Investing in the tort system.
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Fees and Charges↗
Biomedical subjects
R D Johnson
Publications and source records attributed to R D Johnson.
Modern health care economics.
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Health Facility Merger↗
Aspirin induces increased expression of both prostaglandin H synthase-1 and prostaglandin H synthase-2 in cultured human placental trophoblast.
OBJECTIVE: We tested the hypothesis that aspirin affects trophoblast like other epithelial cells do, by inhibiting prostanoid production, inducing prostaglandin H synthase-2 expression, and enhancing secretion of 15-hydroxyeicosatetraenoic acid. STUDY DESIGN: Cytotrophoblast from placentas (n = 15) of uncomplicated singleton pregnancies were cultured in medium 199 for 4 to 72 hours in the presence or absence of aspirin. RESULTS: Aspirin (10(-4) M) inhibited (p < 0.01) average trophoblast prostaglandin E2 release by 60% and thromboxane B2 by 86%. Western immunoblotting showed the prostaglandin H synthase-1 was constitutively expressed in cytotrophoblast, and aspirin treatment caused a twofold increase in prostaglandin H synthase-1 expression. Prostaglandin H synthase-2 was also constitutively expressed in untreated cytotrophoblast but at lower levels than prostaglandin H synthase-1. Aspirin enhanced prostaglandin H synthase-2 expression in trophoblast cultures, but prostaglandin H synthase-2 contributed a range of only 10% to 33% (n = 4) of the total cellular prostaglandin H synthase protein pool even after aspirin induction. The increased prostaglandin H synthase expression depended on both transcription and translation because actinomycin D and cycloheximide each inhibited the increased prostaglandin H synthase protein expression after aspirin treatment. The aspirin induction of prostaglandin H synthase was accompanied by decreased release of 15-hydroxyeicosatetraenoic acid. CONCLUSIONS: Trophoblast differs from other cells studied because aspirin enhances expression of both prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes while decreasing, instead of increasing, the secretion of 15-hydroxyeicosatetraenoic acid. The aspirin effects on prostaglandin H synthase synthesis and 15-hydroxyeicosatetraenoic acid release in trophoblast suggest that the mechanisms of action for aspirin in the prophylaxis of preeclampsia may be more diverse than simply altering platelet thromboxane production.
Anti-Inflammatory Agents, Non-Steroidal↗
Improved detection of recurrent bladder cancer using the Bard BTA stat Test.
OBJECTIVES: To evaluate the BTA stat Test in the detection of recurrent bladder cancer. METHODS: Sensitivity and specificity were determined using frozen voided urine samples from patients with recurrent bladder cancer, volunteers, patients with nonurologic conditions, and patients with a history of bladder cancer but free of disease. Results of cytology and the original BTA Test were compared with the sensitivity of the BTA stat Test in a large subgroup of the patients with cancer. RESULTS: The BTA stat Test detected 147 (67%) of 220 recurrent cancers. For those urine samples with previous cytologic and BTA Test results available, cytology had a sensitivity of 23%, the BTA Test 44%, and the BTA stat Test 58% for detection of recurrent cancer (P < 0.001, stat versus cytology). The specificity of the BTA stat Test was 72% for benign genitourinary disease and 95% in healthy volunteers. CONCLUSIONS: The BTA stat Test has high sensitivity and is significantly superior to voided urine cytologic analysis in the detection of recurrent bladder cancer.
Aged↗
Localization of unmyelinated axons in rat skin and mucocutaneous tissue utilizing the isolectin GS-I-B4.
The alpha-D-galactose specific isolectin I-B4 from Griffonia simplicifolia (GS-I-B4) labels CNS microglia and certain peripheral neurons, including a subpopulation of small dark, type B dorsal root ganglion cells, some post-ganglionic sympathetic axons, and nearly all peripheral gustatory axons. The innervation patterns of GS-I-B4 reactive sensory ganglion cells are unknown for many peripheral target tissues, including their probable primary target, the skin. The present study describes the distribution of GS-I-B4 reactive axons in hairy and glabrous hindpaw skin and in the glans penis of rats, using both single and double-labelling histochemical techniques. Neuronal processes were identified using (1) histochemistry with horseradish peroxidase conjugated GS-I-B4 or (2) immunohistochemistry against PGP 9.5 to identify all axons, and biotinylated lectin histochemistry with avidin-FITC to identify the subpopulation of GS-I-B4 reactive axons. GS-I-B4 strongly labelled unmyelinated cutaneous sensory afferents, as well as some sympathetic efferents and visceral afferents. lectin reactive axons were seen to innervate the upper hair shaft epidermis in hairy skin, and were abundant in the shallow dermis in hairy and glabrous skin and glans penis. Lectin reactive axons were also abundant in the lamina propria and distal urethral epithelium of the penis. These results provide new evidence for the cutaneous sensory role of GS-I-B4 reactive primary afferents, as well as evidence to support the contention that the lectin is a specific marker for a subpopulation of unmyelinated axons and not simply a marker for the myelination state of an axon.
Animals↗
The role of trophoblast interferons in the maintenance of early pregnancy in ruminants.
PROBLEM: Are the effects of ruminant trophoblast interferon-tau (IFN-tau) on uterine prostaglandin (PG) secretion a specific action of this cytokine and what are the effects of IFN-tau on expression of uterine genes not generally associated with pregnancy maintenance? METHODS: The effects of IFN-tau and IFN-alpha on bovine uterine explant and epithelial cell production of PGF2 alpha and PGE2 were determined in the presence and absence of oxytocin (OT). The effects of intrauterine administration of IFN-tau were determined on uterine expression of retinol-binding protein (RBP) and transforming growth factor-beta (TGF-beta) isoforms. RESULTS: IFN-tau attenuated uterine endometrial secretion of PGF2 alpha and PGE2 in vitro and diminish PG stimulation by OT. IFN-tau and IFN-alpha were observed to be equipotent. Intrauterine infusion of IFN-tau resulted in a significant decrease in steady-state RBP mRNA levels and expression of TGF-beta 1, 2, and 3 mRNA levels were lowest in IFN-tau treated animals. CONCLUSION: Negative regulation of gene expression may be a general strategy in IFN activity. This may explain the similar activities of IFN-tau and IFN-alpha on a broad variety of cell types, including ruminant uterine endometrium.
Animals↗
NT-3 increases amplitude of EPSPs produced by axotomized group Ia afferents.
We tested the hypothesis that neurotrophin-3 (NT-3) in adult cats can rescue the central synapses made by muscle afferents from the effects of peripheral axotomy. The medial gastrocnemius (MG) muscle nerve in cats was axotomized and capped or axotomized and the distal end provided with either saline or NT-3 by mini-osmotic pump. Four to five weeks later monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by electrical stimulation of the axotomized MG nerve were recorded in intact lateral gastrocnemius/soleus (LGS) motoneurons. The axotomized MG afferents without NT-3 treatment generated EPSPs averaging one-half of the amplitude of those generated by normal intact MG afferents. Axotomized MG afferents treated with NT-3 elicited EPSPs averaging 2.5 times normal amplitude and 5 times the amplitude of those from afferents axotomized but not treated. The very large EPSPs generated by NT-3-treated afferents remained as susceptible to depression during high-frequency stimulation (32 shocks at 167 Hz) as those elicited by untreated axotomized afferents. The arrival of the afferent volley of the cord dorsum potential and the onset of EPSPs were both delayed by axotomy of the group Ia afferents and were both restored by exposure to NT-3. This result suggests that the conduction velocity and thus the caliber of group Ia afferents are also controlled by NT-3. We conclude that the neurotrophin NT-3 has a continuing role in the maintenance of physiological function of muscle afferents in adult mammals.
Animals↗
Transcriptional regulation of prostaglandin-H synthase-2 gene in human trophoblasts.
Abnormal PG production by placental PG-H synthase (PGHS) is associated with preeclampsia. There are two PGHS isozymes, and their regulation in trophoblasts is presently unknown. We hypothesized that the PGHS isozymes are differentially regulated in human trophoblasts. To test this hypothesis, we transfected primary trophoblasts and JEG3 cells with promoter constructs of either PGHS-1 or PGHS-2 genes. We found that in both cell systems, the basal activity of PGHS-2 promoter was 10- to 30-fold higher than the activity of PGHS-1 promoter. In response to either 12-0-tetradecanoylphorbol-13-acetate (TPA) or 8-bromo-cAMP, we observed an increase in PGHS-2 promoter activity but no change in activity of PGHS-1 promoter. Similarly, both agents enhanced PGHS-2 expression, as well as prostaglandin E2 production. The activity of PGHS-2 promoter was potentiated by coexpression of protein kinase A and inhibited by coexpression of kinase A inhibitor. Aspirin attenuated the stimulatory effect of TPA on PGHS-2 promoter. We conclude that both PGHS-1 and PGHS-2 promoters are active in trophoblasts. The activity of PGHS-2 promoter is stimulated by either TPA or cAMP, and the stimulatory effect of TPA is attenuated by aspirin. These pathways may play a role in modulation of prostanoid synthesis by trophoblasts.
Aspirin↗
The expression and activity of prostaglandin H synthase-2 is enhanced in trophoblast from women with preeclampsia.
Preeclampsia is associated with altered biosynthesis of vasoactive prostanoids in placental villi. The two isozymes of prostaglandin H synthase (PGHS) are essential for prostanoid synthesis. We tested the hypothesis that PGHS-2 expression is elevated in trophoblast from preeclamptic women, compared with trophoblast from healthy women. Using immunofluorescent staining, we demonstrated a higher PGHS-2 expression in villi from preeclampsia, compared with normal pregnancy. Cytotrophoblasts cultured from placentas of preeclamptic women expressed higher levels of PGHS-2 compared with cytotrophoblasts from normal placentas. This enhanced expression of PGHS-2 correlated with increased media levels of both thromboxane and prostaglandin E2, two products of PGHS activity. The increased prostanoid production by trophoblast from preeclamptic women was markedly reduced by NS-398, a specific inhibitor of PGHS-2. We conclude that both expression and activity of PGHS-2 are enhanced in trophoblasts from preeclamptic women compared with trophoblast from normal pregnancies. The increased production of prostanoids may contribute to the clinical syndrome of preeclampsia. Our data suggest that a selective inhibitor of PGHS-2 might provide a therapeutic alternative to prophylactic low-dose aspirin in modifying the prostanoid profile in preeclampsia.
Blotting, Northern↗
The serum anion gap. Has the reference interval really fallen?
OBJECTIVE: To compare the anion gap (calculated as the sodium concentration minus the sum of the chloride and total carbon dioxide concentrations) reference interval for three automated chemistry analyzers. DESIGN: We measured serum sodium, chloride, and total carbon dioxide on aliquoted specimens using three commercial instruments. Quality control and proficiency survey materials were run to ensure that the analyzers were functioning optimally. SETTING: Three separate clinical laboratories affiliated with one university medical center participated in the study. PARTICIPANTS: Healthy volunteers from 20 to 60 years of age were recruited from within a clinical laboratory. MAIN OUTCOME MEASURES: The mean and standard deviations of the anion gaps measured by each method were calculated. RESULTS: The parametric reference intervals (+/-2 SD from the mean) were 5 to 10 mmol/L for the Beckman Synchron CX3 analyzer, 9 to 14 mmol/L for the Boehringer Mannheim Hitachi 717 analyzer, and 8 to 13 mmol/L for the Johnson & Johnson Vitros 950 analyzer. CONCLUSIONS: Our results suggest that while it may be appropriate to lower the anion gap reference interval to 5 to 10 mmol/L for some analyzers, as suggested by earlier reports, 9 to 14 mmol/L may be a more appropriate reference interval for other analyzers. For the anion gap to be an effective tool for diagnosing acid-base disorders, clinical laboratorians need to establish (or at least verify) the anion gap reference interval for the instrumentation used in their laboratory, inform clinicians of this reference interval, and perform quality control studies to ensure that the reference interval for this calculated result remains valid.
Acid-Base Equilibrium↗
Multipoint binding in metal-affinity chromatography II. Effect of pH and imidazole on chromatographic retention of engineered histidine-containing cytochromes c.
Protein binding in immobilized metal affinity chromatography (IMAC) was studied using a set of Saccharomyces cerevisiae iso-1-cytochrome c variants which differed only in their histidine content and placement. Elution with an imidazole gradient enabled separation of cytochrome c variants based on their histidine multiplicity. Millimolar concentrations of imidazole dramatically decreased protein partitioning to the IMAC support as measured by the chromatographic capacity factors under isocratic conditions. Fitting the partitioning data to the "stoichiometric displacement" model indicates that cytochrome c variants containing from one to four surface histidines each displaced approximately three equivalents of imidazole upon adsorption. Therefore even a protein with a single surface histidine appears to coordinate to multiple copper sites on the IMAC support at neutral pH. The effect of pH on the capacity factors of these variants measured in the absence of imidazole further supports this interpretation. Although the presence of a surface histidine was required for retention at neutral pH, a variant with no surface histidines still partitioned strongly to the IMAC support at higher pH (pH > 7.5). These results indicate the contribution of additional protein-metal-coordinating groups, presumably surface amines, to chromatographic retention in IMAC.
Chromatography, Affinity↗
Colorectal adenocarcinoma: staging and histopathology.
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Adenocarcinoma↗
Bronchogenic cyst causing unilateral ventilation-perfusion mismatch.
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Adult↗
Patent ductus arteriosus causing infradiaphragmatic activity on perfusion lung scintigraphy.
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Adult↗
Case report: pneumomediastinum and pneumothorax complicating colonoscopy.
Colonic perforation is potentially the most serious complication of colonoscopy. Both the clinical manifestation and rapidity of onset of symptoms can vary depending on whether the perforation occurs directly into the peritoneal cavity or into the retroperitoneal space. Colonic perforation is often associated with abdominal pain, although more uncommon presentations have been documented. A case report of a unilateral pneumothorax and pneumomediastinum complicating colonoscopy is described, which responded well to conservative measures without recourse to surgical intervention, antibiotic therapy or parenteral alimentation.
Aged↗
Responses of medullary reticular formation neurons to input from the male genitalia.
1. The medullary reticular formation (MRF) is known to be involved in the modulation of certain reproductive behaviors. Ejaculation in the male, disrupted after spinal transection, may depend on a spinal-bulbo-spinal connection. To determine whether single neurons in the MRF receive sensory input from the male genitalia, the present study was undertaken using electrophysiological techniques. 2. The MRF of 14 urethan-anesthetized mature male rats was searched for single neurons responsive to bilateral electrical stimulation of the dorsal nerve of the penis (DNP). In addition, each DNP-responsive neuron was tested for responsiveness to bilateral electrical stimulation of the pelvic nerve (PN) and to mechanical stimulation (gentle touch, pressure, pinch) of the external genitalia, anus, urethra, and skin over most regions of the body. 3. A total of 165 single neurons responsive to bilateral electrical stimulation of the DNP were isolated and characterized throughout the MRF. All neurons responded to both ipsilateral and contralateral DNP stimulation. The majority of responses were excitatory, and most neurons had no background activity. Some neurons required wind-up with bilateral electrical stimulation of the DNP to respond. 4. About half of the neurons were located in the nucleus reticularis gigantocellularis (Gi); the remainder were located in surrounding (dorsal, ventral, lateral) regions of the MRF. Variations in response properties were found among neurons located in different MRF regions. 5. Eighty-eight DNP-responsive neurons were additionally responsive to bilateral electrical stimulation of the PN. None of the responses to bilateral PN were stronger than those for bilateral DNP and many (48%) were weaker. 6. Of the 165 DNP-responsive neurons, all were responsive to pressure/pinching of the penis; 16% responded to gentle stroking of the glans. Most of these neurons were additionally responsive (bilaterally) to pinching more than one (often all) of the following areas: perineum, scrotum, anus, ears, and toes (forefoot and hindfoot). 7. In conclusion, neurons located in the MRF of male rats are involved in the processing of bilaterally convergent inputs from multiple cutaneous and visceral regions of the body, including the penis and male urogenital tract. These neurons likely exert their effects by directly and/or indirectly activating ascending pathways to rostral regions of the brain important for somatovisceral sensation and motor behavior, and descending pathways to the spinal cord for modulation of segmental sexual reflexes. Contributions are likely for a wide spectrum of sensations and reproductive behaviors.
Animals↗
The Temkin isotherm describes heterogeneous protein adsorption.
Here we examine how heterogeneous protein adsorption arises from multivalent interactions with a seemingly homogeneous functional surface. During adsorption, some arrangement of functional groups on the protein (e.g., charged or hydrophobic amino-acid residues or specific ligand binding sites) interacts with complementary sites distributed on the adsorbent surface. The protein will show the highest affinity for the surface arrangements which best match its own distribution of functional sites, resulting in a distribution of binding energies. To support this interpretation, we show that changing the density of affinity ligands on a surface (immobilized metal ions) is equivalent to changing the number of target groups on a protein (surface histidines). We also report that reversible protein adsorption obeys the Temkin isotherm and propose that model as a practical framework for describing the behavior of proteins adsorbing via multivalent interactions onto surfaces densely derivatized with a random distribution of binding functionalities. This result has important implications for the design of separations materials and the interpretation of biological recognition phenomena.
Adsorption↗
Acute and long-term effects of nine chemicals on the Japanese medaka (Oryzias latipes).
Ninety-six-hour acute and 28-day larval survival and growth tests were conducted with nine organic chemicals, using the Japanese medaka (Oryzias latipes) as the test organism. The nine tested chemicals were allyl isothiocyanate, aniline, benzyl acetate, 4-chloroaniline, 2-chloroethanol, 2,4-diaminotoluene, 1,2-dibromoethane, 2,4-dichlorophenoxyacetic acid (2,4-D), and phenol. The derived 96-h LC50 values for medaka for all chemicals ranged from 0.077 mg/L for allyl isothiocyanate to 2,780 mg/L for 2,4-D. The chronic values for six of the nine chemicals tested ranged from 0.013 mg/L for allyl isothiocyanate to 42.5 mg/L for 2,4-D. Acute-to-chronic ratios for these six chemicals ranged from 1.4 for 2-chloroethanol to 70.9 for 2,4-D. Growth of medaka was significantly reduced in the lowest exposure concentration during 28-dy larval tests with aniline, 4-chloroaniline, and 2,4-diaminotoluene. The estimated maximum acceptable toxicant concentration was reported as less than the lowest exposure concentration of 4.6, 2.2 and 40.3 mg/L for tests with aniline, 4-chloroaniline and 2,4-diaminotoluene, respectively. Chronic values for 2-chloroethanol and medaka were 12.6 mg/L during an embryo-larval test and 22.1 mg/L during the 28-day larval test.
2,4-Dichlorophenoxyacetic Acid↗