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The facultative anaerobic energy metabolism of Schistosoma mansoni sporocysts.

Schistosoma mansoni miracidia in water are known to possess an aerobic energy metabolism, the Krebs cycle being the main terminal of the breakdown of endogenous glycogen reserves. The present study demonstrated that after in vitro transformation of miracidia into sporocysts, the organisms degraded glucose to lactate and carbon dioxide in a more anaerobic ratio than do miracidia. The occurrence of a large Pasteur effect demonstrated, however, that oxidative phosphorylation was still the major process used for energy generation. After 24 h in vitro cultivation the sporocysts had consumed more external glucose and their metabolism had shifted towards lactate production. Sporocysts could cope with inhibited respiration: they had a large anaerobic capacity and survived perfectly in the presence of cyanide, producing a large amount of succinate in addition to lactate. It was demonstrated that this succinate was largely produced via phosphoenolpyruvate carboxykinase (PEPCK). This pathway, which is known to occur in most parasitic helminths, has never been demonstrated in schistosomes, not even in the miracidial stage immediately preceding the sporocysts. It was also shown that in sporocysts part of the lactate was not formed directly by glycolysis, but via a detour including fumarate and the action of PEPCK. The results demonstrated that S. mansoni sporocysts are facultative anaerobes, fully equipped to adjust their energy metabolism to the variable conditions inside their intermediate host, the snail. In the presence of oxygen, they derive most of their energy from the aerobic degradation of glucose to carbon dioxide, but under anaerobic conditions they switch towards lactate and succinate production.

Anaerobiosis↗

Glucose tolerance in rural diabetic Thais, first-degree relatives and non-diabetic controls.

To determine whether non-insulin-dependent diabetes mellitus (NIDDM) in a rural Thai population is characterised by insulin resistance and hyperinsulinaemia, 17 unselected diabetic outpatients from a regional hospital, five first-degree relatives and 10 healthy controls were studied. Subjects in these groups were matched as closely as possible for age and sex, and mean body mass indices were similar (mean +/- S.D.; 21.8 +/- 5.5, 20.6 +/- 1.4 and 21.8 +/- 2.3 kg/m2, respectively, P > 0.5). Beta-cell function (%B) and insulin sensitivity (%S), expressed relative to values for non-diabetic Caucasians, were assessed mathematically using the 'CIGMA' model and plasma glucose and insulin achieved after a standard 1-h glucose infusion. The diabetic patients had higher fasting plasma glucose concentrations than the controls (8.6 +/- 4.0 vs. 4.6 +/- 0.4 mmol/l, P < 0.01) but plasma insulin levels were comparable (geometric mean [-S.D.-+S.D.]; 4.0 [1.7-9.4] vs. 4.0 [1.7-9.2] mU/l, P > 0.1). %B in the diabetic group (21% [10-41]) was lower than in the controls (128% [88-187], P < 0.001) while %S tended to be higher (185% [86-400] vs. 111% [49-251], 0.1 > P > 0.05). Relatives had intermediate values of both variables. %S and %B correlated poorly in the diabetic group (P > 0.1) but together accounted for 90% of the variation in basal plasma glucose (multiple r = 0.95, n = 17, P < 0.0001). Beta-cell dysfunction appears the primary defect in diabetic patients from a Thai subsistence farming population. Insulin resistance may not always characterise NIDDM in geographical areas where a 'thrifty genotype' would be expected; other factors associated with diabetes in developing countries (such increased susceptibility to serious infections) may also influence diabetes prevalence.

Adult↗

Non-differential underestimation may cause a threshold effect of exposure to appear as a dose-response relationship.

It is generally believed that non-differential misclassification will lead to a bias toward the null-value. However, using one graphical and one numerical example, we show that in situations where underestimation more than overestimation is the problem, non-differential misclassification may lead to a bias away from the null-value for intermediate categories of exposure variables. We show that a true threshold level for an exposure may, subsequently, appear as a dose-response relationship. Underestimation more than overestimation is likely to occur in studies in which self-reports are used to obtain data on activities which respondents voluntarily engage in and which are socially not acceptable or known to be potentially dangerous. Researchers should be aware that both a shown deleterious effect at a low level of exposure and a dose-response relationship may in fact be spurious and due to underestimation of exposure at higher levels.

Bias↗

Interaction of N-acetylmethionine with a non-C2-symmetrical platinum diamine complex.

The reaction of N-acetylmethionine (N-AcMet) with the complex [Pt(Et(2)en)(D(2)O)(2)](2+) (Et(2)en=N,N-diethylethylenediamine) was studied by NMR spectroscopy and molecular mechanics calculations. Complexes containing two methionine residues coordinated to the platinum atom were calculated to be relatively high in energy unless the bulk of the methionine residues was directed away from the diethyl group of the Et(2)en ligand. In contrast, sulfur-oxygen chelates were found to be relatively free of steric clashes. Experimentally, two sets of NMR resonances were observed when [Pt(Et(2)en)(D(2)O)(2)](2+) was reacted with N-AcMet; variable temperature experiments indicated intermediate chemical exchange between the two sets of resonances. NMR studies indicated that the resonances corresponded to [Pt(Et(2)en)(N-AcMet-S,O)](+) complexes with the sulfur atom trans to the diethyl group of the Et(2)en ligand. No product with the sulfur atom cis to the diethyl group was observed experimentally even though molecular mechanics calculations suggested that such forms have few steric clashes. The NMR results suggested that the chemical exchange was a result of sulfur chirality inversion. In early stages of the reaction, a [Pt(Et(2)en)(N-AcMet-S)(D(2)O)](+) complex was observed, indicating that coordination of the oxygen to form the chelate is relatively slow.

Chelating Agents↗

Magnetic resonance imaging characterization of osteochondral defect repair in a goat model at 8 T.

OBJECTIVE: This study was performed to non-invasively visualize and characterize osteochondral (OC) repair in ex vivo goat stifles using an 8 T magnetic resonance imaging (MRI) scanner and to compare the MR morphology with images obtained from 1.5 T, gross morphology and histology. METHODS: Mature, neutered male goats were assigned to an 8-week (n = 4) or 16-week (n = 4) study period. Two cylindrical OC defects (7 mm diameter, full cartilage thickness and 1mm into subchondral bone) were surgically created in the right stifle: one in the medial femoral condyle (MFC) and the other in the trochlear groove (TG). The implant matrices (non-woven or foam) were secured in the defect using a bottom anchored fixation device (FD). The contralateral left stifles served as time zero controls. At the day of necropsy, implants were placed at both defect sites (MFC and TG) on the normal left stifles. Following necropsy, the ex vivo goat stifles (intact and encapsulated) were disarticulated. Within 24 h postnecropsy, MR scans of the stifles along the mid-sagittal plane of the OC defect were acquired at 8 T and 1.5 T. MR relaxation times, T1 and T2, were measured at the region of repair tissue (RT) and adjacent native cartilage. Immediately after MR imaging, the stifles were dissected, grossly examined, and a sagittal OC block corresponding to the MR region of interest was prepared for formalin fixation. RESULTS: The high-resolution MR images enabled visualization of cartilage and bone integrity surrounding the implant as well as delineating the margins of RT/implant matrix and the FD. On spin echo sequence, the RT variably appeared as high, intermediate or low MR signal intensity; whereas, the FD always appeared as low signal intensity. In general, the MR signal intensity of 8-week RT was slightly higher compared to 16-week RT; however, there was no difference in RT morphology of stifles implanted with the non-woven matrix or foam matrix. Subchondral sclerosis appeared as low signal intensity. The 8 T MR images showed better delineation of the stifle tissues compared to the images acquired at 1.5 T. The T2 relaxation time of the RT appears to indicate (inconclusive due to small number of samples) a slight variation in the RT type between 8 weeks and 16 weeks. At both study times, the defects grossly appeared whitish to reddish but did not have the characteristic hyaline appearance typical of articular cartilage (AC). The gross appearance of the MFC and TG RT differed, which was predominantly mottled and recessed with fissuring of adjacent native AC in the MFC. Histologically, the RT of both 8-week and 16-week postsurgical defects predominantly comprised fibrovascular connective tissue with only few samples showing the presence of fibrocartilaginous and/or hypertrophic chondrocytes within the defect RT at 8 weeks. Also, compared to 8-week, the 16-week RT appeared to be more fibrotic. CONCLUSION: Using 8 T scanner, high-resolution MR images of ex vivo encapsulated goat stifles confirmed the capability of high-field MR imaging to distinguish the defect RT from the FD and adjacent joint tissues. The extent of OC repair and adjacent bone lesions (at 8 weeks and 16 weeks) observed in the MR images compared well with those observed on the corresponding histological sections.

Animals↗

The evolution of electrophoretic mobility of proteins.

A model was constructed that predicts the electric charge of a protein and its isoelectric point from its primary and quaternary structures. By using two different patterns of mutation and purifying selection, four schemes of nucleotide substitution were simulated. In the absence of selection for a specific value of pI, proteins are expected to evolve toward a mildly basic pI. Thus, the selection for maintaining extreme values of pI must be stringent, and proteins with extreme pI's will evolve very slowly. This prediction is consistent with observations on the evolution of histones and ubiquitin. The mean charge change is expected to be about 0.005 units pI per nucleotide substitution. The amount of electrophoretically hidden variation is expected to be considerable even for large degrees of divergence at the nucleotide and amino acid levels. Electrophoretic detectability depends on the size of the protein. The longer the protein the larger the amount of variation at the amino acid level that is undetectable by isoelectric focusing. This property may be partially responsible for the imperfect correlation between molecular weight and gene diversity observed for electrophoretic data. Very basic and very acidic proteins are expected to generate less electrophoretic variability than proteins with intermediate pI's. Unequal rates of mutation between nucleotides and asymmetrical patterns of purifying selection have almost no effect on the equilibrium pI of proteins, but affect the rates of change in pI, and increase the amount of electrophoretically hidden variation in comparison to the expectations derived from random patterns of mutation and constant selection. Comparison of detectability of protein differences among four electrophoretical techniques suggests that the best performance is obtained by the sequential electrophoresis method.

Amino Acid Sequence↗

Polymorphism in the subtelomeric regions of chromosomes of Kinetoplastida.

Leishmania spp. and the related kinetoplastid Trypanosoma brucei are single-celled parasites. In Leishmania, the nuclear genome comprises 36 diploid chromosomes and occasional amplified minichromosomes, while the T. brucei nucleus contains 11 larger diploid chromosomes and a variable number of intermediate-sized and minichromosomes. This paper primarily describes the subtelomeric structure of the larger diploid chromosomes of L. major and T. brucei, although some aspects may also apply to smaller chromosomes. The diploid chromosomes contain most protein-coding genes and vary in size. The telomeric sequence is common to both species, but adjacent subtelomeric repeats vary between species and chromosomes. It is possible that some of the complex repeats described here play a role in stabilizing replication and copy number of the chromosomes. The subtelomeric regions of T. brucei chromosomes differ from those of other protozoan parasites, as they are dedicated to expression sites for variant surface glycoprotein genes, used by the parasite to evade immune destruction by antigenic variation. Variation in these sites creates segmental aneuploidy in many T. brucei chromosomes.

Animals↗

Evidence for curvilinear interpolation from dot alignment judgements.

Visual interpolation between dots responsible for rectilinear versus curvilinear contour interpretation was examined with the psychophysical forced directional response (FDR) paradigm. Regular four-dot polygon segments, together with a target dot, were presented to the subjects for 150 ms. Subjects were required to indicate the direction of deviation of the target dot from the midpoint of the intermediate line segment. Crucial variables were the outer angle of the line segments and symmetry axis orientation of the polygon segment. Logistic regression analyses showed that curvilinear interpolation occurred for angles up to 30 degrees, but emerged more pervasively under the vertical symmetry axis orientation for angles up to 60 degrees.

Form Perception↗

Detection of the alpha-subunit of inhibin in trophoblastic neoplasia.

Placental trophoblasts are the primary source of serum inhibin during pregnancy. We sought to characterize inhibin immunolabeling in trophoblastic neoplasms and compare the results with those for established markers of trophoblastic differentiation. Formalin-fixed, paraffin-embedded tissues from three normal term placentas, 13 hydatidiform moles (HM), five choriocarcinomas (CC) (three gestational, one testicular, one mediastinal), and five placental site trophoblastic tumors (PSTT) were immunolabeled with antibodies to the alpha-subunit of inhibin, hPL, and beta-hCG. Additionally, six first-trimester placentas were immunolabeled with antibody to inhibin alone. Trophoblastic subpopulations were assessed for the number of positive cells (1% to 24% = 1+,25% to 49% = 2+,50% to 74% = 3+, 75% to 100% = 4+). Immunolabeling in term placenta and HM was similar, because beta-hCG was the most sensitive marker (4+) of syncytiotrophoblasts followed by inhibin (3-4+) and hPL (2-3+). Immunolabeling of syncytiotrophoblasts in CC was similar to that in term placenta and HM, except for negative hPL staining in two cases. In HM, inhibin labeling of intermediate trophoblasts (2-3+) was less than that for hPL (3-4+). In CC, inhibin and hPL labeling of intermediate trophoblasts was more variable with negative hPL reactivity in two cases. Inhibin and hPL did not stain cytotrophoblasts. In PSTT, inhibin immunolabeling was a better marker than hPL in two cases, inferior in two, and similar in one. Inhibin labeling of syncytiotrophoblasts was less than that for beta-hCG, but did not have the often marked background staining that was present with beta-hCG. Immunolabeling of trophoblast subpopulations for inhibin was similar between first-trimester placenta, term placenta, and HM. We conclude that inhibin is a useful immunohistochemical marker of trophoblastic neoplasia and should be included in the antibody panel with beta-hCG and hPL.

Adult↗

A numerical study of spatial structure during oscillatory combustion in closed vessels in microgravity.

The existence and spatial development of gas-phase, thermokinetic oscillations under the influence of mass and thermal diffusion have been investigated by numerical methods in a 1-dimensional system. The conditions correspond to those that would be experienced under microgravity. The interest arises because there have been recent experimental investigations of oscillatory reactions, involving cool flames during butane oxidation, as part of the NASA, KC135 microgravity flight programme. The Sal'nikov, thermokinetic scheme, which is a two-variable model representing an intermediate chemical species and reactant temperature (taking the form P-->A-->B), forms the basis of the present work. In this model, thermal feedback occurs through the exothermicity of the second step and the non-linearity is derived from its temperature dependence. There are no known chemical examples that satisfy Sal'nikov's formal structure but Griffiths and co-workers conceived an experimental analogue under terrestrial conditions whereby a gaseous reactant was allowed to flow from an external reservoir into a closed, heated reactor at a controlled rate via a capillary tube which fed the reactant to the centre of the vessel. The exothermic reaction that occurred in the vessel satisfied the necessary conditions for the second step and the inflow, with no temperature dependence, represented a physical analogue to the first step of the Sal'nikov scheme. Thermokinetic oscillations were observed and the range of conditions for their existences was investigated. One of the experimental systems was the exothermic reaction between hydrogen and chlorine. To represent the Sal'nikov conditions hydrogen was fed slowly into the reactor, which already contained chlorine. We have exploited this chemical system and its experimental implementation in the present paper to investigate the behaviour when no convection or bulk gas motion occurs and when heat and mass transport is driven solely by diffusion. We study the response of alternative numerical approaches to the way in which the first step of the scheme is simulated. In the first, the precursor (P) is supplied at the same rate simultaneously throughout the cells representing the reactor. This is close to the concept of the Sal'nikov model. In the second method, a fixed rate of supply is applied at the inner boundary of the axisymmetric, 1-dimensional system. This is analogous to the experimental procedure. The numerical results show how oscillatory states can be sustained as a result of heat and mass transport by diffusion. The temporal and spatial evolution of reaction in a range of circumstances is discussed.

Journal Article↗

Human monoclonal antibodies encoded by the V4-34 gene segment show cold agglutinin activity and variable multireactivity which correlates with the predicted charge of the heavy-chain variable region.

We have characterized the reactivities of a panel of V4-34-encoded human IgM monoclonal antibodies (mAb) which bind the erythrocyte Rh D antigen, derived from an immunized individual. These were compared with the specificities of V4-34-encoded autoantibodies with I/i reactivity produced from patients with cold agglutinin disease (CAD), and other V4-34-encoded autoantibodies. The antibodies were evaluated for cold agglutinin activity using haemagglutination tests, immunofluorescence microscopy for reactivity with tissue components, and in solid phase radiobinding assays with purified antigens. We found that (i) cold agglutinin activity was a property of all the V4-34-encoded mAb (ii) the cold agglutinins from CAD patients were generally monospecific for I/i whereas most of the anti-D and the other V4-34-encoded mAb displayed multireactive properties, frequently binding to strongly acidic antigens (iii) computation of the net charge of the heavy-chain V regions showed that the multireactive mAb were generally more positively charged than the monospecific cold agglutinins, which could contribute to their multireactive phenotype. The involvement of charge interactions was further indicated by the effects of pH and ionic strength on the immunofluorescence staining patterns.

Adult↗

Characterization of melanophore morphology by fractal dimension analysis.

Fractal or focal dimension (FD) analysis is a valuable tool to identify physiologic stimuli at the cellular and tissue levels that allows for quantification of cell perimeter complexity. The FD analysis was determined on fluorescence images of caffeine- or epinephrine-treated (or untreated control) killifish Fundulus heteroclitus (Linneaus) melanophores in culture. Cell perimeters were indicated by rhodamine-phalloidin labeling of cortical microfilaments using box-counting FD analysis. Caffeine-treated melanophores displayed dispersed melanosomes in cells with less serrated edges and reduced FD and complexity. Complexity in epinephrine-treated cells was significantly higher than the caffeine-treated cells or in the control. Cytoarchitectural variability of the cell perimeter is expected because cells change shape when cued with agents. Epinephrine-treated melanophores demonstrated aggregated melanosomes in cells with more serrated edges, significantly higher FD and thus complexity. Melanophores not treated with caffeine or epinephrine produced variable distributions of melanosomes and resulted in cells with variably serrated edges and intermediate FD with a larger SE of the regression and greater range of complexity. Dispersion of melanosomes occurs with rearrangements of the cytoskeleton to accommodate centrifugal distribution of melanosomes throughout the cell and to the periphery. The loading of melanosomes onto cortical microfilaments may provide a less complex cell contour, with the even distribution of the cytoskeleton and melanosomes. Aggregation of melanosomes occurs with rearrangements of the cytoskeleton to accommodate centripetal distribution of melanosomes. The aggregation of melanosomes may contribute to centripetal retraction of the cytoskeleton and plasma membrane. The FD analysis is, therefore, a convenient method to measure contrasting morphologic changes within stimulated cells.

Animals↗

Hyaline cell-rich chondroid syringoma: case report and review of the literature.

Hyaline cell-rich chondroid syringoma (HCRCS) is a rare benign cutaneous neoplasm composed of cells with eosinophilic hyaline cytoplasm and plasmacytoid features, the origin of which remains elusive. To the best of our knowledge, only eight cases of this entity have been reported so far, and none of them was submitted to a large panel of myoepithelial markers. We report on a case of a previously healthy 29-year-old male patient who presented with a slowly enlarging flesh-colored nodule on the palmar aspect of the tenar region of his left hand, measuring 2 cm in maximum diameter. The nodule was "shelled-out" and submitted to light microscopy, immunohistochemistry, and ultrastructural examination. Histopathologic analysis disclosed a lobulated neoplasm composed of hyaline cells with plasmacytoid features showing ovoid nuclei, with occasional invaginations, finely granular chromatin, and discrete nucleoli; the cytoplasm was deeply eosinophilic with occasional dot-shaped paranuclear hyaline inclusions. On immunohistochemical evaluation, hyaline cells were strongly and diffusely positive for S-100 protein, vimentin, pan (CAM 5.2) and high molecular weight (34betaE12) cytokeratins; these cells were focally positive for GFAP, maspin, neuron-specific enolase, and cytokeratin 14. Alpha-smooth muscle actin, epithelial membrane antigen, carcinoembryonic antigen, collagen IV, Gp100 (HMB-45), and p63 were negative in neoplastic hyaline cells. Ultrastructural analysis disclosed cells with ovoid nuclei showing occasional invaginations and nuclear pockets; the cytoplasm was rich in meshworks of non-bundling intermediate filaments and a variable amount of rough endoplasmic reticulum cisternae. Based on our findings and those previously reported, hyaline cells of HCRCS might posses an aberrant myoepithelial differentiation. Most importantly, pathologists need to be aware of the histologic and immunohistochemical features of HCRCS to avoid a misdiagnosis of highly malignant neoplams, such as malignant melanoma and extra-skeletal myxoid chondrosarcoma.

Adenoma, Pleomorphic↗

Fine-needle aspiration cytology of peripheral T-cell lymphoma. A cytologic, immunologic, and cytometric study.

The diagnosis of peripheral T-cell lymphoma (PTCL) is difficult. This entity can be misdiagnosed as Hodgkin's disease or a reactive process such as nonnecrotizing granulomatous lymphadenitis or it can present a problem in lymphoma classification. Fine-needle aspirates from 13 patients with histologically proven PTCL were evaluated by cytology, immunochemistry, and flow cytometry. Of the 13 patients with PTCL, initial cytologic diagnoses were atypical lymphocytic infiltrate (2), mixed-cell lymphoma (6), mixed-cell lymphoma with associated histiocytes (2), large cell lymphoma (2), and small cell lymphoma (1). Surface marker studies were performed on cytospin preparations. Antibodies against cytotoxic-suppressor (Leu-2a) and helper-inducer (Leu-3a,b) antigens were used in 11 cases. Ten lymphomas demonstrated helper phenotype and one showed phenotypic heterogeneity in two different sites. The most prominent cytologic features of PTCL were a variable combination of small, intermediate, and large lymphoid cells with irregular nuclei, presence of epithelioid histiocytes, and atypical mononuclear cells. Flow cytometry studies showed a diploid stem line with intermediate proliferative activity (mean S-phase of 6.7%) in most cases, despite the clinical aggressiveness of this neoplasm.

Adult↗

The health of Latin Americans exposed to polluted rivers: a triple-blind observational study. Interamerican Group for Research in Environmental Epidemiology.

Accelerating development in South America, with consequent contamination of rivers as the final common pathway of waste, raises concern about adverse effects on the health of riverine populations. We conducted a cross-sectional survey simultaneously in six Latin American nations among people living near a river known to be polluted in each country. Trace metals (arsenic, mercury and lead) were selected as indicators of exposure to industrial effluents. Within each country, we contrasted probability samples from three types of communities: one upstream of point sources of pollution and thus little exposed; one downstream from a site of major development; and one with intermediate exposure. The outcome variables were health status measures elicited by questionnaire and biochemical measures of blood and urine. We examined several possible explanatory and confounding variables, including housing conditions, nutrition, and source of drinking water. The field work was done with triple blinding in that data-gatherers and study subjects were unaware of their group membership and of the study hypotheses, those analysing, specimens and questionnaires were blind to country and community of origin of the material and the investigators reviewed the results in code, committing themselves to conclusions in writing before the codes were broken. Methods were carefully standardized across six countries during training, when pretesting data-gathering instruments and with double coding and extensive accuracy checks of computerized data. There were 900 eligible subjects from 18 communities in six countries. The overall response rate was 92%, the lowest 86%. Results showed an acceptable level of health in all communities and no relationship to exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-Sectional Studies↗

Plasticity in the positive selection of T cells: affinity of the selecting antigen and IL-7 affect T cell responsiveness.

The current study examines how responsiveness of T cells is affected by the avidity of the peptide/MHC engaged during positive selection of their thymocyte precursors. We used a thymus reaggregate culture system in which CD4(+)CD8(+) thymocytes from AND TCR transgenic mice were induced to undergo positive selection by pigeon cytochrome c (PCC) peptide or its analogs presented by I-E(k) class II MHC on a thymic epithelial cell line. When low-affinity peptide analogs drove positive selection, up to 100 microM was needed to produce >50% CD4(+) T cells, and these cells were highly responsive to PCC. In contrast, <0.2 microM high-affinity peptides was required to achieve similar selection efficiency, but the resultant cells failed to respond to PCC. However, these cells were not dead based on dye exclusion and capacity to respond to phorbal ester and to agonist if IL-2 was also present, supporting the view that non-responsiveness of cells selected on high-affinity peptides is a form of central T cell tolerance distinct from deletion. Cells selected on intermediate-affinity peptides showed variable responsiveness which was suppressed 5- to 10-fold by addition during reaggregate culture of antibody to the IL-7R. Similarly, supplementary IL-7 in the reaggregate culture produced CD4(+) T cells that were promiscuously responsive. Overall, this study demonstrates that the responsiveness of T cells is not rigidly controlled and that the presence of IL-7 during T cell development has the potential to negate central T cell tolerance and produce autoreactive T cells.

Animals↗

Information about transmission opportunities triggers a life-history switch in a parasite.

Many microbial pathogens can switch to new hosts or adopt alternative transmission routes as environmental conditions change, displaying unexpected flexibility in their infection pathways and often causing emerging diseases. In contrast, parasitic worms that must develop through a fixed series of host species appear less likely to show phenotypic plasticity in their transmission pathways. Here, I demonstrate experimentally that a trematode parasite, Coitocaecum parvum, can accelerate its development and rapidly reach precocious maturity in its crustacean intermediate host in the absence of chemical cues emanating from its fish definitive host. Juvenile trematodes can also mature precociously when the mortality rate of their intermediate hosts is increased. Eggs produced by precocious adults hatch into viable larvae, capable of pursuing the parasite's life cycle. In the absence of chemical cues from fish hosts, the size of eggs released by precocious trematodes in their intermediate hosts becomes more variable, possibly indicating a bet-hedging strategy. These results illustrate that parasitic worms with complex life cycles have development and transmission strategies that are more plastic than commonly believed, allowing them to skip one host in their cycle when they perceive limited opportunities for transmission.

Amphipoda↗

Control of immunoactive inhibin production by human granulosa cells.

OBJECTIVE: The aim was to determine the relation between stage of antral follicular development and granulosa cell production of immunoactive inhibin. DESIGN: Primary granulosa cell cultures in serum-free Medium 199 were incubated at 37 degrees C for 96 hours with a change of medium at 48 hours. Inhibin and steroid levels in culture medium were determined by radioimmunoassay. The inhibin assay was based on the N-terminal 1-26 amino acid sequence of the alpha-chain of porcine 32 kDa inhibin using pl alpha 1-26-GLY27-TYR28 as the immunogen, tracer and standard. PATIENTS: Granulosa cells were obtained from the ovaries of women with regular menstrual cycles undergoing hysterectomy with unilateral or bilateral oophorectomy to treat non-malignant gynaecological disease. RESULTS: Basal production of immunoactive inhibin by granulosa cells from presumptive preovulatory follicles (greater than 15 mm diameter) was 5-13 times higher than that by granulosa cells from immature (less than 10 mm diameter) or intermediately mature (10-15 mm diameter) follicles. Basal production of progesterone and oestradiol followed a qualitatively similar pattern, establishing a positive relation between functional granulosa cell maturity and inhibin production. Treatment of granulosa cell cultures from immature follicles with follicle-stimulating hormone (FSH), but not luteinizing hormone (LH), increased inhibin production, time and dose dependently. FSH, but not LH, also brought about similar increases in steroid hormone synthesis by granulosa cells from immature follicles. The stimulatory effect of FSH on granulosa cell inhibin production was augmented at least twofold by the presence of testosterone or 5 alpha-dihydrotestosterone (1.0 mumol/l) but was unaffected by oestradiol. Granulosa cells from intermediately mature follicles undertook variable degrees of both FSH and LH-responsive inhibin production which generally corresponded with gonadotrophin-responsive steroid production. Granulosa cells from presumptive preovulatory follicles showed inconsistent inhibin responses to FSH. However, LH caused marked (at least twofold) increases in inhibin production, paralleling LH-responsive steroid production. CONCLUSION: These results show that for human beings, granulosa cell capacity to produce immunoactive inhibin in vitro increases with follicular maturity. FSH, but not LH, stimulates inhibin production by immature granulosa cells and this response to FSH is subject to modulation by androgen. During preovulatory follicular development, production of inhibin, like steroids, becomes increasingly responsive to LH. Such a development-related pattern of granulosa cell inhibin production helps explain how, post-ovulation, the corpus luteum is able to secrete inhibin as well as steroids. It is also compatible with the concept that locally produced inhibin could participate in the paracrine control of follicular development during the human menstrual cycle.

Adult↗