Colonoscopic diagnosis of grumbling appendicitis.
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Adult↗
Biomedical subjects
T R Johnson
Publications and source records attributed to T R Johnson.
Population differences affect the interpretation of fetal nonstress test results.
OBJECTIVE: The object of the study was to determine whether population differences exist with respect to outcomes of women with reactive and nonreactive nonstress test results. STUDY DESIGN: An epidemiologic evaluation was conducted on 2579 women who underwent nonstress tests in the Fetal Assessment Center of the Johns Hopkins Hospital within a week of delivery. Risk factors such as hypertension, diabetes, and postterm pregnancy were used in a logistic regression model to evaluate the ability of the nonstress test to predict outcomes including proxies of fetal distress and fetal and neonatal death. The sensitivities, specificities, and predictive values of the nonstress test for predicting these outcomes in cohorts of black and white women were also determined. RESULTS: The nonstress test was consistently more sensitive for black women than for white women in predicting several perinatal outcomes, but specificity and negative predictive value were consistently lower for black women. The positive predictive value for fetal and neonatal death was higher for white women than for black women. Although the nonreactive nonstress test result seemed to be predictive of certain perinatal events, the odds ratio for predicting perinatal mortality in any study population was no greater than when the nonstress test result was reassuring. CONCLUSIONS: Epidemiologic characteristics affecting test results, such as disease prevalence and population differences, may lead to clinically significant differences in outcome prediction when these tests' results are used. These differences should be considered in the implementation of antepartum fetal testing programs.
Adult↗
Exposure to 60 Hz magnetic fields and risk of lymphoma in PIM transgenic and TSG-p53 (p53 knockout) mice.
The results of a number of epidemiology studies suggest that exposure to power frequency (50 and 60 Hz) magnetic fields may be a risk factor for hematopoietic neoplasia. To generate experimental data to test this hypothesis, the influence of magnetic field exposure on lymphoma induction was determined in two strains of mice that are genetically predisposed to the disease. PIM mice, which carry the pim-1 oncogene, are highly sensitive to lymphoma induction by N-ethyl-N-nitrosourea (ENU); ENU-treated PIM mice were studied as a 'high incidence' lymphoma model. TSG-p53 (p53 knockout) mice, in which the p53 tumor suppressor gene has been deleted from the germ line, develop lymphoma as an age-related change; hemizygous TSG-p53 mice were studied as a 'low incidence' lymphoma model. Beginning 1 day after a single i.p. injection of 25 mg ENU/kg body wt, groups of 30 PIM mice/sex were exposed for 18.5 h/day to pure, linearly polarized, transient-free 60 Hz magnetic fields at field strengths of 0 (sham control), 0.02, 2.0 or 10.0 Gauss (G). An additional group of 30 PIM mice/sex was exposed intermittently (1 h on, 1 h off) to 10.0 G fields. Groups of 30 TSG-p53 mice/sex were exposed continuously to magnetic field strengths of 0 (sham control) or 10.0 G; TSG-p53 mice received no ENU. Studies were terminated after 23 weeks of magnetic field exposure. Lymphoma incidence in male PIM mice exposed continuously to 10.0 G magnetic fields was significantly reduced from that seen in sex-matched sham controls; survival, lymphoma incidence and lymphoma latency in other groups of PIM mice did not differ from sham controls. Survival and lymphoma incidence in all groups of TSG-p53 mice was 7% or less, regardless of magnetic field exposure regimen. These data do not support the hypothesis that exposure to magnetic fields is a significant risk factor for lymphoid neoplasia in mice with a genetic predisposition to the disease.
Animals↗
Priming with secreted glycoprotein G of respiratory syncytial virus (RSV) augments interleukin-5 production and tissue eosinophilia after RSV challenge.
The respiratory syncytial virus (RSV) G glycoprotein promotes differentiation of type 2 CD4+ T lymphocytes and induces an eosinophilic response in lungs of RSV-infected mice. A unique feature of G is that a second initiation codon in the transmembrane region of the glycoprotein results in secretion of soluble protein from infected cells. Recombinant vaccinia viruses that express wild-type G (vvWT G), only secreted G (vvM48), or only membrane-anchored G (vvM48I) were used to define the influence of G priming on immunopathogenesis. Mice immunized with vvM48 had more severe illness following RSV challenge than did mice primed with vvWT G or vvM48I. Coadministration of purified G during priming with the construct expressing membrane-anchored G shifted immune responses following RSV challenge to a more Th2-like response. This was characterized by increased interleukin-5 in lung supernatants and an increase in G-specific immunoglobulin G1 antibodies. Eosinophils were present in the infiltrate of all mice primed with G-containing vectors but were greatest in mice primed with regimens including secreted G. These data suggest the form of G protein available for initial antigen processing and presentation is an important factor in promoting Th2-like immune responses, including the induction of lung eosinophilia. The ability of RSV to secrete G protein may therefore represent a viral strategy for immunomodulation and be a key determinant of disease pathogenesis.
Animals↗
Fetal neurobehavioral development: associations with socioeconomic class and fetal sex.
This longitudinal study investigated neurobehavioral development in the human fetus from 24 to 36 weeks gestation. Subject (N=103) were stratified by socioeconomic class. Fetal data were collected for 50 min at three intervals, and included measures of heart rate, movement, and biobehavioral patterns. Repeated measures analysis of variance by fetal sex and maternal socioeconomic status was used to detect maturation effects and group differences. With advancing gestation, fetuses exhibited reduced heart rate, increased heart rate variability and coupling between movement and heart rate, increased movement vigor, and more biobehavioral concordance. Male fetuses displayed higher heart rate variability throughout gestation and somewhat earlier emergence of biobehavioral organization than females. Fetuses of women of lower socioeconomic status had reduced heart rate variability, moved less often and with less vigor, showed less coupling between movement and heart rate, and had fewer episodes of synchronous quiescence/activity. Results are discussed in terms of development of the central nervous system.
Brain↗
Suppression of insulin-like growth factor type I receptor by a triple-helix strategy inhibits IGF-I transcription and tumorigenic potential of rat C6 glioblastoma cells.
Homopurine (AG) and homopyrimidine (CT) oligodeoxyribonucleotides predicted to form triple-helical (triplex) structures have been shown to specifically suppress gene expression when supplied to cultured cells. Here we present evidence that homopurine RNA (effector) sequences designed to form a triplex with a homopurine. homopyrimidine sequence 3' to the termination codon of the insulin-like growth factor type I receptor (IGF-IR) structural gene can efficiently suppress IGF-IR gene transcription. Transfection vectors were constructed to drive transcription of either AG or CT variant triplex-forming strands. To increase the probability of obtaining stable transfectants with adequate expression of effector sequences, these were designed to be transcribed together with cDNA sequences conferring neomycin resistance as a fusion transcript. Rat C6 glioblastoma cells transfected with the AG variant showed dramatic reduction of IGF-IR transcripts compared with untransfected cells. The AG transfectants also exhibited marked down-regulation of the IGF-I, and an enhanced accumulation of serine protease inhibitor nexin-I mRNA. Similar changes in gene expression were observed following transfection of C6 cells with constructs transcribing antisense RNA to IGF-IR transcripts, but were not observed in C6 cells transfected with either the CT triplex variant or with vector lacking triplex-forming sequences. Moreover, C6 cells transfected with AG triplex variant displayed a dramatic inhibition of tumor growth when injected into nude mice. The results suggest that a triple-helix strategy can be used to inhibit transcription elongation of the IGF-IR gene, and emphasize the efficacy of triplex-mediated gene inhibition in an animal model.
Amyloid beta-Protein Precursor↗
Eight-week toxicity study of 60 Hz magnetic fields in F344 rats and B6C3F1 mice.
Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice (10 animals per sex per species per group) to transient-free, linearly polarized 60 Hz magnetic fields for 8 weeks. Targeted magnetic fields strengths used were 0 gauss (G; sham control fields did not exceed 0.001 G), 0.02 G, 2 G, and 10 G. Exposure was whole-body and continuous for 18.5 hr per day, 7 days per week. An additional group of rats and mice was exposed intermittently (1 hr on/1 hr off) to 10 G fields for the same period of time. Endpoints evaluated included morbidity, mortality, gross pathology, histopathology, body/organ weights, clinical chemistry (rats only), and hematology (rats only). All mice and all male rats survived until the end of the study. One female rat (2-G exposure group) died during Week 7 of the study; the death was not attributed to magnetic field exposure. In both studies, the mean body weight gains of exposed animals were similar to those of the respective controls. There were no gross, histological, hematological, or biochemical lesions attributed to magnetic field exposure. Statistically significant increases in liver weight and liver to body weight ratio occurred in female rats of all exposure groups but only at the termination. These data suggest that, for the variables evaluated in these studies, an 8-week exposure to linear-polarized, transient-free 60 Hz magnetic fields at field intensities of up to 10 G is not associated with significant toxicity in F344/N rats and B6C3F1 mice. Furthermore, there was no toxicity observed in animals receiving intermittent (1 hr on/1 hr off) exposures to 10-G fields. A 2-year study in F344/N rats and B6C3F1 mice is nearing completion of the in-life phase without overt toxicity in any exposed group. It is premature, however, to make any prediction concerning the possible influence of exposure to 60 Hz magnetic fields on cancer rates.
Animals↗
Obstetrician-gynecologists and the public health.
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Adolescent↗
Complementary and non-coincident increases in heart rate variability and irregularity during fetal development.
1. Two distinct notions of variability have been defined to assess heart rate: deviation from a constant output (SD) and irregularity. One statistical measure of irregularity is approximate entropy, with greater irregularity corresponding to larger approximate entropy values. The specific aims of this investigation were to determine the manner in which SD and irregularity evolve during fetal development and whether this evolution is coincident or distinct. 2. Fetal heart rate was computed in 14 males and 17 females for 15 min of undisturbed recording using a fetal actocardiograph at 4 week intervals from 20 to 36 weeks gestation. 3. Mean heart rate decreased significantly with gestational ages (P < 0.05). SD increased significantly from 4.4 +/- 0.3 ms (SEM) at 20 weeks to 7.7 +/- 0.4 ms at 36 weeks (P < 0.05) and was similar between male and female fetuses (P = 0.57). Fixed approximate entropy increased significantly from 0.47 +/- 0.04 to 0.78 +/- 0.03, paralleling the change in SD (P < 0.01). Notably, normalized approximate entropy, which decorrelates SD from regularity, increased significantly with gestational age (P < 0.01) for males, while it remained relatively constant for females (P = 0.68). Approximate entropy was significantly lower at 20 weeks in males than females (P < 0.05); however, the values were similar by 28 weeks gestation. 4. Our results demonstrate that variability increases, and that irregularity increases, independently in male fetuses but not female fetuses, consistent with an increase in the coupling of emerging networks with gestational age. The present study demonstrates the complementary information obtained by analyses of both measures of variability and regularity. This reinforces a difference in gender-based development as noted in the separate context of fetal lung maturation.
Electrocardiography↗
Increase in ambient temperature may explain decrease in amniotic fluid index.
In the third trimester, the amniotic fluid index (AFI) may be affected by maternal fluid status. As the ambient temperature increases, there is an increase in insensible fluid loss and the potential for dehydration. We hypothesize that as temperature increases there would be a concomitant decrease in AFI. From June 11 to August 16, 1993, during a period of unusual high heat, 42 women with singleton pregnancies between 27 and 40 weeks' gestation undergoing serial antenatal testing had AFI determinations recorded at least weekly. The daily high ambient temperature in our urban area was subsequently obtained. A 2-, 3-, and 4-day mean temperature prior to the test date was compared to AFI using a Spearman-rank Correlation. The daily high temperature ranged from 71 to 104 degrees F and AFI values ranged from 1.7 to 24.7 cm during the study period. There was a significant correlation between the 2-, 3-, and 4-day mean temperature and AFI, with the 4-day mean being the most significant (r = 0.31, p < 0.001). Fluctuations in ambient temperature are inversely correlated to changes in AFI. This relationship should be taken into account when interpreting the AFI as a measure of fetal well-being.
Adult↗
Overexpression of interleukin-4 delays virus clearance in mice infected with respiratory syncytial virus.
Although interleukin-4 (IL-4) expression has been implicated in vaccine-enhanced respiratory syncytial virus (RSV) disease, its role in mediating the immune response to primary RSV infection remains unclear. To assess the effect of IL-4 production on typical RSV infection, transgenic mice which either overexpress or fail to express IL-4 were challenged intranasally with RSV and their responses were compared to those of the parent strains. IL-4-deficient mice eliminated virus from the lung as quickly as did C57BL/6 controls. In contrast, mice which constitutively overexpress IL-4 showed delayed virus clearance compared with mice of the FVB/N control strain, although peak viral titers did not differ. IL-4 overexpression increased the magnitude of the subsequent antibody response. Lung lymphocytes harvested from IL-4-overexpressing mice post-RSV challenge showed diminished RSV-specific cytolytic activity compared with controls. Both IL-4-deficient and IL-4-overexpressing strains resisted rechallenge. These data imply that constitutive IL-4 expression delays or suppresses the development of a virus-specific cytotoxic lymphocyte population important in clearing primary RSV infection.
Animals↗
Effects of dietary supplementation on nutrient digestion and the milk yield of intensively grazed lactating dairy cows.
Fourteen midlactation Holstein cows were used in an 80-d study to examine supplementation strategies during intensive rotational grazing. Factors examined were the concentration of protein in the supplement [12 or 16% crude protein (CP) on a dry matter basis] and the amount of supplement offered (6.4 or 9.6 kg/d per cow). The supplement was offered in equal portions three times daily after milking. Pasture, composed of alfalfa (Medicago sativa) and orchardgrass (Dactylis glomerata), was divided into 27 0.16-ha paddocks that were grazed for 12 to 24 h. Intake of forage tended to increase as CP in the supplement increased but was unaffected by the amount of supplement offered. Intakes of organic matter and dry matter and the digestion of these nutrients in the total tract increased as CP in the supplement increased and as the amount of supplement increased. Ruminal pH and concentrations of volatile fatty acids were unaffected by treatments, but concentrations of NH3 N increased as CP in the supplement increased. An increase in CP resulted in a greater intake and flow of total N to the duodenum. The flow of microbial N to the duodenum and the efficiency of microbial protein synthesis were unaffected by treatment. Flows of total amino acids and essential amino acids to the duodenum tended to increase as CP in the supplement increased. Yield of fat-corrected milk and concentrations of fat and protein in milk were unaffected by treatment. These results suggested that the supply and digestion of nutrients in grazing dairy cows may be improved through an increase in the CP concentration of the supplement or the amount of supplement offered. However, effects on the yield of milk and milk components may be small.
Ammonia↗
Structure and chromosomal localization of the human homeobox gene Prox 1.
The genomic organization and nucleotide sequence of the human homeobox gene Prox 1 as well as its chromosomal localization have been determined. This gene spans more than 40 kb, consists of at least 5 exons, and encodes an 83-kDa protein. It shows 89% identity with the chicken sequence at the nucleotide level in the coding region, while the human and chicken proteins are 94% identical. Among the embryonic tissues analyzed (lens, brain, lung, liver, and kidney), the human Prox 1 gene is most actively expressed in the developing lens, similar to the expression pattern of the chicken Prox 1 gene. The Prox 1 gene was mapped to human chromosome 1q32.2-q32.3.
Adult↗
Development of fetal movement--fetal heart rate coupling from 20 weeks through term.
This study documents the development of fetal heart rate (FHR) change in response to fetal movement (FM) in healthy fetuses from 20 weeks' gestational age through term. Thirty-one fetuses received 50 min of Doppler-based monitoring at 20, 24, 28, 32, 36 and 38-39 weeks. FHR and FM were continuously digitized. A coupling index was computed as the percentage of FMs associated with increases in FHR of 5 beats/min or more within -5 or +15 s of movement onset. The latency between FM onset and FHR change was also computed, as were the amplitude and duration of all movements. FM and FHR became more integrated with advancing gestation. Coupling increased and the latency between FM and FHR changes decreased. Maternal age, blood pressure and fetal sex did not affect FM-FHR coupling, but fetuses of women who reported greater stress in their daily lives and had faster heart rates displayed reduced coupling. These data suggest that the development of FM-FHR coupling reflects the development of the central nervous system during gestation, and that development may be affected by maternal factors.
Adult↗
Developmental toxicity study of 60 Hz (power frequency) magnetic fields in rats.
Considerable public concern has developed regarding possible adverse reproductive outcomes resulting from exposure to power frequency magnetic fields (MF). To identify possible effects of MF exposure on fetal development, timed-pregnant female Sprague-Dawley rats (55/ group) received continuous exposure to linearly polarized, transient-free 60 Hz MF at field strengths of 0 Gauss (G; sham control), 0.02 G, 2 G, or 10 G, or intermittent (1 hr on/1 hr off) exposure to 10 G fields. Dams received MF or sham exposures for 18.5 hr/day on gestation days 6 through 19. A positive control group of 15 dams received daily oral doses of 85 mg ethylenethiourea (ETU)/kg body weight on gestation days 11, 12, and 13; positive control dams received no MF exposure. Ambient and experimentally generated MF were monitored continuously throughout the study. Experimentally generated MF were within 2% of the target field strengths at all times, and ambient MF to which sham controls were exposed did not exceed 0.7 mG at any point in the study. No evidence of maternal toxicity was identified in any MF-exposed dam; mean maternal body weight and organ weights in groups exposed to MF did not differ from those in sham controls. Comparisons of fetal viability and body weight demonstrated no biologically significant differences between MF-exposed groups and sham controls. Similarly, a battery of gross external, visceral, skeletal, and cephalic examinations demonstrated no significant differences in the incidence of fetal malformations or anomalies in MF-exposed groups vs. sham controls. By contrast, 100% of the fetuses in the positive control group treated with ETU demonstrated malformations and reduced body weight. Exposure of pregnant Sprague-Dawley rats to 60 Hz at field strengths up to 10 G during gestation days 6-19 did not produce biologically significant effects in either dams or fetuses. These results do not support the hypothesis that exposure to pure, linearly polarized 60 Hz MF is a significant risk factor for the developing fetus.
Abnormalities, Drug-Induced↗
Changes in immunologic cell surface markers during cocaine withdrawal in pregnant women.
To evaluate the effects of acute cocaine withdrawal on the immune system of pregnant women, we analyzed changes in a panel of cell surface markers and plasma proteins that have immunological importance. The cell surface markers included complement receptors [CR1 (CD35), CR2 (CD21), CR3 (CD11b, CD18)], immunoglobulin Fc receptors [FcgammaRII (CD32), FcgammaRIII (CD16)], proteins important for lymphocyte function [CD3, CD4, CD8, CD19, CD25, CD45RA], and the framework antigen HLA-ABC. We also measured levels of the plasma proteins C3, C4, IgG, IgM, and IgA, along with the cytokine interleukin-2, soluble lymphocyte markers sCD25, sCD4, sCD8, IL-2, and soluble immune complexes. While no significant changes were seen in the levels of plasma proteins, changes paralleling the course of acute withdrawal were seen in complement receptors and immunoglobulin Fc receptors on leukocyte subpopulations. By contrast, proteins important for lymphocyte function were relatively unperturbed. There was an increase in receptor expression at the onset of withdrawal that peaked 3-5 days after last cocaine use, followed by a decrease in expression to initial (pre-withdrawal) levels. These changes in cell surface receptors may reflect altered immune function in the women who were withdrawing from cocaine.
Adult↗
Immune function and host defense in rodents exposed to 60-Hz magnetic fields.
This study was conducted to evaluate the influence of subchronic exposure to pure, linearly polarized 60-Hz magnetic fields (MF) on the host immune response in mice. The experimental design was as follows: three groups were exposed continuously (18.5 hr/day) to MF at field strengths of 0.02, 2, or 10 gauss (G), one group was exposed intermittently (1 hr on/1 hr off) to MF at a field strength of 10 G, and one group served as a sham control. Experimental endpoints included spleen and thymus weights and cellularity, antibody-forming cell (AFC) response, delayed-type hypersensitivity (DTH) response, splenic lymphocyte subset analysis, susceptibility to infection with Listeria monocytogenes, and natural killer (NK) cell activity. No differences in body weight, lymphoid organ weight, or lymphoid organ cellularity were observed in any MF-exposed group in comparison to sham controls. Likewise, no statistically significant differences were found in comparisons of AFC responses. Isolated statistically significant differences from control were observed in MF-exposed mice in the DTH assay, although no clear dose-related pattern of altered activity was seen. Splenic lymphocyte subset parameters examined were within normal limits in all groups, and no differences between control and MF-exposed mice were found. Host resistance to bacterial infection was not altered at any MF exposure examined in this study. Finally, although apparently dose-related, statistically significant alterations were observed in an initial study of NK cell function, repeat studies failed to demonstrate a consistent pattern of alteration.
Animals↗
Surgery for pancreatic tumors during pregnancy: a case report and review of the literature.
Seven cases of surgery of pancreatic tumors during pregnancy have been reported in the literature. Six of the cases resulted in live term births. The patient discussed herein, a 37-year-old para 2-0-0-2 white female, had surgery for the removal of a pancreatic mass at 20 2/7 weeks' gestation. No intraoperative complications occurred, and both mother and fetus appeared to have done well. The postoperative course was complicated by pseudomembranous enterocolitis caused by C. difficile, which was treated with antibiotics. Despite treatment, diarrhea continued, and the patient was readmitted to the hospital for hydration and further antibiotics at 27 weeks. Three days after admission, the fetus was noted to have poor biophysical testing and a caesarean delivery was performed. The infant was found to have a large intracerebral hemorrhage, which most likely occurred antenatally, and life support was discontinued shortly after birth. We conclude from this that surgery for a pancreatic mass in pregnancy should be approached cautiously, and the risk to both the mother and fetus should be considered.
Adult↗