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Biomedical subjects

A Jackson

Publications and source records attributed to A Jackson.

At least 235 records · Page 13Linked to original sources

Vitrification of human oocytes following minimal exposure to cryoprotectants; initial studies on fertilization and embryonic development.

Investigations were made into the low temperature preservation of pre-ovulatory human oocytes by vitrification using a method of brief exposure of the oocytes to the vitrification solution at room temperature. Assessments of morphological survival, fertilization and embryonic development were recorded. All those oocytes exposed to the vitrification solution alone were morphologically normal and 86% of them were fertilized after incubation with spermatozoa. All the fertilized ova (86%) underwent cell division. Following cooling to -196 degrees C, morphological survival (65%) and fertilization (45%) rates remained high. However, in all vitrified oocytes, embryonic cell division and further development were inhibited. From our study it appears that fresh human oocytes can be vitrified using only brief exposure to cryoprotective agents and survive to undergo fertilization. However, progress remains to be made in achieving further embryonic development.

Cell Survival↗

Interobserver variation in the chest radiograph component of the lung injury score.

The lung injury score is a semi-quantitative system used in the definition and grading of the acute respiratory distress syndrome. It is composed of two, three or four equally weighted components. One component is derived from the chest radiograph, which may contribute up to 50% of the total score. A score of 1 is awarded for each quadrant on the chest radiograph which contains alveolar consolidation. We examined the interobserver variation between two anaesthetists, two radiologists and two critical care physicians who scored blindly 100 chest radiographs from patients with adult respiratory distress syndrome. There was very good agreement between the two radiologists in the total scores (kappa 0.97) and in individual scores in each of the 4 quadrants (kappa 0.97-1.0). The agreement between anaesthetists and radiologists was only fair for the total score (kappa 0.37-0.42), but moderate to good for individual quadrant scores (kappa 0.43-0.73). The agreement between the two anaesthetists was moderate for individual quadrant scores (kappa 0.44-0.60), but only fair for total score (kappa 0.34). There was poor agreement between the two critical care physicians for total score (kappa 0.05) and for individual quadrant scores (kappa 0.04-0.20). Agreement between the physicians and other observers was poor to fair for the total score (kappa 0.12-0.32) and poor to moderate for the individual quadrant scores (kappa 0.15-0.63). Both anaesthetists and physician 2 underestimated the overall chest scores (median scores 2, 3 and 1 respectively) in comparison to the radiologists (median scores 3.5). Physician 1 significantly overscored (median score 4). The chest radiograph component of the lung injury score can be consistently assessed by radiologists, but significant variations may be introduced when assessed by other clinicians. This has significant implications for the use of the lung injury score in studies of adult respiratory distress syndrome and other studies which incorporate radiographic appearances in the definition.

Acute Disease↗

Sciatica.

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Female↗

Neurosarcoidosis masquerading as glioma of the optic chiasm in a child.

We present a case of sarcoidosis in a 14-year-old girl who presented with a short history of visual disturbance. Computed tomography and magnetic resonance imaging (MRI) demonstrated enlargement of the optic chiasm and prechiasmic optic nerves. Post-contrast MRI showed marginal enhancement of the affected areas of the optic pathways. A diagnosis of optic nerve glioma and arachnoid gliomatosis was made; surgical confirmation was not sought due to the risk to vision associated with biopsy. A rapid clinical deterioration led to repeat MRI which demonstrated extensive enhancing soft tissue throughout the basal cisterns with extension into the brain. Biopsy confirmed a diagnosis of sarcoidosis.

Adolescent↗

CT and MR appearance of otolaryngologic packing materials.

PURPOSE: To examine the CT and MR appearances of four packing materials commonly used in otolaryngologic surgery. METHODS: The CT and MR appearances of bismuth and iodoform paraffin paste, aqueous betadine gauze, calcium sodium alginate, and triadocortyl cream were examined. CT attenuation values were measured using phantoms containing packing materials. MR characteristics were examined by packing the external auditory meati of volunteers. Two illustrative case reports also are presented. RESULTS: Bismuth and iodoform paraffin paste has a high CT attenuation (> 3000 Hounsfield units) resulting in severe image degradation attributable to streak artifact. Aqueous betadine gauze was of high attenuation (258 Hounsfield units; SD, 16.5) but did not cause image degradation. The attenuation values of calcium sodium alginate and triadocortyl creme coincided with those of muscle and fat, respectively. On MR, calcium sodium alginate and bismuth and iodoform paraffin paste had imaging characteristics similar to muscle and aqueous betadine gauze had appearances similar to bone marrow. Triadocortyl cream had a high signal equal to that of fat on T1-weighted images but a lower signal similar to bone marrow on T2-weighted images. CONCLUSIONS: The presence of bismuth and iodoform paraffin paste can give rise to clinically important image degradation on CT. More seriously, residual packing material may be misinterpreted as infection or tissue necrosis.

Adolescent↗

Transient global amnesia and cortical blindness after vertebral angiography: further evidence for the role of arterial spasm.

We describe a series of six patients who experienced severe retrograde amnesia (five cases) or cortical blindness (one case) during selective vertebral angiography. All angiograms were obtained with the same nonionic contrast medium. Analysis of the contrast batch demonstrated no abnormalities, but investigation of the angiographic suite revealed a faulty contrast warming cabinet resulting in injection of contrast material above body temperature. The warming cabinet was withdrawn, and the complication has not recurred. We believe that these symptoms reflect ischemia caused by vertebral arterial spasm.

Adult↗

Prevention, early detection and team management of skin cancer in primary care: contribution to The health of the nation objectives.

The incidence of all skin cancers is increasing. If The health of the nation targets are to be addressed, incidence figures need to be more accurate. Solar damage is the major causal factor in all skin cancers. Certain individual risk factors also play an important part, especially in the development of malignant melanoma. Prevention and early detection are crucial in reducing morbidity and mortality from skin cancer. This paper considers the role of primary care skin screening clinics and cutaneous surgery facilities in the early detection and management of skin cancer. It also illustrates the value of a team approach in primary care in the prevention and early detection of skin cancer and in the more accurate recording of incidence rates.

Adult↗

Long-term modulation of inward currents in O2 chemoreceptors by chronic hypoxia and cyclic AMP in vitro.

In mammals, ventilatory acclimatization to hypoxia is associated with an enhanced chemosensitivity of the O2-sensing carotid body, resulting in an increased respiratory drive. To test whether this sensitization involves long-term modulation of ion channel function in endogenous O2 chemoreceptors, i.e., type 1 cells, we exposed cultures of dissociated rat carotid body to chronic hypoxia (6% O2) for 1-2 weeks, before monitoring the electrophysiological properties of type 1 cells using whole-cell, perforated patch recording. Chronic hypoxia augmented voltage-dependent inward Na+ and Ca2+ currents in type 1 cells, without significant changes in voltage dependence of activation or steady-state inactivation. However, after normalizing for the concomitant increase in cell size, indicated by the whole-cell capacitance, only the Na+ current density was significantly enhanced. The Na+ current was sensitive to tetrodotoxin (TTX; 0.5-1 microM) or choline substitution, whereas most of the Ca2+ current was sensitive to the L-type calcium channel blocker, nifedipine (10 microM). Several of these effects of hypoxia were mimicked qualitatively by growing normoxic cultures in the presence of agents that elevate intracellular cyclic AMP, including dibutyryl cAMP (db-cAMP; 200 microM-1 mM) and forskolin (10 microM); treatment with similar concentrations of dibutyryl cyclic GMP was ineffective. Na+ channel induction by db-cAMP was abolished by the protein synthesis inhibitor, cycloheximide (90-180 microM). In current-clamp mode, these altered chemoreceptors had typical resting potentials of approximately -55 mV, and following depolarization often fired multiple spikes that appeared to consist of both short-duration Na+ and long-duration Ca2+ components. We propose that chronic hypoxia, acting in part through cAMP-dependent pathways, increases electrical excitability and calcium mobilization in type 1 cells, and these adaptations may help enhance chemosensitivity during hypoxic acclimatization.

Action Potentials↗

Non-specific inhibition of dopamine receptor agonist-induced behaviour by the tachykinin NK1 receptor antagonist CP-99,994 in guinea-pigs.

Evidence that tachykinin NK1 receptors selectively modulate activity in the mesolimbic dopamine pathway suggests an antipsychotic potential for tachykinin NK1 receptor antagonists. We investigated the ability of the antagonist CP-99,994 (and the less active enantiomer CP-100,263) to block dopamine receptor agonist-induced behaviour in guinea-pigs. The active dose range for inhibition of [Sar9,Met(O2)11]substance P-induced behaviour by CP-99,994 was 1-3 mg/kg s.c. The same doses of CP-100,263 were without effect. In contrast, both CP-99,994 (20 or 30 mg/kg) and CP-100,263 (10-30 mg/kg) antagonised behavioural stimulation induced by the dopamine receptor agonists amphetamine (1 mg/kg i.p.) or (+)-PHNO ((+)-4-propyl-9-hydroxy-naphthoxazine hydrochloride; 0.1 mg/kg s.c.). Lower doses of CP-99,994 or CP-100,263 were not active. These findings do not support the proposal that tachykinin NK1 receptors in the terminal projection area of the mesolimbic system can modify dopamine-mediated behaviour.

Amphetamine↗

Cloning and characterization of human phosphatase inhibitor-2 (IPP-2) sequences.

cDNA clones similar to rabbit muscle phosphatase inhibitor-2 (IPP-2) were isolated from human libraries. On Northern blots two transcripts of approximately 2kbp and approximately 4kbp were detected in all tissues tested. Analysis of cDNA sequences showed that the longer transcripts were similar to the shorter clones but contained extended 3' ends. The human nucleotide sequence was highly homologous (94% identity) to the rabbit IPP-2 sequence and encoded a peptide of 205 amino acids. IPP-2 sequences were highly conserved throughout vertebrates. Southern hybridization results were consistent with the existence of a family of related IPP-2 sequences in the human genome. Most of these are likely to be pseudogenes, since all of the cDNA clones examined could have originated from a single gene. By in situ hybridization IPP-2 sequences were mapped to several different human chromosomes. We sequenced one gene located in the major histocompatibility complex (MHC) on Chromosome (Chr) 6 that contained the entire coding region of IPP-2.

Amino Acid Sequence↗

Hormone sensitivity of germ cells in stage XIV and in stage I of the rat spermatogenic cycle.

Previous data have been inconclusive with respect to whether the meiotic degenerations that occur in stage XIV of the spermatogenic cycle are increased after hypophysectomy. Meiotic cell degenerations in Stage XIV and early Stage I of the spermatogenic cycle were enumerated to determine if the advanced generation of meiotic cells were influenced by hormonal deprivation subsequent to hypophysectomy and, if so, could cellular degenerations be prevented by supplementation with either testosterone or recombinant FSH during the period of hypophysectomy. The animals utilized were either pituitary-intact rats or rats hypophysectomized for 3 or 10 days. Hormone supplementation began at day 3 post-hypophysectomy and continued until day 10 at which time all animals were sacrificed. The numbers of degenerating meiotic figures (metaphase to telophase of the first and second meiotic division) as expressed per Sertoli cell nucleus or nucleolus were not increased significantly 10 days after hypophysectomy as compared with animals hypophysectomized for 3 days or with pituitary-intact controls. Exogenously administered testosterone and FSH had no effect on the numbers of degenerating meiotic germ cells in hypophysectomized animals. These data indicate that stage XIV metaphase to telophase spermatocytes are not hormone sensitive. However, it was determined that there were new cell types degenerating at Stage XIV and I of the spermatogenic cycle. These were interphase secondary spermatocytes and step 1 spermatids and were seen in stages XIV and I, respectively. These cell degenerations were found in low numbers in Stage XIV and I in either FSH-treated or testosterone-treated rats, suggesting their hormone sensitivity. Thus it is possible that Stages XIV and I are hormone sensitive stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An investigation into the discriminative stimulus and reinforcing properties of the CCKB-receptor antagonist, L-365,260 in rats.

The discriminative stimulus properties of the selective CCKB-receptor antagonist, L-365,260 were evaluated in rats trained to discriminate diazepam (2 mg/kg) or morphine (5 mg/kg) from vehicle, using a two-lever food reinforced technique. In the diazepam drug discrimination, the benzodiazepine-receptor agonist FG8205 (0.063-2 mg/kg) produced dose-related drug associated responding, whereas L-365,260 (0.125-4 mg/kg) treated animals showed vehicle appropriate behaviour. In rats trained to discriminate morphine from saline, L-365,260 (0.063-4 mg/kg) produced saline lever responding. When a dose of 1 mg/kg L-365,260 was administered in combination with morphine, the dose response curve for drug lever responding was not significantly affected. This was in contrast to the effect produced by the opiate antagonist naloxone (0.3 mg/kg) which shifted the dose-response curve to the right. Another group of rats underwent training to discriminate a dose of 6 mg/kg L-365,260 from vehicle. None of the animals learned the discrimination within 50 daily training sessions. In addition, unlike morphine (3 mg/kg), or changing the training dose of cocaine, intravenous administration of L-365,260 (0.3-10 mg/kg) did not modify lever pressing or the number of injections received by rats trained to self administer cocaine (0.25 mg/injection). L-365,260 (0.1-3 mg/kg) produced a dose-related inhibition of pentagastrin-stimulated gastric acid secretion in vivo. When administered dissolved in a mixture of ethanol/propylene glycol/saline, the ID50 was 0.83 mg/kg, and when suspended in an ethanol/carboxymethylcellulose vehicle, it was 0.7 mg/kg. It was concluded: 1) that L-365,260 does not produce discriminative stimuli similar to either diazepam or morphine; 2) that the potentiation of morphine-induced behaviour by L-365,260 does not extend to the discriminative stimulus properties of morphine; 3) that L-365,260 itself does not produce readily discriminable interoceptive stimuli in rats; and 4) that L-365,260 does not substitute for the reinforcing drug cocaine.

Animals↗

The potential and limitations of the inverse radiotherapy technique.

The objective of the work presented in this paper is to explore the scope of the applicability of the inverse radiotherapy technique for designing optimized intensity distributions to achieve a desired dose distribution. A specified desired uniform dose to the target volume is inverted, subject to constraints on the surrounding normal tissue dose, to produce optimum intensity distributions in a set of beams arranged around the target volume. We employed the inverse technique and software developed by Bortfeld and evaluated results both qualitatively and quantitatively using dose distribution displays, dose-volume histograms and biological indices including tumor control probability and normal tissue complication probabilities. So far we have applied this methodology to prostate and lung treatment plans. For prostate the inverse technique produces satisfactory approximations of the desired dose distributions. However, for lung its performance is considerably inferior. Our investigations point to a number of factors for this difference, the primary ones being differences in the tolerance doses of neighboring normal tissues, magnitudes of volume effect, tissue architectures, and the achievability of the specified desired dose distributions. We conclude that, for certain clinical situations, it is not sufficient to specify the objectives of optimization purely in terms of the desired pattern of the dose. The objectives must also include dose-volume effects and biological indices. Furthermore, the mathematics of optimization must be able to incorporate these factors into the process. We find that the inverse technique is not suitable for situations where dose-volume considerations and biological indices are important and that other methods of optimization of intensity distributions should be explored.

Adenocarcinoma↗

Cloning of the region between HLA-DMB and LMP2 in the human major histocompatibility complex.

The human MHC is one of the most extensively mapped regions of the human genome. Almost all of the class II region of the MHC has already been cloned in cosmids but a gap remained between the DMB and LMP2 genes. Previously, screening of several complete cosmid libraries had failed to bridge this gap, which may contain novel antigen processing or presentation genes. We constructed cosmid libraries from two different sources in order to clone the region: (a) a library with fourfold coverage made from flow-sorted human chromosome 6 DNA and (b) a library derived from a yeast artificial chromosome clone spanning the region. Using this saturation approach, cosmid clones were eventually isolated over the region of interest. A single bacteriophage P1 clone was also obtained spanning the region. The YAC, cosmid, and P1 physical maps were consistent and the distance between the DMB and LMP2 genes was measured as 70 kb. It is not clear why DMB to LMP2 is infrequently represented in cosmid libraries, but the clones that we have obtained will now enable us to search for new coding sequences.

Bacteriophage P1↗