Search PubMed⌕ Search

Biomedical subjects

S Hayward

Publications and source records attributed to S Hayward.

At least 73 records · Page 4Linked to original sources
PubMed1991

Effect of chronic exposure of PCB (Aroclor 1254) on specific and nonspecific immune parameters in the rhesus (Macaca mulatta) monkey.

The immunomodulatory effects of low-level, chronic polychlorinated biphenyl PCB; (Aroclor 1254) exposure were investigated in female rhesus (Macaca mulatta) monkeys. Five groups of monkeys (initially 16 monkeys/group) were orally administered PCB at levels of 0, 5, 20, 40 or 80 micrograms/kg body wt/day. Tests for immunomodulation were initiated after 55 months of exposure to PCBs. Statistically significant observed immune changes included a dose-related decrease in the anamnestic (IgM and IgG) response to sheep red blood cells. Conversely, the antibody response to pneumococcus antigen did not differ significantly across the test groups. A statistically significant dose-related decrease in lymphoproliferation was noted with increasing doses of PCBs when phytohemagglutinin and Concanavalin A, but not when pokeweed mitogen, were used as mitogens. A trend toward reduced peak chemiluminescence (mV/min) was observed in zymosan-activated peripheral blood monocytes. The time to peak chemiluminescence of phorbol myristate acetate activation was statistically increased in a dose-response fashion. Flow cytometric analysis results of peripheral blood lymphocytes using the markers CD4, CD8, and CD20 were similar across the test groups. The mean percentage levels for the CD2 marker in the treated groups were statistically lower than the mean in the control, while absolute numbers for CD2 were similar across the test groups. Serum hydrocortisone levels did not differ among the test groups. Taken together these results indicate that low-level, chronic PCB exposure alters a number of rhesus monkey immune system components and that these effects may be due to altered T-cell and/or macrophage function. These data may be of use in extrapolating potential human health effects following chronic PCB exposure.

Animals↗
PubMed1991

Quantitation of serum immunoglobulins G, M, and A in the rhesus monkey (M. mulatta) using human monospecific antisera in the enzyme-linked immunosorbent assay: developmental aspects.

Using human monospecific antisera, several parameters have been optimized for the micro-ELISA "sandwich" technique used in the quantitative measurement of total serum IgG, IgM and IgA levels in rhesus monkeys. Representation of the optical density as a four-parameter logistic function provided excellent fits of the data over a wide choice of dilutions of human antisera used for coating the ELISA plates and for the peroxidase-conjugated antisera used in the system. The micro-ELISA "sandwich" technique was shown to be specific, reliable, sensitive, and economical for use in the routine measurement of total serum IgG, IgM and IgA levels in the rhesus monkey.

Animals↗
PubMed1990

Inhibin and estradiol responses to ovarian hyperstimulation: effects of age and predictive value for in vitro fertilization outcome.

We have compared the time courses of serum inhibin and estradiol responses to ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer as well as their predictive value for outcome of intermediate variables and pregnancy in in vitro fertilization and embryo transfer. Blood samples (n = 749) were collected for up to 6 days before hCG administration in 100 consecutive treatment cycles, of which 44 resulted in pregnancy, as defined by elevated luteal phase serum hCG beta levels. Inhibin and estradiol levels increased markedly in parallel during hyperstimulation and were highly correlated (r = 0.89; P less than 0.001). Inhibin responses were significantly lower in women 35 yr of age or older (P less than 0.001), although estradiol responses were not influenced by age. Gravidity and tubal disease also had marginal effects on the time course of inhibin responses, but not on overall mean inhibin levels or estradiol responses. The time course of hormonal responses to hyperstimulation was not influenced by any other demographic or etiological factors. Peak values of both hormones correlated with the total number of follicles (inhibin, r = 0.70; estradiol, r = 0.65; P less than 0.001) and oocytes retrieved per cycle (inhibin, r = 0.49; estradiol, r = 0.39; P less than 0.001). The time course and peak values of inhibin and estradiol responses to hyperstimulation did not differ significantly between conception or nonconception cycles whether judged by biochemical (luteal hCG beta) or clinical (viable ongoing pregnancy) criteria. Luteal phase serum inhibin, estradiol, progesterone, and hCG levels were significantly higher in conception than in nonconception cycles (P less than 0.001). These data suggest that the rises in serum inhibin and estradiol levels during hyperstimulation have similar predictive properties for IVF-ET outcomes and could, therefore, be used interchangeably to monitor hyperstimulation regimens. The age-related reduction in inhibin, but not estradiol, responses suggests that these two hormones reflect different granulosa cell functions and that serum inhibin responses to maximal ovarian stimulation may be a sensitive and early index of declining ovarian function with advancing age.

Adult↗
PubMed1990

Analysis of the ratio of biological to immunological LH secreted during the oestrogen-induced LH surge in the ewe.

Plasma concentrations of in-vitro biological and immunological LH were measured throughout the LH surge in cyclic ewes and in ovariectomized ewes treated i.m. with oestradiol benzoate. Both activities increased in parallel during the LH surge in both groups, although the ratio of biological to immunological activities (B/I ratio) was highest at the peak of the LH surge. The two activities were highly correlated (r = 0.86-0.92), with similar slopes from their regression analysis for the cyclic and ovariectomized groups (1.15 and 1.16 respectively). However, the intercepts of the regression lines did not pass through the origin, but intersected the y (radioimmunoassay) axis, suggesting that these serum samples contained immunoactivity not associated with LH bioactivity. In conclusion, an increase in the LH B/I ratio was observed during the LH surge in oestrogen-treated ovariectomized ewes and in cyclic ewes. This increase was not attributable to a change in the relationship between these two LH activities during the LH surge, but rather to the detection of bioinactive immunoactive material in plasma of unknown composition.

Animals↗
PubMed1990

The role of endoscopic retrograde pancreatography (ERP) in blunt abdominal trauma.

The diagnosis of pancreatic injury is often difficult because it lies retroperitoneally in a protected area. Delayed diagnosis and treatment of blunt pancreatic trauma can result in significant morbidity and mortality. Endoscopic Retrograde Pancreatography (ERP) is infrequently used in the diagnosis of pancreatic injury. We reviewed our experience with the use of ERP in patients with blunt pancreatic injury. Two stable patients with traumatic pancreatitis underwent ERP shortly after injury. CT scans revealed a transverse fracture of the distal pancrease in one and fluid accumulation in the other around the pancreas extending to the right kidney and left hepatic lobe. The absence of ductal disruption on ERP allowed nonoperative management of the pancreatitis. Resolution was documented by the absence of symptoms on regular oral intake, normal serum amylase levels, and normal follow-up CT scans. A third patient with persistent fistulae three months postinjury underwent preoperative ERP revealing ductal obstruction. This facilitated the planning of a distal pancreatectomy and subsequently the fistulae healed. A fourth patient underwent an exploratory laparotomy on the basis of clinical and CT scan findings that could have been circumvented with preoperative ERP. ERP in selected patients allows nonoperative treatment in the absence of ductal injury or earlier operative treatment of ductal injury. It also aids the treatment of late complications by delineating ductal anatomy.

Adult↗
PubMed1989

Immunotoxicity studies of PCB (Aroclor 1254) in the adult rhesus (Macaca mulatta) monkey--preliminary report.

The effects of PCB (Aroclor 1254) on the immune system of adult female rhesus monkeys were investigated in a chronic study wherein five groups of monkeys (16/group) were administered (orally) PCB at levels of 0.0, 5.0, 20.0, 40.0 or 80.0 micrograms/kg body wt daily. Tests for immunotoxicity were initiated at 23 months of exposure to PCB, at which time the monkeys had achieved an apparent pharmacokinetic steady state based on the PCB concentration in fat and/or blood. A statistically significant (P less than 0.05) dose response reduction in antibody levels (IgG and IgM) to sheep red blood cells (SRBC) was observed following i.v. administration of three immunizing doses of SRBC at weekly intervals. A statistically significant decrease in the percent TH and an increase in the percent and absolute TS lymphocyte levels was found in the 80 micrograms/kg body wt group compared to the control. The TH/TS ratio was also significantly lower in the 80 micrograms/kg body wt group compared to the control. Other parameters investigated including percent of B-lymphocytes and total T-lymphocytes, total serum immunoglobulin levels (IgG, IgM and IgA), other serum proteins, glucocorticosteroid levels and lymphocyte transformation results following stimulation with the mitogens PHA-P and Con A were not affected significantly by PCB treatment. Additional immunologic parameters are currently being investigated to further elucidate the mechanism by which PCB induces immunotoxicity.

Animals↗
PubMed1989

Divergent effects of interferons on the growth of human benign prostatic hyperplasia cells in primary culture.

Epithelial cells from human benign prostatic hyperplasia tissues were grown in primary cultures for up to 21 days and the effects of interferons on the growth of the cells were investigated. Interferon-alpha (Wellferon) showed growth inhibition both in the presence and in the absence of 3 x 10(-10)M testosterone propionate (TP) whereas interferon-gamma stimulated growth in a dose dependent manner under similar conditions. Interferon-beta had little effect on growth at the dose levels used in the study. The growth inhibition by interferon-alpha can be induced after stimulation of growth is achieved either with TP or with interferon-gamma. Implications of these findings for clinical use of these lymphokines is discussed.

Cell Division↗
PubMed1989

Enzyme studies in human transitional cell carcinoma of the urinary bladder.

The activities of six enzymes of carbohydrate metabolism were estimated in tissue samples from 99 patients with transitional cell carcinoma of the urinary bladder undergoing transurethral resection. The results were analysed according to the stage of the disease and the malignancy grade of the carcinoma. There were statistically significant differences in the activities of three enzymes between various stages and grades. The activities of phosphofructokinase (PFK), alpha-glycerolphosphate dehydrogenase (alpha-GPDH), and phosphohexose isomerase (PHI) showed significant decreases with increased stage and grade. Of the total of 64 patients with superficial disease at presentation, five developed progressive disease during the course of this investigation. The activities of the three enzymes in these patients were compared to the median values for the group of patients with superficial disease. The activity of PFK was observed to be below the median value in all the five patients whereas the activities of alpha-GPDH and PHI showed similar patterns in four of the five patients. These preliminary data indicate that, in association with established clinical parameters, the measurement of the activity of these three enzymes may prove useful in selecting patients with an increased potential for developing progressive disease.

Adult↗
PubMed1988

Enumeration of lymphocyte subsets in peripheral blood of rhesus monkeys prior to and following monocyte removal using a modified indirect avidin-biotin immunoperoxidase technique.

A modified avidin-biotin immunoperoxidase technique has been used to enumerate B lymphocytes, T inducer/helper (TH) and T cytotoxic/suppressor (TS) cells in the peripheral blood of normal and immunosuppressed rhesus monkeys (Macaca mulatta) prior to and following adherent-cell depletion. The levels of each of the B, TH and TS cells detected in the normal monkeys using monoclonal antibodies which recognized specific surface antigens on human lymphocytes were comparable to the levels reported in human peripheral blood using direct immunofluorescence, immunoperoxidase or flow cytometry techniques. Adherent cell depletion did not result in a significant loss of any of the lymphocyte subpopulations examined. The technique is reproducible and sensitive in detecting differences between normal and immunosuppressed animals, and would prove to be useful in studies pertaining to chemical and drug immunomodulation.

Animals↗
PubMed1988

Radioimmunoassay of rat serum inhibin: changes after PMSG stimulation and gonadectomy.

A heterologous inhibin radioimmunoassay (RIA) method has been developed which is highly specific and of sufficient sensitivity to detect inhibin in female and male rat serum. Purified bovine 31 kDa inhibin was used in the generation of the antiserum and following iodination as tracer in the assay. Parallel logit-log dose-response lines were observed between a rat ovarian extract used as standard and serial dilutions of female and male serum and testicular interstitial fluid. The within-assay variation based on index of precision was 0.049 (n = 5) and the between-assay variation (n = 4) was 9.8%. The specificity of the assay was assessed from: (a) the failure of a number of structurally related proteins (activin-A, transforming growth factor-beta (TGF-beta), Müllerian inhibitory substance) as well as inhibin subunits to crossreact (less than 0.5%) in the assay relative to bovine 31 kDa inhibin; (b) nondetectable levels of immunoactivity in the serum of gonadectomised rats; and (c) a close correlation (r = 0.96) between serum levels of in vitro biological and immunological activities from rats following pregnant mare serum gonadotropin (PMSG) stimulation. Similar initial t 1/2 values (14-15 min) of serum inhibin following gonadectomy were obtained in both sexes. This RIA method will be useful in the study of the physiology of inhibin in the female and male rat.

Animals↗
PubMed1988

Comparison of inhibin immunological and in vitro biological activities in human serum.

A comparison of serum inhibin levels in men and women was undertaken using a sensitive sheep pituitary cell in vitro bioassay and a newly developed heterologous RIA. The RIA was based on an antiserum raised to bovine 31K inhibin using [125I]31K inhibin as tracer. Bovine inhibin alpha- and beta-subunits, bovine activin-A, transforming growth factor-beta, and Mullerian inhibitory substance did not cross-react in the RIA. In both assays, dilutions of serum gave response lines parallel to that of the partially purified human follicular fluid inhibin preparation used as standard. Negligible levels of both bio (B)- and immuno (I) activities were found in serum from women with premature ovarian failure or castrated men. In ovulation-induced cycles, serum B inhibin levels increased progressively from the early to the late follicular phase and remained at the late follicular phase level during the early and midluteal phases. Serum I inhibin levels also rose during the follicular phase, but declined during the early luteal phase before increasing again in the midluteal phase. As a consequence, inhibin B:I ratios varied during the treatment cycle, with high ratios in early follicular (2.86) and early luteal (2.25) phases and a low ratio in the midluteal phase (1.09). Similar changes in serum B:I ratios also occurred during the midcycle and midluteal phases of normal cycles. The B:I ratio was lower (0.35) in normal men. We conclude that the largely similar pattern of inhibin biological and immunological activities in serum obtained during a variety of physiological conditions support the validity of the RIA procedure, and the B:I ratio of serum inhibin varies during the follicular and luteal phases of the cycle and is low in men. Potential reasons for these changes in B:I ratio include the presence of interfering substances in either the bioassay or the RIA, the presence of inhibin isoforms, and/or modulation of secreted forms by sex steroids.

Adult↗
PubMed1987

Statistical considerations in the quantitation of serum immunoglobulin levels using the enzyme-linked immunosorbent assay (ELISA).

Several methods for analyzing ELISA data have been evaluated using optical density values derived by reacting serial two-fold dilutions of a rhesus monkey (Macaca mulatta) reference serum with dilutions of peroxidase-conjugated monospecific antisera to human IgG and IgM in the micro-ELISA 'sandwich' technique using microplates coated with appropriately diluted antisera to human IgG and IgM. Representation of optical density as a linear function of log serum dilution was shown to be inappropriate and potentially misleading. Weighted non-linear least squares analysis of a 4-parameter logit was demonstrated to be inappropriate because it required the specification of a somewhat arbitrary variance function and weight estimates varied substantially depending on the function used. Representation of optical density as a 4-parameter logistic function with estimation carried out on the log scale was shown to be the most appropriate procedure for determining the concentration of antigens or antibodies by the ELISA method.

Animals↗
PubMed1987

Effects of antioxidants on aflatoxin-induced hepatic tumors in rats.

Female Wistar rats pretreated with Aflatoxin B1 (AFB) were administered reduced glutathione, butylated hydroxytoluene, methionine or ascorbic acid on a daily basis, p.o., for 8 months. None of the treatments produced a decrease in incidence or size of hepatic nodules. While there was some evidence that ascorbic acid reduced the incidence of cystic cholangioma, the ascorbic acid and methionine treatment groups also contained significantly fewer animals surviving to the 26-month sacrifice. The lack of effect of glutathione is not consistent with previous work showing a marked glutathione dependent regression of AFB-induced hepatocellular carcinoma.

Aflatoxin B1↗
PubMed1987

The effects of interferons on the activity of alpha-glycerolphosphate dehydrogenase in benign prostatic hyperplasia cells in primary culture.

Human benign prostatic hyperplasia (BPH) tissues were obtained from patients undergoing transurethral resection of the prostate and viable cells from these were successfully maintained in primary cultures grown on collagen gel. The prostatic origin of the cells was confirmed by the measurement of prostate specific acid phosphatase and by scanning and transmission electron microscopy before and after immunostaining with human prostate specific antigen-antibody. The cell cultures were treated with various interferons (IFNs), both in the presence and absence of testosterone propionate (TP), for 72 hours and the activities of seven enzymes of carbohydrate metabolism were estimated in the cytosolic fraction of the cells. Treatment with TP induced a significant decrease in the activity of alpha-glycerolphosphate dehydrogenase (alpha-GPDH). Using this enzyme activity as a marker, the effects of various types of IFNs were investigated. IFN-alpha (wellferon) increased the activity of the enzyme both in the presence of one microgram./ml. of TP and in its absence whereas IFN-gamma inhibited the activity under similar conditions. The effect of treatment with IFN-beta in the presence of TP was biphasic in that there was an increase in the activity of the enzyme at the lowest concentration while at higher concentrations an inhibition of enzymic activity was observed. In the absence of TP IFN-beta inhibited the activity. The significance of these findings in terms of the clinical usefulness of IFNs is discussed and it is postulated that IFN-alpha (wellferon) might be effective in the treatment of metastatic carcinoma of the prostate in selected patients.

Cells, Cultured↗
PubMedDate not supplied

Chronic feeding study of deoxynivalenol in B6C3F1 male and female mice.

A 2 year feeding study was conducted with male and female B6C3F1 mice that consumed diets containing 0, 1, 5, or 10 ppm deoxynivalenol (DON). Survivability was good and, while the test animals gained less weight with increasing levels of DON in the diet, there were no consistent toxic manifestations associated with DON consumption. There was some evidence for an increase in serum IgA and IgG in females, and there were sporadic changes noted in the clinical chemistry and hematology parameters conducted at the terminal sacrifice. However, these changes were not considered to be biologically significant. The pathology results provided statistically significant dose-related evidence for a decrease in liver preneoplastic and neoplastic lesions as the dose level of DON increased. This negative trend probably results from the known positive correlation between body weight and the appearance of spontaneous hepatic neoplasms in this strain of mouse.

Analysis of Variance↗
PubMedDate not supplied

The ability of the rat to metabolize myristoyl-methionine: an acylamino acid with potentially useful antibacterial properties.

Two experiments with Sprague Dawley rats tested their ability to hydrolyse myristoyl-methionine (M-M) into myristic acid and L-methionine (M). In the first experiment, lasting for 3 days. male rats were orally administered [9,10-3H]myristoyl-L-[35S]methionine. The recovery of radioactivity was approximately 90% for both isotopes; 19% of the administered 3H was recovered in the urine and 16% in the faeces, while the recovered 35S activity was 13 and 12%, respectively. The balance of the radioactivity was found among the tissues, organs and blood. In the second experiment, male and female rats received soybean-based diets which were supplemented with either 0.305% M-M or 0.2% M (both diets contained equal amounts of M) for periods up to 4 weeks. The growth rate of the rats receiving the 0.305% M-M diets was slightly slower than that for the rats on the 0.2% M diet, but the difference was not statistically significant (P > 0.05). The M-M rats had a transitory decrease in feed consumption, suggesting that palatability may have contributed to the growth difference and that a somewhat greater amount of M-M was necessary for the rat to attain the same growth rate as that produced by 0.2% M. When the amount of dietary M-M was increased to 3.05% M-M, a greater reduction in feed consumption and body weight gain was observed. This latter diet was an initial attempt to study the potential toxicity of M-M. None of the haematological, clinical chemistry or organ weight data suggested that M-M was overtly toxic per se, but longer-term feeding studies are needed to evaluate the potential toxicity of M-M more fully.

Administration, Oral↗