Alanine scan reveals modifiable residues in teixobactin.

An alanine scan of Lys10-teixobactin reveals that a cationic residue at position 10 is not necessary for antibiotic activity and that position 3 tolerates substitution without loss of activity. An unexpected correlation between poor aqueous solubility and better antibiotic activity of the teixobactin analogues is observed.

Regional pulmonary blood flow in the lung of the chicken.

It is known that alterations in respiratory gases in birds can cause a nonhomogenous redistribution of pulmonary blood flow between the 2 separate gas-exchanging regions of the avian lung, the paleopulmo (PALEO) and neopulmo (NEO); however, the effect of alterations in respired gas content on the distribution of pulmonary blood flow in birds, such as the chicken, that possess a highly developed NEO is not known. This study used a colorimetric microsphere method to determine the effects of hypoxia and hypercapnia on the relative distribution of pulmonary blood flow in anesthetized chickens (Gallus domesticus) during control (normoxic) and experimental (hypoxic or hypercapnic) conditions, where the relative regional distribution of blood flow in the lung is expressed as the ratio NEO/PALEO. Administration of a hypoxic gas mixture (16.0% O(2)) produced a 13.4% increase in NEO/PALEO, and, administration of a hypercapnic gas mixture (5.0% CO(2)) resulted in a 27.8% increase in NEO/PALEO. Our results are consistent with a mechanism in which the regional redistribution of pulmonary blood flow is mediated by local intrapulmonary factors.

Differential hormonal regulation of leukemia inhibitory factor (LIF) in rabbit and mouse uterus.

Leukemia inhibitory factor (LIF) has been shown to be essential for the implantation of mouse blastocysts. The present study was designed to determine how LIF protein was hormonally regulated in rabbit and mouse uterus using immunohistochemistry. In unmated rabbits, LIF protein was at a low level in the uterine epithelium and glands, and up-regulated by progesterone alone or estradiol-17 beta and progesterone combined. Estradiol-17 beta alone had no apparent effect. In ovariectomized mice, the level of LIF protein was very low in the uterine epithelium and glands, and was up-regulated by estradiol-17 beta alone or estradiol-17 beta and progesterone combined. Progesterone alone had no apparent effect. These results suggest that LIF protein is differentially regulated in rabbit and mouse uterus by progesterone and estrogen, respectively. This would explain the high level of LIF protein observed in uterine epithelium and glands prior to blastocyst implantation in the two species with different hormonal requirements for implantation.

Localization of leukemia inhibitory factor in human endometrium during the menstrual cycle.

Leukemia inhibitory factor (LIF) has been shown to be imperative for the implantation of mouse blastocysts. The objective of this study was to examine the pattern of LIF protein in the human endometrium during the menstrual cycle. A low level of LIF was detected in endometrial glands during the proliferative phase. During the luteal phase, LIF staining in the glands appeared stronger in the mid- and late luteal phase than immediately after ovulation. However, a low level of LIF was detected in the stromal cells during the early and midproliferative phase, while only a minimal level was observed during the late proliferative and luteal phases.

Leukemia inhibitory factor, LIF receptor, and gp130 in the mouse uterus during early pregnancy.

Leukemia inhibitory factor (LIF) has been shown to play an important role in the implantation of mouse blastocysts. The present study was designed to investigate the changes of LIF protein, LIF receptor, and gp130 in the mouse uterus during the early pregnancy. LIF protein and LIF receptor were at high levels in the mouse uterus near the time of ovulation and on day 4 of pregnancy. gp130 was highest on days 3 and 4 of pregnancy. Both LIF receptor and gp130 showed strong staining in the stroma of the day 5 uterus, at a time when LIF protein was low. The presence of LIF receptor and gp130 in the luminal epithelium on day 4 and in the stroma on day 5 may indicate the site of the high affinity LIF receptor. The coexistence of a high level of LIF protein, LIF receptor, and gp130 in the day 4 uterus is consistent with the previously observed high level of uterine LIF mRNA on the same day and the importance of LIF for the blastocyst implantation in mouse.

Stimulation of prostaglandin (PG) F2 alpha and PGE2 release by tumour necrosis factor-alpha and interleukin-1 alpha in cultured human luteal phase endometrial cells.

Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) are important mediators of cell signalling in the uterus. Prostaglandins (PG) have been implicated in the increase of endometrial vascular permeability which occurs during the implantation process. This study evaluates the effect of these two pleiotropic cytokines on PGF2 alpha and PGE2 release from human luteal phase endometrial glandular epithelial cells (GEC) and stromal cells (STC) in culture. Basal PGF and PGE release did not differ significantly from each other or among cell types, and declined significantly with increasing number of days in culture. On day 3, basal PG release had decreased to half of that on day 1 of culture. However, both cell types were still able to respond to the addition of exogenous arachidonic acid (5 microM) on day 3 of culture, with PG release by GEC being elevated 7- to 10-fold and by STC moderately, but still significantly, on day 4. The permissive effect of arachidonic acid on the stimulation of PG release may indicate the down-regulation of phospholipase A2 with continued time in culture. However, the addition of arachidonic acid (5 microM) on day 0 of culture, while able to cause significantly increased PG release from GEC, had no effect on STC. In contrast, the addition of a combination of arachidonic acid (5 microM), and either recombinant human TNF-alpha (10 micrograms rhTNF-alpha/l) or 10 micrograms rhIL-1 alpha/l, had a synergistic action and caused the significantly increased release of PGF and PGE from both cell types, compared with that achieved with either arachidonic acid or the cytokine alone (although GEC responded more than STC). During the first 24 h after the addition of rhTNF-alpha or rhIL-1 alpha, both cytokines stimulated PG release from both cell types in a dose- and time-dependent fashion. Neither cycloheximide (10 microM) nor actinomycin D (10 microM) affected basal PG release, but both blocked cytokine-induced PG release from both cell types. These results suggest that there is a differential control of human endometrial cell PG biosynthesis, and that PG release may be regulated through gene activation.

Interleukin-1 alpha in the rabbit uterus during early pregnancy.

Immunoreactive (ir) interleukin-1 alpha (IL-alpha) was present in the endometrium and myometrium of the rabbit uterus during early pregnancy. Interleukin-1 alpha was at a high level in endometrial epithelium from days 3 to 6 of pregnancy. A similar level of IL-1 alpha was detected on day 6 of pseudopregnancy. Interleukin-1 alpha declined rapidly on day 7 at both the implantation and non-implantation areas. Our results suggest that IL-1 alpha may play a role in rabbit blastocyst implantation.

Leukaemia inhibitory factor in human endometrium during the menstrual cycle: cellular origin and action on production of glandular epithelial cell prostaglandin in vitro.

Leukaemia inhibitory factor (LIF) is a pleiotrophic cytokine which plays an obligatory role in mouse implantation. To investigate its potential role in the regulation of uterine function in the human, LIF secretion by isolated human endometrial glandular epithelial and stromal cells in primary culture was determined. Endometrial cells secreted a detectable amount of LIF protein during the first 48 h of culture. In the follicular and late-luteal phases, LIF secretion by both cell types was low. At every stage of the menstrual cycle, the epithelial cells secreted significantly more LIF than did stromal cells. Glandular epithelial cells of the mid-luteal phase, at the expected time of implantation in the human, secreted significantly more LIF than at other stages of the cycle. Stromal cells showed a similar, but nonsignificant, LIF secretion pattern. It could be concluded that endometrial LIF expression was dependent on cell type and stage of the menstrual cycle, and might thus play a role in human implantation. Oestradiol-17 beta stimulated both prostaglandin (PG) F and E release by the epithelial cells in both follicular and luteal phases. PGE release during the luteal phase was greater than in the follicular phase. However, addition of recombinant human LIF did not change either PGF or PGE release in either follicular or luteal phases, in the presence or absence of oestradiol.

Expression patterns of leukaemia inhibitory factor receptor (LIFR) and the gp130 receptor component in rabbit uterus during early pregnancy.

The presence of leukaemia inhibitory factor (LIF) binding and expression of the gp130 component of the LIF receptor were studied in the rabbit uterus during pregnancy. LIF binding to myometrium was moderate in oestrous and non-oestrous animals and on day 1 of pregnancy, declined on days 2 and 3, and increased to a peak value on days 5 and 6 of pregnancy. Binding to stromal cells was not observed. Binding of LIF to luminal and glandular epithelium was low in unmated animals and on days 1 and 2 of pregnancy. Binding to luminal epithelium increased from day 3, and to glandular epithelium from day 5 of pregnancy. Highest binding was seen on days 5 and 6, with a slight decline observed on day 7, and with little difference between the mesometrial and antimesometrial regions of the implantation site. In all cases, binding of LIF was similar in the uteri of day 6 pseudopregnant and pregnant animals. At all stages, gp130 was absent from stroma and almost absent from myometrium and glandular epithelium. It was expressed in luminal epithelium, reaching maximal expression on day 6 of pregnancy and pseudopregnancy, but diminished on day 7 of pregnancy, particularly in the antimesometrial area of the implantation site. The coexpression of LIF binding and gp130 may indicate the presence of high-affinity LIF receptor, which matches the pattern of LIF protein expression and, as in mice, suggests its importance for implantation.

Hexokinase binding in ischemic and reperfused piglet brain.

Hexokinase catalyzes the first step in cerebral glucose utilization and is a rate-limiting enzyme in glycolysis. Glucose utilization is tightly coupled to cerebral blood flow so that during ischemia the brain has a decreased supply of glucose, as well as oxygen. We studied hexokinase enzymatic activity in a newborn piglet model of ischemia-reperfusion to determine if any changes in the activity or mitochondrial binding of the enzyme occurred. We observed that mitochondrial binding of cortical HK increased from 55 to 71% with ischemia and returned toward control levels, but did not completely recover, after 2 h of reperfusion.

[Systematic concept and development model for the production base of Gynostemma pentaphyllum (Thunb.) Madino].

Based on the theories and methods of systematic engineering, the economic, ecological and social benefits of the whole set of regenerating techniques for Gynostemma pentaphyllum are evaluated comprehensively under the consideration of modern agroforestry and stereoscopic agriculture. As a result of the evaluation an optimal model of artificial complex ecosystem circulation for the agricultural-forestry-medicinal materials in the production base of Gynostemma pentaphyllum is selected.

Temporal and spatial expression of leukemia inhibitory factor in rabbit uterus during early pregnancy.

Leukemia inhibitory factor (LIF) has been shown to play an important role in the implantation of mouse blastocysts. The present study was designed to document the appearance of LIF in the rabbit uterus during early pregnancy and to determine whether changes just prior to implantation, similar to those in mice, occurred. LIF was localized in endometrial epithelium, myometrium, and endometrial glands. A low level of LIF was detected in the uterus of nonestrous and estrous females. LIF expression reached its highest level on day 5 of pregnancy and declined on days 6 and 7. By day 13 of pregnancy, little endometrial LIF was apparent. The expression of LIF on day 5 of pseudopregnancy was similar to that on day 5 of pregnancy. LIF expression was much higher at implantation sites than that at nonimplantation areas on day 7 of pregnancy. It is concluded that LIF may be important for the implantation of rabbit blastocysts.

[Agronomic standardization of Gynostemma pentaphyllum (Thunb.) Makino].

In this paper, the simulation models for 3 main agronomic measures, plants/mu, cuttage date and supplement of nitrogen that affect the yield and economic effect of Genostemma:pentaphyllum, are analyzed by the quadratic orthogonal rotative regression design. As a result of the analysis optimal agronomic combination models are suggested.

[Intercropping techniques for Gynostemma pentaphyllum (Thunb.) Makino].

By the grey correlational analysis and AHP method, the economic, ecological and social benefits of some combination models for intercropping Gynostemma pentaphyllum are evaluated. As a result of the evaluation optimal combination models and management measures are presented.