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Biomedical subjects

B Johnson

Publications and source records attributed to B Johnson.

At least 145 records · Page 8Linked to original sources

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↗

Selective uptake of estrogenic compounds by Saccharomyces cerevisiae: a mechanism for antiestrogen resistance in yeast expressing the mammalian estrogen receptor.

Estrogen antagonists such as ICI164,384 do not inhibit 17 beta-estradiol (E2)-dependent gene activity in yeast expressing the mammalian estrogen receptor although these compounds bind to receptors isolated from these cells. Various explanations have been offered for antiestrogen resistance in yeast systems including differences in cell-specific components and lack of permeability of the yeast cell wall to these compounds. We have used a strain of Saccharomyces cerevisiae transformed with the human estrogen receptor gene, and two estrogen response elements linked to a lacZ reporter gene to study the pharmacology of estrogen agonists and antagonists. The rank order of potency of estrogen agonists in this strain (CY525) is similar to that in estrogen-dependent mammalian cells: DES > or = E2 > E1 > E3 = zeranol. Competitive binding with 3H-E2 by these compounds in cell-free extracts of CY525 results in a similar order of potency with a reverse order for E1 and E3. The pure estrogen antagonist ICI164,384 also binds to the receptor from cell-free extracts of CY525 with an IC50 of approximately 14nM. As in mammalian cells ICI164,384 does not induce E2-dependent gene activity. However, unlike mammalian cells, E2-induced gene activity in CY525 is not inhibited by ICI164,384. Intact CY525 cells incubated with 3H-17 beta estradiol were found to specifically bind the labeled ligand since excess unlabeled E2 effectively competed for binding. Unlabeled DES and E1 were also found to compete, however, excess unlabeled ICI164,384, E3 and the second generation antagonist ICI182,720 were unable to displace 3H-E2 binding in intact cells. These results indicate that certain compounds enter the intact yeast cell more readily than others and offer an explanation for antagonist resistance in these organisms.

Base Sequence↗

Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.

OBJECTIVE: To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue. BACKGROUND: Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known. METHODS: Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response. RESULTS: Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo. CONCLUSION: Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability.

Adolescent↗

Kinematic and electromyographic analysis of elbow flexion during inertial exercise.

Inertial exercise protocols are currently used clinically to improve and restore normal muscle function even though research to substantiate their effectiveness cannot be cited in the literature. The purpose of this study was to compare simultaneous kinematic and electromyographic (EMG) data obtained from 12 subjects during elbow flexion on the Impulse Inertial Exercise System. Testing sessions consisted of inertial exercise performed using phasic and tonic techniques with loads of: a) 0 kg, b) 2.27 kg, c) 4.54 kg, d) 6.80 kg, e) 9.07 kg. Greater peak angular velocities, peak platform accelerations (change in velocity of platform during elbow flexion), mean and peak triceps brachii muscle EMG activity, and less range of motion were observed during phasic exercise. There was also a general trend for peak angular velocities and peak platform acceleration to increase as the load decreased. No significant difference in mean or peak EMG activity of the biceps brachii muscle was seen between techniques. Clinicians and athletic trainers using inertial exercise should consider both the exercise technique and load characteristics when designing protocols to meet the specific needs of patients.

Journal Article↗

Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis.

BACKGROUND: The monocyte-derived cytokine, tumor necrosis factor alpha (TNF alpha), is essential for host immunity, but overproduction of this cytokine may have serious pathologic consequences. Excess TNF alpha produced in pulmonary tuberculosis may cause fevers, weakness, night sweats, necrosis, and progressive weight loss. Thalidomide (alpha-N-phthalimidoglutarimide) has recently been shown to suppress TNF alpha production by human monocytes in vitro and to reduce serum TNF alpha in leprosy patients. We have therefore conducted a two-part placebo-controlled pilot study of thalidomide in patients with active tuberculosis to determine its effects on clinical response, immune reactivity, TNF alpha levels, and weight. MATERIALS AND METHODS: 30 male patients with active tuberculosis, either human immunodeficiency virus type 1 positive (HIV-1+) or HIV-1-, received thalidomide or placebo for single or multiple 14 day cycles. Toxicity of the study drug, delayed type hypersensitivity (DTH), cytokine production, and weight gain were evaluated. RESULTS: Thalidomide treatment was well tolerated, without serious adverse events. The drug did not adversely affect the DTH response to purified protein derivative (PPD), total leukocyte, or differential cell counts. TNF alpha production was significantly reduced during thalidomide treatment while interferon-gamma (IFN gamma) production was enhanced. Daily administration of thalidomide resulted in a significant enhancement of weight gain. CONCLUSIONS: The results indicate that thalidomide is well tolerated by patients receiving anti-tuberculosis therapy. Thalidomide treatment reduces TNF alpha production both in vivo and in vitro and is associated with an accelerated weight gain during the study period.

Adult↗

Incisional hernias: incidence following abdominal aortic aneurysm repair.

It is thought there is an increased incidence of incisional herniation after the repair of an abdominal aortic aneurysm. We sought to assess this premise by reviewing 281 patients who had undergone abdominal aortic aneurysm repair over the preceding eight years at Concord Hospital. Incisional hernias were found in fourteen patients. This made up 5% of the total group having surgery (281 patients) or 6% of those surviving 12 months or more after operation (231 patients). Of these 231 patients, seven had transverse incision hernias (6.7% of all those with transverse incisions), and seven had vertical incision hernias (5.4% of all those with vertical incisions). Six of the fourteen patients with a hernia had needed an urgent repair of an abdominal aortic aneurysm. We conclude from this study, that there is no evidence of an increased incidence of incisional hernias associated with aneurysmal disease itself. Rather, the factors causing such hernias are common to all laparotomies for major disease in sick, elderly patients, in the absence of intra-abdominal sepsis.

Aged↗

Unusual abdominal location of a dermal cylindroma.

Cylindromas are rare benign adenexal tumors that classically arise on the head and neck, thus earning the name of turban tumor. They are usually benign, but may be multiple and recurrent. A 78-year-old woman noted an abdominal cylindroma, an unusual presentation of this rare cutaneous tumor. The clinical presentation, histologic characteristics, and variations of the dermal cylindroma are reviewed.

Abdominal Muscles↗

Tissue ablation by a free-electron laser tuned to the amide II band.

Efforts to ablate soft tissue with conventional lasers have been limited by collateral damage and by concern over potential photochemical effects. Motivated by the thermal-confinement model, past infrared investigations targeted the OH-stretch mode of water with fast pulses from lasers emitting near 3,000 nm (refs 1, 7-9). What does a free-electron laser offer for the investigation of tissue ablation? Operating at non-photochemical single-photon energies, these infrared sources can produce trains of picosecond pulses tunable to the vibrational modes of proteins, lipids and/or water. We report here that targeting free-electron laser radiation to the amide II band of proteins leads to tissue ablation characterized by minimal collateral damage while maintaining a substantial ablation rate. To account for these observations we propose a novel ablation mechanism based on compromising tissue through resonant denaturation of structural proteins.

Amides↗