PubMed Health⌕ Search

Biomedical subjects

T Larson

Publications and source records attributed to T Larson.

At least 19 recordsLinked to original sources
PubMed2001

Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir.

The natural history of cytomegalovirus (CMV) disease associated with solid organ transplantation has been modified as a result of the widespread use of antiviral prophylaxis. Anecdotal reports have indicated a reduction of CMV disease at the expense of its later occurrence after completion of ganciclovir prophylaxis. The present study investigated the occurrence of CMV disease and its risk factors among 37 liver and kidney transplant recipients with CMV D+/R- status who received oral ganciclovir during the first 100 days posttransplantation. CMV disease occurred in 9 patients (24.3%) at a median of 144 days posttransplantation (range, 95-190 days). Allograft rejection was found to be strongly associated with the occurrence of late-onset CMV disease (risk ratio, 6.6; 95% confidence interval, 1.4-32.1; P=.02). Thus, CMV D+/R- solid organ transplant recipients receiving 3 months of oral ganciclovir who develop allograft rejection during the period of antiviral prophylaxis may benefit from extended and/or enhanced antiviral prophylaxis to prevent late-onset CMV disease.

Administration, Oral↗
PubMed2001

Impaired mucosal immunity in L-selectin-deficient mice orally immunized with a Salmonella vaccine vector.

Lymphocyte trafficking in the gastrointestinal tract is primarily mediated by interactions with the mucosal addressin cell adhesion molecule 1 and its lymphocyte ligand, alpha(4)beta(7), and partly by L-selectin (L-Sel) interactions with peripheral node addressin coexpressed on some mucosal addressin cell adhesion molecule 1. We inquired whether intestinal responses in mice lacking L-Sel would be enhanced. L-Sel-deficient (L-Sel(-/-)) mice were orally immunized with either Salmonella vaccine vector or Salmonella vector-expressing colonization factor Ag I (CFA/I) from enterotoxigenic Escherichia coli. In L-Sel(-/-) mice, mucosal IgA anti-CFA/I fimbrial responses were greatly reduced, and systemic IgG2a anti-CFA/I fimbrial responses were 26-fold greater compared with C57BL/6 (L-Sel(+/+)) mice. L-Sel(-/-) Peyer's patch (PP) CD4(+) Th cells revealed IFN-gamma-dominated responses and an unprecedented absence of IL-4, whereas the expected mixed Th cell phenotype developed in L-Sel(+/+) mice. PP CD4(+) Th cell anti-Salmonella responses were nearly nonexistent in L-Sel(-/-) mice immunized with either Salmonella vaccine. Splenic CD4(+) Th cell anti-Salmonella responses were reduced but did show cytokine production in Ag restimulation assays. Increased colonization of PP and spleen was noted only with the Salmonella vector in L-Sel(-/-) mice, resulting in increased splenomegaly, suggesting that the Salmonella-CFA/I vaccine was not as infectious or that the presence of the fimbriae improved clearance, possibly because of reduced neutrophil recruitment. However, sufficient anti-Salmonella immunity was induced, because Salmonella vector-immunized L-Sel(-/-) mice showed complete protection against wild-type Salmonella challenge, unlike L-Sel(+/+) mice. This evidence shows that L-Sel is important for development of mucosal immunity, and absence of L-Sel is protective against salmonellosis.

Administration, Oral↗
PubMed2001

Sampling artifacts from the use of denuder tubes with glycerol based coatings in the measurement of atmospheric particulate matter.

Chemical speciation studies use sampling configurations that often require the deployment of denuder tubes of various types to measure certain species or control particulate sampling artifacts. Concurrent sets of measurements on Teflon membrane and quartz filters in specific sampling configurations were used to evaluate the potential influence of denuder tubes with glycerol-based coatings on particulate mass and carbon measurements on downstream filters. Positive biases were observed in the measurement of gravimetric mass and carbon on Teflon and quartz filters, respectively, downstream of sodium carbonate/ glycerol and citric acid/glycerol coated denuder tubes relative to those without upstream denuder tubes. The magnitude of the bias is dependent on the level of ambient particulate loading.

Aerosols↗
PubMed2001

Minimally invasive therapies for benign prostatic hyperplasia.

Currently, 3 categories of treatment are available for men with benign prostatic hyperplasia (BPH): (1) medicine, such as alpha-blockers and finasteride; (2) minimally invasive treatment, such as transurethral microwave thermotherapy and interstitial ablation using either radiofrequency or laser; and (3) surgical therapy. The 1990s have seen an explosion of transurethral technology to treat symptoms caused by bladder outlet obstruction secondary to BPH. Unlike surgical debulking procedures, the minimally invasive therapies attempt to treat patients without general or regional anesthesia, and even ambulatory procedures are performed in the office. Because of the demographics of patients with BPH, it is hoped that these minimally invasive options will relieve symptoms without any surgical complications and the side effects and compliance issues associated with medical therapy. It is important that urologists have a clear understanding of the clinical usefulness of these devices, so that the overall role of such treatment may be determined by science rather than marketing. Clinically, the degree of symptom score, peak flow, and quality-of-life improvement seen with all the minimally invasive techniques are similar. The techniques may differ in their ability to reach the maximum number of responders and achieve an acceptable duration of response, and the need for analgesia/sedation associated with each technique. This study will define the minimally invasive therapies and present the differences in catheter design and technique. The pathologic basis for these therapeutic options and the advantages and disadvantages of each will be discussed. Urologists must decide which therapy can be used in their office practice. The maximum numbers of responders and enhanced durability of the treatment can be achieved based on realistic expectations, proper selection of patients, and complete information on the potential of these devices.

Adrenergic alpha-Antagonists↗
PubMed2001

N-terminal fatty-acylation of sonic hedgehog enhances the induction of rodent ventral forebrain neurons.

The adult basal ganglia arise from the medial and lateral ganglionic eminences, morphologically distinct structures found in the embryonic telencephalon. We have previously shown that temporal changes in sonic hedgehog (Shh) responsiveness determine the sequential induction of embryonic neurons that populate the medial and lateral ganglionic eminences. In this report, we show that Shh-mediated differentiation of neurons that populate the lateral ganglionic eminence express different combinations of the homeobox-containing transcription factors Dlx, Mash1 and Islet 1/2. Furthermore, we show that N-terminal fatty-acylation of Shh significantly enhances its ability to induce the differentiation of rat E11 telencephalic neurons expressing Dlx, Islet 1/2 or Mash1. Recent evidence indicates that in utero injection of the E9.5 mouse forebrain with retroviruses encoding wild-type Shh induces the ectopic expression of Dlx2 and severe deformities in the brain. In this report, we show that Shh containing a mutation at the site of acylation prevents either of these phenotypes. These results suggest that N-terminal fatty-acylation of Shh may play an important role in Shh-dependent signaling during rodent ventral forebrain formation.

Animals↗
PubMed2001

Functional analysis and treatment of inappropriate verbal behavior.

The present study examined the possible function of inappropriate verbal behavior of an adult man who had been diagnosed with both mental retardation and psychosis. Results of a functional analysis indicated that inappropriate verbal utterances were maintained by attention. An intervention consisting of the differential reinforcement of appropriate verbal behavior effectively reduced the inappropriate behavior.

Adult↗
PubMed2000

Estimating the benefits of solitary pancreas transplantation in nonuremic patients with type 1 diabetes mellitus: a theoretical analysis.

BACKGROUND: The goal of early pancreas transplantation in type 1 diabetes mellitus is to achieve euglycemia and thereby prevent the renal, retinal, and vascular complications of this disease. The purpose of this analysis was to examine the conditions and assumptions that would make early solitary pancreas a viable therapeutic option. METHODS: A Markov model was constructed to compare outcomes for patients with type 1 diabetes mellitus and early overt nephropathy assigned to either standard insulin therapy or solitary pancreas transplantation. Probabilities for development of end stage renal disease (ESRD), blindness, mortality, and direct health care costs were taken from the literature. Utility scores for the relevant health states were determined by the standard gamble method on 16 type 1 diabetic patients suitable for pancreas transplantation. RESULTS: Assuming a baseline graft life expectancy for the pancreas of 10 years, early pancreas transplantation could provide 0.42 more life years and 2.2 more quality adjusted life years (discounted at 3%) to patients above standard insulin therapy. The model was sensitive to estimates of pancreas graft life expectancy (<8 years being inadequate to extend patient life), timing of pancreas transplantation with respect to rate of progression to ESRD, and drug nephrotoxicity rates. The incremental costs (charges) for early pancreas transplantation over standard therapy were estimated to be modestly high (about $56,600/quality adjusted life year for the baseline case). Pancreas transplant costs were also a very sensitive parameter in the cost utility analysis. CONCLUSIONS: The success of early solitary pancreas transplantation may well be at the stage to consider a trial in selected type 1 diabetic patients at risk for renal and retinal disease.

Costs and Cost Analysis↗
PubMed2000

Use of permanent interstitial temperature self-regulating rods for ablation of prostate cancer.

BACKGROUND AND PURPOSE: We have examined a new technique for the thermal treatment of prostate cancer involving the percutaneous placement of small magnetic alloy rods into the gland in a procedure analogous to the placement of permanent brachytherapy seeds. When the patient and the implanted rods are placed in an extracorporeal alternating magnetic field, the rods heat and can produce tissue necrosis. The rods are temperature self-regulating and produce temperatures no higher than their preprogrammed regulation value. The rods are biocompatable permanent implants, comprised of cobalt and palladium. MATERIALS AND METHODS: We examined rods that heat to 55 degrees, 60 degrees, and 70 degrees C. Patients are treated for 1-hour sessions and easily have multiple sessions. RESULTS: Isolated rods produced little or asymmetrical necrosis. However, arrays of 70 degrees C rods placed within 1 cm of each other caused consistent necrosis between the rods. The temperature at the edge of the array dropped off quickly, and therefore, the rods can be placed within 2 mm of the capsule even posteriorly near the rectum. CONCLUSIONS: Arrays of high-temperature rods can be employed for tissue ablation, while lower-temperature arrays could be used to produce hyperthermia in order to achieve synergism with adjuvant radiation therapy. The technique is applicable in an outpatient setting.

Electromagnetic Fields↗
PubMed2000

Cell-kill modeling of microwave thermotherapy for treatment of benign prostatic hyperplasia.

PURPOSE: We investigated whether cell-kill modelling could be used as a mean for predicting the outcome of microwave thermotherapy for benign prostate hyperplasia (BPH). METHODS: The two models--Henriques' damage integral and Jung's compartment model--were implemented in a computer program. Real treatment data for 22 patients with BPH who were in chronic retention were used as input, including measured intraprostatic temperatures and microwave power. To test if modelling gives results that are consistent with actual observations, comparison with transrectal ultrasound (TRUS) measurements of the prostate volume before and after treatment was made. The sensitivity of the computer model for variations in the heat cytotoxicity and the temperature probe location in the adenoma was also tested. RESULTS: The average TRUS volume reduction 3 months after treatment was 26 cc, whereas the corresponding cell kill calculation was 27 cc. The computer model appears to be rather insensitive to minor uncertainties in heat sensitivity and location of the intraprostatic reference temperature sensors. CONCLUSION: Cell-kill modelling appears to give results that are consistent with actual observations. The coagulated tissue volume is calculated in real time during the treatment, thereby providing an immediate prediction of the treatment outcome. By using cell-kill modelling, the endpoint of a treatment can be set individually; e.g., when a certain volume reduction has been achieved.

Cell Death↗
PubMed2000

Analysis of capsid formation of human polyomavirus JC (Tokyo-1 strain) by a eukaryotic expression system: splicing of late RNAs, translation and nuclear transport of major capsid protein VP1, and capsid assembly.

Human polyomavirus JC (JCV) can encode the three capsid proteins VP1, VP2, and VP3, downstream of the agnoprotein in the late region. JCV virions are identified in the nucleus of infected cells. In this study, we have elucidated unique features of JCV capsid formation by using a eukaryotic expression system. Structures of JCV polycistronic late RNAs (M1 to M4 and possibly M5 and M6) generated by alternative splicing were determined. VP1 would be synthesized from M2 RNA, and VP2 and VP3 would be synthesized from M1 RNA. The presence of the open reading frame of the agnoprotein or the leader sequence (nucleotides 275 to 409) can decrease the expression level of VP1. VP1 was efficiently transported to the nucleus in the presence of VP2 and VP3 but distributed both in the cytoplasm and in the nucleus in their absence. Mutation analysis indicated that inefficiency in nuclear transport of VP1 is due to the unique structure in the N-terminal sequence, KRKGERK. Within the nucleus, VP1 was localized discretely and identified as speckles in the presence of VP2 and VP3 but distributed diffusely in their absence. These results suggest that VP1 was efficiently transported to the nucleus and localized in the discrete subnuclear regions, possibly with VP2 and VP3. By electron microscopy, recombinant virus particles were identified in the nucleus, and their intranuclear distribution was consistent with distribution of speckles. This system provides a useful model with which to understand JCV capsid formation and the structures and functions of the JCV capsid proteins.

Alternative Splicing↗
PubMed2000

Asthma aggravation, combustion, and stagnant air.

BACKGROUND: The relationship between current concentrations of ambient air pollution and adverse health effects is controversial. We report a meteorological index of air stagnation that is associated with daily visits to the emergency department for asthma in two urban areas. METHODS: Data on daily values of a stagnation persistence index and visits to the emergency department for asthma were collected for approximately two years in Spokane, Washington, USA and for 15 months in Seattle, Washington, USA. The stagnation persistence index represents the number of hours during the 24 hour day when surface wind speeds are less than the annual hourly median value, an index readily available for most urban areas. Associations between the daily stagnation persistence index and daily emergency department visits for asthma were tested using a generalised additive Poisson regression model. A factor analysis of particulate matter (PM(2.5)) composition was performed to identify the pollutants associated with increased asthma visits. RESULTS: The relative rate of the association between a visit to the emergency department for asthma and the stagnation persistence index was 1. 12 (95% CI 1.05 to 1.19) in Spokane and 1.21 (95% CI 1.09 to 1.35) in Seattle for an increase of 11 and 10 hours, respectively, of low wind speed in a given day. The stagnation persistence index was only correlated with one set of factor loadings; that cluster included the stagnation persistence index, carbon monoxide, and organic/elemental carbon. CONCLUSION: Increased air stagnation was shown to be a surrogate for accumulation of the products of incomplete combustion, including carbon monoxide and fine particulate levels of organic and elemental carbon, and was more strongly associated with asthma aggravation than any one of the measured pollutants.

Air Pollutants↗
PubMed1999

Episodes of high coarse particle concentrations are not associated with increased mortality.

Fine particle concentration (i.e., particles <2.5 microm in aerodynamic diameter; PM2.5), but not coarse particle concentration, was associated with increased mortality in six U.S. cities. Others criticized this result, arguing that it could result from differences in measurement error between the two size ranges. Fine particles are primarily from combustion of fossil fuel, whereras coarse particles (i.e., particles between 2.5 and 10 microm in aerodynamic diameter) are all crustal material, i.e., dust. One way to determine if coarse particles are a risk for mortality is to identify episodes of high concentrations of coarse, but not fine, particles. Spokane, Washington, is located in an arid area and is subject to occasional dust storms after crops have been harvested. Between 1989 and 1995, we identified 17 dust storms in Spokane. The 24-hr mean PM10 concentration during those storms was 263 microg/m3. Using control dates that were the same day of the year in other years (but with no dust storm on that day) and that had a mean PM10 concentration of 42 microg/m3, we compared the rate of nonaccidental deaths on the episode versus nonepisode days. There was little evidence of any risk [relative risk (RR) = 1.00; 95% confidence interval (CI), 0.81-1.22] on the episode days. Defining episode deaths as those occurring on the same or following day as the dust storm produced similar results (RR = 1.01; CI, 0.87-1.17). Sensitivity analyses, which tested more extensive seasonal control, produced smaller estimates. We conclude that coarse particles from windblown dust are not associated with mortality risk.

Air Pollutants↗
PubMed1998

The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells.

The LIM-only protein LMO2 is expressed aberrantly in acute T-cell leukaemias as a result of the chromosomal translocations t(11;14) (p13;q11) or t(7;11) (q35;p13). In a transgenic model of tumorigenesis by Lmo2, T-cell acute leukaemias arise after an asymptomatic phase in which an accumulation of immature CD4(-) CD8(-) double negative thymocytes occurs. Possible molecular mechanisms underlying these effects have been investigated in T cells from Lmo2 transgenic mice. Isolation of DNA-binding sites by CASTing and band shift assays demonstrates the presence of an oligomeric complex involving Lmo2 which can bind to a bipartite DNA motif comprising two E-box sequences approximately 10 bp apart, which is distinct from that found in erythroid cells. This complex occurs in T-cell tumours and it is restricted to the immature CD4(- )CD8(-) thymocyte subset in asymptomatic transgenic mice. Thus, ectopic expression of Lmo2 by transgenesis, or by chromosomal translocations in humans, may result in the aberrant protein interactions causing abnormal regulation of gene expression, resulting in a blockage of T-cell differentiation and providing precursor cells for overt tumour formation.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Viability of Escherichia coli O157:H7 in salami following conditioning of batter, fermentation and drying of sticks, and storage of slices.

The fate of Escherichia coli O157:H7 was monitored in salami during conditioning of batter, fermentation and drying of sticks, and storage of slices. The raw batter (75% pork: 25% beef, wt/wt, fat content about 20%) was inoculated with a pediococcal starter culture (about 10(8) CFU/g) and a five-strain cocktail of E. coli O157:H7 ( > or = 2 x 10(7) CFU/g) and stuffed into 104-mm diameter fibrous casings. After being refrigerated at 4 degrees C or being tempered at 13 degrees C, frozen at -20 degrees C, and thawed at 4 degrees C, or being frozen at -20 degrees C, and thawed at 4 degrees C, the inoculated batter was fermented at 24 degrees C and 90% relative humidity (RH) to pH < or = 4.8, dried at 13 degrees C and 65% RH to a moisture/protein ratio of < or = 1.9:1, and then stored at 4 or 21 degrees C under air or vacuum. For salami sticks sampled immediately after drying, appreciable differences were evident among the various batter-conditioning treatments; pathogen numbers were reduced from original levels by 2.1, 1.6, or 1.1 log10 units when batter was tempered, frozen, and thawed, frozen and thawed, or refrigerated, respectively. Similarly, regardless of storage temperature or atmosphere, within 7 days salami slices cut from sticks prepared from batter that was tempered, frozen, and thawed (2.7- to 4.9-log10-unit reduction) or frozen and thawed (2.3- to 4.8-log10-unit reduction) displayed a greater impact on pathogen numbers than slices cut from sticks prepared from batter that was refrigerated (1.6- to 3.1-log10-unit reduction). The effects of batter conditioning notwithstanding, a greater reduction in levels of E. coli O157:H7 was observed when slices were stored at 21 degrees C compared to otherwise similar slices stored at 4 degrees C. After storage for 60 days the pathogen was only detected by enrichment in slices stored at 21 degrees C, whereas pathogen levels ranged from 1.4 to 4.5 log10 CFU/g in slices stored at 4 degrees C. Differences related to storage atmosphere were first observed after slices were stored for 21 days. Such differences were more readily demonstrable after 60 and 90 days, with pathogen numbers for treatments that were statistically different ranging from 0.6- to 1.5-log10 units higher on slices stored under vacuum than in air. These data emphasize the need to implement multiple barriers to appreciably reduce numbers of E. coli O157:H7 in salami.

Animals↗
PubMed1997

Viability of Escherichia coli O157:H7 in pepperoni during the manufacture of sticks and the subsequent storage of slices at 21, 4 and -20 degrees C under air, vacuum and CO2.

A raw, pepperoni batter (75% pork:25% beef with a fat content of about 32%) was inoculated with a pediococcal starter culture (about 10(8) cfu/g) and a five-strain cocktail of Escherichia coli O157:H7 (> or = 2 x 10(7) cfu/g), mixed with non-meat ingredients, and then hand-stuffed into 55 mm fibrous casings to form sticks. The numbers of the pathogen were determined before stuffing, after fermentation, after drying/slicing, and after periods of storage. For storage, slices were packaged under air, vacuum or CO2 and stored at -20, 4 and 21 degrees C. Sticks were fermented at 36 degrees C and 85% relative humidity (RH) to < or = pH 4.8 and then dried at 13 degrees C and 65% RH to a moisture/protein ratio (M/Pr) of < or = 1.6:1. Fermentation and drying resulted in the numbers of the pathogen decreasing by about 2 log10 units. During storage, the temperature rather than the atmosphere had the greater effect on pathogen numbers. The greatest reductions in numbers were observed during storage at 21 degrees C, when numbers decreased to about 2 and 3.8 log10 cfu/g within 14 days in product stored under air and vacuum, respectively, and a 5 log10 reduction was observed for both atmospheres within 28 days. Regardless of the storage atmosphere, numbers did not decrease below 3.6 or 3.7 log10 cfu/g after 90 days of storage at -20 or 4 degrees C, respectively. These data confirm that fermentation and drying are sufficient to eliminate only about 2 log10 cfu/g of E. coli O157:H7 from fermented sausage, and that additional strategies, such as storage for at least 2 weeks at ambient temperature in air, are required to achieve a 5 to 6 log10 reduction in the numbers of the pathogen in sliced pepperoni.

Escherichia coli O157↗
PubMed1995

The Hox11 gene is essential for cell survival during spleen development.

The HOX11 homeobox gene was identified via the translocation t(10;14) in T cell leukaemia. To determine the function of this gene in mice, null mutations were made using homologous recombination in ES cells to incorporate lacZ into the hox11 transcription unit. Production of beta-galactosidase from the recombinant hox11 allele in +/- mutants allowed identification of sites of hox11 expression which included the developing spleen. Newborn hox11 -/- mice exhibit asplenia. Spleen formation commences normally at E11.5 in hox11 -/- mutant embryos but the spleen anlage undergoes rapid and complete resorption between E12.5 and E13.5. Dying spleen cells exhibit molecular features of apoptosis, suggesting that programmed cell death is initiated at this stage of organ development in the absence of hox11 protein. Thus hox11 is not required to initiate spleen development but is essential for the survival of splenic precursors during organogenesis. This function for hox11 suggests that enhanced cell survival may result from the t(10;14) which activates HOX11 in T cell leukaemias, further strengthening the association between oncogene-induced cell survival and tumorigenesis.

Animals↗
PubMed1995

Managing the child infected with HIV.

Care of the HIV-infected/exposed infant and child is both routine and challenging. Routine well child care and immunizations are an important part of maintaining and monitoring health status. Challenges arise in the management of acute illnesses and the numerous crises that are experienced by the family caring for that child. Therapy guidelines now provide a logical way in which to initiate antiretroviral treatment and PCP prophylaxis. In HIV-infected children with early disease, common pathogens initially predominate, and only in advanced immune suppression does care become complicated enough to require expert consultation. With increasing numbers of HIV-infected women, perinatally acquired infections in infants will become more common. Early testing and identification will increasingly be important as a way to impact on the significant morbidity and mortality seen in infants less than 6 months old. A caring, compassionate, and comprehensive approach to the care of HIV-infected infants and children results in increased survival and lengthening of disease-free time. Providing this vitally needed care is both satisfying and stimulating.

AIDS-Related Opportunistic Infections↗