The effect of endocervical PGE2-gel (Prepidil™) gel on plasma levels of 13,14-dihydro-15-keto-PGE2(PGEM) in women at term

Term pregnant patients undergoing preinduction cervical softening were randomized to receive no treatment (controls) or 0.5 mg PGE₂-triacetin gel (Prepidil™ gel) endocervically. Plasma samples containing PGEM collected 4 hrs post-treatment and converted to the stable bicyclo degradation product (bicyclo-PGEM) were assayed by RIA. Positive clinical effect (responders) during 12 hrs after treatment (Bishop score increase≥3, in labor or delivered) were assessed. All evaluations were blind.In nonresponders (n=35), the means of the bicyclo-PGEM variables (mean, maximum, area under the curve) were all about 18% higher in gel-treated patients (n=6) than controls (n.s.). In responders (n=38), the variables were all about 80% higher in gel-treated women (n=32) than controls (p<.01). In controls (n=35), the responders (n=6) had 50% higher levels than nonresponders (n.s.). In the gel-treated women (n=38), responders (n=32) had about 140% higher levels than nonresponders (<.01).The results suggest that both exogenous and endogenous bicyclo-PGEM were measured. Differences in pairwise comparisons suggest that there may be substantially less exogenous bicyclo-PGEM in the gel nonresponders than in gel responders or substantially more endogenous bicyclo-PGEM in gel responders than in control-responders.     

Attempts to alter the heterogeneous response to ANP in sodium-retaining caval dogs.

Chronic caval dogs with ascites were identified as being natriuretic "responders" or "nonresponders" (delta UNaV less than 20 microequiv./min) following an infusion of atrial natriuretic peptide (ANP) (100 ng.kg-1.min-1). To learn more about the factors modulating tubular resistance to ANP, we attempted to convert responders into nonresponders and vice versa by manipulating the physiological environment. To responding dogs, we readministered ANP in the presence of noradrenaline (n = 5), angiotensin (n = 5), indomethacin (n = 4), and adenosine receptor blockage with theophylline (n = 4), and with purposeful reduction of blood pressure (n = 5). To nonresponding dogs, we readministered the ANP in the face of alpha-adrenergic blockade (n = 4), saralasin (n = 4), dipyridamole to block adenosine cellular uptake (n = 5), and elevation of blood pressure (n = 4). In no case were we able to alter the initial natriuretic response to ANP. Binding parameters of ANP receptors in suspensions of renal papillary cells were equivalent in responding caval dogs (n = 6), nonresponding dogs (n = 7), and normal controls (n = 7), as was cGMP generation. We conclude that the tubular resistance to ANP in caval dogs unresponsive to this natriuretic peptide is not due to antagonism from catecholamines or angiotensin but may be due to a post-cGMP problem in signal transduction, or a reduction in the delivery of ANP to the distal nephron.     

Serum concentrations of sIL-2R, IL-6, TGF-beta1, neopterin, and zinc in chronic hepatitis C patients treated with interferon-alpha

T lymphocytes and immunoregulatory cytokines play an important role in the host response to hepatitis C virus (HCV) infection. Zinc is required for a wide spectrum of immune functions, including T-cell activity. To determine the clinical significance of the cytokines sIL-2R, IL-6, TGF-beta1, neopterin, and of zinc in chronic heptatitis C virus (HCV) infection, we investigated their concentrations in the serum of 16 patients with chronic HCV infection before, during and at the end of therapy with interferon (IFN) alpha (Roferon A), and after 6 months follow-up. Elevated concentrations of sIL-2R, IL-6, TGF-beta1, and neopterin were found in the serum of all patients prior to therapy, as compared to healthy controls. sIL-2R patterns differed in responders and non-responders. While the mean concentration of sIL-2R (335.75 pg/ml) before therapy was about 40% higher in complete responders (n=4) than in controls (272.20 pg/ml), the mean concentration in non-responders (n=6) was 4-fold higher than in controls (1153.33 pg/ml). During therapy, sIL-2R levels in responders decreased by about 40%. Mean IL-6 concentrations in both complete and partial responders (n=6) decreased continuously during treatment, while mean concentrations in non-responders decreased for only a short time, and increased again after cessation of therapy. Mean levels of TGF-beta1 behaved similarly to those of IL-6. Only negligible differences in mean neopterin levels were found between responders and non-responders over the entire observation time. The mean serum zinc concentrations slightly decreased in all 3 patient groups, the greatest reduction occurring in 3 of the 4 responders. The present findings underscore the importance of the immune system in the pathogenesis of chronic HCV infection. Serum sIL-2R levels may be used as a serological marker of outcome following IFN-alpha treatment.     

Different effects of endotoxic shock on the respiratory function of liver and heart mitochondria in rats

This study was designed to clarify whether mitochondrial function/dysfunction and reactive oxygen species (ROS) production have a temporal relationship with organ failure during endotoxic shock. Adult male Sprague-Dawley rats were divided into three groups receiving 1) isotonic saline (control group, n = 16); 2) 8 mg/kg lipopolysaccharide (LPS; n = 8); or 3) 20 mg/kg LPS (n = 8) intraperitoneally under short anesthesia with 3.5% of isoflurane. After 16 h, animals were killed to analyze plasma, rat liver mitochondria (RLM), and rat heart mitochondria (RHM). In accordance with plasma analysis, LPS-treated rats were divided into "responders" and "nonresponders" with high and low levels of alanine aminotransferase and creatine, respectively. RHM from responders had significantly lower respiratory activity in state 3, suggesting a decreased rate of ATP synthesis. In contrast, RLM from responders had significantly higher respiratory activity in state 3 than both nonresponders and the control group. This increase was accompanied by a decrease in phosphate-to-oxygen ratio values, which was not observed in RHM. ROS generation determined with a spin probe, 1-hydroxy-3-carboxypyrrolidine, neither revealed a difference in RHM between LPS and control groups nor between responders and nonresponders. In contrast, RLM isolated from responders showed a marked increase in ROS production compared with both the control group and nonresponders. Our data demonstrate that 1) RHM and RLM respond to endotoxic shock in a different manner, decreasing and increasing respiratory activity, respectively, and 2) there is a temporal relationship between ROS production in RLM (but not in RHM) and tissue damage in rats subjected to LPS shock.     

Acute creatine monohydrate supplementation: a descriptive physiological profile of responders vs. nonresponders

The purpose of this study was to describe the physiological profile of responders (>20 mmol.kg(-1) dry weight [dw] increase in total intramuscular creatine monohydrate [Cr] + phosphorylated creatine [PCr]) versus nonresponders (<10 mmol.kg(-1) dw increase) to a 5-day Cr load (0.3 g.kg(-1).d(-1)) in 11 healthy men (mean age = 22.7 years). Pre-post 5-day cellular measures included total resting Cr content (Cr + PCr), fiber type composition, and fiber type cross-sectional area (CSA) determined from muscle biopsies of the vastus lateralis. Body mass, daily dietary intake, 24-hour urine outputs, urinary Cr and creatinine (CrN), and strength performance measures (1 repetition maximum [1RM] bench and leg press) were also assessed before and after the 5-day loading period. Results indicated that there were 3 levels of response to the 5-day supplementation: responders (R), quasi responders (QR), and nonresponders (NR) with mean changes in resting Cr + PCr of 29.5 mmol.kg(-1) dw (n = 3), 14.9 mmol.kg(-1) dw (n = 5), and 5.1 mmol.kg(-1) dw (n = 3), respectively. The results support a person-by-treatment interaction to acute Cr supplementation with R possessing a biological profile of lowest initial levels of Cr + PCr, greatest percentage of type II fibers, and greatest preload muscle fiber CSA and fat-free mass. Responders also showed improvement in 1RM leg press scores following the 5-day loading period. NR had higher preload levels of Cr + PCr, less type II muscle fibers, small preload muscle CSA, and lower fat-free mass and displayed no improvements in 1RM strength scores. The results suggest that to be considered a responder to acute oral supplementation, a favorable preexisting biological profile may determine the final extent to which an individual responds to supplementation. Physiologic profiles of nonresponders appear to be different and may limit their ability to uptake Cr. This may help partially explain the reported equivocal performance findings in the Cr supplementation literature.     

Changes in muscle activation can prolong the endurance time of a submaximal isometric contraction in humans.

Fourteen young subjects (7 men and 7 women) performed a fatiguing isometric contraction with the elbow flexor muscles at 20% of maximal voluntary contraction (MVC) force on three occasions. Endurance time for session 3 [1,718 +/- 1,189 (SD) s] was longer than for session 1 (1,225 +/- 683 s) and session 2 (1,410 +/- 977 s). Five men and four women increased endurance time between session 1 and 3 by 60 +/- 28% (responders), whereas two men and three women did not (-3 +/- 11%; nonresponders). The MVC force was similar for the responders and nonresponders, both before and after the fatiguing contraction. Fatiguing contractions were characterized by an increase in the electromyogram (EMG) amplitude and number of bursts during the fatiguing contractions. The responders achieved a similar level of EMG at exhaustion but a reduced rate of increase in the EMG across sessions. The rate of increase in EMG across sessions declined for the nonresponders, but it remained greater than that of the responders. The increase in burst rate during the contractions declined across sessions with a negative relation between burst rate and endurance time (r = -0.42). Normalized force fluctuations increased during the fatiguing contractions, and there was a positive relation (r = 0.60) between the force fluctuations and burst rate. Changes in mean arterial pressure and heart rate during the fatiguing contraction were similar for the responders and nonresponders across the three sessions. The results indicate that those subjects who increased the endurance time of a submaximal contraction across three sessions did so by altering the level and pattern of muscle activation.     

Afternoon plasma cortisol in depressed patients: A measure of diagnosis or severity?

Plasma cortisol concentration was measured at 20 min intervals from 3 p.m. (1500 hrs) to 6 p.m. (1800 hrs) in 26 hospitalized patients classified according to the Newcastle Index as endogenously depressed (n = 16) or non-endogenously depressed (n = 10). When examined in depressed state, before treatment, maximum, mean and range of plasma cortisol concentration in this time interval was significantly higher in the endogenously depressed patients than in the non-endogenously depressed patients (p less than 0.01-0.02). The diagnostic identification of endogenous depression on the basis of these cortisol concentration measurements was at least as good as that reported by others using post-dexamethasone cortisol levels. The plasma cortisol levels (maximum, mean) and fluctuations (range) correlated significantly with the degree of depression (Hamilton Depression Scale), and differences in severity of depression could explain most of the differences in cortisol levels between the two diagnostic groups. Nine patients were reexamined after 3-12 months in a non-depressed state, and all unipolar endogenously depressed patients (n = 6) then had clearly reduced cortisol levels and fluctuations.     

Effect of acute intravenous administration of delta-9-tetrahydrocannabinol on the episodic secretion of immunoassayable growth hormone in the rat.

Blood samples from unrestrained, unanesthetized, male rats (300-350 g) were obtained every 15 min. for 9 consecutive hrs. (1000-1900 h). Each rat received, intravenously, a vehicle injection (controls) or a 2.0 mg/kg dose of delta-9-tetrahydrocannabinol (THC) at 1300 h to determine the effect of this drug on the spontaneous episodic secretion of plasma immunoassayable rat growth hormone (rGH). Acute administration of THC suppressed the secretion of rGH, as is evident from mean plasma level (p less than .01), peak height (p less than .02), and integrated peak amplitude (p less than .02) analyses. Episodic secretion was inhibited in all animals (n = 7) receiving THC. Although further investigation is needed to define clearly the physiological mechanisms involved in this response, these data indicate that THC can inhibit the hypothalamic-pituitary control of normal episodic growth hormone secretion in the rat.     

Mechanical discoordination rather than dyssynchrony predicts reverse remodeling upon cardiac resynchronization

By current guidelines a considerable part of the patients selected for cardiac resynchronization therapy (CRT) do not respond to the therapy. We hypothesized that mechanical discoordination [opposite strain within the left ventricular (LV) wall] predicts reversal of LV remodeling upon CRT better than mechanical dyssynchrony. MRI tagging images were acquired in CRT candidates (n = 19) and in healthy control subjects (n = 9). Circumferential strain (epsilon(cc)) was determined in 160 regions. From epsilon(cc) signals we derived 1) an index of mechanical discoordination [internal stretch fraction (ISF), defined as the ratio of stretch to shortening during ejection] and 2) indexes of mechanical dyssynchrony: the 10-90% width of time to onset of shortening, time to peak shortening, and end-systolic strain. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) were determined before and after 3 mo of CRT. Responders were defined as those patients in whom LVESV decreased by >15%. In responders (n = 10), CRT increased LVEF and decreased LVEDV and LVESV (11 +/- 6%, 21 +/- 16%, and 30 +/- 16%, respectively) significantly more (P < 0.05) than in nonresponders (1 +/- 6%, 3 +/- 4%, and 5 +/- 10%, respectively). Among mechanical indexes, only ISF was different between responders and nonresponders (0.53 +/- 0.25 vs. 0.31 +/- 0.16; P < 0.05). In patients with ISF >0.4 (n = 10), LVESV decreased by 31 +/- 18% vs. 5 +/- 11% in patients with ISF <0.4 (P < 0.05). We conclude that mechanical discoordination, as estimated from ISF, is a better predictor of reverse remodeling after CRT than differences in time to onset and time to peak shortening. Therefore, discoordination rather than dyssynchrony appears to reflect the reserve contractile capacity that can be recruited by CRT.     

Sympathetic control after cardiac resynchronization therapy: responders versus nonresponders

Cardiac resynchronization therapy (CRT) decreases muscle sympathetic nerve activity (MSNA) in patients with severe congestive heart failure (CHF) and cardiac asynchrony. Whether this affects equally patients who clinically respond or not to CRT is unknown. We tested the hypothesis that the favorable effects of CRT on MSNA disappear on CRT interruption only in those who respond to CRT. Twenty-three consecutive CHF patients participated in the study, among whom 16 presented a symptomatic improvement by one or more New York Heart Association (NYHA) functional classes 15 +/- 5 mo after CRT (responders), and seven had not improved after 12 +/- 4 mo of CRT (nonresponders). MSNA and echocardiographic recordings were obtained in random order during atrio-right ventricular pacing (ARV), without stimulation in patients who were not pacemaker dependent (OFF, n = 17), and during atrio-biventricular pacing (BIV). Responders had a longer 6-min walking distance, a lower NYHA class and brain natriuretic peptide levels, and a better quality of life than did nonresponders (all P < 0.05). MSNA increased by 25 +/- 7% in the responders, whereas it remained unchanged in the nonresponders, when shifting from the BIV mode to a nonsynchronous condition (ARV and OFF modes) (P < 0.01). Cardiac output decreased by 0.7 +/- 0.2 l/min in the responders but did not change when shifting from the BIV mode to the nonsynchronous pacing mode in the nonresponders (P < 0.01). In conclusion, reversible sympathoinhibition is a marker of the clinical response to CRT.     

Paradoxical growth hormone response following thyroid-stimulating hormone administration in the polycystic ovary syndrome

Growth hormone (GH) and prolactin (PRL) responses after TRH administration were studied in 31 women presenting with the clinical, biochemical and ultrasonographic characteristics of the polycystic ovarian (PCO) syndrome; their results were compared with those of 20 normally menstruating women investigated during the early follicular phase of the cycle. Based on the GH responses two PCO subgroups were observed: (a) nonresponders (n = 16) who showed delta max GH responses (0.7 +/- 0.27 ng/ml, x +/- SE) similar to those of the normals (0.97 +/- 0.20 ng/ml), and (b) responders (n = 15), 48.4% of the PCO patients who showed a paradoxical increase in GH levels (delta max GH, 18.0 +/- 1.96 ng/ml) following thyrotropin-releasing hormone (TRH) administration significantly higher than those observed either in nonresponder PCO patients or in normals. Furthermore, basal GH levels were found to be significantly higher in the responder PCO subgroup (5.65 +/- 0.75 ng/ml) compared to either nonresponders (1.58 +/- 0.21 ng/ml) or normals (1.8 +/- 0.18 ng/ml). However, no correlation was found between basal GH levels and delta max GH responses observed. Additionally, basal PRL and delta max PRL levels following TRH administration did not differ either between the two PCO subgroups or those observed in normal controls. delta 4A, T and E2 levels were similar between the two PCO subgroups. No correlation was found between the delta max GH responses to delta max PRL or the post-luteinizing hormone-releasing hormone stimulation test delta max luteinizing hormone:follicle-stimulating hormone ratio observed or to steroid levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between an alpha(2) macroglobulin DNA polymorphism and late-onset Alzheimer's disease.

An association between a five-base-pair deletion/insertion DNA polymorphism at the alpha(2) macroglobulin gene (A2M) and late-onset Alzheimer's disease (LOAD) has been recently described. We developed a PCR assay to analyze this polymorphism in 190 LOAD patients (older than 65 years) and 400 controls from Spain. Controls were stratified into three groups: <65 years (n = 200), 65 to 80 years (n = 100), and 81 years or older (n = 100). We found a significantly higher frequency of carriers of the D allele in patients older than 81 years compared to controls older than 81 years (p = 0.0012). In addition, the frequency of the D allele was significantly lower in controls older than 81 years compared to controls younger than 65 (p = 0.048). Our work suggests that the D allele confers an age-dependent increased risk to develop late-onset Alzheimer's disease.     

IL-1β is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease

Autoimmune inner ear disease is an enigmatic disorder characterized by recurring episodes of sudden or progressive sensorineural hearing loss. Hearing loss can be improved by timely corticosteroid administration, but only half of those treated respond, and for many responders, that response is lost over time. The mechanisms that control corticosteroid responsiveness in this disorder are largely uncharacterized. We have previously identified that the induction by dexamethasone of IL-1R type II (IL-1R2) expression in PBMC predicts corticosteroid responsiveness in this disorder. In this study, we asked whether IL-1β was overexpressed, and whether clinical corticosteroid responders differentially regulated IL-1β expression or release in response to dexamethasone, as compared with nonresponders. IL-1β has been reported to induce matrix metalloproteinase-9 (MMP-9) expression. Given that metalloproteinases can cleave IL-1R2, we also asked whether MMP-9 expression was altered in this disorder. In this study, we demonstrate that corticosteroid nonresponders have elevated plasma levels of IL-1β and MMP-9 as compared with clinically responsive patients (p = 0.0008 and p = 0.037, respectively). Increasing MMP-9 expression correlated with increasing IL-1β concentration, suggesting that IL-1β expression regulates MMP-9 expression. As expected, monocytes were the predominant producers of IL-1β. In vitro exposure of PBMC to dexamethasone from clinical corticosteroid responders suppressed IL-1β release. PBMC of corticosteroid nonresponders have substantially higher release of IL-1β into the conditioned media, and when exposed to dexamethasone, failed to repress IL-1β release (p = 0.05). Treatment of PBMC from clinical corticosteroid nonresponders with anakinra resulted in repression of IL-1β release, suggesting that IL-1β blockade may be a viable therapy for these patients.     

Comparison of two Ovsynch protocols (GnRH versus LH) for fixed timed insemination in buffalo (Bubalus bubalis)

We evaluated the efficiency of replacing GnRH with LH in the ovulation synchronization protocol in buffaloes. Buffaloes received GnRH on Day 0, (Buserelin; Conceptal, 20 microg), PGF2alpha (Luprostiol; Prosolvin, 15 mg) on Day 7 and GnRH (Buserelin; Conceptal, 10 microg; Group 1) or porcine LH (LH; Lutropin-V, 12.5 mg; Group 2) on Day 9. In Experiment 1, we studied the follicular dynamics of 30 buffaloes (Group 1, n = 15 and Group 2, n = 15). We performed ultrasonography every 12 h from Days 0 to 2, then on Day 7 and then every 6 h from the time of GnRH or LH treatment (Day 9) until the time of ovulation. All females not ovulating by 48 h after the second GnRH or LH injection were considered as nonresponders. In Experiment 2, we evaluated 305 buffaloes (Group 1, n = 154; Group 2, n = 151), using the same two treatments studied in Experiment 1. We also recorded and evaluated aspects like parity, lactational status, the presence of mucus, and uterine tone at the time of artificial insemination (Al). In Experiment 1, ovulation rate after the first GnRH was 86.6% (26/30). Ovulation rates were 93.3% (14/15; Group 1) after the second dose of GnRH and 93.3% (14/15) after LH (Group 2). Ovulation occurred 36.4+/-10.4 h after the first GnRH. The interval for treatment to ovulation was 26.5+/-9.6 h for buffaloes treated with GnRH (Group 1) and 24.4+/-7.9 h for buffaloes treated with LH (Group 2); the time of ovulation did not differ statistically between the two groups (GnRH versus LH; P > 0.05). In Experiment 2, conception rates of the animals AI in the field were 56.5% (Group 1) and 64.2% (Group 2), respectively (P = 0.08). The response to the treatment with LH was not different to the treatment with GnRH; however, multiparous buffaloes had higher conception rates than the primiparous buffaloes in both groups (P > 0.05). Buffaloes with mucus at the time of AI in Group 2 had higher conception rates than the buffaloes that had mucus in Group 1 (P < 0.05). Uterine tone and lactational status did not influence conception rates (P > 0.05). In summary, the results showed that both treatments resulted in synchronization of ovulation and acceptable conception rates. Therefore, the exogenous injection of LH can substitute the GnRH injections in the Ovsynch program in buffaloes.     

Pulmonary arterial pressure-flow plots in dogs: effects of isoflurane and nitroprusside

We investigated the effects of nitroprusside and isoflurane on multipoint pulmonary arterial pressure (PAP)/cardiac index (Q) plots in pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia (fraction of inspired O2, FIO2, 0.4) and hypoxia (FIO2 0.1). Over the entire range of Q studied, 2-5 l.min-1.m-2, hypoxia increased PAP in 16 dogs ("responders") and did not affect PAP in 16 other dogs ("nonresponders"). A hypoxic pulmonary vasoconstriction (HPV) was restored in the nonresponders by intravenous administration of 1 g of acetylsalicylic acid (ASA). Nitroprusside (5 micrograms.kg-1.min-1) inhibited HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). End-tidal 1.41% isoflurane (a minimal alveolar concentration equal to one for dogs) did not affect HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). In the latter group isoflurane increased PAP at the highest Q studied (3-5 l.min-1.m-2) in hyperoxia and hypoxia. In a final group of eight dogs with Q kept constant, PAP remained unchanged during two consecutive sequences of alternated 30-min periods (maximum time to generate a PAP/Q plot) successively at FIO2 0.4 and 0.1, and the hypoxia-induced increase in PAP was reproducible. Thus the present experimental model appeared suitable for the study of the effects of hypoxia and drugs on pulmonary vascular tone of intact dogs. At the given doses HPV was inhibited by nitroprusside and not affected by isoflurane. Products of arachidonic acid metabolism possibly could be implicated in the pulmonary vascular effects of isoflurane.     

Genetic heterogeneity of hypervariable region 1 of the hepatitis C virus (HCV) genome and sensitivity of HCV to alpha interferon therapy

Hepatitis C virus (HCV) populations persist in vivo as a mixture of heterogeneous viruses called quasispecies. The relationship between the genetic heterogeneity of these variants and their responses to antiviral treatment remains to be elucidated. We have studied 26 virus strains to determine the influence of hypervariable region 1 (HVR-1) of the HCV genome on the effectiveness of alpha interferon (IFN-alpha) therapy. Following PCR amplification, we cloned and sequenced HVR-1. Pretreatment serum samples from 13 individuals with chronic hepatitis C whose virus was subsequently eradicated by treatment were compared with samples from 13 nonresponders matched according to the major factors known to influence the response, i.e., sex, genotype, and pretreatment serum HCV RNA concentration. The degree of virus variation was assessed by analyzing 20 clones per sample and by calculating nucleotide sequence entropy (complexity) and genetic distances (diversity). Types of mutational changes were also determined by calculating nonsynonymous substitutions per nonsynonymous site (K(a)) and synonymous substitutions per synonymous site (K(s)). The paired-comparison analysis of the nucleotide sequence entropy and genetic distance showed no statistical differences between responders and nonresponders. By contrast, nonsynonymous substitutions were more frequent than synonymous substitutions (P 相似文献   

Deficits in T helper cells after total lymphoid irradiation (TLI): reduced IL-2 secretion and normal IL-2 receptor expression in the mixed leukocyte reaction (MLR)

Spleen cells from BALB/c mice treated with total lymphoid irradiation (TLI) and from normal, unirradiated mice were compared in the mixed leukocyte reaction (MLR). Although the percentage of CD4+ cells in the spleen was close to normal, 4 to 6 weeks after TLI, the MLR of unfractionated spleen cells from irradiated mice was more than 10-fold lower than controls. A similar reduction was observed when purified CD4+ cells were used as responders in the MLR. Secretion of IL-2 by cells from irradiated mice was also about 10-fold lower than controls. However, the percentage of CD4+ and CD8+ cells which expressed IL-2 surface receptors during the MLR was similar using spleen cells from irradiated and control mice. Addition of an exogenous source of IL-2 restored the proliferative capacity of the irradiated cells and suggests that the lack of IL-2 secretion is the likely explanation of the marked deficit in the MLR of CD4+ spleen cells after TLI.     

Thyroid hormones determine developmental mode in sand dollars (Echinodermata: Echinoidea)

Evolutionary transitions in larval nutritional mode have occurred on numerous occasions independently in many marine invertebrate phyla. Although the evolutionary transition from feeding to nonfeeding development has received considerable attention through both experimental and theoretical studies, mechanisms underlying the change in life history remain poorly understood. Facultative feeding larvae (larvae that can feed but will complete metamorphosis without food) presumably represent an intermediate developmental mode between obligate feeding and nonfeeding. Here we show that an obligatorily feeding larva can be transformed into a facultative feeding larva when exposed to the thyroid hormone thyroxine. We report that larvae of the subtropical sand dollar Leodia sexiesperforata (Echinodermata: Echinoidea) completed metamorphosis without exogenous food when treated with thyroxine, whereas the starved controls (no thyroxine added) did not. Leodia sexiesperforata juveniles from the thyroxine treatment were viable after metamorphosis but were significantly smaller and contained less energy than sibling juveniles reared with exogenous food. In a second starvation experiment, using an L. sexiesperforata female whose eggs were substantially larger than in the first experiment (202+/-5 vs. 187+/-5 microm), a small percentage of starved L. sexiesperforata larvae completed metamorphosis in the absence of food. Still, thyroxine-treated larvae in this experiment completed metamorphosis faster and in much higher numbers than in the starved controls. Furthermore, starved larvae of the sand dollar Mellita tenuis, which developed from much smaller eggs (100+/-2 microm), did not complete metamorphosis either with or without excess thyroxine. Based on these data, and from recent experiments with other echinoids, we hypothesize that thyroxine plays a major role in echinoderm metamorphosis and the evolution of life history transitions in this group. We discuss our results in the context of current life history models for marine invertebrates, emphasizing the role of egg size, juvenile size, and endogenous hormone production for the evolution of nonfeeding larval development.     

Immune response to CagA protein is associated with improved platelet count after Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura

BACKGROUND: Improvement in platelet counts has been reported after eradication of Helicobacter pylori in patients with idiopathic thrombocytopenic purpura (ITP). We examined the levels of serum markers of gastritis and anti-CagA (cytotoxin-associated gene A) IgG antibody in patients with ITP to investigate whether these factors are associated with the platelet response after H. pylori eradication therapy. MATERIALS AND METHODS: One hundred and sixteen consecutive patients with ITP were assessed for H. pylori infection by (13)C-urea breath test and serum H. pylori antibody test. Patients with H. pylori infection received eradication therapy. Before and after eradication therapy, we evaluated serum levels of gastrin, pepsinogen (PG)-I, and PG-II and the anti-CagA IgG antibody titer. RESULTS: H. pylori infection was found in 67 (58%) of the 116 patients with ITP. Fifty-two infected patients received eradication therapy, which was successful in 44 patients (85%). Twenty-seven patients (62%) showed an increased platelet count and were identified as responders. The duration of ITP was shorter in responders than in nonresponders (p = .017). There was no difference of the levels of gastrin and PGs between responders and nonresponders. Before eradication therapy, the serum anti-CagA antibody titer did not differ significantly between responders and nonresponders. However, reduction in the anti-CagA antibody titer after eradication therapy was significantly greater in responders than in nonresponders (p = .013). CONCLUSIONS: H. pylori eradication therapy improves the platelet count in H. pylori-positive patients with ITP of short duration. Immune response of hosts to CagA protein of H. pylori may play a role in the pathogenesis of ITP.     

Non-surgical embryo transfer in cattle embryo-recipient interactions

Results from 2286 non-surgical embryo transfers were analyzed to find relationships between embryo factors and recipient factors that affect pregnancy. Pregnancy rates from morulae (44%) and advanced morulae (53%) were reduced (P < .05) when compared to early blastocysts (65%), blastocysts (65%), blastocysts (66%) and advanced blastocysts (64%). Pregnancy rates from good quality Grade 1 embryos (64%) were higher (P < .05) than from Grade 2 (45%) or Grade 3 (33%) embryos. Pregnancy rates related to synchronization of estrus between donor and recipients are: -36 hrs. (before donor) (59%), -24 hrs. (61%), -12 hrs. (68%), 0 hr. (59%), +12 hrs. (61%), +24 hrs. (58%) and +36 hrs. (41%). Differences in pregnancy rate were significant for -12 hrs. (P < .01) and +36 hrs. (P < .01) recipients. Overall pregnancy rates in recipients on day 5 (48%), 5 1/2 (50%) and 6 (53%) were reduced (P < .02) when compared to day 6 1/2 (62%), 7 (63%), and 7 1/2 (66%) and 8 (62%). Pregnancy rates within each embryo stage of development were not related to synchronization with the donor cow (-36 hrs. to +36 hrs.) or the day of the recipient cycle (day 5 to 8).