Human immune responses to hapten-conjugated cells. II. The roles of autologous and allogeneic histocompatibility determinants in proliferative responses in vitro.

Proliferative responses of human lymphocytes primed in vitro to autologous TNP-cells were found to be associated with autologous D-region determinants irrespective of HLA-B locus antigens. Family studies of secondary TNP-conjugate proliferative responses demonstrated a gene dosage effect in this phenomenon. Moreover, co-culture with allogeneic cells did not affect the net TNP-conjugate proliferative responses of primed responder cells, suggesting that HLA-D region preference was due to a requirement for representation of TNP-molecules in association or combination with autologous MHC structures. Alloantigens were found to influence the sensitization of lymphocytes to autologous hapten-conjugated cells. Co-culture of allogeneic and TNP-modified autologous stimulator cells in primary cultures enhanced the secondary TNP proliferative response. Sensitization of human lymphocytes to allogeneic cells alone did not prime responses to autologous modified cells. However, priming lymphocytes to modified autologous cells potentiated responses to allogeneic cells. The data suggest a complex relationship between responses to alloantigens and modified autologous cells.     

Abnormal methylation does not prevent X inactivation in ICF patients.

DNA undermethylation is a characteristic feature of ICF syndrome and has been implicated in the formation of the juxtacentromeric chromosomal abnormalities of this rare syndrome. We have previously shown that in female ICF patients the inactive X chromosome (Xi) is also undermethylated. This result was unexpected since female ICF patients are not more severely affected than male patients. Here we show that CpG island methylation is abnormal in some ICF patients but in other ICF patients, the difference in methylation pattern between Xi and Xa (active X) is maintained. The consequences of Xi undermethylation on gene expression were investigated by enzyme assays. They showed that significant gene expression did not correlate with CpG island methylation status. The widespread Xi undermethylation does not affect overall Xi replication timing and does not prevent Barr body formation suggesting that a normal methylation pattern is not required for normal chromatin organization of Xi. Molecular investigation of some X-chromosome intron regions showed that the methylation changes in ICF female patients extend to non CpG islands sequences. Our results suggest that the genetic alteration of DNA methylation in ICF syndrome has little consequence on X chromosome gene expression and chromatin organization.     

Competitive protein-binding radioassay of corticosterone in the plasma of the frog, Rana esculenta L. (author's transl)]

1. Plasma corticosterone levels were measured in the plasma of the edible frog, Rana esculenta, by a competitive protein-binding radioassay method using baboon plasma as CBG source. 2. This technique was sensitive enough to make the assessment of corticosterone levels in 50 microliter plasma samples possible. The assay sensitivity threshold reached 0.5 ng per tube and the corticosterone rate assessment was correct between 0 and 5 ng. The specificity was tested, using 12 different steroids (fig. 2) : baboon CBG had very slight avidity for aldosterone, the second circulating steroid in frog plasma. 3. Using this technique, we have shown that plasma corticosterone underwent seasonal variations. Plasma corticosterone levels, in animals captured in nature during February and June, were 1.51 +/- 0.06 microgram/100 ml (n = 60) and 2.76 +/- 0.14 microgram/100 ml (n = 36), respectively, as appeared in table III. 4. It appeared that the interrenal gland of the frog was not totally dependent on pituitary ACTH, since total hypophysectomy reduced, but did not suppress, corticosterone secretion (table III).     

Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in previously untreated patients with clinical stage D2 prostate cancer: today's therapy of choice

One hundred and ninety-nine patients with clinical stage D2 prostate cancer who had not received previous endocrine therapy or chemotherapy were treated with the combination therapy using the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 26 months (3-59 months). The objective response to the treatment was assessed according to the criteria of the U.S. NPCP. There was a 5.7-fold increase (26.3 vs 4.6%) in the percentage of patients who achieved a complete response compared with the results obtained in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 12 of the 186 evaluable patients (6.5%) did not show an objective positive response at the start of the combination therapy compared with an average of 18% in the same five studies using monotherapy. The duration of response was also significantly improved in the patients who received the combination therapy while the death rate was decreased by approximately two-fold during the first 4 yr of treatment. In fact, while an approximately 50% death rate is observed at 2 yr in all studies using monotherapy, the same 50% death rate is delayed by 2 yr in the present study. It should be mentioned that at the time of relapse under combination therapy, the treatment is continued and, in addition, further blockade of adrenal androgen secretion is achieved with aminoglutethimide. The marked (5.7-fold) improvement in the rate of complete objective responses coupled with the three-fold decrease in the number of non-responders, the increased duration of the positive responses and the two-fold decrease in the death rate during the first 4 yr of treatment are obtained with the combination therapy using Flutamide and castration, thus improving the quality and duration of life with no or minimal side-effects. By blocking the androgen receptors in the prostatic cancer tissue, the antiandrogen decreases the action of the androgens of adrenal origin and thus inhibits the growth of a large number of tumors which, otherwise, would continue to be stimulated by the adrenal androgens left after medical or surgical castration.     

Clinical chronopharmacology of ACTH 1-17. I. Effects on plasma cortisol and urinary 17-hydroxycorticosteroids

The aim of the investigation was to study the effects of ACTH 1-17 on both plasma cortisol and urinary 17-OHCS in health adult young males with regard to the time (clock hours) at which this polypeptide was injected. Eight healthy adults (males from 18-30 years) volunteered for the study. They were synchronized with a diurnal activity from 0700 to 0000 and a nocturnal rest. Each week, during 6 consecutive weeks (January 19 to February 25, 1980), a 3-day test was performed on Saturday, Sunday and Monday. On Sundays 3 control-tests and 3 ACTH-tests were programmed during which either saline or 100 micrograms ACTH 1-17 were injected i.m. at respectively 0700, 1400 and 2100. During each 3 day-test (72 h) the urinary excretion of 17-OHCS was determined every 4 h at fixed clock hours. In addition, on Sundays, venous blood was sampled prior to control or ACTH injections at respectively 0700, 1400, and 2100 and 20, 40, 60, 90, 120, 150 and 180 min thereafter. Plasma cortisol (radioimmunoassay) was determined in samples thus collected. Both conventional and cosinor methods were used for statistical analyses. A strong and statistically significant rise of plasma cortisol was observed after all of the ACTH 1-17 injections. The obtained mean response curves were observed after all of the ACTH 1-17 injections. The obtained mean response curves were similar in form and parallel. The highest plasma cortisol curve corresponded to ACTH injected at 0700, the lowest to ACTH injected at 2100. The curve corresponding to ACTH injected at 1400 went in-between. The 24-h urinary excretion of 17-OHCS after ACTH 1-17 was approximately 4 times greater than the control value when injected at 0700, approximately 3 times greater than control when injected at 1400 and only twice greater than control when injected at 2100. In terms of changes in plasma cortisol and 17-OHCS the greatest best benefit of ACTH 1-17 is achieved when this polypeptide is injected at 0700, rather than at 1400 or 2100 in diurnally active subjects.     

Vegetation state changes in the course of shrub encroachment in an African savanna since about 1850 CE and their potential drivers

1. Shrub encroachment has far‐reaching ecological and economic consequences in many ecosystems worldwide. Yet, compositional changes associated with shrub encroachment are often overlooked despite having important effects on ecosystem functioning.
2. We document the compositional change and potential drivers for a northern Namibian Combretum woodland transitioning into a Terminalia shrubland. We use a multiproxy record (pollen, sedimentary ancient DNA, biomarkers, compound‐specific carbon (δ¹³C) and deuterium (δD) isotopes, bulk carbon isotopes (δ¹³Corg), grain size, geochemical properties) from Lake Otjikoto at high taxonomical and temporal resolution.
3. We provide evidence that state changes in semiarid environments may occur on a scale of one century and that transitions between stable states can span around 80 years and are characterized by a unique vegetation composition. We demonstrate that the current grass/woody ratio is exceptional for the last 170 years, as supported by n‐alkane distributions and the δ¹³C and δ¹³Corg records. Comparing vegetation records to environmental proxy data and census data, we infer a complex network of global and local drivers of vegetation change. While our δD record suggests physiological adaptations of woody species to higher atmospheric pCO₂ concentration and drought, our vegetation records reflect the impact of broad‐scale logging for the mining industry, and the macrocharcoal record suggests a decrease in fire activity associated with the intensification of farming. Impact of selective grazing is reflected by changes in abundance and taxonomical composition of grasses and by an increase of nonpalatable and trampling‐resistant taxa. In addition, grain‐size and spore records suggest changes in the erodibility of soils because of reduced grass cover.
4. Synthesis. We conclude that transitions to an encroached savanna state are supported by gradual environmental changes induced by management strategies, which affected the resilience of savanna ecosystems. In addition, feedback mechanisms that reflect the interplay between management legacies and climate change maintain the encroached state.

     

From speciation to introgressive hybridization: the phylogeographic structure of an island subspecies of termite, <Emphasis Type="Italic">Reticulitermes lucifugus corsicus</Emphasis>

Background  

Although much research has been carried out into European Reticulitermes taxonomy in recent years, there is still much discussion about phylogenetic relationships. This study investigated the evolution from intra- to interspecific phylogeny in the island subspecies Reticulitermes lucifugus corsicus and threw new light on this phenomenon. An integrative approach based on microsatellites and mitochondrial and nuclear DNA sequences was used to analyze samples taken from a wide area around the Tyrrhenian sea and showed how the subspecies evolved from its origins to its most recent form on continental coasts.