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Biomedical subjects

T R Johnson

Publications and source records attributed to T R Johnson.

At least 127 records · Page 7Linked to original sources

RedSoar--a system for red blood cell antibody identification.

The primary goal of our research is to build an intelligent tutoring system for red blood cell antibody identification. In this paper, we describe the basis for a tutoring system--an expert system called RedSoar. RedSoar is built from two task-specific architectures that were designed for building flexible systems (i.e. systems that can use a variety of problem-solving strategies, and to which knowledge can easily-be added). RedSoar solves the antibody identification task correctly 81% of the time and new knowledge can be added in a straightforward manner. The system is capable of exhibiting human-like behavior which we believe is a necessary condition for building a successful tutoring system.

Blood Grouping and Crossmatching↗

Activity patterns in a panel of outdoor workers exposed to oxidant pollution.

We investigated summer activity patterns in a panel of volunteers drawn from a population segment with potentially high exposure to ambient oxidant pollution. The subjects were 15 men and 5 women aged 19-50, all of whom worked outdoors in the Los Angeles area at least 10 hr per week. The general approach was to (i) calibrate the relationship between ventilation rate (VR) and heart rate (HR) for each subject in controlled exercise; (ii) have subjects monitor their own normal activities with diaries and electronic HR recorders; (iii) estimate VR from HR recordings; and (iv) relate VR with diary descriptions of activities. Calibration data were fit to the equation log (VR) = (intercept) + (slope x HR), intercept and slope being determined separately for each individual to provide a specific equation to predict her/his VR from measured HR. Individuals' correlation coefficients relating log (VR) with HR ranged from 0.83 to 0.95. Subjects monitored themselves for three 24-hr periods during one week, including their most active work day and their most active non-work day. They wore Heart Watch(R) athletic training instruments which recorded HR once per minute; and recorded each change in their activity, location, or breathing rate in diaries. Breathing rates were classified as sleep, slow (like slow or normal walking), medium (like fast walking), or fast (like running). Diaries showed that sleep occupied about 33% of subject's time, slow activity 59%, medium 7%, and fast 1%. Fast activity was reported only at leisure, never at work. For the group, arithmetic means and standard deviations of predicted VR were 7 +/- 3 L/min for sleep, 12 +/- 7 for slow activity, 14 +/- 8 for medium, and 44 +/- 36 for fast. For the group and for most individuals, distributions of predicted VR within a given activity level (breathing rate) were approximately lognormal, with many values in a narrow range below the arithmetic mean and fewer values in a broader range above it. In the most active individuals, predicted VR exceeded 100 L/min for a total of 5 to 30 min during the three days. These data should prove useful in estimating outdoor workers' inhaled doses of ambient pollutants at existing or projected levels of air quality. Activity diary records are of significant value in pollutant dose estimation, but concurrent heart rate recording improves the estimates substantially.

Adult↗

Gestational age assessment in preterm neonates weighing less than 1500 grams.

Postnatal assessment of gestational age in preterm neonates traditionally has been performed using the methods of Dubowitz and Ballard. This study was designed to determine the accuracy of these methods in a sample of very low birth weight preterm neonates. Dubowitz and Ballard examinations were done on 110 preterm neonates within the first 72 hours of life by a neonatologist masked to the gestational age assessed antenatally. Mean birth weight was 1066 +/- 256 g (SD). These data were compared with gestational age assessments using last menstrual period and best obstetric estimate calculated by an obstetrician unaware of the neonatal examination. Mean gestational age using last menstrual period was 28.3 +/- 2.9 weeks. Mean differences between last menstrual period and Dubowitz/Ballard were -2.8 +/- 2.1 weeks and -2.6 +/- 2.2 weeks, respectively. Results using best obstetric estimate were similar. An ophthalmologist examined lens vessels of 89 neonates. A similar pattern toward overestimation of gestational age interval by Dubowitz/Ballard was seen at each lens vessel grade. The Dubowitz and Ballard examinations are inaccurate methods of assessing gestational age in preterm neonates with birth weights less than 1500 g.

Birth Weight↗

Enhanced expression of factor XII (Hageman factor) in isolated livers of estrogen- and prolactin-treated rats.

Estrogens and prolactin may raise the plasma titer of factor XII (Hageman factor) by enhancing gene expression at the level of transcription and RNA processing, protein synthesis, or secretion (or a combination of these). Alternatively, these hormones may protect factor XII or its transcripts from degradation. Because the liver is a major site of factor XII synthesis, we studied the expression and metabolism of factor XII in isolated livers of estrogen- and prolactin-treated rats. All rats were ovariectomized to reduce the effect of endogenous estrogen and prolactin on the expression of factor XII. When a phosphorus 32-labeled factor XII complementary DNA probe for Northern blot analysis was used, increased factor XII messenger RNA was found in poly (A) RNA prepared from livers of estrogen- and prolactin-treated rats relative to those of untreated rats. Simultaneously, enhanced release of immunoreactive factor XII was noted when isolated liver perfusion techniques were used. Cycloheximide, an inhibitor of protein synthesis, blocked the hepatic release of immunoreactive factor XII in both hormone-treated and untreated rats, suggesting that factor XII translation was directly affected. The biologic half-life of injected rat iodine 125-labeled factor XII in estradiol- and prolactin-treated rats was not significantly different from that in untreated rats. By inference from these data, the high plasma titer of factor XII observed in estrogen- and prolactin-treated rats is caused by enhanced hepatic expression at both transcriptional and translational levels, as well as by increased secretion of factor XII.

Animals↗

Population differences affect nonstress test reactivity.

The nonstress test (NST) is the most widely used test of fetal well-being. Recently it has been suggested that race may play a role in NST reactivity. The objective of this research was to explore population variables in addition to race that may influence NST reactivity. Study subjects were 1263 black and 658 white women who underwent NST in the week preceding delivery at a tertiary facility. Retrospective analysis of data from a comprehensive database was conducted. It was found that the percentage of black women with a nonreactive NST was more than three times the percentage of white women, and that from 35 weeks' to 42 weeks' gestation there were significantly fewer reactive NSTs for blacks than for whites (P less than .05). Racial differences in NST results persisted in a logistic regression analysis controlling for several population variables including pregnancy complications and demographic and behavioral factors (odds ratio 3.81; 95% CI 3.03 to 4.78). Regression analysis also confirmed that gestational age, maternal education, epilepsy, and smoking significantly influenced NST reactivity. These results indicate that population differences in NST reactivity exist at our facility. Further prospective study of population determinants of NST reactivity is needed to determine how race, test indication, and other clinical, demographic, and behavioral variables should be used in interpretation of tests of fetal well-being. Standard criteria for NST testing may not be useful in all obstetrical populations.

Black People↗

Prolactin and plasma prostaglandin metabolite levels in patients undergoing nipple stimulation contraction stress tests.

Twenty-five patients undergoing nipple stimulation contraction stress tests were enrolled in this study. Plasma 13,14-dihydro, 15-keto prostaglandin F2 alpha and plasma prolactin concentrations were analyzed before and during the contraction stress tests. Prolactin concentrations were significantly higher (p less than 0.01) in patients who responded with a successful stress test versus those who did not. No significant changes were observed in the mean concentration of plasma 13,14-dihydro, 15-keto prostaglandin F2 alpha levels between the two groups.

Breast↗

Prevalence of human papillomavirus infections in term pregnancy.

The prevalence of human papillomavirus (HPV) infections in the lower genital tracts of pregnant and nonpregnant women was studied. Cervical and vaginal exfoliated cells were obtained during a routine pelvic examination in 45 pregnant women in early labor, and in 44 nonpregnant women. A detailed questionnaire with emphasis on sexual history and sexually transmitted diseases was administered. The two groups of women were comparable with respect to mean age, prior pregnancy experiences, and number of lifetime sexual partners. Compared with pregnant women, the nonpregnant women had a more frequent history of sexually transmitted diseases (61% versus 39%; p = 0.06), and of genital warts (16% versus 0%; p = 0.01). Utilizing Southern transfer and hybridization with 32P-labeled viral DNA probes for HPV types 6, 11, 16, 18, and 31, DNAs extracted from cervicovaginal exfoliated cells were assessed for HPV genomic sequences. HPV genomic sequences were identified in 25% of nonpregnant women compared with 13.5% of term pregnant women. This difference was not statistically significant (p = 0.26). Six HPV isolates identified in pregnant women were distributed as follows: type 6/11, 1; type 16, 1, type 31, 1; and unknown type, 3. Eleven isolates were identified in nonpregnant women and were distributed as follows: type 6/11, 2; type 16, 6; type 18, 2; and type 31, 1. HPV type 6/11, the type responsible for laryngeal papillomatosis of juvenile onset, was identified in 2% of the pregnant population and accounted for only one of six isolates. HPV DNA-positive pregnant and nonpregnant women were predominantly asymptomatic and had normal Papanicolaou smears and normal clinical examinations.

Adolescent↗

Transcription of the testis-specific mouse protamine 2 gene in a homologous in vitro transcription system.

Transcriptionally active nuclear extracts were prepared from mouse testes to study the transcription of the testis-specific mouse protamine 2 (Prm-2) gene in vitro. The testicular system is unique among mammalian in vitro transcription systems in regard to its temperature optimum. In extracts made from prepuberal testes, the temperature optimum for in vitro transcription of Prm-2 is 30 degrees C, similar to somatic in vitro systems. However, in adult testis extracts, the optimum temperature for Prm-2 transcription is 20 degrees C. The different temperature optima seen in vitro for prepuberal and adult testes extracts parallels in vivo physiological temperature sensitivities of the differentiating male germ cells. The testis system also differs from other in vitro transcription systems in its divalent metal cation and ionic strength requirements for optimal transcription. The mouse Prm-2 gene is maximally transcribed at a MgCl2 concentration of 3-5 mM and over a KCl concentration range of 40-100 mM. By using the testis in vitro transcription system to study the Prm-2 gene by deletion analysis, we have determined that positive promotion for the gene lies within the region -170 to -82 from the start of transcription. This region contains a putative Sp-1 binding site. Additional upstream sequences appear to repress Prm-2 transcription in a heterologous transcription system.

Animals↗

Transport of N1-methylnicotinamide by organic cation-proton exchange in rat liver membrane vesicles.

The characteristics of hepatic organic cation transport were examined in basolateral (blLPM) and canalicular (cLPM) rat liver plasma membrane vesicles, using the naturally occurring organic cation, N1-methylnicotinamide (NMN). In blLPM vesicles, an outwardly directed H+ gradient (pHin 5.9/pHout 7.9) stimulated [3H]NMN uptake compared with [3H]NMN uptake under pH-equilibrated conditions. The time course of [3H]NMN uptake exhibited a transient "over-shoot" phenomenon, consistent with active transport. The proton ionophore, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, had no effect on [3H]NMN uptake, demonstrating that pH-dependent [3H]NMN uptake was not the result of a H+ diffusion potential. An outwardly directed H+ gradient also stimulated [3H]NMN uptake under voltage-clamped conditions, consistent with electroneutral NMN-H+ exchange. Under conditions that effectively dissipated the H+ gradient, no active transport of [3H]NMN was observed. In the absence of a pH gradient, the intravesicular presence of NMN trans-stimulated the uptake of [3H]NMN. NMN-H+ exchange was differentiated from sinusoidal Na(+)-H+ exchange by determining sensitivity to amiloride. The substrate specificity of NMN-H+ exchange in blLPM vesicles was examined by determining the cis-inhibitory effects of typical endogenous and exogenous substrates of other epithelial organic cation-H+ exchangers. Kinetic analysis of initial rates of carrier-mediated [3H]NMN uptake over a NMN concentration range of 0.05-15 mM demonstrated that uptake occurred via two saturable transport systems, one a high-affinity low-capacity process and the other a low-affinity high-capacity type. In contrast, in cLPM vesicles, no pH gradient-dependent [3H]NMN uptake was demonstrated. These findings are consistent with the presence of an organic cation-H+ antiport on the sinusoidal membrane, with features distinct from the renal antiport, such as substrate specificity and membrane localization, that may account for differences in drug disposition by these two organs.

Amiloride↗

Doppler recordings of fetal movement: II. Comparison with maternal perception.

Twenty-seven women were studied to assess the relationship between maternally perceived fetal movement and that recorded by a Doppler device. Eighty-eight percent (433 of 492) of maternally perceived movements were detected by Doppler, but only 16% of movements detected by Doppler were maternally perceived (433 of 2196). When complex movements were classified by duration, those movements lasting between 20-60 seconds were most likely (correlation greater than 0.9) to be perceived by the mother. This Doppler method has the potential to replace maternal event marking and other techniques in the recording of fetal movement.

Adult↗

Hepatocytes express blood coagulation factor XII (Hageman factor).

The liver synthesizes blood coagulation factor XII (Hageman factor). The specific cell that expresses factor XII, however, has not been previously identified. We used primary rat hepatocytes cultured in serum-free medium to study the transcription, de novo synthesis, and secretion of factor XII. A 32P-labeled human factor XII complementary DNA probe was used for RNA blot hybridization. A single band of hybridization at 2.4 kilobases appeared in blots of polyadenylated RNA derived from 24-hour hepatocyte cultures. This corresponds to the known size of factor XII-processed primary transcript (messenger RNA). Cultured hepatocytes secreted labeled factor XII when tritiated leucine was added to the medium, indicating that the hepatocytes used 3H-leucine to synthesize factor XII de novo. In these hepatocyte cultures immunoreactive factor XII levels progressively increased in 24 hours and factor XII clotting activity increased in parallel. Cycloheximide inhibited the accumulation of both immunoreactive and coagulant factor XII. Secreted factor XII from the rat hepatocytes comigrated with authentic rat plasma factor XII at 80,000 molecular weight in a Western immunoblot. These data indicate that cultured hepatocytes transcribe, synthesize, and secrete authentic factor XII.

Animals↗

Inhibition of bile acid transport by cyclosporine A in rat liver plasma membrane vesicles.

In selectively isolated basolateral (bILPM) and canalicular (cLPM) rat liver plasma membrane vesicles, the in vitro effect of cyclosporine A (CsA) on specific hepatic membrane transport processes was examined. CsA (0.1-200 microM) caused a concentration-dependent inhibition of initial rates of Na(+)-dependent taurocholate uptake in bILPM and cLPM vesicles and Na(+)-independent taurocholate efflux from cLPM vesicles. In contrast, CsA had no effect on Na(+)-dependent L-alanine uptake in bILPM and in cLPM vesicles. In addition, electroneutral pH gradient-driven Na+ uptake in bILPM vesicles was unaffected by CsA treatment. CsA-induced inhibition of taurocholate transport in bILPM and cLPM vesicles was competitive in nature. A hydroxylated (OL-17) and a N-demethylated (OL-21) metabolite of CsA had no effect on taurocholate transport in either membrane vesicle population. These findings suggest that the mechanism of CsA-induced cholestasis is, in part, the result of selective inhibition of bile acid transport by the parent compound at both domains of the hepatocyte plasma membrane.

Alanine↗

Cyclic AMP-dependent protein kinase phosphorylates and inactivates the yeast transcriptional activator ADR1.

It has been proposed in several eukaryotic systems that the regulation of gene transcription involves phosphorylation of specific transcription factors. We report here that the yeast transcriptional activator ADR1 is phosphorylated in vitro by cyclic AMP-dependent protein kinase and that mutations which enhance the ability of ADR1 to activate ADH2 expression decrease ADR1 phosphorylation. We also show that increased kinase activity in vivo inhibits ADH2 expression in an ADR1 allele-specific manner. Our data suggest that glucose repression of ADH2 is in part mediated through a cAMP-dependent phosphorylation-inactivation of the ADR1 regulatory protein.

Aldehyde Dehydrogenase↗

Preterm and term fetal cardiac and movement responses to vibratory acoustic stimulation.

To assess fetal response to vibratory acoustic stimulation, 24 preterm (group A; less than 36 weeks' gestation) and 30 term (group B; greater than or equal to 36 weeks' gestation) pregnancies were studied. Study variables were perceived fetal movement, fetal heart rate, and fetal heart rate pattern. Observer- and patient-perceived fetal movement responses were noted in most cases but were slightly more common in term patients (group A: + fetal movement, patient 87.5%/observer 87.5%) group B: + fetal movement, patient 96.7%/observer 90%). Baseline changes in fetal heart rate (greater than or equal to 10 beats/min) were observed in 46% of preterm fetuses and 70% of term fetuses. Tachycardia (fetal heart rate greater than 160 beats/min) was a common finding in both groups. In group A, tachycardia after vibratory acoustic stimulation persisted more than 1 minute in 29.2% and more than 5 minutes in 12.5% of patients. In group B tachycardia beyond 1 and 5 minutes was noted in 73.3% and 50% of patients, respectively. A significant shift to "awake" fetal heart rate patterns occurred in both groups; 29% to 79% was noted in group A (p less than 0.001) and 46.7% to 90% in group B (p less than 0.001). When vibratory acoustic stimulation was used, the high occurrence of increased baseline, tachycardia, and emergence of unusual fetal heart rate patterns must be recognized to adequately interpret fetal heart rate tracings.

Acoustic Stimulation↗

Sinusoidal fetal heart rate pattern during breathing is related to the respiratory sinus arrhythmia: a case report.

The sinusoidal fetal heart rate pattern is a phenomenon of elusive pathophysiologic features and uncertain clinical significance. We present a case of sinusoidal fetal heart rate that occurred in association with fetal breathing. The degree and type of synchrony between the sinusoidal fetal heart rate and breathing movements suggest that the sinusoidal fetal heart rate and the respiratory sinus arrhythmia are related phenomena.

Adult↗

Expression of insulin-like growth factor I in cultured rat hepatocytes: effects of insulin and growth hormone.

The effects of GH and insulin the accumulation of insulin-like growth factor I (IGF-I) RNA transcripts and the secretion of immunoreactive IGF-I protein were studied in rat liver hepatocytes cultured in serum-free medium. GH at concentrations of 10 ng/ml or greater stimulated the accumulation of IGF-I RNA transcripts relative to actin transcripts in poly(A)+ RNA isolated from cultured hepatocytes. The time course of IGF-I transcript accumulation in response to GH appeared to be biphasic. The transcript levels rose dramatically during the first 2 h after exposure of the cultures to GH, declined between 3 and 6 h, but reaccumulated by 24 h after exposure to GH. The presence of insulin did not influence the effect of GH on the accumulation of IGF-I RNA transcripts, although insulin did elevate IGF-I transcript levels in the absence of GH. Analysis of RNA pulse-labeled with thiouridine followed by purification of the thiol-labeled RNA using mercurated agarose indicated that GH probably acts by increasing IGF-I transcription. Insulin also affected the release of immunoreactive IGF-I into the culture medium. In the presence of insulin, immunoreactive IGF-I accumulated in the culture medium to approximately the same extent over a 24-h period regardless of whether GH was also present. In the absence of insulin, immunoreactive IGF-I accumulated in the medium only if GH was present. The results suggest that insulin may play an important role in both IGF-I transcript accumulation and the secretion of IGF-I from cultured hepatocytes.

Animals↗

Doppler recording of fetal movement: clinical correlation with real-time ultrasound.

Processed Doppler signals can be used to detect fetal movements during antepartum fetal heart rate (FHR) testing. The purpose of this project was to evaluate the ability of a commercially available Doppler system, the Toitu Fetal Actocardiograph MT-320, to detect and discriminate various fetal activities during routine antepartum FHR testing. Simultaneous visualization with real-time ultrasound allowed correlation of isolated and complex fetal activities with the processed actograph signals. This apparatus was able to detect 95.9% of all major fetal movements observed, 94.3% of isolated fetal movements, 95.6% of isolated spinal flexion-extension, 97.1% of isolated rolling movements, and 100% of all multiple (P less than .001) fetal movements. Based on the amplitude (P less than .0001) and duration of the isolated actograph signals, it was possible to discriminate among fetal limb movements (mean amplitude 87.3 units, mean duration less than 2.0 seconds), spinal flexion-extension movements (66.3 units, 14.8 seconds), and rolling movements (43.8 units, 22.1 seconds). The routine detection of fetal breathing, hand movements, and rapid eye movements appears to be beyond the sensitivity of this particular apparatus. The ability to evaluate fetal activity reliably may be clinically useful during routine antepartum FHR testing.

Female↗

Improving a university hospital obstetric clinic: better but not best.

The Obstetric Clinic at the Johns Hopkins Hospital was evaluated on four occasions during the past 8 years. In 1980, there were major inefficiencies because of a block patient appointment system and late physician arrival. Clinic goals were largely undefined. The institution of a staggered appointment system, the naming of an on-site physician director who encouraged physicians to arrive on time, and the delegation of specific responsibilities to the nurses and clerks resulted in improved patient transit time. In 1981, 72% of patients had left by 2 hours after their arrival, compared with only 4% in 1980. The departure of the physician director was associated with considerable backsliding in patient transit time because of late physician arrival. There was a corresponding decrease in appointment-keeping from 90 to 78%. Patients were satisfied with their care but very dissatisfied with the waiting time. The return of the physician director and the reaffirmation of the roles of nurses and clerks reversed much of the backsliding. Our study suggests that improvements in teaching-hospital obstetric clinics are difficult to sustain without strong leadership. We believe that further improvement will require a major reorganization of ambulatory care for women. The feasibility of establishing a comprehensive program based on a group practice model is currently being studied.

Appointments and Schedules↗