Search PubMed⌕ Search

Biomedical subjects

T A Johnson

Publications and source records attributed to T A Johnson.

At least 19 recordsLinked to original sources
PubMed2006

Fast ground state manipulation of neutral atoms in microscopic optical traps.

We demonstrate Rabi flopping at MHz rates between ground hyperfine states of neutral 87Rb atoms that are trapped in two micron sized optical traps. Using tightly focused laser beams we demonstrate high fidelity, site specific Rabi rotations with cross talk on neighboring sites separated by 8 microm at the level of 10(-3). Ramsey spectroscopy is used to measure a dephasing time of 870 micros, which is approximately 5000 longer than the time for a pi/2 pulse.

Journal Article↗
PubMed2005

A LabVIEW model incorporating an open-loop arterial impedance and a closed-loop circulatory system.

While numerous computer models exist for the circulatory system, many are limited in scope, contain unwanted features or incorporate complex components specific to unique experimental situations. Our purpose was to develop a basic, yet multifaceted, computer model of the left heart and systemic circulation in LabVIEW having universal appeal without sacrificing crucial physiologic features. The program we developed employs Windkessel-type impedance models in several open-loop configurations and a closed-loop model coupling a lumped impedance and ventricular pressure source. The open-loop impedance models demonstrate afterload effects on arbitrary aortic pressure/flow inputs. The closed-loop model catalogs the major circulatory waveforms with changes in afterload, preload, and left heart properties. Our model provides an avenue for expanding the use of the ventricular equations through closed-loop coupling that includes a basic coronary circuit. Tested values used for the afterload components and the effects of afterload parameter changes on various waveforms are consistent with published data. We conclude that this model offers the ability to alter several circulatory factors and digitally catalog the most salient features of the pressure/flow waveforms employing a user-friendly platform. These features make the model a useful instructional tool for students as well as a simple experimental tool for cardiovascular research.

Animals↗
PubMed2001

Electrical properties and conduction in reperfused papillary muscle.

The reversibility of ischemia-induced changes of extracellular K(+) concentration ([K(+)](o)), resting membrane potential (E(M)), and passive cable-like properties, ie, extracellular resistance and cell-to-cell electrical coupling, and their relationship to recovery of conduction and contraction is described in 25 reperfused rabbit papillary muscles. No-flow ischemia caused extracellular K(+) accumulation, depolarization of E(M), an increase in whole-tissue (r(t)), external (r(o)), and internal (r(i)) longitudinal resistances, and failure of conduction and contraction. Muscles were reperfused 10 minutes after the onset of ischemia related cell-to-cell electrical uncoupling, ie, 26+/-1 minutes after arrest of perfusion. In 11 muscles, incomplete reflow occurred with only partial recovery of [K(+)](o) and r(t). In the remaining 14 muscles, reperfusion caused a rapid and parallel decrease in [K(+)](o), r(t), and r(o). When complete tissue reperfusion occurred, cell-to-cell electrical uncoupling was largely reversible. Thus, cell-to-cell electrical uncoupling did not indicate irreversible injury. Reperfusion induced a depolarizing current widening the difference between the K(+) equilibrium potential and the E(M). This difference decreased after longer periods of reperfusion. Conduction was restored and conduction velocity approached preischemic values as cell-to-cell electrical interaction was reestablished and E(M) recovered. The recovery of r(o) preceded r(i), decreasing the ratio of the extracellular to intracellular resistance early in reperfusion, an effect predicted to influence the amplitude of the extracellular voltage field and electrocardiographic ST segments during reperfusion.

Animals↗
PubMed2000

Synergistic cytotoxicity of iodine-131-anti-CD20 monoclonal antibodies and chemotherapy for treatment of B-cell lymphomas.

Preliminary clinical trials suggest that iodine-131 ((131)I)-labeled anti-CD20 monoclonal antibodies (MAbs) are effective single agents for the treatment of relapsed non-Hodgkin's B-cell lymphomas. However, despite high initial response rates, most patients treated in this manner will eventually relapse. We hypothesized that regimens combining (131)I-anti-CD20 antibodies with standard chemotherapeutic agents may provide synergistic anti-tumor effects, and may improve the durability of responses in patients with lymphoma. To identify promising agents for clinical testing, we assessed the in vitro cytotoxicity of combinations of (131)I-anti-B1 (anti-CD20) antibody and 8 chemotherapeutic agents using 2 human CD20-expressing lymphoma cell lines and 2 corroborative assays, the thiazolyl tetrazolium bromide (MTT) and the Trypan blue dye exclusion assays. ID(50) isobolographic and dose modification factor (DMF) analyses were used to classify interactions between the (131)I-anti-B1 antibody and the chemotherapeutic agents as supra-additive (synergistic), additive or sub-additive. Cytarabine and fludarabine were markedly supra-additive when combined with the radioimmunoconjugate, with the combination enhancing cytotoxicity 3. 5- to 5.2-fold over the level expected by simple addition of the 2 agents (DMFs 3.5-5.2). Etoposide, doxorubicin and SN-38 were moderately supra-additive (DMFs 2.0-2.8). Cisplatin and 4-hydroxycyclophosphamide exhibited merely additive cytotoxicity (DMFs 1.0-1.1). Thus, combination regimens containing (131)I-labeled anti-CD20 antibodies and nucleoside analogs or topoisomerase inhibitors appear particularly attractive for future clinical trials.

Antibodies, Monoclonal↗
PubMed2000

Therapy of B-cell lymphomas with monoclonal antibodies and radioimmunoconjugates: the Seattle experience.

Monoclonal antibodies (mAbs) and radioimmunoconjugates targeting B-cell differentiation antigens have emerged as promising new treatments for patients with relapsed non-Hodgkin's lymphoma. This review focuses on our experience in Seattle over the past decade treating relapsed B-cell non-Hodgkin's lymphomas. In initial pilot studies, we administered escalating doses of the unmodified murine anti-CD20 mAb 1F5 to four patients with multiply relapsed lymphoma and-documented the dose-dependent penetration of antibody into the bone marrow and lymph nodes. The two patients who received the higher doses (1032 mg and 2380 mg) had remissions of brief duration, including one minor response lasting 2 weeks and one partial response lasting 6 weeks. Sequential phase-I and -II trials with myeloablative doses of iodine-131-mAbs have documented complete responses in 30 of 36 (83%) patients treated and, most importantly, many of these responses have been durable. A recent long-term follow-up study of the 29 patients treated with myeloablative doses of the I-131-labeled murine anti-B1 (anti-CD20) antibody has documented estimated overall and progression-free survival rates of 68% and 42%, respectively, with a median follow-up time of 42 months. To optimize the durability of responses, we are currently conducting a phase-I/II trial studying the toxicity and efficacy of I-131-anti-B1 antibody given in combination with high-dose etoposide and cyclophosphamide and autologous hematopoietic stem cell rescue.

Antibodies, Monoclonal↗
PubMed2000

Cloning and sequencing of the Candida albicans C-4 sterol methyl oxidase gene (ERG25) and expression of an ERG25 conditional lethal mutation in Saccharomyces cerevisiae.

The ERG25 gene encoding the Candida albicans C-4 sterol methyl oxidase was cloned and sequenced by complementing a Saccharomyces cerevisiae erg25 mutant with a C. albicans genomic library. The Erg25p is comprised of 308 amino acids and shows 65 and 38% homology to the enzymes from S. cerevisiae and Homo sapiens, respectively. The protein contains three histidine clusters common to nonheme iron-binding enzymes and an endoplasmic reticulum retrieval signal as do the proteins from S. cerevisiae and humans. A temperature-sensitive (ts) conditional lethal mutation of the C. albicans ERG25 was isolated and expressed in S. cerevisiae. Sequence analysis of the ts mutant indicated an amino acid substitution within the region of the protein encompassed by the histidine clusters involved in iron binding. Results indicate that plasmid-borne conditional lethal mutants of target genes have potential use in the rescue of Candida mutations in genes that are essential for viability.

Amino Acid Sequence↗
PubMed2000

Effect of rates of perfusion on dominant frequency and defibrillation energy in isolated fibrillating hearts.

This study assessed the influence of rates of reperfusion on excitability of the myocardium using dominant frequency (DF) (in Hz) of VF and the relationship of DF to the minimum defibrillation energy (MDE) (in J). Our hypothesis was that increasing flow during reperfusion increases DF that raises MDE. Initially, six Langendorff perfused swine hearts were serially fibrillated and perfusion arrested for 4 minutes followed by reperfusion and defibrillation to establish reproducibility of the model. The epicardial ECG was analyzed for DF. In subsequent studies (n = 8), no flow VF was followed by 1-minute reperfusion at normal flow or 10% flow (low flow) and shocked with increasing energy via epicardial pads until defibrillation. The DF at onset of no flow VF was 9.5 +/- 1.4 and decreased to 3.6 +/- 1.4 after 4 minutes. Reperfusion at normal flow increased the DF of VF compared to low flow after 1 minute (10.8 +/- 1.1 vs 4.5 +/- 1.1 Hz, P = 0.0002) and was associated with increased defibrillation energy requirements (13.5 +/- 5.0 vs 7.3 +/- 6.2 J, P = 0.047). In summary, defibrillation energy requirements are lower when myocardial excitability is reduced during low flow reperfusion.

Animals↗
PubMed2000

Modulation of pituitary somatostatin receptor subtype (sst1-5) messenger ribonucleic acid levels by changes in the growth hormone axis.

The role of individual components of the hypothalamic-pituitary-GH axis in the modulation of pituitary somatostatin (SRIF) receptor subtype (sst1-5) synthesis was assessed using multiplex RT-PCR to measure receptor messenger RNA (mRNA) levels in normal rats and spontaneous dwarf rats (SDRs). In SDRs, a strain with no immunodetectable GH, pituitary sst1 and sst2 mRNA levels were elevated, sst5 mRNA levels were reduced, and sst3 and sst4 mRNA levels did not significantly differ from those in normal controls. Treatment of SDRs with GH (72 h), but not insulin-like growth factor I, significantly decreased sst2 mRNA levels and increased sst4 and sst5 mRNA levels above vehicle-treated control levels. To test whether more rapid changes in circulating GH levels could alter SRIF receptor subtype expression, normal rats were infused (iv) with GH-releasing hormone (GHRH) for 4 h in the presence or absence of SRIF antiserum. GHRH infusion increased pituitary sst1 and sst2 and decreased sst5, but had no effect on sst3 and sst4 mRNA levels. Immunoneutralization of SRIF, which produced a rise in circulating GH levels, did not alter basal or GHRH-mediated SRIF receptor subtype expression. These observations indicate that acute suppression of SRIF tone does not regulate pituitary SRIF receptor subtype mRNA levels in vivo. The possibility that elevated circulating GH concentrations induced by GHRH infusion were responsible for the observed changes in SRIF receptor subtype mRNA levels was examined by infusing SDRs with GHRH for 4 h. GHRH did not increase sst1 mRNA levels in SDRs above their already elevated value. However, GHRH infusion produced an increase in sst2 and a decrease in sst5 mRNA levels similar to those observed in normal rats, indicating that the acute effects of GHRH on SRIF receptor subtype expression are independent of circulating GH levels. Primary rat pituitary cell cultures were incubated with GHRH (10 nM) or forskolin (10 microM) for 4 h to determine whether GHRH could directly mediate SRIF receptor subtype mRNA. GHRH treatment increased sst1 and sst2 mRNA levels and decreased sst5 mRNA levels, but had no effect on sst3 and sst4, similar to the results in vivo. The effect of forskolin mimicked that of GHRH on sst1, sst2, and sst5 mRNA, suggesting that GHRH acts through cAMP to directly mediate gene transcription or mRNA stability of these SRIF receptor subtypes. In addition, forskolin reduced sst3 and sst4 expression. These results strongly suggest that rat pituitary sst1, sst2, and sst5 mRNA levels are regulated both in vivo and in vitro by GHRH. The stimulatory action of GHRH on sst1 and sst2 and the inhibitory action on sst5 indicate that these receptor subtypes have independent and unique roles in the modulation of pituitary GH release.

Animals↗
PubMed1999

Effects of moisture and sorption on bioavailability of p-hydroxybenzoic acid to Arthrobacter sp. in soil.

Effects of bioavailability on degradation of 14C-p-hydroxybenzoate were examined using sterile soil inoculated with Arthrobacter sp. Physical accessibility of p-hydroxybenzoate was controlled by varying pore continuity with a range of moisture regimes (-33 to -420 kPa), whereas sorption was controlled via addition of an exchange resin. Arthrobacter sp. accessed 94% of p-hydroxybenzoate in soil at -33 kPa, owing to continuity of soil pores and sufficient cells to exploit available space. A deviation in degradation kinetics at -420 kPa soil was attributed to inaccessible p-hydroxybenzoate in solution. Addition of resin decreased extent of degradation, though the effect diminished as pore continuity decreased. Subtle differences in effects of these processes on degradation kinetics may facilitate their separate treatment in environmental fate models.

Absorption↗
PubMed1999

Anterior cervical plating for the treatment of neoplasms in the cervical vertebrae.

OBJECT: To assess clinical outcome and survival in patients with cervical vertebral spinal neoplasms after they have undergone anterior decompression and cervical plate stabilization (ACPS) by using either autologous bone graft or polymethylmethacrylate (PMMA) as the anterior load-bearing support structure. METHODS: This was a retrospective case study composed of 30 patients harboring cervical spinal vertebral neoplasms who underwent anterior cervical decompression and (ACPS) within a 7-year period. Postoperative immobilization included treatment in a halo brace in two cases and in a hard cervical collar for the remaining patients. Postoperatively most patients underwent radio- and/or chemotherapy. All patients except one benefited from a significantly improved quality of life with decreased pain and/or improved neurological status. The mean Kaplan-Meier survivoral estimate was 35.8 months (range 8 days-11.3 years, with 10 patients alive at most recent follow-up contact). Patients achieved long-term or lifelong mechanical stability in the cervical spine, and only one patient required a repeated posterior stabilization procedure. No hardware-related complications occurred. One patient died 8 days postoperatively of pneumonia. A nonsignificant difference in survival (p = 0.2164) was observed between patients harboring metastatic neoplasms (26.8 months) and those harboring lymphomatous and multiple myeloma neoplasms (54 months). CONCLUSIONS: Favorable clinical outcome of both neurological symptoms and pain can be achieved using ACPS after surgery for neoplasms in the cervical vertebrae. Furthermore, long-term or lifelong cervical spine mechanical stability with bone fusion is achieved using this technique even when radiation therapy is delivered to the site of the bone graft.

Adult↗
PubMed1998

Electrodeposited iridium oxide pH electrode for measurement of extracellular myocardial acidosis during acute ischemia.

In the present paper, fabrication, characterization, and physiological applications of a solid-state pH electrode are described. The pH sensing layer was based on an anodic electrodeposited iridium oxide film (AEIROF). Sputtered platinum electrodes (1 mm diameter) fabricated on flexible Kapton films or platinum wires were used as planar or cylindrical supports. Each electrode site was coated with Nafion to attenuate the interference of anionic redox species and to protect the electrode surface during in vivo measurements. Performance of the AEIROF was evaluated, for the first time, as a pH electrode and proved to have a slightly super-Nernstian response with slope of -63.5 +/- 2.2 mV/pH unit for both wire and planar sputtered platinum electrodes. Linear pH responses were obtained in the pH range 2-10. The electrodes have a working lifetime of at least 1 month with accuracy of about 0.02 pH unit and fast response time. The electrodes showed very low sensitivities for different species, such as Na+, K+, Li+, NH4+, Ca2+, Mg2+, dissolved oxygen, lactate, ascorbate, and urate, which are important for physiological applications. The electrodes were applied in extracellular pH measurements during brief regional ischemia in a swine heart and no-flow ischemia in an isolated rabbit papillary muscle. A first report on extracellular pH, K+, and lactate simultaneous measurements during no-flow ischemia using the AEIROF pH electrode and the previously described K+ and lactate electrodes is presented as well.

Acidosis↗
PubMed1998

Negative inotropic vagal preganglionic neurons in the nucleus ambiguus of the cat: neuroanatomical comparison with negative chronotropic neurons utilizing dual retrograde tracers.

The vagal postganglionic controls of cardiac rate and left ventricular contractility are mediated by separate intracardiac ganglia, the sino-atrial (SA) and cranio-ventricular (CV) ganglia, respectively. We injected a different retrograde tracer into each of these ganglia (in the same animal) and subsequently examined the brain for the presence of single labeled or double labeled vagal preganglionic neurons. Retrogradely labeled cells from either ganglion were found exclusively in the ventrolateral nucleus ambiguus (NA-VL). There was considerable overlap in the distribution of labeled cells from either ganglion, however fewer than 3% of labeled neurons were double labeled. The data are consistent with the hypothesis that the preganglionic controls of cardiac rate and left ventricular contractility are mediated by largely separate but overlapping groups of cardioinhibitory neurons originating from the NA-VL. These neurons have parallel but morphologically independent pathways projecting to the SA and CV ganglia. Physiological experiments are needed to support this hypothesis.

Animals↗
PubMed1998

Reoperation in patients after anterior cervical plate stabilization in degenerative disease.

STUDY DESIGN: Consecutive case retrospective chart review. OBJECTIVES: First, to assess whether the number of' patients requiring a second cervical surgical intervention was changed as a result of using anterior cervical plate stabilization, and second, to determine the additional risks and/or benefits associated with the hardware implantation. SUMMARY OF BACKGROUND DATA: The optimal technique of performing stabilization, arthrodesis, and alignment of a cervical segment after discectomy with neural decompression in degenerative disease has yet to be determined. METHODS: The charts of 402 patients who had undergone an anterior cervical discectomy and arthrodesis for degenerative disease performed both with and without anterior cervical plate stabilization were reviewed, and reoperation data were compiled. The average follow-up time was 3.8 years (range, 1.5-9.4 years). RESULTS: Of 365 patients with 1- or 2-level cervical arthrodesis, 22 required a second surgical intervention (20 bone alone, 2 with anterior cervical plate stabilization). The Log-Rank test, which uses all patients and their total follow-up periods, was statistically significant favoring anterior cervical plate stabilization at one and two levels (P = 0.015). CONCLUSIONS: The addition of anterior cervical plate stabilization in one- and two-level cervical degenerative disease supplements the internal stabilization initially provided by the bone graft, and yields a lower reoperation rate.

Adult↗
PubMed1998

Substance P immunoreactive nerve terminals in the dorsolateral nucleus of the tractus solitarius: roles in the baroreceptor reflex.

Physiological and light microscopic evidence suggest that substance P (SP) may be a neurotransmitter contained in first-order sensory baroreceptor afferents; however, ultrastructural support for this hypothesis is lacking. We have traced the central projections of the carotid sinus nerve (CSN) in the cat by utilizing the transganglionic transport of horseradish peroxidase (HRP). The dorsolateral subnucleus of the nucleus tractus solitarius (dlNTS) was processed for the histochemical visualization of transganglionically labeled CSN afferents and for the immunocytochemical visualization of SP by dual labeling light and electron microscopic methods. Either HRP or SP was readily identified in single-labeled unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS. SP immunoreactivity was also identified in unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS, which were simultaneously identified as CSN primary afferents. However, only 15% of CSN terminals in the dlNTS were immunoreactive for SP. Therefore, while the ultrastructural data support the hypothesis that SP immunoreactive first-order neurons are involved in the origination of the baroreceptor reflex, they suggest that only a modest part of the total sensory input conveyed from the carotid sinus baroreceptors to the dlNTS is mediated by SP immunoreactive CSN terminals. Five types of axo-axonic synapses were observed in the dlNTS. SP immunoreactive CSN afferents were very rarely involved in these synapses. Furthermore, SP terminals were never observed to form the presynaptic element in an axo-axonic synapse with a CSN afferent. Therefore, SP does not appear to be involved in the modulation of the baroreceptor reflex in the dlNTS.

Afferent Pathways↗
PubMed1998

Ultrastructural circuitry of cardiorespiratory reflexes: there is a monosynaptic path between the nucleus of the solitary tract and vagal preganglionic motoneurons controlling atrioventricular conduction in the cat.

We have tested the hypothesis: (1) that presumptive negative dromotropic vagal preganglionic neurons in the ventrolateral nucleus ambiguus (NA-VL) can be selectively labelled from the heart, by injecting one of two fluorescent tracers into the two intracardiac ganglia which independently control sino-atrial (SA) rate or atrioventricular (AV) conduction; i.e., the SA and AV ganglia, respectively. The NA-VL was examined for the presence of single and/or double labelled cells. Over 91% of vagal preganglionic neurons in the NA-VL projecting to either intracardiac ganglion did not project to the second ganglion. Consequently, we also tested the hypothesis: (2) that there is a monosynaptic connection between neurons of the medial, and/or dorsolateral nucleus of the solitary tract (NTS), rostral to obex, and negative dromotropic neurons in the NA-VL. An anterograde tracer was injected into the NTS, and a retrograde tracer into the AV ganglion. The anterograde marker was found in both myelinated and unmyelinated axons in the NA-VL, as well as in nerve terminals. Axo-somatic and axo-dendritic synapses were detected between terminals labelled from the NTS, and retrogradely labelled negative dromotropic neurons in the NA-VL. This is the first ultrastructural demonstration of a monosynaptic pathway between neurons in the NTS and functionally associated (negative dromotropic) cardioinhibitory neurons. The data are consistent with the hypothesis that the neuroanatomical circuitry mediating the vagal baroreflex control of AV conduction may be composed of as few as four neurons in series, although interneurons may also be interposed within the NTS.

Animals↗
PubMed1998

Diastolic shape of the right ventricle of the heart.

BACKGROUND: Knowledge of right ventricular (RV) shape is important to the understanding of RV mechanical function and for the improvement of clinically important RV volume estimation techniques. Refinements to the simplest conceptions of RV shape are presented statistically here, based on a quantitative analysis of three-dimensional magnetic resonance (MR) images of excised lamb hearts. METHODS: The passive shape of the heart in six freshly excised lamb hearts was studied with MR imaging with independent passive pressurization of both ventricles. Global features of shape were assessed, including measurement of short-axis, cross-sectional shape parameters associated with the pinched-arc model. RESULTS: The slice-area x apex-base length was found to be highly correlated with the volume of the RV, with little sensitivity to the degree of filling of the ventricle or to the exact slice chosen (r = 0.987; n = 22 from five hearts). The RV was shown to follow a clockwise helical path around the left ventricle of 47 +/- 17 degrees, below the outflow tract, as seen from the apical view, progressing from the apex to the base. Based on the pinched-arc model, the anterior arc is shallower than the posterior arc, with a larger radius of curvature and a smaller angle between the arc and the septal axis. As the RV is passively filled, opposite changes in shape occur between the anterior and posterior regions tending to equalize their shapes. CONCLUSIONS: A high degree of regularity of shape does exist in the RV and, thus, can be characterized effectively in terms of a representative cross-sectional shape and in terms of the changes in that shape proceeding from the base to the apex.

Animals↗