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PubMed1985

Development of graft-vs.-host disease-like syndrome in cyclosporine-treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity.

Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs.-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of autoreactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia-reactive cells. These results suggested that the anti-class II autoreactive cell associated with syngeneic GVHD either recognizes a common class II determinant ("public" epitope) shared by multiple strains of rats, or was polyspecific with respect to "private" class II determinants.

Animals↗

PubMed1999

Use of stage of change (SOC) to develop an STD/HIV behavioral intervention: phase 1. A system to classify SOC for STD/HIV sexual risk behaviors--development and reliability in an STD clinic.

This paper reports on the initial phase in the development, program implementation, and inter-rater reliability of an application of Stage of Change (SOC) behavioral theory for use in STD/HIV risk reduction. SOC was adapted to assess readiness for sexual behavior change in an urban STD clinic in Rochester, New York. A standardized staging grid and protocol were developed and implemented as part of HIV pre- and post-test counseling. A "client instructor" methodology was used to assess standardization and staff inter-rater reliability. Percent agreement for stage assessment for target behaviors was calculated. The Rochester STD/HIV Behavioral Counseling (RoSHBeC) Staging Grid and Protocol was used to train staff and this staging system was implemented in the STD clinic. After training, staff identified the correct behavioral target and stage 90% of the time. Inter-rater agreement for SOC classification was greater than 70%. Our experience demonstrates that it is possible to develop, implement, and sustain an integrated provider-delivered STD/HIV behavioral intervention in a busy urban STD Clinic. This staging system has the potential for use in other settings and for other health-related behaviors.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Vitamin A deficiency increases the in vivo development of IL-10-positive Th2 cells and decreases development of Th1 cells in mice.

Vitamin A deficiency impairs both T helper type 1 (Th1)- and type 2 (Th2)-mediated immune responses, although Th2 responses seem to be principally affected. Multiple mechanisms are involved in this immune suppression, but the hypothesis that deficiency affects development of Th1/Th2 memory cell phenotype has not been tested directly in vivo. To do so, lymphocytes from DO11.10 T cell receptor (TCR)-transgenic mice were transferred to vitamin A-deficient or control BALB/c recipients. Recipients were then immunized with the cognate peptide antigen for the TCR-transgenic DO11.10 T cells (OVA(323-339)). After 2-5 wk, the transferred OVA(323-339)-specific T cells were identified from draining lymph nodes with the TCR-clonotypic antibody KJ1-26, and their Th1/Th2 phenotype was characterized by intracellular cytokine staining after in vitro stimulation with phorbol myristate acetate and ionomycin. The percentage of CD4(+)KJ1-26(+) cells positive for IL-10 was 100% greater in vitamin A-deficient mice (3.49 +/- 0.41%; mean +/- SE) than in control mice (1.74 +/- 0.37%). IL-4 did not differ between groups. In addition, the percentages of CD4(+)KJ1-26(+) cells from vitamin A-deficient mice that were positive for interferon (IFN)-gamma (8.8 +/- 0.73%) and interleukin (IL)-2 (39.5 +/- 3.1%) were both lower than the percentages in control mice (11.4 +/- 0.67 and 47.0 +/- 2.8%, respectively). Thus vitamin A deficiency, at the time of initial antigen exposure, enhances the development of IL-10-producing Th2 or T regulatory cells and diminishes the development of Th1 memory cells.

Animals↗

PubMed1997

National Institutes of Health Consensus Development Conference Statement: Breast Cancer Screening for Women Ages 40-49, January 21-23, 1997. National Institutes of Health Consensus Development Panel.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the effectiveness of mammography screening for women ages 40-49. PARTICIPANTS: A non-Federal, nonadvocate, 12-member panel representing the fields of oncology, radiology, obstetrics and gynecology, geriatrics, public health, and epidemiology and including patient representatives. In addition, 32 experts in oncology, surgical oncology, radiology, public health, and epidemiology, presented data to the panel and to a conference audience of 1,100. EVIDENCE: The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised draft statement at the end of the conference. The final statement with a minority report was completed within several weeks after the conference. CONCLUSIONS: The Panel concludes that the data currently available do not warrant a universal recommendation for mammography for all women in their forties. Each woman should decide for herself whether to undergo mammography. Her decision may be based not only on an objective analysis of the scientific evidence and consideration of her individual medical history, but also on how she perceives and weighs each potential risk and benefit, the values she places on each, and how she deals with uncertainty. However, it is not sufficient just to advise a woman to make her own decision about mammograms. Given both the importance and the complexity of the issues involved in assessing the evidence, a woman should have access to the best possible relevant information regarding both benefits and risks, presented in an understandable and usable form. Information should be developed for women in their forties regarding potential benefits and risks to be provided to enable each woman to make the most appropriate decision. In addition, educational material to accompany this information should be prepared that will lead women step by step through the process of using such information in the best possible way for reaching a decision. For women in their forties who choose to have mammography performed, the costs of the mammograms should be reimbursed by third-party payors or covered by health maintenance organizations so that financial impediments will not influence a woman's decision. Additionally, a woman's health care provider must be equipped with sufficient information to facilitate her decisionmaking process. Therefore, educational material for physicians should be developed to assist them in providing the guidance and support needed by the women in their care who are making difficult decisions regarding mammography. The two panel members writing a minority report believed the risks of mammography to be overemphasized by the majority and concluded that the data did support a recommendation for mammography screening for all women in this age group and that the survival benefit and diagnosis at an earlier stage outweigh the potential risks.

Adult↗

PubMed2003

Mouse round spermatids developed in vitro from preexisting spermatocytes can produce normal offspring by nuclear injection into in vivo-developed mature oocytes.

It has been shown that mature oocytes injected with nuclei from round spermatids collected from mouse testis can generate normal offspring and that round spermatids can develop in vitro. An undetermined issue is whether spermatids developed in vitro are capable of generating fertile offspring by nuclear injection into oocytes. Herein, we report the production of normal and fertile offspring by nuclear injection using haploid spermatid donors derived from mouse primary spermatocyte precursors cocultured with Sertoli cells. Cocultured spermatogonia and spermatocytes were characterized by their nuclear immunoreactive patterns determined by an antibody to phosphorylated histone H2AX (gamma-H2AX), a marker for DNA double-strand breaks. Cocultured round spermatid progenies display more than one motile flagellum, whose axonemes were recognized by antitubulin immunostaining. Flagellar wavelike movement and flagellar-driven propulsion of round spermatids developed in vitro were documented by videomicroscopy (http://www.sci.ccny.cuny.edu/ approximately kier). We also show that breeding of male and female mouse offspring generated by spermatid nuclear injection produced fertile offspring. In addition to their capacity to produce fertile offspring, cocultured, flagellated round spermatids can facilitate the analysis of the mechanisms of centriolar polarity, duplication, assembly, and flagellar growth, including the intraflagellar transport of cargo proteins.

Animals↗

PubMed2002

Intake retention fractions developed from models used in the determination of dose coefficients developed for ICRP publication 68--particulate inhalation.

ICRP Publication 68 presents dose coefficients developed using systems of new models for the respiratory tract and metabolism of certain elements. The utility of these dose coefficients and associated models is limited without a method for calculating intake from bioassay results using the same models as in that publication. The calculation of a radionuclide intake requires values of expected fractions of the intake in bioassay samples collected at specific times after intake. The general system of models has been solved using a commercial software package and a method for solution of systems of first-order linear differential equations that uses eigenvectors and eigenvalues derived from the system of equations. The result of this work is a series of tables of fractions of acute inhalation intakes for different bioassay methods, times, and compound classes for intakes for those elements listed in ICRP Publication 68. The values in these tables can be used for intake calculations, development of bioassay frequencies, and development of action levels.

Administration, Inhalation↗

PubMed1993

Physiological characteristics of spontaneously developed diabetes in male WBN/Kob rat and prevention of development of diabetes by chronic oral administration of synthetic trypsin inhibitor (FOY-305).

The male WBN/Kob rats spontaneously develop diabetes mellitus with age. In this study, we examined how glucose tolerance, potency of insulin release, and histology of the pancreas were changed with age in this model. Furthermore, we examined the effect of FOY-305, a synthetic trypsin inhibitor, on this model. Male WBN/Kob rats were divided into two groups: one group fed on standard pellet diet (STD group) and the other on pellet containing 0.1% FOY-305 (FOY group) for 56 weeks after age 4 weeks. Oral glucose (2 g/kg) tolerance test, histology of the pancreas, and glucose (8.3 mM)- and arginine (10 mM)-stimulated insulin release from the isolated perfused pancreas were examined at 8, 20, 40, and 60 weeks of age in both groups. Pancreatic insulin content was examined at 60 weeks. In the STD group, impairment of glucose tolerance and destruction and fibrosis of pancreatic tissues progressed with age. Glucose-stimulated insulin release was remarkably reduced with age, while arginine-stimulated insulin release was preserved. By contrast, in the FOY group, development of glucose intolerance was delayed and the pancreas showed fewer pathologic changes compared with the STD group. Insulin releases in response to both glucose and arginine were preserved at all ages examined. Total pancreatic insulin content at 60 weeks of age was significantly greater than that of the STD group. The male WBN/Kob rat is a new type of diabetic model that shows a similar pattern of insulin release to that in rat with non-insulin-dependent diabetes mellitus and also shows unique histopathological changes in exocrine pancreas. FOY-305 was effective in preventing the development of diabetes in this model, although its mechanism is still unknown.

Administration, Oral↗

PubMed2001

The maize MADS box gene ZmMADS3 affects node number and spikelet development and is co-expressed with ZmMADS1 during flower development, in egg cells, and early embryogenesis.

MADS box genes represent a large gene family of transcription factors with essential functions during flower development and organ differentiation processes in plants. Addressing the question of whether MADS box genes are involved in the regulation of the fertilization process and early embryo development, we have isolated two novel MADS box cDNAs, ZmMADS1 and ZmMADS3, from cDNA libraries of maize (Zea mays) pollen and egg cells, respectively. The latter gene is allelic to ZAP1. Transcripts of both genes are detectable in egg cells and in in vivo zygotes of maize. ZmMADS1 is additionally expressed in synergids and in central and antipodal cells. During early somatic embryogenesis, ZmMADS1 expression is restricted to cells with the capacity to form somatic embryos, and to globular embryos at later stages. ZmMADS3 is detectable only by more sensitive reverse transcriptase-PCR analyses, but is likewise expressed in embryogenic cultures. Both genes are not expressed in nonembryogenic suspension cultures and in isolated immature and mature zygotic embryos. During flower development, ZmMADS1 and ZmMADS3 are co-expressed in all ear spikelet organ primordia at intermediate stages. Among vegetative tissues, ZmMADS3 is expressed in stem nodes and displays a gradient with highest expression in the uppermost node. Transgenic maize plants ectopically expressing ZmMADS3 are reduced in height due to a reduced number of nodes. Reduction of seed set and male sterility were observed in the plants. The latter was due to absence of anthers. Putative functions of the genes during reproductive and vegetative developmental processes are discussed.

Amino Acid Sequence↗

PubMed1987

Genetic Regulation of Development in Sorghum bicolor: IV. GA(3) Hastens Floral Differentiation but Not Floral Development under Nonfavorable Photoperiods.

Sorghum bicolor (L.) Moench lines with genetic differences in photoperiod requirement were planted in the field near Plainview, Texas (about 34 degrees northern latitude) around June 1 and treated with gibberellic acid (GA(3)) solutions applied in the apical leaf whorl. GA(3) hastened the date of floral differentiation (initiation). The greatest responses to GA(3) were by 90M and 100M, the latest of the genotypes, for which floral initiation dates were hastened an average of 19.5 and 21.7 days, respectively, for the 4 years beginning in 1980. There were very small differences in dates of anthesis between control and GA(3)-treated plants. Microscopic examination of apical meristems collected between the date of floral initiation of GA(3)-treated plants and the later date of initiation of control plants revealed: (a) several morphological characteristics of floral differentiation in the apical meristem of treated plants, (b) consistent occurrence of vegetative morphology in control plants, (c) a few meristems from GA(3)-treated plants that appeared to be regressing in floral development and thus possibly exhibiting dedifferentiation. Dedifferentiation of prepanicle primordia into leaves would explain the observed equal or greater number of leaves in GA(3)-treated plants rather than the expected smaller number. It is apparent that the presence of a morphological differentiated floral meristem in sorghum does not drive subsequent floral development in the absence of inductive photoperiods. This further suggests that initial floral differentiation and subsequent floral development may be controlled separately in sorghum.

Journal Article↗

PubMed1990

Water Relations of Seed Development and Germination in Muskmelon (Cucumis melo L.) : III. Sensitivity of Germination to Water Potential and Abscisic Acid during Development.

Muskmelon (Cucumis melo L.) seeds are germinable 15 to 20 days before fruit maturity and are held at relatively high water content within the fruit, yet little precocious germination is observed. To investigate two possible factors preventing precocious germination, the inhibitory effects of abscisic acid and osmoticum on muskmelon seed germination were determined throughout development. Seeds were harvested at 5-day intervals from 30 to 65 days after anthesis (DAA) and incubated either fresh or after drying on factorial combinations of 0, 1, 3.3, 10, or 33 micromolar abscisic acid (ABA) and 0, -0.2, -0.4, -0.6, or -0.8 megapascals polyethylene glycol 8000 solutions at 30 degrees C. Radicle emergence was scored at 12-hour intervals for 10 days. In the absence of ABA, the water potential (Psi) required to inhibit fresh seed germination by 50% decreased from -0.3 to -0.8 megapascals between 30 and 60 DAA. The Psi inside developing fruits was from 0.4 to 1.4 megapascals lower than that required for germination at all stages of development, indicating that the fruit Psi is sufficiently low to prevent precocious germination. At 0 megapascal, the ABA concentration required to inhibit germination by 50% was approximately 10 micromolar up to 50 DAA and increased to >33 micromolar thereafter. Dehydration improved subsequent germination of immature seeds in ABA or low Psi. There was a linear additive interaction between ABA and Psi such that 10 micromolar ABA or -0.5 megapascal osmotic potential resulted in equivalent, and additive, reductions in germination rate and percentage of mature seeds. Abscisic acid had no effect on embryo solute potential or water content, but increased the apparent minimum turgor required for germination. ABA and osmoticum appear to influence germination rates and percentages by reducing the embryo growth potential (turgor in excess of a minimum threshold turgor) but via different mechanisms. Abscisic acid apparently increases the minimum turgor threshold, while low Psi reduces turgor by reducing seed water content.

Journal Article↗

PubMed2006

Why do inhibitors develop? Principles of and factors influencing the risk for inhibitor development in haemophilia.

The formation of inhibitory alloantibodies is, in the postinfectious era, the most severe and costly complication of replacement therapy in patients with haemophilia. The complexity of the immune response to the infused factor becomes more and more obvious as knowledge in the area increases. Antibodies develop as a result of a complex multi-factorial interaction between antigen-presenting cells, T- and B-lymphocytes. Genetic susceptibility of cell surface molecules, such as the major histocompatibility complex, the T-cell receptor and cytokine receptors, as well as various immunomodulatory molecules have a major impact on the outcome. In addition, environmental factors probably influence the risk of inhibitor development. The current concept of inhibitor development is reviewed. A better understanding of the pathophysiological mechanisms involved will facilitate improvement of therapy in the future, and hopefully provide an opportunity to prevent this complication of treatment.

Blood Coagulation Factor Inhibitors↗

PubMed1989

Theory development in perspective: the role of conceptual frameworks and models in theory development.

An analysis of most scientific theories reveals the presence of a variety of components which function as constitutive elements of theories. Wider cultural paradigms often influence the construction and content of theories in a decisive way. Analogies between incongruent domains provide significant points of departure for the development of models which are often metaphoric in nature. Different metaphors provide alternative conceptual frameworks in terms of which it is possible to describe and explain nursing phenomena. Scientific theories that are developed on the basis of such metaphorical models are limited in their explanatory capacity. When the intrinsic limitations of such scientific models are not recognized, they often lead to distorted, one-sided and reductionistic explanations of phenomena. Metaphysical assumptions concerning the nature of human beings, illness, health, etc., are also of decisive significance in this process, e.g. mechanistic models based on a naturalistic view of man lead theorizing astray. These theses are illustrated with reference to behavioral systems theory as developed by Dorothy Rogers.

Holistic Health↗

PubMed1985

X chromosome abnormalities and cognitive development: implications for understanding normal human development.

Recent advances in the biological sciences have offered new opportunities to identify biological contributions as they interact with social experience to help determine psychological development. The role of biological factors is more easily demonstrated in subhuman species in which extensive experimental manipulations of variables are possible. One strategy for the study of human behaviour genetics has been the systematic analysis of behaviour in individuals with naturally occurring X chromosome variations. The aim has been to demonstrate whether or not the range of expected variability in particular areas of behavioural development was narrowed by the specific genotypic abnormality. The knowledge obtained from these studies can be applied meaningfully to enhance our understanding about human behavioural development in chromosomally unaffected individuals.

Auditory Perception↗

PubMed1990

Effects of prenatal ethanol and long-chain n-3 fatty acid supplementation on development in mice. 1. Body and brain growth, sensorimotor development, and water T-maze reversal learning.

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. In addition, the diet contained 20% oil; this was either of two mixtures, one comprised of predominantly n-6 (18:2n-6) fatty acids, and the other containing an equivalent amount of n-6, but supplemented with a source of long chain n-3 (20:5n-3, 22:6n-3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Ethanol decreased maternal weight gain and pup body and brain weight; it also retarded both sensory and motor development in the pups and impeded reversal learning in a water maze. The n-3 supplementation lowered maternal blood alcohol concentration, but counteracted only some of the effects of ethanol, by increasing maternal weight gain and pup body weight, and also by enhancing sensory development in the pups. Such effects were additive, in that they were also present in the maltose-dextrin control group. These findings suggest that n-3 supplementation may ameliorate some of the effects of ethanol on neurobehavioral development, but the magnitude of the effect appears to be small.

Animals↗

PubMed1989

Functional development of the visual system in normal and protein-deprived rats. VIII. Post-natal development of optic nerve axons.

Protein deprivation results in a persistent impairment of transmission of impulses from the specific cortical projection within the visual cortex. In order to evaluate changes in subcortical structures during pre-weaning development, a study was made on number, calibre and myelination of optic nerve axons in control (C) and protein-deprived (PD) rats 5, 12, 20 and 30 days of age. Protein deprivation was induced by giving rat mothers a diet containing 7% protein by weight (control diet 14%, during gestation and lactation. The cross-sectional area of the nerve was measured on a digitizer. Between 3000 and 4000 axons collected from 7-13 field areas sampled by a random, systematic procedure from a cross-shaped area of the nerve were counted and measured. Between 5 and 12 days after birth, the number of axons was reduced by 50% in C rats. The total number of optic nerve axons was not significantly different in PD compared to C rats, indicating that protein deprivation does not affect the formation or naturally occurring nerve cell death of retinal ganglion cells. At all ages examined there were significant reductions in the number of axons larger than 0.52 micron as well as the number of myelinated axons. The rates of growth/maturation and myelination of axons in C rats and PD rats suggested that the reductions seen in PD rats up to 20 days of age may represent a developmental delay of approximately 4 days. At 30 days, a delay or a distortion of development may present. The retarded development of optic nerve axons is discussed in relation to delays, distortions and deficits during visual system maturation in protein-deprived rats.

Animals↗

PubMed1966

Effect of hydroxyurea on virus development. I. Electron microscopic study of the effect on the development of bacteriophage T4.

Margaretten, William (College of Physicians and Surgeons of Columbia University, New York, N.Y.), Councilman Morgan, Herbert S. Rosenkranz, and Harry M. Rose. Effect of hydroxyurea on virus development. I. Electron microscopic study of the effect on the development of bacteriophage T4. J. Bacteriol. 91:823-833. 1966.-Double fixation in gluteraldehyde and osmium tetroxide and the application of lead staining revealed details of viral structure not previously observed in thin sections. Bacteriophage presumed to have injected its deoxyribonucleic acid (DNA) exhibited a dense, hollow, disc-shaped core. Within the cytoplasm of infected bacteria, the peripheral membrane of the viral heads was clearly visible. Aberrant forms containing the hollow core and believed to be devoid of DNA were encountered in studies of the normal course of development. Hydroxyurea, which is believed to interfere with the production of infective bacteriophage by inhibiting DNA synthesis, resulted in the appearance of viral particles with the hollow disc or with bizarre, distorted cores. However, a significant number of viral heads looked entirely normal and presumably contained a full complement of DNA. Hypotheses are presented to explain these observations.

Coliphages↗

PubMed1986

Enhancement of fluorescence development of end products by use of a fluorescence developer solution in a rapid and sensitive fluorescent spot test for specific detection of microbial beta-lactamases.

A fluorescent spot test method for specific detection of microbial beta-lactamases as previously published (K. C. S. Chen, J. S. Knapp, and K. K. Holmes, J. Clin. Microbiol. 19:818-825, 1984) was improved by the use of a fluorescence developer solution. The fluorescence developer solution used in this study consisted of 0.78 M sodium tartrate buffer containing 12% formaldehyde at a final pH of 4.5. An addition of 1 volume of fluorescence developer solution to 5 volumes of ampicillin or cephalex substrate solution incubated with beta-lactamase-producing organisms, followed by heating the mixture at 45 degrees C for 10 min resulted in enhancement of fluorescence of the end products of beta-lactamase activity. This provides a more sensitive assay for microbial beta-lactamases and offers the potential for direct detection of beta-lactamases in clinical specimens.

Amidohydrolases↗

PubMed2000

Characterization of tissue outgrowth developed in vitro in patients with rheumatoid arthritis: involvement of T cells in the development of tissue outgrowth.

BACKGROUND: The aim of this study was to analyze cellular and cytokine interactions governing the development of synovial tissue outgrowth in patients with rheumatoid arthritis (RA). METHODS: A single-cell suspension of dissociated synovial tissues of RA patients was cultured for a long period to develop tissue outgrowth. The resulting tissue outgrowth was characterized by immunohistochemical staining and ELISA. RESULTS: The tissue outgrowth developed in vitro included various cell types, such as macrophage-like synovial cells, fibroblast-like synovial cells and lymphocytes. Even after prolonged cultivation, synovial cells devoid of infiltrating T lymphocytes did not form tissue outgrowth. The outgrowth contained CD3+ cells, LeuM3 (CD14)+ cells and HLA-DR+ cells. The T cells expressed lymphocyte function-associated antigen (LFA)-1 and CD2, and the synovial cells expressed intracellular adhesion molecule (ICAM)-1 and LFA-3, suggesting possible interactions via LFA-1/ICAM-1 and CD2/LFA-3. Production of T-cell derived IFN-gamma and IL-17 and synovial-cell-derived fibroblast growth factor (FGF)-1 and IL-15 was confirmed in the tissue outgrowth as well as in RA synovial tissue. These cell types stimulate each other by secreting cytokines, leading to the secretion of proinflammatory cytokines and matrix metalloproteinase (MMP)-1 by the tissue outgrowth and proliferation of both lymphocytes and synovial cells. CONCLUSION: This study emphasizes the importance of cellular interactions between T cells and synovial cells, via adhesion molecules and the secretion of cytokines with stimulatory activity towards other cell types, for the hyperactivity of RA synovial cells.

Arthritis, Rheumatoid↗