Biomedical subjects

J E Miller

Publications and source records attributed to J E Miller.

At least 19 recordsLinked to original sources

PubMed1998

A comparative study of in vivo mutation assays: analysis of hprt, lacI, cII/cI and as mutational targets for N-nitroso-N-methylurea and benzo[a]pyrene in Big Blue mice.

We have compared the response of the native hprt gene and the lacI, cII, and cI transgenes in Big Blue B6C3F1 mice following treatment with either N-nitroso-N-methylurea (MNU) or benzo[a]pyrene (BaP). Three weeks after mutagen treatment splenic T cells were isolated from the animals, and samples were either cultured to measure mutation at the native hprt locus or used to extract genomic DNA for transgene mutation analysis. Phage rescued from extracted DNA were plated in the presence of 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside (X-gal) to score lacI mutations, or plated on a hflAB lawn to score cII and cI mutants. With MNU hprt mutant frequency increased in a dose-related, sublinear manner up to 78-fold above background at the highest dose tested (20 mg/kg). In comparison, the lacI transgene yielded only a 3.1-fold increase at this dose, and the cII and cI transgenes did not show any increase. With 150 mg/kg BaP a 5.8- and 8.7-fold increase in mutant frequency was observed at hprt and lacI, respectively, while only a 1.3-fold increase was observed at cII. DNA sequencing revealed an increase in GC-->TA transversions among the cII mutants, suggesting that the increase was related to BaP exposure. No significant increase in cI mutant frequency was observed. Therefore, the order of mutation assay sensitivity was hprt>lacI>cII/cI with MNU, and hprt approximately lacI> cII/cI with BaP. While the hflAB selection system offers significant advantages with respect to cost and effort when compared to the lacI assay, additional evaluation of its sensitivity is warranted.

Animals↗

PubMed1998

DNA synthesis inhibition as an indirect mechanism of chromosome aberrations: comparison of DNA-reactive and non-DNA-reactive clastogens.

Positive results in the in vitro assay for chromosome aberrations sometimes occur with test chemicals that apparently do not react with DNA, being negative in tests for mutation in bacteria, for DNA strand breaks, and for covalent binding to DNA. These chromosome aberrations typically occur over a narrow concentration range at toxic doses, and with mitotic inhibition. Indirect mechanisms, including oxidative damage, cytotoxicity and inhibition of DNA synthesis induced by chemical exposure, may be involved. Understanding when such mechanisms are operating is important in evaluating potential mutagenic hazards, since the effects may occur only above a certain threshold dose. Here, we used two-parameter flow cytometry to assess DNA synthesis inhibition (uptake of bromodeoxyuridine [BrdUrd]) associated with the induction of aberrations in CHO cells by DNA-reactive and non-reactive chemicals, and to follow cell cycle progression. Aphidicolin (APC), a DNA polymerase inhibitor, induces aberrations without reacting with DNA; 50 microM APC suppressed BrdUrd uptake during a 3-h treatment to <10% of control levels. Several new drug candidates induced aberrations concomitant with marked reductions in cell counts at 20 h (to 50-60% of controls) and suppression of BrdUrd uptake (<15% of control). Several non-mutagenic chemicals and a metabolic poison, which induce DNA double strand breaks and chromosome aberrations at toxic dose levels, also suppressed DNA synthesis. In contrast, the alkylating agents 4-nitroquinoline-1-oxide, mitomycin C, methylnitrosourea, ethylnitrosourea, methylmethane sulfonate and ethylmethane sulfonate, and a topoisomerase II inhibitor, etoposide, produced many aberrations at concentrations that were less toxic (cell counts >/=73% of controls) and gave little inhibition of DNA synthesis during treatment (BrdUrd uptake >/=85% of controls), although cell cycle delay was seen following the 3-h treatment. Thus, inhibition of DNA synthesis at the time of treatment is supporting evidence for an indirect mechanism of aberrations, when there is no direct DNA reactivity.

Animals↗

PubMed1998

Epidemiology of gastrointestinal nematode parasitism in Suffolk and Gulf Coast Native sheep with special emphasis on relative susceptibility to Haemonchus contortus infection.

An eight-year study was conducted to define the epidemiology of gastrointestinal nematode infection in Suffolk and Gulf Coast Native (Native) breeds of sheep, and to determine if the Native sheep is more resistant to infection. For the initial three years, each breed grazed separate pastures where anthelmintic treatments were administered to individual animals on a salvage basis. For the last five years, both breeds grazed concurrently; anthelmintic treatments were administered to individual animals on a salvage basis for the first three years, and to all animals, when treatment criteria were met, for the last two years. The fecal egg count (FEC) and blood packed cell volume (PCV) were monitored, and tracer lamb nematode burdens were determined. Overall, FEC for both breeds increased in the spring (periparturient rise) for most years and in the summer for all years. Under separate grazing conditions, Native ewes and lambs had consistently lower infection levels than Suffolk ewes and lambs. During the haemonchosis season (June-September) each year, Suffolk ewe and lamb PCV decreased, and Native ewe and lamb PCV remained relatively stable. The salvage treatment protocol resulted in 27 treatments for Suffolk and one for Native ewes; similarly for lambs, 13 for Suffolk and zero for Native. Tracer lambs grazed with their respective breed, and the FEC and mean total nematode burden corresponded with the pattern of infection for their respective breed. The predominant nematodes found in Suffolk and Native tracer lambs were Haemonchus contortus and Trichostrongylus spp., respectively. Under concurrent grazing conditions, the same seasonal repeatable pattern of infection was present and was exhibited by both breeds, with the Native ewes and lambs being consistently and significantly (p < or = 0.05) lower for FEC and higher for PCV. The salvage treatment protocol resulted in 57 and zero treatments for Suffolk and Native ewes, respectively; for lambs, 46 and 11. Tracer lamb nematode burdens again corresponded to their respective breed pattern of infection, with H. contortus and Trichostrongylus spp. being predominant in Suffolk and Native lambs, respectively. Data from all tracer lambs showed a relatively low level of hypobiosis (H. contortus only), and, although there was no consistent hypobiosis season, the tendency was for a higher level to occur in the fall. These results showed that the classic repeatable seasonal pattern of gastrointestinal nematode infection occurred in both breeds of sheep, and that Native sheep were more resistant to infection (specifically H. contortus) than Suffolk sheep.

Animal Feed↗

PubMed1998

Developmental screening scores among preschool-aged children: the roles of poverty and child health.

OBJECTIVES: To investigate, using a nationally representative sample of preschool-aged children, the relationship among poverty history, child health, and risk of an abnormal developmental screening score. METHODS: Data were derived from the 1988 National Maternal and Infant Health Survey and 1991 Longitudinal Follow-up. Family income in the child's prenatal year and at 2 years old defined a poverty history for each child. Multivariate logistic regression was used to estimate the effects of poverty history on risk of an abnormal screening score or delays in large-motor, personal-social, or language subscales. RESULTS: Poor and near-poor children were 1.6 to 2.0 times as likely as nonpoor children to be classified as abnormal, even when maternal and household characteristics and the child's health history were taken into account. Preterm birth, chronic illness, dearth of reading materials in the home, and maternal depression were also associated with elevated risks of abnormal scores. CONCLUSIONS: Poverty is the largest single predictor of an abnormal developmental screening score. The implications of inadequate medical care among poor children for the interpretation of individual screening scores and for amelioration of problems are also discussed.

Child Health Services↗

PubMed1998

Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus.

Human serum paraoxonase (PON1) is located on high density lipoprotein and has been implicated in the detoxification of organophosphates and possibly in the prevention of low density lipoprotein lipid peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine (A genotype) and arginine (B genotype) at position 192 and the other leucine (L genotype) and methionine (M genotype) at position 55. We investigated the effect of these polymorphisms on serum PON1 activity and concentration in 252 non-insulin dependent diabetes mellitus (NIDDM) individuals and 282 non-diabetic controls. Serum PON1 activity in the controls (214.6 nmol/min per ml (26.3-620.8)) was significantly higher than in NIDDM (158.7 nmol/min per ml (3.6-550.5) (P < 0.001) as was serum PON1 concentration (89.1 microg/ml (16.8-527.4)) compared to 76.7 microg/ml (3.6-443.8) (P < 0.01). In the control population MM homozygotes had significantly lower serum PON1 activity regardless of the 192 polymorphism whereas in NIDDM both LM and MM genotypes had lower serum PON1 activity than LL homozygotes only when the 192 AA genotype was present. Serum PON1 concentration was lower in NIDDM with AA/LM, AA/LL, AB/LL and AB/MM genotypes than in controls. Differences in PON1 activity were the major cause of differences in specific activity between genotypes. Neither the PON1 55 or 192 polymorphisms consistently influenced the serum lipid or lipoprotein concentrations in either population. Low serum PON1 activity in NIDDM may be related to an increased tendency to lipid peroxidation and may also increase susceptibility to toxicity from organophosphate exposure. Our findings thus raise the possibility that PON1 may be of importance in both the genetic and acquired predisposition to premature atherosclerosis and neuropathy in diabetes.

Adult↗

PubMed1998

Bladder petechiae after cystoscopy and hydrodistension in men diagnosed with prostate pain.

PURPOSE: We determined if men with prostate pain syndromes have petechiae in the bladder after hydrodistension. MATERIALS AND METHODS: A total of 60 men with the diagnosis of prostate pain and without bacteriuria underwent cystoscopy and hydrodistension under a general or regional anesthetic. RESULTS: Of the 60 men 35 (58%) had moderate to severe petechiae similar in appearance to women with interstitial cystitis after hydrodistension. Men with moderate to severe bladder petechiae had fewer leukocytes in expressed prostatic secretions, smaller bladder capacities and less often testicular pain than men with more normal appearing bladders after hydrodistension. Symptomatic improvement 2 to 6 weeks after hydrodistension was more common in men with moderate to severe petechiae than in those with fewer petechiae. Absence of rectal pain predicted symptomatic improvement after hydrodistension. CONCLUSIONS: We suggest that bladder petechiae, and possibly interstitial cystitis or a related condition, may be more frequently associated with prostate pain syndromes in men than previously appreciated.

Adult↗

PubMed1998

Biomedical risk factors for hospital admission in older adults.

OBJECTIVES: This study examines the influence of risk factors such as cigarette smoking, blood pressure, serum cholesterol, or chronic illness on frequency of hospital admission in a population-based sample. METHODS: Data from the National Health and Nutrition Examination Survey I Epidemiologic Followup Study for 6,461 adults aged 45 years and older were used to assess the influence of risk factors measured by interview, physical examination, and laboratory tests on frequency of hospital admission over a 12- to 16-year follow-up period. Cox proportional hazard regressions were estimated separately for men and women and for ages 45 to 64 years and 65 years and older. SUDAAN software was used to correct for clustering, stratification, unequal weighting, and multiple observations per respondent. RESULTS: Risk of hospitalization was higher for current but not former smokers (relative risk [RR] = 1.17-1.34 for different age-sex groups; P < 0.01), higher blood pressure (RR = 1.25-1.28 for ages 45-64; RR = 1.07-1.15 for ages 65 and older; P < 0.01), and lower serum albumin (RR = 1.08-1.14; P < 0.01). Diabetes, lung conditions, heart attack, and ulcer each were associated with higher risk in at least three of the four age-sex groups, as was arthritis among the middle-aged (45-64 years). Serum cholesterol was not associated with hospitalization. CONCLUSIONS: Chronic conditions with high morbidity as well as many factors associated with mortality are associated with a higher frequency of hospitalization.

Age Factors↗

PubMed1997

Cell-specific regulation of expression of plasma-type platelet-activating factor acetylhydrolase in the liver.

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that causes hypotension, increases vascular permeability, and has been implicated in anaphylaxis, septic shock and several other inflammatory responses. PAF is hydrolyzed and inactivated by the enzyme PAF-acetylhydrolase. In the intact rat, a mesenteric vein infusion of lipopolysaccharide (LPS) served as an acute, liver-focused model of endotoxemia. Plasma PAF-acetylhydrolase activity increased 2-fold by 24 h following LPS administration. Ribonuclease protection experiments demonstrated very low levels of plasma-type PAF-acetylhydrolase mRNA transcripts in the livers of saline-infused rats; however, 24 h following LPS exposure, a 20-fold induction of PAF-acetylhydrolase mRNA was detected. In cells isolated from endotoxin-exposed rat livers, Northern blot analyses demonstrated that Kupffer cells but not hepatocytes or endothelial cells were responsible for the increased PAF-acetylhydrolase mRNA levels. In Kupffer cells, plasma-type PAF-acetylhydrolase mRNA was induced by 12 h, peaked at 24 h, and remained substantially elevated at 48 h. Induction of neutropenia prior to LPS administration had no effect on the increase in PAF-acetylhydrolase mRNA seen at 24 h. Although freshly isolated Kupffer cells contain barely detectable levels of plasma-type PAF-acetylhydrolase mRNA, when Kupffer cells were established in culture, PAF-acetylhydrolase expression became constitutively activated concomitant with cell adherence to the culture plates. Alterations in plasma-type PAF-acetylhydrolase expression may constitute an important mechanism for elevating plasma PAF-acetylhydrolase levels and an important component in minimizing PAF-mediated pathophysiology in livers exposed to endotoxemia.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1997

Endothelin-1 production by hepatic endothelial cells: characterization and augmentation by endotoxin exposure.

Activation of endothelin (ET) receptors in the liver causes vasoconstriction, glucose production, and lipid and peptide mediator synthesis. In the intact rat, a bolus infusion of endotoxin into a mesenteric vein served as an acute exposure model of endotoxemia. In response to this challenge, a ninefold increase in hepatic ET-1 mRNA occurred within 3 h. The plasma level of immunoreactive ET-1 (irET-1) increased correspondingly by 8.5-fold within 6 h. ET-1 mRNA levels in liver endothelial cells (EC) isolated from livers of endotoxin-treated rats at various times after endotoxin challenge showed a more gradual increase. Northern blot analyses of the major liver cell types demonstrated that ET-1 mRNA was most abundant in the EC. The present results document a significant increase in the circulating level of irET-1 during episodes of endotoxemia. The increased hepatic ET-1 production in response to endotoxin infusion suggests that ET-1 produced in the liver could make a significant contribution to the plasma irET-1 and may be an important component in the hepatic responses to systemic trauma.

Animals↗

PubMed1997

Erythrocyte incorporation and absorption of 58Fe in premature infants treated with erythropoietin.

We hypothesized that treatment of very low birth weight premature infants with r-HuEPO would increase erythrocyte incorporation and gastrointestinal absorption of iron. Infants with birth weights < or = 1.25 kg and gestational ages < 31 wk were randomized to receive 6 wk of 500 U of r-HuEPO/kg/wk (epo group, n = 7) or placebo (placebo group, n = 7). All infants received daily enteral supplementation with 6 mg of elemental iron per kg. An enteral test dose of a stable iron isotope, 58Fe, was administered after the 1st ("early dosing") and 4th ("late dosing") wk of treatment. Mean (+/-SD) erythrocyte incorporation of the dose of 58Fe administered determined 2 wk after early dosing was significantly greater in the epo group compared with the placebo group (4.4% +/- 1.6 versus 2.0 +/- 1.4%, p = 0.013). In contrast, after late 58Fe dosing, there was no difference between groups in incorporation (3.8 +/- 1.6% versus 5.5 +/- 2.7%). Within the epo group, percentage erythrocyte incorporation of 58Fe did not differ between early and late dosing, whereas in the placebo group it increased 3-fold (p < 0.01). Percentage absorption of 58Fe was not different between the epo and placebo groups after both early dosing (30 +/- 22% versus 34 +/- 8%) and late dosing (32 +/- 9% versus 31 +/- 6%). Absorption of nonlabeled elemental iron and 58Fe were significantly correlated with one another. The percentage of the absorbed 58Fe dose incorporated into Hb was not different between groups. We conclude that, although erythropoietin treatment stimulates erythrocyte iron incorporation in premature infants, it has no effect on iron absorption at the r-HuEPO dose studied.

Double-Blind Method↗

PubMed1997

Incidence and significance of subdiaphragmatic air following laparoscopic cholecystectomy.

Subdiaphragmatic free-air may be indicative of a perforated viscus; however, it is normally present after open abdominal surgery. The objective of this study was to determine the significance and incidence of subdiaphragmatic free air following laparoscopic cholecystectomy (LC). Cases of intestinal perforation following laparoscopic cholecystectomy from 1991 to 1995 at The University of Texas Health Science Center at San Antonio were reviewed and their association with subdiaphragmatic free air was determined. Twenty-five patients undergoing LC and 20 patients undergoing open cholecystectomy (OC) were prospectively evaluated with chest radiographs to determine the incidence and quantity of nonpathologic postoperative free air. Four cases of intestinal perforation resulting from trocar injuries or electrocautery burns occurred among 1603 LCs during this study period, for an incidence of 0.2 per cent. Three of the four patients with perforations were diagnosed postoperatively (2-5 days), and two patients had a moderate volume of subdiaphragmatic free air that aided the diagnosis. The incidence of subdiaphragmatic air following LC was 24 per cent, compared to 60 per cent for OC (P < 0.05). Eighty-three per cent of patients with retained air after LC had a minimal volume, compared to 67 per cent of patients after OC (P < 0.05). Nonpathologic subdiaphragmatic free air may normally be present following laparoscopic cholecystectomy but is uncommon 24 hours after the operation. When present, only a small volume is usually detectable. In the rare situation of intestinal perforation resulting from LC, subdiaphragmatic free air may be an important diagnostic finding.

Adult↗

PubMed1997

Adequacy of hormone replacement therapy for osteoporosis prevention assessed by serum oestradiol measurement, and the degree of association with menopausal symptoms.

BACKGROUND: Patients on hormone replacement therapy (HRT) for osteoporosis prevention rather than menopausal symptom control may be asymptomatic, despite inadequate replacement and low serum oestradiol (E2) levels. In the primary health care setting, therapeutic monitoring of HRT is not carried out routinely so that patients with serum E2 levels inadequate to protect bone may be missed. AIM: To determine the proportion of women on transdermal E2 preparations with serum E2 levels insufficient to protect bone and to assess the value of a questionnaire-derived menopausal symptom score (MSS) for detecting these patients. METHOD: A cross-sectional analysis of 45 patients aged 35-70 years using transdermal E2 preparations obtained from a computer register of 14500 patients in a suburban practice. One blood sample was obtained from each patient at the time the MSS questionnaire was completed. Serum E2 concentration was measured using a fluoroimmunoassay and compared with the MSS. Levels below 150 pmol/l were considered to be insufficient to protect bone. The diagnostic accuracy of the MSS in screening for levels below 150 pmol/l was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: The median (95% CI) serum E2 was 147 pmol/l (126-198 pmol/l) and levels were below 150 pmol/l in 24 out of 45 patients. There was no difference in the MSS (median, 95% CI) between those with serum E2 < 150 pmol/l (8.5, 5.0-17) and > or = 150 pmol/l (9.0, 5.0-14; P = 0.477). The degree of association between the serum E2 and the MSS, using the Spearman rank correlation coefficient, rs (95% CI) was small and not significant (-0.04, -0.34 to 0.26; P = 0.398). ROC curve analysis revealed an area under the curve (95% CI) of 0.51 (0.33-0.68). CONCLUSIONS: More than half the women were inadequately replaced to protect against osteoporosis. Furthermore, the MSS was of no value in screening for those with low serum E2 levels. Serum E2 levels should be monitored in women on HRT for osteoporosis prevention and the E2 dosage adjusted accordingly.

Adult↗

PubMed1996

Susceptibility of Suffolk and Gulf Coast Native suckling lambs to naturally acquired strongylate nematode infection.

Three trials compared responses to naturally-acquired strongylate nematode infection between suckling Suffolk and Gulf Coast Native (Native) lambs which grazed together. In Trial 1 (1992), infection in 14 lambs of each breed was monitored from birth to 12 weeks of age using fecal egg count (FEC) and blood packed cell volume (PCV). In Trial 2 (1993), two age-matched lambs of each breed were sacrificed at seven and ten weeks of age to estimate nematode burdens. In Trial 3 (1994), infection in 18 lambs of each breed was monitored (FEC, PCV, white blood cell count, differential leukocyte count, and anti-Haemonchus contortus immunoglobulin level) from birth to 8 weeks of age, at which time six age-matched lambs of each breed were sacrificed to estimate nematode burdens. The remaining 24 lambs were monitored until 12 weeks of age. In both Trials 1 and 3, infection in Native lambs peaked and then declined between 6-10 weeks of age. Infection in Suffolk lambs continued to increase as evidenced by increasing FEC with concomitant reduction in PCV, higher morbidity and mortality (Trial 1), and number of anthelmintic treatments required (Trial 3). In Trials 2 and 3, the principal nematode found at necropsy was H. contortus, and infection level was consistently lower (> 64%) in Native compared with Suffolk lambs. In Trial 3, there was no difference between breeds for WBC, any leukocyte type, or anti-H. contortus immunoglobulin level. These results demonstrated that suckling Native lambs developed resistance to H. contortus infection during their first exposure to infection at an age when they are considered immune incompetent and colostrally transferred anti-H. contortus immunoglobulin did not appear to be involved in the resistance.

Age Factors↗

PubMed1996

Antigen-presenting function of the mouse CD1 molecule.

CD1 molecules are distantly related to major histocompatibility complex (MHC)-encoded class I molecules, and they are coexpressed with beta2 microglobulin (beta2m). In the mouse, CD1 is expressed by intestinal epithelial cells and also by some cells in spleen and lymph node. We have shown that surface expression of mouse CD1 (mCD1) is not dependent upon a functional transporter associated with antigen processing (TAP). This, and other data, suggest that mCD1 may acquire peptides in an intracellular compartment other than the endoplasmic reticulum, where classical class I molecules bind peptide. mCD1 molecules also are distinct from classical class I molecules with regard to the types of peptides that they bind. We have demonstrated that mCD1 molecules preferentially bind peptides much longer than the 8-9 amino acids typical of the peptides that bind to classical class I molecules. The sequence motif for mCD1 peptide binding is characterized by the presence of bulky and hydrophobic amino acid side chains. We have generated mCD1-restricted and peptide-specific T-cell lines, thereby demonstrating the immunologic relevance of peptide binding to mCD1. The reactive T cells are TCR alphabeta+ and CD8+, a phenotype typical of many lymphocytes in both lymph node and intestinal mucosae. We speculate that mCD1 molecules may be capable of sampling peptides from the gut lumen and presenting them to mucosal T lymphocytes. In this way, they may function in the maintenance of normal mucosal homeostasis, and perhaps also in the induction of systemic tolerance to antigens delivered by the oral route. In summary, CD1 molecules are a novel category of antigen-presenting molecules that have features in common with class I molecules, features in common with class II, and properties distinct from either subset of antigen-presenting molecules. Further studies of the antigen-presenting function of these molecules are certain to yield new insight into immune regulation and perhaps also into the mechanism of oral tolerance.

Administration, Oral↗

PubMed1996

Evidence for altered cellular calcium in the pathogenetic mechanism of acute pancreatitis in rats.

Although several pathophysiological sequences, such as protease activation, free radical generation, and inflammatory mediator release, have been described in acute pancreatitis, the precise mechanism by which acute pancreatitis is initiated is unknown. Cellular calcium, a key physiological signaling element in cell function and also a crucial pathological intracellular messenger in cell injury, appears to be involved in the initiation and development of acute pancreatitis. The present study provides several lines of evidence supporting this suggestion. First, verapamil (a calcium channel blocker) administration was associated with a significant protection of rats from acute pancreatitis induced by high doses of cerulein (50 micrograms/kg/hr, subcutaneously), as evidenced both histologically and biochemically. Second, verapamil was found to minimize the increased tissue levels of calcium, platelet-activating factor, and thromboxane B2 detected during acute pancreatitis. Third, acute pancreatitis could be observed in rats with elevated serum calcium levels at low doses of cerulein (5 micrograms/kg/hr, subcutaneously), but could not be observed in rats with normal serum calcium levels treated with low doses of cerulein. It is proposed that cellular calcium, which is a critical signaling component in the synthesis and release of inflammatory mediators and several other events, may be an important factor in the pathogenesis of cerulein-induced acute pancreatitis.

Acute Disease↗

PubMed1996

Hormonal stimulation of calcium mobilization in the isolated perfused rat pancreas.

Hormone-stimulated cellular Ca2+ mobilization in the isolated perfused rat pancreas was investigated by analyzing the efflux profiles of 45Ca2+ from 45Ca(2+)-loaded pancreata following agonist stimulation. The increased 45Ca2+ efflux reflects the enhanced exchange of Ca2+ across the plasma membrane as a result of increased [Ca2+]i. Both high and low concentrations of the cholecystokinin analog, cerulein, applied to the isolated perfused pancreas gave rise to an increased release of 45Ca3+. The patterns of the increase in 45Ca2+ release were consistently different for high and low concentrations of the agonist. Cerulein infused at a concentration of 10(-11) M induced a release of a small but significant amount of 45Ca2+ which could be abolished by 8-(N,N-diethylamine)octyl-3,4,5-trimethoxy-benzoate (TMB-8), but was not affected by ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Cerulein stimulation at 10(-9) M elicited a marked increase in 45Ca2+ release which was minimized by EGTA, but not by TMB-8. Also, infusion of cerulein stimulated a concentration-dependent amylase secretion response which displayed the same TMB-8- and EGTA-sensitivity pattern as the 45Ca2+ release response. The present study suggests (i) that cellular Ca2+ influx is a prominent feature of the increased 45Ca2+ efflux (i.e., increased [Ca2+]i) induced by pharmacological concentrations of cerulein while physiological concentrations of cerulein cause an increase in [Ca2+]i which is due predominantly to a release of internal Ca2+; and (ii) [Ca2+]i changes are essential for pancreatic enzyme secretion. Although isolated pancreatic acini or cells may lose their sensitivity and physiological responses to various agonists during isolation and preparation, the isolated perfused pancreas is a suitable and very sensitive model in which to study the physiology of Ca2+ mobilization and enzyme secretion.

Amylases↗

PubMed1996

Serum IgE levels in dairy calves: evaluation of parasite and pasture exposure as possible determinants of IgE response.

Immunoglobulin E (IgE) has been regarded as an antibody isotype important in the host response to helminth infection and allergic conditions. Level of parasitic infection has been associated with serum total IgE level and the highest levels have been observed during the spring when environmental allergen levels are also high. Two groups of five parasite-native calves were maintained in a barn and one of the groups received an experimental gastrointestinal nematode infection. One group of five parasite-native calves was placed on clean pasture and another group of five was placed on a nematode-contaminated pasture. The contaminated pasture group acquired an acute gastrointestinal nematode infection, compared with a relatively low infection in the experimentally infected group. The only difference between the groups was a significant change (increase) in IgE level in calves on contaminated pasture, compared with the other three groups. This suggested that the infection acquired on pasture and not the experimental infection or environmental allergens encountered while grazing or in the barn stimulated an IgE response.

Allergens↗

PubMed1996

AIDS knowledge among New Jersey adults.

Data were collected from New Jersey adults. Most respondents know the major means by which the disease is transmitted and that a cure and vaccine are not available.

Acquired Immunodeficiency Syndrome↗