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Biomedical subjects

R A Johnson

Publications and source records attributed to R A Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1993

Data on prior pesticide use collected from self- and proxy respondents.

Proxy respondents have often been used in case-control studies of cancer and pesticides. To evaluate the effect of exposure misclassification, we compared data collected during 1981-1983 from participants interviewed for a case-control study of leukemia and non-Hodgkin's lymphoma with data collected during 1990-1991 from proxy respondents for participants who died or became incompetent since the initial interview (328 self-proxy pairs). As questions increased in detail, agreement percentages decreased. Agreement percentages were highest for demographic and general farming information (averages = 88-90%) and lowest for specific pesticide use (averages = 68-74%). Generally, odds ratios calculated from proxy respondent data were less than those from self-respondent data; however, several exceptions occurred. The findings indicate that pesticide data provided by proxy respondents will not necessarily result in the same estimate of risk and/or lead to the same conclusions as data provided by self-respondents.

Adult↗
PubMed1993

Neurohumoral modulators and sodium balance in experimental heart failure.

The acute and chronic interactions of the renal nerves, atrial natriuretic factor (ANF), and mineralocorticoids for the regulation of sodium balance were examined in dogs with an arteriovenous (AV) fistula and the syndrome of high-output heart failure (HOHF) (n = 6). After the AV fistula and bilateral renal denervation, the animals avidly retained sodium for 5-7 days and then regained sodium balance for the subsequent 3 wk. This compensation was associated with the sustained elevations of plasma ANF and the normalization of plasma renin. Subsequent administration of deoxycorticosterone acetate (DOCA) for 10 days produced consistent sodium retention despite additional elevations in plasma ANF. All of these responses were similar to previous studies in AV fistula dogs with intact renal nerves. In a separate part of the study, the renal actions of acute synthetic ANF infusions were examined in these renal-denervated AV fistula dogs before and after DOCA. In the pre-DOCA experiments, ANF infusions at 15, 30, and 100 ng.kg-1.min-1 produced dose-related increases in urinary sodium excretion and significant elevations in creatinine clearance. In the presence of DOCA, urinary sodium excretion was markedly attenuated during identical ANF infusions. The composite results suggest that mineralocorticoids have an important modulatory role for the regulation of sodium balance in experimental HOHF. However, compared with earlier studies in compensated AV fistula dogs with intact renal nerves, the present studies demonstrate that blockade of efferent renal sympathetic nerve activity can restore the natriuretic expression of acute elevations in circulating ANF.

Animals↗
PubMed1993

Explant culture of rabbit tracheobronchial epithelium: structure and prostaglandin metabolism.

This study examines the potential usefulness of explant culture of rabbit tracheal epithelium as a model for the study of epithelial function under normal and potentially pathologic conditions. Accordingly, we assessed the structure and prostaglandin E2 (PGE2) release of tracheal epithelial explants obtained from adult pathogen-free rabbits. Epithelial cells attached to their native connective tissue substratum were maintained in culture for 5 days in serum-free medium, under bipolar conditions (air-liquid interface) on a permeable membrane (pore size, 0.2 mm), and nourished from the basolateral surface. At 5 days in culture, scanning and transmission electron microscopy and light microscopy demonstrated a pseudostratified, ciliated columnar epithelium with prominent folds and mucus secretion identical in appearance to the mucosa before culture. On the day of dissection (day 0) and after 4 days in culture (day 4), explants released PGE2 into the medium spontaneously. However, day 4 explants produced 3- to 4-fold greater amounts of PGE2 than day 0 explants. Moreover, day 4 explants demonstrated increased PGE2 release in response to bradykinin, a receptor-dependent agonist, and ionomycin, a calcium ionophore, while day 0 explants did not. Primary tracheal epithelial cell cultures grown to confluence (day 9) on a collagen substrate demonstrated PGE2 responses to bradykinin and ionomycin that qualitatively resembled those of day 4 explants. We conclude that rabbit tracheal explants cultured in vitro under the above conditions maintain cellular differentiation, in situ three-dimensional organization, and PGE2 synthetic pathways over several days in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Dopaminergic activity measured in D1- and D2-transfected fibroblasts by silicon-microphysiometry.

The dopaminergic system implicated in human disorders such as Parkinson's disease, schizophrenia and prolactinomas, exerts its effects through several dopamine receptors. The diversity of the dopaminergic system has been revealed by the application of molecular biology techniques to this system, which allowed the identification of five different types of dopamine receptors to date. Even though the structure of these receptors has now been identified, their physiological roles are still under investigation. The coupling of the D1 and D2 dopamine receptor to second messengers has been investigated using cell lines transfected with the cDNAs of these receptors. However, until recently, there was no technique allowing non-invasive real-time measurement of the metabolic activity of cells after agonist stimulation. We present here real-time measurement of events induced by dopaminergic agents on either the D1 or the D2 dopamine receptors using a novel technique employing a silicon-based microphysiometer.

Animals↗
PubMed1993

Magnetoencephalographic localization of a language processing cortical area adjacent to a cerebral arteriovenous malformation. Case report.

In order to accurately estimate the risk of surgery for dominant perisylvian arteriovenous malformations, the topographical relationship of the lesion to language cortex must be determined. A case is presented in which a magnetoencephalographic (MEG) study was used to map preoperatively and noninvasively an intracortical source of speech-receptive cortex in a 25-year-old right-handed man with a dominant left temporal lobe arteriovenous malformation. The speech-evoked magnetic field was analyzed at 36 positions over the left hemisphere in response to presentations of the consonant-vowel syllables "da" and "ga." A topographical map of the magnetic component evoked at 110 msec after stimulus onset, which was negative going to the vertex in concurrent electrical recordings, was congruent with a superficial cortical neuronal current source. This source was displaced from that usually observed in normal individuals to tonal or click stimuli, being superior to the probable location of auditory cortex, and superior and anterior to the probable location of Wernicke's area as conventionally described. The MEG results were in accord with the determination of position of a language-processing cortical area as assessed by direct electrical stimulation of the cortex during surgery under local anesthesia, and by superselective Amytal (amobarbital) injection during angiography. The MEG recordings and exposed brain stimulation sites were coordinated by cranial measurements, skull x-ray landmarks, and angiographic anatomy. Investigations such as this, which compare MEG findings with those from established clinical procedures, are an essential step in determining the physiological and anatomical utility of magnetoencephalography for noninvasive clinical functional localization.

Adult↗
PubMed1992

Molecular cloning and characterization of an adenosine receptor: the A3 adenosine receptor.

We have previously reported the selective amplification of several rat striatal cDNA sequences that encode guanine nucleotide-binding regulatory protein (G protein)-coupled receptors. One of these sequences (R226) exhibited high sequence identity (58%) with the two previously cloned adenosine receptors. A full-length cDNA clone for R226 has been isolated from a rat brain cDNA library. The cDNA clone encodes a protein of 320 amino acids that can be organized into seven transmembrane stretches. R226 has been expressed in COS-7 and CHO cells and membranes from the transfected cells were screened with adenosine receptor radioligands. R226 could bind the nonselective adenosine agonist tritiated N-ethyladenosine 5'-uronic acid ([3H]NECA) and A1-selective agonist radioiodinated N6-2-(4-amino-3-iodophenyl)-ethyladenosine ([125I]APNEA) but not A1-selective antagonists tritiated 1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX) and 8-(4-[([[(2-aminoethyl)amino]carbonyl]methyl)oxy]-phenyl)-1, 3-dipropylxanthine ([3H]XAC) or the A2-selective agonist ligands tritiated 2-[4-(2-carboxyethyl)phenyl]ethyl-amino 5'-N-ethylcarboxamidoadenosine ([3H]CGS21680) and radioiodinated 2-[4-([2-[(4-aminophenyl)methylcarbonylamino] ethylaminocarbonyl]ethyl)phenyl]ethylamino 5'-N-ethylcarboxamidoadenosine. Extensive characterization with [125I]APNEA showed that R226 binds [125I]APNEA with high affinity (Kd = 15.5 +/- 2.4 nM) and the specific [125I]APNEA binding could be inhibited by adenosine ligands with a potency order of (R)-N6-phenyl-2-propyladenosine (R-PIA) = NECA greater than S-PIA greater than adenosine greater than ATP = ADP but not by antagonists XAC, isobutylmethylxanthine, and DPCPX. In R226 stably transfected CHO cells, adenosine agonists R-PIA, NECA, and CGS21680 inhibited by 40-50% the forskolin-stimulated cAMP accumulation through a pertussis toxin-sensitive G protein with an EC50 of 18 +/- 5.6 nM, 23 +/- 3.5 nM, and 144 +/- 34 nM, respectively. Based on these observations we conclude that R226 encodes an adenosine receptor with non-A1 and non-A2 specificity, and we thus name it the A3 adenosine receptor. mRNA analyses revealed that the highest expression of R226 was in the testis and low-level mRNAs were also found in the lung, kidneys, heart, and some parts of the central nervous system such as cortex, striatum, and olfactory bulb. The high-expression level of the A3 receptor in the testis suggests a possible role for adenosine in reproduction.

Adenosine↗
PubMed1992

Marked increase in veno-occlusive disease of the liver associated with methotrexate use for graft-versus-host disease prophylaxis in patients receiving busulfan/cyclophosphamide.

The use of cyclosporine-A/methotrexate (CyA/MTX) for graft-versus-host disease (GVHD) prophylaxis is safe and effective for patients undergoing allogeneic bone marrow transplantation after preparation with cyclophosphamide and total body irradiation. We report 87 patients prepared for allogeneic transplant with busulfan 4 mg/kg/d orally for 4 days, followed by cyclophosphamide 60 mg/kg/d intravenously for 2 days (Bu4Cy2). A marked increase in hepatotoxicity was observed in 20 patients administered CyA/MTX, compared with 67 historical control patients who received CyA/methylprednisolone (CyA/MP) for GVHD prophylaxis with all other treatment and support variables remaining constant. The incidence of hyperbilirubinemia (bilirubin greater than or equal to 2 mg/dL) increased from 48% to 80% (P = .02), and the mean maximal bilirubin increased from 4.67 +/- 7.27 to 8.72 +/- 8.73 mg/dL (P = .04), when CyA/MTX was used in place of CyA/MP for GVHD prophylaxis. In addition, the incidence of veno-occlusive disease (VOD) increased from 18% to 70% (P = .0001), and death caused by VOD increased from 4.5% to 25% (P = .02). Survival was not significantly different for the two groups because of a higher non-VOD death rate in patients receiving CyA/MP for GVHD prophylaxis (P = .77). We suggest caution when using Bu4Cy2 in combination with CyA/MTX for GVHD prophylaxis.

Actuarial Analysis↗
PubMed1992

The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13.

Extracts from human Jurkat cells or from calf thymus contain a 60-kDa protein that is bound to immobilized FK506. As expected, the NH2-terminal sequences of the 60-kDa protein from these two species were found to be nearly the same. We were surprised to discover, however, that the sequence of the human protein was identical to that of Hsp56, a heat shock protein of unknown function that has been shown to be a component of several steroid receptor complexes. Further analysis of the calf thymus protein revealed a peptide with homology to a region near the COOH terminus of both FKBP-12 and FKBP-13. It would appear, therefore, that this 60-kDa protein, or as we refer to it provisionally, "Hsp56," could have the capacity to bind FK506 directly. These observations lead us to speculate that "Hsp56" may mediate immunosuppression and inhibition of T-cell proliferation by FK506 and may do so via a cytosolic signal transduction pathway separate, but not necessarily exclusive, from that of FKBP-12 and FKBP-13.

Amino Acid Sequence↗
PubMed1992

Adapting the chronic disease model in the treatment of dually diagnosed patients.

This article suggests that while the focal point of inpatient treatment in the field of addiction should continue to be abstinence and 12-step programs, there should be considerable modification of the process of treatment. Many of the present inpatient psychiatric hospitals that treat addiction seem to be largely unaware of the biochemistry and physiology of early recovery. A model of treatment is proposed that takes into account the neurocognitive impairment and emotional augmentation that is present in early recovery. The focus of active treatment in this program is the treatment of the addictive process. The psychiatric diagnosis is managed through supportive psychotherapy and/or education if appropriate. Active treatment of the psychiatric diagnosis is deferred to outpatient treatment.

Alcoholism↗
PubMed1992

Sustained hypertension in the rat induced by chronic blockade of nitric oxide production.

It is well established that acute systemic blockage of L-arginine conversion to nitric oxide by NW-nitro-L-arginine methyl ester (L-NAME) and other substituted analogs of L-arginine produces vasoconstriction and elevates the blood pressure. The present study in rats reports that chronic L-NAME injections (185 mumol/L/kg body weight, intraperitoneally; every 12 h) for 4 days produces sustained arterial hypertension which is fully and rapidly reversed by acute administration of excess L-arginine. The magnitude of the hypertension is not different between L-NAME treated rats fed normal or high sodium diets. The results from this simple experimental model suggest that chronic blockade of nitric oxide synthesis results in sustained arterial hypertension that is not enhanced by sodium loading.

Animals↗
PubMed1992

Captopril enhances renal responsiveness to ANF in dogs with compensated high-output heart failure.

The systemic hemodynamic, hormonal, and renal effects of chronic angiotensin-converting enzyme inhibition (CEI) with captopril and the responses to synthetic atrial natriuretic factor (ANF) infusions in the presence and absence of captopril were examined in normal dogs (n = 6) and in dogs with an arteriovenous (AV) fistula and compensated high-output heart failure (n = 6). This experimental model is characterized by normalization of the circulating renin-angiotensin-aldosterone system (RAAS) and persistent elevations in central filling pressures and plasma ANF. In both normal and AV-fistula dogs, oral captopril for 1 wk at 35 mg.kg-1.day-1 in three divided doses produced progressive reductions in arterial and atrial pressures (P less than 0.05), plasma ANF (P less than 0.05), and aldosterone (P less than 0.05). After 1-2 days of a modest increase in urinary sodium excretion (UNaV) (P less than 0.05), all of the dogs regained and maintained sodium balance during captopril administration. On the 8th day of the captopril regimen, synthetic ANF was infused at 15 and 30 ng.kg-1.min-1 for 75-min periods each. Control infusion experiments were performed in the same animals before captopril administration. The normal dogs exhibited dose-related elevations in UNaV (P less than 0.05) that were not augmented with captopril (P greater than 0.05). In contrast, in the AV-fistula dogs the observed renal unresponsiveness to synthetic ANF in the control experiments was reversed with chronic CEI, and ANF-induced UNaV achieved levels comparable to those obtained in the normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Pressure natriuresis in rats during blockade of the L-arginine/nitric oxide pathway.

The natriuretic response was studied in anesthetized rats during the intravenous infusion of L-arginine analogues to inhibit the production of endothelium-derived nitric oxide. In an initial experimental series, rats were administered saline vehicle or vehicle containing 300 mumol/kg body wt N omega-monomethyl-L-arginine, N omega-nitro-L-arginine methyl ester, N omega-monomethyl-D-arginine, or L-arginine. Infusion of the competitive inhibitors N omega-monomethyl-L-arginine and N omega-nitro-L-arginine methyl ester significantly increased mean arterial pressure to 155 +/- 3 and 145 +/- 5 mm Hg, respectively, compared with a mean arterial pressure of 118 +/- 3 mm Hg determined in the vehicle control group. Sodium excretion averaged 3.27 +/- 1.08 and 2.52 +/- 0.78 mu eq/min in the N omega-monomethyl-L-arginine- and N omega-nitro-L-arginine methyl ester-treated rats, respectively, and each was significantly higher than the basal sodium excretion of 0.20 +/- 0.05 mu eq/min in the vehicle-treated control animals. Plasma renin activity was significantly lower in the N omega-monomethyl-L-arginine- and N omega-nitro-L-arginine methyl ester-treated groups than in the vehicle-treated group. Neither L-arginine nor N omega-monomethyl-D-arginine administration significantly altered any of the measured variables compared with vehicle alone. In a second experimental series, an adjustable snare was placed around the suprarenal aorta for the purpose of controlling renal perfusion pressure independently of increases in the systemic mean arterial pressure initiated by infusion of N omega-nitro-L-arginine methyl ester (75 mumol/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Scholarship and socialization: reflections on the first year of doctoral study.

The first year of study in our PhD program has both broadened and intensified our knowledge. We have come to expect ourselves to attain better understandings of any given issue or topic within its attendant context and within the larger context of our profession. We have begun to appreciate and to strive for the clarity, thoroughness, and precision of thought and analysis that typify the nurse scholar. We are beginning to recognize who the nurse scholar is, why we want to emulate this person, and how we can become this person. As members of the fourth generation, we are now beginning, through our doctoral program, to live the vision of scholars who preceded us. To fulfill this vision, we understand that learning is a lifelong process that does not end with achievement of the doctorate or with postdoctoral study, but that it is continually evolving. We recognize the crucial role of research in nursing, but temper this recognition with the knowledge that research must progress in a planned manner dovetailing with existing research lest it fail to strengthen the web of nursing knowledge.

Education, Nursing, Graduate↗
PubMed1992

Two-sample nonparametric estimation and confidence intervals under truncation.

We consider point estimates and confidence intervals for the difference in location or scale between two populations when the observations are subject to truncation. We suggest procedures analogous to those for the complete-sample case. A rigorous justification is presented to support the proposed confidence interval procedure. Finally, some simulations verify the properties of the estimators and confidence intervals. We illustrate the procedure using data on tumor size.

Algorithms↗
PubMed1991

Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes.

Three genes closely related to the D1 dopamine receptor were identified in the human genome. One of the genes lacks introns and encodes a functional human dopamine receptor, D5, whose deduced amino acid sequence is 49% identical to that of the human D1 receptor. Compared with the human D1 dopamine receptor, the D5 receptor displayed a higher affinity for dopamine and was able to stimulate a biphasic rather than a monophasic intracellular accumulation of cAMP. Neither of the other two genes was able to direct the synthesis of a receptor. Nucleotide sequence analysis revealed that these two genes are 98% identical to each other and 95% identical to the D5 sequence. Relative to the D5 sequence, both contain insertions and deletions that result in several in-frame termination codons. Premature termination of translation is the most likely explanation for the failure of these genes to produce receptors in COS-7 and 293 cells even though their messages are transcribed. We conclude that the two are pseudogenes. Blot hybridization experiments performed on rat genomic DNA suggest that there is one D5 gene in this species and that the pseudogenes may be the result of a relatively recent evolutionary event.

Amino Acid Sequence↗
PubMed1991

Impedance measurement of absolute blood flow using an angioplasty catheter: a validation study.

An angioplasty catheter was developed to allow measurement of absolute coronary blood flow during interventional procedures. This method uses electrical impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and indicator-dilution principles. The indicator is injected through a port located just proximal to the dilating balloon and the resulting changes in blood impedance are measured by electrodes at the catheter tip. Excellent linear correlations were found between known flow in 2 to 4 mm to diameter plastic tubes and catheter measurements (r = 0.99) and between timed collection canine femoral artery flow and catheter measurements (r = 0.97). Final validation was performed in canine coronary arteries using electromagnetic flowmeter data as the standard (r = 0.94). Thus accurate clinical determination of absolute coronary blood flow can be accomplished using this relatively inexpensive and simple catheter technique.

Angioplasty, Balloon, Coronary↗