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Effect of occupational exposure to benzene on phytohaemagglutinin (PHA) stimulated lymphocytes in man.

This study was carried out to investigate the effects of potential low level exposure to benzene on phytohaemagglutinin (PHA) stimulated lymphocytes. Sixty six male workers of a refinery population were studied and compared with 33 control workers in the same refinery who were not known to have been exposed to benzene. The responsiveness of the lymphocyte to PHA as a measure of blastogenesis was measured by the incorporation of radio labelled thymidine by the stimulated lymphocytes in vitro. Questionnaires were used to determine various lifestyle factors such as smoking, drinking, and exposure to ionising radiation. The results showed that there was no difference between the exposed group (mean 28928 + 1524 SE (decays per minute (DPM] as compared with the control group (mean 28304 + 2483 SE DPM). Furthermore, it was not possible to determine any effects attributable to various social factors. There was, however, a suggestion of a decrease in mitogenic response with age in both exposed and control workers that was consistent with other studies. It has been shown that products of benzene metabolism may affect the mitogenic response of lymphocytes in a similar way to known promoting agents. This study was unable to show these effects, probably as a result of the low exposures encountered by the individuals.

Adult↗

Suppression of PHA-stimulated lymphocyte transformation in cynomolgus monkeys following infection with Coxiella burnetii.

Phytohemagglutin (PHA) induced blastogenesis of peripheral blood lymphocytes from cynomolgus monkeys infected with C. burnetii was suppressed between 14 and 28 days after infection. Lymphocytes became responsive to PHA again on day 35 with an increase in stimulation index when cultured with specific antigens. In contrast, production of specific humoral antibodies was not diminished during the acute and early convalescent stages of infection.

Animals↗

Measurement of dead space ventilation using a pHa servo-controlled ventilator.

A control system for the systemic arterial pH (pHa) servo control of mechanical ventilation has recently been developed. If pHa is maintained constant by the change, separation of minute volume into alveolar ventilation and physiological dead space ventilation (VE = fVA VDp) can be manipulated to show that VDp = (VE1 - VE 2)/(f1 - fe) where f1 and f2 are different ventilator frequencies and VE1 and VE2 are expired minute volumes at these frequencies. Also, added dead space can be measured. VDadded = (VE2 - VE1)/f where VE1 and VE2 are the minute volumes before and after the dead space was added. The validity of these equations was tested in the anesthetized dog. The measured added dead space was in close agreement with the volume of dead space which was added and with that measured by another independent method. The measurement of VDp, probably as a result of tidal volume-related changes in VDp, did not agree as well with VDp measured by an independent method.

Animals↗

Specific inhibitory action of polyunsaturated fatty acids on lymphocyte transformation induced by PHA and PPD.

Both saturated (SFA) and unsaturated fatty acids (UFS) inhibited PHA- and PPD-induced lymphocyte transformation. The degree of inhibition varied with the nature of the fatty acid (FA) and further comparison with their effect on unstimulated lymphocyte cultures suggests a specific action of polyunsaturated fatty acid (PUFA) on the lymphocyte PHA- and -PPD interaction. These findings are briefly discussed in the light of similar observations with PUFA-derived prostaglandins.

Arachidonic Acids↗

Phytohaemagglutinin (PHA) skin test in predicting prognosis in cancer patients.

The response to intradermal injection of 1 mug of purified PHA was found to correlate with survival of patients with advanced solid tumours treated by chemotherapy, with responders surviving longer than non-responders. In patients with prolonged survival, the reaction was enhanced. Negative intradermal response to PHA was found to be less common in cancer patients than negative responses to tuberculin or streptokinase, and was more easily reversed by successful chemotherapy.

Adult↗

Continuous measurement of intraarterial pHa, PaCO2, and PaO2 in the operating room.

Miniaturized sensors based upon the principles of optical fluorescence can measure the pH, PCO2, and PO2 of liquid or gas media. A prototype of a three-component fiberoptic sensor has been developed for intraarterial application by CDI, 3M Health Care, Irvine, California. We report the first study of this continuous intraarterial monitor in patients undergoing surgical procedures under general anesthesia. Fourteen patients participated in the study. The fiberoptic sensor was calibrated before insertion and then passed through an existing 18-gauge radial artery cannula. Blood samples were drawn at frequent intervals through the same cannula for in vitro blood gas analysis. For each of the 87 arterial blood gas samples obtained, the in vitro values of pHa, PaCO2, and PaO2 were compared with simultaneous readings from the fiberoptic sensor. For pHa, the mean error (error = fiberoptic value minus in vitro value) or "bias" of the fiberoptic data was -0.032 and the standard deviation of error or "precision" was 0.042. For PaCO2, the bias was -3.8 mm Hg and the precision was 4.7 mm Hg. For PaO2, the bias was -9.0 mm Hg and the precision was 23.3 mm Hg. For PaO2 values less than 175 mm Hg, the bias was -8.5 mm Hg and the precision was 8.3 mm Hg. Expressed in terms of percentage errors, the bias +/- precision values were -11.5% +/- 13.3% for PaCO2, and -6.2% +/- 10.0% for PaO2. The duration of the surgical procedures ranged from 1.6 to 8 h with an average of 4.2 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Origin and mediation of secretion induced by oral phytohaemagglutinin (PHA) in rats.

After oral administration several gut-binding lectins induce accumulation of liquor and amylase in the proximal small intestine. Orally administered Phaseolus vulgaris phytohaemagglutinin (PHA) was used to study the mediation of these effects in rats. The regulation of amylase secretion clearly differed from that of the liquor. The amylase activity was of pancreatic origin, in agreement with the known cholecystokinin-releasing effect of PHA. It appears that CCK exerts its effect both directly and by facilitating neural stimulatory pathways. Intestinal secretion was identified as the source of the liquor, without a contribution by other secretions. It was mediated by a local cholinergic reflex with the involvement of both muscarinic and nicotinic acetylcholine receptors. It is speculated that the observed enteric reflex may enable the gut to transport secreted antibacterial peptides or secretory antibodies from the crypts to adherent bacteria on adjacent villi.

Administration, Oral↗

Polyhydroxyalkanoates (PHA) production using wastewater as carbon source and activated sludge as microorganisms.

Activated sludge from different full-scale wastewater treatment plants (municipal, pulp and paper industry, starch manufacturing and cheese manufacturing wastewaters) was used as a source of microorganisms to produce biodegradable plastics in shake flask experiments. Acetate, glucose and different wastewaters were used as carbon sources. Pulp and paper wastewater sludge was found to accumulate maximum concentration (43% of dry weight of suspended solids) of polyhydroxy alkanoates (PHA) with acetate as carbon source. Among the different wastewaters tested as a source of carbon, pulp and paper industry and starch industry wastewaters were found to be the best source of carbon while employing pulp and paper activated sludge for maximum accumulation of PHA. High concentration of volatile fatty acids in these wastewaters was the probable reason.

Acetates↗

Capacity of sera from patients with mammary carcinoma to promote PHA-stimulation of human lymphocytes.

Lymphocytes from patients with carcinoma have been reported to exhibit impaired immunologic reactivity and responsiveness to non-specific stimuli both in vivo and in vitro due to inhibitory serum factors. In the present investigation it is tested whether sera from patients with mammary carcinoma may inhibit the response of lymphocytes from normal donors to phytohaemagglutinin (PHA) in vitro. Neither sera from patients with newly diagnosed breast malignancy nor patients with wide spread disease differed from control patients with benign breast lesions. Serum activity did not change within 3 weeks after radical mastectomy or local irradiation but increased slightly after 6 weeks. It is suggested that the impaired PHA-responsiveness of lymphocytes in patients with mammary carcinoma is not due to blocking serum factors but to intrinsic cellular abnormality.

Adult↗

Estimation of PHA induced transformation in peripheral blood lymphocytes through measurement of their increased glycolysis. An enzymatic micromethod.

Peripheral blood lymphocytes undergoing blast transformation after contact with PHA, show a rapid increase in glycolysis. The phenomenon can be quantitated by measuring the amount of lactate released in the culture medium. This measurement has been adapted to a micromethod which allows the study of PHA induced transformation in a large number of samples in a short time. The present method which avoids the use of radioisotopes correlates in 90% of the cases with the 3H-thymidine incorporation test.

Adolescent↗

5-Ethyl-2'-deoxyuridine. Cytotoxicity and DNA incorporation demonstrated with human leukemic cells and PHA-stimulated lymphocytes in vitro.

5-Ethyl-2'-deoxyuridine (5EtdUrd) is a biologically active thymidine analogue. The cytotoxicity of 5EtdUrd was investigated with seven established human leukemia cell lines as well as with human peripheral blood PHA-stimulated lymphocytes. All types of leukemia cells were susceptible to the toxicity of 5EtdUrd as assayed with a [U-14C]-L-leucine incorporation system developed for this study. A 50% inhibition of leucine incorporation in 3-day cultures was induced by 1.3-3.8 microM 5EtdUrd with leukemic cells, but the concentration required to induce similar inhibition with PHA-stimulated lymphocytes was approximately was approximately 100-fold. The toxicity of 5EtdUrd seemed to require active DNA synthesis, since the inhibition of leucine incorporation became obvious only after the first 24 hours of culture. The DNA incorporation studies were based on a new isotopically labeled 5EtdUrd derivative, [2-14C]5EtdUrd, synthesized for this study in our laboratory. It was demonstrated for the first time that most of the radioactivity derived from [2-14C]5EtdUrd in DNA was in 5-ethyluracil. 5EtdUrd has a powerful antileukemic potency in vitro. Its effects against human leukemia in vivo remain to be tested.

Burkitt Lymphoma↗

In vitro response of subpopulations of human tonsil lymphocytes. I. Cellular collaboration in the proliferative response to PHA and Con A.

Human tonsil lymphocytes have been separated into three subpopulations of cells: purified B cells and two subsets of purified T cells (F1 and F2). B cells were obtained by rosetting with neuraminidase treated SRBC. F1 and F2 were separated by filtration on a nylon wool column using different speeds of elution. Purified B cells contained less than 5% T cells, the T cells preparations contained less than 5% B cells for F1 and 10 to 15% for F2, respectively. A significant contamination in cells not identified by any B or T marker was observed in purified B cells and in F1. Adherent cells enhanced the response of each lymphochte population to PHA and Con A. This explained the paradoxically low responsiveness of the purified T cells. Purified B cells did not respond to these mitogens in different culture conditions. However, a small B cell response was observed when they were cultured in the presence of mitomycin-treated T cells. Striking was the enhancing effect of B cells on the T cell response to PHA and Con A. This enhancing effect was observed even when B cells were treated with mitomycin or depleted in adherent cells. The comparison of the F1 and F2 response suggested that they contained distinct types of T cells.

B-Lymphocytes↗

Measurement of microorganisms with PHA production capability in activated sludge and its implication in activated sludge model no. 3.

In Activated Sludge Model No.3 (ASM3), it is hypothesized that all heterotrophic microorganisms (X(H)) can store substrate. However, in reality, both microorganisms with and without substrate storage capability (X(H/STO) and X(H/S), respectively) could exist. If the ratio of X(H/STO) in activated sludge is influenced by operational and environmental conditions, kSTO (storage rate constant of heterotrophic microorganisms which is defined in ASM3) may not be a universal parameter and can change from case to case. In this study, polyhydroxyalkanoate (PHA) is assumed as the principal storage product, and the ratio of microorganisms with PHA production capability (X(H/PHA)) in various activated sludges was estimated by the dual staining of Nile Blue A (NB) and DAPI. It was shown that the ratio of X(H/PHA) in sludge varied among different municipal and laboratory activated sludges.

Environmental Monitoring↗

Circadian rhythmicity of human plasma cortisol and PHA-induced lymphocyte transformation.

In two experiments, lymphocytes from six healthy subjects were sampled every 4 hr, counted, and cultured with PHA. Plasma cortisol in the same blood samples was measured and showed an expected circadian variation in level. A circadian rhythm in lymphocyte transformability to PHA was found to coincide directly with the cortisol level but varied inversely with lymphocyte numbers. The relationship between cortisol and lymphocyte transformability could be fortuitous or might indicate a role for cortisol in controlling lymphocyte function in vivo.

Adult↗

Change in metabolism of PHA accumulation by activated sludge modifying operating conditions.

In the present work, sludge from a stable and efficient phosphorus removal process was used to evaluate the change in the metabolism when the reactor operation was modified from anaerobic/aerobic to aerobic dynamic substrate feeding. The change in operational conditions allowed the population to modify the metabolism of phosphorus and polyhydroxyalkanoates (PHA) accumulation. Under aerobic dynamic feeding, phosphorus accumulation was almost hindered while the amount of PHA accumulation increased significantly. After ten days of operation under dynamic substrate feeding, the reactor operation turned back to anaerobic/aerobic cycles and the metabolism of phosphorus was progressively recovered.

Bacteria, Aerobic↗

Platelet inhibition of human lymphocyte PHA-induced blastoid transformation.

The reduced PHA responsiveness of human lymphocytes obtained from heparinized as compared to defibrinated blood has been shown to be due to platelet contamination in the former. Inhibition of blastoid transformation and lymphocyte death is directly related to the number of platelets added to a culture. Divalent ions partially reduce this platelet inhibitor phenomenon but do not block if completely. The "toxic" platelet components appear to be localized in the membranes and particulate matter after homogenization and hard centrifugation. Comparative studies of PHA transformation must control platelet contamination of the cultures in order to avoid severe difficulties of interpretation.

Blood Cell Count↗

Electron microscopic evidence for phagocytic properties of human peripheral mononuclear cells cultured with PHA.

The time course of the ultrastructural changes induced in human peripheral mononuclear cells, when cultured with PHA, has been studied. In addition to findings common to many mitotic cells, such as an increase in nuclear and nucleolar size, the presence of free polyribosomes, glycogen and lipid globules in the cytoplasma, and a high number of mitochondria, agglutinating properties due to PHA per se were observed in the first 12 hours. At 72 hours certain cells developed phagocytic-like properties, i.e. they were able to incorporate both material from the extracellular compartment and syngeneic cells. These results are discussed suggesting the possible presence of macrophages in culture or the ability of activated T cells to express it.

Cells, Cultured↗