Biomedical subjects
B Davies
Publications and source records attributed to B Davies.
Calculating projected increases in the number of dementia sufferers.
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Structure of an inverted duplication formed as a first step in a gene amplification event: implications for a model of gene amplification.
Inverted duplications have been observed to be a common feature of gene amplification in mammalian cells and appear to be generated as a primary event in the amplification process (Ford et al., 1985; Ford and Fried, 1986). The structural features of the amplified inverted duplication, containing the polyoma virus oncogene middle T-antigen, were analysed in transformed 3B rat cells. No unusual sequences such as transposition elements were detected at the site of the inversion. The inversion was generated by a simple illegitimate recombination event in which only a single nucleotide directly at the point of the inversion cannot be accounted for from the sequence of the two parental strands. Possible structural (hairpin formation) and sequence (rich AT) features may have been involved in the illegitimate recombination event at the inversion join. In the cellular DNA near one of its joins with polyoma virus DNA an unusual sequence of 198 bp composed of 99 consecutive purine-pyrimidine pairs has been detected. A model for the generation of amplified DNA containing inverted duplications is proposed.
Prediction of outcome in depressed patients by weekly monitoring with the dexamethasone suppression test.
Forty-three depressed patients in hospital were studied with weekly dexamethasone suppression tests (DSTs) and were followed as out-patients for at least three months after discharge. The detection rate of patients with LHPA axis dysfunction increased from 41% with a single DST to 59% with serial DSTs. There was a poor correlation between weekly post-dexamethasone cortisol levels and Hamilton depression rating scores. In patients with evidence of LHPA axis dysfunction, a DST at discharge discriminated effectively between a good and a poor outcome group; persistent non-suppression was strongly linked with a relapse of depression in the first three months after discharge. In general, our results support previous claims that the DST is a state marker for depressive illness.
Family responses to the death of a child: the meaning of memories.
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Reply to "Comments on Abraham's intrinsic interface structure"
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Didemnin B. The first marine compound entering clinical trials as an antineoplastic agent.
A new class of marine compounds, the didemnins, with potent antitumor activity has been identified. They share the novel structure of a cyclic depsipeptide. Among three structurally related compounds, didemnin B is by far the most potent in its in vitro cytotoxicity and in vivo antitumor activity (0.001 microgram/ml inhibits the growth of L1210 leukemia cells by 50%). It also demonstrates good antitumor activity against B16 melanoma and moderate activity against M5076 sarcoma and P388 leukemia. The compound also has good antiviral and potent immunosuppressive properties. Although the precise mechanism of action for the cytotoxicity remains unknown, the agent inhibits protein synthesis more than DNA synthesis and the inhibition of protein synthesis is closely correlated with inhibition of L1210 cell growth. Toxicology studies in CD2F1 mice, Fischer 344 rats and beagle dogs reveal that major target organs are the lymphatics, gastrointestinal tract, liver and kidney. Phase I trials are currently in progress under the auspices of the National Cancer Institute.
Secretion of neuron-specific enolase, prolactin, growth hormone, luteinising hormone and follicle stimulating hormone by "functionless" and endocrine-active pituitary tumours in vitro.
Secretion of the neuroendocrine marker neuron-specific enolase by 24 pituitary tumours was measured in maintenance tissue culture. Eleven endocrine-active and 13 "functionless" tumours were defined by measurement of prolactin, growth hormone, luteinising hormone (LH) and follicle stimulating hormone (FSH) secretion rates in vitro and the corresponding plasma hormone levels. Measurement of prolactin secretion provided a clear distinction between true prolactinomas and "functionless" tumours causing hyperprolactinaemia by stalk compression (pseudoprolactinomas). A previous report of LH and/or FSH secretion by the majority of "functionless" tumours was confirmed, but plasma levels of LH and FSH were usually normal. It is argued that LH and FSH are not the major hormones secreted by "functionless" tumours. A high production rate of neuron-specific enolase appears to be characteristic of the cell type from which most "functionless" tumours derive.
Progression of addiction careers in young adult solvent misusers.
Four case histories of a representative sample of young adult glue sniffers who had progressed to using illicit drugs or abusing alcohol or both contained several common factors that may have been relevant in the transition. For example, all had suffered parental deprivation or rejection in childhood leading to a state of chronic stress, and all had progressed from sniffing glue to inhaling heroin and thence to "snorting" and injecting heroin. The exact reason for the transition from glue sniffing to misusing other substances was not clear. Nevertheless, although these cases represent only a minority of glue sniffers, the problem of transition may be more common than hitherto supposed.
Aortitis and large vessel arteritis in a newborn.
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Isolation of a gene enhancer within an amplified inverted duplication after "expression selection".
We have attempted to isolate and identify cellular expression sequences from F9 teratocarcinoma DNA by utilizing their ability to reactivate a selectable gene devoid of its own expression sequences (expression selection). Restriction nuclease-digested F9 cellular DNA was ligated to a polyoma virus (Py) DNA fragment which contains an intact transforming region but is incapable of inducing transformation because it lacks the viral 5' enhancer sequence. The ligation mixture was used to transfect Rat-1 cells and a transformed cell line, 3B, was isolated. The 3B cell line contained a single type of Py DNA insert, which was molecularly cloned as an 18-kilobase BglII fragment. A weak cellular enhancer was identified in a 4.7-kilobase BamHI fragment upstream from the Py sequences. Both the Py DNA and the enhancer sequences were found to be present in an inverted duplication in the 3B clone. The presence of this structure in 3B genomic DNA was confirmed by the analysis of selectively isolated inverted duplicated sequences, and the structure was found to be at least 22 kilobases long. In the 3B cell line, the inverted duplicated sequences containing the Py and enhancer sequences are quite stable and are amplified 20- to 40-fold. The strongly transformed phenotype of the 3B cells may be a result of this amplification. The formation of inverted duplications as a part of the amplification mechanism as well as a general strategy for the cloning of inverted duplicated (amplified) sequences is discussed.
Acoustic neuromas presenting as sudden deafness.
Caution is required in diagnosing even apparently "obvious" causes of hearing loss. A patient is described who came to medical attention through referral from a lawyer for sudden deafness allegedly caused by exposure to noise in an industrial setting. Thorough evaluation revealed an acoustic neuroma. Review of the literature suggests that presentation of acoustic neuromas as sudden deafness is more common than generally recognized. Clinicians must be alert to this possibility and diligent in their evaluation of any unilateral ear symptoms.
Psychiatric aspects of coronary artery surgery. A prospective study.
A psychiatric assessment was carried out before operation, and at three months and 12 months after operation, in 77 men undergoing coronary artery bypass graft surgery. Neither psychiatric assessment before the operation nor perioperative surgical assessment could predict the physical outcome of surgery. The physical results of surgery were good, but there was a 20% decrease in the number of patients who were in employment after the operation. Abnormally high scores on measures of anxiety and depression were present in about 50% of patients before the operation, and in about one-third of patients after the operation. Impairment in various aspects of personality-functioning since surgery was reported by 7%-29% of patients. These complaints were not correlated with the surgical result. Attention is drawn to this area of persisting postoperative morbidity.
Maximum oxygen uptake utilising different treadmill protocols.
The study compared five treadmill protocols (four utilising a motorised, and one a non-motorised, treadmill) on maximum oxygen uptake. The five male and five female subjects, all actively engaged in training, were assigned the tests in random order. Statistical analysis revealed no significant differences between the five protocols for maximal oxygen uptake, maximum ventilation, maximum heart rate and blood lactate inflection point, relative to maximal oxygen uptake. Significant differences were observed between the 3' protocol with incline increments of 1.5% and all other protocols on time to exhaustion (p = less than 0.01) and maximum blood lactate levels (HLA, p = less than 0.05). The results indicate that the protocols used in this study did not significantly influence the maximum oxygen uptake attained.
Physiological changes and sleep responses during and following a world record continuous walking record.
Physiological changes, and subsequent sleep responses, were recorded in a male subject during and following 338 miles of continuous walking and consequent sleep deprivation. One hundred and thirty hours of walking and a seventy-two hours post-walk recovery period were monitored. The subject walked at approximately 55% of maximum oxygen uptake (VO2 max), heart rate ranged between 102-106 b/min, and blood lactate (LA) remained below the 2 mmol/l level. No electrocardiograph abnormalities were observed either during the walk or pre- and post-functional diagnostic graded exercise test (FDGXT). Creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) levels rose throughout the walk but exhibited differing depletion patterns. The ratio of CK-MB to CK (MB/CK%) did not exceed levels which are suggestive of myocardial ischaemia. Haematological variables demonstrated signs of anaemia towards the end of the walk. Catecholamine levels rose throughout the walk, with greater rises being observed in nor-adrenaline and dopamine. During the post-walk recovery phase, adrenaline concentration remained elevated. Following this extreme period of exertion, the subject demonstrated very short sleep latency and rapid entry into slow wave sleep (SWS). These sleep patterns were compared to sleep recordings made over a similar period (72 h) six months post-walk, when the subject was not exercising. Nocturnal growth hormone (GH) levels were significantly raised on the post-walk nights.
A study of the dexamethasone suppression test in hospitalized depressed patients.
90 patients with a primary depressive illness, admitted consecutively to one psychiatric ward were studied. All patients had the dexamethasone suppression test (DST) done before initial treatment. First treatment response was correlated with the DST results. The non-suppressors, as a group, improved with treatment better than the suppressors. However, unlike in previous studies, no relationship was found between non-suppression and poor response to antidepressant medication.
Parenteral augmentin: pharmacokinetics.
The pharmacokinetics of intravenous Augmentin have been investigated and the data found to fit a two compartment model. In the first study, to a crossover design, a bolus injection of 1.2 g Augmentin was given to 8 healthy volunteers with and without probenecid. It was found that the serum concentrations of amoxycillin were increased in the presence of probenecid, but those of clavulanic acid were unaffected. In a second study a further 8 volunteers received an infusion over 30 min of 2.2 g Augmentin. At the end of the infusion, peak concentrations in excess of 100 micrograms/ml were recorded for amoxycillin and 14 micrograms/ml for clavulanic acid. In both studies the serum and urinary concentrations of amoxycillin and clavulanic acid obtained were well above those considered necessary to achieve a therapeutic effect.
An inside view. Clinical.
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