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Biomedical subjects

B Johnson

Publications and source records attributed to B Johnson.

At least 37 records · Page 2Linked to original sources

Persistent pain associated with long-term intrathecal morphine administration.

A 32-year-old man with chronic intractable right lower extremity pain unresponsive to multiple neurosurgical and pharmacologic treatments, including intrathecal morphine administration, was successfully treated with sciatic nerve block, discontinuance of opioid therapy, and psychologic interventions. Plasma and urine ratios of morphine metabolites morphine-3-glucuronide and morphine-6-glucuronide were analyzed at the beginning of our interventions, and the results indicated that morphine-3-glucuronide levels were significantly higher than morphine-6-glucuronide levels. The possible association between the observed morphine metabolite ratio and the intractable pain in patients resistant to opioids may have potential clinical implications.

Adult

Effect of detergent combined with large tidal volume ventilation on alveolocapillary permeability.

The combined effect of large tidal volume ventilation (LTVV) and detergent-induced surfactant dysfunction on the clearance kinetics of technetium-99m-labelled diethylene triamine pentaacetate was investigated. Four groups of rabbits (n = 6 in each) were studied: (1) controls, (2) detergent, (3) LTVV, and (4) detergent + LTVV. Clearance was measured for 3 h and the kinetics was analysed by fitting mono- and biexponential equations to the clearance curve and was expressed as a half-life (T 1/2). Pulmonary clearance of 99mTc-DTPA was monoexponential in control animals (T 1/2 = 194 min) and in animals ventilated with LTVV (T 1/2 = 43 min, P < 0.01 compared with controls). In contrast, clearance was biexponential after detergent administration with or without LTVV. T 1/2 values of the fast and slow compartments were 5.4 and 80 min, respectively, with the fast fraction comprising 81% of the radioactivity after detergent alone. When detergent was combined with LTVV, clearance was bicompartmental as with detergent alone, with the same size of the fast fraction. However, clearance from each of the slow (P < 0.01) and fast compartments (P < 0.05) increased significantly. Clearance from the slow compartment was thus similar to T 1/2 during LTVV alone. Large tidal volume ventilation induced a faster than normal clearance of a single compartment, whereas detergent induced kinetics that was distinctly bicompartmental. The mechanisms increasing permeability of the alveolocapillary barrier after detergent and during LTVV seem different and may be additive.

Aerosols

Efficacy of quantitative digital subtraction radiography using radiographs exposed in a multicenter trial.

Digital subtraction radiography (DSR) has been shown to be a sensitive and specific method for the detection of small bony changes in periodontitis. The purpose of this study was to perform a multicenter validation of the DSR in human subjects. Seventeen subjects were enrolled at 3 centers. Feather-edged hydroxyapatite chips (approximately 1, 7 and 10 mg) were used to simulate osseous lesions. Bilateral radiographs were taken with and without chips. Geometry was standardized using a cephalostat and the order of radiographs was determined using a randomization plan. Radiographs were subtracted, lesions isolated, and quantified at a single center without knowledge of the randomization code or location of the chips used in each subject. The overall sensitivity and specificity in detecting 1 mg changes was 87.8% and 100%, respectively. Sensitivity and specificity in detecting 7 mg and 10 mg chips was 100%. A strong linear relationship between actual lesion mass and calculated mass was observed (R2 = 0.94, slope = 0.98, p < 0.0001). No significant differences were observed by center. These data indicate that the DSR is a valid technique for the assessment of alveolar bone changes in multicenter trials.

Adult

IL-1 beta stimulates superoxide and delayed peroxynitrite production by pulmonary vascular smooth muscle cells.

Our previous studies have shown that rat pulmonary microvascular smooth muscle cells (RPMSMC) upregulate inducible nitric oxide synthase (iNOS) and produce nitric oxide (NO) when treated with interleukin-1 beta (IL-1 beta). We now report that an additional effect of IL-1 beta stimulation in RPMSMC is an increase in production of superoxide (O2-) that results in the formation of peroxynitrite (ONOO-). IL-1 beta produced a rapid (within 1 h) concentration-dependent increase in O2-, as detected by ferricytochrome c reduction and lucigenin-enhanced chemiluminescence. O2- production was sensitive to quinacrine and diphenyliodinium, suggesting that NADH and NADPH oxidoreductases were responsible. After induction of iNOS and production of iNOS-derived NO, ONOO- was detected by luminol-enhanced chemiluminescence and was found to cause lipid peroxidation and to form nitrotyrosine in the cytoskeleton, detected by immunostaining. Cell viability, however, appeared to be unaffected. IL-1 beta-mediated induction of RPMSMC-derived ONOO- may have significant effects on pulmonary vascular function in sepsis and inflammatory states.

Animals

Glycine regulation of synaptic NMDA receptors in hippocampal neurons.

1. Although glycine has been identified as a required coagonist with glutamate at N-methyl-D-aspartate (NMDA) receptors, the understanding of glycine's role in excitatory synaptic neurotransmission is quite limited. In the present study, we used the whole cell patch-clamp technique to examine the ability of glycine to regulate current flow through synaptic NMDA receptors at excitatory synapses between cultured hippocampal neurons and in acutely isolated hippocampal slices. 2. These studies demonstrate that the glycine modulatory site on the synaptic NMDA receptor is not saturated under baseline conditions and that increased glycine concentrations can markedly increased NMDA-receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal neurons in both dissociated cell culture and in slice. Saturation of the maximal effect of glycine takes place at different concentrations for different cells in culture, suggesting the presence of heterogenous NMDA receptor subunit compositions. 3. Bath-applied glycine had no effect on the time course of EPSCs in either brain slice or culture, indicating that desensitization of the NMDA receptor is not prevented by glycine over the time course of an EPSC. 4. When extracellular glycine concentration is high, all miniature EPSCs recorded in the cultured hippocampal neurons contained NMDA components, indicating that segregation of non-NMDA receptors at individual synaptic boutons does not occur.

Animals

Evaluation of a pneumonia practice guideline in an interventional trial.

There are few available data to define the medically necessary duration of stay for patients hospitalized with pneumonia. Therefore, we investigated the safety and effectiveness of a practice guideline that provided information about switching patients from parenteral to oral antimicrobials and early hospital discharge. The study was a prospective controlled study with an alternate month design. The practice guideline was studied in 146 "low-risk" pneumonia patients hospitalized during a 22-month period. Medical care consistent with the practice guideline occurred in 64% and 76% of patients during control and intervention periods, respectively (p=0.15). There were no differences in patient outcomes in the control and intervention groups when measured 1 mo after hospital discharge, including hospital readmission rates, health-related quality of life, and patient satisfaction. Explicit and implicit review revealed that 98.6% (95% confidence interval [CI]: 95.1%, 99.8%) of low-risk patients would not have benefited from continued hospitalization after the fourth hospital day. The 30-d survival rate of the low-risk pneumonia patients was 99.3% (95% CI: 96.2%, 100%) and patient outcomes appeared to be favorable compared with previously published values. We conclude that duration of hospital stay was frequently consistent with the practice guideline in both study groups, and patient outcomes remained unchanged. The guideline will require additional testing before it can be recommended for use.

Administration, Oral

Diagnosis of oleander poisoning in livestock.

Since mid-1989, 37 cases of oleander poisoning in livestock have been diagnosed at the California Veterinary Diagnostic Laboratory System. The most frequent source for oleander exposure was plant clippings. Sudden death was the most common presenting complaint. Other signs reported included diarrhea, pulmonary edema, tachycardia, cardiac arrhythmias, colic, and lethargy. In the past, a presumptive diagnosis of oleander poisoning could be based only on matching clinical signs with evidence of consumption of oleander. A new 2 dimensional Thin-layer chromatography analysis of ingesta for oleandrin and an awareness of lesions in heart muscle have greatly improved the ability to diagnose oleander toxicosis.

Animal Feed

Toxicity profile of the investigational new biotherapeutic agent, B43 (anti-CD19)-pokeweed antiviral protein immunotoxin.

The investigational biotherapeutic agent, B43(anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin, has shown substantial anti-leukemic activity in SCID mouse models of human B-lineage leukemia and lymphoma. In this report, we describe the results of a comprehensive preclinical toxicity study which determined the toxicity profile of B43-PAP in BALB/c mice. Administration of unconjugated B43 monoclonal antibody was not associated with any toxicity, whereas B43-PAP caused dose-limiting and cardiac and renal toxicities which were fatal. In addition, B43-PAP also caused multifocal skeletal myofiber necrosis, which was associated with abnormal gait and lethargy. Notably, parenteral administrations of methylprednisolone, pentoxyphylline, or dopamine were able to markedly reduce B43-PAP related toxicity. This study provides a basis for further evaluation of the toxicity of B43-PAP in monkeys and humans.

Animals

Paediatric rheumatology: clinical practice review. Physiotherapy and occupational therapy for juvenile chronic arthritis: custom and practice in five centres in the UK, USA and Canada

Physiotherapy and occupational therapy are widely accepted as being of central importance for the treatment of juvenile chronic arthritis (JCA). However, these approaches have rarely been subject to critical scrutiny. The aims of this report are to highlight some of the inter-centre similarities and differences observed in the implementation of physical and occupational therapy for JCA, and to emphasize the need for scientifically controlled research in this area. During a series of visits to several paediatric rheumatology units in the UK, USA and Canada, three aspects of the service were noted: treatment philosophy, physical interventions used for the treatment of JCA and quality-of life and independence training activities. There was general consensus with the philosophy that early physical intervention was a vital part of the treatment plan for JCA, although all therapists were concerned that compliance with treatment modalities was poor. Differences between units in the approach to acute arthritis, the use of foot othoses and wrist splints, the treatment of joint contractures and the use of general quality-of-life training activities were noted. Although it was widely recognized that controlled research into the efficacy of physical intervention was needed, no centre had a co-ordinated plan for such investigations. Keywords: Juvenile chronic arthritis, Physiotherapy, Occupational therapy

Journal Article

Heavy metal concentrations in injured racehorses.

Records were reviewed of horses that had fatal injuries at California racetracks over a 16-mo period. Horses were categorized based on injury type, sex, age and breed. Arsenic, cadmium, copper, iron, lead, molybdenum and zinc concentrations were measured in the liver and kidneys from each horse. Arsenic and lead were not detected in any tissues. Liver heavy metal concentrations were not related to the injury type. Kidney iron concentrations were significantly (P < 0.05) higher in horses with ligament ruptures and in horses with fractured sesamoid, carpus or metacarpus/metatarsus bones. Liver cadmium, kidney cadmium, and liver iron were higher (P < 0.05) in horses > 2 y old than in 2-y-olds. Liver cadmium concentrations were higher (P < 0.05) in Thoroughbreds than in Quarter Horses.

Aging

Physiotherapy and occupational therapy for juvenile chronic arthritis: custom and practice in five centres in the UK, USA and Canada.

Physiotherapy and occupational therapy are widely accepted as being of central importance for the treatment of juvenile chronic arthritis (JCA). However, these approaches have rarely been subject to critical scrutiny. The aims of this report are to highlight some of the inter-centre similarities and differences observed in the implementation of physical and occupational therapy for JCA, and to emphasize the need for scientifically controlled research in this area. During a series of visits to several paediatric rheumatology units in the UK, USA and Canada, three aspects of the service were noted: treatment philosophy, physical interventions used for the treatment of JCA and quality-of-life and independence training activities. There was general consensus with the philosophy that early physical intervention was a vital part of the treatment plan for JCA, although all therapists were concerned that compliance with treatment modalities was poor. Differences between units in the approach to acute arthritis, the use of foot orthoses and wrist splints, the treatment of joint contractures and the use of general quality-of-life training activities were noted. Although it was widely recognized that controlled research into the efficacy of physical intervention was needed, no centre had a co-ordinated plan for such investigations.

Arthritis, Juvenile

Variability of regurgitation in Björk-Shiley mitral valves and relationship to disc occluder design: an in vitro two-dimensional color-Doppler flow mapping study.

BACKGROUND AND AIMS OF THE STUDY: Normal prosthetic valves have regurgitation that varies according to valve type and design. The Björk-Shiley prosthetic mitral valve is a tilting disc valve that has undergone design changes since its introduction. From 1969 to 1981, Delrin, was used to make the disc occluder. After 1971, the occluder was made from Pyrolite (i.e. Conical and Radiopaque-Spherical valves). Our aim was to quantify the regurgitation of Delrin and Radiopaque-Spherical Björk-Shiley prosthetic mitral valves with color-Doppler flow mapping in an in vitro model that simulates transesophageal echocardiography imaging. MATERIALS AND METHODS: Normal unimplanted Björk-Shiley Delrin (BSD), Björk-Shiley Radiopaque-Spherical (BSS) and explanted (17 +/- 3 yrs) BSD valves (25, 27, and 29 mm) were studied in a pulse duplication system. The regurgitant leakage volume of the valves was measured with an electromagnetic flow probe at flow rates of 3.0, 5.0, and 7.0 L/min, a pulse rate of 70 beats/min, and a mean systemic pressure of 100 mmHg. Color-Doppler flow mapping was performed with a 3.7 MHz transducer positioned on the atrial chamber at an image depth of eight centimeters. The maximal regurgitant jet areas were measured offline and averaged from three beats. RESULTS: Maximal jet area, measured with color-Doppler flow mapping, correlated with regurgitant leakage volume (r = 0.82). Normal unimplanted and explanted BSD valves had greater regurgitant leakage volumes and jet areas than BSS valves for all sizes and flow rates studied. Regurgitant jet areas of normal unimplanted and explanted BSD valves were similar. CONCLUSION: Knowledge of the type of Björk-Shiley valve is important in the clinical evaluation of regurgitation severity by transesophageal echocardiography. The echocardiographic appearance of regurgitation of BSD valves does not necessarily imply valve dysfunction.

Blood Flow Velocity

High-speed exercise history and catastrophic racing fracture in thoroughbreds.

OBJECTIVE: To investigate the relation between several racing speed history characteristics and risk of fatal skeletal injury (FSI) in racing Thoroughbreds. ANIMALS: 64 Thoroughbreds euthanatized during a 9-month period in 1991 at a California racemeet because of a catastrophic fracture incurred while racing (cases), identified retrospectively. For each race in which an FSI occurred, 1 control horse was randomly selected from the noncatastrophically injured participants. PROCEDURE: Racing and officially timed workout histories were obtained for each horse. Several history characteristics were calculated to summarize racing career patterns and high-speed exercise schedules prior to date of injury and included age at first race, proportion of career spent laid up, average duration of laid up periods, average lifetime racing frequency, time from last lay up to date of injury, and total and rate of distance accumulated 1 to 6 months prior to date of injury. History characteristics associated with FSI were screened by paired t-test and studied in detail, using conditional logistic regression. RESULTS: High total and high average daily rates of exercise distance accumulation within a 2-month period were associated with higher risks for FSI during racing, yet career patterns, such as age at first race or total proportion of career spent laid up, were not found to be associated with risk for FSI. A horse that had accumulated a total of 35 furlongs of race and timed-work distance in 2 months, compared with a horse with 25 furlongs accumulated, had an estimated 3.9-fold increase in risk for racing-related FSI (95% confidence interval = 2.1, 7.1). A horse that had accumulated race and timed-work furlongs at an average rate of 0.6 furlong/d within a 2-month period, compared with a horse with an average of 0.5 furlong/d, had an estimated 1.8-fold increase in risk for racing-related FSI (95% confidence interval = 1.4, 2.6). CONCLUSIONS AND CLINICAL RELEVANCE: Thoroughbred racehorses that either accumulate large total high-speed distances or rapidly accumulate high-speed distances within a 2-month period may be at increased risk for FSI during racing.

Animals

A 110-kD nuclear shuttling protein, nucleolin, binds to the neurite-promoting IKVAV site of laminin-1.

The basement membrane protein laminin and the IKVAV-containing sequence from the laminin alpha 1 chain have been found to promote the differentiation of primary neurons and a variety of neural cell lines. We previously reported that a 110-kd IKVAV-binding protein (LBP110) isolated from brain appears to be a member of the beta-amyloid precursor protein (APP) family by immunologic and functional studies, which showed that LBP110/APP is also important in neurite outgrowth (Kibbey et al.: Proc Natl Acad Sci USA 90:10150-10153, 1993). In the preparation of this binding protein, a contaminating IKVAV-binding protein of identical molecular weight, nucleolin, was also identified. Here we have studied the relationship between these binding proteins. We find that nucleolin binds specifically to the IKVAV sequence independently of LBP110/ApP. We have also demonstrated significant levels of nucleolin in mature brain and in differentiating neural cells, suggesting that nucleolin functions not only in cell proliferation and in ribosome biogenesis as was previously reported, but also in the differentiation and maintenance of neural tissue. Our identification of cytoplasmic and cell-surface nucleolin, an IKVAV-binding protein, suggests that this protein may function in signalling by extra-cellular matrix.

Amino Acid Sequence

Neurotoxicity of the human immunodeficiency virus type 1 tat transactivator to PC12 cells requires the Tat amino acid 49-58 basic domain.

The acquired immunodeficiency syndrome (AIDS) frequently involves the central nervous system (CNS) and manifests as dementia due to encephalitis or diffuse neurodegeneration. Human immunodeficiency virus type 1 (HIV-1) proteins, potentially transported into the CNS by mononuclear inflammatory cells, have been implicated in the etiology of this HIV-1 associated neurological dysfunction. Here we investigate the neurotoxicity of the essential HIV-1 regulator protein Tat in vivo after microinfusion into the rat brain and in vitro using PC12, NG108-15, and GT17 neuronal cell lines. Infusion of either chemically synthesized Tat (Tat86) or recombinant Tat (rTat) into the striatal gray matter in Sprague-Dawley rats resulted in postural deviation ipsilateral to the infusion, a clinical presentation in rats associated with complete striatal dysfunction. Histologic examination 3 days after infusion revealed massive necrosis in the area of the distribution of the infusion. Infusion of heat denatured rTat, peptide Tat49-58, or peptide Tat57-86 did not result in clinically or histologically detectable brain damage. After 3 days incubation in vitro, the lethal dose for half (LD50) of PC12 cells due to rTat was 5 micrograms/ml. The LD50 for Tat86 under the same conditions was 10 micrograms/ml. Tat49-58 and Tat57-86 peptides were not toxic in vitro even at 10-fold higher doses. At 5 micrograms/ml, rTat was toxic to 100% of GT17 cells after 24 hr. At 5 micrograms/ml, Tat86 was toxic to 90% of the NG108-15 cells after 7 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

Genetic construction of a phosphorylation site in ricin A chain: specific radiolabeling of recombinant proteins for localization and degradation studies.

Ricin A chain was modified by the addition of the heptapeptide LRRASLG (Kemptide) and a histidine tag for bacterial expression. The mutagenized toxin was purified by nickel column and could be phosphorylated in vitro by protein kinase A as demonstrated by labeling with [gamma-32P] ATP. Kemptide-A chain could be labeled even after reassociation with ricin B chain or disulfide linkage to antibody to form an immunotoxin. The 32P label in all cases was associated only with the A chain; ricin B chain and antibody were not kinase substrates alone or after conjugation. Kemptide-immunotoxin was tested in cytotoxicity assays and used to monitor internalization of the toxin moiety after [32P] phosphorylation.

Amino Acid Sequence

Melatonin biosynthesis in photoreceptor-enriched chick retinal cell cultures: role of cyclic AMP in the K(+)-evoked, Ca(2+)-dependent induction of serotonin N-acetyltransferase activity.

The roles of cyclic AMP and calcium in the regulation of serotonin N-acetyltransferase (NAT) activity were studied in low density monolayer cultures of chick retinal photoreceptors and neurons. Photoreceptor-enriched retinal cell cultures were prepared from embryonic day 6 retinas and cultured for 6 days. NAT activity in these cultures could be induced by treatment with cyclic AMP protagonists, 8Br-cyclic AMP, forskolin, and 3-isobutyl-1-methylxanthine (IBMX), or by treatment with depolarizing concentrations of extracellular K+. The stimulatory effect of K+, which involves Ca2+ influx through dihydropyridine-sensitive channels, was mediated at least in part by cyclic AMP, as indicated by the following observations. Depolarizing concentrations of K+ stimulated the formation of cyclic AMP, and the stimulatory effects of K+ on both cyclic AMP formation and on NAT activity were synergistically potentiated by the cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). MDL 12,330A, a putative adenylate cyclase inhibitor, inhibited K(+)-evoked cyclic AMP accumulation and induction of NAT activity over the identical concentration range. In contrast, MDL 12,300A failed to inhibit the induction of NAT elicited by 8Br-cyclic AMP. H-89, an inhibitor of cyclic AMP-dependent protein kinase, antagonized the induction of NAT activity by either forskolin or K+ with equal potency for both stimuli. These results suggest that cyclic AMP plays an essential role in the induction of NAT activity that occurs as a consequence of membrane depolarization. Cyclic AMP and Ca2+ may also interact at a step distal to adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine