Recent developments in the human maternal-fetal immune interaction.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A King.
Explore the source record for details and available documents.
MICs of penicillin, methicillin, clindamycin, erythromycin, sodium fusidate and gentamicin were determined by an agar dilution method for 300 current isolates of Staphylococcus aureus and 100 of S. epidermidis, collected from four centres, and 38 stock strains of methicillin-resistant S. aureus (MRSA). All but one of the 300 current isolates of S. aureus were sensitive to clindamycin (MIC less than 0.5 mg/l), with an MIC90 of 0.12 mg/l. Of a total of 39 MRSA strains, 11 (28.2%) were resistant to clindamycin (MIC greater than 32 mg/l); all of these strains were also resistant to erythromycin. Ten of the 100 strains of S. epidermidis were resistant to clindamycin; they came from a reasonably equal geographical distribution and were also resistant to erythromycin. The results suggest that clindamycin might still be useful as a second-line agent for infections caused by S. aureus and S. epidermidis, although its activity against MRSA was limited to approximately two-thirds of the MRSA strains tested in this study.
Temafloxacin, like other 4-quinolones, was highly active against most isolates of Enterobacteriaceae. It was slightly less active than ciprofloxacin but approximately as active as ofloxacin and enoxacin. It was the most active of the quinolones against Acinetobacter spp. and Xanthomonas maltophilia but was slightly less active than ciprofloxacin against Pseudomonas spp. Temafloxacin was highly active against Haemophilus influenzae, Moraxella catarrhalis and Neisseria gonorrhoeae and was the most active of the quinolones against Gardnerella vaginalis and Campylobacter coli/jejuni. It was more active than ciprofloxacin against most staphylococci and equally active against streptococci and enterococci. Temafloxacin was the most active quinolone against anaerobic bacteria and, with the exception of a few isolates of Bacteroides spp. and some clostridia, all anaerobes were within the sensitive range (MIC less than or equal to 2 mg/l).
Tosufloxacin was highly active in vitro against most isolates of Enterobacteriaceae. It was slightly less active than ciprofloxacin for most species but more active than temafloxacin. It was the most active agent against Acinetobacter spp., Xanthomonas maltophilia and some Pseudomonas spp. but was slightly less active than ciprofloxacin against the fluorescent pseudomonads. Tosufloxacin was highly active against strains of Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae and Campylobacter coli/jejuni. It was the most active of the fluoroquinolones tested against staphylococci (MICs 0.016-0.25 mg/L), streptococci (MICs 0.06-1 mg/L) and enterococci (MICs 0.12-4 mg/L). Tosufloxacin was also the most active quinolone tested against anaerobic bacteria and, with the exception of a few isolates of Bacteroides spp. and some clostridia, all anaerobes had tosufloxacin MICs less than 1 mg/L.
Thirteen renal allograft recipients (6 patients on cyclosporine/7 patients on azathioprine) participated in a short-term oral protein-loading study to determine the effect of cyclosporine on an allograft's functional reserve. The baseline glomerular filtration rate of the two groups were similar (52 +/- 18 ml/min/1.73 m2 for the azathioprine/conventional therapy (CT) group and 47 +/- 12 ml/min/1.73 m2 for the cyclosporine (CsA) group), as were the baseline effective renal plasma flows (218 +/- 78 ml/min/1.73 m2 and 222 +/- 75 ml/min/1.73 m2, respectively). At 3 hr following the protein load there was an increase in GFR to 66 +/- 28 ml/min/1.73 m2 in the CT group. The GFR (39 +/- 8 ml/min/1.73 m2) of the CsA group at this time was unchanged. The responses in ERPF were similar. No significant difference was found between the two groups baseline RAA profiles (4.7 +/- 3.3 ng/ml/hr (CT) and 4.7 +/- 1.7 ng/ml/hr [CsA]), or those at the third hour (8.1 +/- 8.3 ng/ml/hr (CT) and 3.5 +/- 1.9 ng/ml/hr [CsA]). The data in this study indicate that CsA alters the renal allograft's response to a protein meal. This difference may be related to an altered vasodilatory response. This altered vascular reactivity may be mediated through renin activation and/or other hemodynamic regulators such as prostaglandins.
In this study, the CD3- LGL/NK cells present in the pregnant human uterus have been characterized. Phenotypic and morphologic analyses of decidual LGL revealed many similarities to the minor CD56bright+, CD16- subset in peripheral blood, but there were some important differences. The relative surface density of CD56+ is greatly increased on decidual LGL to 22x that found on the majority of CD56+ peripheral blood NK cells. The CD56bright+ cells in decidua show LGL morphology, whereas in peripheral blood, they are mainly agranular. Proliferation of CD56+ cells occurs predominantly during the nonpregnant secretory (luteal) phase, indicating these CD56+ uterine LGL do not migrate as terminally differentiated cells. The appearance of CD56+ cells was examined at the ultrastructural level using immunoelectron microscopy. Cells with phenotypic characteristics of decidual LGL occur in a higher percentage (1.11%) in the peripheral blood of women of reproductive age than in men (0.66%). On the basis of these results, it is proposed that the CD56bright+ uterine leukocytes represent a distinctive, hormonally regulated subset possibly adapted to control human placentation.
Eighteen healthy people over 65 years of age were studied to compare the 99mTC-diethylenetriamine pentaacetic acid (DTPA) clearance, the measured 24-hour creatinine clearance and the assessed creatinine clearance using the Cockcroft and Gault (C-G) formula to measure their glomerular filtration rate. Significant correlations were found between the isotopic method and the measured creatinine clearance (r = 0.71; p less than 0.001); the measured creatinine clearance and the C-G formula (r = 0.81; p less than 0.001), and the isotopic method and the C-G formula (r = 0.70; p less than 0.001). The C-G formula correlated better with both the 99mTc-DTPA clearance and the measured creatinine clearance when the female correction factor was used. This study has shown that in healthy, elderly people, the C-G formula for assessing the creatinine clearance correlated extremely well with the standard clinical tests for measuring the glomerular filtration rate. Whilst the formula has clinical value and allows rapid and accurate assessment of renal function in the elderly, the clinician must be aware that the formula relatively underestimates the true renal clearance.
The aim of this study was to investigate the localization of endothelin-like immunoreactivity (ET-IR) in human placenta, chorion and amnion and to compare the endogenous concentration of immunoreactive endothelin (ET) in these tissues before and after the onset of labour. ET-IR was detected in the endothelium of stem vessels in placental villi, as well as in decidual stromal cells in the basal maternal plate, by immunocytochemistry using primary polyclonal rabbit antibody. A specific radioimmunoassay was used to detect endogenous concentration of ET in homogenized placental tissues. The endogenous concentration of ET-IR was significantly greater in amnion than in chorion and placenta (amnion 249 +/- 13 fmol/g; chorion 190 +/- 11 fmol/g; placenta 169 +/- 14 fmol/g; means +/- S.E.M.; n = 12; P less than 0.01). No significant difference was seen before or after the onset of labour. The detection of ET-IR in placenta, chorion and amnion suggests that the ETs may play a role in the paracrine control of human uterine function.
Many reports show that interleukin 1 (IL-1) is produced by mouse and human placenta but the cell type that is responsible for this production has yet to be identified. For this reason we attempted to localize IL-1 alpha and IL-1 beta directly on formalin-fixed paraffin-embedded normal human placentae at different stages of pregnancy using immunohistochemical techniques and specific antibodies. The results obtained show that both IL-1 forms are localized to villous syncytiotrophoblast and to extravillous trophoblast, while villous cytotrophoblast and cytotrophoblast columns are unreactive. A gradual decrease of reactivity was observed with increasing gestation age for both IL-1 forms, but the staining for IL-1 beta was in all sections higher than for IL-1 alpha. Although the physiological role of IL-1 in pregnancy has yet to be established, the presence of this cytokine in the cells facing maternal blood and tissues suggests a possible involvement in the immunoregulation of fetal acceptance.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We describe the ontogeny of feline temporal lobe epilepsy after amygdala kindling in 24 cats, aged 2.5 months to over 1 year. In so doing, we report the first experimental model of spontaneous epilepsy in immature animals. Preadolescent kittens (n = 12 less than or equal to 6.5 months) are far more likely to develop epilepsy, indexed by spontaneous seizures, than are adult cats (n = 12 greater than 1 year). Moreover, youth accelerated the development of epilepsy. The younger the kitten at the beginning of kindling, the more probable and rapid the onset of spontaneous seizures. Failed postictal depression was the most reliable precursor of spontaneous seizures in immature cats. However, spontaneous epilepsy continued after postictal refractory periods stabilized and was still present when kittens matured to adulthood. Collectively, the results suggest that failed inhibition contributes to the onset of spontaneous epilepsy in immature animals but that other morphologic, physiological and/or chemical changes might sustain epilepsy afterwards.
In in vitro tests the broad-spectrum cephalosporins cefpirome and cefepime were highly active against Enterobacteriaceae, although often less so against strains resistant to amoxicillin-clavulanate and ticarcillin-clavulanate, and against most strains of Acinetobacter spp. and Aeromonas hydrophila. They were also active against Pseudomonas aeruginosa, although strains with non-plasmid mediated beta-lactam resistance were sometimes less sensitive. Other Pseudomonas spp. varied in their sensitivity. Both agents were highly active against Haemophilus influenzae, but beta-lactamase-producing Branhamella catarrhalis were somewhat less sensitive. Neisseria gonorrhoeae were susceptible, although non-beta-lactamase producing penicillin-resistant strains had higher MICs. Gardnerella vaginalis was also susceptible and Campylobacter coli/jejuni usually susceptible. Both antibiotics had good activity against Staphylococcus aureus and coagulase-negative staphylococci except for methicillin-resistant strains and Staphylococcus haemolyticus which were of borderline sensitivity. All streptococci were sensitive, with the exception of highly penicillin-resistant pneumococci and enterococci against which cefpirome had greater activity than cefepime. Both antibiotics had little useful activity against the Bacteroides fragilis group or Bacteroides oralis group but were active against most other anaerobes. Clostridium difficile and some other Clostridium species were resistant.
Explore the source record for details and available documents.
Leukocytes in endometrium and decidua are phenotypically and morphologically similar to granulated lymphocytes at other mucosal surfaces. Although their exact functions are not known, we suggest they may have a role in the control of implantation and the transformation of the uterine vasculature by trophoblast on which the blood supply to the fetoplacental unit depends.
We have previously shown that human cultured trophoblast cells are resistant to lysis by natural killer (NK) cells from both peripheral blood and decidua although cells are present in decidua which do exhibit NK activity against K562(1). Using a cold-target inhibition assay and a single-cell conjugate assay we have now examined whether these trophoblast cells have NK target structures on their surfaces. Our findings indicate that first-trimester human trophoblast cells do not express surface structures recognized by decidual Leu19+ (CD56+) large granular lymphocytes (LGLs) isolated from human decidua. Immunostaining of the conjugates formed between decidual NK effectors and K562 cells confirmed that these effector cells are CD56+ LGLs.
Freshly isolated decidual large granular lymphocytes (LGL) show natural killer (NK) activity against K562 cells but not against normal human trophoblast. We now show that these decidual LGL proliferate in vitro in response to recombinant interleukin-2 (rIL-2) and that these rIL-2-stimulated cells acquire a broad cytolytic potential that is characteristic of lymphokine-activated killer (LAK) cells. Both fetal fibroblasts and JEG-3 choriocarcinoma cells are resistant to lysis by freshly isolated decidual effectors but are readily killed by IL-2-stimulated decidual LGL. The ability to kill these target cells is acquired after only 18 hr exposure to rIL-2. rIL-2-activated decidual LGL also kill cultured normal trophoblast cells but much lower levels of cytolysis were seen even after the effectors had been stimulated with rIL-2 for 4-6 days. The preferential killing of malignant over normal human trophoblast cells raises questions about the potential role of IL-2-activated decidual LGL in the control of unduly invasive or malignant trophoblast populations in vivo.