Constitutive production of lymphocyte activating factors by normal tissues in the adult rat

Lymphocyte activating factors (LAFs), e.g., interleukin-1 (IL-1) and IL-1-like factors, have previously been demonstrated outside the immune system in the skin, thymus epithelium, and the human and rat testis. We have studied the presence of LAFs in normal tissues of the adult rat, utilizing a highly IL-1 sensitive murine thymocyte proliferation assay. We have demonstrated high amounts of LAF activity in the tongue, esophagus, proventricular part of the stomach, and the liver. Some activity was also demonstrated in the duodenum, placenta, spleen, Peyer's patches, glandular stomach, and jejunum, but no bioactivity was present in other gastrointestinal, endocrine, lymphoid, or haematopoeitic tissues. We were also unable to detect any LAF activity in the reproductive organs (except for the testis), urinary tract, skeletal and muscular tissues, brain, eyes, salivary glands, or lung. In the esophagus the activity was mainly localized to the mucosa. The LAF activity in the skin was partly inhibited by treatment with a mixture of antibodies against human IL-1 alpha and IL-1 beta. Dose response curves and gel filtration on a Sephacryl S-200 column suggested the presence of a high molecular weight (90,000-100,000 Da) LAF inhibitory factor in the liver. In all positive tissues, the demonstrated LAFs had a molecular weight of 15,000-25,000 Da, as determined by Sephacryl S-200 gel filtration. Of the positive tissues, the skin, tongue, esophagus, and the proventricular part of the stomach all contain stratified squamous epithelium. It is tempting to suggest that the detected LAFs have a similar function in these barrier tissues, e.g., to serve as host defence factors, or, alternatively or additionally, as tissue growth factors.     

Steric factors in lymphocyte stimulation by organomercurials.

Resting human lymphocytes were stimulated to initiate DNA synthesis by divalent mercury ions or by the divalent organomercurial, 1,4-bismercury-3, 4-dihydroxybutane. Monovalent methylmercury was ineffective, as was mercury-substituted dextran which is a polyvalent compound where the mercury atoms are farther apart than in the divalent butane derivative. These findings suggest that for organomercurials to stimulate lymphocyte DNA synthesis, they must crosslink protein sulfhydryl groups and bring these groups into close proximity.     

Maternal and genetic factors determine early life telomere length

In a broad range of species—including humans—it has been demonstrated that telomere length declines throughout life and that it may be involved in cell and organismal senescence. This potential link to ageing and thus to fitness has triggered recent interest in understanding how variation in telomere length is inherited and maintained. However, previous studies suffer from two main drawbacks that limit the possibility of understanding the relative importance of genetic, parental and environmental influences on telomere length variation. These studies have been based on (i) telomere lengths measured at different time points in different individuals, despite the fact that telomere length changes over life, and (ii) parent–offspring regression techniques, which do not enable differentiation between genetic and parental components of inheritance. To overcome these drawbacks, in our study of a songbird, the great reed warbler, we have analysed telomere length measured early in life in both parents and offspring and applied statistical models (so-called ‘animal models'') that are based on long-term pedigree data. Our results showed a significant heritability of telomere length on the maternal but not on the paternal side, and that the mother''s age was positively correlated with their offspring''s telomere length. Furthermore, the pedigree-based analyses revealed a significant heritability and an equally large maternal effect. Our study demonstrates strong maternal influence on telomere length and future studies now need to elucidate possible underlying factors, including which types of maternal effects are involved.     

Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats

Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures.     

Production of factors regulating macrophage motility in the early stages of mixed lymphocyte culture

The macrophage migration stimulation factor (MSF) is produced during the first hours of mixed lymphocyte culture (MLC) in the H-2 system. The activity of MSF is characterized by sharp peaks of migration stimulation in the culture fluids of allogeneic MLC. The peaks appeared every 5 hours. After 12--16 hours in the culture fluids of allogeneic MLC, there has been demonstrated macrophage migration inhibition factor whose activity rose by 48 hours. Optimal concentrations were revealed for stimulation and inhibition of macrophage migrations on the dilution of 1--2-day MLC culture fluids. The existence of the biorhythmical mechanism that controls the macrophage mobility through the balance of soluble mediators with alternative activity is suggested.     

Influence of environmental factors in early ontogenesis on aging and life span

A possible dependence of aging and life span in man on specific features of early ontogenesis has been analyzed on the basis of published and author's data. It was shown that the life span depended on climatic factors acting during prenatal and/or early postnatal period. When analyzing a sample of 101,634 humans died in Kiev in 1990-2000, a reliable relationship was established between the age of death and month of birth. The lowest and highest death ages were observed in persons born in April-June and in the end of the year, respectively. The lowest and highest average monthly values of death age differed in men and women by 2.6 and 2.3 years, respectively. In persons survived for more than 60 years, a "birthday" effect was demonstrated: dependence of the mortality level on the month of individual annual cycle was the highest in its first and last month. It has been proposed that this effect is related imprinting of the "birth stress" in the structure of biological rhythms, which may lead to periodic changes in viability during the individual annual cycle. The mechanisms underlying long-term effects of stresses in early ontogenesis have been studied on Drosophila melanogaster. X-irradiation of eggs at 0.50 and 0.75 Gy led to an increased level of survival of imago. The described radiation hormesis was accompanied by an increased resistance of DNA to S1-nuclease, which could be due to a long-term activation of the repair system in irradiated insects. The results obtained suggest that long-term changes in the range of gene expression induced by mild stresses in early ontogenesis can be a key mechanism of early "programming" of the potential of longevity and hormesis for life span.     

Effects of maternal conditions on early life history traits of black porgy Acanthopagrus schlegeli

This work examined the effects of maternal conditions on early life history traits of black porgy Acanthopagrus schlegeli . Age-II females produced significantly larger eggs as compared to the same size of Age-III females. Also, within each of the age groups, there was a positive relationship between egg size and female size. The larger eggs generally had larger volumes of oil globules, required longer incubation periods (hatching age), and produced larger larvae that endured longer to starvation. Hatching age was covaried negatively with yolk volume at hatching, indicating that embryonic development consumed primarily yolk as its energy resource. The condition factor, gonadosomatic index, hepatosomatic index, and lipid content of the females were not related to the early life history traits of their offspring.     

Do early life factors affect the development of knee osteoarthritis in later life: a narrative review

Osteoarthritis (OA) mainly affects older populations; however, it is possible that early life factors contribute to the development of OA in later life. The aim of this review is to describe the association between childhood or early adulthood risk factors and knee pain, structural imaging markers and development of knee OA in later life. A narrative overview of the literature synthesising the findings of literature retrieved from searches of computerised databases and manual searches was conducted. We found that only a few studies have explored the long-term effect of childhood or early adulthood risk factors on the markers of joint health that predispose people to OA or joint symptoms. High body mass index (BMI) and/or overweight status from childhood to adulthood were independently related to knee pain and OA in later life. The findings regarding the association between strenuous physical activity and knee structures in young adults are still conflicting. However, a favourable effect of moderate physical activity and fitness on knee structures is reported. Childhood physical activity and performance measures had independent beneficial effects on knee structures including knee cartilage in children and young adults. Anterior knee pain syndrome in adolescence could lead to the development of patellofemoral knee OA in the late 40s. Furthermore, weak evidence suggests that childhood malalignment, socioeconomic status and physical abuse are associated with OA in later life. The available evidence suggests that early life intervention may prevent OA in later life.     

Immunoreactive growth hormone production by human lymphocyte cell lines

1. Two human lymphocyte cell lines, a T-cell line and a B-cell line, were shown to produce and secrete immunoreactive growth hormone (irGH). The irGH molecules secreted by the two cell lines appeared to be de novo synthesized and their molecular size was similar to that of pituitary GH as well as irGH secreted by peripheral blood lymphocytes. 2. Affinity-purified irGH molecules had human growth hormone (hGH)-like mitogenic activity on Nb2 cells. These findings indicate that the irGH molecules produced by H9 and IM9 were similar to hGH in structure. 3. However, the irGH messages could not be amplified by polymerase chain reaction (PCR) primers which had been demonstrated to be able to amplify reverse-transcribed hGH messenger RNA successfully, suggesting that the lymphocyte-derived irGH and pituitary hGH are not exactly identical molecules. 4. We conclude that the H9 and IM9 cells produce a growth hormone-related molecule whose structure is different from that in the anterior pituitary.     

Involvement of proteolytic acivity in early events in lymphocyte transformation by phytohemagglutinin

The stimulation by phytohemagglutinin (PHA) of DNA synthesis in cultured blood lymphocytes of guinea pig was markedly inhibited by addition of leupeptin, a well-characterized, powerful protease inhibitor of tripeptide nature. About 30 to 40 per cent inhibition was observed at 40 μg/ml of leupeptin when leupeptin was added 30 min prior to or together with PHA. Per cent inhibition by the appropriate amount of leupeptin was proportional to the amount of PHA added in the range of 0.6 to 3.0 μg of PHA at which the per cent inhibition reached maximum. This inhibitory effect of leupeptin on PHA stimulation was abolished when the lymphocytes were preincubated with PHA for more than 10 min before addition of leupeptin or preincubated with leupeptin for more than 60 min prior to PHA addition.     

Growth factors involved in lymphocyte differentiation

We report here that an interleukin-3-dependent precursor B-cell line, LyD9, differentiated in vitro into mature B cells, producing immunoglobulin (Ig)M and IgG by co-culture with bone marrow stroma cells. Induced LyD9 cells underwent heterogenous immunoglobulin gene rearrangement and synthesized mRNAs encoding immunoglobulin mu (mu), gamma (gamma) and kappa (kappa) chains. LyD9 was also shown to differentiate into myeloid cells. We have established an interleukin-4-dependent derivative clone K-4 that is an intermediate between myeloid-lymphoid cells and the LyD9 clone. This differentiation required direct contact between LyD9 and stromal cells.     

Induction of cytotoxic lymphocyte responses by antigen-specific helper factors

Antigen-specific helper factors (ASHF) were purified by antigen-affinity chromatography from supernatants of long-term helper T lymphocyte (TH) lines. We have modified an established helper-dependent assay system to demonstrate the antigen specificity and H-2 restriction properties of ASHF in the induction of cytotoxic T lymphocyte precursors (CTLp). Antigen specificity is demonstrated by the binding of ASHF molecules only to nominal antigen, both during purification and in tests of functional activity. Our ASHF preparations do not contain any interleukin 2 (IL 2) activity. The ASHF, purified by antigen-affinity chromatography in the presence of Ca++, is defined as Ca++-sufficient ASHF, whereas ASHF purified on antigen-affinity columns in the absence of Ca++ is defined to be Ca++ deficient. Ca++-sufficient ASHF is not H-2 restricted (as defined by the phenotype of the ASHF-producing cells) in the recognition of nominal antigen or in its interactions with CTLp or adherent stimulator cells. In contrast, when the "complete" (Ca++-sufficient) ASHF is functionally dissociated into subunits by removal of Ca++, the "incomplete" antigen-specific subunit of ASHF (Ca++-deficient ASHF) is still H-2-unrestricted in its ability to bind nominal antigen, but requires products from syngeneic adherent cells to trigger CTLp. When adherent cells that are H-2 identical to the ASHF are provided in culture, the "incomplete" ASHF is able to trigger either syngeneic or allogeneic CTLp in an antigen-specific manner. We interpret the results of our experiments to suggest that an H-2-restricted molecular interaction occurs in CTLp induction by ASHF. An antigen-specific, TH-derived receptor appears to require association with Ca++ and self major histocompatibility complex (MHC)-encoded molecules to form a "complete" ASHF that is able to trigger CTLp in an apparently H-2-unrestricted manner.