may be consistent with a recruitment of latent pumps to the basolateral cell plasma membrane and/or increased turnover of the sodium pump. However, the increase of Bmax was no more than 126% of the air control, while 86Rb uptake increased to 184%, suggesting that an increased turnover is the more predominant effect. Incubation of GPTE monolayers during NO2 exposure with nordihydroguaiaretic acid, an antioxidant, blocked the increase of ouabain-sensitive 86Rb uptake almost completely and partially protected transepithetial resistance, suggesting that lipid peroxidation processes may play a role in alterations of airway epithelial barrier and active ion transport properties.

Animals↗
PubMed1996

Effects of EGF on alveolar epithelial junctional permeability and active sodium transport.

We evaluated the effects of epidermal growth factor (EGF) on transepithelial resistance (Rt) and active ion transport by alveolar epithelial cell (AEC) monolayers on tissue culture-treated polycarbonate filters. Rat type II cells were cultured in completely defined serum-free medium (MDSF) or MDSF supplemented with EGF. The addition of EGF from either day 0 (chronic) or day 4 (subacute) resulted in significant increases in Rt and short-circuit current (ISC) on day 5. After subacute exposure, these effects were delayed in onset by 6-12 h and sustained for > 24 h. Basolateral (but not apical) EGF was responsible for these effects, which were prevented by preincubation with tyrphostin RG-50864, a reversible specific inhibitor of the EGF receptor tyrosine kinase. ISC decreased, with a sensitivity to apical inhibitors of sodium transport in the order benzamil > amiloride > 5-(N-ethyl-N-isopropyl) amiloride in MDSF +/- EGF, and was completely inhibited by the addition of basolateral ouabain. Net sodium flux and Na+, K+ -ATPase activity both increased approximately 50% in the presence of EGF. These results indicate that 1) EGF decreases tight junctional permeability and increases active sodium transport by AEC monolayers via basolaterally located EGF receptors, and 2) the pathways for AEC sodium entry and exit (+/- EGF) are apical high amiloride affinity sodium channels and basolateral sodium pumps.

Amiloride↗
PubMed1996

Alveolar epithelial clearance of protein.

Substantial progress has been made in understanding the rate, the pathways, and the mechanisms regulating alveolar protein removal from the uninjured lung. Whole animal studies and cellular studies have demonstrated that the majority of alveolar epithelial protein clearance occurs by passive nondegradative diffusional pathways. Some evidence, however, has been recently presented that alveolar epithelial cells express an albumin-binding receptor as well as a polymeric immunoglobulin receptor, both of which might be important for alveolar epithelial clearance of protein. However, the contribution of these receptors requires further studies. Little is known about alveolar clearance of protein during pathological conditions; further studies are required to determine the roles of the different cell types in the lung for removal of protein from the alveolar spaces of the lung. Alveolar macrophages are likely to play an important role in the degradation and removal of insoluble protein from the distal air spaces after acute lung injury. In conclusion, the present data suggest that most proteins and peptides deposited on the epithelial surfaces in the distal air spaces are cleared as intact molecules, predominantly via paracellular routes. The contribution of pinocytic processes appear to be of minor importance for translocation of bulk quantities of proteins or peptides across the alveolar epithelium.

Animals↗
PubMed1996

Generation of glycolaldehyde from guinea pig airway epithelial monolayers exposed to nitrogen dioxide and its effects on sodium pump activity.

Pulmonary injury from nitrogen dioxide (NO2) may in part be related to the generation of aldehydic compounds, which bind with cellular proteins and subsequently impair or inhibit cell function. We examined the generation of aldehydes from guinea pig tracheobronchial epithelial (GPTE) cell monolayers exposed to NO2. With the use of dinitrophenylhydrazine (DNP) to derivatize aldehydic compounds, glycolaldehyde, a two carbon alpha-hydroxyaldehyde, was identified in elevated levels in the basolateral fluid from monolayers exposed to NO2. DNP-glycolaldehyde levels were 81.2 +/- 2.7 and 234.0 +/- 42.6 nM in response to a 1-hr exposure to 1 and 5 ppm NO2, respectively, as compared to an air-control value of 20.3 +/- 6.8 nM. Taking into account dilution and reactivity, cellular glycolaldehyde levels could have reached as high as 3 mM for the 60-min exposure period (i.e., 0.05 mM/min). The effects of exogenous glycolaldehyde on GPTE ouabain-sensitive basolateral 86Rb uptake (an index of Na+,K(+)-ATPase activity) were examined and compared with the actions of NO2 exposure. Bolus addition of glycolaldehyde to the basolateral fluid at concentrations > or = 5 mM led to an inhibition of ouabain-sensitive 86Rb uptake, while lower concentrations had no effect. the effects of exogenous glycolaldehyde differ from NO2 exposure, which led to a sustained elevation of ouabain-sensitive 86Rb uptake with presumed generation of glycolaldehyde at a continuous low level. Glycolaldehyde does not appear to play a significant role in the acute alterations of sodium pump activity, suggesting that the NO2-induced changes in Na+,K(+)-ATPase activity of GPTE monolayers probably are further mediated by other lipid peroxidation products/oxidation processes yet to be identified.

Acetaldehyde↗
PubMed1996

A primary culture model of rabbit conjunctival epithelial cells exhibiting tight barrier properties.

PURPOSE: The present study was conducted to develop and characterize a functional primary culture of pigmented rabbit conjunctival epithelial cells on permeable support exhibiting tight barrier properties. METHODS: Conjunctival epithelial cells were isolated by 0.2% protease treatment, cultured at 0.5-1.8 x 10(6) cells/cm2 onto collagen-treated Transwell filters, and were maintained either in the presence of 1% fetal bovine serum throughout or serum-free media from day 3 onwards. Transepithelial potential difference (PD) and transepithelial electrical resistance (TEER) were measured and equivalent short-circuit current (Ieq = PD/TEER) estimated. RESULTS: There appears to be a critical plating density of 1.5 x 10(6) cells/cm2 for functional development of tight epithelial cell cultures. The culture conditions as noted above did not affect either the time when peak bioelectric parameters were attained (days 8-10) or the magnitude of these parameters at a plating density of 1.5 x 10(6) cells/cm2. Specifically, cells grown in a serum-free media showed a peak TEER of 1.9 +/- 0.2 k omega.cm2, a PD of 14.2 +/- 1.6 V (apical side negative), and and Ieq of 8.0 +/- 0.4 microA/cm2 (mean +/- SEM, n = 45). Electron microscopy of serum-weaned cultures revealed a multilayered epithelium with numerous microvilli on the outermost layer of cells, while sporadic positive Periodic Acid Schiff (PAS) staining under light microscopy suggested the presence of mucin-secretory goblet cells. CONCLUSIONS: A functional, tight, epithelial barrier of the pigmented rabbit conjunctiva on a permeable support has been developed, which may be useful for mechanistic studies of ion and drug transport at the cellular level.

Animals↗
PubMed1996

Permeability characteristics of primary cultured rabbit conjunctival epithelial cells to low molecular weight drugs.

PURPOSE: To evaluate the permeability characteristics of primary cultured rabbit conjunctival epithelial cell (RCEC) layers to low molecular weight drugs of varying lipophilicity. METHODS: 3H-mannitol; hydrophilic sotalol and atenolol; moderately lipophilic metoprolol, timolol, propranolol; and highly lipophilic betaxolol were used as model compounds. RESULTS: The conjunctival apparent permeability coefficient (Papp) of mannitol (1 x 10(-7) cm/s) was 2.4 times lower than that of the most hydrophilic beta-blocker, sotalol (Papp = 2.4 x 10(-7) cm/s). Differences in the degree of tightness of the epithelial cell layers brought about a 30-fold difference in the transport of atenolol in favor of the leaky cell layers, while not affecting the transport of the lipophilic drug, propranolol. Within the log partition coefficient (PC) range of -0.62 (sotalol) and 3.44 (betaxolol), there was a hundred-fold difference in the Papp. A sigmoidal curve was used to depict the influence of lipophilicity on solute permeation across conjunctival epithelial cell layers. An effective half-maximal Papp was observed at a log PC value of 1.2. CONCLUSIONS: These findings on the lipophilicity effect on drug transport are generally similar to those reported for the isolated rabbit conjunctiva, suggesting the utility of cultured rabbit conjunctival epithelial cell layers as an in vitro model for evaluating drug transport.

Adrenergic beta-Antagonists↗
PubMed1996

Contribution of Na(+)-glucose cotransport to the short-circuit current in the pigmented rabbit conjunctiva.

The objective of this study was to determine whether Na(+)-glucose cotransport contributed to the residual short-circuit current (Isc) in the pigmented rabbit conjunctiva not accounted for by Cl- secretion. The Isc of the pigmented rabbit conjunctiva was measured following exposure of its mucosal or serosal side to varying concentrations of D-glucose or phloridzin in a glutathione-bicarbonated Ringer's solution (GBR). Addition of D-glucose to the mucosal side of the conjunctiva bathed in glucose-free GBR elevated Isc up to 26 +/- 6% in a dose-dependent manner (K0.5 = 1.2 mM), while mucosal (but not serosal) addition of phloridzin reduced the Isc (IC50 = 0.05 mM) of the conjunctiva bathed in regular GBR. In a mucosal Na(+)-free medium, neither 20 mM D-glucose nor 0.5 mM phloridzin was effective. In a mucosal glucose-containing medium, deletion of Na+ reduced Isc up to 27 +/- 4%. It was, however, restored to its initial value upon the addition of 17.5-141 mM Na+ to a medium containing 5 mM D-glucose. Hill plot analysis of Isc elevation at 141 mM Na+ in the presence of varying D-glucose concentrations in the mucosal bathing fluid yielded a Hill coefficient of 0.86. There is, therefore, evidence for the apical localization of phloridzin-sensitive Na(+)-coupled D-glucose transport that exhibits apparent 1:1 stoichiometry, being responsible for the maximal 26% increase in the Isc.

Animals↗
PubMed1996

Targeted drug delivery to the respiratory tract: solute permeability of air-interface cultured rabbit tracheal epithelial cell monolayers.

The permeability characteristics of air-interfaced rabbit tracheal epithelial cell monolayers to model macromolecules and low molecular weight solutes were evaluated. The model macromolecules were fluorescein isothiocyanate (FITC)-labeled dextrans of varying molecular sizes (4,000 to 70,000 daltons). The model low molecular weight solutes were beta-adrenergic compounds of similar sizes with widely different log octanol/pH 7.4 buffer partition coefficients (log P). FITC-dextrans were assayed spectrofluorimetrically and beta-adrenergic compounds were assayed by reverse phase HPLC with UV detection. The apparent permeability coefficients (Papp) for FITC alone to FITC-dextran 70,000 in the tracheal epithelial barrier were in the range of 11.2 to 0.3 x 10(8) cm/sec. A molecular cut-off at about 20,000 daltons, consistent with a single equivalent pore population of about 5 nm in radius, was found. A sigmoidal relationship best described the influence of drug lipophilicity on the Papp of beta-adrenergic compounds, where the log P at the half maximal Papp was 2.08. Thus, the air-interfaced rabbit tracheal epithelial cell culture model has been successfully applied to elucidate the permeability of tracheal epithelial barrier to model macromolecules and small solutes. It appears that the tracheal epithelial cell monolayers absorb drugs in a similar manner as do native excised tracheal and other epithelia.

Adrenergic beta-Agonists↗
PubMed1996

Topical tretinoin (retinoic acid) improves early stretch marks.

BACKGROUND AND DESIGN: Stretch marks are disfiguring lesions usually caused by excessive stretching of skin. We investigated the response of early, clinically active stretch marks to topical 0.1% tretinoin (retinoic acid) cream. In a double-blind, randomized, vehicle-controlled study, 22 patients applied either 0.1% tretinoin (n = 10) or vehicle (n = 12) daily for 6 months to the affected areas. Patients were evaluated by physical examination monthly and by analysis of biopsy specimens of stretch marks obtained before and at the end of therapy in comparison with untreated normal skin. RESULTS: After 2 months, patients treated with tretinoin had significant improvements in severity scores of stretch marks compared with patients who received vehicle (P < .05). After 6 months, eight (80%) of the 10 tretinoin-treated patients had definite or marked improvement compared with one (8%) of the 12 vehicle-treated patients (P = .002). Targeted stretch marks in patients treated with tretinoin had a decrease in mean length and width of 14% and 8%, respectively, compared with an increase of 10% (P < .001) and 24% (P = .008), respectively, in patients who received vehicle. There were no significant differences in various measures of quality and quantity of dermal collagen and elastic fibers in stretch marks when tretinoin and vehicle treatments were compared. CONCLUSIONS: Topical application of tretinoin significantly improves the clinical appearance of early, active stretch marks. The processes that are responsible for the clinical improvement remain unknown.

Administration, Cutaneous↗
PubMed1995

ndhF sequence evolution and the major clades in the sunflower family.

An extensive sequence comparison of the chloroplast ndhF gene from all major clades of the largest flowering plant family (Asteraceae) shows that this gene provides approximately 3 times more phylogenetic information than rbcL. This is because it is substantially longer and evolves twice as fast. The 5' region (1380 bp) of ndhF is very different from the 3' region (855 bp) and is similar to rbcL in both the rate and the pattern of sequence change. The 3' region is more A+T-rich, has higher levels of nonsynonymous base substitution, and shows greater transversion bias at all codon positions. These differences probably reflect different functional constraints on the 5' and 3' regions of ndhF. The two patterns of base substitutions of ndhF are particularly advantageous for phylogenetic reconstruction because the conserved and variable segments can be used for older and recent groups, respectively. Phylogenetic analyses of 94 ndhF sequences provided much better resolution of relationships than previous molecular and morphological phylogenies of the Asteraceae. The ndhF tree identified five major clades: (i) the Calyceraceae is the sister family of Asteraceae; (ii) the Barnadesioideae is monophyletic and is the sister group to the rest of the family; (iii) the Cichorioideae and its two basal tribes Mutisieae and Cardueae are paraphyletic; (iv) four tribes of Cichorioideae (Lactuceae, Arctoteae, Liabeae, and Vernonieae) form a monophyletic group, and these are the sister clade of the Asteroideae; and (v) the Asteroideae is monophyletic and includes three major clades.

Amino Acid Sequence↗
PubMed1995

Bacteriophage P2: genes involved in baseplate assembly.

The sequences of two previously defined tail genes, V and J, of the temperate bacteriophage P2, and those of two new essential tail genes, W and I, were determined. Their order is the late gene promoter, VWJI, followed by the tail fiber genes H and G, and a transcription terminator. The V gene product is the small spike at the tip of the tail, and the J gene product lies at the edge of the baseplate. The W gene product may be homologous to the product of gene 25 of T4 phage, which is part of the T4 baseplate. A temperature-sensitive mutation in gene V affects satellite phage P4 production more than it affects the production of P2 helper phage. P4 mutations that partially compensate for this defect of gene V lie in the P4 capsid size determination gene, sid.

Amino Acid Sequence↗
PubMed1995

Regulation of the expression of IL-8 receptor A/B by IL-8: possible functions of each receptor.

We investigated the regulatory mechanism of the expression of IL-8R, IL-8R type A (IL-8RA), and IL-8R type B (IL-8RB) on human neutrophils by IL-8. The expression of IL-8RA/B was analyzed by flow cytometry using mAb specific for each receptor. IL-8 down-modulated > 90% of IL-8RA and IL-8RB expression within 5 min. A related C-X-C chemokine, melamona growth stimulatory activity, down-modulated IL-8RB but not IL-8RA. It required 7 to 13 times more IL-8 to down-modulate IL-8RA than IL-8RB, as determined by the half-maximal effective concentration of IL-8. Scatchard analysis showed that the affinity of IL-8RA for IL-8 was lower than that of IL-8RB. The possible functions of each IL-8R were explored by comparing 1) the expression levels of IL-8RA/B on migrated neutrophils during in vitro chemotaxis assay and 2) the recovery rate of IL-8RA/B expression after down-modulation by IL-8. Results obtained from the in vitro chemotaxis show that the expression level of IL-8RB, but not IL-8RA, on neutrophils that migrated into the chamber containing low concentrations (< 1 nM) of IL-8 was significantly reduced compared with the control level. This suggests that IL-8RB may play as active role in the initiation of neutrophil migration distant from the site of inflammation, where the concentration of IL-8 is at the picomolar level. After down-modulation by 119 nM IL-8, the expression of IL-8RA fully recovered within 1.5 h, while the recovery rate of IL-8RB expression was slow and never reached more than 40% of the control level during a 3-h culture period. The rapid reexpression of IL-8RA suggests that the low affinity IL-8RA may play a more active role in mediating IL-8 signal at the site of inflammation, where the concentration of IL-8 is high.

Antibodies, Monoclonal↗