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1.
J Undergrad Neurosci Educ ; 16(2): A112-A119, 2018.
Article in English | MEDLINE | ID: mdl-30057492

ABSTRACT

Many pre-health students pursue extracurricular shadowing opportunities to gain clinical experience. The Virginia Tech School of Neuroscience introduced a formal course that provides a clinical experience superior to that received by many medical students. This course is composed of weekly 75-minute seminars that cover diseases affecting the nervous system, their diagnosis and treatment, complemented by weekly half-day intensive clinical experiences with unprecedented access to a team of neurosurgeons (in hospital operating rooms, Intensive Care Units, emergency room, angiographic suites, and wards). In the operating rooms, students routinely "scrub-in" for complex surgeries. On hospital rounds, students experience direct patient care and receive in-depth exposure to modern nervous system imaging. Students participate in two 24-hour "on-call" experiences with team providers. After call, students participate in cognitive and psychological studies to assess physiological and psychological effects of call-related sleep deprivation. Students prepare weekly essays on challenging socioeconomic and ethical questions, exploring subjects such as the cost of medicine and inequalities in access to health care. Towards the end of the course, students meet with the admission dean of the Virginia Tech Carilion medical school; they prepare a personal statement for medical school/graduate school applications, and attend a half-day block of mock medical school/graduate school interviews delivered by experienced clinicians. In lieu of a final exam, each student presents to the entire neurosurgery department, an in-depth clinical analysis of a case in which they participated. We provide details on implementation, challenges and outcomes based on experiences from three semesters with a total enrollment of approximately 60 students.

2.
Mucosal Immunol ; 5(3): 311-9, 2012 May.
Article in English | MEDLINE | ID: mdl-22377931

ABSTRACT

As most pathogens enter through the mucosa, it is important to develop vaccines that induce mucosal immunity. To this end, we generated a novel adenovirus (Ad) vaccine that displays the σ1 protein from reovirus to target junctional adhesion molecule 1 and sialic acid. Replication-defective Ad5 vectors were modified by replacement of the Ad fiber protein with σ1 (T3Dσ1) protein of reovirus T3D in previous work. Ad5 and Ad5-σ1 were compared in mouse models for gene delivery and vaccination to monitor cytokine, antibody, and T-cell responses. The viruses were also tested for the ability to transduce and mature dendritic cells. Ad5-σ1 was 40-fold less efficient at gene delivery in vivo, yet it was capable of inducing equal or greater cellular immune responses and systemic interferon-γ levels than Ad5 after intranasal administration. Despite weaker gross transduction, intranasal administration of Ad5-σ1 produced more green fluorescent protein-positive (GFP+) major histocompatibility complex class II (MHC II) cells in the draining lymph nodes, less GFP+/MHC II+ cells in the lungs, and mediated modestly better maturation of dendritic cells in vitro. These data suggest that targeting gene-based vaccination via the σ1 protein may enhance the T-cell immune response, perhaps by skewing immune responses to encoded antigens.


Subject(s)
Adenoviridae Infections/immunology , Adenoviridae/physiology , Capsid Proteins/metabolism , Reoviridae/physiology , Respiratory Mucosa/metabolism , T-Lymphocytes/immunology , Adenoviridae Infections/virology , Animals , Capsid Proteins/genetics , Capsid Proteins/immunology , Cell Differentiation , Cells, Cultured , Cross-Priming/genetics , Dendritic Cells/immunology , Genetic Engineering , Genetic Vectors/immunology , Immunity, Cellular/genetics , Interferon-gamma/metabolism , Mice , Mice, Inbred BALB C , Respiratory Mucosa/immunology , Respiratory Mucosa/virology
3.
Cancer Gene Ther ; 18(10): 744-50, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21886190

ABSTRACT

Although there are 55 serotypes of adenovirus (Ad) that infect humans, Ad serotype 5 (Ad5) is the most widely studied because of the availability of commercial kits for its genetic manipulation. In fact, engineered Ad 5 is currently being used in all of the 87 global clinical trials utilizing Ad for the treatment of cancer. Unfortunately, Ad5 is one of the most seroprevalent serotypes, meaning that this virus has to confront additional immunological barriers to be effective in Ad5-immune patients. In this work, we compare Ad5 to 13 other adenoviral serotypes from species B, C, D and E for oncolytic potential in both immunodeficient mouse and immunocompetent hamster models. Our results indicate that species D Ads are not effective oncolytics against most solid tumors. Conversely, lower seroprevalent Ad6 and Ad11 had anti-cancer activity comparable to Ad5. This work strongly supports the consideration of Ad6-based oncolytic therapies for the treatment of breast, ovarian, kidney and liver tumors.


Subject(s)
Adenoviruses, Human/immunology , Neoplasms/immunology , Oncolytic Virotherapy , Oncolytic Viruses/immunology , Adenoviruses, Human/classification , Adenoviruses, Human/genetics , Animals , CHO Cells , Cell Line, Tumor , Cell Survival , Cricetinae , Cytopathogenic Effect, Viral , Female , HEK293 Cells , Humans , Mice , Mice, Nude , Neoplasms/metabolism , Neoplasms/therapy , Oncolytic Viruses/classification , Oncolytic Viruses/genetics , Phylogeny , Xenograft Model Antitumor Assays
4.
Eur Respir Rev ; 19(116): 141-9, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20956183

ABSTRACT

Descending necrotising mediastinitis is a rare and serious infection with a high mortality rate, which complicates pharyngeal or odontogenic infection. Early recognition and treatment are essential in order to minimise morbidity. Evaluation with computed tomography is necessary to confirm the diagnosis and facilitate surgical planning. In addition to prompt empirical antibiotic therapy, surgical intervention is necessary in nearly all cases. Surgical drainage and debridement may be performed through cervicotomy alone, or through combined cervicotomy and thoracotomy, depending upon the extent of disease. Hyperbaric oxygen therapy may play an auxiliary role. We present two recent cases with characteristic imaging findings, and review the relevant literature.


Subject(s)
Mediastinitis/diagnostic imaging , Mediastinitis/therapy , Tomography, X-Ray Computed , Adult , Humans , Male , Mediastinitis/pathology , Middle Aged , Necrosis , Respiration, Artificial , Streptococcal Infections/diagnostic imaging , Streptococcal Infections/pathology , Streptococcal Infections/therapy , Streptococcus intermedius
5.
AIDS Res Hum Retroviruses ; 26(5): 577-84, 2010 May.
Article in English | MEDLINE | ID: mdl-20438382

ABSTRACT

Consensus HIV-1 genes can decrease the genetic distances between candidate immunogens and field virus strains. To ensure the functionality and optimal presentation of immunologic epitopes, we generated two group-M consensus env genes that contain variable regions either from a wild-type B/C recombinant virus isolate (CON6) or minimal consensus elements (CON-S) in the V1, V2, V4, and V5 regions. C57BL/6 and BALB/c mice were primed twice with CON6, CON-S, and subtype control (92UG37_A and HXB2/Bal_B) DNA and boosted with recombinant vaccinia virus (rVV). Mean antibody titers against 92UG37_A, 89.6_B, 96ZM651_C, CON6, and CON-S Env protein were determined. Both CON6 and CON-S induced higher mean antibody titers against several of the proteins, as compared with the subtype controls. However, no significant differences were found in mean antibody titers in animals immunized with CON6 or CON-S. Cellular immune responses were measured by using five complete Env overlapping peptide sets: subtype A (92UG37_A), subtype B (MN_B, 89.6_B and SF162_B), and subtype C (Chn19_C). The intensity of the induced cellular responses was measured by using pooled Env peptides; T-cell epitopes were identified by using matrix peptide pools and individual peptides. No significant differences in T-cell immune-response intensities were noted between CON6 and CON-S immunized BALB/c and C57BL/6 mice. In BALB/c mice, 10 and eight nonoverlapping T-cell epitopes were identified in CON6 and CON-S, whereas eight epitopes were identified in 92UG37_A and HXB2/BAL_B. In C57BL/6 mice, nine and six nonoverlapping T-cell epitopes were identified after immunization with CON6 and CON-S, respectively, whereas only four and three were identified in 92UG37_A and HXB2/BAL_B, respectively. When combined together from both mouse strains, 18 epitopes were identified. The group M artificial consensus env genes, CON6 and CON-S, were equally immunogenic in breadth and intensity for inducing humoral and cellular immune responses.


Subject(s)
AIDS Vaccines/immunology , Consensus Sequence/immunology , HIV-1/immunology , T-Lymphocytes/immunology , Vaccines, DNA/immunology , env Gene Products, Human Immunodeficiency Virus/immunology , AIDS Vaccines/genetics , Amino Acid Sequence , Animals , Consensus Sequence/genetics , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Female , HIV Antibodies/blood , HIV Infections/immunology , HIV Infections/prevention & control , HIV-1/classification , HIV-1/genetics , Immunization , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Molecular Sequence Data , Vaccines, DNA/genetics , Vaccinia virus/genetics , Vaccinia virus/immunology , env Gene Products, Human Immunodeficiency Virus/chemistry , env Gene Products, Human Immunodeficiency Virus/genetics
6.
Vet Rec ; 163(18): 536-8, 2008 Nov 01.
Article in English | MEDLINE | ID: mdl-18978366

ABSTRACT

An experiment was conducted to determine whether spray-dried porcine plasma containing 2.47 x 10(5) dna copies of porcine circovirus type 2 (pcv-2) could infect weanling pigs when fed to them. Five specific pathogen-free (spf) weanling pigs were fed ad libitum for 45 days a control diet and six pigs were fed a test diet containing 8 kg sdpp per 100 kg feed. The two groups were housed in separate biosecurity level-3 rooms. None of the pigs in either group developed any clinical signs or became pcv-2 viraemic or seroconverted.


Subject(s)
Circoviridae Infections/veterinary , Circovirus/pathogenicity , DNA, Viral/administration & dosage , Swine Diseases/transmission , Animal Feed , Animals , Animals, Newborn , Circoviridae Infections/transmission , Plasma , Random Allocation , Specific Pathogen-Free Organisms , Swine , Weaning
7.
J Dairy Sci ; 90(12): 5726-31, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18024765

ABSTRACT

The objective of this study was first to evaluate whether irradiation treatment of a commercial colostrum replacer (CR) affected acquisition of passive immunity. If the irradiation treatment negatively affected the acquisition of passive immunity, the second objective was to evaluate whether an increased total IgG mass, in a single feeding of CR derived from bovine serum fractions, could compensate for this effect. Acquisition of passive immunity was assessed by 24-h serum IgG levels, serum protein levels, apparent efficiency of absorption (AEA) of IgG, and the ability to prevent failure of passive transfer (FPT) in day-old dairy calves fed a single feeding of CR. Single-dose packs of CR were sent to a commercial irradiation facility for electron-beam irradiation at 3 to 7 kGy (low irradiation) or 15 to 20 kGy (high irradiation). Fifty-six Holstein, Jersey, or crossbred calves were randomly assigned to 1 of 5 treatments: 1) 130 g of IgG (460 g of CR), no irradiation; 2) 130 g of IgG (460 g of CR), low irradiation; 3) 160 g of IgG (518 g of CR), low irradiation; 4) 190 g of IgG (575.4 g of CR), low irradiation; and 5) 130 g of IgG (460 g of CR), high irradiation. All CR were reconstituted in water and mixed in a household blender to a constant solids concentration of 18.7%. Increasing doses of irradiation (130 g of Ig with no, low, or high irradiation) resulted in a linear decrease in 24-h serum IgG and AEA of IgG, and increased the percentage of calves with FPT. Increasing the IgG mass in the CR (130, 160, and 190 g of Ig with low irradiation) resulted in a linear increase in 24-h serum IgG and serum total protein levels, and a linear decrease in AEA of IgG. There was no effect of increasing the mass of IgG fed on the percentage of calves with FPT. The correlation between serum IgG and serum total protein at 24 h was positive; however, at 24 h the irradiation treatments reduced the serum IgG-to-serum total protein ratio. In this study, CR isolated from bovine serum, providing 130 g of IgG in the first feeding and receiving either no irradiation or a low irradiation treatment, was sufficient to prevent FPT in calves.


Subject(s)
Cattle/immunology , Food Irradiation , Immunity, Maternally-Acquired/immunology , Immunoglobulin G/metabolism , Milk Substitutes/administration & dosage , Absorption , Animal Feed , Animals , Animals, Newborn/immunology , Blood Proteins/analysis , Colostrum/immunology , Dose-Response Relationship, Immunologic , Dose-Response Relationship, Radiation , Food Irradiation/adverse effects , Immunoglobulin G/administration & dosage , Immunoglobulin G/blood , Male , Random Allocation
8.
Eur J Clin Invest ; 37(9): 746-52, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17696966

ABSTRACT

RATIONALE: Nitric oxide (NO) is present at higher concentrations in the nasal cavity than in the lower airway, and at even higher concentrations within the paranasal sinuses proper. When the paranasal sinus ostia are patent, acoustic activity produced by vocalization with closed lips (humming) promotes mixing of sinus with nasal gases, producing a further increase in nasal NO. We wished to evaluate procedures for the documentation of the nasal NO response to humming. MATERIALS AND METHODS: We compared two ATS-recommended sampling methods: 1) active exhalation of lower airway gas (parallel technique) and 2) passive aspiration of nasal gas with closed velopharynx (series technique). Variables controlled for included sampling rate, external resistance (parallel method), humming frequency, humming duration, and intertrial interval. Prior to upper airway sampling, exhaled lower airway NO was determined utilizing ATS-standardized technique. RESULTS: Ten volunteers (seven males and three females, aged 21-58) with no history of respiratory allergies or sino-nasal disease were studied in a single session each. The parallel technique documented an increase in nasal NO during the humming manoeuvre in all subjects (mean ratio of humming-to-quiet NO, 4.2), whereas the series technique did so in eight of 10 subjects (mean ratio 2.1). Correcting for admixture from the lower airway, the ratio of humming-to-quiet NO was greater with the parallel than series sampling technique (P < 0.05). CONCLUSIONS: Documentation of the response of nasal NO to humming in subjects without sino-nasal disease was consistently achievable by parallel sampling using commercially available equipment. Specific operational procedures are proposed.


Subject(s)
Bronchodilator Agents/therapeutic use , Nasal Cavity , Nitric Oxide/therapeutic use , Paranasal Sinuses/physiology , Sinusitis/etiology , Adult , Breath Tests/methods , Exhalation , Female , Humans , Male , Middle Aged
9.
J Anim Sci ; 83(12): 2876-85, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16282627

ABSTRACT

Five experiments were conducted to evaluate the effects of dietary spray-dried porcine plasma (SDPP) and spray-dried bovine plasma (SDBP) and their various molecular weight fractions on performance of pigs weaned at approximately 14 or 21 d of age. In addition, the efficacy of various levels of the immunoglobulin G (IgG)-rich fraction of SDPP and SDBP were evaluated. Experiment 1 evaluated the dietary addition of SDPP and three of its fractions (IgG-rich, albumin-rich, and low molecular weight fractions). Pigs fed SDPP grew faster and consumed more feed than the controls during the first week (P < 0.05). The IgG-rich fraction resulted in improvements in ADG and ADFI that were similar to those of pigs fed SDPP. The albumin-rich fraction had no effect on growth rate, but the low molecular weight fraction decreased feed intake as well as growth rate. Experiments 2 and 3 evaluated SDPP and graded levels of its IgG-rich fraction in pigs weaned at 21 or 14 d, respectively. In Exp. 2, pigs fed SDPP grew faster and consumed more feed than the controls during the first week (P < 0.05). Pig performance was enhanced with the addition of the IgG-rich fraction that provided 80% of the amount of IgG in the SDPP diet. In Exp. 3, there was no response to SDPP during the first week, but a positive growth response to SDPP (P < 0.01) occurred by the end of wk 2 (0 to 14 d). Feeding the IgG-rich fraction increased growth rate compared with controls (P < 0.05). Over the entire experiment, the greatest ADG occurred with the IgG-rich fraction that provided 128% of the amount of IgG provided by SDPP (quadratic; P < 0.05). Two additional experiments assessed feeding SDBP and bovine IgG-rich fractions to early weaned pigs. In Exp. 4, SDPP was superior to SDBP in stimulating growth and feed intake, but this difference did not occur in Exp. 5. In both experiments, the IgG fraction of bovine plasma seemed to be as effective at improving growth as SDPP and more effective than SDBP. The results indicate that both porcine and bovine plasma are beneficial to young pig performance during the first week after weaning and that the IgG fraction of plasma is the component that is responsible for the enhancement in growth rate and feed intake.


Subject(s)
Animal Feed/analysis , Animal Husbandry/methods , Immunoglobulins/pharmacology , Plasma/metabolism , Swine/growth & development , Animals , Cattle , Diet , Immunoglobulins/chemistry , Plasma/chemistry , Weaning , Weight Gain/drug effects
10.
J Mot Behav ; 37(4): 311-24, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15967756

ABSTRACT

The authors measured postural sway while participants (N = 20 in each experiment) stood on a rigid or a compliant surface, with their eyes open or closed, and while they did or did not perform a short-term memory (STM) task. In Experiment 1, the STM stimuli were presented visually; in Experiment 2, the stimuli were presented auditorily. In both experiments, fine-scaled, mediolateral postural-sway variability decreased as the cognitive load imposed by the STM task increased. That effect was independent of support surface and vision manipulations. The spatiotemporal profile of postural sway was affected by both visual and auditory STM tasks, but to a greater degree by the auditory task. The authors discuss implications of the results for theories and models of postural control.


Subject(s)
Auditory Perception/physiology , Memory, Short-Term/physiology , Posture , Space Perception/physiology , Time Perception/physiology , Visual Perception/physiology , Adolescent , Adult , Attention/physiology , Cognition , Electrophysiology/instrumentation , Female , Humans , Male
11.
J Anim Sci ; 82(8): 2397-404, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15318740

ABSTRACT

Three experiments were conducted to evaluate spray-dried blood cells (SDBC) and crystalline isoleucine in nursery pigs. In Exp. 1, 120 pigs were used to evaluate 0, 2, 4, and 6% SDBC (as-fed basis) in a sorghum-based diet. There were six replicates of each treatment and five pigs per pen, with treatments imposed at an initial BW of 9.3 kg and continued for 16 d. Increasing SDBC from 0 to 4% had no effect on ADG, ADFI, and G:F. Pigs fed the 6% SDBC diet had decreased ADG (P < 0.01) and G:F (P = 0.06) compared with pigs fed diets containing 0, 2, or 4% SDBC. In Exp. 2, 936 pigs were used to test diets containing 2.5 or 5% SDBC (as-fed basis) vs. two control diets. There were six replicates of each treatment at industry (20 pigs per pen) and university (six pigs per pen) locations. Treatments were imposed at an initial BW of 5.9 and 8.1 kg at the industry and the university locations, respectively, and continued for 16 d. Little effect on pig performance was noted by supplementing 2.5% SDBC, with or without crystalline Ile, in nursery diets. Pigs fed the 5% SDBC diet without crystalline Ile had decreased ADG (P < 0.01), ADFI (P < or = 0.10), and G:F (P < 0.05) compared with pigs fed the control diets. Supplementation of Ile restored ADG, ADFI, and G:F to levels that were not different from that of pigs fed the control diets. In Exp. 3, 1,050 pigs were used to test diets containing 5, 7.5, or 9% SDBC (as-fed basis) vs. a control diet. There were six replicates of each treatment at the industry (20 pigs per pen) location and five replicates at the university (six pigs per pen) locations. Treatments were imposed at an initial BW of 6.3 and 7.0 kg at the industry and university locations, respectively, and continued for 16 d. Supplementation of 5% SDBC without crystalline Ile decreased ADG and G:F (P < 0.01) compared with pigs fed the control diet, but addition of Ile increased ADG (P < 0.01) to a level not different from that of pigs fed the control diet. The decreased ADG, ADFI, and G:F noted in pigs fed the 7.5% SDBC diet was improved by addition of Ile (P < 0.01), such that ADG and ADFI did not differ from those of pigs fed the control diet. Pigs fed diets containing 9.5% SDBC exhibited decreased ADG, ADFI, and G:F (P < 0.01), all of which were improved by Ile addition (P < 0.01); however, ADG (P < 0.05) and G:F (P = 0.09) remained lower than for pigs fed the control diet. These data indicate that SDBC can be supplemented at relatively high levels to nursery diets, provided that Ile requirements are met.


Subject(s)
Animal Feed , Blood Cells , Blood Proteins/administration & dosage , Isoleucine/administration & dosage , Swine/growth & development , Animal Nutritional Physiological Phenomena , Animals , Animals, Newborn , Dose-Response Relationship, Drug , Energy Intake/drug effects , Female , Male , Random Allocation , Swine/metabolism , Time Factors , Weaning , Weight Gain/drug effects
12.
Gut ; 53(4): 514-22, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15016745

ABSTRACT

BACKGROUND: L-Arginine is a nutritional supplement that may be useful for promoting intestinal repair. Arginine is metabolised by the oxidative deiminase pathway to form nitric oxide (NO) and by the arginase pathway to yield ornithine and polyamines. AIMS: To determine if arginine stimulates restitution via activation of NO synthesis and/or polyamine synthesis. METHODS: We determined the effects of arginine on cultured intestinal cell migration, NO production, polyamine levels, and activation of focal adhesion kinase, a key mediator of cell migration. RESULTS: Arginine increased the rate of cell migration in a dose dependent biphasic manner, and was additive with bovine serum concentrate (BSC). Arginine and an NO donor activated focal adhesion kinase (a tyrosine kinase which localises to cell matrix contacts and mediates beta1 integrin signalling) after wounding. Arginine stimulated cell migration was dependent on focal adhesion kinase (FAK) signalling, as demonstrated using adenovirus mediated transfection with a kinase negative mutant of FAK. Arginine stimulated migration was dependent on NO production and was blocked by NO synthase inhibitors. Arginine dependent migration required synthesis of polyamines but elevating extracellular arginine concentration above 0.4 mM did not enhance cellular polyamine levels. CONCLUSIONS: These results showed that L-arginine stimulates cell migration through NO and FAK dependent pathways and that combination therapy with arginine and BSC may enhance intestinal restitution via separate and convergent pathways.


Subject(s)
Arginine/pharmacology , Dietary Supplements , Enterocytes/drug effects , Protein-Tyrosine Kinases/physiology , Animals , Cell Movement/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Enterocytes/physiology , Enzyme Inhibitors/pharmacology , Focal Adhesion Protein-Tyrosine Kinases , Nitric Oxide/metabolism , Ornithine Decarboxylase/physiology , Ornithine Decarboxylase Inhibitors , Phosphorylation/drug effects , Polyamines/pharmacology , Swine , Transfection , Tyrosine/physiology
13.
Abdom Imaging ; 27(2): 196-8, 2002.
Article in English | MEDLINE | ID: mdl-11847581

ABSTRACT

Rarely, hepatic metastases can simulate hepatic infiltrative diseases. We present a case of a patient with advanced metastatic renal cell carcinoma who developed hepatomegaly and clinical signs of hepatocellular injury. On magnetic resonance imaging, the injury simulated a diffuse process, e.g., acute fulminant viral or chemical hepatitis or drug toxicity. Despite its high resolution, magnetic resonance imaging might not depict focal lesions in patients with extensive metastases. In correlation with clinical history, malignant disease should be considered when diffusely abnormal hepatic signal intensity is noted.


Subject(s)
Carcinoma, Renal Cell/secondary , Kidney Neoplasms/pathology , Liver Neoplasms/secondary , Magnetic Resonance Imaging , Carcinoma, Renal Cell/diagnosis , Diagnosis, Differential , Humans , Kidney Neoplasms/diagnosis , Liver Diseases/diagnosis , Liver Neoplasms/diagnosis , Male , Middle Aged
14.
Anal Quant Cytol Histol ; 23(5): 339-44, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11693559

ABSTRACT

OBJECTIVE: To explore the potential utility of immunostaining for CK20 and CD44 protein isoforms in evaluating cases of upper urinary tract transitional cell carcinoma (UTTCC). STUDY DESIGN: Of 105 consecutive patients diagnosed cytologically with UTTCC, 33 subsequently underwent open surgical procedures. Cytologic samples from these patients retrieved by aspiration and biopsy, and corresponding surgical specimens were graded and staged using World Health Organization/International Society of Urologic Pathologists criteria. Immunostaining for CK20, CD44 standard (CD44s) and CD44v6 isoform (CD44-v6) was performed on all available cytologic and surgical materials. Expression levels and distributions of these markers were correlated semiquantitatively with grade and stage. RESULTS: Cytologically assigned grade correlated with final histologic grade in 19 of 31 cases examined (61%). However, tumor invasion was not accurately assessable in cytologic samples from the majority of these cases. Statistically significant correlations of both increasing tumor grade and stage with abnormal CK20 expression were found. In addition, a significant relationship between focal CD44 isoform expression loss and tumor grade was identified. However, CD44 isoform expression loss did not significantly correlate with increasing tumor stage. CONCLUSION: Although cytologic tumor grading of UTTCC was accurate, invasion could not be adequately assessed. As an adjunct to morphologic analysis, immunostaining for CK20 and CD44 may aid in the clinical evaluation of UTTCC tumor stage and biologic behavior prior to definitive therapy.


Subject(s)
Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/ultrastructure , Hyaluronan Receptors/metabolism , Intermediate Filament Proteins/metabolism , Neoplasm Staging/classification , Staining and Labeling/methods , Urologic Neoplasms/diagnosis , Urologic Neoplasms/ultrastructure , Humans , Hyaluronan Receptors/analysis , Intermediate Filament Proteins/analysis , Keratin-20 , Urothelium/pathology
15.
Radiology ; 221(1): 117-21, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11568328

ABSTRACT

Two patients with breast carcinoma, without a prior diagnosis of liver lesions, had proved desmoplastic hepatic metastases that resembled cirrhosis at magnetic resonance (MR) imaging. The cirrhotic appearance of the livers may have resulted from the hepatotoxic effects of chemotherapy and/or hepatic infiltration by the metastatic tumor itself. Despite its high soft-tissue contrast, MR imaging may fail to depict extensive metastases from breast carcinoma, especially when they simulate other diseases (eg, cirrhosis). Correlation of MR imaging findings with clinical history is mandatory.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/secondary , Breast Neoplasms/pathology , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Magnetic Resonance Imaging , Diagnosis, Differential , Female , Humans , Middle Aged
16.
Environ Microbiol ; 3(1): 43-52, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11225722

ABSTRACT

Biofilm formation and function was studied in mixed culture using 20 bacterial strains isolated from a karst aquifer. When co-cultured in a glucose-limited chemostat, Vogesella indigofera and Pseudomonas putida were the dominant planktonic and biofilm organisms respectively. Biofilm formation and resistance to the iodine disinfectant betadine were then studied with monoculture and binary cultures of V. indigofera and P. putida and a 20-strain community. Biofilm population size [measured as colony-forming units (CFU) cm(-2)] increased with increasing species diversity. Significantly larger populations formed at dilution rates (DRs) of 0.0083 h(-1) than at 0.033 h(-1). P. putida populations were higher and V. indigofera lower in binary than in monoculture biofilms, suggesting that P. putida outcompeted V. indigofera. In binary biofilms, V. indigofera, a betadine-resistant organism, enhanced the survival of P. putida, a betadine-susceptible organism. In the 20-strain biofilms, this protective effect was not observed because of low concentrations of V. indigofera (< 1% of the total population), suggesting that resistant organisms contribute to overall biofilm disinfectant resistance. Growth at 0.033 h(-1) enhanced survival of V. indigofera biofilms against betadine. Although DR did influence survival of the other communities, its effects were neither consistent nor significant. All told, biofilm formation and betadine resistance are complex phenomena, influenced by community composition, growth rate and betadine concentration.


Subject(s)
Betaproteobacteria/growth & development , Biofilms/growth & development , Disinfectants/pharmacology , Ecosystem , Povidone-Iodine/pharmacology , Pseudomonas putida/growth & development , Bacteriological Techniques , Betaproteobacteria/isolation & purification , Colony Count, Microbial , Culture Media , Fresh Water/microbiology , Pseudomonas putida/isolation & purification
17.
Laryngoscope ; 111(10): 1783-90, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11801946

ABSTRACT

OBJECTIVES: To estimate the treatment effect of temperature-controlled radiofrequency (TCRF) reduction of turbinate hypertrophy in patients with sleep-disordered breathing (SDB) treated with nasal continuous positive airway pressure (CPAP), and to assess the impact of study design on this estimate. STUDY DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical pilot trial. METHODS: Twenty-two CPAP-treated patients with SDB with turbinate hypertrophy were randomly assigned to either TCRF turbinate treatment (mean energy 415 +/- 37 J/turbinate; n = 17) or placebo control (n = 5). Changes in nasal obstruction were evaluated between pretreatment and 4 weeks post-treatment. The primary outcome assessed changes in the blinded examiners' findings of nasal obstruction on a visual analogue scale (VAS). Secondary outcomes included blinded patients' and unblinded examiner assessments of nasal obstruction (VAS), nightly CPAP use, adherence, and tolerance, along with sleepiness and general health status scales. The treatment group findings were subtracted from the changes in the placebo group to yield treatment effect. RESULTS: The primary outcome treatment effect by VAS was -0.9 cm (95% confidence interval [CI], -2.4, 0.7), and beyond the placebo effect of -1.5 cm (95% CI: -3.4, 0.3). The secondary treatment effect of the unblinded examiner was -3.0 cm (95% CI, -4.9, -1.1). A beneficial treatment effect was also seen on every secondary outcome except general health status, but only self-reported CPAP adherence (P = .03) was statistically significant. CONCLUSIONS: TCRF turbinate treatment appears to benefit nasal obstruction and CPAP treatment for SDB. Placebo control and double blinding are critical for establishing the true treatment effect. A future definitive trial is feasible to establish statistical significance of these findings.


Subject(s)
Hyperthermia, Induced , Nasal Obstruction/therapy , Positive-Pressure Respiration , Sleep Apnea, Obstructive/therapy , Turbinates/pathology , Adult , Double-Blind Method , Feasibility Studies , Female , Humans , Hypertrophy , Male , Middle Aged , Outcome Assessment, Health Care , Pilot Projects
18.
Plant J ; 24(5): 625-36, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11123801

ABSTRACT

ATFIM1 is a widely expressed gene in Arabidopsis thaliana that encodes a putative actin filament-crosslinking protein, AtFim1, belonging to the fimbrin/plastin class of actin-binding proteins. In this report we have used bacterially expressed AtFim1 and actin isolated from Zea mays pollen to demonstrate that AtFim1 functions as an actin filament-crosslinking protein. AtFim1 binds pollen actin filaments (F-actin) in a calcium-independent manner, with an average dissociation constant (Kd) of 0.55+/-0.21 microM and with a stoichiometry at saturation of 1:4 (mol AtFim1 : mol actin monomer). AtFim1 also crosslinks pollen F-actin by a calcium-independent mechanism, in contrast to crosslinking of plant actin by human T-plastin, a known calcium-sensitive actin-crosslinking protein. When micro-injected at high concentration into living Tradescantia virginiana stamen hair cells, AtFim1 caused cessation of both cytoplasmic streaming and transvacuolar strand dynamics within 2-4 min. Using the 'nuclear displacement assay' as a measure of the integrity of the actin cytoskeleton in living stamen hair cells, we demonstrated that AtFim1 protects actin filaments in these cells from Z. mays profilin (ZmPRO5)-induced depolymerization, in a dose-dependent manner. The apparent ability of AtFim1 to protect actin filaments in vivo from profilin-mediated depolymerization was confirmed by in vitro sedimentation assays. Our results indicate that AtFim1 is a calcium-independent, actin filament-crosslinking protein that interacts with the actin cytoskeleton in living plant cells.


Subject(s)
Arabidopsis Proteins , Arabidopsis/metabolism , Microfilament Proteins/metabolism , Plant Proteins/metabolism , Actins/metabolism , Arabidopsis/genetics , Binding, Competitive , Calcium/pharmacology , Cross-Linking Reagents , DNA, Recombinant , Plant Cells , Plant Proteins/genetics , Plant Proteins/pharmacology , Plants/drug effects , Plants/metabolism , Pollen/chemistry , Protein Binding/drug effects
19.
J Nutr ; 130(8): 2016-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10917918

ABSTRACT

We compared the effects of supplementing either animal plasma or extruded soy protein in the diet based on the efficiency of dietary protein utilization for lean tissue growth in early-weaned pigs. Twenty-four 14-d-old pigs (4 kg body weight) were pair-fed (per kg body weight) either a control diet containing extruded soy protein (C; n = 12) or a diet with 10% animal plasma (P; n = 12) for 24 d. During the 24 days, protein intake was not different, yet mean daily body weight gains (+23%) and food conversion efficiencies (expressed as the ratio of body weight gain to protein intake) (+19%) were greater (P < 0.05) in the P group than in the C group. Lean body mass measured after 24 d, using both dual-energy X-ray absorptiometry and total body potassium analysis, was significantly (P < 0.05) greater (approximately 16%) in P than in C pigs. The circulating urea concentrations were 40% lower (P < 0.05) in P than in C pigs. Our results demonstrate that supplementing early-weaned pig diets with animal plasma rather than extruded soy protein increased the efficiency of dietary protein use for lean tissue growth and that this response is mediated in part by decreased amino acid catabolism.


Subject(s)
Dietary Proteins/blood , Soybean Proteins/metabolism , Swine/growth & development , Animal Feed , Animals , Body Composition , Female , Male , Weight Gain
20.
Acta Cytol ; 44(3): 301-4, 2000.
Article in English | MEDLINE | ID: mdl-10833982

ABSTRACT

OBJECTIVE: To investigate cyclin E expression as a possible marker for early cervical neoplasia using ThinPrep gynecologic specimens from premenopausal women. STUDY DESIGN: Archived ThinPrep liquid-based cervical/endocervical specimens (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) diagnosed as human papillomavirus infection (HPV) (20), atypical squamous cells of undetermined significance (ASCUS) (48) and within normal limits (WNL)/benign cellular changes (BCC) (21) were resampled in duplicate, fixed in 95% ethanol, subjected to immunocytochemical staining with the cyclin E antibody (clone 13A3, Novocastra Laboratories Ltd., Newcastle upon Tyne, U.K.) and HPV antibody (clone K1H8, Dako Corporation, Carpinteria, California, U.S.A.) and the expression scored by two pathologists and correlated with the cytologic diagnosis. A case was scored as positive if it contained > 10 abnormal squamous cells with nuclear immunocytochemical staining. RESULTS: The cylin E antibody assay was positive in 20 (100%) cases cytologically diagnosed as HPV. These cases were also anti-HPV antibody positive. Four cases (19%) cytologically diagnosed as WNL/BCC were cyclin E positive. Of these, two were anti-HPV antibody positive. Thirty-four (73%) cases cytologically diagnosed as ASCUS were positive for the cyclin E assay and for anti-HPV antibody staining. CONCLUSION: Cyclin E expression correlates strongly with morphologic features of HPV in ThinPrep specimens and may serve as a surrogate marker for HPV infection and early cervical preneoplastic lesions.


Subject(s)
Cyclin E/biosynthesis , Neoplasms, Squamous Cell/immunology , Papillomaviridae/immunology , Papillomavirus Infections/immunology , Tumor Virus Infections/immunology , Uterine Cervical Dysplasia/immunology , Uterine Cervical Neoplasms/immunology , Adult , Antibodies, Viral/analysis , Biomarkers , Cyclin E/immunology , Feasibility Studies , Female , Humans , Neoplasms, Squamous Cell/pathology , Papillomavirus Infections/pathology , Time Factors , Tumor Virus Infections/pathology , Uterine Cervical Neoplasms/pathology , Vaginal Smears , Uterine Cervical Dysplasia/pathology
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