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1.
Front Microbiol ; 15: 1322151, 2024.
Article in English | MEDLINE | ID: mdl-38741734

ABSTRACT

Escalating wildfire frequency and severity, exacerbated by shifting climate patterns, pose significant ecological and economic challenges. Prescribed burns, a common forest management tool, aim to mitigate wildfire risks and protect biodiversity. Nevertheless, understanding the impact of prescribed burns on soil and microbial communities in temperate mixed forests, considering temporal dynamics and slash fuel types, remains crucial. Our study, conducted at the University of Tennessee Forest Resources AgResearch and Education Center in Oak Ridge, TN, employed controlled burns across various treatments, and the findings indicate that low-intensity prescribed burns have none or minimal short-term effects on soil parameters but may alter soil nutrient concentrations, as evidenced by significant changes in porewater acetate, formate, and nitrate concentrations. These burns also induce shifts in microbial community structure and diversity, with Proteobacteria and Acidobacteria increasing significantly post-fire, possibly aiding soil recovery. In contrast, Verrucomicrobia showed a notable decrease over time, and other specific microbial taxa correlated with soil pH, porewater nitrate, ammonium, and phosphate concentrations. Our research contributes to understanding the intricate relationships between prescribed fire, soil dynamics, and microbial responses in temperate mixed forests in the Southern Appalachian Region, which is valuable for informed land management practices in the face of evolving environmental challenges.

2.
Front Microbiol ; 14: 1101205, 2023.
Article in English | MEDLINE | ID: mdl-36846780

ABSTRACT

The COVID-19 pandemic brought about an urgent need to monitor the community prevalence of infection and detect the presence of SARS-CoV-2. Testing individual people is the most reliable method to measure the spread of the virus in any given community, but it is also the most expensive and time-consuming. Wastewater-based epidemiology (WBE) has been used since the 1960s when scientists implemented monitoring to measure the effectiveness of the Polio vaccine. Since then, WBE has been used to monitor populations for various pathogens, drugs, and pollutants. In August 2020, the University of Tennessee-Knoxville implemented a SARS-CoV-2 surveillance program that began with raw wastewater surveillance of the student residence buildings on campus, the results of which were shared with another lab group on campus that oversaw the pooled saliva testing of students. Sample collection began at 8 am, and the final RT-qPCR results were obtained by midnight. The previous day's results were presented to the campus administrators and the Student Health Center at 8 am the following morning. The buildings surveyed included all campus dormitories, fraternities, and sororities, 46 buildings in all representing an on-campus community of over 8,000 students. The WBE surveillance relied upon early morning "grab" samples and 24-h composite sampling. Because we only had three Hach AS950 Portable Peristaltic Sampler units, we reserved 24-h composite sampling for the dormitories with the highest population of students. Samples were pasteurized, and heavy sediment was centrifuged and filtered out, followed by a virus concentration step before RNA extraction. Each sample was tested by RT-qPCR for the presence of SARS-CoV-2, using the CDC primers for N Capsid targets N1 and N3. The subsequent pooled saliva tests from sections of each building allowed lower costs and minimized the total number of individual verification tests that needed to be analyzed by the Student Health Center. Our WBE results matched the trend of the on-campus cases reported by the student health center. The highest concentration of genomic copies detected in one sample was 5.06 × 107 copies/L. Raw wastewater-based epidemiology is an efficient, economical, fast, and non-invasive method to monitor a large community for a single pathogen or multiple pathogen targets.

3.
Microbiol Resour Announc ; 10(47): e0104921, 2021 Nov 24.
Article in English | MEDLINE | ID: mdl-34817217

ABSTRACT

Reported here is a coding-complete genome sequence of a SARS-CoV-2 variant obtained from raw wastewater samples at the University of Tennessee-Knoxville campus. This sequence provides insight into SARS-CoV-2 variants that circulate on large college campuses but remain mostly undetected.

4.
Med Phys ; 39(6Part5): 3640-3641, 2012 Jun.
Article in English | MEDLINE | ID: mdl-28517640

ABSTRACT

PURPOSE: To examine schemes to grade the severity of metal susceptibility artifacts on image quality using cardiac MRI pulse sequences. METHODS: A post-thoracotomy patient was simulated with a stainless steel sternal wire (Syneture,MA; size=6, diameter=48mm), placed securely on an ACR MRI phantom. Phantom was scanned on a 1.5-T Siemens using cardiac MRI sequences:1)TrueFISP, 2)Gradient-Recalled-Echo (GRE), 3)Turbo-Spin- Echo (TSE), 4)Turbo-Inversion-Recovery-Magnitude (TIRM), 5)Dark- blood-IR-FS (DBFS) with and without the wire (FOV=30×30cm, slice- thickness/slice-gap=7.0/1.5mm, matrix size=192×192, slices=17). Image quality degradation was assessed in terms of signal loss and spatial deformation; signal loss by a) measuring the largest diameter of signal drop and b) number of slices with a signal drop and spatial deformation in VelocityAI (Atlanta,GA) by computing the rigid transformation indices between the phantom's internal grid with and without the metal. RESULTS: Image quality was evaluated in terms of signal loss, spatial deformation and ring artifacts. Signal loss: TruFISP and GRE showed the largest signal drop diameter (13 and 16cm respectively). GRE sequence showed a signal drop in -12 slices where as signal drop occurred in only ∼4-5 slices with other sequences. Spatial deformation: GRE sequence showed the maximum with a ∼9mm grid deflection followed by TSE and DBFS (∼8mm). An average deflection of 5.4mm was observed on most of the sequences except T rueFISP and TIRM (Omm). Rigid body transformation showed a maximum x,y,z-translation of -4.7, 0.3 and 1.69 mm and x,y,z-angular rotation of 0.2, - 1.5 and 0.5° for GRE sequence followed by TSE and DBFS confirming the spatial distortion results. Concentric ring artifacts with signal loss were also observed on TrueFISP and DBFS images. CONCLUSIONS: Quantification of cardiac MR sequences to metal tolerance and the impact on image quality has shown that GRE and TrueFISP are the most metal-susceptible and TIRM is the most metal-tolerant sequence in terms of both signal loss and spatial deformation. This study helped in creating a separate cardiac metal protocol comprising of mainly metal-tolerant sequences thus reducing scan time and patient discomfort.

5.
Neuroscience ; 158(4): 1460-8, 2009 Feb 18.
Article in English | MEDLINE | ID: mdl-19047013

ABSTRACT

In this study, we examined protein-protein interactions between two neuronal receptors, low density lipoprotein receptor-related protein (LRP) and sorLA/LR11, and found that these receptors interact, as indicated by three independent lines of evidence: co-immunoprecipitation experiments on mouse brain extracts and mouse neuronal cells, surface plasmon resonance analysis with purified human LRP and sorLA, and fluorescence lifetime imaging microscopy (FLIM) on rat primary cortical neurons. Immunocytochemistry experiments revealed widespread co-localization of LRP and sorLA within perinuclear compartments of rat primary neurons, while FLIM analysis showed that LRP-sorLA interactions take place within a subset of these compartments.


Subject(s)
LDL-Receptor Related Proteins/metabolism , Receptors, LDL/metabolism , Animals , Binding Sites , Cells, Cultured , Embryo, Mammalian , Green Fluorescent Proteins/genetics , Humans , Immunoprecipitation/methods , LDL-Receptor Related Proteins/genetics , Mice , Microscopy, Fluorescence , Neuroblastoma , Neurons/metabolism , Protein Binding , Protein Interaction Domains and Motifs , Protein Interaction Mapping/methods , Rats , Rats, Sprague-Dawley , Receptors, LDL/genetics , Surface Plasmon Resonance/methods , Transfection/methods
6.
Tissue Antigens ; 68(1): 19-27, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16774536

ABSTRACT

Recommendations have been advanced recently for the use of cancer/testis (CT) immunotherapy against sarcomas. CT antigens are encoded by cancer-germline genes (e.g., hMAGE family) that are expressed in tumors and male germline cells but typically not in normal tissues. At present, little information is available regarding CT expression in mesenchymal neoplasms, and it remains uncertain whether CT immunotherapy will serve as a viable alternative or adjunct to current sarcoma therapies involving resection, followed by adjuvant radiotherapy and/or chemotherapy. In this study, hMAGEA2, hMAGEA3, hMAGEA4, and hMAGEC1 mRNA content in 21 benign mesenchymal tumors (representing seven histotypes) and 28 primary sarcomas (10 histotypes) was inventoried using real-time-PCR and then compared against hMAGE mRNA expression in non-sarcomatous malignancies, three cell lines, and muscle. hMAGEA2, hMAGEA3, and hMAGEC1 transcripts were infrequent in mesenchymal tissues in general, whereas hMAGEA4 mRNA was present in 84% of all mesenchymal tumors, 100% of non-sarcomatous tumors, all three cell lines, and in four of five muscle samples. Although hMAGEA4 mRNA was detected in four of five muscle preparations, there was no indication that the mRNA was translated into protein. The presence of hMAGEA4 mRNA in muscle, plus the inconsistent and infrequent occurrence of hMAGEA2, hMAGEA3, and hMAGEC1 mRNA within and among mesenchymal tumor histotypes, makes these four hMAGE antigens unlikely candidates for sarcoma-specific immunotherapy.


Subject(s)
Antigens, Neoplasm/metabolism , Neoplasm Proteins/metabolism , Neoplasms, Connective Tissue/metabolism , Neoplasms/metabolism , Sarcoma/metabolism , Testis/immunology , Antigens, Neoplasm/genetics , Cell Line , Cell Line, Tumor , Gene Expression , Humans , Male , Melanoma-Specific Antigens , Muscle, Skeletal/metabolism , Neoplasm Metastasis/pathology , Neoplasm Proteins/genetics , Neoplasms/genetics , Neoplasms/pathology , Neoplasms, Connective Tissue/genetics , Neoplasms, Connective Tissue/pathology , RNA, Messenger/metabolism , RNA, Neoplasm/analysis , Sarcoma/genetics , Sarcoma/pathology
7.
Phys Ther ; 80(11): 1076-86, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11046195

ABSTRACT

BACKGROUND AND PURPOSE: Based largely on data from young subjects, intense physical exercise is believed to suppress immune function. In addition, immune function, including secondary antibody response, declines with advancing age. Therefore, intense exercise in old subjects may further suppress the secondary antibody response. The purpose of this in vivo study was to investigate the effects of intense physical exercise on secondary antibody response in young (6-8 weeks) and old (22-24 months) C57BL/6 mice. SUBJECTS AND METHODS: Data were obtained from 22 young and 18 old C57BL/6 mice that were immunized to human serum albumin (HSA) and randomly divided into 3 groups. Two groups were exposed to a single bout of intense exercise to exhaustion and immediately boosted with an injection of HSA. The first group did not exercise further, but the second group continued with daily bouts of intense exercise to exhaustion for 9 days. The third group (control group) did not undergo intense exercise, but received the booster injection of HSA at the same time as the other groups. Ten days after the HSA booster injection, when high level of antibodies are produced in secondary antibody response, serum anti-HSA antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Young mice did not show suppression of secondary antibody response following intense exercise. However, old mice, exposed to a single bout of intense exercise, had an enhanced response similar to the response seen in young control mice. CONCLUSION AND DISCUSSION: The widely accepted hypothesis of immunosuppression resulting from intense exercise may not be true for old mice.


Subject(s)
Aging/physiology , Antibody Formation/physiology , Physical Conditioning, Animal/physiology , Analysis of Variance , Animals , Female , Mice , Mice, Inbred C57BL , Random Allocation
8.
J Rheumatol ; 27(2): 358-64, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10685797

ABSTRACT

OBJECTIVE: Superantigens (SAg) are potent immunomodulatory microbial proteins that can activate T cells, B cells, natural killer cells, and monocytes and are known to trigger experimental autoimmune disease. We investigated whether sera from patients with rheumatic diseases contained elevated antibodies to Mycoplasma arthritidis mitogen (MAM) or staphylococcal enterotoxins A and B (SEA and SEB). METHODS: Standard ELISA were used to measure IgG responses to SAg and IgM and IgG rheumatoid factors and total IgM and IgG levels. Modifications of standard lymphocyte proliferation assays were used to determine functional consequences of the observed antibodies. RESULTS: Antibodies to MAM were elevated in sera from patients with rheumatoid arthritis (RA) compared to sera from patients with systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome, or healthy controls. Responses to other SAg were also elevated in rheumatic disease sera, but the levels were not specific for a given rheumatic disease. Anti-superantigen antibody levels did not correlate with the presence of rheumatoid factor. CONCLUSION: The selected elevation of antibodies to MAM in RA sera suggests that MAM or a MAM-like molecule might be associated with RA, whereas elevation of antibodies to SEA and SEB in sera from patients with rheumatic diseases was less specific.


Subject(s)
Arthritis, Rheumatoid/immunology , Mitogens/blood , Mitogens/immunology , Superantigens/immunology , Antibodies/blood , Antibodies/immunology , Antigens , Antigens, Bacterial , Arthritis, Rheumatoid/blood , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Proteins , Superantigens/blood
9.
Infect Immun ; 65(12): 4965-71, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9393783

ABSTRACT

Mycoplasma arthritidis mitogen (MAM), is a soluble protein with classical superantigenic properties and is produced by an organism that causes an acute and chronic proliferative arthritis. Unfortunately, the process of obtaining purified MAM from M. arthritidis culture supernatants is extremely time-consuming and costly, and very little material is recovered. Thus, our laboratory has expressed MAM in Escherichia coli by using a protein fusion expression system. The construction and expression of recombinant MAM (rMAM), as well as a comparison of the biological properties of rMAM to those of native MAM, are discussed. Briefly, conversion of the three UGA codons to UGG codons was required to obtain full-length expression and mitogenic activity of rMAM. Antisera to native MAM recognized both rMAM and the fusion protein. The T-cell receptor Vbeta and major histocompatibility complex class II receptor usages by rMAM and the fusion protein were identical to that of native MAM. In addition, the ability to induce suppression and form the superantigen bridge could also be demonstrated with rMAM. Importantly, dose-response experiments indicated that homogeneous native MAM and rMAM were of equal potency. Thus, MAM has been successfully expressed in E. coli, thereby creating a viable alternative to native MAM.


Subject(s)
Escherichia coli/genetics , Mitogens/genetics , Superantigens/genetics , Antigens , Antigens, Bacterial , Proteins , Recombinant Fusion Proteins/genetics
10.
Toxicol Appl Pharmacol ; 145(2): 388-98, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9266813

ABSTRACT

Data from laboratory animal experiments are often used in setting guidelines for safe levels of human exposure to inhaled materials. The F344 rat has been used extensively in laboratory experiments to determine effects of exposure to inhaled materials in the nasal passages. Many inhaled materials induce toxic responses in the olfactory (posterior) region of the rat nasal passages. The location of major airflow routes has been proposed as playing a dominant role in determining some olfactory lesion location patterns. Since nasal airflow patterns differ significantly among species, methods are needed to assess conditions under which these differences may significantly affect extrapolation of the effects of local dose in animals to potential disease outcome in humans. A computational fluid dynamics model of airflow and inhaled gas uptake has been used to predict dose to airway walls in the anterior F344 rat nasal passages (Kimbell et al., Toxicol. Appl. Pharmacol., 1993; 121, 253-263). To determine the role of nasal airflow patterns in affecting olfactory lesion distribution, this model was extended to include the olfactory region. Serial-step histological sections of the nasal passages of a F344 rat were used to construct the computer model. Simulations of inspiratory airflow throughout the rat nasal passages were consistent with previously reported experimental data. Four of the five major simulated flow streams present in the anterior nose (dorsal lateral, middle, ventral lateral, and ventral medial streams) flowed together to exit ventrally at the nasopharyngeal duct, bypassing the ethmoid recesses. The remaining dorsal medial stream split to flow both medially and laterally through the olfactory-epithelium-lined ethmoid recesses in a Z-shaped pattern when viewed sagitally. Simulated flow in the ethmoid recesses was more than an order of magnitude slower than flow in the anterior and ventral parts of the nasal passages. Somewhat higher volumes of flow were predicted in the dorsal medial stream when the nasal vestibule was reshaped to be upturned, and more flow was allocated to the dorsal medial stream with increased inspiratory airflow rate, suggesting that rats may be able to allocate more airflow to this stream by both modifying the shape of the nasal vestibule and increasing inhaled air velocity during sniffing. The present study provides the first description of flow in the complex olfactory region of the nose of the F344 rat. This model will be used to evaluate the role of airflow patterns in determining the distribution of xenobiotically induced olfactory mucosal lesions. This information, combined with models of disposition in the airway lining, will provide comprehensive dosimetry models for extrapolating animal response data to humans.


Subject(s)
Computer Simulation , Models, Anatomic , Models, Biological , Nasal Cavity/anatomy & histology , Nasal Cavity/physiology , Pulmonary Ventilation/physiology , Animals , Male , Rats , Rats, Inbred F344
11.
Int Arch Allergy Immunol ; 113(1-3): 87-95, 1997.
Article in English | MEDLINE | ID: mdl-9130491

ABSTRACT

Over the past 5 years, we have been engaged in a cross-sectional evaluation of risk factors for higher asthma severity in adolescents aged 13-18. All recruitment takes place through public and private schools. The sample from which our current findings are derived includes 151 adolescents covering a wide spectrum of asthma severity and socioeconomic status (SES) and representing both African American and Caucasians. An asthma severity instrument has been developed and validated for the purpose of this study. This yields an asthma severity score which is a continuous variable. Female gender and the number of positive skin tests are the best independent correlates to the asthma severity score. Among the 18 aeroallergens used in the study, the American cockroach Periplaneta americana is the only one that relates to the asthma severity score in a stepwise regression model. The two other cockroaches, German and oriental, as well as the dust mites Dermatophagoides farinae and Dermatophagoides pteronyssinus, correlate with the asthma severity only in simple regression analysis. The relationship between asthma severity and cockroach sensitivity is strongest within the lowest-income per family member quartile. This is consistent with the additional observations that (1) significantly higher rates of sensitization for cockroaches are observed in the lowest-income quartile subjects and (2) higher levels of the cockroach allergen Bla g 1 are found in their homes. Preliminary analysis suggests that ethnic background may interact with environmental exposure in that, within the lowest-income quartile, Caucasians have lower sensitization rates to cockroaches and other allergens compared to African Americans. Within the Caucasian population, income does not appear to influence sensitization rates. The treatment that adolescents with asthma receive for their respiratory disease is characterized by an overall low rate of prescribed inhaled corticosteroids (37% in the moderately severe and severe groups). This inadequacy in treatment is accentuated by SES: 28% of adolescents in the highest and 6% in the lowest-income quartile are prescribed these medications. Our findings are consistent with the hypothesis that the higher asthma morbidity and mortality observed in the African American population is related to higher exposure and sensitization to allergens such as those from cockroaches that are more prevalent in lower SES environments. It is possible that genetic factors contribute to the higher degree of sensitization. In addition, individuals of low SES are subjected to inadequate medical management of their asthma.


Subject(s)
Asthma/etiology , Adolescent , Allergens/immunology , Animals , Asthma/therapy , Cockroaches/immunology , Dust/adverse effects , Female , Humans , Male , Socioeconomic Factors
12.
Phys Sportsmed ; 25(3): 45-55, 1997 Mar.
Article in English | MEDLINE | ID: mdl-20086891

ABSTRACT

Exercise-induced asthma (EIA) can be easily overlooked and underdiagnosed, especially in school children or recreational athletes. It affects individuals of all levels of activity, from recreational sports to competition. This article summarizes the results of the Olympic Exercise Asthma Summit Conference, organized by the Sports Medicine Division of the US Olympic Committee. Making the correct diagnosis of EIA is very important and usually requires some form of pulmonary function testing. Because effective pharmacologic and nonpharmacologic treatment is available for this condition, patients should be followed until the condition is controlled.

13.
Toxicol Pathol ; 22(4): 353-72, 1994.
Article in English | MEDLINE | ID: mdl-7817125

ABSTRACT

Knowledge of patterns of lesion distribution can provide insight into the relative roles played by regional tissue dose and local tissue susceptibility in toxic responses to xenobiotics in the nose and assist assessment of potential human risk. A consistent approach is needed for recording lesion distribution patterns in the complex nasal airways of rats and mice. The present work provides a series of diagrams of the nasal passages of the Fischer-344 rat and B6C3F1 mouse, designed for mapping nasal lesions. The diagrams present each of the major cross-sectional airway profiles, provide adequate space for nasal mucosal lesion recording, and are suitable for duplication in a commercial photocopier. Sagittal diagrams are also provided to permit transfer of lesion location data observed in transverse sections onto the long axis of the nose. The distribution of lesions induced by a selected range of xenobiotics is presented. Approaches to application of the diagrams and interpretation of results obtained are discussed in relation to factors responsible for lesion distribution in the nose and their relevance to interspecies extrapolation. A modified approach to anatomical classification of the ethmoturbinates of the rodent is also presented.


Subject(s)
Medical Illustration , Mice, Inbred Strains/anatomy & histology , Nasal Cavity/anatomy & histology , Rats, Inbred F344/anatomy & histology , Animals , Male , Mice , Nasal Cavity/drug effects , Nasal Cavity/pathology , Rats , Toxicology/methods
14.
J Biomater Sci Polym Ed ; 5(4): 303-24, 1994.
Article in English | MEDLINE | ID: mdl-8025029

ABSTRACT

Three water soluble copolymers based on N-(2-hydroxypropyl)methacrylamide were prepared. Copolymer I contains adriamycin, a chemotherapeutic agent, attached via enzymatically degradable oligopeptide (glycylphenylalanylleucylglycine; G-F-L-G) side chains. The other two copolymers contained the photosensitizer, meso-chlorin e6 monoethylene diamine disodium salt (Mce6). In Copolymer II, the chlorin is attached via the degradable G-F-L-G sequence, and it was bound by the nondegradable glycyl spacer in Copolymer III. Initially, the copolymers were characterized separately in vitro and in vivo. Combinations of the copolymer bound chemotherapeutic agent and each of the copolymer bound photosensitizers were then assessed for antitumor effect in vivo. Localization/retention studies (A/J mice; Neuro 2A neuroblastoma solid tumor) were performed with the two copolymers containing Mce6 as well as the free drug. Results of these experiments demonstrated a very different tumor uptake profile for the two copolymers. While the free drug was rapidly cleared from tumor tissue, the copolymer containing Mce6 attached via the non-degradable bond was retained for an extended period; drug concentrations in the tumor were high even after 5 days. On the other hand, a high concentration of the copolymer containing Mce6 bound via the degradable sequence was taken up by the tumor, yet its concentration in the tumor was substantially diminished at 48 h after administration. This shows indirect evidence of in vivo cleavage of Mce6 from the copolymer in the lysosomal compartment which is supported by direct evidence of cleavage by cathepsin B (a lysosomal enzyme) in vitro. Antitumor effects were assessed on Neuro 2A neuroblastoma induced in A/J mice for all three copolymers. Photodynamic therapy (PDT) proved the copolymer with Mce6 bound via the degradable oligopeptide sequence to be a more effective photosensitizer in vivo than the other chlorin containing copolymer. The difference in activity was consistent with the results obtained by photophysical analyses in which the free drug had a higher quantum yield of singlet oxygen generation than the polymer bound drug in buffer. The quantum yield of singlet oxygen generation increased with the enzymatic cleavage of the chlorin from the copolymer. Conditions were subsequently determined for which chemotherapy or PDT would show some antitumor effect, yet be incapable of curing tumors. Finally, combination therapy experiments were performed in which the copolymer bound adriamycin was mixed with either of the copolymer bound chlorin compounds and injected intravenously (i.v.) into the tail veins of mice.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Acrylamides/chemistry , Doxorubicin/administration & dosage , Light , Mesoporphyrins/chemistry , Neuroblastoma/drug therapy , Photochemotherapy , Animals , Cathepsin B , Doxorubicin/chemistry , Drug Carriers , Mice , Mice, Inbred A , Molecular Structure , Neoplasm Transplantation , Neuroblastoma/pathology , Time Factors
15.
Toxicol Appl Pharmacol ; 121(2): 253-63, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8346542

ABSTRACT

For certain inhaled air pollutants, such as reactive, water soluble gases, the distribution of nasal lesions observed in F344 rats may be closely related to regional gas uptake patterns in the nose. These uptake patterns can be influenced by the currents of air flowing through the upper respiratory tract during the breathing cycle. Since data on respiratory tract lesions in F344 rats are extrapolated to humans to make predictions of risk to human health, a better understanding of the factors affecting these responses is needed. To assess potential effects of nasal airflow on lesion location and severity, a methodology was developed for creation of computer simulations of steady-state airflow and gas transport using a three-dimensional finite element grid reconstructed from serial step-sections of the nasal passages of a male F344 rat. Simulations on a supercomputer used the computational fluid dynamics package FIDAP (FDI, Evanston, IL). Distinct streams of bulk flow evident in the simulations matched inspiratory streams reported for the F344 rat. Moreover, simulated regional flow velocities matched measured velocities in concurrent laboratory experiments with a hollow nasal mold. Computer-predicted flows were used in simulations of gas transport to nasal passage walls, with formaldehyde as a test case. Results from the uptake simulations were compared with the reported distribution of formaldehyde-induced nasal lesions observed in the F344 rat, and indicated that airflow-driven uptake patterns probably play an important role in determining the location of certain nasal lesions induced by formaldehyde. This work demonstrated the feasibility of applying computational fluid dynamics to airflow-driven dosimetry of inhaled chemicals in the upper respiratory tract.


Subject(s)
Nose/physiology , Pharmacokinetics , Pulmonary Ventilation/physiology , Radiotherapy Planning, Computer-Assisted/methods , Administration, Inhalation , Air Pollutants/adverse effects , Air Pollutants/pharmacokinetics , Animals , Computer Simulation , Gases/adverse effects , Gases/pharmacokinetics , Male , Nose/anatomy & histology , Nose/drug effects , Rats , Rats, Inbred F344
16.
Radiat Res ; 114(1): 105-13, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3353498

ABSTRACT

The injectable anesthetic etomidate and a clip that facilitates hyperthermia by water bath immersion (the "Gibbs clip") were evaluated for their suitability with subcutaneous flank RIF-1 tumors in C3H/HeJ mice. For tumors between 100 and 250 mg (mean, 160 mg), etomidate at 40 mg kg-1 ip did not significantly increase the radiobiologic hypoxic fraction (RHF); as calculated from an in vitro assay after treatment in vivo the RHF increased from 0.06 (95% C.I.:0.03-0.13) to 0.08 (0.04-0.16). In contrast, for larger tumors (270-650 mg; mean, 400 mg) etomidate increased the RHF from 0.08 (0.04-0.17) to 0.28 (0.14-0.60). Holding 250-mg-or-less tumors 3-mm laterally away from the flank in an X-ray jig did not significantly reduce tumor blood flow as inferred from the clearance rates of Xe, but the RHF of 0.15 (0.08-0.26) was significantly (P less than 0.05) greater than the RHF in unanesthetized mice, although not the RHF in anesthetized mice. The Gibbs clip, which folded skin around a tumor to enhance thermal conduction from a water bath, did not impair the increase in tumor blood flow in response to the cardiovascular arousal associated with exposure to a hyperthermic stimulus. Intratumor temperature was within 0.25 degrees C of bath temperature 3 min after the tumor and clip were immersed, but only when rectal temperatures were at 37 degrees C or above; tumor blood flow increased intratumor temperature gradients by 0.10 degrees C for each 1.5 degrees C that the body temperature was below 37 degrees C.


Subject(s)
Anesthesia , Neoplasms, Experimental/therapy , Oxygen , Animals , Blood Flow Velocity , Etomidate/administration & dosage , Female , Hyperthermia, Induced/instrumentation , Injections, Intraperitoneal , Male , Mice , Neoplasm Transplantation , Neoplasms, Experimental/blood supply , Neoplasms, Experimental/radiotherapy , Radiotherapy/instrumentation , Research Design
17.
Int J Hyperthermia ; 3(3): 235-44, 1987.
Article in English | MEDLINE | ID: mdl-3655437

ABSTRACT

The RIF-1 cell line at the University of Utah is comprised of approximately 65 per cent diploid and 35 per cent tetraploid cells. Because sensitivity to heat cell killing has been shown to be ploidy dependent (Lucke-Huhle 1978), the responses of these subpopulations were examined independently. Diploid and tetraploid cells were separated from stock in vitro cultures by centrifugal elutriation and maintained entirely in vitro. No influence of ploidy on Do or Dq of heat dose survival curves could be detected. Neither did ploidy affect sensitivity to X-irradiation. However, separation of the diploid and tetraploid subpopulations was imperfect. The ratio of diploid to tetraploid cells in the separated and parent (mixed ploidy) lines was therefore monitored at each passage. Tetraploid contamination of the diploid cell subline was undetectable at the time of separation but regrew to 35 per cent by 40 days after separation. Diploid contamination of the tetraploid subline was initially less than 5 per cent and remained quite low until it became undetectable at 74 days. Differences in regrowth of the contaminating subline could not be accounted for by differences in plating efficiency or doubling time, but might result from subpopulation interactions. If so, such phenomena should be considered when using ploidy-dependent cytotoxic treatments.


Subject(s)
Fever , Tumor Cells, Cultured/radiation effects , Cell Line , Cell Survival/radiation effects , Diploidy , Dose-Response Relationship, Radiation , Flow Cytometry/methods , Time Factors , Tumor Cells, Cultured/cytology
18.
Clin Endocrinol (Oxf) ; 17(2): 173-9, 1982 Aug.
Article in English | MEDLINE | ID: mdl-6127179

ABSTRACT

The species specificity of TSH binding inhibitory antibodies was compared for patients with untreated Graves' hyperthyroidism, past Graves' hyperthyroidism, active ophthalmopathy with past hyperthyroidism, and subacute thyroiditis, by measuring inhibition of TSH binding to plasma membranes prepared from human, guinea-pig, calf, pig, and dog thyroid glands in a radioreceptor assay. Results were expressed as TSH binding inhibition indices (TBII). Broad species reactivity was demonstrated. This was greatest with pig and least with guinea-pig thyroid membranes. Immunoglobulin (Ig) from patients in whom strongly positive tests with human thyroid preparations were demonstrated were usually strongly positive with all other species tested, whereas Ig from patients which were less strongly positive with human were, generally, also less positive with the other species. There was a tendency for greater species reactivity of TSH binding inhibiting antibodies from patients with treated Graves' hyperthyroidism (with or without eye disease) than of those from untreated patients with Graves' hyperthyroidism or subacute thyroiditis. Combining the data from all groups, correlation between TBII for human membranes and those of other species was best for dog and least for guinea-pig. It is concluded that the TSH binding inhibiting antibody is a polyclonal antibody against a single antigen at or near the TSH receptor, and that the degree of reactivity with its antigen in other species depends, mainly, on the amount of antibody present in the serum.


Subject(s)
Immunoglobulin G/metabolism , Receptors, Cell Surface/immunology , Thyroid Diseases/immunology , Thyrotropin , Adult , Animals , Cattle , Dogs , Female , Graves Disease/immunology , Guinea Pigs , Humans , Immunoglobulins, Thyroid-Stimulating , Male , Middle Aged , Radioligand Assay , Receptors, Thyrotropin , Species Specificity , Swine , Thyroid Gland/immunology , Thyroiditis/immunology
19.
J Clin Immunol ; 2(1): 15-9, 1982 Jan.
Article in English | MEDLINE | ID: mdl-6284789

ABSTRACT

Thyroid-stimulating hormone (TSH) receptor antibodies and antibodies stimulating adenyl cyclase were measured in 47 relatives of patients with Graves' hyperthyroidism from two families with a high prevalence of the disease, in whom bioassays for the long-acting thyroid stimulator (LATS) had been performed 10 years earlier. Tests were also carried out in six propositi from the two families and age- and sex-matched normal subjects from six families. There had been no new cases of hyperthyroidism since the first study, although one subject was clinically and biochemically hyperthyroid at the time of study and two more were biochemically borderline hyperthyroid but clinically euthyroid. Levels of serum T4 thyrotropin, and percentage T3 resin uptake and free thyroxine indices were similar for relatives and normal subjects, although the mean serum T3 level for relatives was significantly greater than that for the normal subjects. Antibodies were not detected by either assay in any relative. Significant titers of antithyroglobulin antibodies were demonstrated in 4 of 44 relatives but in none of 46 normals tested, while thyroid cytoplasmic antibodies were detected in 8 of 44 relatives and 3 of 45 normals. The mean serum IgG for Graves' relatives was significantly greater than that for the normals, although the mean IgM and IgA levels for the two groups were not significantly different.


Subject(s)
Adenylyl Cyclases/metabolism , Autoantibodies/biosynthesis , Graves Disease/immunology , Receptors, Cell Surface/immunology , Adenylyl Cyclases/genetics , Adolescent , Adult , Aged , Animals , Autoantibodies/analysis , Autoantibodies/genetics , Child , Child, Preschool , Female , Follow-Up Studies , Graves Disease/enzymology , Graves Disease/genetics , Guinea Pigs , Humans , Hyperthyroidism/diagnosis , Immunoglobulin G/analysis , Long-Term Care , Male , Middle Aged , Receptors, Cell Surface/genetics , Receptors, Thyrotropin , Thyroid Function Tests
20.
Am J Sports Med ; 9(4): 225-32, 1981.
Article in English | MEDLINE | ID: mdl-7258461

ABSTRACT

In an attempt to correct anterolateral rotatory instability of the knee, 30 consecutive patients underwent a surgical procedure similar to that described by Ellison (Ellison AE: A modified procedure for the extra-articular replacement of the anterior cruciate ligament. American Orthopaedic Society for Sports Medicine Symposium, New Orleans, LA, July 15, 1975), called the iliotibial band transfer. Fashioning the passageway for the transfer closer to the attachment of the fibular collateral ligament on the femur and meticulous fascial closure over the transplant were not found to be crucial to success. Twenty-nine of the 30 patients were injured during athletic activities, and the remaining patient was injured in a motorcycle accident. They often complained of an unstable knee with symptoms of pain and giving way. Twenty-eight patients with a minimum followup of nine months (the average followup was 25 months) were evaluated subjectively by an interview and by objective clinical examination. Subjective results (including asymptomatic return to their previous level of athletic activity) and clinical improvement of anterolateral rotatory instability (based on the flexion-extension-valgus test or the Slocum anterolateral rotatory instability test) were encouraging. Areas of concern were that a small number of patients developed asymptomatic varus instability and a few had relative strength deficits which may or may not have long-term significance.


Subject(s)
Athletic Injuries/surgery , Joint Dislocations/surgery , Knee Injuries/surgery , Ligaments, Articular/injuries , Accidents, Traffic , Adolescent , Adult , Athletic Injuries/rehabilitation , Female , Humans , Joint Dislocations/rehabilitation , Knee Injuries/rehabilitation , Ligaments, Articular/surgery , Male , Methods , Postoperative Care
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