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[Production of antithyroid hormone antibodies. 2. Genetic control of the production of anti-human thyroglobulin and antithyroid hormone antibodies in mice immunized with human thyroglobulin].

Recently anti-thyroid hormone antibodies have been found in many cases of thyroidal and non-thyroidal disorders. However, the exact mechanism(s) of production of anti-thyroid hormone antibodies in these patients is so far obscure. Thyroxine (T4) and triiodothyronine (T3) are haptens and are not immunogenic in free form. In this respect, human thyroglobulin (HTg) has long been suggested as an antigen of the anti-thyroid hormone antibodies observed in them because it carries thyroid hormones on its surface. In our previous communication, we reported the production of anti-HTg antibodies and anti-thyroid hormone antibodies in two rabbits and various strains of mice immunized with HTg. In order to elucidate the gene(s) which controls the production of anti-HTg and anti-thyroid hormone antibodies, various strains of mice which have different H-2 and Igh allotypes were immunized with HTg. The titers of anti-HTg and anti-thyroid hormone antibodies were measured, and the locus (loci) which controls the immune response against them was determined. Our present investigation has revealed that the Ir-gene(s) which controls the production of anti-HTg and anti-T4 antibodies is located in the I-A subregion. Concerning the production of anti-T4 antibodies in mice, the presence of Ir-gene(s) outside of H-2 is also suggested. The significance of the genetic mechanisms controlling the immune response against thyroid hormones in various thyroidal disorders is discussed.

Animals↗

Lifetime lamb and wool production of targhee or Finn-Dorset-Targhee ewes managed as farm or range flock: II. Cumulative lamb and wool production.

Cumulative lifetime (five lamb crops) lamb production and wool production of 681 ewes were evaluated in this study. Lamb production and wool production from each ewe at the end of age 2, 3, 4, 5, and 6 yr were added to the previous year's production and analyzed within age of ewe. If a ewe failed to lamb, died, or was culled, it received a zero for that year and subsequent years. Main effects in the model included ewe breed and management system. Per ewe entering the study, Finn-Dorset-Targhee (FDT) ewes had a higher (P < .01) number of lambs born (7.42 vs 5.70), number of lambs weaned (5.39 vs 4.48), and total lamb weight weaned (131.7 vs 110.5 kg) than did Targhee ewes. Targhee ewes produced more (P < .01) wool (16.1 vs 13.6 kg) than FDT ewes. Range flock ewes had a higher number of lambs born (6.74 vs 6.38; P < .05), number of lambs weaned (5.39 vs 4.48; P < .01), and total lamb weight weaned (135.8 vs 106.5 kg; P < .01) than did farm flock ewes. Farm flock ewes produced more (P < .01) wool (15.2 vs 14.5 kg). A second analysis based on only those ewes retained at the start of each subsequent breeding season showed FDT ewes had a higher (P < .01) number of lambs born (9.96 vs 8.11), number of lambs weaned (7.61 vs 6.57), and total lamb weight weaned (183.8 vs 165.7 kg) after five lamb crops. Targhee ewes produced more (P < .01) wool (22.5 vs 17.6 kg). Farm flock ewes had a higher (P < .10) number of lambs born (9.18 vs 8.89) and produced more (P < .01) wool (21.1 vs 19.0 kg) than range flock ewes. Range flock ewes weaned more (P < .05) lambs (7.27 vs 6.92) and had more (P < .01) total lamb weight weaned (184.3 vs 165.2 kg) than farm flock ewes.

Aging↗

Evaluation of carcass, live, and real-time ultrasound measures in feedlot cattle: II. Effects of different age end points on the accuracy of predicting the percentage of retail product, retail product weight, and hot carcass weight.

Data from 970 feedlot steers and bulls were used to evaluate effects of different age end points on the accuracy of prediction models for percentage of retail product, retail product weight, and hot carcass weight. Cattle were ultrasonically scanned three to five times for fat thickness, longissimus muscle area, and percentage of intramuscular fat. Live animal measures of body weight and hip height were also taken during some of the scan sessions. Before development of prediction equations, live and ultrasound data were adjusted to four age end points using individual animal regressions. Age end points represented mean age at slaughter (448 d), mean age at the second-to-last scan before slaughter (414 d), mean age at the third-to-last scan before slaughter (382 d), and an age end point of 365 d. Ultrasound and live animal measures accounted for a large proportion of the variation in the dependent variables regardless of the age end point considered. For all three traits, final models based on independent variables adjusted to earlier ages of 365 and 382 d showed better or at least similar model R2 and root mean square errors than those based on independent variables adjusted to a mean slaughter age of 448 d. Validation of the models using independent data from 282 steers resulted in a mean across-age rank correlation coefficient of .78, .88, and .83 between actual and predicted values of the percentage of retail product, hot carcass weight, and retail product weight, respectively. Mean across-age rank correlation of breeding values for the corresponding traits were .92, .89, and .82. The results of this study suggest that live and ultrasound traits measured as early as 365 d could be used to predict end product traits as accurately as similar measures made before slaughter at age 448 d.

Aging↗

Nitrogen balance, microbial protein production, and milk production in dairy cows fed fodder beets and potatoes, or barley.

Fourteen multiparous midlactation dairy cows were used in a change-over experiment with 3 periods and 3 diets to evaluate the effects of fodder beets and potatoes on N metabolism, microbial protein production, and milk production. A basal ration of alfalfa/grass silage offered ad libitum, 1 kg of grass hay and 1 kg of heat-treated rapeseed cake was supplemented with 5 kg DM of either rolled barley/raw potatoes 80:20 (BAP), fodder beets/raw potatoes 80:20 (BEP) or rolled barley (BA). Urine and feces were collected quantitatively from 8 cows and ruminal samplings, and evacuations were performed on 4 cannulated cows. Intake and production did not differ between BAP and BA, but the BEP diet lowered intake of both silage and total ration by 0.9 kg DM. Daily yield of energy-corrected milk (ECM) was decreased by 1.7 and 2.3 kg compared with BAP and BA, respectively. Milk urea concentration was 1 mM lower with the BEP diet. The proportion of feed N recovered in milk was 20 to 21% for all diets. With the BEP diet, urinary N amount and proportion were reduced correspondingly to the lower total N intake. Fecal N amount remained unchanged, and hence nitrogen apparent digestibility decreased by 5 percentage units with the BEP diet. Microbial protein production, assessed by allantoin excretion, tended to be highest with the BAP diet. Acetate proportion of VFA was lowered by the BEP diet, while proportions of propionate and butyrate both tended to increase. Different fermentation patterns, probably related to differences in rumen microbiota, could explain why changes in energetic efficiency and milk composition reported in the literature did not occur in the actual experiment when roots replaced barley. Compared with barley, roots appeared to have a greater negative effect on silage intake in conjunction with a prewilted silage with high intake potential allowed ad libitum and this decreased milk production by a magnitude corresponding to the lower intake of ME.

Acetates↗

Dry period length to maximize production across adjacent lactations and lifetime production.

The primary objectives of this research were to determine the dry period lengths that maximize production across adjacent lactations and also dry period length that maximizes lifetime yield. Effect of days dry (DD) after lactations 1 through 3 were determined separately for both adjacent lactation sums and lifetime yield. Field data, collected through the Dairy Herd Improvement Association, on US Holstein cows first calving between January 1997 and January 2004 were utilized. Lifetime records were restricted to cows first calving no later than December 1999. Actual lactation yields, in contrast to standardized records, were used to calculate lactation sums and lifetime records. Herds were required to be on test for the entire period to avoid partial records. Another important edit was that actual calving dates had to agree with expected calving dates, based on reported days open, within 10 d. This edit ensured that the producer knew, at least at one point in time, when the cow was going to calve. Cow effects were corrected for in both the adjacent lactation and lifetime analyses. The minimum DD to maximize production across adjacent lactations depended on parity. For yield across first and second lactations, there was little loss in production with a minimum of 40 to 45 DD. Longer dry periods (55 to 65 DD) were required after second and third lactations however, presumably due to the lower persistency of second and later lactation cows. Lifetime production was maximized by 40 to 50 DD after first lactation and 30 to 40 DD after second and later lactations. Fewer DD were required to maximize lifetime yield than adjacent lactation yield because cows with fewer DD also had more lifetime days in milk. Although dry periods of 30 to 40 d can be used after second and later lactations without cost in lifetime yield, their benefit to lifetime production is minimal. Dry periods shorter than 30 d or longer than 70 d are costly to lifetime yield and should be avoided. Dry periods longer than 80 d are even more costly than dry periods less than 30 d.

Animals↗

Genotype by environment interaction for milk production traits between organic and conventional dairy cattle production in The Netherlands.

Estimates of genetic parameters for organic dairy farming have not been published previously, and neither is information available on the magnitude of genotype by environment interaction (GxE) between organic and conventional farming. However, organic farming is growing worldwide and basic information about genetic parameters is needed for future breeding strategies for organic dairy farming. The goal of this study was to estimate heritabilities of milk production traits under organic farming conditions and to estimate the magnitude of GxE between organic and conventional dairy farming. For this purpose, production records of first-parity Holstein heifers were used. Heritabilities of milk, fat and protein yield, and somatic cell score (SCS) were higher under organic farming conditions. For percentages of fat and protein, heritabilities of organic and conventional production were very similar. Genetic correlations between preorganic and organic, and organic and conventional milk production were 0.79 and 0.80, respectively. For fat yield, these correlations were 0.86 and 0.88, and for protein yield, these were 0.78 and 0.71, respectively. Our findings indicate that moderate GxE was present for yield traits. For percentage of fat and protein and SCS, genetic correlations between organic and conventional and preorganic production were close to unity, indicating that there was no GxE for these traits.

Analysis of Variance↗

Prediction of transmitting abilities for productive life and lifetime profitability from production, somatic cell count, and type traits in milk markets for fluid milk and cheese.

Two net income functions were constructed to reflect differences in value of carrier, protein, and somatic cell score (SCS) between milk markets for fluid milk and those for cheese. Individual costs were for production of carrier (water, lactose, and minerals), fat, and protein. Totals for net income from a lactation were adjusted for the opportunity cost of postponed replacement using all herdmates on test. Heritabilities and correlations were estimated with a multiple-trait sire model using 52,688 registered and grade (24%) cows that were classified daughters of 844 bulls included in the Sire Evaluation for Type program of the Holstein Association of America. Although the genetic correlation between the net income traits was high (0.92), the resulting economic weights were quite different. Indexes to select for net income for a fluid milk market weighted milk production much more than it weighted fat or SCS and selected against protein yield. Indexes for a cheese market gave more weight to milk components, SCS, and traits related to productive life. The removal of some type traits had little effect on the evaluation of either net income trait. In contrast, weights for prediction of productive life from SCS and the production and type traits became more stable when strength, fore udder, and rear udder heights were removed. Removal of some of the type traits that were used for prediction reduced multicollinearity and the variance of weights without sacrificing accuracy.

Animals↗

Excretory-secretory product of Paragonimus westermani newly excysted metacercariae inhibits superoxide production of granulocytes stimulated with IgG.

It is well known that the cysteine proteases in excretory-secretory product (ESP) of Paragonimus westermani newly excysted metacercariae (PwNEM) are capable of degrading IgG in vitro. Recent evidence suggests that the IgG-coated surface, such as found on parasites, is one of the most effective physiologic stimuli for granulocyte activation. Therefore, this study was designed to investigate the effect of excretory-secretory product (ESP) of PwNEM on superoxide production of granulocytes stimulated with IgG. The 96-well plates were coated with human IgG (0, 10, 30, 100 micrograms/ml) in the absence or presence of ESP. When granulocytes were incubated in the wells coated with human IgG in the presence of ESP, the level of superoxide production of granulocytes was reduced to about 90% when compared to the cells incubated in the wells coated with IgG alone. This inhibitory effect of the ESP on IgG-induced superoxide production of granulocytes was concentration-dependent. These results suggest that ESP secreted by PwNEM may be important in the control of effector functions of granulocytes stimulated with IgG in human paragonimiasis.

Animals↗

Research note: effect of tu-chung leaf (Eucommia ulmoides) on egg production performance, egg quality, and fat metabolism in laying hens at a late production stage.

The effects of tu-chung leaf (Eucommia ulmoides) supplementation on egg production performance, egg quality, and fat metabolism were investigated in laying hens at a late production stage. White Leghorn laying hens at 20 mo of age were provided ad libitum access to a practical diet with or without tu-chung leaf supplement for 3 mo. During the experimental period, egg production rate, egg weight, and feed intake were recorded every day. Egg samples from the last 3 days were collected to measure Haugh units and cholesterol concentration in the egg yolk. Plasma cholesterol concentration and abdominal fat weight were also determined. The results showed that no significant improvement in egg production was observed with tu-chung leaf addition. No significant effect of tu-chung was observed on Haugh units, plasma cholesterol, or egg yolk cholesterol, whereas abdominal fat weight was greater in hens fed the tu-chung diet than in those given the unsupplemented control diet. It was concluded that the beneficial effects of tu-chung leaf supplementation on egg production performance and egg quality were ambiguous and of little practical significance.

Animals↗

Autoregulation of human monocyte-derived dendritic cell maturation and IL-12 production by cyclooxygenase-2-mediated prostanoid production.

PG added to cell culture profoundly affect the in vitro maturation and function of monocyte-derived dendritic cells (MDC). Because unstimulated monocytes express cyclooxygenase (COX)-1, and COX-2 when activated, we examined whether MDC express these enzymes and produce prostanoids that autoregulate maturation and IL-12 production. Immature MDC (I-MDC) and mature MDC express COX-1, but, unlike monocytes, both MDC populations constitutively express COX-2. However, COX-2 regulation in both MDC populations differs from monocytes, as IL-4 does not suppress enzyme expression. COX-2 is functional in MDC as a specific inhibitor, NS-398, significantly reduces PGE(2) production. I-MDC undergoing maturation with soluble CD40 ligand (sCD40L) increase PGE(2) synthesis, but prostanoid synthesis is switched to COX-1. However, with IFN-gamma present, sCD40L-stimulated PG metabolism is redirected to COX-2, and PGE(2) synthesis increases severalfold. Endogenous PG production by MDC does not regulate CD40, CD80, CD86, or HLA DR expression; however, it does promote MDC maturation, as NS-398 significantly reduces CD83 expression in I-MDC matured with sCD40L/IFN-gamma. PG produced through COX-2 also autoregulate IL-12, but the effects are dependent on the MDC maturation state. Blocking COX-2 reduces I-MDC secretion of IL-12p40, whereas it increases IL-12p40 and p70 production by maturing MDC. COX-2-mediated PG production impacts MDC function as maturing these cells in the presence of NS-398 yields MDC that stimulate significantly more IFN-gamma in an allogeneic mixed lymphocyte response than MDC matured without this inhibitor. These studies demonstrate that MDC express both COX isoforms constitutively and produce prostanoids, which autoregulate their maturation and function.

Adjuvants, Immunologic↗

Gangliosides GD1b, GT1b, and GQ1b enhance IL-2 and IFN-gamma production and suppress IL-4 and IL-5 production in phytohemagglutinin-stimulated human T cells.

Gangliosides are sialic acid-containing glycolipids. We studied the in vitro effects of gangliosides on Th1 and Th2 cytokine production in PHA-stimulated human T cells. Gangliosides GD1b, GT1b, and GQ1b (each 100 nM) enhanced PHA-induced IL-2 secretion of peripheral blood T cells approximately 4-fold and enhanced that of IFN-gamma 3- to 4-fold compared with controls. These gangliosides decreased PHA-induced IL-4 secretion by 50-53% and that of IL-5 by 53-63% compared with controls, respectively. The other gangliosides did not alter the secretion of Th1 or Th2 cytokines. RT-PCR showed that GD1b, GT1b, and GQ1b enhanced PHA-induced IL-2 and IFN-gamma transcription and suppressed that of IL-4 and IL-5. Transient transfection assays of Jurkat T cells showed that GD1b, GT1b, and GQ1b enhanced PHA-induced IL-2 and IFN-gamma promoter activities but suppressed those of IL-4 and IL-5. The cAMP analogue dibutyryl cAMP and the cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine each reversed GD1b-, GT1b-, and GQ1b-induced stimulation of IL-2 and IFN-gamma production and inhibition of IL-4 and IL-5 production at the levels of proteins, transcription, and promoter activities. GD1b, GT1b, and GQ1b suppressed PHA-induced increase in cAMP level in T cells. These gangliosides suppressed PHA-stimulated adenylate cyclase activity in T cells. These results suggest that GD1b, GT1b, and GQ1b may enhance Th1 cytokine production while suppressing Th2 production by inhibiting adenylate cyclase activity.

Adenylyl Cyclase Inhibitors↗

T cells associated with tumor regression recognize frameshifted products of the CDKN2A tumor suppressor gene locus and a mutated HLA class I gene product.

The dramatic tumor regression observed following adoptive T cell transfer in some patients has led to attempts to identify novel Ags to understand the nature of these responses. Nearly complete regression of multiple metastatic melanoma lesions was observed in patient 1913 following adoptive transfer of autologous tumor-infiltrating lymphocytes. The autologous 1913 melanoma cell line expressed a mutated HLA-A11 class I gene product that was recognized by the bulk tumor-infiltrating lymphocytes as well as a dominant T cell clone derived from this line. A second dominant T cell clone, T1D1, did not recognize the mutated HLA-A11 product, but recognized an allogeneic melanoma cell line that shared expression of HLA-A11 with the parental tumor cell line. Screening of an autologous melanoma cDNA library with clone T1D1 T cells in a cell line expressing the mutated HLA-A11 gene product resulted in the isolation of a p14ARF transcript containing a 2-bp deletion in exon 2. The T cell epitope recognized by T1D1, which was encoded within the frameshifted region of the deleted p14ARF transcript, was also generated from frameshifted p14ARF or p16INK4a transcripts that were isolated from two additional melanoma cell lines. The results of monitoring studies indicated that T cell clones reactive with the mutated HLA-A11 gene product and the mutated p14ARF product were highly represented in the peripheral blood of patient 1913 1 wk following adoptive transfer, indicating that they may have played a role in the nearly complete tumor regression that was observed following this treatment.

Adult↗

Transgenic expression of insulin receptor substrate 2 in murine B cells alters the cell density-dependence of IgE production in vitro and enhances IgE production in vivo.

Previous studies have shown that insulin receptor substrate (IRS)1 and IRS2 mediate proliferative and antiapoptotic signaling through the IL-4R in 32D cells; however their role in regulating normal B cell responses is not clear. To investigate the role of IRS2 in normal B cell function, we developed IRS2 transgenic (Tg) mice on the C57BL/6 background. Western blot analysis revealed a 2-fold elevation in IRS2 protein levels in Tg(+) mice compared with littermate controls and a 3-fold increase in basal tyrosine phosphorylated IRS2 in the absence of IL-4 stimulation. IL-4-induced tyrosine phosphorylation of IRS2 was elevated in Tg(+) B cells, whereas IL-4-induced phosphorylation of STAT6 was similar between Tg(+) and Tg(-) B cells. Tg expression of IRS2 had little effect on IL-4-mediated proliferation and no effect on protection from apoptosis. However, production of IgE and IgG1 by Tg(+) B cells using standard in vitro conditions was diminished 50-60%. Because Ig production in vitro is known to be highly cell concentration-dependent, we performed experiments at different cell concentrations. Interestingly, at very low B cell concentrations (1000-5000 B cells/well), IgE and IgG1 production by Tg(+) B cells was greater than that of controls, whereas at higher cell concentrations (10,000-20,000 cells/well) Ig production by Tg(+) B cells was less than controls. Furthermore, in vivo immunization with OVA-alum or goat anti-IgD resulted in elevated serum IgE levels in the Tg(+) mice. These results indicate that overexpression of IRS2 alters the B cell intrinsic density-dependence of IgE and IgG1 production in vitro and enhances IgE responses in vivo.

Adjuvants, Immunologic↗

Monoclonal antibody production in murine ascites. II. Production characteristics.

OBJECTIVE: To characterize monoclonal antibody production parameters of five hybridoma cell lines in murine ascites for correlation with clinicopathologic changes in mice. METHODS: Five hybridoma cell lines were grown in groups of 20 mice. Fourteen days prior to inoculation with 10(6) hybridoma cells, mice were primed with 0.5 ml of pristane given intraperitoneally. Ascites fluid was collected a maximum of three times by abdominal paracentesis; volume was measured and antibody concentration was determined by ELISA for each sample. RESULTS: Trends differed among cell lines when comparing ascites volumes and antibody concentrations over time from the first to the third tap. Antibody production was greatest at tap 1 for Groups 2B11 and 2C6D9; tap 2 for Group 3C9; and tap 3 for Groups RMK and 3D6. Total antibody production ranged from 422.90 to 996.64 mg; total ascites fluid volume ranged from 74.2 to 115.7 ml; and mean antibody concentration for taps 1, 2, and 3 ranged from 2.50 to 15.03 mg/ml among cell lines. CONCLUSION: Production characteristics were significantly different among hybridoma cell lines. Determination of production characteristics of hybridomas and correlation with clinicopathologic changes in mice may be valuable in making recommendations for managing mice with ascites.

Abdominal Neoplasms↗

Effects of spatial variation of cells and nutrient and product concentrations coupled with product inhibition on cell growth in a polymer scaffold.

The effects of spatial variation of cells and nutrient and product concentration, in combination with product inhibition in cell growth kinetics on chondrocyte generation in a polymer scaffold, are analyzed. Experimental studies reported previously have demonstrated spatial dependence in the cultivation of chondrocytes. In the present study, the cell-polymer system is assumed to consist of two distinct phases. The cells, fluid, polymer matrix, and extracellular matrix comprise one phase, and the other phase consists of a fluid and polymer matrix. The only two species in the fluid considered to affect cell growth are the nutrient and product. The multiphase transport process of these two species in the cell-polymer system is described by the species continuity equations and corresponding boundary conditions for each individual phase. A volume-averaging approach is utilized for this system to derive averaged species continuity equations for the nutrient and product concentrations. The volume-averaging approach allows for a single species in a two-phase system to be represented by a single averaged continuity equation. Competitive product inhibition, saturation kinetics of substrate, and cell population control are assumed to affect the cell growth kinetics. A modified Contois growth kinetic model is used to represent the three factors that affect cell growth. A parameter analysis is performed and the results are compared qualitatively with experimental data found in the literature.

Animals↗

Inhibition of activator protein-1 binding activity and phosphatidylinositol 3-kinase pathway by nobiletin, a polymethoxy flavonoid, results in augmentation of tissue inhibitor of metalloproteinases-1 production and suppression of production of matrix metalloproteinases-1 and -9 in human fibrosarcoma HT-1080 cells.

Medicinal plants contain pharmacological substances including flavonoids, and their extracts have been therapeutically administered for cancer therapy in vitro and in vivo. We investigated the efficacy of a polymethoxy flavonoid, nobiletin, from Citrus depressa on tumor invasion in vitro. Nobiletin inhibited the tumor-invasive activity of human fibrosarcoma HT-1080 cells in the Matrigel model, whereas a similar inhibition was observed upon exogenously adding tissue inhibitors of metalloproteinases (TIMPs)-1 and -2. The gene expression and production of pro-matrix metalloproteinase 9 (proMMP-9)/progelatinase B and proMMP-1/interstitial procollagenase were specifically suppressed by nobiletin in 12-O-tetradecanoylphorbol 13-acetate-stimulated HT-1080 cells. In contrast, the gene expression and production of TIMP-1, but not TIMP-2, were enhanced by nobiletin. We also demonstrated that nobiletin suppressed the 12-O-tetradecanoylphorbol 13-acetate-induced binding activity of activator protein-1. Furthermore, a phosphatidylinositol 3-kinase inhibitor, LY-294002, was found to mimic the different actions of nobiletin on the production of proMMP-9 and TIMP-1. These results suggest that nobiletin inhibits tumor cell invasive activity not only by suppressing the expression of MMPs but also augmenting TIMP-1 production in tumor cells, and that the nobiletin-mediated inhibition of activator protein-1 binding activity is at least partly involved in the suppression of MMP expression. Furthermore, we suggest a possible mechanism by which nobiletin may interfere in the phosphatidylinositol 3-kinase pathway, which divergently regulates the production of MMP and TIMP-1.

Anticarcinogenic Agents↗

[Effect of shale kerogen oxidation products on biodegradation of petroleum and petroleum products in soil and water].

Effect of oxidation products of shale kerogen (high-molecular-weight acids with 6-22 carbon atoms) on biodegradation of oil and oil products in soil and water was studied. High-molecular-weight acids (HMWA) not only affected the layer of oil and/or oil products and dispersed it into small particles, but also stimulated growth of Rhodococcus erythropolis VKM AS-1339D, degraders of oil and oil products. Addition of 0.001-0.003% HMWA to a medium to be purified from oil products increased the extent of bacterial biodegradation by a factor of 1.1-5.0.

Acids↗

[Correlation of tuberculin skin reaction with lymphocyte proliferation, interferon-gamma production and tumor necrosis factor-alpha production after in vitro stimulation with PPD and killed Mycobacterium tuberculosis using peripheral blood of healthy donors].

The quantitative relationships among the in vitro lymphocyte proliferation in peripheral blood in 19 healthy donors to purified protein derivative (PPD) and the killed Mycobacterium tuberculosis, interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) production in these culture supernatants, and the in vivo skin reaction to PPD which were simultaneously measured were studied. Statistical analysis was performed with t-test and multiple regression analysis: The results obtained were as follows; 1) The magnitude of the in vitro lymphocyte proliferation by PPD and the killed M. tuberculosis failed to correlate with the erythema and the induration of the in vivo skin reaction to PPD. 2) The erythema of skin test correlates with TNF alpha production in the culture supernatants that the lymphocytes in peripheral blood were cocultured with these antigens for 7 days. (R = 0.566062, 0.01 less than p less than 0.02) 3) There is a correlation between the erythema and the induration of skin test. (R = 0.526662, 0.02 less than p less than 0.05). 4) Though the magnitude of the lymphocyte proliferation to PPD correlates IFN gamma production in the culture supernatants (R = 0.525915, 0.02 less than p less than 0.05), these response to the killed M. tuberculosis correlates both IFN gamma production (R = 0.55049, 0.01 less than p less than 0.02) and TNF alpha production (R = 0.51283, 0.02 less than p less than 0.05) in the culture supernatants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗