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R F Johnson

Publications and source records attributed to R F Johnson.

At least 19 recordsLinked to original sources
PubMed2004

Hypothesis: selective phosphodiesterase-5 inhibition improves outcome in preeclampsia.

The pathogenesis of preeclampsia stems from aberrant changes at the placental interface. The trophoblastic endovascular invasion of tonic spiral arteries that converts them to passive conduits falters. Uteroplacental insufficiency and fetoplacental hypoxemia result. Secondary maternal oxidative stress and an excessive inflammatory response to pregnancy generate the clinical syndrome of preeclampsia. Current treatment focuses on preventing seizures, controlling hypertension, preserving renal function and delivering the baby. We propose that the pathophysiological changes induced by preeclampsia in the placenta parallel those caused by persistent hypoxemia in the lungs at high altitude or with chronic obstructive pulmonary disease. Unrelenting pulmonary hypoxic vasoconstriction induces pulmonary hypertension and cor pulmonale. Inhalation of nitric oxide and phosphodiesterase-5 inhibitors opposes pulmonary hypoxic vasoconstriction, alleviates pulmonary hypertension and improves systemic oxygenation. Notably nitric oxide donor therapy also counters hypoxemic fetoplacental vasoconstriction, a biological response analogous to pulmonary hypoxic vasoconstriction. Fetal oxygenation and nutrition improve. Placental upstream resistance to umbilical arterial blood flow decreases. Fetal right ventricular impedance falls. Heart failure (cor placentale) is avoided. Emergency preterm delivery can be postponed. Other than low dose aspirin and antioxidants vitamins C and E no available therapy specifically targets the underlying disease profile. We hypothesize that, like nitric oxide donation, pharmacological inhibition of placental phosphodiesterase-5 will also protect the fetus but for a longer time. Biological availability of guanosine 3'5'-cyclic monophosphate is boosted due to slowed hydrolysis. Adenosine 3'5'-cyclic monphosphate levels increase in parallel. Cyclic nucleotide accumulation dilates intact tonic spiral arteries and counters hypoxemic fetoplacental vasoconstriction. Intervillous and intravillous perfusion pick up. Maternal to fetal placental circulatory matching improves. Enhanced placental oxygen uptake alleviates hypoxemic fetal stress. Appropriate fetal nutrition resumes. Cor placentale and severe intrauterine growth restriction are averted. Increased maternal cyclic nucleotide concentrations promote systemic vasodilatation so that blood pressures fall. Preemption of oxidative stress initiated by "consumptive" oxidation of nitric oxide stabilizes the vascular endothelium and corrects coagulopathy. Anti-inflammatory and immunosuppressant adenosine 3'5'-cyclic monphosphate offsets the extreme gestational inflammatory response. Cellular injury and multi-organ damage are prevented. One tablet a day of the new long acting phosphodiesterase-5 inhibitor, tadalafil (half life of 17.5 h) theoretically should allow a preterm pregnancy affected by preeclampsia to continue safely. Selective monitoring of vital organ functions guards against life-threatening maternal complications. Regular biophysical profiling warns the obstetrician of impending fetal compromise. Fetal growth and vital organ maturation can continue. As a result workloads imposed upon neonatal intensivists will lighten. Parental anxiety and concern will be allayed. The cost of treating preeclamptic mothers and their extremely low birth weight infants will decrease. Money saved by midwifery services in poorer states can be used to pay for better prenatal care. Severe preeclampsia/eclampsia will be less common. Maternal and perinatal morbidity and mortality will be reduced. Because the human immunodeficiency virus often infects individuals at a workforce eligible age, the global acquired immunodeficiency syndrome pandemic has already brought many nations to the brink of economic ruin. Potentially productive lives saved for the future will help restore them fiscally.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Mitochondrial HSP70, HSP40, and HSP60 bind to the 3' untranslated region of the Murine hepatitis virus genome.

We have previously shown that mitochondrial-aconitase binds specifically to the 3' terminal 42 nucleotides of the Murine hepatitis virus (MHV) RNA along with three additional proteins of 70, 58 and 40 kDa to form a stable RNA-protein complex. Supershift and western blot assays have identified these three proteins as mitochondrial HSP70 (mtHSP70), HSP60, and HSP40. A series of co-immunoprecipitation assays have established that these four MHV RNA binding proteins are associated, even in the absence of MHV RNA. However, the presence of a synthetic RNA containing the sequence bound by these four proteins does increase the amount of co-precipitated protein, in particular the amount of HSP60 which is brought down with antibodies directed against HSP40 and mtHSP70. We have provided evidence for the interaction of these four proteins with the 3' end region of MHV RNA in infected cells by a series of immunoprecipitation RT-PCR assays. We believe it is likely that MHV RNA interacts with m-aconitase prior to its import into mitochondria in cooperation with extra-mitochondrial mtHSP70, HSP60, and HSP40.

3' Untranslated Regions↗
PubMed2001

Adenovirus-mediated gene delivery to cells of the magnocellular hypothalamo-neurohypophyseal system.

The objective of the present study was to define the optimum conditions for using replication-defective adenovirus (Ad) to transfer the gene for the green fluorescent protein (GFP) to the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei and cells of the neurohypophysis (NH). As indicated by characterizing cell survival over 15 days in culture and in electrophysiological whole cell patch-clamp studies, viral concentrations up to 2 x 10(7) pfu/coverslip did not affect viability of transfected PVN and NH cultured cells from preweanling rats. At 2 x 10(7) pfu, GFP gene expression was higher (40% of GFP-positive cells) and more sustained (up to 15 days). Using a stereotaxic approach in adult rats, we were able to directly transduce the PVN, SON, and NH and visualize gene expression in coronal brain slices and in the pituitary 4 days after injection of Ad. In animals receiving NH injections of Ad, the virus was retrogradely transported to PVN and SON neurons as indicated by the appearance of GFP-positive neurons in cultures of dissociated cells from those brain nuclei and by polymerase chain reaction and Western blot analyses of PVN and SON tissues. Adenoviral concentrations of up to 8 x 10(6) pfu injected into the NH did not affect cell viability and did not cause inflammatory responses. Adenoviral injection into the pituitary enabled the selective delivery of genes to the soma of magnocellular neurons. The experimental approaches described here provide potentially useful strategies for the treatment of disordered expression of the hormones vasopressin or oxytocin.

Adenoviridae↗
PubMed2001

Comparison of two different temperature maintenance strategies during open abdominal surgery: upper body forced-air warming versus whole body water garment.

BACKGROUND: A new system has been developed that circulates warm water through a whole body garment worn by the patient during surgery. In this study the authors compared two different strategies for the maintenance of intraoperative normothermia. One strategy used a new water garment warming system that permitted active warming of both the upper and lower extremities and the back. The other strategy used a single (upper body) forced-air warming system. METHODS: In this prospective, randomized study, 53 adult patients were enrolled in one of two intraoperative temperature management groups during open abdominal surgery with general anesthesia. The water-garment group (n = 25) received warming with a body temperature (rectal) set point of 36.8 degrees C. The forced-air-warmer group (n = 28) received routine warming therapy using upper body forced-air warming system (set on high). The ambient temperature in the operating room was maintained constant at approximately 20 degrees C. Rectal, distal esophageal, tympanic, forearm, and fingertip temperatures were recorded perioperatively and during 2 h after surgery. Extubated patients in both groups were assessed postoperatively for shivering, use of additional warming devices, and subjective thermal comfort. RESULTS: The mean rectal and esophageal temperatures at incision, 1 h after incision, at skin closure, and immediately postoperatively were significantly higher (0.4-0.6 degrees C) in the group that received water-garment warming when compared with the group that received upper body forced-air warming. The calculated 95% confidence intervals for the above differences in core temperatures were 0.7-0.1, 0.8-0.2, 0.8-0.2, and 0.9-0.1, retrospectively. In addition, 14 and 7% of patients in the control upper body forced-air group remained hypothermic (< 35.5 degrees C) 1 and 2 h after surgery, respectively. No core temperature less than 35.5 degrees C was observed perioperatively in any of the patients from the water-garment group. A similar frequency of the thermal stress events (shivering, use of additional warming devices, subjective thermal discomfort) was observed after extubation in both groups during the 2 h after surgery. CONCLUSIONS: The investigated water warming system, by virtue of its ability to deliver heat to a greater percentage of the body, results in better maintenance of intraoperative normothermia that does forced-air warming applied only to the upper extremities, as is common practice.

Abdomen↗
PubMed2001

Virtual endoscopic evaluation of labyrinthine fistulae resulting from cholesteatoma.

OBJECTIVES/HYPOTHESIS: Fistulae of the otic capsule occur in approximately 10% of cholesteatoma cases. Preoperative imaging of this complication is valuable in limiting intraoperative morbidity. Three-dimensional virtual endoscopic imaging provides a new method for analysis of conventional computed tomography (CT) imaging data. The purpose of the study was to examine the feasibility and efficacy of this technique in detecting labyrinthine fistulae caused by cholesteatoma. STUDY DESIGN: Retrospective case study. METHODS: Fifteen patients with surgically confirmed lateral semicircular canal fistula and preoperative CT scan were included. Scans meeting inclusion criteria were imported into a software program for production of virtual endoscopic images. Dehiscent and normal lateral semicircular canals were navigated while varying threshold values for surrounding bone. Changes in threshold values produce the effect of thickening or thinning the bone enveloping the semicircular canal. Threshold parameters that produced easy circumnavigation ("open") and intact inner surface of the lateral canal ("closed") were recorded. RESULTS: The fistula group demonstrated a significantly lower "closed" threshold level and, consequently, a greater range of navigation between "open" and "closed" thresholds. Intrasubject absolute differences in threshold values between normal and abnormal ears appeared to be the most accurate method for detecting a fistula. The suggested imaging parameters displayed an overall sensitivity for fistula detection of 67% with a specificity of 93%. CONCLUSIONS: The three-dimensional virtual endoscopic algorithm shows promise as a method for confirmation of otic capsule dehiscences. Sensitivity for detection is suboptimal but can be improved by alterations in image acquisition parameters.

Adolescent↗
PubMed2001

Blood and urinary measures of hydration status during progressive acute dehydration.

PURPOSE: To determine whether: a) plasma osmolarity (Posm) is sensitive to small incremental changes in hydration status, b) urine specific gravity (Usg) can accurately identify a state of euhydration, c) Usg is a sensitive indicator of a change in hydration status, and d) Usg correlates with Posm. METHODS: Euhydrated (Posm = 288 +/- 4 mOsm.L-1) subjects (N = 12) were dehydrated by 5% of their body weight via exercise in the heat (40 degrees C, 20% RH). Posm, urine osmolarity (Uosm), and Usg were measured at 1%, 3%, and 5% dehydration, and 30 and 60 min of recovery (rec). Subjects consumed water in recovery equal to their loss of body weight. RESULTS: Posm increased incrementally with each successive increase in percent body weight loss (%BWL). Usg was not significantly different from baseline until 3% BML. Uosm was not significantly different from baseline until 5% BWL. Usg correlated moderately (r = 0.46, P > 0.10) with Posm but reasonably well (r = 0.68, P < 0.02) with Uosm. CONCLUSIONS: Posm accurately identifies a state of euhydration and is sensitive to changes in hydration status during acute dehydration and rehydration. Usg and Uosm are also sensitive to changes in hydration status but lag behind during periods of rapid body fluid turnover and therefore correlate only moderately with Posm during acute dehydration.

Adult↗
PubMed2001

Secondary structural elements within the 3' untranslated region of mouse hepatitis virus strain JHM genomic RNA.

Previously, we characterized two host protein binding elements located within the 3'-terminal 166 nucleotides of the mouse hepatitis virus (MHV) genome and assessed their functions in defective-interfering (DI) RNA replication. To determine the role of RNA secondary structures within these two host protein binding elements in viral replication, we explored the secondary structure of the 3'-terminal 166 nucleotides of the MHV strain JHM genome using limited RNase digestion assays. Our data indicate that multiple stem-loop and hairpin-loop structures exist within this region. Mutant and wild-type DIssEs were employed to test the function of secondary structure elements in DI RNA replication. Three stem structures were chosen as targets for the introduction of transversion mutations designed to destroy base pairing structures. Mutations predicted to destroy the base pairing of nucleotides 142 to 136 with nucleotides 68 to 74 exhibited a deleterious effect on DIssE replication. Destruction of base pairing between positions 96 to 99 and 116 to 113 also decreased DI RNA replication. Mutations interfering with the pairing of nucleotides 67 to 63 with nucleotides 52 to 56 had only minor effects on DIssE replication. The introduction of second complementary mutations which restored the predicted base pairing of positions 142 to 136 with 68 to 74 and nucleotides 96 to 99 with 116 to 113 largely ameliorated defects in replication ability, restoring DI RNA replication to levels comparable to that of wild-type DIssE RNA, suggesting that these secondary structures are important for efficient MHV replication. We also identified a conserved 23-nucleotide stem-loop structure involving nucleotides 142 to 132 and nucleotides 68 to 79. The upstream side of this conserved stem-loop is contained within a host protein binding element (nucleotides 166 to 129).

3' Untranslated Regions↗
PubMed2001

Agonist activation of cytosolic Ca2+ in subfornical organ cells projecting to the supraoptic nucleus.

The subfornical organ (SFO) is sensitive to both ANG II and ACh, and local application of these agents produces dipsogenic responses and vasopressin release. The present study examined the effects of cholinergic drugs, ANG II, and increased extracellular osmolarity on dissociated, cultured cells of the SFO that were retrogradely labeled from the supraoptic nucleus. The effects were measured as changes in cytosolic calcium in fura 2-loaded cells by using a calcium imaging system. Both ACh and carbachol increased intracellular ionic calcium concentration ([Ca2+]i). However, in contrast to the effects of muscarinic receptor agonists on SFO neurons, manipulation of the extracellular osmolality produced no effects, and application of ANG II produced only moderate effects on [Ca2+]i in a few retrogradely labeled cells. The cholinergic effects on [Ca2+]i could be blocked with the muscarinic receptor antagonist atropine and with the more selective muscarinic receptor antagonists pirenzepine and 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP). In addition, the calcium in the extracellular fluid was required for the cholinergic-induced increase in [Ca2+]i. These findings indicate that ACh acts to induce a functional cellular response in SFO neurons through action on a muscarinic receptor, probably of the M1 subtype and that the increase of [Ca2+]i, at least initially, requires the entry of extracellular Ca2+. Also, consistent with a functional role of M1 receptors in the SFO are the results of immunohistochemical preparations demonstrating M1 muscarinic receptor-like protein present within this forebrain circumventricular organ.

Acetylcholine↗
PubMed2001

Projectile cylinder accidents resulting from the presence of ferromagnetic nitrous oxide or oxygen tanks in the MR suite.

OBJECTIVE: The purpose of this study is to alert MR users to the potentially lethal consequences of projectile cylinder accidents in the MR environment. CONCLUSION: Projectile cylinder tank accidents still occur and may be increasing, despite adherence to screening policies before MR imaging and safety education of hospital personnel. Four of the last five accidents at our institutions occurred within the past 3 years.

Accidents↗
PubMed2001

Relation of rifle stock length and weight to military rifle marksmanship performance by men and women.

15 male and 13 female soldiers participated in a study to examine the effects of sex, rifle stock length 117.8 cm, 22.3 cm, and 26.2 cm), and rifle weight (3.2 kg vs 3.8 kg) on military marksmanship performance. The Noptel simulator was used to assess marksmanship accuracy (proximity of shots to the target center) and precision (proximity of shots to one another regardless of proximity to the target center). There were no significant differences in either measure of marksmanship performance as a function of sex. Marksmanship accuracy was significantly better with the shortest rifle stock, and marksmanship precision was significantly better with the lighter rifle. Regardless of the sex of the shooter, stock length and weapon weight should be considered in any new combat rifle design as these results indicate they significantly affect marksmanship.

Adult↗
PubMed2001

Heat strain evaluation of chemical protective garments.

BACKGROUND: The purpose of this study was to compare thermoregulatory and subjective responses of 12 test subjects (10 male, 2 female) wearing 5 different Joint Service Lightweight Integrated Suit Technology (JSLIST) prototype and 3 different currently fielded control chemical/ biological (CB) protective overgarments. METHODS: The overgarments were compared while subjects attempted to complete 100 min of moderate exercise (400 W) in an environmental chamber (35 degrees C/50% rh). Rectal temperature (Tre), skin temperature, heart rate, sweating rate, and test time, as well as subjective symptoms of heat illness were measured. Data were analyzed for times earlier than 100 min because subjects were not usually able to complete the 100-min trials. RESULTS: At 50 min, of the 3 controls, the Army/Air Force Battledress Overgarment (BDO) imposed significantly greater heat strain (indicated by Tre 37.90 degrees C) than the Marine Saratoga (SAR) (Tre 37.68 degrees C) and Navy Chemical Protective Overgarment (CPO) (Tre 37.69 degrees C). The JSLIST prototype garments imposed heat strain (50 min Tre 37.73-37.86 degrees C) as well as subjective perception of heat strain, that ranged between the warmest and coolest controls. CONCLUSIONS: In the environmental and exercise test conditions of this study, we did not find the five JSLIST overgarments to be consistently different from one another. Subjects in the control garments were and felt generally warmer (BDO) or cooler (SAR, CPO) than in the JSLIST prototype garments.

Adult↗
PubMed2000

Transfer of methohexital across the perfused human placenta.

STUDY OBJECTIVES: To evaluate the transfer properties of methohexital and the influence of protein binding using the in vitro human placental perfusion model. DESIGN: Fresh term human placentae from healthy parturients were perfused bidirectionally via a cannulated fetal chorionic artery and vein and needles placed into the maternal intervillous space. Maternal-to-fetal (M-->F) and fetal-to-maternal (F-->M) transfer and ultimate distribution of methohexital was investigated using a closed (recirculating) placental perfusion model. SETTING: Obstetric anesthesia laboratories of two university medical centers. PATIENTS: No patient participation occurred as placentae were obtained after delivery. INTERVENTION: M-->F and F-->M transfer of methohexital was compared in vitro in perfusates with equal protein concentrations (2 g/100 mL in both perfusates) or albumin-simulated physiologic protein binding concentrations (maternal 8 g/100 mL; fetal 4 g/100 mL). MEASUREMENTS AND MAIN RESULTS: Data obtained consisted of measurements of methohexital and antipyrine concentrations by high-performance liquid chromatography. Glucose and lactate concentrations and perfusate loss were measured to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium dialysis. The transfer index of 0.83 +/- 0.11 for the M-->F perfusions was significantly greater (p < or = 0.05) than in the F-->M direction (0.61 +/- 0.04) when albumin concentration was equal in both perfusates. This transfer asymmetry disappeared when albumin concentrations simulating maternal (8 g/100 mL) versus fetal (4 g/100 mL) protein concentrations in the perfusate were used (M-->F 0.87 +/- 0.12 and F-->M 0.95 +/- 0.11). CONCLUSION: Methohexital readily crosses the placenta in both directions. Protein binding has significant effects on the degree of transfer of methohexital at any time when compared with antipyrine and its ultimate fetal/maternal distribution.

Adolescent↗
PubMed2000

Screening to the converted: an educational intervention in African American churches.

BACKGROUND: African American women have higher incidences of breast and cervical cancers and African American men present with more advanced stages of colon and prostate cancers than do their non-African American counterparts. Since the church is central to the organization of the African American community, the authors set out to determine whether a church-directed educational project could influence parishioners to obtain cancer screening. METHODS: Three African American churches having memberships of 250, 500, and 1,500, respectively, were selected for their different socioeconomic strata: one congregation was composed mostly of working poor, the second was more affluent, and the third consisted primarily of retirees. During a five-week summer period, appropriate literature, health fairs, testimonials by cancer survivors, and visits by representatives of the medical community were used to increase awareness of cancer screening. Surveys regarding cancer-screening behaviors were distributed at the end of church services. Using the guidelines established by the American Cancer Society, individual recommendations for screening examinations were developed and sent to parishioners based on their survey responses. RESULTS: Of 437 parishioners surveyed (73% female, 27% male), 75% were 40 years old or older. Many reported up-to-date screening for breast (84%), cervical (78%), colon (62%), and prostate (89%) cancers. The results were remarkably similar in all three churches. Telephone follow-up seven months after the survey directed at the 120 parishioners identified as noncompliant for at least one cancer screening revealed that 49% had obtained the appropriate screenings. CONCLUSIONS: These African American churchgoers were well screened compared with estimated national averages, possibly due to previous efforts of the activist ministers in the churches selected. The message for cancer screening is heeded when delivered through the African American church.

Adult↗
PubMed2000

Intravenous chloroprocaine attenuates hemodynamic changes associated with direct laryngoscopy and tracheal intubation.

We compared the effects of an IV administration of chloroprocaine and lidocaine on circulatory responses associated with endotracheal intubation. Thirty patients were randomly allocated to receive normal saline (placebo), lidocaine (1.5 mg/kg), or preservative-free chloroprocaine (4.5 mg/kg) 45 s before endotracheal intubation. Blood pressures and heart rate and rhythm were recorded before laryngoscopy and at 0.5, 1, 1.5, 2, 3, and 5 min after intubation. Blood samples were analyzed for catecholamine and chloroprocaine concentrations. Chloroprocaine reduced increases in blood pressure in response to intubation when compared with patients receiving normal saline and lidocaine. Systolic blood pressures at 0.5 and 1 min after intubation were significantly lower in the chloroprocaine group when compared with both the control and lidocaine groups (P < 0.05). Diastolic and mean blood pressures were significantly lower in the chloroprocaine group at all time points until 5 min after intubation (P < 0.05). Chloroprocaine and, to a lesser degree, lidocaine, produced marked attenuation of intubation-induced increases in plasma concentration of epinephrine and norepinephrine. Plasma concentrations of norepinephrine were significantly smaller in the chloroprocaine group at 0.5, 1, and 1.5 min, and plasma concentrations of epinephrine were significantly smaller at 0.5 after intubation when compared with control and lidocaine groups (P < 0.05). Measurable concentrations of chloroprocaine were recorded in plasma samples for 2 min after its administration. No adverse chloroprocaine effects (i.e., circulatory disturbances, venous irritation) were detected. The IV administration of chloroprocaine effectively blunted cardiovascular response produced by laryngoscopy and endotracheal intubation, and this effect was more pronounced when compared with IV lidocaine.

Adult↗
PubMed1999

Characterization of ionic currents of cells of the subfornical organ that project to the supraoptic nuclei.

The subfornical organ (SFO) is a forebrain structure that converts peripheral blood-borne signals reflecting the hydrational state of the body to neural signals and then through efferent fibers conveys this information to several central nervous system structures. One of the forebrain areas receiving input from the SFO is the supraoptic nucleus (SON), a source of vasopressin synthesis and control of release from the posterior pituitary. Little is known of the transduction and transmission processes by which this conversion of systemic information to brain input occurs. As a step in elucidating these mechanisms, the present study characterized the ionic currents of dissociated cells of the SFO that were identified as neurons that send efferents to the SON. A retrograde tracer was injected into the SON area in eleven-day-old rats. After three days for retrograde transport of the label, the SFOs of these animals were dissociated and plated for tissue culture. The retrograde tracer was used to identify the soma of SFO cells projecting to the SON so that voltage-dependent ionic currents using whole-cell voltage clamp methods could be studied. The three types of currents in labeled SFO neurons were characterized as a 1) rapid, transient inward current that can be blocked by tetrodotoxin (TTX) characteristic of a sodium current; 2) slow-onset sustained outward current that can be blocked by tetraethylammonium (TEA) characteristic of a delayed rectifier potassium current; and 3) remaining outward current that has a rapid-onset and transient characteristic of a potassium A-type current.

Afferent Pathways↗