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Biomedical subjects

J Lang

Publications and source records attributed to J Lang.

At least 37 records · Page 2Linked to original sources
PubMed2004

Safety and efficacy of chimeric yellow Fever-dengue virus tetravalent vaccine formulations in nonhuman primates.

To construct chimeric YF/DEN viruses (ChimeriVax-DEN), the premembrane (prM) and envelope (E) genes of yellow fever (YF) 17D virus were replaced with those of each wild-type (WT) dengue (DEN) virus representing serotypes 1 to 4. ChimeriVax-DEN1-4 vaccine viruses were prepared by electroporation of Vero cells with RNA transcripts prepared from viral cDNA (F. Guirakhoo, J. Arroyo, K. V. Pugachev, C. Miller, Z.-X. Zhang, R. Weltzin, K. Georgakopoulos, J. Catalan, S. Ocran, K. Soike, M. Ratteree, and T. P. Monath, J. Virol. 75:7290-7304, 2001; F. Guirakhoo, K. Pugachev, J. Arroyo, C. Miller, Z.-X. Zhang, R. Weltzin, K. Georgakopoulos, J. Catalan, S. Ocran, K. Draper, and T. P. Monath, Virology 298:146-159, 2002). Progeny viruses were subjected to three rounds of plaque purifications to produce the Pre-Master Seed viruses at passage 7 (P7). Three further passages were carried out using U.S. current Good Manufacturing Practices (cGMP) to produce the Vaccine Lot (P10) viruses. Preclinical studies demonstrated that the vaccine candidates are replication competent and genetically stable and do not become more neurovirulent upon 20 passages in Vero cells. The safety of a tetravalent vaccine was determined and compared to that of YF-VAX in a formal monkey neurovirulence test. Brain lesions produced by the tetravalent ChimeriVax-DEN vaccine were significantly less severe than those observed with YF-VAX. The immunogenicity and protective efficacy of four different tetravalent formulations were evaluated in cynomolgus monkeys following a single-dose subcutaneous vaccination followed by a virulent virus challenge 6 months later. All monkeys developed low levels of viremia postimmunization, and all the monkeys that had received equal concentrations of either a high-dose (5,5,5,5) or a low-dose (3,3,3,3) formulation seroconverted against all four DEN virus serotypes. Twenty-two (92%) of 24 monkeys were protected as determined by lack of viremia post-challenge. This report is the first to demonstrate the safety of a recombinant DEN virus tetravalent vaccine in a formal neurovirulence test, as well as its protective efficacy in a monkey challenge model.

Animals↗
PubMed2003

Correlation of urinary nitric oxide concentrations with the development of hip dysplasia in Labrador retrievers.

Urinary nitric oxide was determined in terms of the ratio of the concentrations of total urinary nitrite and nitrate:creatinine in 40 juvenile labrador retrievers, and radiographic signs of hip dysplasia and distraction indices were investigated in the same dogs in later life. The ratio was correlated significantly with the Norberg angle and with subchondral sclerosis in both hips, and with the grade of dysplasia in each hip and the dogs' overall grade of hip dysplasia. No correlations were observed between the ratio and the distraction indices or other radiographic criteria for hip dysplasia.

Animals↗
PubMed2003

Search for time-reversal violation in the beta decay of polarized 8Li nuclei.

The transverse polarization of electrons emitted in the beta decay of polarized 8Li nuclei has been measured. For the time-reversal violating triple correlation parameter we find R=(0.9+/-2.2)x10(-3). This result is in agreement with the standard model and yields improved constraints on exotic tensor contributions to the weak interaction. Combined with other experimental results and using a model for the coupling constants, a new limit for the mass of a possible scalar leptoquark, m(LQ)>560 GeV/c(2) (90% C.L.), is obtained.

Journal Article↗
PubMed2003

Influence of food composition on splanchnic blood flow during digestion in unsedated normal dogs: a Doppler study.

The effect of dietary components in gastrointestinal blood flow was investigated non-invasively in dogs. Doppler ultrasound (US) waveform analysis of the celiac artery (CA) and the cranial mesenteric artery (CMA) of eight healthy dogs was performed both in the fasting state and at 20, 40, 60 and 90 min after feeding maintenance, high protein, high carbohydrate and high fat diets. Resistive index (RI), pulsatility index (PI) and the percentage differences between measurements were calculated. In fasted dogs, the CA showed significantly (p<0.05) lower resistance than the CMA. With all diets, post-prandial RI and PI values decreased significantly in both vessels (CA: RI=-12-13%; PI=-25-29%; CMA: RI=-13-15%; PI=-27-29% [p<0.05]), and in all cases significantly earlier in the CA than in the CMA (p<0.05). With all diets except high fat the maximum decrease in RI and PI was reached in the CA at 40 min and in the CMA at 60 min. High fat diets were unique in that the maximum decrease in RI and PI in the CMA occurred earlier (at 20 min) and values were slower to return to normal (p<0.05). We conclude that Doppler US can be used in dogs to quantify significant differences in the response of splanchnic blood flow to different dietary components.

Animals↗
PubMed2003

[Influence of cardiopulmonary bypass (CPB) on the natriuretic peptides ANP and BNP. A comparison between long and short duration of CPB and off pump surgery].

OBJECTIVE: Plasma atrial and brain natriuretic peptide (ANP and BNP) are cardiac hormones secreted mainly due to cardiac overload. The study was designed to assess plasma concentrations of ANP and BNP in patients undergoing coronary bypass grafting (CABG) with long and short duration of cardiopulmonary bypass (CPB) and without CPB (off-pump surgery). METHODS: We studied 45 patients scheduled for elective CABG. Patients were allocated in three groups: group A received CPB with a duration less than 60 minutes, group B more than 60 minutes and patients without CPB were allocated in group C. ANP and BNP were measured after induction of anaesthesia (T0), at the end of surgery (T1), 4 hrs. (T2), 24 hrs. (T3) and 120 hrs. postoperatively (T4). RESULTS: In all groups, ANP-levels increased from T0 to T4 (group A: from 3.7 +/- 2.1 to 8.9 +/- 8.0; group B: from 3.3 +/- 1.7 to 8.0 +/- 6.0; group C: from 3.0 +/- 1.6 to 5.3 +/- 2.3 pg/ml), but there were no significant differences between the groups. BNP-concentrations increased also from T0 to T4 (group A: from 34 +/- 18 to 234 +/- 164; group B: from 33 +/- 26 to 219 +/- 182; group C: from 33 +/- 24 to 77 +/- 55 pg/ml). Furthermore we measured significant higher BNP-levels in group B compared to group C at T3 and T4. No significant differences between group A and B were found. CONCLUSIONS: CPB influenced BNP, but not ANP plasma concentrations. An influence of the duration of CPB on ANP and BNP was not seen.

English Abstract↗
PubMed2003

[Is levosimendan an inoprotective drug in patients with acute coronary syndrome undergoing surgical revascularization?].

Levosimendan, is a new calcium sensitiser with 2 major effects. First, levosimendan acts as a positive inotropic agent by binding calcium dependently to cardiac troponin C. Second, levosimendan activates adenosine triphosphate-regulated potassium (K (ATP)) channels. Thus it has vasodilatory properties and cardioprotective effects at a dose enhancing myocardial contractility. These unique properties of levosimendan might be of great advantage in patients with myocardial ischemia simultaneously requiring inotropic support. The concept of perioperative inoprotection is presented in 6 patients with acute ischemia undergoing emergent cardiac surgery.

ATP-Binding Cassette Transporters↗
PubMed2003

Comparison of three distraction methods and conventional radiography for early diagnosis of canine hip dysplasia.

Two radiographic distraction techniques (one employing a wooden lath and, the other, a PennHip distractor), an ultrasonographic distraction method and conventional radiographic Fédération Cynologique Internationale (FCI) hip score were evaluated in eight-month-old Labrador retrievers to determine the most reliable method for predicting radiographic FCI hip score at the age of one year. With reference to the FCI hip score, sensitivity and specificity of the PennHip method were 100 per cent and 54 per cent; sensitivity and specificity of the lath technique were 85 per cent and 71 per cent; whereas they were 62 per cent and 67 per cent for the ultrasonographic method. For all distraction methods, the positive predictive value (PPV) was moderate and the negative predictive value (NPV) was high. Sensitivity, specificity, PPV and NPV were 100 per cent for the FCI hip score. It is concluded that, at the age of eight months, FCI hip score is the most reliable method for predicting FCI hip score at the age of one year in the colony of dogs investigated. Both the PennHip and lath method were also clinically reliable techniques in predicting true negatives. The ultrasonographic distraction method was moderately reliable.

Animals↗
PubMed2003

Fibrocartilaginous embolism in 75 dogs: clinical findings and factors influencing the recovery rate.

The records of 75 dogs with fibrocartilaginous embolism of the spinal cord were evaluated retrospectively. The diagnosis was confirmed histopathologically in 21 dogs (group A) and remained suspected in 54 patients (group B). The two groups were compared. Particular emphasis was placed on the description of physiotherapy procedures, recovery rates and prognostic criteria. Results demonstrated that fibrocartilaginous embolism affected mainly middle-aged, large- or giant-breed dogs. Clinical signs were peracute in onset, non-progressive and often asymmetric. Cerebrospinal fluid analysis was normal in the majority of dogs. Intramedullary swelling was the only abnormality detected on myelograms of these patients. A positive correlation was found between a poor prognosis and the involvement of intumescences, symmetrical clinical signs and decreased deep pain sensation. However, physio/hydrotherapy instituted immediately after the diagnostic work-up seemed to have a major influence on the recovery rate.

Animals↗
PubMed2003

Unusual radiographic appearance of lung carcinoma in a cat.

A 15-year-old, female Siamese cat presented with multiple cavitary lung lesions on thoracic radiographs. This was confirmed histologically to be a well-differentiated bronchioloalveolar carcinoma. To the authors' knowledge, this radiographic pattern has not previously been reported in association with bronchioloalveolar carcinoma in cats.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2002

Spin-dependent electron-proton scattering in the Delta-excitation region.

We report on measurements of the cross section and provide first data on spin correlation parameters A(TT') and A(TL') in inclusive scattering of longitudinally polarized electrons from nuclear-polarized hydrogen. Polarized electrons were injected into an electron storage ring operated at a beam energy of 720 MeV. Polarized hydrogen was produced by an atomic beam source and injected into an open-ended cylindrical cell, located in the electron storage ring. The four-momentum transfer squared ranged from Q2 = 0.2 GeV(2)/c(2) at the elastic scattering peak to Q2 = 0.11 GeV(2)/c(2) at the Delta(1232) resonance. The data provide a stringent test of pion electroproduction models.

Journal Article↗
PubMed2002

Spin-momentum correlations in quasielastic electron scattering from deuterium.

The spin-momentum correlation parameter A(V)(ed) was measured for the 2H-->(e-->,e'p)n reaction for missing momenta up to 350 MeV/c at Q2 = 0.21 (GeV/c)(2) for quasielastic scattering of polarized electrons from vector-polarized deuterium. The data give detailed information about the deuteron spin structure and are in good agreement with the results of microscopic calculations based on realistic nucleon-nucleon potentials and including various spin-dependent reaction mechanism effects. The experiment reveals in a most direct manner the effects of the D state in the deuteron ground-state wave function and shows the importance of isobar configurations for this reaction.

Journal Article↗
PubMed2002

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency.

AIMS/HYPOTHESIS: Several studies have investigated the lipoprotein phenotype in heterozygous carriers of a defective lipoprotein lipase allele. We studied whether heterozygosity for lipoprotein lipase deficiency also affects glucose metabolism beyond its effect on plasma lipids. METHODS: To address this question 85 heterozygous carriers of either a missense mutation (Gly188Glu) or a splice site mutation (C-->A in position -3 at the acceptor splice site of intron 6) in the LPL gene which both result in a catalytically inactive product were compared with 108 unaffected subjects from the same families. RESULTS: Carriers for one of these mutations had higher fasting insulin levels but only a trend towards increased fasting blood glucose concentrations could be detected. HOMA index values were significantly higher in carriers than in non-carriers. Furthermore, in carriers, a significantly higher BMI and a trend towards higher systolic and diastolic blood pressure were observed. Carriers also had significantly higher fasting triglycerides, lower HDL cholesterol, and lipoprotein lipase particles of smaller size, confirming previous reports. Among carriers, subjects with one rare allele of the SstI polymorphism in the apo CIII gene had significantly higher plasma triglyceride levels than those with two common SstI alleles. This difference could not be observed in non-carriers of a mutant lipoprotein-lipase allele. The mean intima media thickness of the carotid arteries was slightly, but not significantly higher in carriers when compared with non-carriers. CONCLUSION/INTERPRETATION: This study shows that carrier status of one defective lipoprotein-lipase allele is associated with impaired insulin sensitivity, an atherogenic lipoprotein profile and other characteristics of the metabolic syndrome, which are risk factors for atherosclerotic vascular disease. A higher incidence of atherosclerotic vascular disease, however, could not be firmly established in carriers of this study population.

Adipose Tissue↗
PubMed2002

Delayed hydrocephalus after resection of supratentorial malignant gliomas.

BACKGROUND: To report our experience with 12 patients who developed delayed hydrocephalus after resection of supratentorial malignant gliomas. METHOD: The charts of all affected patients were analysed retrospectively for clinical presentation, time interval between initial operation and occurrence of hydrocephalus, neuroradiological findings, constituents of cerebrospinal fluid (CSF), surgical treatment, and outcome. FINDINGS: After initial good recovery following tumour resection all patients deteriorated secondarily due to development of hydrocephalus which was not encountered in the first postoperative CT-scans. Incidence is 3.4% overall and is 8.3% if exclusively calculated for frontal gliomas but increases to 15.2% if specified for patients with ventricular entry during tumour resection. Development of hydrocephalus is suggested to be due to proteinic precipitation since analysis of CSF revealed marked elevation of proteins in all patients. Whereas shunting of mere hydrocephalus yields satisfactory results outcome in cases of multiloculated hydrocephalus necessitating placement of multiple catheters is questionable. INTERPRETATION: Development of hydrocephalus after resection of malignant gliomas is not rare. It should be considered in patients with delayed deterioration after initial improvement. Outcome in relation to hydrocephalus is favourable in cases of mere communicating hydrocephalus, occurrence of multiloculated hydrocephalus, however, heralds a poor prognosis.

Adult↗
PubMed2002

A T-cell functional phenotype common among autoimmune-prone rodent strains.

The genetic basis and familial clustering of autoimmunity suggest that common phenotypic traits predispose individuals to disease. We found a hyporesponsive T-cell phenotype that was shared by all autoimmune-prone mouse and rat strains tested, including MRL, nonobese diabetic (NOD), NZB, NZW, NZB/W F1, SJL and SWR mice, as well as DA and BB rats, but was not evident in nonautoimmune-prone rodents. This T-cell intrinsic, age-independent hyporesponsiveness is measured as an increased activation threshold for upregulation of activation markers upon T-cell receptor (TCR) cross-linking both in vitro and in vivo. Inefficient deletion of CD4 and CD8 single-positive, heat stable antigen (HSA)hi medullary thymocytes was also observed in hyporesponsive donors. We interpret these data to suggest that increased TCR-mediated signalling thresholds in autoimmune-prone individuals may contribute to the escape of autoreactive thymocytes from negative selection.

Animals↗
PubMed2002

[Epidemiology of snake envenomations in northern Cameroon].

Epidemiological surveys concerning snakebites were carried out in the savannah area of North Cameroon according to two methods. A retrospective survey carried out in 5 hospitals or dispensaries covering a 3- to 8-year period according to locality was followed by a prospective survey in 4 of these health centres lasting 1 or 2 years according to location. These studies involved respectively 1,710 and 359 patients. The annual incidence varied between 50 and 250 envenomations per 100,000 inhabitants according to year and locality. The average annual incidence was close to 200 cases. Echis ocellatus corresponded to 85% of the identified snakebites. Lethality ranged from 0 to 23.9% of the envenomations. It significantly decreased during the prospective study due to the systematic use of antivenoms administered through the venous route (IPSER Africa then FAV Afrique). During the prospective study, we observed that 25% of snakebite victims did not present any symptoms: 71% presented an oedema, 63% a coagulopathy and less than 5% a necrosis. The population at risk involved people aged 15 to 44 years, especially males. Most of the bites had occurred during agricultural activity. In the cotton zone, more than 40% of the envenomations took place during the 3 months of the field preparation and cotton sowing. Elsewhere, the snakebites were spread out over time with a clear increase during the rain season.

Adolescent↗
PubMed2001

Expression of P450(arom) in Malaclemys terrapin and Chelydra serpentina: a tale of two sites.

The formation of estrogens from androgens in all vertebrates is catalyzed by the "aromatase" complex, which consists of a membrane bound P(450) enzyme, P(450) aromatase (which binds the androgen substrate and inserts an oxygen into the molecule), and a flavoprotein (NADPH-cytochrome P450 reductase). Among vertebrates, the two major sites of aromatase expression are the brain and gonads. Given the importance of estrogen in reptile sex determination, we set out to examine whether P450arom was involved in the initiation and/or stabilization of sex determination in turtles. We examined the expression of aromatase activity in the brain and gonads of two turtle species exhibiting temperature dependent sex determination (TSD), the diamondback terrapin (Malaclemys terrapin), and the common snapping turtle (Chelydra serpentina). Estradiol when applied at stage 14 of the terrapin induces expression of aromatase in the gonad of embryos incubated at male temperatures (26.5 degrees C). The level of expression is similar to that of a normal embryonic ovary. When applied at stage 22, estradiol does not induce aromatase expression in the terrapin. The xenoestrogen, nonylphenol, sex reverses terrapin embryos at 26.5 degrees C. Letrazole, a nonsteroidal aromatase inhibitor, suppresses aromatase activity in the brain at either incubation temperature. Ovotestes are produced by letrazole administration in the terrapin when incubated at 30.5 degrees C. In the snapping turtle at stage 23, gonadal and brain aromatase activity in embryos incubated at female temperatures (30.5 degrees C) is nearly half that exhibited in terrapin embryos at the same temperature. Moreover, letrazole administration suppresses aromatase expression to nearly basal levels. At male incubation temperatures (26.5 degrees ), brain aromatase expression is nearly three times higher than at female temperatures, while gonadal expression levels are nearly one third lower. However, the gonadal expression levels at male temperatures in the snapping turtle are nearly 25 times higher than that found in the terrapin. Estradiol administration elevates this level nearly three fold. These data suggest that is not merely the expression of aromatase that is important for ovarian development, but that the level of expression may be more important.

Animals↗
PubMed2001

Immune defence against HIV-1 infection in HIV-1-exposed seronegative persons.

Rare individuals who are repeatedly exposed to HIV-1 through unprotected sexual contact fail to acquire HIV-1 infection. These persons represent a unique study population to evaluate mechanisms by which HIV-1 replication is either prevented or controlled. We followed longitudinally a group of healthy HIV-1 seronegative persons each reporting repeated high-risk sexual activities with their HIV-1-infected partner at enrollment. The volunteers were primarily (90%) male homosexuals, maintaining high risk activities with their known infected partner (45%) or multiple other partners (61%). We evaluated the quantity and specificity of HIV-1-specific T cells in 31 exposed seronegatives (ES) using a IFN-gamma ELISPOT assay to enumerate T cells recognizing epitopes within HIV-1 Env, Gag, Pol and Nef. PBMC from only three of the 31 volunteers demonstrated ex vivo HIV-1-specific IFN-gamma secretion, in contrast to nearly 30% exhibiting cytolytic responses in previous studies. These findings suggest that if T cell responses in ES are induced by HIV-1 exposure, the frequency is at low levels in most of them, and below the level of detection using the ELISPOT assay. Alternative approaches to improve the sensitivity of detection may include use of dendritic cells as antigen-presenting cells in the ex vivo assay and more careful definition of the risk behavior and extent of HIV-1 exposure in conjunction with the evaluation of T cell responses.

CD8-Positive T-Lymphocytes↗