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Biomedical subjects

T Jensen

Publications and source records attributed to T Jensen.

At least 19 recordsLinked to original sources

Effects of marked hyperthermia with and without dehydration on VO(2) kinetics during intense exercise.

This study determined whether marked hyperthermia alone or in combination with dehydration reduces the initial rate of rise in O(2) consumption (VO(2) on-kinetics) and the maximal rate of O(2) uptake (VO(2 max)) during intense cycling exercise. Six endurance-trained male cyclists completed four maximal cycle ergometer exercise tests (402 +/- 4 W) when euhydrated or dehydrated (4% body wt) with normal (starting esophageal temperature, 37.5 +/- 0.2 degrees C; mean skin temperature, approximately 31 degrees C) or elevated (+1 and +6 degrees C, respectively) thermal strain. In the euhydrated and normal condition, subjects reached VO(2 max) (4.7 +/- 0.2 l/min) in 228 +/- 34 s, with a mean response time of 42 +/- 2 s, and fatigued after 353 +/- 39 s. Hyperthermia alone or in combination with dehydration reduced mean response time (17-23%), VO(2 max) (16%), and performance time (51-53%) (all P < 0.01) but did not alter the absolute response time (i.e., the time to reach 63% response in the control trial, 3.2 +/- 0.1 l/min, 42 s). Reduction in VO(2 max) was accompanied by proportional decline in O(2) pulse and significantly elevated maximal heart rate (195 vs. 190 beats/min for hyperthermia vs. normal). Preventing hyperthermia in dehydrated subjects restored VO(2 max) and performance time by 65 and 50%, respectively. These results demonstrate that impaired high-intensity exercise performance with marked skin and internal body hyperthermia alone or in combination with dehydration is not associated with a diminished rate of rise in VO(2) but decreased VO(2 max).

Adult↗

The influence of mannose binding lectin polymorphisms on disease outcome in early polyarthritis. TIRA Group.

OBJECTIVE: To determine whether variant alleles of the mannose binding lectin (MBL) gene causing low serum concentrations of MBL are associated with increased susceptibility to rheumatoid arthritis (RA) and erosive outcome in an inception cohort of patients with early polyarthritis. METHODS: MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 68 Danish patients with incident early polyarthritis observed for one year. The associations between MBL and specific HLA-DRB1 genotypes and disease outcomes were analyzed. RESULTS: Among the patients with early polyarthritis 7.4% (5/68) and 41.2% (28/68) were homozygous and heterozygous for MBL variant alleles, compared with 2.8% (7/250) and 34.4% (86/250) of healthy controls (p = 0.09), while the corresponding figures in the patients with RA were 10% (5/50) and 42% (21/50) (p = 0.03), and in the patients with erosive RA 18.8% (3/16) and 35.3% (6/16), respectively (p = 0.004). Patients with early polyarthritis homozygous for MBL variant alleles had an increased risk of having erosive RA at inclusion by a factor of 4.7 (p = 0.02) and after one year by a factor of 3.6 (p = 0.04). MBL deficiency was associated with increased levels of C-reactive protein (CRP) and IgM rheumatoid factor (RF) at inclusion (p < 0.05). HLA-DRB1 alleles were not found to be associated with disease outcome. CONCLUSION: MBL variant alleles appear to be weak susceptibility markers for RA, and patients with early polyarthritis and homozygous for MBL structural variant alleles have a higher risk of developing early erosive RA. These findings, together with the positive association between MBL variant alleles and the increased serum levels of IgM RF and CRP, point at the MBL gene as a relevant locus in the pathophysiology of RA.

Adult↗

Discrepancy between fibrinogen concentrations determined by clotting rate and clottability assays during the acute-phase reaction.

Assays based on clotting rate are commonly used as a routine method for determining the fibrinogen concentration in plasma. However, little is known about the influence of the acute-phase reaction on this assay. In order to disclose discrepancies between the fibrinogen concentrations obtained by a clotting rate assay (as described by Clauss) and a reference assay for total clottable protein (according to Jacobsson), we compared the fibrinogen concentrations determined by these two methods in plasma-samples collected preoperatively and on postoperative days 1, 3, and 5 in patients undergoing major elective surgery. The HMW (High Molecular Weight)-, LMW- and LMW'-fibrinogen fractions of the patient samples were also determined. In preoperative samples, good agreement between the two assays was found. In samples collected on postoperative days 1 and 3, the fibrinogen concentrations measured with the clotting rate assay were significantly higher than the concentrations measured with the total clottable protein assay (p=0.015 on both days). SDS-gel electrophoresis showed an increase in the median HMW-fraction from 69.7% (range 64.3-70.4) in preoperative samples to 85.8% (80.7-87.6) in samples drawn on day 3. The difference between fibrinogen concentrations obtained by the two methods was significantly correlated to the HMW-fraction of the samples. We conclude that during an acute-phase reaction, fibrinogen concentrations obtained by a clotting rate assay (as described by Clauss) are significantly higher than those measured by a total clottable protein assay (according to Jacobsson). The difference between the two methods correlates well with the relative HMW-fraction, indicating that the increase in HMW-fibrinogen is the main contributor to the observed discrepancy.

Acute-Phase Reaction↗

Synthesis of tumor associated sialyl-T-glycopeptides and their immunogenicity.

Sialyl-T-glycopeptides were synthesized by solid-phase techniques, using a PEGA resin as the solid support. An appropriately protected building block containing alpha-Neu5Ac-(2 --> 3)-beta-Gal-(1 --> 3)-alpha-GalN3-(1-->) attached to Fmoc-Thr/Ser-OPfp was employed in a solid phase glycopeptide assembly of a 10-mer glycopeptide, using a general Fmoc/OPfp-ester strategy. Reduction of the azido group of the GalN3 residue was effected on solid-phase, using DTT and DBU. After acidolytic cleavage from the resin, the methyl ester of the sialic acid residue and acetyl groups were removed with 30% NaOMe/MeOH in MeOH and water pH 14, at -30 degrees C for 2 h. At this low temperature, the highly basic conditions did not result in any detectable beta-elimination. However, one O-acetyl group, located at the 2-position of the Gal was resistant to hydrolysis. To remove this remaining acetyl group, reaction with hydrazine hydrate in CHCl3 and MeOH at room temperature for 2.5 h was successful. The two target sequences of sialyl-T-glycopeptides were obtained in good yield. In contrast to the the analogs carrying the T-antigen, the Sial-T-glycopeptides were nonimmunogenic, supporting the idea that the sialylation is a method of circumventing the recognition by the immune system.

Animals↗

Effects of sustained-release methoprene and a combined formulation of liquid methoprene and Bacillus thuringiensis israelensis on insects in salt marshes.

Aquatic insects are an important component of the food web in salt marshes, therefore it is necessary to test whether pesticides used to control mosquitoes in salt marshes are safe for nontarget insects. We tested the nontarget effects of a combined formulation (duplex) of Bacillus thuringiensis israelensis (B.t.i.) and liquid methoprene (an insect development regulator) or sustained-release methoprene pellets (Altosid(R) pellets) by applying these materials to replicated salt marsh ponds at maximum label rates. Untreated ponds served as controls. We measured effects of the pesticides by rearing immature mosquitoes (Aedes dorsalis) and water boatmen (Trichocorixa reticulata) in predator-exclusion cages and by monitoring uncaged populations of invertebrates using replicated sweep-net samples. Both pesticides killed caged mosquitoes, and the activity of the Altosid(R) pellets continued through 99 days. There were no detectable effects of either pesticide on the survival or maturation of T. reticulata, or on abundances of uncaged invertebrates. The long-term activity of the pellets could help minimize mosquito abatement activity in salt marshes where there are breeding birds or endangered species. However, other studies suggest that this advantage needs to be balanced against the risks that sustained-release formulations could lead to development of resistance in mosquitoes or that initially undetected nontarget effects could build over time.

Aedes↗

Field efficacy of commercial antimosquito products in Illinois.

We evaluated the efficacy of commercial antimosquito products in field trials in Illinois in June 1998 by comparing mosquito landing rates. Products tested were a sonic mosquito repeller, an insect killing grid using ultraviolet light and 1-octen-3-ol as lures, mosquito smoke coils containing a pyrethroid, citronella candles, the mosquito plant Pelargonium citrosum, and a N,N-diethyl-3-methylbenzamide (deet)-impregnated wrist band. The sonic mosquito repeller, insect killing grid, and mosquito smoke coils were evaluated in 16 trials over 5 days; the citronella candles and mosquito plants in II trials over 4 days; and the wrist bands in 4 trials on 1 day. In all 3 studies, we compared landing rates with the antimosquito products to both positive (topical application of a deet formulation) and negative (no treatment) controls. The deet topical repellent had a consistently lower landing rate than all the nontopically applied products tested. However, the mosquito coils and the deet-impregnated wrist bands did significantly reduce mosquito landing rates relative to untreated controls.

Animals↗

Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus.

To define the role of IFN-gamma in the control of acute infection with a noncytopathogenic virus, mice with targeted defects of the genes encoding IFN-gamma, perforin, or both were infected i.v. with two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus-specific TCR are adoptively transferred before virus challenge, indicating that the disease is the result of an unfortunate balance between virus replication in internal organs, e.g., liver and spleen, and the host response; resetting this balance by increasing host responsiveness will again lead to a rapidly controlled infection and limited tissue damage. Thus, the presence or absence of IFN-gamma determines whether CTLs will clear infection with this noncytopathogenic virus or induce severe immunopathology.

Adoptive Transfer↗

A novel vascular sealing device for closure of percutaneous arterial access sites.

The purpose of this study was to investigate the safety and efficacy of a novel vascular sealing device that incorporates a unique low-profile balloon-positioning catheter and a procoagulant delivered after diagnostic cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA) procedures. Current management of the vascular access site after percutaneous interventions is associated with patient discomfort and complications. Based on previously reported successful results in canine models, we proceeded with this first human feasibility and safety study. Immediately after an invasive procedure, the sealing device was successfully deployed at the femoral arterial access site in 24 of 24 procedures (diagnostic 19, PTCA 5). All patients were followed up at 1 month with clinical assessment, ankle-brachial index measurement, and Doppler ultrasound. Successful hemostasis was achieved in all patients. The activated clotting time before sealing device deployment was 125.5 +/- 22.2 and 267.8 +/- 60.0 seconds for diagnostic and PTCA patients, respectively. The time to hemostasis was 2.5 +/- 0.9 minutes for diagnostic and 6.0 +/- 2.2 minutes for PTCA patients. No major complications were observed. Coagulation markers (fibrinogen, D-dimer, thrombin-antithrombin-3 complex, and prothrombin fragment 1 and 2) measured before and after sealing device deployment did not reveal excessive intravascular thrombin generation or other coagulopathy. This novel vascular sealing device successfully achieves safe and effective vascular access site hemostasis immediately after cardiac catheterization and PTCA. These promising first human results will need to be confirmed by a multicenter randomized trial.

Aged↗

Shared structural motifs in TCR of glycopeptide-recognizing T cell hybridomas.

The TCR structure of T cell hybridomas recognizing a tumor glycan-defined epitope has been studied using reverse transcriptase-PCR and gene sequencing. The hybridomas had been raised against a glycopeptide, T72(Tn), consisting of the mouse hemoglobin-derived decapeptide Hb(67 - 76), O-glycoslated in position 72 with alpha-D-GalNAc. The glycan-specific hybridomas varied widely in their use of Valpha genes although Valpha4 was predominant, being present in one third of them. The Vbeta gene usage was more restricted and dominated by Vbeta1 and Vbeta15. There was no correlation between Valpha and Vbeta usage and antigen fine specificity of the hybridomas. The overall amino acid composition of the complementarity-determining region (CDR) 3 of the hybridomas was dominated by small polar residues such as Gly, Asn, Ser, Glu and Ala, amino acids reported in the literature to be frequent in glycan-recognizing proteins. Furthermore, the CDR3 of most hybridomas also contained an aromatic residue with preference for Tyr. A few of the hybridomas raised against the T72(Tn) glycopeptide were peptide specific, i. e. they responded to the unglycosylated peptide only. The amino acid usage of their CDR3 regions was not radically different from that of the glycopeptide specific hybridomas. They also preferentially used Valpha4. However, Vbeta4 and Vbeta8 were the dominating beta chains.

Amino Acid Sequence↗

The Duett closure device: concept and experimental results.

Purpose of this paper is to investigate the hemostatic capabilities of a novel vascular sealing device consisting of a balloon catheter and procoagulant. Vascular sheaths were placed percutaneously in the femoral arteries of dogs. The sealing device was evaluated using the balloon catheter alone in 6 femoral arteries and with the addition of a procoagulant in 21 femoral arteries. The balloon catheter alone was successfully deployed in 6 of 6 femoral arteries achieving immediate hemostasis. In a second study in which the procoagulant was delivered following balloon placement, the sealing device was successfully deployed and hemostasis was achieved in 20 of 21 attempts (95%) despite removal of the balloon catheter. In a subset of fully anticoagulated animals, hemostasis was achieved in the sealing device-treated arteries at 6.5 +/- 3.4 minutes but in none of the controls (p < 0.001). This novel vascular sealing device successfully achieves rapid hemostasis in normal and anticoagulated dogs following percutaneous vascular procedures.

Animals↗

Glucosaminyl N-deacetylase mRNA expression in diabetic rats.

Glucosaminyl N-deacetylase is a key enzyme in the synthesis of heparan sulphate. N-deacetylase activity is inhibited in experimental diabetes. The mechanism by which diabetes influences N-deacetylase activity is unknown. Using reverse transcription PCR we quantified hepatic N-deacetylase mRNA in normal and streptozotocin diabetic rats. A negative correlation was found between final blood glucose and N-deacetylase mRNA expression in diabetic rats, r = -0.44, p < 0.05. N-deacetylase mRNA expression was also correlated to N-deacetylase activity (r = 0.48, p < 0.05). N-deacetylase:cyclophilin mRNA ratio was not significantly affected by diabetes, 0.26 (0.2-0.35) vs 0.31 (0.16-0.5), p =0.48, in 10 weeks and 0.21 (0.15-0.37) vs 0.27 (0.19-0.32), p = 0.65, in 8 months rats, diabetic and normal rats respectively, median (interquartile range). The negative correlation between blood glucose and N-deacetylase mRNA in diabetic rats suggests however that altered gene expression may contribute to the altered N-deacetylase activity seen in experimental diabetes.

Amidohydrolases↗

CD4(+) T cell-mediated protection against a lethal outcome of systemic infection with vesicular stomatitis virus requires CD40 ligand expression, but not IFN-gamma or IL-4.

To investigate the mechanism(s) whereby T cells protect against a lethal outcome of systemic infection with vesicular stomatitis virus, mice with targeted defects in genes central to T cell function were tested for resistance to i.v. infection with this virus. Our results show that mice lacking the capacity to secrete both IFN-gamma and perforin completely resisted disease. Similar results were obtained using IL-4 knockout mice, indicating that neither cell-mediated nor T(h)2-dependent effector systems were required. In contrast, mice deficient in expression of CD40 ligand were more susceptible than wild-type mice, and residual resistance in these mice was almost completely abrogated by depletion of CD8(+) T cells. In keeping with this, mice lacking both MHC class I and class II expression succumbed to the infection, whereas most class II-deficient mice normally survive. Adoptive transfer experiments using B cell- and T cell-deficient recipients revealed that no protection could be obtained in the absence of B cells, whereas treatment with virus-specific immune (IgG) serum controlled viral spreading to the central nervous system (CNS), but did not necessarily accomplish virus elimination. Taken together, these results underscore that B cells are essential in preventing early infection of the CNS, but T cells are required for long-term survival. CD4(+) T cells are most efficient in this context and the key function is to provide cognate help to B cells. However, if CD4(+) cell function is compromised, CD8(+) T cells become critical and may suffice for survival.

Animals↗

Bcl-X(LONG) protein expression and phosphorylation in granulosa cells.

Expression of Bcl-x protein was evaluated in hen ovarian follicles, relative to stage of development, and in cultured granulosa cells after treatment with various apoptosis-suppressing or -inducing agents. Using Western blot analysis, Bcl-X(LONG) was most frequently observed migrating as a doublet with a molecular mass of approximately 28 kDa; the apparent higher molecular mass band of this doublet was determined to represent a phosphorylated form. Consistent with previous findings reported for bcl-x messenger RNA, only the Bcl-X(LONG) (apoptosis-suppressing) form of protein was detected in the hen granulosa cells, and highest levels of Bcl-X(LONG) protein (sum of the protein doublet) expression were found in granulosa from preovulatory follicles together with tissues with immune function (e.g. spleen and bone marrow). Evidence for Bcl-X(SHORT) expression was found only in the theca and several nonovarian tissues. Immunocytochemical analysis of preovulatory vs. prehierarchal follicles confirmed the comparatively greater expression of cytoplasmic Bcl-X(LONG), particularly in preovulatory follicle granulosa. Levels of Bcl-X(LONG) were significantly increased after 20 h of culture in the presence of 8-bromo-cAMP (8-br-cAMP; compared with culture in control medium) in granulosa cells from both stages of follicle development. Such results are correlated with the protein's proposed function to protect against cell death in apoptosis-resistant, preovulatory follicle granulosa cells and are consistent with the ability of this cAMP agonist to increase bcl-X(LONG) messenger RNA levels in cultured cells. Furthermore, several factors that have previously been demonstrated to suppress apoptosis in granulosa cells, in vitro, (e.g. 8-br-cAMP, LH, FSH) were found to rapidly (within 15 min) increase levels of phosphorylated Bcl-X(LONG), compared with control cells, whereas an inhibitor of protein kinase A (H-89) blocked such phosphorylation. By comparison, transforming growth factor alpha, a factor previously found to attenuate apoptosis and apoptosis-inducing agents (e.g. paclitaxel, C8-ceramide, daunorubicin, UV irradiation) failed to phosphorylate Bcl-X(LONG). From these studies, it is concluded that both the phosphorylation of Bcl-X(LONG) (a short-term response) and increased levels of Bcl-X(LONG) (a comparatively slower response) in hen granulosa cells are promoted by gonadotropins via the adenylyl cyclase/cAMP signaling pathway. Moreover, elevated levels of chicken Bcl-X(LONG) protein expression and its phosphorylated state are correlated with resistance to apoptotic cell death in granulosa cells in vitro and ultimately a resistance to ovarian follicle atresia in vivo.

Animals↗

Arterial switch with internal pulmonary artery banding. A new palliation for TGA and VSD in complex cases.

In most cases, one stage repair by arterial switch operation (ASO) is the optimal treatment for neonates with transposition of the great arteries (TGA). Nevertheless, a ventricular septal defect (VSD) associated with TGA remains a major risk factor for early death and reoperation after complete repair in neonates with complex anatomy. A new palliative approach for such specific cases is proposed. An internal pulmonary artery banding (IPAB), as that already used to palliate other cardiac malformations, is performed in association with ASO instead of VSD closure. At the end of ASO, a circular polytetrafluorethylene (PTFE) patch with a 4-mm central hole is oversewn into the neo-pulmonary trunk. We adopted this method in a 17-day-old boy with TGA, VSD, hypoplastic tricuspid valve and diminutive right ventricle. After the operation the child thrived and was doing well without medication. Satisfactory growth of the right ventricle and tricuspid valve was observed by echocardiography during the following months. The patient successfully underwent VSD closure and IPAB removal 2 years after the first procedure. ASO with IPAB could be appropriate in all forms of TGA and VSD in which VSD closure appears too challenging in the neonatal period and in patients with uncertain suitability for biventricular repair. We preferred to use IPAB instead of classic PAB in order to reduce the risk of pulmonary valve damage, pulmonary artery distortion, and above all pulmonary artery dilatation and related coronary compression. In the presented case the strategy as well as IPAB worked according to our expectations.

Blood Vessel Prosthesis Implantation↗

Culiseta impatiens (Walker) in Illinois, a new state record.

We report the 1st collection of Culiseta impatiens (Walker) from Illinois. Larvae of Culiseta subsequently identified as Cs. impatiens were collected from roadside ditches near Savoy, Champaign County, in east central Illinois in June 1997. This extends the known distribution of this species further south and east in the midwestern United States.

Animals↗

Effects of ultra-low volume pyrethrin, malathion, and permethrin on nontarget invertebrates, sentinel mosquitoes, and mosquitofish in seasonally impounded wetlands.

Wildlife managers are concerned that insecticides used to control mosquitoes could suppress invertebrates on which wildlife feed. We assessed whether ultra-low volume (ULV) applications of pyrethrin, permethrin, and malathion for control of adult mosquitoes reduced macroinvertebrate abundance and biomass or killed mosquitofish in seasonal wetlands in California. Pyrethrin was applied over 3 seasonal wetlands on Sutter National Wildlife Refuge (NWR), and malathion or permethrin were each applied over 2 seasonal wetlands on the Colusa NWR. Three control wetlands were used per site. We measured aquatic macroinvertebrate abundance and biomass before and after insecticide application and compared the survival of mosquito larvae held in sentinel cages. At Colusa, we also used mosquitofish as sentinels, caged adult mosquitoes over the wetlands to test for pesticide efficacy and drift, and sampled night-flying insects using ultraviolet light traps. Results showed no detectable reductions in the abundance or biomass of aquatic macroinvertebrates in treated wetlands. Larval mosquitoes showed high survival in all areas. All adult mosquitoes died when caged over wetlands treated with malathion or permethrin, but all survived in controls. All mosquitofish survived. Flying insect abundance decreased after insecticide application in both treated and control wetlands but rebounded in 48 h. Results indicated that ULV applications of these insecticides to control adult mosquitoes are unlikely to have substantial effects on the aquatic insects or fish in seasonal wetlands.

Animals↗