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Biomedical subjects

K Young

Publications and source records attributed to K Young.

At least 19 recordsLinked to original sources

Cardiotoxicity after accidental herb-induced aconite poisoning.

Aconitine and its related alkaloids are known cardiotoxins with no therapeutic role in modern western medicine. The rootstocks of Aconitum plants, which contain aconite alkaloids, have been common components of Chinese herbal recipes. We have documented life-threatening intoxication in 17 Chinese subjects after accidental herb-induced aconite poisoning. All patients developed symptoms of aconite toxicity within 2 h of herb ingestion. Most developed tachyarrhythmias, including ventricular tachycardia and fibrillation from which 2 patients died. Toxicological evaluation revealed that aconites from the Aconitum rootstocks were the only plausible casual factor for intoxication. These cases point to the need for strict surveillance of herbal substances with low safety margins.

Accidents

Sequence-specific DNA-binding proteins within the Mbcr on the Ph1 chromosome.

The Philadelphia1 (Ph1) chromosome results from a reciprocal translocation between chromosome 9 and chromosome 22, which fuses a portion of the ABL oncogene to the BCR gene, forming the BCR/ABL fusion gene. This produces a fusion protein with a greatly increased protein tyrosine kinase activity in comparison to that of the normal ABL protein. The BCR/ABL gene is transcribed from the promoter of the normal BCR gene, but little is known about the regulation of its expression. In this study, we asked whether there are sequence-specific DNA-binding proteins (DBP) that bind to the breakpoint cluster region (bcr, or Mbcr) within the BCR gene. Sequence-specific DBP located within the Mbcr could have a transcription-regulating effect, and they could participate in the recombination that generates BCR/ABL. Our data show that there are sequence-specific DBP that bind within the Mbcr.

DNA, Neoplasm

The use of prosody in highlighting alterations in repairs from unrestricted speech.

A speaker has several ways in which he or she may highlight the fact that an error or imprecision of speech has been made and subsequently altered. The three principal ones are by signalling through the structure of the speech that surrounds the error (the repair-syntax), by the use of prosody, and through the semantic content. The role of prosody in the correction process is investigated in the current studies. Analysis of the prosody of a number of errors and their alterations drawn from unrestricted speech are reported. The analysis shows that pauses occur at the moment of interruption and that an increase in stress occurs at the start of the alteration. Pauses could indicate the moment of interruption, and stress could highlight what has been altered. Two sets of perceptual experiments were carried out to assess whether these cues are salient for listeners who hear constructions containing an error and its alteration. Two paradigms were employed in each set of experiments: (1) direct judgement about the comprehensibility of sentences containing errors and alterations, and (2) repeating a message that had an error and alteration without the error. The effects of stress and pauses on (Experiments 1A and 1B) or pauses around (Experiment 2A and 2B) the alterations were assessed. In the first set of experiments it was shown that pauses and stress help listeners process repairs. When a word is spoken in error, the speaker may repeat a section of speech immediately preceding the alteration and/or a section immediately following that word. Inclusion of these repeated sections allows assessment of whether pauses signal where the interruption occurred. The second experiment shows that the placing of the pause before the retrace, rather than at other locations, indicates to listeners where the repair starts.

Adult

Piebaldism: an autonomous autosomal dominant entity.

Piebaldism is a disorder in which the major clinical features are patchy hypopigmentation of the skin and a white forelock. The manifestations of piebaldism overlap with those of other genodermatoses, in particular the Waardenburg syndrome, and it is uncertain whether piebaldism is a distinct entity. We have documented a family in which seven affected members in three generations have gross piebaldism without any additional stigmata. The intrafamilial phenotypic consistency is suggestive that this autosomal dominant disorder has independent syndromic status. Linkage studies using conventional gene markers failed to identity the locus of the faulty gene.

Adolescent

Hearing impairment and pigmentary disturbance.

Hearing impairment is a variable manifestation of several heritable conditions in which pigmentation of the skin or eyes is abnormal. Some of these disorders are well recognized although uncommon, while others are virtually private syndromes. Practical issues concerning the major conditions of this type are reviewed in this article on a basis of a survey of 4452 profoundly deaf children attending special schools in Southern Africa, together with investigations in affected families. The Waardenburg syndrome (WS), which is the most common deafness-depigmentation disorder, was present in 121 (2.7%) of the 4452 deaf scholars. Further studies in 7 multigeneration affected families confirmed phenotypic variability and indicated a need for internationally agreed diagnostic criteria. In 4 Cape Town families of mixed ancestry the WS-I gene was linked to the 2q37 locus, but in another large kindred no linkage could be demonstrated. Nonallelic heterogeneity is possible. There is uncertainty concerning possible interrelationship between WS and piebaldism. The phenotypic consistency of a South African family in which 7 persons in 3 generations had gross piebaldism in the absence of disturbance of hearing or involvement of the eyes and periorbital structures is suggestive that this disorder and WS are separate entities. Molecular investigations indicate that the gene for piebaldism in this kindred is not situated at the WS-I locus 2q37. Deafness and hyperpigmentation are present in neurofibromatosis type II (acoustic neuromata) and the multiple lentigines syndrome, while retinal pigmentation is a feature of the Usher syndrome. This latter entity is apparently much less common in Southern Africa than in other parts of the world.

Albinism

Leakage of periplasmic enzymes from envA1 strains of Escherichia coli.

Previous work ascribed antibiotic hypersensitivity of the envA1 mutant to lowered lipopolysaccharide levels and exposure of the lipid bilayer. In the detailed characterization of the EnvA permeability phenotype presented here, the envA1 mutation was shown to confer leakage of the periplasmic enzymes beta-lactamase and RNase I. Leakage was observed in three different genetic backgrounds, including the original envA1 strain and its parent. In contrast, no detectable leakage of the cytoplasmic enzyme beta-galactosidase was observed. Sensitivity of envA1 strains to a range of antibiotics not previously reported was tested, and lipophilicity (partition coefficient) of a number of antibiotics was determined. On the basis of observations of periplasmic leakage and sensitivity to large hydrophilic antibiotics and lysozyme, part of the permeability phenotype of the envA1 mutant is proposed to be due to transient rupture and resealing of the EDTA-sensitive outer membrane layer. In this regard, the EnvA permeability phenotype falls into a general class of permeability/leaky mutants of both Escherichia coli and Salmonella typhimurium.

Anti-Bacterial Agents

High resolution CT and bronchography in the assessment of bronchiectasis.

To elucidate the reliability of CT in the assessment of bronchiectasis, a retrospective study of high resolution CT and bronchography was carried out. A segment by segment comparison of 259 segmental bronchi from 70 lobes of 27 lungs in 19 patients was performed using bronchography as standard. CT was positive in 87 of 89 segmental bronchi with bronchiectasis giving a false-negative rate of 2%. CT was negative in 169 of 170 segmental bronchi without bronchiectasis at bronchography, giving a false-positive rate of 1%. There was agreement between the two modalities in identifying the different types of bronchiectasis.

Adult

Rat and human natural killers exhibit contrasting immunoglobulin G subclass specificities in antibody-dependent cellular cytotoxicity reflecting differences in their Fc receptors (Fc gamma R).

Rat and human natural killers (rtNK and huNK, respectively) were compared in quantitative antibody-dependent cellular cytotoxicity (ADCC) assays for their capacity to recognize mouse and rat IgG monoclonal antibodies (MAb) of different subclasses. NK from these two species exhibit considerably different patterns of IgG subclass recognition as determined by the relative antibody concentrations required for comparable levels of target cells lysis. ADCC assays with a panel of 16 MAb revealed that the efficiency of rtNK-mediated target lysis diminished according to IgG subclass in the following order: molgG1 greater than rtlgG2a greater than molgG2b approximately molgG2a greater than rtlgG2b greater than molgG3. By comparison, huNK recognized the same antibodies with nearly the opposite order of efficiency: rtlgG2b much greater than molgG2a greater than molgG3 greater than molgG2b much greater than rtlgG2a approximately molgG1. Only molgG2a antibodies were equally potent with rtNK and huNK. The contrasting difference in IgG subclass recognition by rat and human NK reflects the comparatively low protein sequence homology between their respective IgG Fc receptors (Fc gamma R).

Animals

Is there a preference for different ways of performing faecal occult blood tests?

Low compliance with faecal occult blood screening reduces the power of clinical trials, potential benefit, and efficiency. It has been proposed that the faecal manipulation required to perform conventional guaiac based tests may be an important factor in low compliance. The aim of this study was to evaluate whether use of a new method (vehicle) of stool collection for the faecal occult blood guaiac test would be preferred to the established standard. A novel self-interpreted test, Early Detector (ED), requires the subject to apply a guaiac/peroxide spray to a stool sample collected simply by wiping the anus with a specimen pad. To determine whether this method would be preferred to the stool manipulation required by Haemoccult (HO) and to compare test validity, employees at a London company were invited to use both tests. Eight-hundred and fifty-seven subjects were shown both tests. Before use, 48% indicated a preference for the method of Early Detector; 24% chose Haemoccult (p less than 0.001), while 28% indicated no immediate preference. Seven-hundred and one performed both tests. After use, 74% preferred ED; 5% preferred HO (p less than 0.001); 21% had no preference (NP). The preference for the ED test method was consistent by sex categories, age groups and occupational class. Logistics, aesthetics, and immediacy of results were the main reasons indicated for choosing ED. Whether the preference for ED could result in higher compliance remains to be proven. Its high positivity (14%), however, would preclude its use as a sole test to determine the need for endoscopic and/or radiologic investigation in the screened patient.

Adult

Analysis of periodic and aperiodic components during fluent and dysfluent phases of child and adult stutterers' speech.

The syllable repetitions of 6 child and 6 adult stutterers were investigated to establish whether dysfluent speech had a higher noise-to-signal ratio than fluent speech and whether this differed between children and adults. As predicted, the stuttered speech had a higher noise level for both age groups. During dysfluencies, the level of the noise components in the children's speech was higher than in the adults.

Adult

Sonographic imaging of the fetal azygous vein. Normal and pathologic appearance.

Sonologists should be familiar with the frequency of resolution and the ultrasonic appearance of the normal fetal azygous vein. In this study, 66 consecutive uncomplicated pregnancies were scanned to determine the frequency of imaging the fetal thoracic azygous vein. Between 21.7 and 30 gestational weeks, the azygous vein could be imaged in 50% of the cases and measured 1-2 mm in caliber. In the last 10 weeks of pregnancy, the azygous vein could be imaged in 98% of the cases and measured 2-4 mm. A case of fetal azygous continuation of the inferior vena cava is shown where the vein was abnormally dilated to a caliber of 8 mm.

Abnormalities, Multiple

The effect of diclofenac acid (Voltaren) on bleomycin-induced pulmonary fibrosis in hamsters.

Bleomycin is an anti-neoplastic compound which produces a time- and dose-dependent pulmonary fibrosis. The mechanisms which cause this fibrosis are not known. However, the ability of bleomycin to modulate prostaglandin synthesis, degradation and circulating levels appears to be central to the fibrosis. Previous studies, which have attempt to modulate bleomycin-induced fibrosis by prevention of prostaglandin synthesis have conflicting results. Therefore, the present study was designed to determine the effects of diclofenac acid, a nonsteroidal anti-inflammatory compound, on the development of bleomycin-induced pulmonary fibrosis. Diclofenac acid pretreatment and daily injections prevented lung collagen accumulation after intratracheal bleomycin. In addition diclofenac acid treatment resulted in significantly lower lung collagen level after intratracheal bleomycin at 14 and 21 days when compared with bleomycin alone. These data indicate that diclofenac acid treatment inhibits bleomycin-induced lung fibrosis possible through the prevention of prostaglandins synthesis.

Animals

Trans acting regulation of beta globin gene expression in erythroleukemia (K562) cells.

K562 cells are induced by hemin to produce gamma and epsilon globin but not beta globin, although the beta globin gene is intact, and when isolated is expressed in a transient expression assay (1, 2). We have previously shown that an epsilon globin gene transferred into K562 cells is expressed and inducible (3). In this paper, we report the stable transfer of a sickle or betaS globin gene into K562 cells. Thirty-six different transformed lines were tested; 24 of 36 lines contained an intact betaS globin gene. However, using S1 nuclease, Dot blot, and Northern blotting analyses, none of these lines showed beta globin mRNA expression. These results indicate that trans acting factors are responsible for the lack of expression of the beta globin gene in K562 cells.

Cell Line