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We propose a model for the dynamics of the immune system by considering the subpopulations of virgin and memory T lymphocytes on a time scale corresponding to the human life span. In the deterministic balance equation we introduce a fluctuating term in order to take into account the chronic antigenic stress. Starting from the hypothesis that the depletion of virgin cells with cytotoxic properties (CD8+) is a mortality marker, the model provides survival curves quite similar to the demographic curves.

The effect and the mechanism of light regimen and melatonin on the development of mammary tumors in HER2/neu transgenic mice were investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen (LD) or constant light illumination (LL) and a part of each group was given melatonin (20 mg/l) during the night time.The exposure to LL failed to change the incidence of spontaneous mammary adenocarcinoma development, the size of mammary tumors, as well as the incidence and size of lung metastases. However, the number of tumors per mouse was significantly increased in the LL group as compared to the LD group. The number of mice bearing 4 and more tumors was higher in the LL group than in the LD group, whereas the number of mice bearing 1 to 3 tumors was lower in the LL group in comparison with the LD group. Melatonin decreased the incidence and size of mammary adenocarcinomas, and the incidence of lung metastases in the LD group but not in the LL group. The mean number of tumors per mouse was not changed by melatonin treatment in both light regimens. The number of mice bearing 4 and more tumors was reduced by melatonin more significantly in the LL group than in LD group. Melatonin treatment resulted in a 2.5-fold reduction in the expression of HER-2/neu mRNA in mammary tumors from HER-2 /neu transgenic mice.The data demonstrate the influence of the LD light regiment and melatonin treatment in the development of spontaneous mammary tumors in HER-2/neu mice suggesting a melatonin-dependent modulation of HER-2/neu gene expression in mammary adenocarcinoma.

Diffuse neuroendocrine system (DNES) cells regulate homeostasis via neurocrine, endocrine and paracrine mechanisms. Extensive effects of peptide hormones and biogenic amines necessitate studying of DNES cell biology in aging. In this connection, the functional morphology of gut neuroendocrine cells (NEC), proliferative activity and apoptosis of mucous epithelial cells in aging have been studied.The study was performed on BALB/c-nu mice of 4, 21 and 34 months of age. NEC, proliferative activity and apoptosis of mucous epitheliocytes in stomach and duodenum have been studied by histochemical, immunohistochemical and morphometrical methods.The total number of NEC shows an increasing trend with advancing age. However, the different types of NEC elicit differential patterns. The total number of epithelial cell nuclei does not show any statistically significant difference during aging. The proliferative activity of mucous epitheliocytes also shows no difference among the three animal groups studied. On the contrary, the apoptotic index increases with advancing age.The results demonstrate that various gut NEC show differential behavior with age and their time-courses are dependent on the site of location (stomach or duodenum). The picture seems quite complex to allow a comprehensive interpretation, nonetheless it gives us some useful indications for further investigation. In fact, since the gut does not show evident gross age-related physiological changes, modifications with age in specific biological parameters can suggest the key mechanisms of compensative regulatory processes possibly acting during aging.

Current literature indicates that elevated IL-6 serum levels are associated with diseases, disability and mortality in the elderly. In this paper, we studied the IL-6 promoter genetic variability at -174 C/G locus and its effect on IL-6 serum levels in a total of 700 people from 60 to 110 years of age, including 323 centenarians. We found that the proportion of homozygotes for the G allele at -174 locus decreases in centenarian males, but not in centenarian females. Moreover, we found that, only among males, homozygotes for the G allele at -174 locus have higher IL-6 serum levels in comparison with carriers of the C allele. On the whole, our data suggest that those individuals who are genetically predisposed to produce high levels of IL-6 during aging, i.e. -174 locus GG homozygous men, are disadvantaged for longevity.

In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20-64-year-old subjects. However, when Danish and Italian data were compared, a significant difference (p = 0.0004) was found between the frequencies of Small alleles in youths, which disappeared in centenarians (p = 0.290). Furthermore, the demographic-genetic approach revealed in Danes a significant gene-sex interaction relevant to Long alleles (more than 37 repeats). The different findings in Denmark and Italy suggest that gene/longevity associations are population-specific, and heavily affected by the population-specific genetic and environmental history.

Plasma levels of alpha1-antichymotrypsin (ACT) and interleukin-1beta (IL-1beta) were increased in patients with probable Alzheimer's disease (AD). A common polymorphism within ACT and IL-1beta genes affected plasma levels of ACT or IL-1beta, and AD patients with the ACT T,T or IL-1beta T,T genotype showed the highest levels of plasma ACT or IL-1beta, respectively. The concomitant presence of the ACT T,T and IL-1beta T,T genotypes increased the risk of AD (odds ratio: 5.606, confidence interval: 1.654-18.996) and decreased the age at onset of the disease.

Clinical observations indicate that elderly people are prone to severe, often lethal infectious diseases induced by novel pathogens. Since the ability to mount primary immune responses relies on the availability of naive T cells, the circulating naive T-cell reservoir was evaluated throughout the human life span. Naive T cells were identified as CD95(-) T lymphocytes for their phenotypic and functional features. Indeed, the lack of CD95 marker is sufficient to identify a population of naive T cells, as defined by coincidence with previously characterized CD45RA(+) CD62L(+) T cells. Naive CD95(-) T cells, as expected, require a costimulatory signal, such as CD28, to optimally proliferate after anti-CD3 stimulation. Cytofluorimetric analysis of circulating T lymphocytes from 120 healthy subjects ranging in age from 18 to 105 years revealed that naive T cells decreased sharply with age. The younger subjects had a naive T-lymphocyte count of 825 +/- 48 cells/microL, and the centenarians had a naive T-lymphocyte count of 177 +/- 28 cells/microL. Surprisingly, the naive T-cell count was lower in CD8(+) than in CD4(+) subsets at any age, and the oldest individuals were almost completely depleted of circulating naive CD8(+) T cells (13 +/- 4 cells/microL). Concomitantly, a progressive expansion of CD28(-) T cells occurs with age, which can be interpreted as a compensatory mechanism. These data provide new insights into age-related T-cell-mediated immunodeficiency and reveal some analogies of T-cell dynamics between advanced aging and human immunodeficiency virus (HIV) infection. In conclusion, the exhaustion of the naive CD8(+) T-cell reservoir, which has never been reported before, suggests that this T-cell pool is a major target of the aging process and may define a parameter possibly related to the life span of humans. (Blood. 2000;95:2860-2868)

Gender accounts for important differences in the incidence and prevalence of a variety of age-related diseases. Considering people of far advanced age, demographic data document a clear-cut prevalence of females compared to males, suggesting that sex-specific mortality rates follow different trajectories during aging. In the present investigation, we report data from a nationwide study on Italian centenarians (a total of 1162 subjects), and from two studies on centenarians living in two distinct zones of Italy, i.e., the island of Sardinia (a total of 222 subjects) and the Mantova province (Northern Italy) (a total of 43 subjects). The female/male ratio was about 2:1 in Sardinia, 4:1 in the whole of Italy, and about 7:1 in the Mantova province. Thus, a complex interaction of environmental, historical and genetic factors, differently characterizing the various parts of Italy, likely plays an important role in determining the gender-specific probability of achieving longevity. Gender differences in the health status of centenarians are also reported, and an innovative score method to classify long-lived people in different health categories, according to clinical and functional parameters, is proposed. Our data indicate that not only is this selected group of people, as a whole, highly heterogeneous, but also that a marked gender difference exists, since male centenarians are less heterogeneous and more healthy than female centenarians. Immunological factors regarding the age-related increase in pro-inflammatory status, and the frequency of HLA ancestral haplotypes also show gender differences that likely contribute to the different strategies that men and women seem to follow to achieve longevity. Concerning the different impact of genetic factors on the probability of reaching the extreme limits of the human life-span, emerging evidence (regarding mtDNA haplogroups, Thyrosine Hydroxilase, and IL-6 genes) suggests that female longevity is less dependent on genetics than male longevity, and that female centenarians likely exploited a healthier life-style and more favorable environmental conditions, owing to gender-specific cultural and anthropological characteristics of the Italian society in the last 100 years.

Reproducibility of venous flow measurements with Doppler velocimetry depends on the type of stress test used. The signification of the resulting index varies with the type of calculation used. The Paranà manoeuvre has three advantages: it is easy to perform; has good reproducibility and the stress test is hemodynamically similar to the real situation. Unlike volumetric measurements such as the Psatakis index, the dynamic back flow index can be used to evaluate the degree of incontinence. The Psatakis index does however allow detection and measurement of shunt effect. By calculating these two indices when performing the Paranà manoeuvre (isometric reflex contractions of the lower limbs in stationary standing position), the real hemodynamic conditions controlling deep vein function when walking can be evaluated more precisely.

Ambulatory conservative haemodynamic correction of venous insufficiency (CHIVA) is a surgical treatment of superficial venous insufficiency designed to correct the pathological haemodynamic effects of superficial venous insufficiency apparent on standing. Surgical treatment is based on precise preoperative anatomical and haemodynamic mapping performed by duplex ultrasound, providing preoperative ultrasound-guided marking. Surgical treatment consists of dividing the hydrostatic pressure column and disconnecting venovenous shunts by ligation-section of the superficial venous network at precise points determined by the preoperative ultrasound-guided marking. This strategy should achieve a superficial venous circuit draining perfectly into the competent deep venous network. The operation is performed under local anaesthesia as an outpatient procedure and allows immediate resumption of walking, which promotes a good result due to activation of the calf muscle pump. The results of the technique are very good provided a reliable preoperative ultrasound-guided marking and a precise surgical procedure are performed. Failures are due to poor haemodynamic assessment or inappropriate surgical procedure.

In vertebrates, including man, the study of stress has contributed substantially to unravelling the complex relationship between immune-neuroendocrine interactions and the systems involved. On the basis of data on the presence and distribution of the main actors (POMC products, cytokines, biogenic amines, and steroid hormones) in different species and taxa from invertebrates to vertebrates, we argue that these responses have been deeply connected and interrelated since the beginning of life. Moreover, the study of nitric oxide suggests that the inflammatory reaction is located precisely between the immune and stress responses, sharing the same fundamental evolutionary roots. The major argument in favor of this hypothesis is that the immune, stress, and inflammation responses appear to be mediated by a common pool of molecules that have been conserved throughout evolution and that from a network of adaptive mechanisms. One cell type, the macrophage, appears to emerge as that most capable of supporting this network critical for survival; it was probably a major target of selective pressure. All these data fit the unitarian hypothesis we propose, by which evolution favors what has been conserved, rather than what has changed, as far as both molecules and functions are concerned.

To assess three-year results following "CHIVA".Comparison between our results and data in the literature following stripping.Phlebologic Surgery, 46 Datini Street, Florence, Italy.148 consecutive operated patients suffering from varicose veins (166 procedures)."CHIVA", as described by Franceschi and Bailly.The presence of visible varicose veins, graded in three categories, according to Hobbs and Einarsson, as shown by clinical examination.Very good results were obtained in 100 cases, who presented without any finding of varicose veins throughout the follow-up. Of the remaining 66, in 1 case we found a new varicose network completely developed, whereas in 65 cases only some visible residual or recurrent vessels were present.Significantly better results were observed in the CHIVA group compared with stripping groups (P0,001).

Concursus motus ordo positura figurae cum permutantur, mutari res quoque debent (Lucretius): “It is the combined variation of movement, rank and position that explains the variety of natural forms.”

The immune system represents the set of organs, cells, and factors whose physiological function it is to protect us from diseases, infections, and tumors. This chapter discusses certain fundamental immunophysiological principles. Hormones and peptides produced by endocrine glands modulate most, if not all physiological processes, including, as discussed in this chapter, immune responses. The neuroendocrine system is described in detail elsewhere (see Chap. 19).

Ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine metabolism, has been shown to be required for entry into and progression through the cell cycle. However, the role of ODC and polyamines in apoptosis remains to be determined. We have examined ODC expression and polyamine levels in thymocytes activated to undergo apoptosis by dexamethasone treatment. We have demonstrated a rapid and reversible induction of ODC (mRNA and activity), as previously reported for the mRNA expression of other "early" genes, c-fos, c-jun, and c-myc, in the same experimental model. Surprisingly, polyamine levels diminished progressively starting at 2-4 h after dexamethasone treatment, and spermine was depleted at 8-12 h. This seemed to be relevant since increasing the intracellular polyamine levels by exogenous spermine administration prevented the DNA "laddering" (2-4 h) and the DNA loss from the nucleus (8-18 h) due to dexamethasone treatment. Moreover, the activities of spermidine/spermine N1-acetyltransferase, which controls the cytosolic polyamine interconversion pathway, and of spermidine N8-acetyltransferase, which regulates the nuclear pool and functions of polyamines, were measured in apoptotic cells. Spermidine/spermine N1-acetyltransferase activity progressively increased and might be responsible for spermidine and spermine excretion as acetyl derivatives. In contrast, spermidine N8-acetyltransferase activity remained unchanged. A completely different scenario was observed in proliferating concanavalin A-treated thymocytes, studied for comparison. In this case, polyamine levels increased, remaining at high values until 12 h. This is likely a consequence of the rapid and prolonged induction of ODC (mRNA and activity), accompanied by that of spermidine/spermine N1-acetyltransferase (mRNA and activity).(ABSTRACT TRUNCATED AT 250 WORDS)

We show here that hemocytes and leukocytes with phagocytic activity from both invertebrates ( Planorbarius corneus, Viviparus ater ) and vertebrates ( Carassius auratus, Rana esculenta ) express pro-opiomelanocortin (POMC) mRNA, as assessed by in situ hybridization with a digoxigenin-labeled human DNA probe. These data are in accord with previous observations from our laboratories on the presence in these cells of POMC-derived peptides and strongly suggest that these molecules-highly conserved throughout evolution-play an important role in cell locomotion and phagocytosis. POMC mRNA was also detected in lymphocytes of R. esculenta, but not of C. auratus, suggesting that from anuran amphibians onwards lymphocytes also express this gene. This phenomenon could be related to the appearance of more than one immunoglobulin isotype in anurans.

Varicose veins are not the only symptomatology of chronic venous insufficiency of the lower limbs, which has other clinical manifestations: purely symptomatic problems, varicosities, edema and trophic skin lesions. The management of varicose veins is base upon thorough clinical examination. Doppler and ultrasonography are useful in cases of varicose veins in which radical treatment is envisaged. Ultrasound investigation is essential in the presence of cutaneous ulceration in order to avoid mistaking a trophic lesion due to incompetence of deep veins, most often of post-thrombotic origin, for a varicose ulcer. The treatment of varicose veins varies according to the precise nature of the preoccupations of the patient concerned. Elastic support is useful regardless of the clinical form of the disease. Vasculoprotective and venotonic drugs can be used when venous insufficiency is symptomatic. Radical treatment of varicose veins, whether by sclerosing injections or surgery, depends upon the anatomical nature of lesions, the degree of venous incompetence and the extent of signs, but also the wishes of the patient, properly informed of the advantages and limitations of each technique.

Electromagnetic fields produce a variety of effects in several biological systems, including human peripheral blood lymphocytes. A great concern exists regarding possible carcinogenic effects in subjects exposed environmentally to such fields in the vicinity of power lines and electric domestic appliances. Using human lymphocytes from 33 healthy donors and a sensitive cytogenetic method, the cytokinesis-block micronucleus assay, we have demonstrated that the exposure to 50-Hz AC sinusoidal electric fields over a wide range of intensities (0.5-10 kV/m in air) does not increase the spontaneous frequency of micronuclei. Moreover, these fields did not affect the mitomycin-C-induced micronucleus formation, suggesting that they did not exert any synergistic or antagonistic effect.

In a previous study we demonstrated the presence of NK-like activity in the mollusc Planorbarius corneus. This activity can be ascribed to round hemocytes that have a morphology similar to that of vertebrate lymphocytes. We show here that this NK-like cytotoxicity is evident in serum-free culture medium. Moreover, the type of death induced by molluscan effector cells on their targets is probably similar to that induced by vertebrate effector cells, i.e. apoptosis or programmed cell death, as assessed by the protective effect exerted by 3-aminobenzamide when both types of effector cells were used.

Using a variety of techniques we found the presence of ACTH and opioid-like molecules in the phagocytic spreading hemocytes (SH) and the serum of the mollusc Planorbarius corneus. In vitro experiments have shown that ACTH and beta-endorphin exert chemotactic activity on SH, while ACTH, but not beta-endorphin increases the phagocytic activity of SH. Moreover, ACTH and CRF provoked the release of biogenic amines from the hemocytes, mimicking a proto-stress type of response. Thus, the same mobile cell is capable of immune and proto-stress responses by using as mediators neuropeptides which remained fundamentally similar throughout evolution.

Contrasting with the destructive methods of treating varicose veins, the CHIVA cure (Cure Conservatrice et Hémodynamique de l'Insuffisance Veineuse en Ambulatoire) technique is a conservative and hemodynamic approach of this problem. Based on coherent physiological principles, it proposes rigorous analysis followed by effective correction of the hemodynamic disorders, resulting in lasting benefits on the esthetic, functional and tropic changes associated with varicose veins. The results of the CHIVA technique in several french and european-centers, including over 10,000 procedures performed between 1987 and 1991, confirm the value of the method first described by the author in 1988. They confirm the necessity of respecting the strategic and tactical rules of this new approach and the need for specific theorical and practical training.

From January 1987 to December 1988, 100 conservative and hemodynamic treatments of superficial venous insufficiency in great saphenous vein territory, have been done on 86 patients. They were 32 men, whose mean age was 53.7 years, and 54 women, whose mean age was 44.5 years. Indication for surgery was mainly functional in 28 cases, esthetic in 26 cases, both in 25 cases and trophic problems in 21 cases. Ligation of the sapheno-femoral junction has been done in 91 cases (62 clips, 9 clips and ligations, 11 ligations, 9 sutures). Distal interruption has been done above knee in 24 cases, below knee in 50 cases, and both in 16 cases. Early postoperative complications have been one septic collection of the groin, one hematoma of the groin, one durable contusion of the saphenous nerve, and 21 superficial venous thrombosis. There were six thrombosis of excluded branches, seven subtotal thrombosis of the saphenous and height partial thrombosis of the saphenous vein. Subtotal thrombosis of the saphenous vein were due either to a mistake in position of distal ligation in three cases, either to a too large saphenous vein in four cases. Five out of height partial thrombosis occurred on saphenous veins larger than ten millimeters. Follow up was obtained, in 1990, so that all patients had at least one year of follow-up. Seven patients have been lost for follow-up. Three patients had recurrence because of failure of the clip. An additional procedure was necessary in 30 patients. Functional results were correct in 89% of patients, and esthetical results in 68% of patients.

analysis of Doppler Duplex (DD) contribution to renal artery percutaneous angioplasty (ATL) follow-up.between 1983 and 1989, SO ATL were performed in 47 subjects with renovascular hypertension. Their average age was 50 +/- 12 years. The lesions were fibromuscular dysplasia (n = 20) and atherosclerosis (n = 27). The DD was performed simultaneously with arteriography (A degrees) (considered the gold standard), when the stenosis was discovered (n = 32), before (n = 32) and after (n = 39) ATL, and during the follow-up between the 6th and 12th month (n = 38).during the initial exploration, the concordance between DD and A degrees is 78% and the sensitivity of DD for the diagnosis of stenosis is 90%. ATL was performed once on the basis of DD alone, that showed a tight and significant stenosis with dysplasia, when A degrees failed to detect it. ATL confirmed the lesion and was successful, and hypertension cured. The concordance DD-A degrees before and after ATL is respectively 88% and 77%. At the late control, the concordance is 92%, the sensitivity 73% and the specificity 85% for all stenosis. While maintaining a good specificity, DD recognized the 3 tight found by the A degrees control. The complications encountered during ATL were diagnosed by DD most of the time: all the local complications at the site of entry (n = 5), all the dissections with obliteration (n = 2) and 5 of the 8 dissections without obliteration of the renal artery.the detection and the lesional assessment of post-ATL complications are facilitated by DD. The good sensitivity of DD combined with satisfactory specificity will allow the reduction of angiographic surveillance by taking advantage of a non-invasive method.

C3H mice have been used to investigate the effect of a combination of cyclophosphamide (CY) and electromagnetic fields (PEMF). Mice were injected i.p. with a single dose of 200 mg/kg body weight of CY and then exposed to PEMF 24 h per day. In an initial series of experiments immediately after CY injection mice were exposed to PEMF until sacrifice. WBC counts in the peripheral blood demonstrated a quicker decline in WBC at days 1 and 2 in mice exposed to PEMF. Groups of mice were sacrificed at days 1, 4, 6, 8, and 10 after CY injection. In mice exposed to PEMF the spleen weight was less than in controls at days 6, 8, and 10. Autoradiographic studies demonstrated that the labeling index of bone marrow smears did not significantly differ between controls and experimental mice exposed to PEMF, whereas the spleen labeling index proved to be higher among control mice versus mice exposed to PEMF at day 6, and higher among mice exposed to PEMF versus controls at day 8. In a second series of experiments mice were exposed to PEMF only over the 24 h following CY injection. We found that the spleens of mice exposed to PEMF weighed less than those of controls at days 6 and 8. The labeling index of bone marrow did evidence a slight decrease among mice exposed to PEMF at days 8 and 10 after CY injection versus control mice. The spleen labeling index proved to be lower in experimental mice exposed to PEMF than in controls at days 4, 6, and 8. Mice were then injected with CY, half were exposed to PEMF, and 24 h later bone marrow was recovered from both groups of animals. The same number of bone marrow cells was injected via the tail vein into recipient mice irradiated to 8.5 Gy. The grafting efficiency of the bone marrow was evaluated by examining the number of spleen colonies and the spleen and bone marrow labeling indices at day 8; all parameters proved to be significantly lower among mice grafted with the bone marrow of mice injected with CY and exposed to PEMF than among controls injected with CY only. Finally, we found th at the effect of PEMF is evident only if mice are exposed during the 24 h following CY injection. The data reported here indicates that PEMF exposure after CY injection increases the damage induced in mice by CY.

To ascertain the immune response capacity of Partridges to classical experimental and natural antigens, dose and time response curves to sheep red blood cells (SRBC), Newcastle disease virus (NDV) and Brucella abortus (Buck 19 strain), were determined in two strains reared in two different farms. 1 ml of 20% SRBC, 10(9) NDV particles and 10(7) Buck 19 microorganisms, gave optimal antibody responses seven (SRBC and Buck 19) or fourteen days after immunization. As far as SRBC is concerned, the antibody response was sex independent, but declined markedly in partridges older than 1 year. The immunization schedule used by us allow the identification of high and low responder animals. In fact, highly significant correlation in individual partridges between antibody titers obtained after two successive immunizations to an optimal SRBC dose given three weeks apart, was found. This fact, together with the observed great variability in the antibody response to the three antigens considered, should allow a selection for high and low responder lines, in order to improve the fitness toward environmental pathogens.

We have developed a technique to isolate monocytes from human peripheral blood. The technique takes special care of completely eliminating platelets which are usually present in other preparations. Monocytes obtained in good yelds (2.5-5.0 x 10 5 cells/ml blood), were found to be 70–80% pure on the basis of morphological and histochemical criteria. Contamination was largely due to the presence of lymphocytes. Monocytes were incubated in the presence or absence of arachidonic acid and TXB 2 , PGE 2 and 6-keto-PGF 1α were measured by specific and sensitive radioimmunoassays. It was found that when cells were incubated for up to 1 hr, the production of PGs was low or absent even in the presence of 10 μM arachidonic acid in the incubation medium. However, when incubations were carried out for 24 hrs in the presence of at least 1% fetal calf serum a dramatic increase in TX-, production occurred, with levels as high as 150 ng x 10 cells. The ratio TXB 2 /PGE 2 was around 3, while 6-keto-PGF was produced at a much lower level. In the same conditions, when care was taken to evaluate PGs already present in fetal serum and/or cross reactivity due to media generally employed, purified human lymphocytes appeared unable to produce detectable levels of the three PGs tested.

1. From the latex of two members of the plant family Euphorbiaceae, Hura crepitans L. (sand-box tree) and Euphorbia characias L. (Mediterranean spurge), two lectins were purified by affinity chromatography on acid-treated Sepharose 6B followed by elution with D-galactose. 2. The lectin from E. characias is a single molecular species with Mr 80 000, made up of two identical subunits with Mr 40 000, and is a glycoprotein containing 11% carbohydrate. 3. The lectin from H. creptians appears as a mixture of three isolectins with Mr 140 000, consisting of four different subunits with Mr values 37 500, 35 500, 31 000, and 29 000. 4. Both lectins have haemagglutinating activity, with no specificity for human blood groups. The haemagglutinating activity is inhibited by D-galactose and by galactose-containing oligosaccharides. 5. The lectin from H. crepitans is mitogenic to human T-, but not to B-, lymphocytes. The latex of E. characias is mitogenic to T- and, to a lesser extent, to B-, lymphocytes, but the purified E. characias lectin has no mitogenic activity. 6. The lectin from H. crepitans, but not that from E. characias, inhibits protein synthesis by a rabbit reticulocyte lysate.

C3H/Km flora-defined mice were used to investigate the effect of exposure to pulsing electromagnetic field (PEMF) after total body x-ray irradiation. Prolonged exposure to PEMF had no effect on normal nonirradiated mice. When mice irradiated with different doses of x-ray (8.5 Gy, 6.8 Gy, and 6.3 Gy) were exposed to PEMF 24 h a day, we observed a more rapid decline in white blood cells (WBC) in the peripheral blood of mice exposed to PEMF at all the x-ray dosages used. No effect of exposure to PEMF was observed on the survival of the mice irradiated with 6.3 Gy and 8.5 Gy; in mice irradiated with 6.8 Gy, 2 out of 12 survived when exposed to PEMF as compared to 10 out of 12 control mice that were irradiated only. At day 4 after irradiation autoradiographic studies performed on bone marrow and spleen of 8.5-Gy-irradiated mice showed no difference between controls and mice exposed to PEMF, whereas on 6.8-Gy mice the bone marrow labeling index was lower in mice exposed to PEMF. In mice irradiated to 6.3 Gy we observed that the recovery of WBC in the peripheral blood was slowed in mice exposed to PEMF and their body weight was significantly lower than in control mice that were irradiated only. The spleen and bone marrow of the mice irradiated to 6.3 Gy and sacrificed at days 4, 14, 20, and 25 after irradiation were analyzed by autoradiography to evaluate the labeling index. Half of the spleens from mice sacrificed at day 25 after irradiation were used to evaluate the RNA content. Autoradiography showed that in the spleen and bone marrow of control mice, there were more cells labeled with [3H]thymidine at days 4 and 14 and less at days 20 and 25 after irradiation in comparison with mice irradiated and exposed to PEMF. The Northern blot analysis of histone H3 and p53 protein RNAs extracted from the spleens at day 25 after irradiation showed a slight increase in cycling cells among spleens of mice exposed to PEMF. We suggest that the exposure to PEMF immediately after x-ray irradiation results in increased damage.

Human Tamm-Horsfall glycoprotein inhibits lymphocyte transformation induced by leucoagglutinin and haemagglutinin from Phaseolus vulgaris (red kidney bean). The glycoprotein interacts with the two lectins, giving insoluble precipitates. The interaction with leucoagglutinin is highly specific, and the shape of the precipitin curve is that of an antigen-antibody reaction; precipitation is specifically inhibited by N-acetyl-D-galactosamine. Results are discussed, and it is suggested that inhibition of lymphocyte transformation is due to competition between human Tamm-Horsfall glycoprotein and carbohydrate receptors on lymphocytes for the two lectins. The interaction between human Tamm-Horsfall glycoprotein and Phaseolus vulgaris lectins has been used to develop a one-step procedure for the separation of the two lectins by affinity chromatography on (human Tamm-Horsfall-glycoprotein)-Sepharose.

A reduced responsiveness of peripheral blood lymphocytes from PBC patients to phytohaemagglutinin (PHA) was observed. Such an alteration may be related either to an intrinsic defect of T cells to proliferate or to a derangement of endogenously secreted mediators with regulatory functions, i.e., prostaglandins (PG). The role of the PG mediated suppressor system in 14 PBC patients and in 12 age and sex matched controls was evaluated. After the addition of indomethacin, the lymphocyte responsiveness to PHA increased in both controls and in PBC patients. However, this increment was statistically significantly only in PBC patients. The addition of PGE1 and PGE2 to PHA stimulated cultures decreased the lymphocyte proliferative activity. No differential sensitivity to PGEs was detectable in lymphocytes from PBC patients. Our data suggest, that, after polyclonal stimulation, mononuclear cells from PBC patient may release increased levels of PGEs which in turn affect the proliferative activity of mitogen activated lymphocytes.