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At least 361 records · Page 20Linked to original sources
PubMed1984

Selective reversal of H-2 linked genetic unresponsiveness to lysozymes. I. Non-H-2 gene(s) closely linked to the Ir-2 locus on chromosome 2 permit(s) an antilysozyme response in H-2b mice.

Genes outside of the mouse major histocompatibility complex (H-2) were found to be capable of specifically reversing the previously described nonresponsiveness to hen egg-white lysozyme (HEL) owing to H-2b immune response (Ir) genes. C3H.SW, BALB.B, and C57L, all of the H-2b haplotype, showed responsiveness to HEL, but not to human lysozyme (HUL). Mapping of the reversing gene(s) was attempted by testing H-2b recombinant inbred (RI) strains of mice carrying C3H, BALB, and C57L non-H-2 genes. Analysis of the strain distribution pattern of responsiveness with both CXB and BXH RI strains was consistent with the location of the responsible site within the H-3 region on chromosome 2. The anti-HEL proliferative responsiveness in two H-3 congenic strains of mice, B10.C(28NX)SN and B10.C-H-3cH-3a, that have BALB/c genes within the H-3 region confirmed the mapping, as well as localized the reversing gene(s) near the Ir-2 gene. The data are discussed with regard to the site of expression of the reversing gene(s) and its mechanism of action.

Animals↗
PubMed1986

Blockade of alpha 2-adrenoceptors permits the operation of otherwise silent opioid kappa-receptors at the sympathetic axons of rabbit jejunal arteries.

We sought for presynaptic, release-inhibiting opioid receptors at the postganglionic sympathetic axons innervating the jejunal arteries of rabbits. Evoked excitatory junction potentials (e.j.p.s; trains of 15 pulses at 1 Hz) as well as evoked overflow of tritium after preincubation with [3H]-noradrenaline (trains of 120 pulses at 1 Hz) were used to estimate transmitter release. In otherwise untreated tissues ethylketocyclazocine reduced neither the e.j.p. amplitudes nor the evoked overflow of tritium; [Met5]-enkephalin depressed the evoked overflow of tritium. Ethylketocyclazocine reduced e.j.p. amplitudes, however, in tissues exposed to either yohimbine, tolazoline or phentolamine, but not in tissues exposed to prazosin. Ethylketocyclazocine also depressed the evoked overflow of tritium when yohimbine was present. The inhibition produced by ethylketocyclazocine in the presence of yohimbine was antagonized by (-)-3-furylmethyl)-alpha-noretazocine (MR 2266) but not by N,N-diallyl-Tyr-alpha-aminoisobutyric acid-alpha-aminoisobutyric acid-Phe-Leu-OH (ICI 174864). It is concluded that the sympathetic neurones of rabbit jejunal arteries possess presynaptic kappa-receptors in addition to the previously identified delta-receptors. The kappa-receptors become operative only when presynaptic alpha 2-adrenoceptors have been blocked.

Adrenergic alpha-Antagonists↗
PubMed1988

An MuLV transmission vector system designed to permit recovery in E. coli of proviral and cellular flanking sequences.

We have introduced a bacterial suppressor gene (supF) into the long terminal repeat of a molecular clone of the murine leukemia virus (MuLV) SL3-3. A panel of replication competent virus was derived that replicates to high titers in NIH3T3 cells in culture. The tRNA gene is stably carried in the provirus. The supF and viral sequences are present in equimolar amounts in the RNA genome of the expressed recombinant virus. The proviral sequences containing supF can be recovered by cloning into a lambda vector carrying amber mutations. The DNA sequences in the recovered lambda recombinants show a high degree of stability. The presented system should facilitate the study of the interaction between proviral and cellular sequences flanking the integration site.

Bacteriophage lambda↗
PubMed1982

A displacement servosystem for muscle research permitting 50 micrometers length changes within 40 microseconds.

In order to determine the tension response of a stimulated intact muscle fibre to a very fast length change a servo system has been developed capable of imposing a displacement of 50 micrometers i.e. about 1% of the fibre length, within 40 microseconds. The system is designed so as to limit the displacement overshoot to less then 1%. This paper presents the performance of the system: both unloaded and loaded with a muscle fibre.

Animals↗
PubMed1987

Cloned mouse lymphocytes permit analysis of somatic mutations that occur in vivo.

As part of our mouse model of somatic mutation, we have begun to characterize spontaneously occurring hypoxanthine phosphoribosyltransferase (HPRT) -deficient mouse lymphocytes. Lymphocytes were cloned by in vitro exposure of spleen cells from male C57B1/6 mice to the mitogen concanavalin A, conditioned medium containing lymphocyte growth factors, and thioguanine (TG), in a limiting dilution assay. The 17 TG-resistant clones recovered were all highly deficient in HPRT activity and were found by analysis of surface antigens to be representative of the major subclasses of T lymphocytes. Southern analysis of lymphocyte genomic DNA detected alterations of the hprt gene in 12/17 of the HPRT-deficient lymphocyte clones. Of these 12, 2/17 were lacking the entire hprt locus, 7/17 lacked part of the locus, and 3/17 had other, unidentified alterations.

Animals↗
PubMed1986

Immunohistochemical localization of cell surface receptors using a novel method permitting simple, rapid and reliable LM/EM correlation.

A method is presented which allows correlative serial section analysis by light and electron microscopy of cell surface antigens in monolayer cultures. Sites of antigenicity are shown by deposition of diaminobenzidine after pre-embedding, immunoperoxidase immunocytochemistry. Osmication is replaced by the use of gold chloride which specifically enhances the electron density of diaminobenzidine. In addition gold chloride bound to diaminobenzidine survives embedding and provides the basis for a post-embedding photochemical amplification method. Immunostained cells are embedded in LR White by a rapid technique which preserves their structure and leaves them available for subsequent post-embedding immunocytochemistry. The method is illustrated by the demonstration of epidermal growth factor (EGF) receptors on the EGF receptor-rich human carcinoma cell line A431 using a well characterized monoclonal antibody raised against EGF receptor.

Antigens, Surface↗
PubMed1990

A dual-pipette technique that permits rapid internal dialysis and membrane potential measurement in voltage-clamped cardiomyocytes.

Guinea pig ventricular myocytes were voltage-clamped and dialysed using two glass patch pipettes (P1, P2) with tip openings of around 2 microns. A substantial improvement in the efficacy of dialysis from P2 was achieved by the application of positive pressure (15-30 cm H2O) to P2, and similar negative pressure to P1. Evidence of enhanced dialysis was obtained by measuring the effect on Ca channel current of P2 dialysates containing Ca, cAMP, GTP [gamma-S], trypsin, or the catalytic subunit of protein kinase A. Times to maximum response were 3-5 times shorter than those calculated or observed by others using a single-pipette method. The speeding-up was verified in comparative experiments with 100 microM GTP [gamma-S] dialysates; maximum stimulation of ICa occurred after 1.3-1.8 min with the dual-pipette method, versus 8.2 min with a single pipette. Other advantages of the dual-pipette method include the option of following a control dialysis from P1 with a test dialysis from P2, and the measurement of actual membrane potential. The disadvantages are that the rate of success is lower than with single-pipette experiments, and that smaller cardiomyocytes are difficult subjects.

Animals↗
PubMed2006

[Saving life and permitting death. Decision conflicts in intensive medicine].

Intensive care has achieved major breakthroughs in handling gravely ill patients. However, this has, at least in part, been overshadowed by problems relating to ethical values as well as general psychological conflicts among patients and hospital staff. When dealing with such problems, distinct criteria are required which address the patient's dignity and will to survive. A four-step scheme is suggested, ranging from maximum therapy, via maintenance therapy without adjustments to increased demand and therapy reduction, to cessation of therapy. In the case of therapy reduction, balanced support is maintained ensuring that dehydration is avoided, the respiratory tract is kept clear, pain killers are used to good effect, personal attention is provided, and care is provided to a high standard. A questionnaire tailored to the practical need of how to arrive at an ethically weighted and accepted decision is presented. When searching for a solution involving ethic issues, it is particularly important to involve all individuals concerned in a dialogue until a consensus is reached.

Aged↗
PubMed1997

Multi-joint limbs permit a flexible response to unpredictable events.

The human arm is kinematically redundant, which may allow flexibility in the execution of reaching movements. We have compared reaching movements with and without kinematic redundancy to unpredictable double-step targets. Subjects sat in front of a digitising tablet and were able to view an arc of four targets reflected in the mirror as virtual images in the plane of the tablet. They were instructed to move, from a central starting point, in as straight a line as possible to a target. In one-third of trials, the target light switched to one of its neighbours during the movement. Subjects made 60 movements using shoulder, elbow and wrist and then another 60 movements in which only shoulder and elbow movement were allowed. By restraining the wrist, the limb was made non-redundant. The path length was calculated for each movement. In single-step trials, there was no significant difference between path lengths performed with and without wrist restraint. As expected there was a significant increase in path length during double-step trials. Moreover this increase was significantly greater when the wrist was restrained. The variability across both single- and double-step movements was significantly less while the wrist was restrained. Importantly the performance time of the movements did not alter significantly for single-step, double-step or restrained movements. These results suggest that the nervous system exploits the intrinsic redundancy of the limb when controlling voluntary movements and is therefore more effective at reprogramming movements to double-step targets.

Adult↗
PubMed1997

Foramen of Monro mass: MRI appearances permit diagnosis of cavernous haemangioma.

Cavernous haemangiomas are most commonly found in the subcortical white matter, the pons and the external capsule. We present a case of a cavernous haemangioma that appeared as an intraventricular mass at the foramen of Monro. Despite the unusual location the diagnosis was established by MRI because of the typical appearance. The differential diagnosis included primary and secondary neoplasms at the foramen of Monro.

Cerebral Ventricle Neoplasms↗
PubMed2002

Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDG-PET.

The purpose of this study was to determine the actual standardized uptake value (SUV) by using the lesion size from computer tomography (CT) scan to correct for resolution and partial volume effects in positron emission tomography (PET) imaging. This retrospective study included 47 patients with lung lesions seen on CT scan whose diagnoses were confirmed by biopsy or by follow up CT scan when the PET result was considered negative for malignancy. Each lesion's FDG uptake was quantified by the SUV using two methods: by measuring the maximum voxel SUV (maxSUV) and by using the lesion's size on CT to calculate the actual SUV (corSUV). Among small lesions (2.0 cm or smaller on CT scan), ten were benign and 17 were malignant. The average maxSUV was 1.43+/-0.77 and 3.02+/-1.74 for benign and malignant lesions respectively. When using an SUV of 2.0 as the cutoff to differentiate benignity and malignancy, the sensitivity, specificity, and accuracy were 65%, 70%, and 67% respectively. When an SUV of 2.5 was used for cutoff, the sensitivity, specificity, and accuracy were 47%, 80%, and 59% respectively. The average corSUV was 1.65+/-1.09 and 5.28+/-2.71 for benign and malignant lesions respectively. Whether an SUV of either 2.0 or 2.5 was used for cutoff, the sensitivity, specificity, and accuracy remained 94%, 70%, and 85% respectively. The only malignant lesion that was falsely considered benign with both methods was a bronchioalveolar carcinoma which did not reveal any elevated uptake of fluorine-18 fluorodeoxyglucose (FDG). Of the large lesions (more than 2.0 cm and less than 6.0 cm), one was benign and 19 were malignant and the corSUV technique did not significantly change the accuracy. It is concluded that measuring the SUV by using the CT size to correct for resolution and partial volume effects offers potential value in differentiating malignant from benign lesions in this population. This approach appears to improve the accuracy of FDG-PET for optimal characterization of small lung nodules.

Adult↗
PubMed2006

FDG small animal PET permits early detection of malignant cells in a xenograft murine model.

PURPOSE: The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2-3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time. METHODS: We studied 23 nude mice, in which 7 x 10(6) rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases. RESULTS: The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals) while the negative predictive value was 46% (6/13 animals). In the whole group of animals, mean TBR increased scan by scan. There was a statistically significant difference in TBR between 2 and 20 days after inoculation. Necrosis was present at the second scan in two animals, at the third scan in six animals and at the fourth scan in 11 animals. CONCLUSION: The high positive predictive value of FDG PET 2 days after inoculation means that an animal with a first positive scan has a very high likelihood of developing a mass and can be treated at an early stage with an experimental drug. Animals negative at this point in time will never develop a mass or will eventually do so at a late phase. As 2 of the 16 (12.5%) positive animals had necrosis at the second scan, indicating a vascular mismatch, it may be argued that animals should be treated 2 days after inoculation to guarantee homogeneous vascularisation (thereby ensuring a good drug supply within the tumour) in all subjects.

Animals↗