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Biomedical subjects

M L Simpson

Publications and source records attributed to M L Simpson.

At least 19 recordsLinked to original sources

Formation of ultrasharp vertically aligned Cu-Si nanocones by a DC plasma process.

We report an effective method for the production of ultrasharp vertically oriented silicon nanocones with tip radii as small as 5 nm. These silicon nanostructures were shaped by a high-temperature acetylene and ammonia dc plasma reactive ion etch (RIE) process. Thin-film copper deposited onto Si substrates forms a copper silicide (Cu3Si) during plasma processing, which subsequently acts as a seed material masking the single-crystal cones while the exposed silicon areas are reactive ion etched. In this process, the cone angle is sharpened continually as the structure becomes taller. Furthermore, by lithographically defining the seed material as well as employing an etch barrier material such as titanium, the cone location and substrate topography can be controlled effectively.

Acetylene↗

Gene network shaping of inherent noise spectra.

Recent work demonstrates that stochastic fluctuations in molecular populations have consequences for gene regulation. Previous experiments focused on noise sources or noise propagation through gene networks by measuring noise magnitudes. However, in theoretical analysis, we showed that noise frequency content is determined by the underlying gene circuits, leading to a mapping between gene circuit structure and the noise frequency range. An intriguing prediction from our previous studies was that negative autoregulation shifts noise to higher frequencies where it is more easily filtered out by gene networks--a property that may contribute to the prevalence of autoregulation motifs (for example, found in the regulation of approximately 40% of Escherichia coli genes). Here we measure noise frequency content in growing cultures of E. coli, and verify the link between gene circuit structure and noise spectra by demonstrating the negative autoregulation-mediated spectral shift. We further demonstrate that noise spectral measurements provide mechanistic insights into gene regulation, as perturbations of gene circuit parameters are discernible in the measured noise frequency ranges. These results suggest that noise spectral measurements could facilitate the discovery of novel regulatory relationships.

Algorithms↗

Bioluminescent bioreporter integrated-circuit sensing of microbial volatile organic compounds.

A bioluminescent bioreporter for the detection of the microbial volatile organic compound p-cymene was constructed as a model sensor for the detection of metabolic by-products indicative of microbial growth. The bioreporter, designated Pseudomonas putida UT93, contains a Vibrio fischeri luxCDABE gene fused to a p-cymene/p-cumate-inducible promoter derived from the P. putida F1 cym operon. Exposure of strain UT93 to 0.02-850 ppm p-cymene produced self-generated bioluminescence in less than 1.5 h. Signals in response to specific volatile organic compounds (VOCs) such as m- and p-xylene and styrene, also occurred, but at two-fold lower bioluminescent levels. The bioreporter was interfaced with an integrated-circuit microluminometer to create a miniaturized hybrid sensor for remote monitoring of p-cymene signatures. This bioluminescent bioreporter integrated-circuit device was capable of detecting fungal presence within approximately 3.5 h of initial exposure to a culture of p-cymene-producing Penicillium roqueforti.

Air Microbiology↗

An integrated CMOS microluminometer for low-level luminescence sensing in the bioluminescent bioreporter integrated circuit.

We report an integrated CMOS microluminometer for the detection of low-level bioluminescence in whole cell biosensing applications. This microluminometer is the microelectronic portion of the bioluminescent bioreporter integrated circuit (BBIC). This device uses the n-well/p-substrate junction of a standard bulk CMOS IC process to form the integrated photodetector. This photodetector uses a distributed electrode configuration that minimizes detector noise. Signal processing is accomplished with a current-to-frequency converter circuit that forms the causal portion of the matched filter for dc luminescence in wide-band white noise. Measurements show that luminescence can be detected from as few as 4 x 10(5) cells/ml.

Biosensing Techniques↗

Whole-cell biocomputing.

The ability to manipulate systems on the molecular scale naturally leads to speculation about the rational design of molecular-scale machines. Cells might be the ultimate molecular-scale machines and our ability to engineer them is relatively advanced when compared with our ability to control the synthesis and direct the assembly of man-made materials. Indeed, engineered whole cells deployed in biosensors can be considered one of the practical successes of molecular-scale devices. However, these devices explore only a small portion of cellular functionality. Individual cells or self-organized groups of cells perform extremely complex functions that include sensing, communication, navigation, cooperation and even fabrication of synthetic nanoscopic materials. In natural systems, these capabilities are controlled by complex genetic regulatory circuits, which are only partially understood and not readily accessible for use in engineered systems. Here, we focus on efforts to mimic the functionality of man-made information-processing systems within whole cells.

Computational Biology↗

Use of topical lidocaine in the treatment of muscle tension dysphonia.

This investigation explored the potential usefulness of topical lidocaine in the treatment of muscle tension dysphonia. Three patients with this disorder, who were previously unresponsive to standard voice therapy, were treated with lidocaine. In each case, the outcome was prompt, clinically significant, and sustained. Persistently high-pitched and shrill vocal quality was converted to near normal voice patterns within 15 minutes after transcricothyroid membrane lidocaine injection. We suggest that this temporary and simple laryngeal and tracheal anesthetic technique may have helped to break the perverse cycle of hyperactive glottal and supraglottal muscle contractions evident in each of these patients during phonation efforts. We discuss the possible sensorimotor mechanism of action of this therapeutic technique.

Administration, Topical↗

Videostroboscopy of the pharyngoesophageal segment in laryngectomy patients treated with botulinum toxin.

OBJECTIVES: The purpose of this investigation was to use videostroboscopy to study the physiologic and biomechanical effects of botulinum toxin (Botox) injection on the pharyngoesophageal segment (PES) in total laryngectomy patients with poor-quality tracheoesophageal puncture (TEP) voice caused by PES spasm. METHODS: The following was a prospective study. Videostroboscopy of the PES and videotaped recordings of patients performing TEP voice tasks were conducted before and after Botox injection of the PES. Ratings of videostroboscopic and speech samples were performed by 3 blinded judges with extensive experience with this patient population. RESULTS: Perceptually, TEP voice was more fluent and less strained after injection. Videostroboscopically, patients demonstrated improved PES volitional control and mucosal wave characteristics after Botox injection. CONCLUSION: Botox injection in total laryngectomy patients with poor-quality TEP voice caused by PES spasm provides improved physiologic and biomechanical function of the PES, as demonstrated for the first time videostroboscopically. These findings help explain the perceptual ratings of TEP voice improvement noted after Botox injection. Videostroboscopy can be used to provide diagnostic information to help confirm the clinical impression of PES spasm, as well as to document the effects of Botox injection on PES function.

Adult↗

Botulinum toxin injection to improve tracheoesophageal speech after total laryngectomy.

Total laryngectomy patients, after undergoing a tracheoesophageal puncture (TEP), may have poor TEP speech because of hypertonicity or spasm of the pharyngoesophageal segment (PES). Conventional treatment options include speech therapy, PES dilation, pharyngeal neurectomy, and myotomy. Botulinum toxin injection into the PES has recently been reported to be effective for this disorder. However, data accumulated were based primarily on subjective analyses. This prospective investigation used both qualitative and quantitative measures to assess the effects of videofluoroscopy-guided botulinum toxin injection on TEP voice quality in laryngectomees with PES dysfunction. Patients underwent voice analyses, tracheal air pressure measures, and barium swallows before and after botulinum toxin injection. Seven of 8 patients had significant voice quality improvement, and tracheal air pressures normalized in 6 of 8 patients after injection. Videofluoroscopic botulinum toxin injection into the PES is efficacious, safe, and cost-effective and should be considered as a first-line therapy for the treatment of laryngectomees with poor quality TEP speech caused by PES dysfunction.

Adult↗

Videostroboscopy of the pharyngoesophageal segment in total laryngectomees.

OBJECTIVES: The reconstructed pharyngoesophageal segment (PES) serves as the neoglottis following total laryngectomy, as it provides the source of vibration for production of tracheoesophageal puncture (TEP) voice. To date, little information exists regarding the vibratory characteristics of the PES. The purpose of this investigation was to study the anatomy and physiology of the PES using videostroboscopy. STUDY DESIGN: Prospective study investigating the anatomy and physiology of the PES in 34 laryngectomees who used TEP speech as their primary form of communication. MATERIALS AND METHODS: Videostroboscopy and voice recordings were graded by three trained, blinded judges using a seven-point scale. RESULTS: The patients demonstrated differences that allowed for separation of patients into two main groups: "poor" and "effective" TEP speakers. The voice quality differences were explained by anatomic and physiologic characteristics of the PES. Redundant, thick, and dyssynchronous PES features were observed in patients with poor TEP speech skills; the effective speakers exhibited less redundant, thinner mucosa and more synchronous vibratory patterns. Moreover, the latter subgroup consistently demonstrated a greater degree of volitional PES control and less spasmodic activity than their poorly speaking counterparts. Length of the PES opening (measured in the horizontal plane) as well as amount and consistency of secretions did not appear to influence TEP speech or voice proficiency. CONCLUSION: Videostroboscopy in laryngectomees is a noninvasive, inexpensive, easily performed procedure that may contribute valuable information regarding the anatomy and physiology of the PES, especially in patients who experience difficulties achieving satisfactory TEP voice and speech production.

Adult↗

Antibody class and subclass responses to pneumococcal polysaccharides following immunization of human immunodeficiency virus-infected patients.

Antibodies of the IgM class and IgG2 and IgA2 subclasses are prominent in responses to pneumococcal polysaccharides (PPS) but may be decreased in human immunodeficiency virus (HIV)-infected patients, among whom invasive pneumococcal disease is common. After immunization of HIV-infected and -seronegative subjects with pneumococcal vaccine, the number of PPS-specific antibody-secreting cells (ASC) producing IgM was significantly lower among HIV-infected subjects, whereas PPS-specific IgG and IgA ASC were more comparable. The subclass distribution of PPS-specific IgG2-producing (approximately 80%) and IgA2-producing (approximately 50%) ASC and antibodies in serum were similar. However, before immunization, the proportions of PPS-specific IgG2 for both serotypes 8 and 14 in baseline sera from HIV-infected patients were significantly decreased compared with controls. Thus, the response to PPS among HIV-infected patients may be characterized by lower levels of specific IgG2 before immunization and prominent defects in IgM responses soon after stimulation.

Adult↗

Differential performance on Taylor's Manifest Anxiety Scale by black private college freshmen, a partial report.

Distributions of scores from Taylor's 1953 Manifest Anxiety Scale administered to 295 men and 361 women, selected from the 1052 participating students, were presented in graphic form. Means were higher than those reported by Taylor and gender differences were found. Pictorial views of the polygons for both the current freshman data and those for Taylor were similar, including the positive skewness. Results were expected to contribute to refinement of college counseling interventions.

Adolescent↗

HIV-1 counseling and testing sites, Minnesota: analysis of trends in client characteristics.

We report here a summary of the data obtained from two HIV-1 antibody counseling and testing sites in Minneapolis-St. Paul for the first 48 months of operation (24,911 persons tested). The HIV-1 antibody seroprevalence rate for all persons tested was 5 percent. The highest seroprevalence rates were in male homosexual/bisexual intravenous drug users (23 percent) and homosexual/bisexual men (13 percent). There was a significant decrease in the HIV-1 antibody seroprevalence rate among clients during the 48-month period from 14 percent in the first six months to 3 percent in the last six months. This decrease coincided with an increase in the number of low-risk female clients and low-risk heterosexual male clients, and a decrease in the number of homosexual/bisexual males participating in the programs. These findings suggest the need for development and implementation of other strategies to identify and reach persons at highest risk for HIV-1 infection.

AIDS Serodiagnosis↗

Glycolysis and lipid synthesis in brown adipose tissue during ageing in the rat.

The maximal activity of the enzymes hexokinase and 6-phosphofructokinase were measured in interscapular brown adipose tissue during ageing in the rat. The activity of these glycolytic enzymes increased markedly during the suckling-weaning transition (20-22 days of age), but from 30 to 100 days of age the activities per gram wet weight and per mg protein decreased. The rate of lipogenesis in brown adipose tissue was also increased over the suckling-weaning transition and the contribution of glucose to this fatty acid synthesis was greater in weaned animals especially under the influence of insulin.

Adipose Tissue, Brown↗

Gamma-vinyl-GABA treatment of tardive dyskinesia and other movement disorders.

We conducted a single-blind trial of gamma-vinyl-GABA (GVG) in nine patients: seven with tardive dyskinesia, one with Meige syndrome, and one with Tourette syndrome. Five tardive dyskinesia patients completed the entire 11-week study and, as a group, demonstrated significant decreases in dyskinesia scores. Four of these five tardive dyskinesia patients showed clinically evident improvement, with approximately 30% reduction in dyskinetic symptoms. Other patients had no clinical benefit from GVG. Three patients had transient exacerbation of psychiatric symptoms after sudden withdrawal of GVG, and one patient experienced dose-related confusional episodes. Our results suggest that GABAergic drugs may have a role in treating patients with tardive dyskinesia.

Adult↗

Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

Acute Disease↗