Biomedical subjects

C Hanson

Publications and source records attributed to C Hanson.

At least 19 recordsLinked to original sources

PubMed2006

N-methyl carbamate pesticide residues in conventional and organic infant foods available on the Canadian retail market, 2001-03.

Seven parent N-methyl carbamate insecticides, in addition to two transformation products of aldicarb (aldicarb sulfoxide and aldicarb sulfone), and a single transformation product of carbofuran (3-hydroxycarbofuran) were measured in infant and junior foods available on the Canadian retail market between 2001 and 2003. Carbaryl and methomyl were the only analytes present at levels above the limits of detection in juice, cereals, fruit, vegetables or meat samples analysed. Carbaryl was the most frequently (7.6%) detected compound and concentrations ranged from 0.6 to 18 ng g-1. Detectable levels of carbaryl were most frequently found in foods prepared with fruit. Methomyl was detected (0.8 ng g-1) in one chicken with broth sample analysed in the present study. In all cases, the concentrations observed were orders of magnitude below the maximum residue limits established for these compounds in the corresponding raw food commodities in Canada (100-10 000 ng g-1). Dietary intakes of carbaryl and methomyl based on the consumption of infant foods tested ranged between 0.2-343 and 0.4-2.0 ng kg-1 body weight day-1, respectively.

Carbamates↗

PubMed2004

Development of a structured clinical operative test (SCOT) in the assessment of practical ability in the oral surgery undergraduate curriculum.

Competence in undergraduate oral surgery involves assessment of the students' knowledge, practical skill and attitude. The assessment of practical skills can be achieved using a formative assessment method such as the structured clinical operative test (SCOT) which uses a checklist for the assessment of a clinical task. The aim of this study was primarily to determine whether SCOTs could be integrated into the oral surgery undergraduate course, and secondarily to collect feedback from both the students and the staff on this assessment. A validated checklist was used by trained examiners to assess the performance of 49 students in their second clinical year undertaking simple exodontia. Feedback was collected from the students by questionnaire and from the staff by interview. The SCOT was well received by both students and staff. The main problem highlighted by the students was the perceived inter-examiner variability and by the staff, the disruptive effect on the clinics. The checklist must be objective enough to prevent misinterpretation. Despite these limitations, the SCOT provides a more objective assessment and serves to highlight weaker students, allowing them to be targeted for closer supervision and instruction as well as providing the students with a tool to measure their progress in oral surgery. The use of peer assessment by students may alleviate the burden on the staff.

Clinical Competence↗

PubMed2004

N-methyl carbamate concentrations and dietary intake estimates for apple and grape juices available on the retail market in Canada.

Infants and young children consume fruit juices and drinks at rates exceeding those of older children and adults. Carbamate pesticides are known to be used on a broad spectrum of crops, including orchard and vine crops such as apples and grapes. Concern over potential exposure to these acutely toxic pesticides by infants and young children has increased in the last decade. Liquid chromatography with fluorescence detection was used to determine the concentrations of seven N-methyl carbamates and three transformation products in domestic and imported apple and grape juices collected across Canada. Carbaryl was the most frequently (58.6%) detected N-methyl carbamate in juice samples studied. It was observed more frequently in grape juices than in apple or mixed juices. Oxamyl and methomyl were detected in apple juice samples, although they were below detection limits in all grape and mixed juice samples analysed. Maximum levels of carbaryl, methomyl and oxamyl were 93, 6.7 and 4.6 ng ml(-1), respectively. All other analytes were not present in any juice sample at concentrations above the method detection limit (0.3 ng ml(-1)). In all cases, N-methyl carbamate residues were well below the maximum residue limit established for apples and grapes in the Canadian Food and Drug Regulations. No estimated dietary intakes were above the acceptable daily intakes in any age-sex category, where an acceptable daily intake has been proposed. Carbaryl short-term intake estimates were calculated and all were below the proposed acute reference doses.

Beverages↗

PubMed2003

Carrier-dependent specificity of antibodies to a conserved peptide determinant of gp120.

Amino acid residues 421-436 constitute a comparatively conserved determinant of gp120 that participates in the binding of host cell CD4 receptors by HIV-1. We compared the immunogenicity of synthetic Cys-gp120 (421-436) conjugated to KLH via the N terminal Cys residue (KLH-I) and gp120 (421-436) extended at its N terminus with a 15 residue tetanus toxoid T cell epitope (T-I) in non-autoimmune mice (BALB/cstrain) and Fas-defective autoimmune mice (MRL/lpr strain). Both immunogens elicited high titer Abs detected as the binding to gp120 (421-436) conjugated to bovine serum albumin (BSA-I) immobilized in ELISA plates. Abs from KLH-I immunized mice displayed binding to full-length gp120 but the Abs from T-I immunized mice did not. Proteins unrelated in sequence to gp120 did not bind the Abs. Soluble I and T-I failed to compete with immobilized BSA-I for binding to anti-KLH-I Abs, whereas these peptides inhibited anti-T-I Ab binding by BSA-I (rank potency order: BSA-I > T-I >> I). These results indicate the influence of the carrier protein on the specificity of Abs to synthetic I. Low level BSA-I and gp120 binding Abs were detected in sera from non-immunized MRL/lpr mice. Similar Ab binding titers and specificity profiles were evident in MRL/lpr and BALB/c mice following immunization with KLH-I and T-I, indicating that pre-existing immunity to gp120 in the former strain does not influence the magnitude or specificity of the Ab response.

Amino Acid Sequence↗

PubMed2001

Testicular ultrasonography and extended chromosome analysis in men with nonmosaic Klinefelter syndrome: a prospective study of possible predictive factors for successful sperm recovery.

OBJECTIVE: To investigate whether extended chromosome analysis or testicular sonography, including flow Doppler imaging, before diagnostic testicular sperm extraction have predictive value for successful sperm retrieval in men with nonmosaic Klinefelter syndrome. DESIGN: Prospective clinical study. SETTING: IVF clinic and genetics laboratory at a university hospital. PATIENT(S): Nineteen patients with nonmosaic Klinefelter syndrome and azoospermia. INTERVENTION(S): Collection of blood samples; histopathologic examination of testicular tissue; fluorescence in situ hybridization; sonography, including Doppler imaging; and testicular sperm extraction. MAIN OUTCOME MEASURE(S): Testicular volume, serum FSH and serum testosterone levels, percentage of normal XY cells, ultrasound echogenicity, intratesticular blood flow resistance, and sperm recovery. RESULT(S): Testicular volume and levels of serum FSH and serum testosterone levels did not differ significantly. No differences in testicular echogenicity or intratesticular blood flow resistance were found between 47,XXY men in whom sperm recovery was successful and those in whom sperm recovery failed. Significant differences were seen between all patients with the Klinefelter syndrome and controls with normal sperm values. Fluorescence in situ hybridization of peripheral lymphocytes and buccal tissue showed no correlation between frequency of normal 46,XY cells and testicular spermatogenesis. CONCLUSION(S): In azoospermic men with the Klinefelter syndrome, histopathologic findings seem to be predictive for successful sperm recovery. Infertility work-up, including diagnostic testicular sperm recovery, is recommended, and, if possible, viable sperm should be cryopreserved.

Adult↗

PubMed2001

Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation.

Uneven blastomere cleavage in human embryos of 'good morphology', i.e. those normally used for transfer, is a phenomenon which has been poorly investigated. The main objective in this study was to probe deeper into the aetiology behind previous findings that embryos with uneven cell cleavage have a lower developmental capacity in comparison with evenly cleaved embryos. Our hypothesis was that uneven cleavage may result in embryos with a higher degree of aneuploidy and/or multinuclear rate, which in turn might help to explain their low implantation rate. In the first part of the study, 378 embryo transfers performed over a 3-year period were analysed retrospectively, where all the transferred embryos in each cycle were of identical morphology score and cleavage stage. In the second part of the study, multicolour fluorescence in-situ hybridization (FISH) analyses on good quality embryos, representing the uneven (n = 11) and even (n = 13) study groups were performed. When comparing day 2 transfers between 4-cell embryos, it was found that unevenly cleaved embryos had significantly lower implantation (23.9 and 36.4%) and pregnancy rates (37.6 and 52.9%) compared with evenly cleaved embryos. A significantly higher degree of aneuploidy (29.4 and 8.5%) and multinuclear rate (21.1 and 2.1%) in blastomeres from uneven embryos was also found. It is concluded that uneven blastomere cleavage has a negative effect on both pregnancy and implantation rates in human IVF, and that this can partly be explained by a higher degree of aneuploidy/multinuclear rate. In the light of the results obtained, a new approach in the current embryo scoring system, placing more emphasis on blastomere size, is recommended.

Adult↗

PubMed2001

Genetic analysis of mosaicism in 53 women with Turner syndrome.

Mosaicism involving the sex chromosomes is a common finding in women with Turner syndrome (TS). It is especially important to detect Y-chromosomal material, since this is a risk factor for the development of gonadoblastoma. Recent studies have also indicated that the frequency of 45,X cells may be used to predict prognosis. As part of an ongoing multi-disciplinary study, we have examined the extent of Y-chromosomal material and sex chromosomal mosaicism and its tissue specificity in 53 women with TS. The results of lymphocyte karyotyping were compared with the use of interphase X/Y fluorescence in situ hybridisation (FISH) analysis of lymphocytes and buccal mucosal cells. As could be expected, an extended FISH analysis detected more Y-chromosomal material than karyotyping (in 15% vs. 11% of the women, respectively) and also detected more X-chromosomal mosaicism among the TS women (in 70% vs. 45 % of the women, respectively). In half of the women, tissue-specific differences between lymphocytes and buccal mucosal cells were found. Based on these results, we suggest the use of X/Y interphase FISH as a complement to karyotyping in order to obtain a more complete knowledge of the chromosome constitution of each individual with TS.

Adolescent↗

PubMed2001

Longitudinal variability of human immunodeficiency virus type 1 RNA viral load measurements by nucleic acid sequence-based amplification and NucliSens assays in a large multicenter study.

Human immunodeficiency virus type 1 (HIV-1) RNA measurements were evaluated within an externally controlled multilaboratory program. Three external standards (1.5 x 10(3) to 1.5 x 10(6) copies/ml) were included in 814 assay runs by four laboratories. Results indicate that HIV-1 RNA levels can be measured with a precision equal to that of the pre-highly active antiretroviral therapy era (standard deviations, +/-0.16 to 0.25 log10 units).

HIV Infections↗

PubMed2001

The envelope glycoprotein of friend spleen focus-forming virus covalently interacts with and constitutively activates a truncated form of the receptor tyrosine kinase Stk.

The Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein, gp55, which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). SFFV gp55 has been shown to interact with the Epo receptor complex, causing constitutive activation of various signal-transducing molecules. When injected into adult mice, SFFV induces a rapid erythroleukemia, with susceptibility being determined by the host gene Fv-2, which was recently shown to be identical to the gene encoding the receptor tyrosine kinase Stk/Ron. Susceptible, but not resistant, mice encode not only full-length Stk but also a truncated form of the kinase, sf-Stk, which may mediate the biological effects of SFFV infection. To determine whether expression of SFFV gp55 leads to the activation of sf-Stk, we expressed sf-Stk, with or without SFFV gp55, in hematopoietic cells expressing the Epo receptor. Our data indicate that sf-Stk interacts with SFFV gp55 as well as gp55(P), the biologically active form of the viral glycoprotein, forming disulfide-linked complexes. This covalent interaction, as well as noncovalent interactions with SFFV gp55, results in constitutive tyrosine phosphorylation of sf-Stk and its association with multiple tyrosine-phosphorylated signal-transducing molecules. In contrast, neither Epo stimulation in the absence of SFFV gp55 expression nor expression of a mutant of SFFV that cannot interact with sf-Stk was able to induce tyrosine phosphorylation of sf-Stk or its association with any signal-transducing molecules. Covalent interaction of sf-Stk with SFFV gp55 and constitutive tyrosine phosphorylation of sf-Stk can also be detected in an erythroleukemia cell line derived from an SFFV-infected mouse. Our results suggest that SFFV gp55 may mediate its biological effects in vivo by interacting with and activating a truncated form of the receptor tyrosine kinase Stk.

Animals↗

PubMed2001

Preimplantation genetic diagnosis (PGD): the Gothenburg experience.

BACKGROUND: A program for preimplantation genetic diagnosis of pre-embryos from patients with hereditary disorders was set up in our unit at Sahlgrenska University Hospital in 1994. The majority of the patients were carriers of X-chromosome linked disorders; a few patients were translocation carriers. In this paper we describe our experiences of our first 36 cycles, 30 gender determinations and six analyses of embryos with possible translocations. METHODS: Conventional hormone replacement treatment with intracytoplasmic sperm injection to fertilize the eggs followed by blastomere biopsy and fluorescent in situ hybridization at the eight cell stage was used for sexing as well as detection of translocations. RESULTS: Out of the 30 cycles in 13 patients for gender determination, blastomere biopsies could be carried out in 25 cycles. Transfer of normal female embryos (XX) was performed in 18 cycles, resulting in five pregnancies (pregnancy rate 27.8%) and an implantation rate of 20% per transfer. Three girls have been born. Hence the take home baby rate was 16.7% per transfer and 10% per started cycle. Six cycles (three patients) for detection of translocations in embryos were performed. Diagnosis was possible in four cycles. Transfer of normal embryos was carried out in one cycle. No pregnancy was achieved. CONCLUSION: Successful PGD in its clinical application demands close collaboration between a large group of specialists. Even so, the success rate is considerably lower than after conventional IVF or ICSI procedures. Taking into account the stress caused to the parents facing late interruption of pregnancy following conventional prenatal diagnosis we are convinced that this technique is well worthwhile continuing and refining.

Cytogenetic Analysis↗

PubMed2000

Apoptosis: a method for evaluating the cryopreservation of whole blood and peripheral blood mononuclear cells.

We sought to compare the effect of cryopreservation and storage at -30 degrees C, -70 degrees C and -150 degrees C of human whole blood versus matched peripheral blood mononuclear cell (PBMC) samples using apoptosis as an indicator of cell fitness. Following 10 weeks of storage the samples were thawed and assessed for viability (trypan blue exclusion), levels of apoptosis (using the nuclear stain bis-benzimide) and cell function (ability to be transformed by Epstein-Barr virus, EBV). When comparing storage temperatures, the levels of apoptosis in whole blood and PBMC samples stored at -30 degrees C were significantly higher than the values for samples stored at -70 degrees C or -150 degrees C (P<0.004). Whole blood samples stored at -150 degrees C had significantly less apoptosis than those stored at -70 degrees C (P<0.03). A comparison of the cell preparations showed that at all three storage temperatures there was significant sample deterioration (viability, apoptosis, and function) in whole blood relative to PBMC samples. This study indicates that careful consideration should be given to storage conditions and that apoptosis can be used as a sensitive measure of cell fitness following cryopreservation.

Apoptosis↗

PubMed2000

Human immunodeficiency virus (HIV) type 1 antibodies in perinatal HIV-1 infection: association with human HIV-1 transmission, infection, and disease progression. For the Women and Infants Transmission Study.

Anti -human immunodeficiency virus (HIV) type 1 antibodies in 242 pregnant women and 238 infants were measured at birth and at 1, 2, 4, and 6 months after birth, to estimate their association with perinatal transmission and infant disease progression. Maternal anti-p24 (P=.01) and anti-gp120 (P=.04) antibodies were inversely associated with vertical transmission rates, independent of maternal percentage of CD4 cells, hard drug use, duration of ruptured membranes, serum albumin levels, serum vitamin A levels, and quantitative HIV-1 peripheral mononuclear blood cell culture, but not with maternal plasma immune complex dissociated p24 or HIV-1 RNA copy number, both of which were highly correlated with antibodies. From ages 1-2 months, anti-gp120, -gp41, -p31, and -p66 decayed to a greater extent in infected than in uninfected infants. Infected infants produced anti-p24 antibody by age 2 months, anti-p17 by 4 months, and anti-p41 and anti-gp120 by 6 months. As early as birth, infants with rapid disease progression had lower levels of anti-p24 than did infants whose disease did not rapidly progress, but not independently of HIV-1 RNA levels.

Cohort Studies↗

PubMed2000

AIDSVAX (MN) in Bangkok injecting drug users: a report on safety and immunogenicity, including macrophage-tropic virus neutralization.

A randomized, double-blind, placebo-controlled phase I/II study of AIDSVAX (MN) was conducted among injecting drug users in Bangkok, Thailand. Four doses of vaccine (300 microg of MN-rgp120 in alum) or placebo (alum) were given at study entry and at 1, 6, and 12 months. The objectives of the study were to evaluate (1) the feasibility of conducting vaccine trials in this population; (2) the safety of this candidate AIDS vaccine; and (3) the immunogenicity of this vaccine. Thirty-three volunteers (22 vaccine and 11 placebo recipients) were recruited. None were lost to follow-up during the 18-month study. Mild reactogenicity was noted, which was similar in both vaccine and placebo recipients. The vaccine induced anti-HIV-1 antibody in all vaccine recipients. Maximal titers of binding antibodies of MN-rgp120 and the V3 domain of MN-rgp120 were induced after the third (6 month) dose while maximal neutralizing antibodies followed the fourth (12 month) dose. The vaccine-induced antibodies from several volunteers were capable of neutralizing macrophage-tropic, subtype B viruses (301660 and JRCSF) detected in a PBMC-based assay. Binding and neutralizing antibodies declined about 10-fold in the 6 months after the last boost. Two vaccinees became infected during the trial, both with subtype E viruses. A phase III efficacy trial, using a bivalent gp120 vaccine containing antigens from a subtype B virus (MN) and a subtype E virus (A244), was initiated in March 1999 in injecting drug users in Bangkok.

AIDS Vaccines↗

PubMed2000

HIV-1 genotypic zidovudine drug resistance and the risk of maternal--infant transmission in the women and infants transmission study. The Women and Infants Transmission Study Group.

OBJECTIVES: Although the treatment of pregnant women and their infants with zidovudine (ZDV) has been remarkably effective in preventing the perinatal transmission of human HIV-1, many potentially preventable infections still occur. To examine whether the risk of perinatal infection is increased among women who carry ZDV-resistant HIV-1, the role of genotypic ZDV resistance in perinatal transmission was evaluated. METHODS: The reverse transcriptase (RT) region of clinical isolates from culture supernatants of 142 HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS), who had been treated with ZDV during pregnancy was sequenced. Results from genotypic sequencing were linked to demographic, laboratory, and obstetrical databases, and the magnitude of association of having consensus drug-resistant HIV-1 RT mutations with transmission was estimated. RESULTS: Twenty-five per cent (34/142) of maternal isolates had at least one ZDV-associated resistance mutation. A lower CD4 cell percentage and count (P= 0.0001) and higher plasma HIV-1 RNA (P=0.006) were associated with having any ZDV resistance mutation at delivery. Having any RT resistance mutation [odds ratio (OR): 5.16; 95% confidence interval (CI): 1.40, 18.97; P=0 0.01], duration of ruptured membranes [OR: 1.13 (1.02, 1.26) per 4 h duration; P= 0.02], and total lymphocyte count [OR: 1.06 (1.01, 1.10) per 50 cells higher level; P=0.009] were independently associated with transmission in multivariate analysis. CONCLUSION: Maternal ZDV resistant virus was predictive of transmission, independent of viral load, in these mothers with moderately advanced HIV-1 disease, many of whom had been treated with ZDV before pregnancy.

Anti-HIV Agents↗

PubMed2000

Ear and hearing in relation to genotype and growth in Turner syndrome.

Hearing loss, auricular anomalies and middle ear infections are common findings in many genetic disorders, but the mechanisms have remained unknown. We studied ear and hearing problems in Turner's syndrome (TS) in relation to the degree of X chromosome loss (i.e. degree of mosaicism) and growth. One hundred and nineteen girls and women with TS were studied regarding audiometry, fluorescent in situ hybridisation, serum concentration of insulin-like growth factor-1 (IGF-1) and body height. It was found that sensorineural hearing loss and occurrence of auricular anomalies were significantly increased the greater the proportion of 45,X cells in a particular individual (P<0.05 and P<0.001, respectively). Middle ear infections and sensorineural hearing loss were negatively correlated with IGF-1 (P<0.05 and P<0.001, respectively). Hearing correlated positively with height (P<0.01) and IGF-1 independently of age (P<0.05). Height correlated positively with IGF-1 (P<0.001). Auricular malformations, middle ear infections and hearing impairment in TS were interpreted as due to growth disturbances during development. A new hypothesis on the pathophysiology of external, middle and inner ear disorders due to a delayed cell cycle caused by chromosomal aberrations per se and not only to the specific X chromosome deletion is presented.

Adolescent↗

PubMed2000

Growth factor-independent proliferation of erythroid cells infected with Friend spleen focus-forming virus is protein kinase C dependent but does not require Ras-GTP.

Interaction of erythropoietin (Epo) with its cell surface receptor activates signal transduction pathways which result in the proliferation and differentiation of erythroid cells. Infection of erythroid cells with the Friend spleen focus-forming virus (SFFV) leads to the interaction of the viral envelope glycoprotein with the Epo receptor and renders these cells Epo independent. We previously reported that SFFV induces Epo independence by constitutively activating components of several Epo signal transduction pathways, including the Jak-Stat and the Raf-1/mitogen-activated protein kinase (MAPK) pathways. To further evaluate the mechanism by which SFFV activates the Raf-1/MAPK pathway, we investigated the effects of SFFV on upstream components of this pathway, and our results indicate that SFFV activates Shc and Grb2 and that this leads to Ras activation. While studies with a dominant-negative Ras indicated that Ras was required for Epo-induced proliferation of normal erythroid cells, the Epo-independent growth of SFFV-infected cells can still occur in the absence of Ras, although at reduced levels. In contrast, protein kinase C (PKC) was shown to be required for the Epo-independent proliferation of SFFV-infected cells. Further studies indicated that PKC, which is thought to be involved in the activation of both Raf-1 and MAPK, was required only for the activation of MAPK, not Raf-1, in SFFV-infected cells. Our results indicate that Ras and PKC define two distinct signals converging on MAPK in both Epo-stimulated and SFFV-infected erythroid cells and that activation of only PKC is sufficient for the Epo-independent proliferation of SFFV-infected cells.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Erythroid cells rendered erythropoietin independent by infection with Friend spleen focus-forming virus show constitutive activation of phosphatidylinositol 3-kinase and Akt kinase: involvement of insulin receptor substrate-related adapter proteins.

The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). In an effort to understand how SFFV causes Epo independence, we have been examining erythroid cells rendered factor independent by SFFV infection for constitutive activation of signal-transducing molecules. Previous studies from our laboratory showed that various signal-transducing molecules known to be activated by Epo, including Stat proteins and components of the Raf-1/MAP kinase pathway, are constitutively activated in SFFV-infected erythroid cells in the absence of Epo. Since another signal transduction pathway involving activation of phosphatidylinositol 3-kinase (PI 3-kinase) after Epo stimulation plays an important role in erythroid cell proliferation and differentiation, we carried out studies to determine if this pathway was also activated in SFFV-infected cells in the absence of Epo. Our studies show that PI 3-kinase is constitutively activated in erythroid cells rendered factor independent by infection with SFFV and that PI 3-kinase activity, but not Epo receptor tyrosine phosphorylation, is required for the proliferation of these cells in the absence of Epo. We further show that in SFFV-infected erythroid cells grown in the absence of Epo, PI 3-kinase associates with the insulin receptor substrate (IRS)-related adapter molecules IRS-2, Gab1, and Gab2, which are constitutively tyrosine phosphorylated in SFFV-infected cells. Finally, Akt, a protein kinase that is one of the downstream effectors of PI 3-kinase, and SHIP, a lipid phosphatase that is important for Akt activation through PI 3-kinase, are both tyrosine phosphorylated in SFFV-infected cells grown in the absence of Epo. Our results indicate that induction of Epo independence by SFFV requires the activation of PI 3-kinase and suggest that constitutive activation of this kinase in SFFV-infected cells may occur primarily through interaction of PI 3-kinase with constitutively phosphorylated IRS-related adapter molecules.

Enzyme Activation↗

PubMed2000

Prevention of hypoinsulinemia modifies catecholamine effects in fetal sheep.

Increased epinephrine (Epi) and norepinephrine (NE) production plays an important role in fetal adaptation to reduced oxygen and/or nutrient availability, inhibiting insulin secretion and slowing growth to support more essential processes. To assess the importance of hypoinsulinemia for the efficacy of catecholamines, normoinsulinemia was restored by intravenous insulin infusion (0.18 mU. kg(-1). min(-1)) during prolonged infusion of either Epi (0.25-0. 35 microgram. kg(-1). min(-1) for 12 days, n = 7) or NE (0.5-0.7 microgram. kg(-1). min(-1) for 7 days, n = 6) into normoxemic fetuses in twin-pregnant ewes, from 125-127 days of gestation. Insulin infusion for 8 days during Epi infusion or for 4 days during NE infusion decreased arterial blood pressure, O(2) content, and plasma glucose, but increased heart rate significantly (all P <0.05), despite continuation of Epi or NE infusion. Cessation of insulin infusion reversed these changes. Estimated growth of fetuses infused with insulin during Epi or NE infusion (55 +/- 13.9 and 83 +/- 15.2 g/day) did not differ significantly from that of untreated controls (72 +/- 15.4 g/day, n = 6). Growth of selected muscles and hindlimb bones was not altered either. Restoration of normoinsulinemia evidently counteracts the redistribution of metabolic activity and decreased anabolism brought about by Epi or NE in the fetus. Inhibition of insulin secretion by Epi and NE, therefore, appears essential for the efficacy of catecholamine action in the fetus.

Animals↗