Adiabatic electron thermal pressure fluctuations in tokamak plasmas.

Electron thermal pressure fluctuations measured in the edge plasma of the Texas Experimental Tokamak Upgrade are a fundamental component of plasma turbulence on both sides of the velocity shear layer. The ratio of specific heats, estimated from fluctuations in electron temperature and electron number density measured simultaneously at the same electrode, indicates that observed fluctuations are adiabatic. The observations are made by means of a novel Langmuir probe technique, the time domain triple-probe method, which concurrently measures multiple plasma properties at each of two electrodes with the temporal and the spatial resolution required to estimate thermodynamic properties in a turbulent plasma.

The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction.

To investigate further brain-pituitary-gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted. Female FSH receptor knockout (FSHRKO) mice were infertile. The ovaries were significantly reduced in size, with follicular development arrested at the preantral stage, but there was evidence of stromal hypertrophy. The vagina was imperforate, and the uterus was atrophic. There was no response to administration of PMSG. Inhibins A and B were undetectable in both the serum and gonads. Compared with those in control animals, serum concentrations of FSH and LH were significantly elevated in mutant females. The pituitary content of FSH, but not LH, was also significantly elevated. Estrogen administration in FSHRKO female mice suppressed serum LH levels to those seen in control mice, whereas FSH levels were reduced by only 50%. Male FSHRKO mice were fertile, although testis weight was significantly reduced. However, testicular inhibin A and B concentrations did not differ from those in normal littermates. Serum levels of FSH and LH were elevated in the null mutant male mice, whereas no differences were found in the pituitary content of these hormones. In conclusion, ovarian follicular development cannot progress beyond the preantral stage without FSH. In the absence of mature follicles ovarian estrogen remains low, and consequently accessory sex tissue growth and negative feedback regulation of gonadotropin secretion are severely compromised. In the male, however, inability to respond to FSH does not impair fertility, although testicular weight is reduced, and feedback regulation of pituitary gonadotropins and intratesticular paracrine interactions may be disturbed.

Increasing diagnosis of nicotine dependence in adolescent mental health patients.

OBJECTIVE: The aim of this study was to investigate the routine recording patterns of patients' smoking by clinical staff of an adolescent mental health service over a 3-year period. METHOD: A systematic examination of the clinical files of all patients who underwent an initial assessment or reassessment at the Youth Specialty Service (Mental Health; YSS) over a 2-month period (1 April-31 May) was carried out in 1996, 1997 and 1998. A range of data were collected including: demographics; diagnoses; amount of total information recorded and history of nicotine dependence. RESULTS: A stable historical record of cigarette smoking in the region of 30-40% across the 3 years sampled was found, but the rate of formal diagnosis of nicotine dependence rose from 3.6% in 1996 to 26.3% in 1998. This rise was in the context of relative stability over this time period of: size of reports and relevant sections (alcohol and drug history, cigarette smoking history); three other key diagnoses, major depression, conduct disorder and alcohol dependence; and demographic data. The rise in rate of diagnosis proceeded specific discussion within the clinical team about nicotine dependence. CONCLUSIONS: Adolescent mental health settings are a key venue to address heavy and potentially chronic cigarette smoking, but nicotine dependence has been traditionally a neglected diagnosis in mental health patients. The rate of diagnosis is likely to rise when specific discussion is undertaken within clinical teams.

The 75 g oral glucose tolerance in pregnancy.

A 75 g oral glucose tolerance test was performed between 26 and 32 weeks gestation in 1371 women attending an ante-natal clinic in Melbourne. Gestational diabetes according to various criteria was present in 4.2% (2 h plasma glucose > or = 8.0 mmol/l), 5.2% (2 h plasma glucose > or = 7.8 mmol/l) and 5.5% by the proposed Australian criteria (fasting plasma glucose > or = 5.5 mmol/l and/or 2 h plasma glucose > or = 8.0 mmol/l). The long-term implications of gestational diabetes in the development of diabetes and metabolic abnormalities for both the mother and her child in addition to related infant morbidity emphasise the urgent need for an agreed definition of this condition.

Serum IL-4, IL-10 and IL-6 levels in inflammatory arthritis.

As the available in vitro and in vivo data suggest that interleukin (IL)-4 and IL-10 have immunosuppressive activity, our hypothesis was that serum IL-4 and IL-10 levels would correlate inversely with parameters of inflammation in patients with inflammatory arthritis. IL-4 was detected in the serum of 12 out of 140 patients with rheumatoid arthritis (RA), which was increased compared to the proportion found with patients with osteoarthritis (OA; P < 0.02). In addition, IL-4 was detected in the serum of 2 of 19 patients with systemic lupus erythematosus (SLE), 2 of 24 patients with psoriatic arthritis and 1 of 5 patients with Behçet's syndrome. No IL-4 was detected in patients with the following conditions: OA (58 patients), gout (17 patients), ankylosing spondylitis (6 patients), Reiter's syndrome (6 patients), polymyalgia rheumatica (6 patients), temporal arteritis (5 patients) and scleroderma (3 patients). No IL-10 was detected in any of the sera tested. We discuss the possible relevance of these results to the regulation of the immune response evident in inflammatory arthritis.

Object transfer, intersubjectivity and third position repair: early developmental observations of one child.

Interaction sequences are explored which are initiated by either child requests or adult offers of objects. The focus is on those sequences in which the child does not want an object that is passed to her, and on how the child manages such an interactional contingency. Throughout the age range in question, 1;0 to 1;8, the child uses re-requests where this contingency occurs in request sequences. The analysis traces the development of these re-requests and compares them with other forms of re-request. In addition, differences are uncovered as between request and offer sequences concerning the child's ways of dealing with an unwanted object that is passed to her. Linkages are made between these themes and work on third position repair within conversation analysis. Home based video-recordings of one child between the ages of 1;0 and 1;8 constitute the data base for the study.

Dermatophagoides pteronyssinus II-induced interleukin-4 and interferon-gamma expression by freshly isolated lymphocytes of atopic individuals.

Cytokines are known to play a major role in mediating many of the immunological and pathological features of allergic disease. Much of our understanding of cytokine production in response to allergens has come from studying allergen-specific T cell clones following long-term in vitro culture. This has largely been due to the lack of sufficiently sensitive assays to measure allergen-induced cytokine production by freshly isolated peripheral blood mononuclear cells (PBMCs). Here we have used the polymerase chain reaction to amplify reverse transcribed interleukin-4 (IL-4) and IFN gamma mRNA expressed by allergen-stimulated PBMCs from a variety atopic individuals. Using Der p II, a major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus, we have demonstrated that cells from HDM-sensitive atopic patients (n = 12), can be induced to express either IL-4 alone (three patients), IL-4 and IFN gamma (six patients), IFN gamma alone (two patients) or neither cytokine (one patient). Cells from 13 non-atopic control individuals were also stimulated with Der p II and cytokine mRNA production was studied. None expressed IL-4, while seven of 13 transcribed IFN gamma. Our results suggest that atopic individuals have allergen-reactive T cells at various stages of differentiation, with respect to the cytokines they produce. The use of this technique will aid in the further understanding of specific cellular hypersensitivity in allergic disease.

IL-4 production is increased in cigarette smokers.

Cigarette smoking has been associated with both increases in serum levels of total IgE and an increased risk of developing allergic-like symptoms. IL-4 and interferon-gamma (IFN-gamma) have reciprocal roles in the regulation of IgE synthesis, and as such prompted us to evaluate, in smokers, the production of these two cytokines. We demonstrate that phytohaemagglutinin (PHA)-induced IL-4 production by peripheral blood mononuclear cells (PBMC) of smokers (n = 19) is significantly higher than that of non-smokers (n = 10, P < 0.005). In addition, PBMC from heavy smokers, defined by the number of cigarettes smoked per day, produced significantly higher levels of IL-4 than those of light smokers. No difference between the groups was found for IFN-gamma production. Our data suggest an imbalance in cytokine production occurring in individuals who smoke. This imbalance, favouring IL-4 production, may be part of the mechanism responsible for the observed increases in serum IgE and allergic-like symptoms associated with cigarette smoking.

Hydrocortisone inhibition of human interleukin-4.

Glucocorticoids are known to inhibit mitogen-induced proliferation of T cells by suppressing the production of interleukin-2 (IL-2). These hormones have also been shown to inhibit the production of other cytokines, namely IL-1 and interferon-gamma (IFN-gamma). It is demonstrated here that hydrocortisone is able to inhibit mitogen-induced production of human IL-4, both at the secreted protein, as well as at the mRNA level. This effect may explain, in part, the immunosuppressive effects of glucocorticoids in the treatment of allergic disease.

T cell responses to the purified major allergens from the house dust mite Dermatophagoides pteronyssinus.

Proliferation assays were used to determine peripheral blood T cell responses to affinity-purified Der p I, Der p II, and Der f II allergens. Patients studied were sensitive to the house dust mite (HDM) either alone or in combination with other allergens. Control subjects were both nonatopic and atopic non-HDM sensitive. In general, only HDM-sensitive patients responded to the mite allergens. Mean stimulation indices (SI) were 10.2 +/- 2.8 (SEM) for Der p I and 10.0 +/- 2.2 for Der p II in HDM-sensitive individuals, and 2.0 +/- 0.2 and 2.8 +/- 0.6 for non-HDM sensitive control subjects (p less than 0.001). Patients sensitive to HDM and other allergens had higher responses than subjects sensitive to HDM alone, and the degree of proliferation to Der p I and Der p II was well correlated in individual patients (r = 0.71; p less than 0.001). Total IgE levels were elevated in the allergic patients, and values were highly correlated with the SI for both Der p I and Der p II (p less than 0.001). Responses to Der p II and Der f II were equivalent in 82% of individuals; however, in 18%, there was a marked discordance with strong responses to Der p II only. SIs were compared between different clinical groups of patients, and patients with asthma had significantly higher values to both Der p I and Der p II than patients with rhinitis alone (17.0 +/- 5.4 versus 5.7 +/- 1.0 for Der p I, p less than 0.05; 14.3 +/- 6.8 versus 5.0 +/- 1.0 for Der p II, p less than 0.05).

Interferon-gamma production in atopic dermatitis: a role for prostaglandins?

Peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) have a reduced capacity to produce interferon-gamma (IFN-gamma) in vitro, in response to phytohaemagglutinin (PHA) when compared to healthy non-atopic controls. This defect appears to correlate closely with the severity of AD at the time of sampling, with less IFN-gamma being produced by cells from patients with more severe disease. Enhanced production of IFN-gamma was observed as the patients clinical symptoms improved. In addition, IFN-gamma production could be increased by either pre-culturing the cells for 3 days prior to PHA stimulation or by addition of indomethacin to the culture medium. These observations suggest that the mechanism of reduced IFN-gamma production in AD is unlikely to be due to an intrinsic cellular defect. The possibility that prostaglandins mediate the suppressed production of IFN-gamma in AD was supported by demonstrating that exogenous prostaglandin E2 (PGE2) inhibited IFN-gamma production in PHA-stimulated PBMC. PGE2 at a physiological concentration (10(-9) M) was also shown to enhance interleukin 4 induction of IgE synthesis by PBMC cultures. Our data suggest that alterations in prostaglandin metabolism play a crucial role in the pathogenesis of AD by inhibiting the production of IFN-gamma.

An evaluation of the Sysmex NE-8000 hematology analyzer.

The Sysmex NE-8000 is a new, fully automated hematology analyzer capable of providing a five-part white blood cell differential count and identifying abnormal specimens. This instrument was evaluated on 5,000 consecutive blood specimens and compared to the Coulter S Plus-IV analyzer and manual differential cell counts to determine the efficacy of its five-cell differential and screening capabilities. There was a high correlation between the commercial counters for the standard parameters, white blood cell count, red blood cell count, hemoglobin level, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, and platelet count (r greater than 0.95), except for the mean corpuscular hemoglobin concentration (r = 0.51), for which the NE-8000 was considered the more accurate measurement. Precision and linearity studies were excellent. The white blood cell count, red blood cell count, hemoglobin level, and platelet count were reproducible on specimens stored at 4 degrees C or room temperature for 72 hours and the differential counts were reproducible for 12 hours. The correlations between automated and manual counts for neutrophils, eosinophils, basophils, and lymphocytes were excellent: r = 0.912, 0.945, 0.332, and 0.964, respectively. The monocyte correlation improved with software modification from 0.306 to 0.801. The NE-8000 gave accurate and reproducible differential counts for neutrophils, lymphocytes, and monocytes on specimens with white blood cell counts as low as 0.6 x 10(9)/1. The ability of the instrument to 'flag' abnormal specimens was excellent. The false-positive rate on normal samples was 1.8%, and the false-negative rate on known abnormal samples was 0.3%, due only to nonrecognition of a mild left shift. The identification of specific abnormalities was less precise. The NE-8000 is a powerful hematology analyzer that can perform a five-part white blood cell differential count accurately for a wide range of WBCs and reliably indicate abnormal specimens. It is an excellent screening tool for distinguishing between normal and abnormal specimens and identifying those that require microscopy. Its reliability significantly reduces the need for manual film examination.

Recombinant interferon-gamma inhibits the expression of IL-4 receptors on human lymphocytes.

Interferon gamma (IFN-gamma) has been shown to inhibit many of the activities of IL-4, including the induction of IgE synthesis and the proliferation of T cell clones. Here we demonstrate that IFN-gamma is able to inhibit the expression of IL-4 receptors on peripheral blood lymphocytes from both normal healthy donors and from patients with chronic lymphocytic leukaemia. Inhibition was shown to be dose-dependent and did not affect the binding affinity of the receptor as shown by Scatchard analysis. IFN-gamma was unable to displace labelled IL-4 from its membrane receptor, which demonstrates that IFN-gamma and IL-4 do not compete for the same membrane binding protein. The ability of IFN-gamma to down-regulate IL-4 receptors may be important in controlling certain immune responses.

Offer sequences between parents and young children with Down's syndrome.

Videorecordings were made in the homes of six children with Down's syndrome whose developmental ages ranged between about 1 and 2 years. Analysis of sequences initiated by parental offers to their children suggests that these children's response behaviour is sensitive to both non-verbal aspects of the offerer's behaviour and the context in which the offer is made.

Pointing and interaction initiation: the behaviour of young children with Down's syndrome when looking at books.

Data are derived from videotapes made in the homes of six Down's syndrome children with developmental ages varying between 1;1 and 2;1. The analysis concerns those sequences in which parent and child look at a book together, and more specifically those exchanges where the child initiates communication on a new target on the page. The design of these initiations is examined with respect to their various verbal and non-verbal components. The analysis of pointing, and in particular of point duration, reveals a possible developmental progression from a stage at which point and exchange duration are linked together to one in which the organization of pointing becomes more detached from the exchange as a unit of interaction.

Micronucleus induction by azobenzene and 1,2-dibromo-3-chloropropane in the rat: evaluation of a triple-dose protocol.

A triple-dose protocol was evaluated in the rat bone-marrow micronucleus test using azobenzene and 1,2-dibromo-3-chloropropane (DBCP) as test compounds. Dosing with 250 mg/kg azobenzene over 3 consecutive days led to an accumulation of micronucleated polychromatic erythrocytes. The magnitude of the effect was the same as that obtained after a single dose of 750 mg/kg in a previous study. In the single-dose study the effect was only detected at the 48 h sampling time. With the triple-dose protocol the effect was apparent 24 h after the last dose--thus eliminating the need for more than one sampling time. In the case of DBCP, the positive effect observed after a single dose diminished with increasing number of doses for the low dose but plateaued for the high dose, accompanied by a marked cytotoxic effect. It is therefore concluded, that for one of the compounds, azobenzene, the triple-dose protocol provided an advantage whereas for the other, DBCP, it failed to do so and led to results which are rather difficult to interpret. Furthermore, the number of animals necessary to select an appropriate dose level appears to be higher than in the single-dose protocol.

Laboratory instrument evaluation using a personal computer.

A system in which data from multichannel biochemical analysers is downloaded to a personal computer using a communications package is described. BASIC programs were developed to format the data into a file structure suitable for importing into a commercial statistics software package. This allowed statistical comparisons to be made of patient data obtained from different instruments and facilitated evaluation of these instruments. Using this technique, many hundreds of patient results may be compared without requiring the data to be keyed into a computer. The techniques and programs used are described to show that these facilities can be developed by laboratory scientists with only rudimentary computer programming skills.

Detection of IgM antibodies to delta antigen after coinfection and superinfection with the delta virus.

A sensitive microtitre radioimmunoassay was developed for detection of IgM antibodies to delta antigen. The assay was based on the selective binding of IgM from test sera to antihuman IgM (u-chain specific) fixed to wells of a microtitre plate, and utilized delta antigen extracted from the liver of an experimentally infected chimpanzee. This test proved to be useful in distinguishing between coinfection and superinfection with the hepatitis delta virus (HDV). Transient anti-delta IgM responses were observed in patients coinfected with HDV, while prolonged elevated IgM levels were found in HBsAg carriers with chronic liver disease superinfected with HDV. Two distinct serological patterns were observed in both coinfection and superinfection. In coinfection, only 50% of patients with detectable anti-delta IgM went on to develop a long-lasting antibody response. Following superinfection with HDV either stationary or fluctuating levels of IgM antibody were demonstrated. In patients with fluctuating antibody levels, the presence or absence of IgM antibody related to the level of viral replication.

Epidemiology of hepatitis D virus (delta) infection in Melbourne over a 15-year period.

The prevalence of delta infection was studied in 3986 individuals seropositive for hepatitis B surface antigen (HBsAg), who were seen in Melbourne between 1971 and 1985. The group comprised 2004 patients with acute hepatitis B, 1820 asymptomatic HBsAg carriers, 139 HBsAg carriers with evidence of chronic liver disease, and 23 carriers who had suffered more than two separate attacks of acute hepatitis. Markers of delta infection were found almost exclusively among intravenous drug abusers and their close contacts. Studies of stored sera suggest that delta infection was introduced into this group about 1970. In carriers with no evidence of chronic liver disease, the prevalence of delta infection was highest among intravenous drug abusers (19.2%). In carriers with evidence of chronic liver disease, delta markers were present in 20.1% and all 23 carriers with recurrent acute hepatitis had evidence of infection with the delta virus.